i

VARIATIONS IN THE SIZE AND TIME OF CLOSURE OF THE

ANTERIOR FONTANEL FROM BIRTH TO 24 MONTHS OF AGE IN

NIGERIAN CHILDREN IN PORT HARCOURT

A DISSERTATION SUBMITTED TO THE NATIONAL

POSTGRADUATE MEDICAL COLLEGE OF NIGERIA IN PARTIAL

FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF THE

FELLOWSHIP OF THE COLLEGE IN PAEDIATRICS

BY

DR. OKORIE ELIZABETH-MARTHA C.

MBBS (NIG)

MAY 2013

ii

iii

CERTIFICATION

The study reported in this dissertation was done by Dr (Mrs.) Okorie E-M C. under our

supervision. We have also supervised the writing of the dissertation.

.......................................

Supervisor

DR. P. I. OPARA

CONSULTANT PAEDIATRICIAN

UNIVERSITY OF PORT HARCOURT TEACHING HOSPITAL, PORT HARCOURT

.......................................

Supervisor

Prof. N.A. AKANI

CONSULTANT PAEDIATRICIAN

UNIVERSITY OF PORT HARCOURT TEACHING HOSPITAL, PORT HARCOURT

.......................................

Supervisor

DR . E.A D. ALIKOR

CONSULTANT PAEDIATRICIAN

UNIVERSITY OF PORT HARCOURT TEACHING HOSPITAL, PORT HARCOURT

iv

DEDICATION

To all Nigerian children, who are mis-managed, albeit with good intentions due to

parental ignorance of the normal evolution of the anterior fontanel.

To my family, for their understanding, prayers and support during the residency

programme.

To God Almighty, I owe Him everything.

v

ACKNOWLEDGEMENT

My gratitude goes first and foremost to God Almighty whose infinite grace and mercy

has brought me thus far.

I wish to acknowledge my Supervisors Dr. P. I. Opara, Dr N.A. Akani and Dr. E. A. D.

Alikor whose immense support and guidance enabled me to complete this work. I sincerely

appreciate them. I wish to thank Prof. K.E. O. Nkanginieme for his assistance in the course of

this dissertation. I sincerely thank Dr T. Okpere for her objective criticism of this book and

for her moral support throughout the residency programme.

I am grateful to the management of the University of Port Harcourt Teaching Hospital

(UPTH) and that of Braithwaite Memorial Specialist Hospital (BMSH), the staff of the

Special Care Baby Unit and the Post Natal Ward of UPTH, as well as the staff of the Well

Infant Clinics of both hospitals for their kind assistance in the course of this project.

I will not fail to acknowledge my Research Assistants Dr. Steve Ogboru, Dr. Ben Ishie,

Dr. Chinye Arinze, Dr. Denis Okoye, Dr. Calistus Chukwu, Dr Ine Briggs, Dr Ransome

Chukwu, Dr Mary Okpani, Dr. Peace Toritseju, Dr. Uju Azubogu, Dr. Alero Sagay, Dr.

Ifeyinwa Ugboma, Mr Ikechukwu Opara, Mr Henry Onyegbule, and Chinenye Onyegbule, as

well as Mr Jude of Souldek Consulting who taught and assisted me with the statistical

analysis./

I am grateful to my family and friends for their moral support and prayers.

vi

TABLE OF CONTENTS

TITLE AGE..................................................................................................................................i

DECLARATION.........................................................................................................................ii

CERTIFICATION......................................................................................................................iii

DEDICATION...........................................................................................................................iv

ACKNOWLEDGEMENT...........................................................................................................v

TABLE OF CONTENTS...........................................................................................................vi

LIST OFABBREVIATIONS....................................................................................................vii

LIST OF TABLES...................................................................................................................viii

LIST OF FIGURES.....................................................................................................................x

SUMMARY...............................................................................................................................xi

INTRODUCTION.......................................................................................................................1

REVIEW OF LITERATURE......................................................................................................4

JUSTIFICATION FOR THE STUDY......................................................................................39

AIMS AND OBJECTIVES.......................................................................................................41

SUBJECTS AND METHODS................................................................................................. 42

RESULTS..................................................................................................................................53

DISCUSSION............................................................................................................................86

CONCLUSION.........................................................................................................................92

RECOMMENDATIONS...........................................................................................................93

LIMITATIONS OF THE STUDY............................................................................................94

LINES OF FUTURE STUDIES................................................................................................95

REFERENCES..........................................................................................................................96

APPENDICES.........................................................................................................................105

vii

LIST OF ABBREVIATIONS

AF: Anterior fontanel

ANOVA: Analysis of variance

BMSH: Braithwaite Memorial Specialist Hospital

CT: Computerized Tomography

cm: Centimetre

GA: Gestational Age

hrs: Hours

IUGR: Intra Uterine Growth Retardation

IVH: Intraventricular Haemorrhage

MAX: Maximum

MIN: Minimum

mm: Millimetre

MRI: Magnetic Resonance Imaging

mo: Month

OFC: Occipito-frontal circumference

SCBU: Special Care Baby Unit

SD: Standard Deviation

UCH: University College Hospital

US: Ultrasonography

UPTH: University of Port Harcourt Teaching Hospital

WHO: World Health Organization

wks: Weeks

viii

LIST OF TABLES

Table I: Common causes of large fontanels ..................................................................31

Table II: Less common causes of large fontanels...........................................................32

Table III: Differential diagnosis of microcephaly............................................................35

Table IV: Causes of bulging anterior fontanel.................................................................37

Table V: Distribution of subjects by age and gender….....………………………….....54

Table VI: Distribution of newborns by gestational age and gender.................................55

Table VII:

Table VIII:

Distribution of the subjects by ethnic group....................................................56

Distribution of subjects by social class............................................................57

Table IX: Variation in mean AF sizes by postnatal age..................................................59

Table X: Variation of mean anterior fontanel sizes of newborns by gestational age

And gender......................................................................................................60

Table XI:

Table XII:

Dunnett’s multiple comparisons of differences in mean AF size between

different age groups.........................................................................................61

Mean, range and percentiles of AF in the study group...................................64

Table XIII: Relationship between mean anterior fontanel size, social class and age.........66

Table XIV:

Table XV:

Variation of mean AF size with ethnic group among the newborns................68

Variation of mean occipito-frontal circumference by age and gender.............70

Table XVI:

:

Variation of mean occipito-frontal circumference by gestational age

and gender........................................................................................................72

ix

LIST OF TABLES CONTD.

Table XVII: Dunnett’s multiple comparisons of differences in mean OFC between different

age groups…............................…………………………………………….........73

Table XVIII: Mean, range and percentiles of OFC in the study subjects....................................74

Table XIX: Correlation between the AF size, OFC and post natal age....................................77

Table XX: Relationship between postnatal age and closure of anterior fontanel......................... 79

x

LIST OF FIGURES

Fig.1: Lateral and superior views of the newborn skull showing the anterior and

posterior fontanels.............................................................................................................7

Fig. 2: Popich and Smith's method of measurement of the size of the anterior fontanel..........22

Fig. 3: Fleming and Pedroso's method of AF measurement.....................................................23

Fig. 4: Introduction of the tip of a finger to aid delineation of the extent of the fontanel in

the method of measurement of the AF by Davies et al..................................................24

Fig.5: Method of calculation of the area of anterior fontanel by Davies et al .......................24

Fig.6: Philips's Method of calculation of the area of the AF..................................................25

Fig.7: Scatterplot of variations of AF size by post-natal age and gender...............................62

Fig. 8: Variation in the 5th, 50th and 95th percentile of AF size with postnatal age................65

Fig. 9: Variation of mean AF size by social class…………………………………................67

Fig. 10: Scatterplot of variations of OFC size by postnatal age in males and females.............71

Fig. 11: Variations of the 5th, 50th and 95th percentiles of OFC with postnatal age..................75

Fig. 12: Scatterplot of the correlation between anterior fontanel size and occipito-frontal

circumference with postnatal age....................................................................................78

Fig. 13: Variation in percentage closure of anterior fontanel with postnatal age………..........80

xi

SUMMARY

The size of the anterior fontanel (AF) and the occipito-frontal circumference (OFC) are

useful indices of the rate of brain growth and ossification of the calvarium. They may also reflect

changes in intracranial pressure seen in different disease conditions and so form essential parts of

the neuro-developmental assessment of newborns and infants. However, there is a dearth of data

on AF size from cosmopolitan settings in Nigeria, particularly for infants between 12 and 24

months of age. The wide variation in the size of the AF underscores the need to establish local

reference standards for a given population. This study was done to address the gap in knowledge

on AF size in the South-South Geo-political Zone.

This was a cross-sectional observational and analytical study of 2895 consecutively

recruited children (313 neonates and 2582 infants) from two tertiary health institutions in Port

Harcourt. The AF size (determined by the modified method of Faix) and the OFC (determined by

the Student’s method), were measured in apparently healthy Nigerian children aged 48 hours to 7

days and at 6 weeks, 10 weeks, 14 weeks, 6 months, 9 months, 12 months, 18 months and 24

months of age.

The mean ± SD AF size for the newborns was 4.5 ± 1.7 cm while at 24 months the mean

AF size was 0.2 ± 0.7 cm. The mean ± SD OFC in the newborns was 35.8 ± 2.7 cm while at 24

months the mean ± SD OFC was 48.0 ± 2.3 cm. There was a statistically significant negative

correlation (r = -0.648, p = 0.000) between AF size and OFC with increasing post-natal age,

represented by the formula y = 14 - 0.265x, where y = AF size, and x = OFC.

Of the 2895 subjects, 667 (23.04%) had a closed AF. The number (%) with a closed AF was

9 (2.9%) among the 313 newborns and 288 (88.9%) of the 324 infants at 24 months of age. In

between these two 7/325 (2.2%), 76/321 (23.7%) and 273/321 (85.1%) had a closed AF at 6, 12

and 18 months of age respectively. The proportion of females (57.7%) with a closed AF was

xii

significantly higher than that of males (45.6%), (p< 0.0001). Among the newborns, there was a

statistically significant difference between the ethnic groups in the mean AF size (p < 0.05). The

largest AF size was observed among the Ogoni (6.4 ± 1.5 cm) while the Hausa/Fulani had the

least (3.0 ± 3.5 cm). However at 24 months, the Bini/Esan had the largest AF size (2.2 ± 1.8 cm)

followed by the Hausa/Fulani (1.4 ± 0.0 cm).

It is concluded that there is a strong negative correlation between the AF size and OFC.

This relationship, mathematically represented by the formula AF size = 14 - 0.265 x OFC can be

utilized to derive the expected AF sizes of infants from the OFC especially in a busy clinic setting

instead of physical measurement which is cumbersome and time consuming. This can assist in the

early identification of infants whose AF sizes deviate significantly from expected values for age

and who may benefit from further evaluation.

1

INTRODUCTION

Examination of the anterior fontanel (AF) forms an essential part of the neuro-developmental

evaluation of newborns and offers the physician the possibility of determining changes in

intracranial pressure and abnormalities of skeletal development in infancy.1-3 The word ‘fontanel’

originated from the Latin word ‘fonticullus’ and the old French Word ‘fontaine’ meaning little

fountain or spring.4-6 Fontanels are the fibrous membrane-covered gaps created where more than

two cranial bones are juxtaposed as opposed to sutures which are narrow seams of fibrous

connective tissues that separate any two flat bones of the skull.1,6,7

Variation in size is a key feature of the normal AF.1,3,8 The size of the AF is influenced by factors

such as gestational age, post-natal age and gender as well as by racial and environmental factors.8-

12 Faix,12 in 1982 reported larger AF size in Black neonates compared to their White counterparts

while some Researchers3,9,10,12 have documented increasing AF sizes with advancing gestational

age. In contrast to the findings by other Researchers,9,10,12-16 Mir and Wieslaw11 reported a

significant gender difference in the size of the AF. Kiesler and Ricer3 have put the average time of

closure of the AF at 13.8 months. In the study by Omotade et al14 at Ibadan Nigeria, 53% of the

subjects had a closed AF at 12 months of age.

The size of the anterior fontanel also varies widely between disease conditions and may be

abnormally large or small in certain metabolic, genetic, intra-uterine infections or endocrine

disorders.1,3,10,15,16 Palpating the AF of an infant for tension or depression can give a clue with

regards to the intracranial pressure and hydration status, respectively.1-3Ultrasonographic scan of

the brain through the anterior fontanel demonstrates a satisfactory view of the cerebral anatomy

and ventricular system.17 This can facilitate the early identification of intra cranial anomalies such

as intraventricular haemorrhage, hydrocephalus, cerebral oedema and loss of brain tissue in the

peri-ventricular region (later recognized as peri-ventricular leukomalacia [PVL]).17-19 Common

2

causes of large and or delayed closure of the AF include hydrocephalus, achondroplasia,

hypothyroidism, Down syndrome, raised intracranial pressure and rickets, while the commonest

cause of premature closure of the fontanel is craniosynostosis.4,8,15

There is a dearth of data on the size of the AF in Nigeria in particular and Africa in general

compared to Western nations.14 The range of normal values of various anthropometric parameters

including AF sizes have been established for Caucasian and Asian populations.20-22 In view of the

established racial differences in anthropometric parameters, which are genetically determined,

Caucasian figures may not be universally applicable. Hence there is need to obtain local values

from well-defined populations as a reference in the evaluation of the child with dysmorphic

features in order to avoid errors of classification due to differences arising from variations in the

normal range.1-3,11 Since the size of the AF also varies widely in various disease conditions,

knowledge of the range of normal sizes of the AF derived from a given community which can

then be regarded as reference values for that population is essential for early detection of such

diseases in order to ensure early treatment and a better outcome.

The available works by Nigerian Authors were carried out mainly in South-West Nigeria by

Ogunye et al,23Omotade,24 Omotade et al14 and, Adeyemo and Omotade9and in South Eastern

Nigeria by Ibe and Nwosu25 and Uzoukwu.26 Whereas Omotade et al14 and Ogunye et al 23

reported mean AF sizes of 4.0 cm ± 1.0 and 3.3 ± 2.0 cm among Yoruba neonates at Ibadan and

Ile-Ife respectively, Uzoukwu26 reported a mean AF size of 2.78 ± 0.82 cm among Igbo neonates

in Enugu. It does appear, therefore, that even within a given race, the size of the AF also varies

between the ethnic groups. However, the factors responsible for these differences are yet to be

determined. Moreover, while the study by Omotade et al14 was carried out in children from birth

to 12 months of age, the other Nigerian studies9,24,26 were limited to the neonatal period. Since the

AF may remain patent up to 24 months of age, reference values for AF sizes in Nigerian children

up to 24 months of age are necessary in order to identify deviations from normal in children from

3

birth to 24 months of age. To the best of this Researcher’s knowledge, no similar study has been

done in the South-South Geopolitical Zone nor did this Researcher come across any Nigerian

study on the size of the AF in children up to 24 months of age. This study was therefore carried

out to determine variations in the size and time of closure of the AF from birth to 24 months of

age in Nigerian children in Port Harcourt.

4

REVIEW OF LITERATURE

Overview of the anterior fontanel

At birth, the human baby has six fontanels – the anterior, the posterior, the two mastoid and the

two sphenoid fontanels.2,3,7,9 The diamond shaped AF is the largest and most significant for

clinical purposes.3,7 Useful information can be obtained from examining an infant’s AF as it offers

the clinician a window into an infant’s developing brain and general state of health.1-3,7,17

Studies3,12,16 have shown that the mean AF size in Black newborns is larger than published figures

for Caucasian and Asian populations, but at 12 months the reverse is the case. Due to the wide

variations in the size of the AF in health and disease, it is necessary to have local reference values

for a given population. Such reference values will help clinicians in the early diagnosis of

conditions associated with abnormal fontanels.3,12-15,18

Historical perspective

Interest in the size and time of closure as well as clinical correlation of the AF dates back more than

a century. Early observers28,29 had reported that the dimensions of the AF of the human skull

increases from the time of birth until about the age of 9 months, and that it is, as a rule, closed by

the age of 18 months.13, 28,29 Scammon and Adair 27 reviewing the literature challenged these

observations on the grounds that the subjects studied were European children of the poorer classes,

with many of them born prematurely and with many suffering from rickets. The Authors27 argued

that the observations did not necessarily apply to the 'better’ nourished and more rapidly growing

American children but they did not publish any figures to substantiate this view.

In 1978, Researchers18 at the University College London discovered a very important

clinical application of the AF when an ultrasound probe was accidentally placed over the AF

revealing an astonishing view of the ventricular system and cerebral tissues.18 This was found to

facilitate the early identification of intra-cranial anomalies such as intraventricular haemorrhage,

5

hydrocephalus, cerebral oedema and loss of brain tissue in the periventricular area later

recognised as periventricular leucomalacia.

Among the Igbo of Nigeria, a patent AF known as ’ntiwaisi ’is believed to be the underlying

cause in a child who is failing to thrive including neonates who had intrauterine growth

restriction.26 For this reason, different harmful unorthodox practices are employed in an attempt to

treat it. Famous among these is the topical application of clay based herbal concoction over the

AF predisposing the child to the risk of scalp infection and meningitis.26

Embryology of the fontanels

In foetal life, bone formation begins at the 4th week of intrauterine life.3,29 The flat bones of

the skull which form the borders of the fontanels are derived from mesenchyme originating from

the neural crest cells that differentiate directly into bone via intra membranous ossification.3,6,13,29

These flat bones are separated by narrow seams of fibrous tissue called sutures. Fontanels are

expansions of suture lines formed where more than two flat bones meet.

Anatomy of the newborn skull and the fontanels

The skull is made up of several layers, the neurocranium which forms the protective covering

surrounding the brain and the special sensory organs, the viscerocranium which forms the facial

skeleton, ear ossicles, hyoid bone, laryngeal and tracheal cartilages and certain processes of the

skull, and the dermatocranium which forms the large flat bones of the skull and face including the

frontal, occipital and squamous temporal bones.2, 3,7,13,29 The newborn skull, which appears to be

a single large bone is actually made up of one occipital, two parietal, two temporal and two frontal

bones, separated by fibrous connective tissue called “sutures.''3,4,7,13,29 A suture is considered

widened if its width is broader than 1centimetre (cm).30

There are four cranial sutures: 3,4, 29

(a) The metopic suture : This extends from the top of the head down the middle of the forehead,

6

towards the nose. The two frontal bone plates meet at the metopic suture.

(b) The coronal suture: This extends from either side of the anterior fontanel to the sphenoid

fontanel, between the frontal and parietal bones.

(c) The sagital suture: This lies in the median position between the parietal bones extending from

the AF to the posterior fontanel.

(d) The lambdoid suture: This extends across the back of the head. Each parietal bone plate meets

the occipital bone plate at the lambdoid sutures.

At birth there are six fontanels, namely:

(1) The anterior fontanel (AF) (Fig. 1): The AF is the largest of the fontanels and the most

important for clinical purposes.3,7,9 It is located in the antero-median position at the junction

of the coronal and sagital sutures. It has been described variously as “diamond-shaped'', and

''rhomboid-shaped''.3,7,13However, most Authors3,4,10,15 agree that it is an irregular

quadrilateral. There appears to be no significant difference between the length (anterior-

posterior distance) and the width (transverse distance) of the AF. 3,31,32

(2) The posterior fontanel (Fig.1): This is located in the postero-median position at the junction

of the sagital and lambdoid sutures. It is triangular in shape, and smaller than the AF with

most admitting only the tip of a finger.31

(3) The sphenoid fontanels (Fig.1): These are a pair of fontanels, located antero-laterally at the

junction of the parietal, temporal and frontal bones.4,13,17

(4) The mastoid fontanels (Fig.1): These are also a pair of fontanels located postero-laterally at

the junction of the parietal, squamous and occipital bones3,13,17

7

FIGURE 1: Lateral and superiorviews of the newborn skull showing the anterior and

posterior fontanels [Source - Kiesler J, Ricer3 R. The Abnormal Fontanel. Am Fam

Physician 2003; 67: 2547-52].

In the course of delivery, the sutures provide spaces between the developing bones which

permit changes of skull shape and size called “molding” 3,33 These changes aid delivery through

the birth canal and usually resolve by three to five days of life.2,13 The fontanels allow for rapid

growth of the brain during infancy. Growth of the cranium is triggered by brain growth, two thirds

of which occur by two years of life, and with the exception of the metopic sutures between the

frontal bones, the sutures remain open until brain growth ceases in the second decade of

life.3,13The size of the fontanels is therefore influenced by brain growth, dural attachments, suture

development and osteogenesis3,34

Size of the anterior fontanel

As pointed out by various researchers,3,8,9,15variation in size is a key feature of the AF. By

definition, the AF size is considered small or large when its size is 2 standard deviations (SD)

below or above the mean for a given population.8,24Popich and Smith8 studied 201 healthy term

Caucasian neonates and found a mean AF size of 2.1 ± 1.5 cm. These Researchers took their

8

measurements at 2 weeks of age which certainly obviates the effect of molding. However, at two

weeks, one wonders if the initial increase in the size of the AF in the first few months of life had

not commenced. A longitudinal study at 2 weekly intervals may be required to confirm this.

Srugo and Berger,35 measured AF size on the 3rd day of life in 303 Israeli neonates from different

ethnic groups and found a mean AF size of 2.06 ± 0.6 cm. This value is similar to that by Popich

and Smith; and based on the timing of the measurement at 3 days of life can be regarded as a

baseline value with which subsequent values could be compared. These figures agree with the

mean AF sizes of 2 x 2 cm2 and the 4 cm2 reported by Haslam2 in Philadelphia (USA), and

Philips32 in Hawaii, respectively. Pedroso et al36 found a mean AF size at birth of 1.77 cm among

Brazilian neonates. The study involved 33 neonates selected randomly from a total of 1066. The

actual age of the neonates at which the measurements were taken was not stated. The small

sample size in this study may have contributed to the small mean AF size reported.

Faix12 in America comparing mean AF size in Black and White term newborns, observed a

larger mean fontanel size in Black infants. The mean AF sizes in Black and White infants were

2.67 ± 0.70 cm and 3.08 ± 0.80 cm respectively. The reason for this difference was not clear

although it was thought to be due to better nutrition in the Caucasian newborns.

Chang and Hung31 studied 704 Chinese children aged 3 days to 12 months. Measurements

were taken at 3 days and at 1, 2, 4, 6, 9, 12, 18 and 24 months of age, respectively. The mean AF

size obtained at 3 days was 26.2 millimetres (mm) and 26.7 mm for females and males,

respectively. On account of the large population size studied as well as the timing of the

measurement in neonates at 3 days of life, it is reasonable to assume that these figures are

representative of Chinese neonates.

Mattur et al37 working among Indian children in Kampur reported a mean AF size of 3.37 ±

0.61 cm with a range of 2.2 to 4.5 cm. This is similar to the larger anterior fontanel size in Blacks

9

compared to Caucasians reported by Faix.12 Whether this reflects a closer genetic link between

people of Indian and African descent remains to be determined. It is also possible that this

similarity relates more to the nutritional status of children in both populations.

Ogunye et al23 at Ife studied 1,137 African neonates and found a mean AF size of 3.3 ± 2.0

cm with a range of 1.0 - 6.2.0 cm.23 These figures are similar to the American Negroid population,

and significantly higher than Caucasian values. Since the study criteria excluded known causes of

delayed closure of the AF, like achondroplasia, hypothyroidism and malnutrition, the Researchers

suggested that the relatively higher AF size could be due to delayed intrauterine osseous

maturation which may be a Negroid trait present as a ‘‘minor malformation'' and therefore a

Negroid genetic marker.23Adeyemo and Omotade9 in a study of 200 appropriate for gestational

age term neonates 12 - 48 hours old reported a range of AF size of 1.0 cm to 6.4 cm with a mean

of 4.0 cm. The mean AF size reported in their study9 was larger than previously reported Nigerian

figures,14 a fact which may be due to the exclusion of neonates who still had overriding cranial

bones (from excessive molding) at the time the measurements were taken. This point was not

considered by Ogunye et al.23 Omotade et al14 studied 337 infants aged 1 week to 12 months and

found that the mean AF size fell from 3.4 cm at birth to 0.8 cm at 10 -12 months.

Recently in Enugu, South-East Nigeria, Uzoukwu26 studied 316 Igbo appropriate for

gestational age neonates and found a range of fontanel size of 0.7 cm to 4.8 cm, with a mean size

of 2.78 ± 0.82 cm. The mean AF size obtained by Uzoukwu26 is significantly smaller than the

values reported by the other Researchers from the Western part of the country. The reasons for

these differences are not clear. It is interesting to note that the various studies from the South West

9,14,23,39 were conducted among predominantly Yoruba subjects while Uzoukwu26studied only

Igbo newborns. It is thus possible that there are ethnic differences even among people of the same

race. The role of environmental factors in modifying natural predisposition also remains to be

determined.

10

The posterior fontanel

This triangular shaped fontanel is smaller than the AF,6,7,29 (Fig.1). At birth, it has an average size

of 0.5± 0.22 cm in White infants and 0.70 ± 0.45 cm in Black infants.7,33 The posterior fontanel

may occasionally be closed at birth.3,13 At Ibadan, Adeyemo et al14 found a mean (SD) posterior

fontanel size of 1.4 ± 1.7 cm with a range of 0.0 cm to 5.5 cm. However, the posterior fontanel

was not palpable in 49.5% of the neonates studied. Ogunye et al23 at Ile-Ife, noted that posterior

fontanel was palpable in 45.4% of neonates. The sizes ranged from 0.5 cm to 4.0 cm with a mean

of 1.5 ± 0.8 cm. The anterior and posterior fontanels are commonly examined in routine clinical

practice. Consequently, some authors1,3 recognize them as the only fontanels on the skull of a

newborn. However, this is not so.

Other fontanels

These include the two mastoid fontanels and the two sphenoid fontanels. The mastoid and

sphenoid fontanels as described previously are located on each side of the skull. Although these

fontanels are regarded as less important clinically, some Researchers affirm that trans-fontanel

ultrasound scan of the brain through the mastoid fontanel gives a better view of infra- tentorial

structures. 13,18

Evolution of the fontanels after birth

The membranous bones of the skull enlarge by central resorption and by apposition of new

layers at the edges of the sutures. Ossification starts at about the 9th to 10th week gestational age,

and progresses with gestational age.1,3,26,31 At birth, a term baby's cranial vault is firm, with a

thickness of about 1 to 2 mm, but may depress to pressure along the borders of the bones

producing the popping in and out sensation of a ping-pong ball. This is due to a lag in ossification

at the peripheral portions of the bones.34 Growth of the cranium takes place in response to the

11

growth of the brain which it contains, two thirds of which occurs by two years but continues well

into the second decade of life.1,3.31

The size of the AF is influenced by brain growth, dural attachments, suture development

and osteogenesis1,3,9 It undergoes an initial phase of increase in size during the first few months of

postnatal life, and subsequently reduces after the first six months of life until eventual

closure.3,9,8,3,15,26 In certain cultures such as the Igbo of South-Eastern Nigeria, this initial increase

in an AF size known as 'ntiwaisi' is a major source of concern to parents who worry that it might

result in delayed closure. It is also sometimes mis-interpreted to be the underlying factor in a child

who is failing to thrive.26This is responsible for the wrong cultural practice of topical application

of clay-based herbal mixture on the scalp over the AF area which is thought to reduce the size and

hasten its closure.

In 1988, Chang and Hung31carried out a study of 704 Chinese subjects in Taiwan. They

stratified the subjects into 10 groups recruited from the Nursery and Well Baby Clinics. The ages

of the subjects at the time of measurement of the AF were 3 days, 1, 2, 4, 6, 9, 12, 18 and 24

months. The mean AF size at these ages were 26.2 mm, 24.9 mm, 25.7 mm, 20.2 mm, 14.9 mm,

11.5 mm, 10.2 mm, 13.0 mm and 12.1 mm, respectively. The initial increase in size of the AF

noted in other studies was not observed in this study possibly because the criteria for the selection

of the subjects were neither clear nor specific. However, the tendency for the AF to progressively

decrease in size after 6 months is in conformity with existing literature.2,3,6,8 The AF was closed in

5% of the subjects at six months of age, while at 24 months of age, 8% of the subjects still had

patent AF. It is difficult to conclude that this 8% with delayed closure of the AF are normal

variants since the selection criteria are unclear. No significant gender difference in the mean AF

size was observed. The mean age of closure of the AF of 14.5 months in males was similar to the

14.3 months in females.

12

In another study, Tan16 monitored the evolution of the fontanels till eventual closure in two

groups of normal Chinese infants with normal occipito-frontal circumferences (OFC). The first

group made up of 28 term neonates had widened cranial sutures (greater than 1cm) and large AF,

while the second group (the control) consisted of 60 term neonates with normal cranial sutures,

OFC and fontanels. Skull x-rays were taken of the entire group to exclude cranial anomaly. The

mean AF size of 2.05 ± 0.45 cm at birth showed an initial increase in the first few months of life

followed by a gradual decrease such that by 55 weeks and 18 months, the AF had closed in 25%

and 55% respectively while at 24 months, the AF had closed in all but one subject.16 No

significant relationship was observed between AF size and OFC, and there was no gender

difference with respect to AF size and time of closure.16 The mean AF size among the group with

wide cranial sutures (2.8 ± 0.4 cm) was significantly larger than that the control group (2.05 ±

0.45 cm, p< 0.01). However, similar pattern in terms of decrease in AF size and time of eventual

closure was observed. It thus appears that the width of the sutures in the absence of any pathology

does not influence the post-natal growth of the fontanels. Although skull X-ray may be useful in

excluding certain cranial abnormalities, there are many other anomalies of the cranium and

intracranial structures which influence the size of the AF but which cannot be excluded by the use

of skull x-rays alone. Also the exposure of these infants to X-rays would seem an unnecessary risk

since enough evidence abound in the literature of the adequacy of clinical method in the

assessment of anterior fontanel size.8,16,26,39

In another study of AF size in Kampur, India, among 445 children from the neonatal period

to 2 years of age, Mattur et al37 found a mean AF size of 3.37 ± 0.61 cm. The AF was closed in

40%, 70.4% and 91.3% at 12, 18, and 24 months, respectively. The mean AF size in these Indian

children was higher than that of their Western8,10,12, counterparts and those reported earlier in

some Indian studies40,41 but was similar to some other Indian studies,42,43 as well as values

obtained from studies among Black children.

13

The differences were attributed to regional variation and to poor socio-economic status of a

majority of the subjects while the delayed closure was attributed to under nutrition, a known

course of delayed closure of AF.16 This explanation appears contradictory when viewed against

the fact that the Researchers stated that the subjects had weight for age between the 3rd and the

95th percentiles, and that children with protein-energy malnutrition were excluded from the study.

Perhaps, the Authors did not adhere strictly to their exclusion criteria. Alternatively there may be

need to clarify further the definition of the term 'under-nutrition' said to be prevalent among the

populace.

In Zurich, Duc and Largo44 carried out a study on the size and time of closure of the AF in

111 term and 131 preterm infants. The AF size was taken as the average of both oblique

dimensions as opposed to the average of the antero-posterior and lateral dimensions used by other

Researchers.8,9,11,15,29 When gestational age was corrected for the preterm babies, the size of the

AF was similar in both groups. AF size was comparable in both male and female infants and

subsequent progressive decrease in AF size with age which followed the same pattern in both

term and preterm infants. The Authors found that the AF was closed in 1% of infants by three

months of age, 38% by 12 months and in 96% by 24 months of age. The 38% and 96% closures

in the study44 was similar to the 40% and 91% reported by Mattur et al37but different from the

55% closure at 24 months reported by Chang and Hang.31 Although AF closure occurred earlier in

boys compared to girls in the study by Mattur et al,16 the initial AF size was not predictive of the

time of final closure nor was there a significant relationship between AF size and OFC. In the

study of Brazilian children by Pedrosoet al,37 it was closed in 6-13% of subjects at 6 months and

in 27 % at 12 months. The study was limited to the first year of life but a 2 year follow-up study

found 98-100 % closed AF with a mean time of closure of 13.8 months.36

In a cross sectional study of 337 children at Ibadan, Nigeria, Omotade et al14 found a mean

AF size of 3.4 cm. This progressively decreased such that at 4-6 months, 7-9 months and 10-12

14

months, the AF sizes were 2.5 cm, 1.5 cm and 0.8 cm, respectively and was closed in 11% at 4-

6months and 53% at 10-12 months. Although the mean AF size in neonates in this study

waslarger than published figures for Caucasian and Chinese populations, at 12 months the mean

AF size of 0.8 cm in Nigerian children was smaller than the 1.2 cm and 1.7 cm for Caucasian and

Chinese children, respectively.31,44

The above figures reveal a faster rate of decline of the AF size in Nigerian children

compared to Caucasian and Chinese populations. The reason for the racial difference is not clear

considering the fact that the subjects in these studies were apparently healthy children. However,

it can be speculated that genetic and environmental factors or an inter-play between

environmental and genetic factors may be responsible. Hence the adoption of a single standard for

all races may not be appropriate. This underscores the need to generate population-specific

standards.

Closure of the AF is rare at birth, whereas the posterior fontanel is often closed at birth and

usually by 2-3 months of age.3 The median age of closure of the AF as documented by Kiesler and

Ricer3 was 13.8 months, whereas Haslam2 gave an average closure time of 18 months, with the

possibility of closure as early as 9-12 months. This shows that the time of closure of the AF also

varies widely.

Following the closure of the fontanels, the cranial bones become separated only by sutures.

This is so as to make allowance for brain growth which continues till about the end of the second

decade of life.3 Any deviation from this normal course of growth/closure of the fontanels may

most likely be a reflection of abnormalities and disease conditions.3 However, delayed closure of

the AF has been documented in an apparently healthy 4 year old Indian girl who otherwise had no

neurological or physical abnormality.45

15

Factors influencing the size and evolution of the anterior fontanel

The size of the AF is influenced by a number of factors, which include:

1. Gestational age

Although, Duc and largo44 reported no significant difference in AF sizes and eventual time of

closure between term and preterm infants, several studies9,10,26,45 have documented a strong

positive relationship between AF size and gestational age. The bones of the cranium develop in

membrane, and since fontanels are in essence expansions of the suture lines where these bones

meet, it seems logical to expect that if fontanel sizes reflect the rate of development and

ossification of the calvarium, they should be related to gestational age at birth.9

Davies et al,10 in studying such a relationship found that there was a progressive increase in

fontanel size with advancing gestational age, and a significant difference in the mean value of

fontanel size between preterm infants who were 28-32 weeks and term infants. However, similar

differences were not observed when the size of the fontanel of preterm infants who were born at a

gestational age of 33-36 weeks was compared to that of term infants.10 This study however, did

not take into account the increase in head circumference with advancing gestational age.

Malas and Sulak46 measured AF size in the foetal period and found a progressive increase with

advancing gestation which was most marked in the third trimester. Although these researchers

adopted different methods, their findings are in agreement with others showing that gestational

age does in fact influence the size of the AF in the more immature preterms but this influence

diminishes towards term. 9,10,26,45,46

Adeyemo and Omotade, 9 in a study of 250 Nigerian neonates, noted that the AF size was

positively correlated with gestational age. However, this correlation was further reduced when AF

was controlled for OFC. They also reported that AF size : OFC ratio did not differ significantly in

16

the various groups of preterm and term babies. This shows that the increase in AF size with

gestational age is independent of the OFC. However, the posterior fontanel size showed no linear

relationship with gestational age.9

II. Gender

Mir and Weislaw11 in a study of Arab infants found that there was a significant gender difference

in AF size with boys having a significantly higher AF size than girls at birth. However, the rate of

head growth was not significantly different in both males and females. In an earlier study,

Acheson and Eirlys47 had noted that despite the larger AF size at birth in boys, there was a

tendency for the AF to close earlier in boys. They concluded that skeletal maturation of the cranial

bones was geared differently from that of other bones of the body in which the female's lead in

skeletal maturation has been well documented.47 This finding may not be surprising since

preference for male children which was prevalent in that era may have resulted in better nutrition

for boys at the expense of the girl child leading to earlier skeletal maturation in male subjects.

More recent studies by Popich and Smith,8 and Tan,16 as well as Faix12 found no significant

difference in AF sizes between male and female newborn infants, although in the course of a 3

monthly follow-up, Popich and Smith8 found that the mean values for males tended to be higher

than those for females during the first six months. Pedroso et al37also noted that in the first year of

life, the AF was larger in boys than girls although the difference was not statistically significant.

The reason for the varying results is not clear. Similar comparative study may help to clarify the

presence or otherwise of gender difference in the evolution of the AF.

III. Race

Some researchers have documented variations in the size of the AF between different

races.11,12,15,23Popich and Smith8 in 1972 reported mean AF size of 2.6 cm in White neonates. At

the Duke University Medical centre, USA, Faix12 carried out a comparative study of 293 Black

17

and 73 White neonates. He found that the mean fontanel size was higher in Black neonates. These

infants had weight and head circumference between the 10th and 90th percentiles, respectively. The

values /obtained were 2.67 ± 0.70 cm for Whites and 3.08 ± 0.80 cm for Blacks. According to

Faix,12 the basis for this racial difference in fontanel size is unclear, but it is possible that

differences in nutritional status may be a factor.

In another study, Philips32 found no racial differences in AF size in a group of 63 Oriental,

White, and racially mixed term babies. However, all the subjects in the study were small for

gestational age which may have resulted from intra-uterine growth restriction, a factor known to

affect osseous maturation. This may account for the similarity in AF sizes in the different racial

groups.

Adeyemo et al,39 at UCH Ibadan found AF and posterior fontanel sizes that were 4.0 ± 1.0

cm and 1.4 ± 1.7 cm, respectively. These values are larger than those from Caucasian

populations. About 2/3 of the term neonates in Adeyemo et al's39study had AF sizes that were

larger than the upper limits reported for White American neonates by Popich and Smith.8 These

results are consistent with other works that have documented larger AF size in black neonates

compared to their Caucasian counterparts.12,23,32 Ogunye et al,23in a study of 1,137 African

neonates reported a mean AF and posterior fontanel sizes of 3.3 ± 2.0 cm and 1.5 ± 0.8 cm,

respectively. These values were significantly higher than published values for White American

neonates but similar to the AF sizes of American Negroid populations.12 Known causes of

abnormally large AF such as rickets, congenital hypothyroidism, achondroplasia, trisomies and

malnutrition were excluded by these Researchers.23 The reason for the larger fontanel size in

Black neonates therefore remains unclear. However, Ogunye et al23 has suggested that this may be

due to delayed intra-uterine osseous maturation which may be a Negroid trait present as a minor

malformation, and therefore a Negroid genetic marker.

18

Furthermore, from the various studies in Nigeria, there appear to be ethnic differences, as

the AF size reported by Uzoukwu26 among Igbo neonates in the South-East Nigeria is lower than

those found among Yoruba neonates in the South-West by Adeyemo and Omotade,9 Ogunye et

al,23Omotade et al,14 and Adeyemo et al 39respectively. The reason for these ethnic differences in

AF size in Nigerian children is yet to be determined. It is possible that it is multi-factorial involving

genetic, environmental and nutritional factors.

IV. Genetic influences

Ample evidence abound in the literature in support of the idea that the development of

facial and cranial features are both under genetic (autosomal and X-linked dominant and recessive

inheritance) and non-genetic influences.48 Poswillo48 described a model for mandibulo-facial

dysostosis which occurred after feeding pregnant rats high doses (75,000 to 100,000 IU) of

vitamin A on the 8th day of gestation. The resultant morphologic effect produced was similar to

that due to autosomal dominant gene for Treacher- Collins syndrome.48The typical physical

features include downward slanting eyes, micrognathia, conductive hearing loss, underdeveloped

zygoma, drooping of the lateral part of the lower eyelids, and malformed or absent ears.48 This

finding suggests that different factors produce the same teratogenic effect in different species.

Some Authors48 have, therefore, hypothesized that AF size may be under genetic influences

Melnick et al49 studied the limits of genetic variance in twin populations. Their subjects

were 94 monozygotic (MZ) and 187 dizygotic (DZ) twins. The Researchers also analyzed Black

and White infants separately. Their findings showed no significant chorion effect but the within

pair mean square estimates of genetic variance were highly significant for both Black and White

infants. Qualitative traits in terms of ‘’open’’ vs‘‘ closed’’ and ‘‘concordance’’ vs ‘’discordance’’

were evaluated at 12 months for both twin pairs. No significant difference in proband

concordance rates was observed in both DZ and MZ twins and the Researchers concluded that AF

19

developmental variation has a significant genetic component at 4 months, but not at 12 months.

They attributed this to the rapid brain growth which occurs between 4 to 9 months of life. These

Researchers, however, did not explore the influence of the intra-uterine environment or other

maternal conditions which may impact on foetal development in general and the developing brain in

particular 48

V. Environmental influences

In a comparative study in India, Chakrabarti50 measured the AF of 100 and 130 newborns

living in hilly and non-hilly areas in the district of Darjeeling. He found a significant difference

between the mean AF sizes of the two groups, which were 3.35 ± 1.07 cm and 3.80 ± 1.95 cm,

respectively and concluded that environmental factors such as topography and altitude may have

some influence on ossification and therefore impact on the size of the AF. It is not clear however,

whether the Researcher considered other variables before arriving at this conclusion.

Relationship between anterior fontanel size and occipito-frontal circumference

Various Researchers9,23,26,44 have documented the relationship between AF size a.nd OFC.

Tan16 found no significant association between AF and head circumference. The same finding was

documented by Duc and Largo.44This suggests that at term, increasing OFC with advancing

gestational age (GA) has no effect on the AF size. A negative correlation has instead been

documented by Duc and Largo,44 though it was not statistically significant. Adeyemo et al9 as

well as Uzoukwu26 found no correlation between OFC and AF in term neonates. Ogunye et al23 at

Ile-Ife, Nigeria found a mean OFC of 34.2 ± 3.5 cm, with a range of 27.6 – 40.0 cm. The larger

fontanel size in this series did not correlate with increase in OFC. Since the study population was

unselected, the dimensions obtained may not necessarily represent normal ranges for a healthy

population. To the best of this Researcher's knowledge, there are no previous Nigerian studies on

the relationship between AF and OFC in children up to 24 months of life.

20

Relationship between anterior fontanel size and mode of delivery

In a cohort study of 33 Brazilian neonates, Pedroso et al36 reported no significant difference

in the cranial anthropometry including AF size with respect to mode of delivery, i.e., vaginal vs.

Caesarean section. As previously noted, the small sample size in this study makes it inappropriate

to draw general conclusions. A study involving a larger sample size would be required to confirm

this finding.

Relationship between anterior fontanel size and other parameters

Different Researchers have attempted to determine the relationship between the AF size and

other anthropometric parameters such as bone age, birth weight, etc. Adeyemo and

Omotade,9Ogunye et al23 and Omotade et al14 found no significant correlation between AF size

and birth weight. Ogunye et al,23Adeyemo et al,39 and Duc and Largo44 reported no significant

relationship between AF size and bone age, head circumference or other growth parameters.

Measurement of the size of the anterior fontanel

The size of the AF can be determined clinically by palpation or radiologically using skull x-

rays and ultrasound scan.9,17,18,43 The clinical method relies on determination of the mean of the

antero-posterior and transverse dimensions15 or by calculating the area of the diamond shaped

space enclosed by its boundaries.10 The measurement is best obtained in a calm or sleeping child

and should be taken in both upright and supine positions.2,34 Different Researchers have adopted

different methods in measuring the dimensions of the AF. 10,12,15,36 These include:

I. Elsasser’s method16

This method as cited by Tan,16 appears to be the foremost method employed in the study of

the AF size. In this method, the shortest distance (“diameter”) between the two parallel sides of

the anterior fontanel is measured and the mean of the two ''opposite diameters is taken as the AF

21

size. The method of determining the size of the posterior fontanel is however, not stated.

Moreover, there is a fundamental assumption that the AF has the shape of a quadrilateral.

However, according to Davies et al,10 this is an over simplification since the bony margins of the

fontanel are rarely linear. To arrive at the shortest distance between the two parallel sides of the

AF will also require that several measurements be taken which will be cumbersome and time

consuming.

ii. Popich and Smith’s method

Popich and Smith8 in 1972, obtained the range of normal size of AF among 201 term

Caucasian newborn infants, using the average of the antero-posterior and transverse diameters

(Fig. 2). The anterior, posterior and lateral extents of the fontanel were marked on the skin surface

with a water colour pen. The measurement was by means of a non-extensible tape and recorded to

the nearest millimeter. The mean fontanel size in cm was derived from the formula: [Length (L) +

Width (W) ] / 2. Since then, other Researchers have applied the same method with varying

results.9, 14 However, a major drawback of this method is the difficulty in correctly defining the

boundaries and extent of the AF in the presence of wide sutures. This was pointed out by Tan16

and Philip.32 Popich and Smith8 assessed the newborns within one to two days of birth. Any

fontanel that was too small to be measured accurately was adjudged to be closed.. The timing of

themeasurement in the subjects examined at one day of life appears flawed in that molding is

unlikely to have resolved completely within only one day.

22

Fig. 2: Popich and Smith's8 method of measurement of the size of the anterior fontanel.

iii Fleming and Pedroso’s method36

The limits of the antero-posterior and latero-lateral distances of the anterior fontanel were

obtained by the intersection of lines tangent with the inner border of the fontanel. For this, a

translucent paper is used and marks made with a non-toxic pen, aided by palpation. The size of

the anterior fontanel is given by the formula: anterior fontanel size = (antero-posterior distance +

latero-lateral distance) /2 (Fig. 3). The reproducibility of this method in infants of African descent

with luxuriant scalp hair at birth is questionable since the translucent paper can only be easily

applied on the scalp of a baby with bald head or very scanty hair.

23

Fig. 3: Fleming and Pedroso's method36 of AF measurement.

iv. Davies’s method10

Davies et al10 studied three groups of healthy neonates and determined the size of the AF in

terms of the area enclosed by the boundaries. The neonates were grouped according to gestational

age into preterm (28-36 wks), and term infants (37-42 wks). The third group comprised of small

for gestational age infants with weights less than the 5th percentile, after correcting for sex,

maternal height and birth order. Measurements were taken after 48hrs to reduce the effect of

molding. The four apices of the AF were identified and the index finger introduced in turn into

each of the four corners. A small circular dot was marked with felt pen on the skin immediately

distal to the finger. A piece of white paper was firmly pressed over the AF so that the four dots

were transferred onto the paper (see Fig. 4). This part of the procedure was done by the same

Investigator to reduce errors. The dots on the paper were joined by straight lines to form a

quadrilateral (Fig. 5). Points A and C were joined by a straight line AC which served as a

common baseline for triangles ABC and ADC.A line (a-c) parallel to AC was then drawn through

24

D. A perpendicular was dropped from the apex B of the triangle ABC to intersect the line a-c at

X.AC and BX were then measured in millimeters and the area of the squared-figure ABCD in

millimetres (mm2) was obtained by the formula: Area of ABCD = (AC x BX) / 2.

B

A C

Fig. 5:Method of calculation of the area of anterior fontanel by Davieset al.10

a

c x

D

Area of ABCD =AC x BX

2

Fig 3 Method of calculation of the area of the anterior fontanelle (Davies et al) 12

Fig. 4: Introduction of the tip of a finger to aid delineation of the extent of the

fontanel in the method of measurement of the AF by Davies et al10

25

v. Philip’s method32

Another method of determining the size of the fontanel in terms of the area was described

by Philips32 who studied 24 babies. These were small for gestational age babies who suffered

intrauterine growth retardation. The heads of the babies were stabilized by an assistant and the AF

was covered with a piece of pliable paper (paper towel) which was well applied to the scalp. The

margins of the fontanel were then traced onto the paper. Tangential lines were drawn to the curves

delineated, and from the diameters of the diamond shape curves thus formed, the area was

calculated (Fig. 6). This method is very technical and laborious and would be difficult to apply in

a large population study.

x

a

x D b x Area = a x b

2

A B

vi. Faix’s method12

Faix12 carried out a comparative study of fontanel size in Black and White appropriately

grown newborn infants. Only subjects who met the inclusion criteria were recruited. The criteria

Fig.6: Philips's Method of calculation of the area of the

AF.32

26

included babies delivered at gestational age between 37-42 weeks as determined by maternal age

and Dubowitze score, had weight and head circumference between the 10th and 90th percentile for

gestational age and who did not have any obvious evidence of disease or malformation. Racial

assignment was determined by maternal response when asked the race of her baby. A total of 293

Black and 73 White infants were studied. All measurements were taken after 48 hours of age to

allow for the resolution of molding.To circumvent the problem of where the fontanel ended and

the suture began, the limits of the fontanel dimensions were determined by the method of Davies

et al10 (Fig. 4). The index finger of the examiner was introduced into each corner of the fontanel,

and a small dot was marked with water washable ink on the scalp immediately distal to the finger

tip (see Fig. 4). A translucent white paper was applied firmly over the AF so the dots are

transferred onto the paper.

This part of the procedure was done by the same Investigator assisted by his colleague to

minimize inter-observer error. The distance between the dots along the lateral axis, and the

longitudinal axis were measured using a fresh paper tape for each infant. On multiple occasions

the paper tapes were compared with a steel tape and no discrepancies were found. The fontanel

dimensions were recorded as length (anterio-posterio dimension) and width (transverse

dimension). The elimination of observer error by one Researcher carrying out the actual

measurement would enhance the accuracy of the results obtained but would also limit the sample

size that can be studied over a given time.

Other Researchers including Chang and Hung31 in China, Adeyemo et al,39 Omotade et

al,14Ogunye et al23 as well as Uzoukwu26 in their studies in Nigeria have applied modified

versions of one or other of the above methods with varying results, one major modification being

the age at which measurements were taken. In choosing neonates 1week to 1month, Omotade et

al14 ensured that the effects of molding did not interfere with measurements obtained. This is in

contrast to the timing of the study by Adeyemo and Omotade9 in which measurements were taken

27

at 12- 48 hrs. Although, Adeyemo and Omotade9 found AF size in Blacks that is larger than

published figures for Caucasian populations, and which agreed with other studies, it is possible

that the Researchers may have obtained an even larger AF size if the measurements had been

taken at 48-72 hrs as was the case in the method by Faix12 and Tan.16

The method used by Davies et al,10 Philips,32 and Elsasser16 was based on the assumption

that the shape of the AF is that of a regular quadrilateral. As stated earlier, this is an over

simplification as the edges of the AF are rarely linear resulting in a wide variation in the shape of

the AF.

As shown above, each of the various clinical methods of estimating AF size has its own

limitations. However, Faix12 believes that if planimetry is employed, as formulated by Scammon

and Adair27 and used by other Researchers,9,10,24,32 this method may be more accurate. However,

he still concludes that all the easily performed methods of assessment of fontanel size have their

inherent limitations and it is not clear that any single method is best.12

Age of the neonate at measurement of the anterior fontanel size

In the course of labour and delivery, the newborn’s skull is ‘molded’ and sometimes

distorted resulting in abnormal head shapes. This can present as caput succedaneum (oedema

caused by pressure over the presenting part) which usually resolves in 2 to 3 days, or the firm

skull bones can be greatly molded resulting in override of the cranial sutures.51 This presents as a

step-up feel when the skull is palpated across the suture lines, as opposed to craniosynostosis51 felt

as a ridging due to premature closure of the sutures commonly involving the sagital suture. The

guiding principle has always been the need to allow time for resolution of molding of the skull

before measuring the AF size. No literature was found on the exact day at which complete

resolution of molding occurs. Various Researchers 9,12,14,15,44 have therefore carried out the

measurement of the fontanel on different days ranging from 12 hours to 1 week.

28

Whereas Faix12 assessed the fontanel after 48 hours, Tan16 did so between 24 and 72 hours

of age. Philip32 took measurements on the 2nd or 3rd day of life and Ogunye et al23 took

measurements within 30 hours of birth while Adeyemo et al9 did so between 12-48 hours of birth.

Like most physiologic parameters in the human body, there are bound to be individual variations,

making no particular day universally acceptable. However, it is generally agreed that molding

resolves after a few days,8,10,12,14,16,51 hence following the natural history of resolution of molding,

measurements taken before the end of 24 hours may be too early.

Radiological examination of the anterior fontanel

Imaging studies using X-rays can be employed in the evaluation of the sutures and cranial

bones while ultrasonography via an open AF acting as a window into the brain can be used to

assess ventricular dilatation in hydrocephalus, andintraventricular and periventricular

haemorrhages.51,52 X rays of the skull are useful in the diagnosis of wormian bone as a cause of

delayed closure or widened fontanel.3,16 Other features visible on plain radiographs include

abnormal bridging of the sutures seen in craniosynostosis, sclerosis along suture margins, and

cortical thinning and ''beaten copper'' appearance in raised intracranial pressure.53,54,55

Clinical importance of the anterior fontanel

Although Fletcher53 believes that due to the wide intra and inter racial variations in the size

of the AF as well as variation with gestational age, routine clinical measurement of AF size has

no clinical significance, several Researchers2,9,10,15,36 however, have demonstrated evidence-based

clinical applications of the knowledge of the size and time of closure of the fontanel. Reference

values for local populations are a prerequisite for determining deviations from normal.

Abnormality in the size of the AF at any age can be due to premature or delayed closure3 which

can be congenital or acquired. Important clinical relevance of the knowledge of AF is presented

below.

29

1. Neonatal cranial ultrasonography through the fontanels

Disorders of cerebrospinal fluid accumulation can readily be detected via ultrasonography

through the AF.19,53 Serial intracranial ultra sound scans through the AF can help distinguish

between progressive and static abnormalities in ventricular volume.3,52 Neonatal cranial

ultrasonography (US) has traditionally relied on the AF as the primary acoustic window,17,18,54

which displays supratentorial anatomy and disease processes very well. However, its accuracy in

demonstrating posterior fossa abnormalities is limited, due primarily to the increased distance

between the neonatal cerebellum and the transducer.56

Two alternative neurologic US imaging techniques have been emphasized in recent

literature in the attempt to redress this problem. These are imaging through the posterior fontanel

for improved detection of small intraventricular hemorrhage17,18,56 and imaging through the

mastoid fontanel for improved visualization of the brainstem, cerebellum, and subarachnoid

cisterns.3,56,57 The proximity to the brainstem and posterior fossa afforded by the alternate

windows, i.e., the posterior and mastoid fontanels allows the use of higher frequency probes in

these areas, thereby increasing the resolution.8 However, the use of the posterior fontanel for

cranial sonography is limited to the first three months of life after which it becomes closed in

most children, whereas the AF remains patent beyond 3 months of life.

The mastoid fontanel may not fuse until 2 years of age. Imaging through the posterior

fontanel and the mastoid fontanel can significantly augment the diagnostic power of neurologic

US in detecting small intraventricular haemorrhages, subarachnoid haemorrhage, and brainstem

haemorrhage and in depicting structural abnormalities of the brainstem .54 In neonates and

infants, raised intracranial pressure leads to cortical thinning and widening of the sutures, while in

older children, raised intracranial pressure causes an im-printing of the cortical gyri on the inner

table of the cranium known as ''beaten copper appearance''30

30

Wayenberg and colleagues57 demonstrated the importance of Rotterdam tele- -transducer, a

non-invasive method of monitoring intraventricular pressure. They reported their experience in

200 neonates using this method. Statistical analysis of 25 comparative measurement between AF

pressure and invasive CSF pressure showed an excellent correlation. Hence, it was concluded that

Rotterdam tele-transducer provide accurate and reproducible values of intracranial pressure.57

2. Obstetric landmark

The anterior fontanel is an obstetrical landmark because of its distinctive diamond shape.

Palpating this fontanel on pelvic exam tells you that the forehead is just beneath your fingers.

Early in labour, it is usually difficult to feel the AF. After the cervix is nearly completely dilated,

it becomes easier to feel the fontanel in a baby with cephalic presentation. Palpation of the AF in

the midline beneath the simphysis pubis indicates that the foetal head is in the direct occipito–

anterior position which is the best position for the foetal head to traverse the birth canal.58

3. Abnormalities of anterior fontanel size and age at closure

The fontanel can become abnormal either in terms of size or age at closure.8,18,51,54-57, These

can manifest as large fontanel, delayed fontanel closure, small fontanel, early or premature

fontanel closure, bulging fontanel and sunken fontanel3. The causes of the various forms of

abnormal fontanel size and time of closure are illustrated in the following sections.

Large fontanel and delayed fontanel closure

Several medical conditions are associated with a large fontanel or delay in closure of the

fontanel. 8,15,18,59-61 A large fontanel without raised intracranial pressure may be a feature of

avariety of disorders such as skeletal abnormalities, such as achondroplasia, cleidocranial

dysostosis, osteogenesis imperfecta, chromosomal anomalies (trisomy 213), hypothyroidism,8 and

31

intrauterine malnutrition.3

The most common conditions associated with enlarged fontanels and delayed closures are

congenital hypothyroidism, achondroplasia, Down's syndrome, rickets, and increased intracranial

pressure. 2,3,18 It may also be a feature of familial macrocephaly or just a normal variant.3,5

Although these conditions have widened fontanel or delayed closure as a common feature, certain

clinical and laboratory features serve to distinguish them. The common causes of large fontanels

are shown in Table I and less common causes in Table II.

Table I: Common causes of large fontanels

Condition Characteristic features

Adapted from Kiesler J, Ricer R. The abnormal fontanel.Am Fam Phys 2003; 67: 25

Achondroplasia Widened fontanel, macrocephaly, short limb dwarfism

Congenital hypothyroidism Macrosomia, large protruding tongue, cold intolerance, mental

retardation, low T3 and T4, TSH

Down's syndrome Widened fontanel, macrocephaly, short limb dwarfism

Rickets Widened wrist, beading of the ribs, cranial bossing, low vit D

Raised intracranial pressure Bulging AF, widened cranial sutures

Normal variants Otherwise normal

Familial macrocephly Affected family members

32

Table II: Less common causes of large fontanels.

Condition Enlarged Delayed closure

Adapted from Kiesler J, Ricer R. The abnormal fontanel. Am Fam Phys 2003; 67: 2547-52

Skeletal disorders

Aperts syndrome

Osteogenesis imperfecta

VATER Association

Chromosomal abnormalities

Patau syndrome

Edward syndrome

Congenital infections

Syphilis

Rubella

Drug and toxins

Aminopterine induced

Fetal alcohol syndrome

Dysmophogenesis

Beckwith- Wiedeman syndrome

Miscelleaneous

Malnutrition

Hydranecephaly

Intra-uterine growth retardation

Hydrocephalus

33

According to Popich and Smith12 , in the absence of a raised intracranial pressure, a widened

fontanel or delayed closure is an important clue to the diagnosis of athyrotic hypothyroidism or

other conditions with retarded ossification of the calvarium. An elevated thyroid stimulating

hormone level on a newborn screening test usually detects congenital hypothyroidism, but an

abnormally large AF in conjuction with an open posterior fontanel can be early signs of the

disorder, while myxedema and growth deficiency are later signs. Mental retardation is an

inevitable result of untreated or delayed diagnosis and treatment of congenital hypothyroidism.

Routine neonatal screening tests for congenital hypothyroidism are still not available in

developing countries like Nigeria, hence a high index of suspicion aroused by such clinical

findings as widened fontanel (a component of the neonatal hypothyroid index) is vital for early

diagnosis and prompt treatment. The Presence of open posterior fontanel, a third fontanel, etc, will

help physicians in resource-poor countries in the early detection of congenital ypothyroidism.3,8,63

Infants with Down's syndrome are hypotonic with varying degrees of mental retardation and

often have affectation of other systems including congenital heart defects, flat occiput and facie,

slanting palpebral fissures and low set ears.3 Achondroplasia is an autosomal dominant disorder of

the epiphysial plate cartilage that results in dwarfism. At birth, the infant has enlarged head, low

nasal bridge, prominent forehead and shortened extremities in addition to large fontanels.3, 8,28,64

Nutritional rickets resulting from Vitamin D deficiency is now rare in the United States but

is one of the most common causes of childhood diseases in developing countries.60 Risk factors

include breast feeding without Vitamin D supplementation, dark skin and low sunlight exposure.

In rickets, there is a problem of poor mineralisation and maturation of the long bones.19 One of

the early signs of rickets is craniotabes,16,18,44,60,67 a softening of the of the outer table of the

cranial bones which buckles under pressure producing a reaction similar to the indenting and

popping back out of a ping-pong ball. Other signs of rickets in the older child include widening of

34

the ends of long bones especially at the wrist and ankles, macrocephaly with bossing of the

frontal, parietal and occipital bones , and beading of the costo-chondral junctions of the ribs.1,3,64,

Skeletal growth retardation is well documented among small for date newborns, and appears to be

responsible for a significantly larger fontanel size compared to normal term and appropriate for

date infants. Phillips32 corroborated this in a study in which 10 out of 11 of intrauterine growth

retarded newborns (birth weight < 2500 g at 38-42 wks) had widened AF measuring > 4 cm.15

The Author related the AF size to the epiphysial ossification centre and found that the intrauterine

growth retarded infants had markedly reduced epiphysial ossification which supports exposure to

chronic intrauterine growth restriction.9,31,32

Normal variants

Some infants with widened fontanels who are otherwise well with no clinical or laboratory

abnormalities have been regarded as examples of normal variants.51 Tan,16 demonstrated this with

documented AF size of 2.8 ± 0.4 cm among otherwise healthy Chinese infants which was

significantly larger than the control group.16

Small fontanel and / or premature closure of the fontanel

The AF is one of the most important sites of fusion in the cranium and thus, attracts ectopic

cutaneous tissue. It is the most common site of dermoid cysts of the cranium. 62 AF closure that

occurs as early as 3 months can be within normal range, but careful monitoring of the head

circumference in such cases is essential to exclude pathological conditions. Most pathologic

conditions that lead to early closure of the AF are associated with microcephaly.1,3, 8,15,42,60 This

may be detected using a skull x-ray but this is not done routinely. Closure of the AF is said to be

premature when it occurs before 3 months of age. The most common causes of small AF or

prematurely closed the AF are craniosynostosis and abnormal structural brain development.3

Craniosynostosis is the premature closure of the cranial sutures resulting in abnormal head shape.

Craniosynostosis can be idiopathic, or due to hyperthyroidism, hypophosphatasia, or

35

hyperparathyroidism. It is also associated with more than 50 syndromes such as Aperts,

Crouzon’s and Pfeifer’s.3,15,54,61 There is a high prevalence of clinical disorders such as seizures,

hydrocephalus, increased intracranial pressure, proptosis/papilloedema, respiratory problems,

optic atrophy and deafness (SHIPROD) in patients with craniosynostosis and microcephaly 3,4 The

risk of primary isolated craniosynostosis is 0.4 per 1000 live births.

Microcephaly is defined as head circumference less than three standard deviations below the

mean for age and sex.34,35,61 Abnormal brain growth following prenatal insults to the brain such as

maternal alcohol abuse, intrauterine hypoxia or birth asphyxia8 may result in microcephaly and

thus lead to a small fontanel or early fontanel closure. Other causes of craniosynostosis include

autosomal dominant or recessive types,dysmorphic syndromes, maternal phenylketonuria, and

universal craniosynostosis3 (see Table III). Examination at birth of the infant with

craniosynostosis might reveal a ridge over a suture or lack of movement along a suture when

alternate sides of the suture is gently pressed.3, 54, 68

TABLE III: Differential diagnosis of microcephaly

Adapted from Kiesler J, Ricer R. The abnormal fontanel.Am Fam Phys 2003; 67: 2547-52.

Chromosomal abnormalities Edward syndrome, Couson syndrome, Apert syndrome

Congenital infection Congenital syphylis, congenital rubella

Foetal alcohol syndrome

Hypoxic-ischaemic encephalopathy

Malnutrition

Structural brain defects

Normal variants

36

Overriding of the cranial sutures from the normal molding process in neonates should resolve

within the first few days of life but persists in the infant with craniosynostosis. Later physical

findings in children with primary craniosynostosis include stunted head growth, increased

intracranial pressure, proptosis, strabismus and hearing impairment. In severe cases, mental

retardation may result.54,61,70 Plain radiographs of the skull are used for initial assessment and if

craniosynostosis ispresent, a three-dimensional CT scan is obtained to detect underlying brain

abnormalitiesand to assist in planning for surgery. Prenatal insults to the developing brain such as

maternalalcohol abuse, and intra and post partum hypoxia are potential causes of microcephaly.3, 69

Bulging fontanel

In children in whom the anterior fontanel is still patent, a bulging AF is associated with raised

intracranial pressure.4, 68 Palpation may reveal a tense fontanel.3The causes of a bulging fontanel

are shown in Table IV. Meningitis and encephalitis also cause temperature instability.70 In

suspected cases, a lumbar puncture should be done after exclusion of raised intra cranial pressure

and /or decompression with manitol.71,72 Cerebrospinal fluid obtained should be sent for Gram

stain, protein, glucose, cell count and culture.

Hydrocephalus can result from an imbalance between the production and absorption of

cerebrospinal fluid.73 This condition affects 3 per 1000 live births3 and may result from congenital

malformations, intrauterine infections, intra-partum IVH especially in preterm babies as well as

from post-natal infections.3 Most cases occur before 2yrs of age when the anterior fontanel is still

patent.3 Physical signs include an abnormal rate of head growth, frontal bossing, widened cranial

sutures, and dilated scalp veins. Imaging with ultrasonography, CT or MRI shows enlarged

ventricles in the absence of brain atrophy. Associated findings include poor feeding, decreased

muscle tone, respiratory difficulties, and alterations in consciousness and seizures. Intra-

ventricular bleeds are particularly common in preterm low birth weight babies due to poorly

37

developed supporting structures in the brain. Common findings include decreased muscle tone,

seizures, falling haematocrit, vomiting, and alterations in consciousness.1,3 Dermoid tumours1,3,

59,68 of the scalp are the most frequent lesions presenting over the anterior fontanel and may also

be found over the posterior fontanel. However, they are uncommon, usually slow growing, non-

tender, benign lesions. They are twice as common in girls and can be diagnosed at birth. A CT

scan is necessary to exclude intracranial involvement.3

Adapted from Kiesler J, Ricer R. The abnormal fontanel. Am Fam Phys 2003; 67: 2547-52.

Sunken fontanel.

The primary cause of a sunken fontanel is dehydration, which can result from fluid loss in

gastroenteritis,75 persistent vomiting in hypertrophic pyloric stenosis, pharyngitis and certain

Table IV: Causes of bulging anterior fontanel

CONDITION EXAMPLES

Hydrocephalus Congenital, acquired (post-infectious).

Space occupying lesion Brain tumour, intracranial haemorrhage, brain abscess,

Intracranial Infections Bacterial meningitis, encephalitis, cerebral malaria, cysticercosis

Haematologic disorders Polycythaemia, anaemia, leukaemia.

Endocrine disorders

Hyperparathyroidism, hypoparathyroidism, hypothyroidism, Addison's

disease.

Cardiovascular disorders

Congestive cardiac failure, dural sinus thrombosis.

Miscellaneous

Hypervitaminosis A, lead poisoning, brain contusion

hypoxic–ischaemic encephalopathy.

38

inborn errors of metabolism3. Other signs include reduced peripheral perfusion, loss of skin tugor

and sunken eyes.75 An abnormal fontanel at any age can indicate a serious medical condition.

Therefore, it is important to understand the variations of normal, how to examine the fontanel and

which diagnosis to consider when an abnormality is found. Consultation with a Paediadtric

Neurologist/Neurosurgeon should be considered if a diagnosis or presence of an abnormality is

unclear.

39

JUSTIFICATION FOR THIS STUDY

The existence of racial and ethnic differences in AF size is well documented by various authors

who studied Indian, Caucasian, Israeli, Oriental, Arab and Black infants in an attempt to establish

reference values of AF sizes in their localities.9,10,14,26,35This calls for caution in applying what

may be considered normal values of AF obtained from one population to another. It also

underscores the need to obtain local reference values of normal range of AF sizes for other

populations.

The few studies done in Nigeria were among Yoruba neonates in Ile-Ife23and Ibadan,

South-West Nigeria9,14,39 and recently among Igbo neonates in Enugu in the South-East.26 The

results obtained from these studies show differences between ethnic groups in the mean size of the

AF. However, the factors responsible for these differences are yet to be determined. Also whether

such differences involve other ethnic nationalities is yet to be determined.

This Researcher did not come across any published study from the South-South

Geopolitical Zone. In addition, the previous studies were in neonates and in children not older

than 12 months of age. To the best of this Researcher's knowledge, no published Nigerian studies

are available on the size of the AF in Nigerian children up to 24 months of age.

Port Harcourt, being a cosmopolitan city is inhabited by Nigerians of diverse ethnic groups.

Therefore, a study of AF size in this heterogeneous setting can produce results that may further

highlight the occurrence of ethnic differences and which may be more representative of the

normal range of AF size in Nigerian children. Knowledge of the range of normal values of AF

size can help physicians in identifying children with abnormal AF, which could be a pointer to an

underlying disease condition.

40

It is the hope of this Researcher that the results of this study can help to achieve the

following:

1. Establish the normal range of values of AF size of Nigerian children 0-24

months old in the study population.

2. Establish the normal range of values of OFC in the study population, and

3. Provide AF size and OFC charts for use as reference standards in Nigerian children.

41

AIMS AND OBJECTIVES

General objective

To determine the variations in the size and time of closure of the anterior fontanel (AF)

from 48 hours to 24 months of age in apparently healthy Nigerian children in Port Harcourt.

Specific objectives

1. To determine anterior fontanel size at 48 hours to 7 days and at defined ages (6, 10, and

14weeks and 6, 9,12, 18 and 24 months) during the first 2 years of life.

2. To determine the OFC at 48 hours to 7 days and at defined ages (6, 10, and 14 weeks and 6, 9,

12, 18 and 24 months) during the first 2 years of life.

3. To relate AF size to the OFC at 48 hours to 7 days and at defined ages during the first 2 years

of life.

4. To determine the percentage of children in whom the AF is closed at defined ages during the

first 24 months of life.

42

SUBJECTS AND METHODS

Study design

The study was a cross sectional and analytical study carried out to determine the variations in the

size a#nd time of closure of the anterior fontanel from birth to 24 months of age in apparently

healthy Nigerian children in Port Harcourt. Clearance from the Ethics committee of the University

of Port Harcourt Teaching Hospital (Appendix I), and a written permission from Braithwaite

Memorial Specialist Hospital (Appendix II) were obtained prior to commencement of the study.

Study area

Port Harcourt, the capital city of Rivers State Nigeria, lies along the Bonny River and has a

land mass of 170km.76,77 It was founded in 1912 by the British in an area traditionally inhabited

by the Ikwere. The estimated population is 1,620,214 million according to the national population

census of 2007.76 It boasts of lush green vegetation of the rain forest and mangrove types with an

annual rainfall of 196.3 cm77and temperature range of 28-33.40C. 77 Port Harcourt City is

cosmopolitan and host to major indigenous and multinational companies in the oil and gas,

manufacturing, banking, telecommunications, construction and health sectors, employing staff

from diverse ethnic nationalities. The University of Port Harcourt Teaching Hospital (UPTH) is a

Federal Government hospital and the apex health institution in Rivers State, while Braithwaite

Memorial Specialist Hospital (BMSH) located in the heart of the City is the largest State

Government hospital and acts as a referral centre for hundreds of General Hospitals and Primary

Health Centres in the state. Besides these, there are also several Private Hospitals in Port Harcourt

Metropolis.

43

Study site

The study was carried out at the Post-Natal Ward and Special Care Baby Unit (SCBU) of

the UPTH and the Well Infants Clinics of UPTH and the BMSH, Port Harcourt. The UPTH is a

Federal Tertiary Health Institution serving Rivers State and the neighbouring states of Bayelsa,

Abia, Imo, and Akwa–Ibom. It provides specialized health care in all specialties including

Paediatrics and Obstetrics and Gynaecology. The average number of newborns in the post-natal

ward is 1700 per year. The SCBU of the Paediatrics Department is located adjacent to the Labour

Ward and has a maximum capacity for 30 in-patients. Routine newborn examination is carried out

on all babies delivered in the hospital and includes measurement of anthropometric parameters

and system examination. Preterm, very low birth weight babies, infants of diabetic mothers,

babies with macrosomia and those with birth asphyxia or congenital anomalies are immediately

transferred to the SCBU for expert care. Babies who have no indications for admission or

observation in the SCBU are transferred to the Post-Natal Ward where they are allowed a further

observation time of 48 hours. Well babies are routinely discharged after 48 hours to the Post-Natal

Clinic where they are further reviewed along with their mothers at 6 weeks of age, and if well,

they are sent to the Well Infant Clinic for immunization and further health education of the

mothers. BMSH is the apex state owned tertiary health centre and acts as a referral centre for the

primary health centres especially in the area of maternal and child health including childhood

immunizations.

Study population

All newborns of Nigerian descent admitted at the Post-Natal Ward and the SCBU and all

Nigerian children aged 6 weeks to 2 years attending the Well Infant Clinics of tertiary institutions

in Port Harcourt metropolis (within the study period) constituted the study population.

44

Study group

Neonates at 48 hours to 7 days of age at the Post-Natal Ward and the SCBU and infants of 6

weeks to 2 years of age seen at the Well Infant Clinics who met the inclusion criteria were the

subjects of this study.

Inclusion criteria

The following were included in the study.

1. Nigerian neonates delivered at 28 to 42 weeks gestational age, seen in the Post-Natal Ward

who were 48 hours to 7 days old.

2. Neurologically stable, non-critically ill neonates admitted to the Special Care Baby Unit of

UPTH delivered at a gestational age of 28 to 42 weeks who were 48 hours to 7 days old.

3. Nigerian infants who were 6 weeks to 2 years of age, who were seen at the Well Infant

Clinics of UPTH and BMSH.

4. The subjects who satisfied the above criteria and for whom informed consent (Appendix III)

was given by the parents/caregivers.

Exclusion criteria

The following were excluded from the study.

1. Critically ill babies admitted to SCBU such as those with severe birth asphyxia, severe

respiratory distress, and heart failure from any cause, congenital malformations of the central

nervous system, hydrocephalus, cephalhaematoma and caput succcaedaneum.

2. Babies born to non-Nigerian parents

3. Babies less than 48 hours or > 7 days of age.

45

4. Babies with stigmata of chromosomal anomalies.

5. Babies with stigmata of hypothyroidism.

Sample size

The desired sample size was determined in two stages. First, the sample size appropriate for

an infinite population (greater than 10000) was calculated using the formula78:

n = z2pq/d2

where n = the desired sample size when the population is more than 10000,

z = the standard variation, usually set at 1.96 (which corresponds to 95% confidence interval)

p = the proportion in the target population estimated to have a particular characteristic. If there is

no reasonable estimate, then 50% is used.

q = 1.0 –p, d = degree of accuracy desired, which for the purpose of this study was set at 0.05

Substituting the values into the formula,

n = (1.96)2 (0. 5) (0.5)

(0.05)2

= 384.

However, the population of newborns at UPTH was represented by the average deliveries

per annum in the hospital which is about 1700. While for the Well Infant Clinic, the average

attendance was 1980. These population sizes are less than 10,000.

Therefore the second formula

n= n

Where nf = minimum sample size for population less than 10,000

1+(n)

N NN

(N)

46

n= the desired sample size when the population is more than 10,000

Here n = 384

N = the estimate of the population size which is 1700 for newborns and 1980 for infants

n = 384

Substituting the estimated population sizes in the above formula,

Nf = 1+384

1700

= 384

1.227

= 313

nf2 = 384

1+384

1980

= 384

= 321

Hence the minimum sample sizes for this study were 313 newborns and 321 infants in the

other age categories. A minimum number of 313 subjects was recruited in the newborn period

from the Post-Natal Ward and the SCBU, while a minimum of 321subjects was also recruited at

each of the defined ages from 6 weeks, 10 weeks, 14 weeks,6 months,9 months, 12 months, 18

months and 24 months of age respectively.

Training of research team and standardization of method of measurement

The Investigator trained 15 assistants comprising post-internship doctors and post-NYSC

paramedics. During 4-hour practice sessions, the Research Assistants were trained on the field

techniques and measurement of AF size, weight, length, and occipito-frontal circumference of the

subjects using standard methods recommended by the World Health Organization.79 The training

47

sessions were repeated until there was mastery of the techniques as evidenced by reduction of

inter-observer error to 0.1 centimetre for measurement of anterior fontanel size, OFC and length,

and 0.1kg for weight between the Investigator and the Research Assistants. The Research

Assistants were then divided into 8 groups of 2 members each with each member taking turns to

act either as a measurer or an assistant. While one member of each team read off the

measurement, the other assisted in positioning and stabilizing the subject.

Pilot Study

A pilot study was conducted at the Braithwaite Memorial Specialist Hospital using 50

subjects to determine the feasibility of the study. In the course of the pilot study, several

mothers/care-givers expressed reservation concerning the placement of white handkerchief on the

heads of their children and the marking of same with ink. Consequently, many declined consent.

This challenge was addressed by adopting a modified version of Faix's method.12 The use of

translucent white paper unto which dots made distal to the index finger introduced into the corners

of the AF were transferred in the Faix's method12 was replaced by a pair of dividers (with the

pointed tips detached) applied to the outer border of the index and middle fingers introduced into

the corners of the AF consecutively along the transverse and longitudinal axis. The data collected

at the pilot study was not part of the analysed data.

Field work

The team went as a group to the study sites and were formerly introduced to the medical

staff at these sites. The aim and scope of the study were also explained to the staff to solicit their

cooperation. The Nursing Officer in turn informed the mothers /care-givers of our mission, and

provided a work area for the team.

Prior to taking measurement of the various parameters, the newborns were assessed to exclude

those who did not meet the inclusion criteria. The gestational age of the newborns was determined

48

using the method described by Eregie,80 and corroborated by the mother based on her last

menstrual period. Using Eregie's chart for preterm babies and the Lubchencho81 chart for term

babies, an infant is considered appropriate for gestational age if its weight is between the 10th and

90th percentile for gestational age. Measurement of the AF size and OFC in the newborns was not

done earlier than 48 hours to allow for resolution of the effects of molding.12,32 The choice of the

defined ages was made because the ages corresponded to the National Programme on

Immunization schedule and facilitated the recruitment of large number of subjects. This study

was carried out over a 10-week period. Newborns with caput succaedaneum, cephalhaematoma

were excluded because these might make it difficult to accurately delineate the limits of the AF.

Data collection

The minimum number of 313 subjects was recruited in the newborn period from the Post-Natal

Ward and the SCBU, while a minimum of 321 infants were also recruited from the Well Baby

Clinic at 6 weeks, 10 weeks, 14 weeks 6 months, 9 months, 12 months, 18 months and 24 months

of age, respectively. Data were obtained by means of a Proforma (Appendix IV) designed to elicit

demographic information of the child and mother, as well as other relevant obstetric data. The

questionnaires were separated into 9 groups and labelled according to the defined ages. These

were numbered serially until the minimum sample size for each age category was reached. The

questionnaire was self-administered where the mother /care-giver is literate. For non-literate

mothers/care-givers, it was interviewer administered by the Investigator/Assistants through a face-

to-face interview.

Tools for the field work

1. A pair of dividers which had been made blunt by detaching the traumatic pointed tips

(Appendix V). Measurements taken were read-off on a non- elastic tape stretched over a table

49

Appendix VI).

2. An electronic bassinette weighing scale for infants (Appendix VII)

3. A non- extensible tape measure for measuring occipito -frontal circumference (Appendix

VIII).

4. A wooden Infantometer (Appendix IX)

5. An electronic floor scale (SECA model 874, Secagmbh 7 co.kg, Germany)

Measurement of the size of the anterior fontanel

For the purpose of this study, the size of the AF was taken as the mean of the antero-

posterior and transverse diameters measured along the sagital and coronal sutures, respectively. A

modified version of Faix’s method12 was employed. The subject was held upright in a sitting

position by the mother/care-giver with the head supported and held firmly by the Research

Assistant while the Measurer introduced the tip of the index and the middle fingers of his/her left

hand into the two corners of the lateral dimensions of the anterior fontanel. With the pair of

dividers held in the right hand, the inner margins of the distal end of the pair of dividers were

applied firmly against the outer border of the two fingers of the left hand at the corners of the

fontanel. The pair of dividers was then placed on a tape measure firmly positioned on a table and

the distance between the inner borders of the pair of dividers was read-off on the tape (Appendix

VI). The process was repeated with the index and middle fingers placed at the corners of the

antero-posterior dimension of the AF. The size of the AF in centimetres was derived from the

relationship: (length of AF + width of AF)/2, the length and width representing the antero-

50

posterior and the latero-lateral diameters, respectively. Any fontanel too small to be measured was

adjudged closed.

Occipito-frontal circumference (Appendix VIII)

To measure the occipito-frontal circumference, the method of Student2 was employed. A non-

elastic tape was placed circumferentially over the glabella, the bi-parietal and occipital

prominence (see Appendix VIII). This was read off in centimetres and recorded to the nearest

millimetre. The tension of the tape was such that the hair was firmly pressed against the head.

Three measurements were done for each child. The highest was taken as the OFC. All three

measurements in a given subject were taken by the same Investigator/ Research Assistant.

Length

Supine length was measured using a wooden infantometer/floorboard (Appendix IX). The

Research Assistant firmly held the crown of the head of the subjects against the head board, and

positioned the head in such a way that the right upper margin of the external auditory meatus and

the lower margin of the orbit of the eye were perpendicular. The Measurer then stretched the body

and the legs of the subject and brought the sliding footboard into firm contact with the soles of the

feet. The measurements were read to the nearest millimetre.

Weight

To measure the weight of the subjects, a SECA electronic bassinette scale (Appendix VI) was

used for newborns and infants not more than 12 months old. The infants were weighed naked.

Infants older than 12 months old were weighed using an electronic floor scale (SECA model 874,

Secagmbh 7 co.kg, Germany) with the subject bare footed and naked, standing still at the centre

of the scale. The accuracy of the scales used were ascertained by placing known weights on the

scales and making adjustments where necessary before commencement of weighing of subjects

each day. The scale reading was ascertained to be at zero before each reading was taken.

51

Measurements were read to the nearest 0.1kg when the pointer had stopped oscillating, with the

measurer looking directly at the scale in the vertical plane.

All measured parameters as well as gender, gestational age (for newborns), birth weight,

length and OFC were recorded on a proforma (Appendix IV)

Socio-economic status classification

Using the socio-economic classification described by Oyedeji82 each subject was assigned a socio

-economic class based on the occupation and educational attainment of both the mother and the

father. A socio-economic index score of 1 to 5 was assigned for each parameter. The sum of the 4

scores was divided by 4 to obtain the socio- economic class of the child.

Ethical Consideration

Ethical clearance was obtained from the Ethics Committee of the University of Port

Harcourt Teaching Hospital (Appendix I). A written permission (Appendix II) was also obtained

from BMSH. Detailed explanation of the study procedure and extent of involvement of each

subject was given to the mothers/caregivers. Written informed consent (Appendix III) was

obtained from the parent(s) or care-giver(s) of each child before recruitment into the study. The

children observed to have abnormal fontanel size such as those with a closed fontanel at 2 to 7

days and those with an open fontanel at 24 months were referred to the Paediatric Neurology

Clinic for follow -up.

Analysis of data

Data was analyzed using the Statistical Package for Social Sciences (SPSS) Version

15.0.83The mean, standard deviation and range of each continuous variable and other derived

indices including the 5th, 10th, 25th, 50th 75th, and 95th percentiles were computed and presented as

graphs, and tables in simple proportions. The differences in means were compared using Student’s

52

t test while Chi–square test was used to compare proportions and rates. Pearson’s Correlation

Coefficient was used to determine the relationship between AF and OFC at 48 hours to 7 days and

at defined ages. Analysis of Variance (ANOVA) was used to ascertain the significance of the

differences in the means of AF and OFC at various ages. Multiple comparisons of the differences

in mean AF between age groups was carried out using Dunnette’s83 Test. Statistical significance

at 95% confidence interval was set at p- value < 0.05.

53

RESULTS

SOCIO-DEMOGRAPHIC CHARACTERISTICS OF THE STUDY GROUP

Table V shows the distribution of the subjects. Two thousand eight hundred and ninety nine

subjects were recruited into the study. One newborn and three infants were excluded on the basis

of incomplete data due to mother's uncertainty of the child's age leaving a total study population

of 2,895. Of these, 1391 (47.5%) were males and 1504 (52.5%) females, giving a male to female

ratio of 1:1.1. There was no statistically significant difference between the proportion of males

and females in any of the recruitment ages.

Table VI shows the distribution of the newborns by gender and gestational age. Of the 313

newborns, 250 (79.9%) were term while 63 (20.1%) were preterm. The ratio of males to females

among the term and preterm newborns was 0.96:1 and 0.7:1, respectively. There was no

significant difference in gender ratio among the term newborns (p > 0.05), whereas among the

preterms the number of females (37) was significantly higher than that of males (26), (p < 0.05).

Of the 250 term infants, 146 (58.4%) were delivered at 37-39 weeks of gestation and 104 (41.6%)

at 40-42 weeks gestation. Among the 63 preterm newborns, 47 (74.6%) and 16 (25.4%) were

delivered at 33 - 36 weeks and 28 - 32 weeks of gestation, respectively.

Table VII shows the distribution of the study subjects by ethnic group. The Igbo was the

largest ethnic group followed by the Ikwere/Etche group and the Hausa/Fulani the least.

Table VIII shows the distribution of the study subjects according to social class. One

thousand seven hundred and sixty five (61%) were of the higher social classes (I and II), whereas

269 (9.3%) were of the lower social classes

54

Table V: Distribution of the subjects by age and gender

Age Male

No. (%)

Female

No. (%)

Total

No. (%)

2-7 days 153 (11.00)

160 (10.6) 313 (10.8)

6 wks. 165 (11.9)

157 (10.4) 322 (11.1)

10 wks. 167 (12.0) 158 (10.5) 325 (11.2)

14 wks. 155 (11.1)

168 (11.2) 323 (11.2)

6 mo. 159 (11.4)

166 (11.1) 325 (11.2)

9 mo. 156 (11.2)

165 (11.0) 321 (11.1)

12 mo. 164 (11.8)

157 (10.4) 321 (11.1)

18 mo. 139 (10.0)

182 (12.1) 321 (11.1)

24 mo. 133 (9.6) 191 (12.7) 324 (11.2)

Total 1391 (100.0) 1504 (100.0) 2895 (100)

χ2 = 12.34, df = 8, p = 0.137

55

Table VI. Distribution of newborns by gestational age and gender

Gestational age

Male

No. (%)

Female

No. (%)

Total

No. (%)

Preterm 28-36 wks

26 (17.0)

37 (23.1)

63 (20.1)

Term 37-42 wks

127 (83.0)

123 (76.9)

250 (79.9)

Total 153 (100.0) 160 (100.0)

313 (100)

χ2 = 1.83, df = 1, p = 0.176

56

Table VII. Distribution of the subjects by ethnic group

*Efik, Ekpeye, Ibani, Idoma, Ndoni and others

.

Ethnic Group No. (%)

Igbo 1040 (35.9)

Ikwerre/Etche 505 (17,4)

Yoruba 217 (7.5)

Urhobo/Itsekiri 215 (7.4)

Ijaw/Kalabari/Okirika 195 (6.7)

Anang/Ibibio/Oron 180 (6.2)

Ogoni 119 (4.1)

Bini/Esan 112 (3.9)

Hausa/Fulani/Tiv/Langtan, 31 (1.1)

Others* 284 (9.8)

Total 2895 (100)

57

Table VIII. Distribution of subjects by social class

So Social class No (%)

Class I

686 (23.7%)

Class II

1079 (37.3%)

Class III

861 (29.7%)

Class IV

227 (7.8%)

Class V

42 (1.5%)

Total

2895 (100%)

58

VARIATION IN ANTERIOR FONTANEL SIZE

Table IX shows the variation of mean anterior fontanel size by age and sex. There was a

highly statistically significant trend of decreasing AF size with age in both males and females

with all the p-values < 0.001 for ANOVA. There was no significant difference in mean AF size

between males and females except at 10 weeks (p = 0.029), 6 months (p = 0.04), 12 months (p =

0.008) and 24 months (0.002). The correlation between AF size and age in both males and

females is illustrated graphically in the scatterplot on page 63

Table X shows the mean AF size of term and preterm newborns. There were no significant

differences between males and females or between term and preterm newborns, all p values being

> 0.05.

The results of multiple comparisons of differences in mean AF size between the different

age groups is shown in Table XI. There was a statistically significant difference (p < 0.001)

between the mean AF size of newborns and those of infants aged 6 months, 12 months, 18 months

and 24 months. There was also a statistically significant difference (p < 0.001) between the mean

AF size at 6 months and at 12, 18 and 24 months, and between those at 12 and 18 months. There

was no significant difference (p > 0.05) between the mean AF size at 18 months and 24 months.

Figure 7 is a scatterplot illustrating the variation in AF sizes with increasing post-natal age.

There was a strong negative correlation between AF size and post-natal age in both males (r = -

0.747; p < 0.001) and females (r = -0.782; p < 0.001). The mean AF size in males was

significantly higher than that in the females, with more females having a closed anterior fontanel

with advancing post-natal age beyond 9 months of age (p < 0.05).

59

Table IX. Variation in mean AF sizes by postnatal age and gender

Post Post natal age

Anterior fontanel size (cm)

Male Female All Subjects t-test p-value

No. Mean (SD) No. Mean (SD) No. Mean (SD)

2-7 days 153 4.5 (1.6) 160 4.5 (1.8) 313 4.5 (1.7) -0.06 0.096

6 wks 165 4.3 (1.5) 158 4.2 (1.3) 323 4.3 (1.4) 1.18 0.239

10 wks 167 4.1 (1.3) 158 3.8 (1.6) 325 3.9 (1.5) 2.19 0.029

14 wks 154 3.6 (1.2) 168 3.5 (1.2) 322 3.6 (2.2) 0.43 0.667

6 mo 158 3.3 (1.2) 167 2.9 ( 1.4) 325 3.1 (1.3) 2.21 0.028

9 mo 156 2.3 (1.3) 165 2.6 (1.3) 321 2.5 (1.2) -1.45 0.148

12 mo 164 2.0 (1.6) 157 1.6 (1.0) 321 1.8 (1.3) 2.67 0.008

18 mo 140 0.3 (0.7) 181 0.1 (0.4) 321 0.2 (0.6) 1.89 0.060

24 mo 134 0.4 (1.0) 190 0.1 (0.4) 324 0.2 (0.7) 3.08 0.002

All Subjects 1391 2.9 (2.2) 1504 2.5 (2.0) 2895 2.7 (2.1) 4.39 0.001

*F 226.93 16.07 537.37

p–value < 0.001 < 0.001 < 0.001

*F statistic for ANOVA

60

Table X. Variation of mean AF sizes of newborns by gestational age and gender.

Gestational

age

Anterior fontanel sizes(cm)

Male Female All Subjects t-test p-value

No. Mean (SD) No. Mean (SD) No Mean (SD)

Preterm

28-32 7 4.4 (1.8) 9 3.8 (2.0) 16 4.0 (1.9) 0.62 0.545

33-36 19 4.5 (1.7) 28 4.5 (2.2) 47 4.5 (2.0) 0.05 0.957

Term

37-39

68

4.6 (1.7)

78

4.6 (1.8)

146 4.6 (1.8)

0.07

0.942

40-42

59

4.4 (1.4)

45

4.5 (1.4)

104 4.4 (1.4)

-0.31

0.757

All

Subjects

153

4.5 (1.6)

160

4.5 (1.8)

313 4.5 (1.7)

0.05

0.958

*F 0.18 0.56 0.61

P-value 0.910 0.642 0.608

*F statistic for ANOVA,

61

Table XI. Dunnett’s multiple comparisons of differences in mean AF size between different age groups

Age

Category

(J) Age

Category

Mean

Difference

(I-J)

95% Confidence Interval

p-value

Lower

limit

Upper

limit

2 - 7 days

6 months 1.38 1.06 1.71 < 0.001

12 months 2.72 2.39 3.06 < 0.001

18 months 4.30 4.03 4.58 < 0.001

24 months 4.28 3.99 4.56 < 0.001

6 months

12 months 1.34 1.06 1.63 < 0.001

18 months 2.92 2.70 3.13 < 0.001

24 months 2.89 2.67 3.12 < 0.001

12 months 18 months 1.58 1.36 1.8 < 0.001

24 months 1.55 1.32 1.78 < 0.001

18 months 24 months -0.025 -0.16 0.11 > 0.05

Mean difference and 95% confidence interval are given in cm

62

Figure 7: Scatter plot of variations of AF size by postnatal age and gender

p-value< 0.05

Females R2 Linear = 0.612

Males R2 Linear =0.558

63

The variation in percentile of anterior fontanel size with age is illustrated in Table XII. The

5th, 50th, and 95th percentiles of the AF size at birth were 1.3, 4.7 and 6.7 cm. At 24 months, the

values were 0.0, 0.0 and 1.4 cm respectively. The variations in mean AF size with increasing post-

natal age was statistically significant (ANOVA = 537.37 p < 0.001). The variation in 5th, 50th, and

90th percentiles with age is illustrated in Fig. 8.

Table XIII shows the relationship between AF size and social class at the different ages

studied. Among the newborns, the AF was largest in the subjects belonging to social class V and

least in those of class II. The subjects belonging to social class I had the largest AF size at 2-7

days, 10 weeks, and at 14 weeks of life while the AF size was least in those belonging to class V

at 9, 18 and 24 months of age. The difference in the mean AF sizes between the various social

classes was highly statistically significant in all the age categories except at 2-7 days, 14 weeks, 6

months and 18 months. A graphical illustration of the differences in mean AF size between the

subjects belonging to low, middle and high socio-economic classes is shown in Figure 9.

Table XIV shows the variation in mean AF size among newborns by ethnic group. Those

from the Ogoni ethnic group had the largest AF (6.4 ± 1.5 cm) while the Hausa/Fulani had the

smallest (3.0 ± 3.5 cm). There was a highly statistically significant difference between the mean

AF size of different ethnic groups (p < 0.001).

64

TABLE XII. Mean, range and percentiles of AF in the study group

Age

Days

Weeks

Months

AF Characteristics 2-7

(n = 313)

6

(n = 323)

10

(n = 325)

14

(n = 322) 6

(n = 325)

9

(n = 321)

12

(n = 321)

18

(n = 321)

24

(n = 324)

Mean size ± SD 4.5

±1.7

4.2

±1.4

3.9

±1.5

3.7

±2.2

3.1

±1.0

2.5

±1.3

1.8

±1.3

0.2

±0.6

0.0

±0.7

Minimum size 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0

Maximum size 7.9 6.6 6.9 3.6 6.6 5.0 4.7 3.3 0.0

5th centile 1.3 1.8 1.4 1.5 0.5 0.9 0.0 0.0 0.0

10th centile 2.0 2.2 2.0 1.9 1.5 1.0 0.0 0.0 0.0

25thcentile 3.5 3.5 2.9 2.8 2.1 1.3 0.5 0.0 00.0

50th centile 4.7 4.5 4.1 3.6 3.3 2.4 1.9 0.0 0.0

75th centile 5.8 5.2 5.0 4.3 4.1 3.6 2.8 0.0 0.0

90th centile 6.40 5.9 5.9 5.1 4.7 4.3 3.3 0.7 1.0

95th centile 6.7 6.2 6.2 5.9 5.0 4.7 4.7 1.2 1.4

F statistic for ANOVA = 537.37, p < 0.001 for the variation of mean AF size with postnatal age.

Figures given in cm.

65

Figure 8: Variation in the 5th, 50th and 95th percentile of AF size with postnatal age.

0

1

2

3

4

5

6

7

8

2-7 days 6 wks 10 wks 14 wks 6 months 9 months 12 months 18 months 24 months

5th Percentile

50th Percentile

95th Percentile

2-7 6 10 14 6 9 12 18 24

Days weeks months

Postnatal age

66

Table XIII. Relationship between mean anterior fontanel size, social class and age

* F statistic for ANOVA

Social

class

Mean (SD) AF size (cm)

Days Weeks Months *F p-value

2 - 7 6 10 14 6 9 12 18 24

I 4.6 (1.4) 4.5 (1.6) 4.7 (1.5) 3.8 (1.4) 3.3 (1.2) 2.6 (1.5) 0.9 ( 0.8) 0.1 (0.4) 0.0 223.24 < 0.001

II 4.3 (1.8) 4.1 (1.4) 4.0 (1.3) 3.5 (1.2) 3.1 ( 1.4) 2.3 (1.2) 1.5 (1.1) 0.2 ( 0.6) 0.2 (0.5) 207.32 < 0.001

III 4.6 (1.7) 4.0 (1.2) 3.0 (1.4) 3.5 (1.1) 3.1 (1.2) 2.4 (1.2) 2.4 (1.5) 0.2 (0.7) 0.6 (1.3) 104.84 < 0.001

IV 4.4 (1.8) 4.1 (1.2) 4.1 (0.6) 3.7 (1.4) 3.3 (1.3) 3.2 (1.4) 0.3 (0.8) 0.3 (0.4) 0.0 73.73 < 0.001

V 5.2 (0.0) 6.2 (0.4) 4.1 (0.0) 2.3 (0.0) 2.2 ( 0.7) 0.0 2.6 ( 0.7) 0.0 0.0 67.17 < 0.001

*F 0.84 4.68 21.67 1.08 1.13 5.80 21.48 1.38 10.91

p- value 0.501 0.001 < 0.001 0.389 0.342 0.001 < 0.001 0.241

< 0.001

67

Figure 9: Variation of mean AF size by social class

0.000

1.000

2.000

3.000

4.000

5.000

6.000

Mea

n A

F si

ze in

cm

Upper Class Middle Class Lower Class

2-7 6 10 14 6 9 12 18 24

days weeks months

Postnatal age

68

Table XIV. Variation of mean AF size with ethnic group among the newborns.

Ethnic group No. Mean ± SD AF size

Ogoni 36 6.4 (1.5)

Bini/Esan 9 5.5 (1.4)

Anang/Ibibio/Oron Ibo 20 5.2 (1.6)

Ikwere / Etche 50 5.1 (1.7)

Yoruba 22 5.1 (1.5)

Urhobo/Itsekiri 19 4.2 (1.3)

Igbo 120 3.9 (1.7)

Ijaw/Kalabari/Okirika 22 3.7 (1.6)

Hausa/Fulani/Tiv/Lantan 5 3.0 (3.5)

Others 31 4.9 (1.2)

Total 313

F statistic for ANOVA = 3.59, p < 0.001

AF size given in cm

69

VARIATIONS IN THE MEAN OCCIPITO-FRONTAL CIRCUMFERENCE

Table XV shows the variation of the mean of occipito-frontal circumference with postnatal age in

males and females. The mean OFC of male infants was significantly higher than that of their female

counterparts at 6 weeks, and at 6, 9, 12 and 18 months with p-values of < 0.05 at 6 weeks and 6

months and p-values of between 0.005 to < 0.001 at 9, 12 and 24 months. There was a positive

correlation between increased postnatal age and OFC, with the mean OFC increasing from 35.8 ± 2.8

cm in newborns to 48.0 ± 2.3 cm at 24 months (r = 0.617, p < 0.001). This is illustrated in the scatterplot

in Fig.10. Those from the Ogoni ethnic group had the largest AF (6.4 ± 1.5 cm) while the Hausa/Fulani

had the smallest (3.0 ± 3.5 cm). There was a highly statistically significant difference between the mean

AF size of different ethnic groups (p < 0.001).

Table XVI shows the variation of mean of OFC of newborns by gestational age and gender.

There was a moderate positive correlation (r = 0.346) between OFC and increasing gestational

age, which was, however, not statistically significant (p = 0.004). The difference in the mean OFC

between males and females was also not statistically significant in any gestational age group

except at 37 to 39 weeks (p < 0.05).

The results of Dunnett's multiple comparisons of differences in mean OFC between

different age groups is shown in Table XVII. Highly statistically significant differences (p <

0.001) were observed all through except at 18 versus 24 months (p < 0.05).

Table XVIII shows the mean, range and percentile values of the OFC in the study subjects.

The 5,th 50th and 95th percentiles of OFC of 32.2 cm, 35.2 cm and 38.8 cm, respectively at birth

increased to 45.3 cm, 48.0 cm and 50.6 cm, respectively, at 24 months of age. The variation in 5th,

50th and 95th percentile values with postnatal age is illustrated graphically in Figure 11.

70

Table XV. Variation of mean occipito-frontal circumference by age and gender

Age

Mean SD OFC (cm)

Male Female All Subjects t-test p-value

No. Mean (SD) No. Mean (SD) No. Mean (SD)

2-7 days 153 35.9 (2.5) 160 35.6 (2.8) 313 35.8 (2.7) 0.47 0.335

6 wks 165 36.9 (1.8) 158 36.7 (2.3) 323 36.8 (2.1) 2.02 0.045

10 wks 167 39.7 (2.9) 158 39.1 (2.4) 325 39.4 (2.7) 0.88 0.381

14 wks 154 43.2 (2.3) 168 41.9 (2.8) 322 42.6 (2.6) 1.31 0.190

6 mo 158 44.5 (3.4) 167 46.1 (1.6) 325 45.3 (2.5) 2.00 0.046

9 mo 156 47.1 (1.3) 165 45.2 ( 3.2) 321 42.6 (2.3) 5.27 < 0.001

12 mo 164 47.9 (1.5) 157 47.2 (2.5) 321 47.6 (2.0) 7.15 < 0.001

18 mo 140 47.5 (1.3) 181 47.1 (2.1) 321 47.3 (1.7) 2.85 0.005

24 mo 134 49.0 (2.9) 190 48.0 (1.8) 324 48.0 (2.3) -0.64 0.526

All Subjects 1391 42.7 (4.8) 1504 42.4 ( 2.4 2895 42.6 (4.9)

1.70

0.090

*F 728.70 507.22 7461.14

p-value < 0.001 < 0.001 < 0.001

*F statistic for ANOVA,

mo = months, SD = Standard deviation, OFC = Occipito-frontal circumference, wks = Weeks

71

Figure 10: Scatterplot of variations of OFC by postnatal age in males and females

Males = R2 Linear 0.566

Females: = R2 Linear = 0.653

72

Table XVI. Variation of mean occipito-frontal circumference of newborns by gestational age and gender.

Gestational

Age

Mean (SD) OFC

t-test p-value

Male

No. Mean (SD)

Female

No. Mean (SD)

All Subjects

No. Mean (SD)

28-32 7 33.8 (4.5) 9 33.6 (3.65) 16 33.6 (3.9) 0.10 0.921

33-36 19 35.9 ( 2.0) 28 36.6 ( 3.7) 47 36.2 (3.1) 0.67 0.506

37-39 68 36.4 (2.9) 78 355 ( 2.4) 146 35.9 (2.6) 2.01 0.046

40-42 59 35.6 (1.5) 45 35.7 ( 2.5) 104 35. 9(2.9) 0.09 0.932

Over all

mean (SD) 153 35.9 (2.5) 160 35.6 (2.8) 313 35.8 (2.7)

1.70

0.090

0.090

*F 1.28 0.51 4.45

p-value 0.204 0.611 0.004

*F statistic for ANOVA

cm = centimetres; SD = Standard Deviation; OFC = Occipito-frontal circumference (OFC) given in cm

73

Table XVII. Dunnett’s multiple comparisons of differences in mean OFC between different age groups

Age category (J) Age

category

Mean

difference

(I-J)

95% Confidence Interval

p-value Lower

limit

Upper

limit

2 - 7 days

6 months -7.46 -8.02 -6.91 < 0.001

12 months -10.41 -10.98 -9.84 < 0.001

18 months -11.72 -12.25 -11.27 < 0.001

24 months -12.21 -12.73 -11.68 < 0.001

6 months 12 months -2.95 -3.50 -2.4 < 0.001

18 months -4.26 -4.76 -3.76 < 0.001

24 months -4.74 -5.24 -4.22 < 0.001

12 months 18 months -1.31 -1.83 -0.79 < 0.001

24 months -1.79 -2.31 -1.27 < 0.001

18 months 24 months -0.48 -0.95 -0.02 < 0.05

Mean difference and 95% confidence interval are given in cm

74

Table XVIII. Mean, range and percentiles of OFC in the study subjects

OFC

Characteristics Days Weeks Months

2-7 6 10 14 6 9 12 18 24

(n = 313) (n = 323) ( n = 325) (n = 322) (n = 325) (n = 321 (n = 321) (n = 321) (n = 324)

Mean (SD) OFC 35.8 (2.7) 37.5 (2.1) 139.9 (2.6) 40.23 (2.6) 42.2 (2.5) 45.3 (2.3) 46.2 (2.) 47.4 (1.7) 47.8 (2.3)

Min. OFC 24.4 28.8 33 31.6 31.6 32.0 32.0 32.0 34.0

Max .OFC 47.2 47.6 44.1 48.5 38.8 52.0 50.1 53.2 51.1

5th centile

32.4 35.0 34.15 35.5 39.86 41.2 40.3 45.8 45.3

10th centile 33.1 35.2 36.3 37.0 40.1 43 44.8 46.04 46.1

25th centile 34.2 36.2 38.0 39.1 41.8 44.5 45 46.8 47.0

50th centile 35.8 37.3 39.5 40.5 43.1 45.9 46.7 47.6 48.o

75th centile 37.0 38.4 40.7 42.0 45.0 47.0 47.8 48.3 49.1

90th centile 38.2 39.5 41.5 43.0 46.7 47.2 48.3 49.1 50.3

95th centile 38.8 40.5 42.0 44.46 47.1 48.1 48.79 49.99 50.6

ANOVA = 46.14, p < 0.001 for the variation of mean OFC with postnatal age.

Min. = Minimum,

Max. = Maximum

75

0

10

20

30

40

50

60

2-7 days 6 wks 10 wks 14 wks 6 months 9 months 12 months 18 months 24 months

5th Percentile

50th Percentile

95th Percentile

Age

days weeks months

Fig. 11: Variation of the 5th, 50th and 95th percentiles of OFC with postnatal age.

2-7 6 10 14 6 9 12 18 24

76

COMPARISON OF THE TRENDS OF AF SIZE AND OFC WITH POST NATAL AGE

Table XIX and Figure 12 illustrate the relationship between AF size and OFC with

postnatal age. The mean AF size decreased significantly with age (ANOVA = 784.72, p <

0.001), whereas the mean OFC increased significantly with age (ANOVA = 1368.68, p <

0.001). There was a highly statistically significant correlation (r = 0.648, p = 0 .001) between

AF size and OFC with postnatal age, given by the formula y = 14 - 0.265x, where y = AF and

x = OFC. The mean AF size decreased even as the mean OFC increased with age (Figure 12).

Table XX shows the proportion of the subjects in each age group with a closed anterior

fontanel. The number with a closed AF was 76 (23.7%) at 12 months, 273 (85.1%) at 18

months and 288 (88.9%) at 24 months. Nine (2.9 %) of the 313 newborns had a closed AF.

The proportion of subjects with a closed AF at different age categories is illustrated in Figure

13.

77

Table XIX. Correlation between the AF size and OFC and age

AF = Anterior fontanel; mo = months; OFC = Occipito-frontal circumference

Age 2-7days

(n= 313)

6 mo

(n = 325)

12 mo

(n = 321)

18 mo

(n = 321)

24 mo

(n = 324)

ANOVA p-value

Mean (SD)

AF in cm

4.5 (2.0)

3.1 (1.3)

1.8 (1.3)

0.2 (0.6)

0.2 (0.7)

784.72

< 0.001

Mean (SD)

OFC in cm

35.8 (2.6)

43. 2 (2.5)

46.2 (2.6)

47.5 (2.1)

48.0 (2.2)

1368.68

< 0.001

78

Figure 12. Scatterplot of the correlation between anterior fontanel size and occipito-frontal

circumference with postnatal age.

y = -0.265x + 13.95R² = 0.419

-1

0

1

2

3

4

5

6

7

8

9

20 25 30 35 40 45 50 55

Ave

rage

An

teri

or

Fon

tan

el S

ize

(cm

)

OFCMean Occipito-Frontal Circumference (cm)

Circumference

79

Table XX. Relationship between postnatal age and closure of anterior fontanel

+

Postnatal

age

Males* Females** All subjects*** a χ2 P-value

No. n (%)

with closed AF

No. n (%)

with closed AF

No. n (%; 95% CI) with

closed AF

2-7 days 153

2 (1.3) 160 7 (4.4) 313 9 (2.9; 0.66-2.64) 2.64 0.104

6 weeks 165

5 (3.0) 158 1 (0.0) 323

6 (1.9; 0.66 - 2.64) 2.55 0.111

10 weeks 167

0 (0) 158 0 (0) 325

0 - -

14 weeks 154

4 (2.6) 168 0 (0) 322

4 (1.2; 0.19 - 1.60) 4.42 0.036

6 months 158

2 (1.3) 167 5 (3) 325 7 (2.2; 0.46 - 2.25) 1.15 0.283

9 months 156

0 (0) 165 4 (2.4) 325

4 (1.2; 0.19 -1.64) 3.86 0.050

12 months 164

40 (24.4) 157 36 (22.9) 321 76 (23.7; 18.26 - 28.2) 0.10 0.758

18 months 140

118 (84.3) 181 155 (85.6) 321

273 (85.1; 74.38 - 89.56 ) 0.11 0.737

24 months 133 113 (85.0) 191 175 (91.6) 324 288 (88.9; 78.8- 94.08) 3.52 0.061

aχ2 = proportion with closed fontanel in males vs females in different age categories

*χ2 (Variation of proportion with closed AF with age in males) = 903.64, p < 0.001.

**χ2 (Variation of proportion with closed AF with age in females) = 1081.11, p < 0.001.

***χ2 (Variation of proportion with closed AF with age in all subjects) = 1991.47, p < 0.001.

CI = Confidence interval

80

Figure 13: Variation in percentage closure of anterior fontanel with postnatal age.

2.9 1.90

1.2 2,2 1.2

23.7

85.1

88.9

0

5

10

15

20

25

30

35

40

45

50

per

cen

tage

wit

h c

lose

d A

F

100

90

80

70

60

50

40

30

20

10

2.-7 6 10 14 6 9 12 18 24

days weeks months

Postnatal age

81

DISCUSSION

The mean size of the anterior fontanel in this study decreased significantly with age. This

trend has been documented by previous Authors,4,7,23,30,42 among Caucasian as well as Black

infants.

The mean AF size of 4.5 ±1.7 cm in newborns in this study is higher than that in previous

reports from Nigeria.9,14,23,26,39 However, there was marked variation between the sizes reported

from previous studies. Thus, while Adeyemo et al39reported a mean AF size of 4.0 ± 1.0 cm,

Ogunye, et al23 and Uzoukwu26 reported lower values of 3.3 ± 2.0 cm and 2.78 ± 0.82 cm,

respectively. One possible reason for the difference between the mean AF size in the present

study and those in previous studies could be the timing of the measurements, which was within

12 to 24 hours after birth in the series by Adeyemo et al,39 at 30 hours in that by Ogunye et al23

and at 24-48 hours in that by Uzoukwu.26 Although the exact duration of the effects of molding

on the AF is uncertain, it is likely that measurements taken after 48 hours and up to 7 days post-

natal as was done in the present study could reduce the effects of molding. The implication of

this is that the higher values of AF sizes obtained in this study may be more valid than that from

studies in which measurements were taken at less than 48 hours of age. It is thus possible that, if

the timing of measurements in the previous Nigerian studies had been as in the present study, the

results may have been similar.

Another factor that may be responsible for the differences in mean AF size could be the

method of measurement. In the method used by Popich and Smith,8which was adopted by some

of the other Researchers,9,14,39it is not stated as to how the limits of the AF were delineated. The

method of Faix,12 adopted by Uzoukwu,26 would appear to be less suitable for our newborns with

luxuriant scalp hair, as it can predispose to falsely higher values.10,26 Accurate delineation of the

limits of the AF is paramount to getting a reliable measurement.10 Since the method of

delineation of the AF by Faix12 and Uzoukwu,26 are fraught with inherent errors, and the method

82

by Popich and Smith, which was used by the other Researchers did not state how the AF

dimension was delineated, these may account for the lower values in AF sizes in their reports.

The use of a pair of dividers aided by palpation as was employed in the present study

would appear more appropriate as the limits of the AF can easily be delineated despite the

luxuriant scalp hair in Nigerian newborns. On the other hand, the fact that the pointed tips of the

pair of dividers were detached could be contributory to the higher AF values obtained in this

study. In addition, the subjects in this study were from diverse ethnic groups while the earlier

Nigerian Authors9,14,23,26 surveyed homogenous groups. The factors responsible for the variation

in AF size between different ethnic groups demonstrated in this study are not clear and require

further evaluation.

The mean size of the AF in this study was also higher than the figures obtained from

Caucasian8,12and Oriental populations.16,26This is in accord with previous studies that have

documented racial differences in the size of the anterior fontanel.12,14,16,23,24 It is also possible that

these differences may be related to the different methods employed in the measurement of the

AF size. However, although the extent to which the use of different methodologies influence the

size of the AF remains to be determined, a generally larger AF size has been documented in

Black neonates compared to their White counterparts. This is thought to be due to delayed

osseous maturation akin to that seen in small-for-dates neonates and those with skeletal

dysmorphogenesis.8,23

The relationship between AF size and gestational age as found in this study is similar to

that

documented previously both locally9,26,39 and internationally.10,44,45 However, that no significant

difference in the mean AF size was observed between preterm and term babies in the present

study contrasts with the findings of other Nigerian Authors.14,26The reason for this is not clear

but may be related to the small sample size of the babies born at 28-32 weeks GA compared to

those born at 33-36 weeks GA in the present study.

83

There was no statistically significant gender difference in the mean size of the AF among

the younger infants in the present study. This is in accord with previous studies, both locally

14,24,26,39 and internationally.6,8,45 However at 24 months of age, the mean AF size was

significantly lower in females. This is in contrast with the findings by Tan16 who reported no

gender difference with respect to the size and time of closure of the AF among Chinese children.

In the present study, there was a positive correlation between OFC and gestational age up

to 36 weeks. It thus appears that beyond 37 weeks of intra-uterine life, AF is not significantly

dependent on gestational age and supports the fact that a gestational age of at least 37 weeks is

appropriate as a cut off for considering a baby term. Since the OFC and AF are indices of brain

growth, the correlation may be reflective of the differences in the rate of brain growth in term

and preterm babies. While Malas and Sulak41 reported a gradual but progressive increase in AF

size with head circumference in the third trimester, several other Authors including Adeyemo

and Omotade,9 Tan16 and Ogunye, et al23 and Duc and Largo44 found no association between the

AF size and OFC in term and preterm newborns.

The mean OFC at birth in the present study (35.8 ± 2.7 cm) is significantly higher than the

34.2 ± 3.5 cm reported by Ogunye23et al in Ile-Ife, and the 34.5 ± 3.2 cm reported by Lubchenco

et al81 for United States Caucasians. It is uncertain whether the larger OFC observed in this study

at 0 to 12 months compared to those from previous studies23,81 is a reflection of the previously

reported cyclical trend of a larger OFC in succeeding generations as documented by Ounsted et

al.84

Previous Nigerian scholars had reported on occipito-frontal circumference in newborns and

children up to 12 months.23,26,39, This Author did not come across published Nigerian studies on

OFC in children up to 24 months of age. This is perhaps, therefore, the first of such, and the

values reported in this study may be the only currently available standard for OFC in Nigerian

children from 12 to 24 months of age.

84

The values of OFC obtained in this study were significantly lower at 18 months and 24

months than that reported for Oxford children by Ounsted et al.84It is possible that the lower

occipito-frontal circumferences obtained in this study beyond 12 months compared to that of

Caucasian figures may be due to the high prevalence of malnutrition in our environment.85 This

buttresses the need for local reference standards which should be updated as necessary with each

succeeding generation.

A strong negative correlation between AF and OFC was observed in relation to increasing

post-natal age in the present study. This is in concert with the findings of Chang and

Hung,31Popich and Smith,8 and Tan.16 The growth in OFC of the subjects observed from the

newborn period to 24 months of age is also consistent with the findings in previous reports.16,46

The results of this study show that the anterior fontanel can be derived from the OFC using

the formula: AF = 14 - 0.265 (OFC). The measurement of the AF involves some technicalities,

and requires an assistant to ensure a reliable measurement. Therefore, the availability of a simple

formula can be helpful especially in a busy clinic setting. However, further studies may be

required to validate the application of this formula before it can be recommended for use in

clinical practice.

About 3% of the newborns in this study had a closed anterior fontanel. This is in contrast

to the findings of Ogunye23 and Uzoukwu,26 who reported an open AF in all the newborns

studied. Also this Researcher did not come across any published study that had reported closure

of the AF fontanel in apparently healthy newborns. However, there was no obvious abnormality

among the newborns in the present study and care had been taken to exclude all newborns with

obvious neurological, skeletal, endocrine and chromosomal disorders. Therefore, the reason(s)

for the finding of a closed AF in some of the newborns in the present study is/are not clear. Also,

whether this is a normal variation in Nigerian children remains to be determined.

85

There was a steady increase in the proportion of subjects with a closed anterior fontanel

with increasing post-natal age beyond 9 months of age. The percentage with a closed AF at 24

months (88.9%) in the present study is similar to the 91% reported from Indian by Mattur et al37.

In the series by Omotade et al,14 11% of 6 months infants and 53% of 12 months olds had a

closed anterior fontanel. The percentage of infants with a closed anterior fontanel in the present

study at 6months of age is lower (2.2%) while that at 12 months (23.7%) is higher. Apart from

the differences in methodology noted earlier, the larger sample size in the present study may also

have played a role by increasing the chance of picking ''abnormal'' findings.

About 11% of the subjects in the present study still had an open AF at 24 months. This is

higher than the 4% reported by Duc and Largo44 from Zurich. It is possible that the relatively

high prevalence of nutritional rickets in our environment could explain the high percentage of

subjects with an open AF at 24 months in this study.85

Males had a significantly larger mean AF size At 24 months of age, whereas more females

had a closed AF at same age. The difference in percentage closure between males and females

was, however, not statistically significant. These findings contrast with those of Acheson and

Eirly47 who demonstrated earlier closure of the AF in European boys. However, Acheson and

Eirlys study47 was conducted during a period of male preference with better nutrition in male

children which could explain their findings. Further studies are required to confirm the findings

in this study and to seek explanations for the male-female difference.

Over 60% of the subjects in this study were of the higher social classes while only about

10 % were in the lower classes. However, this may not be a reflection of a higher standard of

living in the inhabitants of Port Harcourt metropolis but rather a reflection of the relatively high

educational status of majority of the mothers/care-givers which has a positive influence on their

health-seeking behaviour.

86

There was a significant relationship between anterior fontanel size and social class. This is

similar to the finding of Acheson and Eirlys47 who noted a larger AF size in the lower social

classes and an earlier closure in the higher social-economic classes. Further studies are required

to establish the relationship between nutritional status and AF size in Nigerian children.

The cosmopolitan nature of Port Harcourt City, the study area, is reflected in the diverse

ethnic nationalities of the inhabitants. The relatively higher number of Igbo infants in this study

may not be unrelated to the migrant nature of the Igbo who are found in every nook and cranny

of the country and beyond. This is in addition to the fact that the Igbo speaking states of Imo and

Abia are neighbouring states to Rivers State and are among the catchment area for UPTH.76

AF size varied widely among the different ethnic groups but among the newborns, the

largest AF size was observed among the Ogoni, while the Hausa/Fulan/Tiv/Lantang had the least

AF size. The mean AF size in Igbo neonates in this study is similar to that reported by

Uzoukwu26 among Igbo neonates in Enugu. This is perhaps a reflection of their common racial

origin. Similarly, the mean AF size for the Yoruba newborns in this study is within the range

reported by Omotade et al.14This, therefore, suggests that inheritance exacts a stronger influence

on AF size than environmental factors. The significant difference in the mean AF sizes between

the various ethnic groups studied is suggestive of inter-ethnic variations in the size of the AF.

The factors responsible for these variations, other than inheritance, remain to be determined.

87

CONCLUSION

1. The size of the anterior fontanel in Nigerian children in the cosmopolitan city of Port Harcourt

decreases progressively with post-natal age even as the occipito-frontal circumference

increases.

2. The relationship between occipito-frontal circumference and anterior fontanel size is given by

the formula AF = 14 - 0.265 (OFC).

3. Three percent (95% confidence interval = 0.66, 2.64) of Nigerian newborns in Port Harcourt

have a closed AF but the anterior fontanel is still open in 11% (95% confidence interval =

78.80, 94.04) of the subjects by 24 months of age.

4. Socio-economic status and ethnicity are important determinants of the size of the anterior

fontanel.

88

RECOMMENDATIONS

1. The values of the 5th, 50th and 95th percentile for anterior fontanel size and occipito-frontal

circumference at various ages obtained in this study are recommended for use as reference

standards in Nigerian infants in Port Harcourt.

2. Mothers/care-givers should be educated at every opportunity especially during ante-natal

visits, and at the Post-Natal and Well-Infant Clinics that the size of the anterior fontanel varies

at different ages, and thereby discourage wrong practices that may predispose them to other

illnesses.

89

LIMITATIONS OF THE STUDY

1. A major limitation of this study was the time constraint posed by the necessity to conclude the

research within the time frame of the senior residency program. For this reason, a cross

sectional study was carried out, and therefore percentage closure was obtained rather than the

actual age at closure of the anterior fontanel which would require a longitudinal study.

2. The method adopted for the estimation of the AF size may be a factor in the finding of a closed

fontanel in 3% of newborns. Estimation of the anterior fontanel size by means of trans-fontanel

ultrasound scan would have given a more accurate result in terms of delineation of the limits of

the AF.17

90

LINES OF FUTURE STUDIES

Further studies are recommended in the following areas:

i. Follow-up of apparently well newborns with closed AF to determine the effect on development

ii. The relationship between nutritional status and AF size, and time of closure

iii. The causes of premature closure and delayed closure of the anterior fontanel in the study

population.

iv. Validation of the formula for the computation of the size of the anterior fontanel from the

occipito-frontal circumference.

91

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