Paediatric and Perinatal Epidemiology 1989, 3, 357-366

Original articles

Association between low gynaecological age and preterm birth

Theresa 0. Scholl*, Mary L. Hediger*, Ruth W. Salmoni-, DanieI H. Belsky* and Isadore G. Ancesl "Department of Obstetrics and Gynecology, Universi ty of Medicine and Dentistry of New Jersey, School of Osteopathic Medicine, tour Lady of lourdes Medical Center, and $Cooper Hospital/ University Medical Center, Camden, N e w jersey

Summary. Low gynaecological age, defined as conception within 2 completed years of menarche, was examined for its association with preterm birth, using data from a geographically based cohort of over 1700 young primigravidae aged 18 or younger at start of prenatal care. After stratifying by chronological age and controlling for confounding variables, low gynaecological age was associated with almost double the risk of preterm delivery whether estimated from the mother's last menstrual period (adjusted odds ratio (AOR)=l.77, 95% CI 1.19-2.64) or using the obstetric estimate of gestation (AOR=2.10, 95y0 CI 1.36-3.25). Low gynaecological age was also associated with an increase in risk of low birthweight (LBW) (AOR--1.70, 95% CI 1.01-2.88), but not of small-for-gestational-age babies (AOR-0.94, 95% CI 0.49-1.81). Thus low gynaecological age may be an important addition to assess- ment systems to detect women at risk of pre tem labour and delivery.

Introduction

Young maternal age is associated with increased risk of low birthweight as well as

Address for correspondence: Dr Theresa 0. Scholl, Department of Obstetrics and Cynerol- ogy, UMDNJ-SOM, 401 Haddon Avenue, Camden, New Jersey 08103, USA.

35 7

358 T.O. Scholl, M.1. Hediger, R.W. Salmon et al.

other poor pregnancy outcomes. Mechanisms which mediate these associations are unclear. Low birthweight, in particular, is a heterogeneous category which combines intrauterine growth retardation (IUGR) and preterm delivery.2 Presum- ably, factors which shorten gestation and result in preterm birth differ from those which give rise to IUGR. Such factors are poorly differentiated in general, and during adolescent pregnancy in particular have yet to be identified.

Low gynaecological age, defined as conception within 2 completed years of menarche, is sometime^'.^ but not always5-' linked to an increased incidence of low birthweight. Studies showing a positive association do not appear to have adequately controlled for background characteristics, such as maternal chrono- logical age or ethnic group, which potentially confound effects of reproductive immaturity on pregnancy outcome. Negative studies have either suffered from inadequate statistical power to declare observed differences as statistically significant or been carried out in developing countries in areas of the world where malnutrition is endemic.

When chronic and clinical malnutrition are prevalent, menarche often is delayed until the completion of breast and pubic hair stages at the end of puberty.8 In such instances, low gynaecological age may be neither a sensitive nor a specific indicator of reproductive immaturity, but this does not appear to be the case in developed countries such as the United States. In this report, using data from a large, geographically based cohort of young pregnant women, we present evidence suggesting that low gynaecological age is an independent risk factor for low birthweight which is specific to a single underlying cause: preterm birth.

Material and methods

Between September 1983 and December 1986,2789 young pregnant women were enrolled into the Camden County Adolescent Family Life Project (CCAFL), a federally-funded demonstration project that provided prenatal care to pregnant teenagers. The five hospitals and clinics in Camden County, New Jersey, that provide prenatal care participated in the demonstration. Clinic patients were given a comprehensive prenatal programme, which was standardised across sites, and included prenatal and postpartum medical care, social services, health education, and obstetric services.

Apart from age (I 18 years at entry to care), subjects were unselected and more than 99% agreed to provide data. Of the 2789 registrants, 10.3% (n-288) moved, terminated the pregnancy, or failed to return to the clinics before delivery. Of the remaining 2501 for whom pregnancy outcomes were available, 4.0% (n= 101) had a fetal demise, and 0.8% (n=20) had a livebom multiple birth. An additional nine Asian patients were excluded, leaving a base sample for analysis of 2371 white, black and Hispanic (Puerto Rican) adolescents who had liveborn singleton

low gynaecological age 359

deliveries. Since only 17 multiparae were of low gynaecological age, this analysis was confined to data from 1784 primigravidae (75.290 of the base sample).

Patients were interviewed either at entry to prenatal care or at the time of their first physical examination, which was usually 1-2 weeks later. During the interview, data on maternal behavioural, demographic and social characteristics, reproductive history (including age at menarche), medical history, and usual prepregnant weight, were obtained by trained clinical personnel following a standard protocol. Information on pregnancy outcomes, complications, maternal height and weight gain during pregnancy was abstracted from the prenatal record, the delivery record, delivery room logbooks, and the infants' charts.

Several additional variables were derived from this information. Low gynaecological age ( 5 2 completed years) was defined as the difference between maternal age at conception and her age at menarche. Body mass index (BMI), calculated as prepregnant weight-for-height2 (kg/m2), was derived to index adiposity and prepregnant nutritional status. Adequacy of weight gain during pregnancy was assessed for the entire pregnancy according to gestation at the week of delivery using published charkg

Low birthweight ((2500 grams) and its two major underlying causes, preterm delivery ( t 3 7 weeks completed gestation) and smallness-for-gestational-age (< 10th percentile for standards), were examined as outcomes. Smallness-for- gestational-age (SGA), usually taken to indicate intrauterine growth retardation, was defined as a birthweight below the 10th percentile for gestational age, using the birthweight standards compiled by Brenner et d . * O which adjust birthweight for ethnicity (white vs black), maternal parity and fetal sex. Gestation was reckoned using two sources: from the first day of the mother's last menstrual period (LMP) and, from the obstetric estimate, based on the LMP confirmed either by serial measurement of uterine fundal height and/or ultrasound (65%). In the face of a size for dates discrepancy (>2 completed weeks) or when the LMP was not known, the obstetric estimate was based on ultrasound examination of the fetus alone. There was excellent agreement between the two estimates of gestation. The LMP and the obstetric (OB) estimates agreed zk 1 week in 77.8% of cases and k 2 weeks in 86.34b. In 4.2% the OB estimate exceeded the LMP estimate by more than 2 weeks, and in another 9.5% the LMP estimate exceeded the OB estimate by more than 2 weeks. Although the agreement was good, in subsequent analyses both estimates of gestation were used separately to ensure that the results were comparable.

The principal statistical technique used in analysis was multiple logistic regression. In order to control more stringently for the effect of chronological age on preterm birth, the logistic regression was stratified by narrow categories (age 12-14, 15, 16, 17, 18-19) of chronological age." This practice more effectively controls for strong confounding, such as by chronological age, than does simple linear adjustment for age. Adjusted odds ratios (AOR), adjusted for confounding,

360

were computed from the logistic regression coefficients; their 95 % confidence intervals (CI) were computed from the covariance matrix. Multiple linear regression,'* with adjustment for confounding, also was used to estimate linear effects of low gynaecological age on birthweight and gestation.

Potential confounders were those variables associated with gynaecological age, as well as with pregnancy outcome. Confounding was assessed by comparing adjusted and crude odds ratiosI2 since the problem of relying on tests of statistical significance alone to assess confounding is well re~ognised.'~ Separate models were fitted for each outcome and for both methods of estimating gestation. Each model contained the risk factor, confounding variables, and interaction terms

Table 1. Selected background characteristics associated with low gynaecologi- cal age

T.O. Scholl, M.L. Hediger, R.W. Salmon et al.

Low gynaecological age Maternal characteristic n % n Yo

High gynaecological age

Chronological age 12-14 83 15 62 16 46 17 31 18-19 24

Ethnic group Black 137 Puerto Rican 40 White 67

119.5 82 19.6-24.5 126 >24.5 27

Quetefet 's Index (Body Mass Index)

Cigarette smoking Yes 198 No 46

Yes 10 No 235

Marijuana smoking

Pregnancy weight gain for gestation Inadequate 41 Adequate 173

Medicaid 194 Insurance 44

Clinic payment status

33.7 25.2 18.7 12.6 9.8

56.2 16.4 27.5

34.9 53.6 11.5

18.9 81.2

4.1 95.9

19.2 80.8

81.5 18.5

58 158 287 448 587

568 327 64 1

392 836 233

498 1028

83 1452

238 1142

412 1095

3.8 10.3 18.7 29.1 38.2

37.0 21.3 41.7

26.8 57.2 15.6

32.6 67.4

5.4 94.6

17.3 82.7

72.7 27.3

Low gynaecologicaf age 361

using forward inclusion and backward deletion.** The maternal characteristics treated as potential confounding variables in preliminary models included chronological age, ethnicity, prepregnant body mass index, cigarette and marijuana smoking, adequacy of pregnancy weight gain for gestation, and clinic payment status. No interaction terms were statistically significant (P>O.l).

Results

The majority of young primigravidae with low gynaecological age were under the age of 16 years. They were more likely to be black, to be non-smokers, and to have prenatal care and delivery costs funded by Medicaid. Low gynaecological age was also correlated with a lower prepregnant BMI and a slightly increased rate of inadequate pregnancy weight gain for gestation (Table 1).

The incidence of preterm delivery, reckoned from the LMP as well as the obstetric estimate, along with rates of low birthweight (LBW) and smallness-for- gestational-age (SGA) were computed within chronological age strata according to gynaecological age (Table 2). At every chronological age, primigravidae with low gynaecological age had higher rates of preterm delivery regardless of whether the LMP or the OB estimate was used to estimate gestation. In addition, low gynaecological age mothers had a tendency toward more low birthweight infants, particularly at low chronological ages ((16 years) but this was not as marked as

Table 2. Rates of low birthweight (LBW), small-for-gestational-age (SGA) and preterm birth by gynaecological age and chronological age

Yo LBW % SGA

Age n Low gyn. High gyn. Low gyn. High gyn.

12-14 141 16.9 5.2 4.9 4.3 15 220 14.5 8.2 6.0 10.2 16 333 6.5 8.0 7.1 4.4 17 4 79 16.1 8.5 6.5 3.3 18-19 61 1 9.1 8.9 7.7 8.7

YO Preterm LMP O/O Pretenn OB

Age n Low gyn. High gyn. Low gyn. High gyn.

12-14 141 39.7 22.4 28.9 17.2 15 220 25.4 15.0 13.1 7.1 16 333 27.9 13.8 15.6 6.8 17 479 18.5 14.3 19.3 9.9 18-19 61 I 17.4 11.7 13.0 8.3

362 T.O. Scholl, M.L. Hediger, R.W. Salmon et al.

Table 3. Adjusted odds ratios; LBW, SGA and preterm birth by gynaeco- logical age

Outcome Unadjusted 70 AOR

1. Low birthweight" Low gyn. 13.4 High gyn. 8.5

2. SGAb Low gyn. 6.3 High gyn. 7.0

3. Preterm LMP'

4. Preterm OBd

Low gyn. 29.1 High gyn. 13.6

Low gyn. 19.8 High gyn. 8.7

1.70 1.00

0.94 1.00

1.77 1 .oo 2.10 1 .oo

1.01-2.88 -

0.49-1.81 - 1.19-2.64 - 1.36-3.25 -

Stratified by chronological age (12-14, 15, 16,17,18-19) and adjusted for ethnicity (black, Puerto Rican vs white), BMI ((19.5 vs other), adequacy of weight gain (yes/no), smoking (yeslno).

Less than 10% of Brenner standards which adjust for maternal ethnicity, panty and fetal sex, stratified by chronological age and adjusted for smoking.

Computed from LMP. Regression is stratified by chronological age and adjusted for ethnicity, adequacy of weight gain during pregnancy, smoking and BMI.

Obstetric estimate of gestation. Regression is stratified by chronologi- cal age and adjusted for ethnicity, smoking, BMI and adequacy of weight gain during pregnancy.

the association with preterm delivery. There was little association between low gynaecological age and SGA after stratification by chronological age.

These associations with low gynaecological age were confirmed in Iogistic regression analyses stratified by chronological age and controlled for additional confounding variables (Table 3). In the logistic models, low gynaecological age was associated with approximately double the adjusted odds ratio for low birthweight (AOR- 1.70, 9546 CI 1.01-2.88), for preterm delivery as assessed from the LMP (AOR- 1.77, 959/0 CI 1.19-2.64), and for preterm delivery assessed from the obstetric estimate of gestation (AOR-2.10, 95% CI 1.36-3.25). Consistent with the univariate analysis, low gynaecological age was not associated with an increased odds ratio for SGA births (AOR=0.94, 95% CI

Logistic regressions for preterm birth were recomputed after confining the analysis to categories of patients where gestation was more secure. These included: patients with entry to care at 24 weeks or earlier, patients with a known LMP, patients with both earlier entry to care and a known LMP, and patients with estimates of gestation which agreed within 2 completed weeks. There was a modest increase in the adjusted odds ratio in the 1218 patients (68.3%) who

0.49-1.81).

Low gynaecological age 363

entered care earlier than 24 weeks (AOR= 1.88, 95% CI 1.19-3.00 from the LMP, AOR=2.51, 9596 CI 1.53-3.11 from the OB estimate). In the other categories examined, the adjusted odds ratio relating low gynaecological age to preterm births stiIl showed an approximate doubling.

Linear models, estimating the effect of gynaecological age on gestation and birthweight also indicated that low gynaecological age was associated with decreased gestation (Table 4). After control for maternal age and other confounding variables, low gynaecological age was associated with a decrease in gestation by 0.69 or 0.59 weeks according to whether gestation was estimated from the LMP or the OB. After controlling for chronological age and other confounding variables but not gestation, infants of low gynaecological age mothers weighed 87.6 grams less. However, after adjusting for gestation from the OB estimate, low gynaecological age was associated with a reduction in birthweight of only 19.1 grams, suggesting shortened gestation as the main reason for the lower birthweights in infants of primigravidae of low gynaecological age.

Comment

In 1977, Zlamik & BurrneisteF' coined the term 'low gynaecological age' to distinguish young gravidae who were not physiologically mature from those who were. Their rationale may have originated in the well-known differences in the onset and timing of adolescent development. l4 At similar chronological ages some girls have experienced a growth spurt, menarche and, according to indicators such as skeletal age, breast and pubic hair development, are physiologically mature, while others are not and may not yet be mature for several months or even

Table 4. Linear models for effects of low gynaecological age on birthweight and gestation

Outcome B SE P r2

Birthweight not adjusted for gestation -87.63 grams. 45.7 0.056 0.118

Birthweight adjusted for gestation - 19.1 grams' 39.8 0.632 0.313

Gestation by LMP -0.694 weeksC 0.284 0.015 0.037

Gestation by OB -0.587 weeksd 0.187 0.002 0.028

a Adjusted for chronological age, ethnicity, smoking, low and high BMI (vs average), adequacy of weight gain during pregnancy.

Adjusted for gestation (obstetric estimate), and other variables in above model. Adjusted for chronological age, maternal ethnicity and adequacy of weight gain

Adjusted for chronological age, maternal ethnicity and smoking. during pregnancy.

364 T.O. Scholl, M.L. Hediger, R.W. Salmon et al. years.I4 Thus, it was suggested, gynaecological age might be used to further refine the risk of low birthweight associated with young maternal age.3 But effects of low gynaecological age were not found in subsequent studies so that its utility was doubted.Is These studies, however, focused on size at birth rather than on any association between a gynaecological age and shortened gestation.

In the present study, low gynaecological age appeared to have had an effect on pregnancy outcome which was detectable even after stringent control for maternal chronological age and other confounding variables. Low gynaecological age was associated with almost double the risk of low birthweight. Furthermore, for the first time, we have demonstrated that the association was specific to length of gestation. Low gynaecological age was associated with a decreased average duration of gestation by approximately two-thirds of a week. However gestation was estimated the risk of preterm delivery was approximately doubled when gynaecological age was low. There was no association between gynaecological age and smallness-for-gestational-age or birthweight adjusted for gestation, again demonstrating specificity for length of gestation.

The sensitivity of these findings to misclassification was tested by recomputing adjusted odds ratios, after excluding certain cases where gestation was less secure. In each sub-group the association between low gynaecological age and preterm birth was confirmed. Adjusted odds ratios were modestly increased by confining the analysis to those entering prenatal care at 24 weeks or earlier. With early entry to prenatal care, the LMP is more likely to be recalled accurately. Furthermore, fetal age estimated using early ultrasonography is less dependent on fetal size than later in pregnancy when fetal size is more variable.I6 Confining the analysis to cases where differences in estimates of gestation were 2 2 weeks did little to increase or diminish adjusted odds ratios for preterm birth.

Use of the LMP as opposed to the obstetric estimate increased the absolute risk of preterm birth from 10.1% to 15.54b. Rates of preterm birth based on the LMP alone are in agreement with US data for minorities" and with information from the Collaborative Perinatal Project.'* A lower incidence of preterm birth with the obstetric estimate accords with published data from large-scale studies which included ethnic minoritie~.'~ Poor memory or vaginal bleeding early in pregnancy would be the most likely causes of higher rates of preterm birth reckoned from the LMP. Despite differences in absolute level of risk, adjusted odds ratios for preterm birth computed from each estimate of gestation were consistent, making inferences about the influence of low gynaecological age on preterm birth more secure. Thus, the addition of low gynaecological age to screening protocols to detect increased risk of preterm labour and delivery may improve predictive value of these instruments. Improved detection is especially important among primi- gravidae, where sensitivity of risk assessment systems is low.

There are several possible explanations for the association between low gynaecological age and preterm birth. For example, low gynaecological age may

Low gynaecological age 365

be a marker for social disadvantage and concomitant risk factors such as exposure to alcohol or drugs which may affect gestation. Alternatively, low gynaecological age may be indicative of poor nutritional status associated with continued maternal growth during pregnancy.20 Another possibility is that low gynaecologi- cal age is associated with maturational differences in the hypothalamic-pituitary axis or in hormonal milieu of pregnancy which theoretically would shorten ge~tat ion.~ Finally, low gynaecological age may reflect immaturity of the uterus, cervix or their blood supply which may predispose young gravidae to infection and secondarily increase the incidence of preterm birth.*'

Preterm birth is a leading cause of perinatal morbidity and mortality in the United States. It is also an important underlying cause of low birthweighk2 Yet few studies have examined specifically the causes of preterm birth, instead mixing preterm and small-for-gestational-age infants into the composite category of low birthweight. To improve utility of risk assessment for preterm birth, risk factors specific to pretenn delivery need to be defined. Based upon the current study, one specific risk factor appears to be low gynaecological age. A prior history of preterm delivery is one of the strongest risk factors for subsequent preterm birth.' Consequently, factors associated with adolescent pregnancy, such as low gynaecological age, may continue to influence the outcome of subsequent pregnancies in the mature years.

Acknowledgements

Supported in part by grants HD 18269 from NICHD and APH 000522 from the Office of Population Affairs, Department of Health and Human Services.

References

1 Committee to Study the Prevention of Low Birthweight. Preventing low birthweight. Washington: Institute of Medicine, National Academy Press, 1985; pp. 46-93. 2 Kessel, S.S., Villar, J., Berendes, H.W. et al. The changing patterns of low birthweight in the United States. Journal of the Anrerican Medical Association 1984; 251:1978-1982. 3 Zlatnik, F.J., Burmeister, L.F. Low 'gynecologic age': an obstetric risk factor. American Journal of Obstetrics and Gynecology 1977; 128:183-186. 4 Erkon, K.A., Rimer, B.A., Stine, O.C. Juvenile pregnancy - role of physiologic maturity. Ma y l a n d State Medical Journal 1971; 2050-52. 5 Hollingsworth, D.R., Kotchen, J.M. Gynecologic age and its relation to neonatal outcome. In Birth Defects: Original Article Series Vol XVZI. New York: Alan R. Liss, 1981; pp.

6 Felice, M.E., James, M., Shragg, P. et al. Observations related to chronologic and gynecologic age in pregnant adolescents. Yale Journal of Biology and Medicine 1984;

7 Frisancho, A.R., Matos, J., Bolletino, L.A. Role of gynecological age and growth

91-105.

5E777-785.

366 T.O. Scholi, M.L. Hediger, R.W. Salmon et al.

maturity status in fetal maturation and prenatal growth of infants born to young still- growing adolescent mothers. Human Biology 1984; 56:583-593. 8 Cameron, N., Mitchell, J., Meyer, D. et al. Secondary sexual development of 'Cape Coloured' girls following kwashiorkor. Annals of Human Biology 1988; 1565-76. 9 Butman, M. Prenatal Nutrition: A Clinical Manual, 2nd edition. Boston: Massachusetts Department of Health, 1983; pp. 23-32. 10 Brenner, W.E., Edelman, D.A., Hendricks, C.H. A standard for fetal growth for the United States of America. American Journal of Obstetrics and Gynecology 1976; 126:555-564. 1 1 Breslow, N.E., Day, N.E. Statistical Methods in Cancer Research. Volume 1. The Analysis of Case-Control Studies. Lyon: IARC Scientific Publications, 1980; pp. 192-247. 12 Kleinbaum, D.G., Kupper, L.L., Morgenstern, H. Epidemiologic Research: Principies and Quantitatiae Methods. Belmont, CA: Lifetime Learning, 1982; pp. 419-491, 13 Dales, L.G., Ury, H.K. An improper use of statistical significance testing in studying covariables. lnternational Journal of Epidemiology 1978; 7:373-375. 14 Tanner, J.M. Growth at Adolescence. Oxford Blackwell Scientific, 1962; pp. 94-155. 15 Stevens-Simons, C., Forbes, G.F., Kreipe, R.E. et al. A comparison of chronologic age and gynecological age as indices of biologic maturity. American journal of Diseases of Children 1986; 140702-705. 16 Manning, F.A. Ultrasound in perinatal medicine. In Maternal-Fetal Medicine, Editors: Robert K. Creasy & Robert Resnick. Philadelphia: W.B. Sanders , 1984; pp. 210-211. 17 National Center for Health Statistics. Advance report of final natality statistics, 1985. Monthly vital statistics report, Volume 36, No. 4, Suppl. DHHS Publication No (PHS) 87- 1120. Hyattsville, MD: Public Health Service, 1985. 18 Hardy, J.B., Drage, J.S., Jackson, E.C. The First Year of Life. The Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders aird Stroke. Baltimore: The John Hopkins University Press, 1979; pp. 40-41. 19 Shiono, P.H., Klebanoff, M.A. Ethnic differences in preterm and very preterm delivery. American Journal of Public Health 1986; 76:1317-1321. 20 Scholl, T.O., Hediger, M.L., Ances, I.G. et al. Growth during early teenage pregnancies. Lancet 1988; i:701-702. 21 MeGregor, J.A. Adolescent misadventures with urethritis and cervicitis. journal of Adolescent Health Care 1985; 6:286-297.