Further evidence of reproductive immaturity among gynecologically young pregnant adolescents*†

Further evidence of reproductive immaturity among gynecologically young pregnant adolescents*†

FERTILITY AND STERILITY Copyright (tJ Vol. 64, No.6, December 1995 1995 American Society for Reproductive Medicine Printed on acid-free paper in U...

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FERTILITY AND STERILITY Copyright

(tJ

Vol. 64, No.6, December 1995

1995 American Society for Reproductive Medicine

Printed on acid-free paper in U.

s. A.

Further evidence of reproductive immaturity among gynecologically young pregnant adolescents*t

Catherine Stevens-Simon, M.D.:j: Elizabeth R. McAnarney, M.D. Division of Adolescent Medicine, Department of Pediatrics, University of Rochester Medical Center, Rochester, New York

Objective: To obtain further information about the reproductive maturity of adolescents who become pregnant soon after menarche. We hypothesized that the length of the follicular phase of the menstrual cycle antedating conception is related inversely to the gynecological age of the adolescent mother at conception. Design: Observational clinical study. Setting: Pregnant volunteers in a multidisciplinary adolescent-oriented maternity program. Patients: Pregnant adolescents with accurate pregnancy dating. Main Outcome Measure: We studied the difference between the estimated date of confinement (EDC) computed from the stated last menstrual period (EDC LMP ) and the EDC computed from ultrasound studies (EDC us ) in a group of 66, 12 to 19 year olds. A prolonged follicular phase was defined as EDC us - EDC LMP > 0 and shortened follicular phase was defined as EDC us - EDC LMP :s O. Results: Pearson correlations revealed a statistically significant inverse relationship between gynecological age and the duration of the follicular phase antedating conception when the follicular phase was prolonged. Within this subgroup of patients EDC us exceeded EDC LMP by 15.6 ± 7.3 days when conception occurred within 3 years of menarche and 6.2 ± 6.0 days when conception occurred 2:3 years after menarche. Conclusions: Our findings support the hypothesis that some adolescents conceive before establishing a fully mature adult ovulatory pattern. Fertil Steril1995;64:1109-12 Key Words: Adolescent pregnancy, reproductive maturity, ultrasound

Menarche does not mark the attainment of reproductive maturity (1, 2). Indeed, it takes 3 to 5 years for most postmenarcheal adolescents to establish an adult ovulatory menstrual pattern (1, 2). During this time the length of the follicular phase of the menstrual cycle decreases, the length of the luteal phase of the menstrual cycle increases, the frequency of ovulation increases, and the luteal phase level of P rises (1, 2). Evidence that adolescents who conceive within 3 years of menarche are at increased risk for February 20, 1995; revised and accepted June 2, 1995. * Supported by The Bureau of Maternal and Child Health and Resources and Development, grant MCJ-360534, Rochester, New York. t Presented at The Society for Adolescent Medicine Annual Meeting, Chicago, Illinois, March 18 to 21, 1993. :j: Reprint requests: Catherine Stevens-Simon, M.D., Department of Pediatrics, Division of Adolescent Medicine, University of Colorado Health Science Center, The Children's Hospital, 1056 East 19th Street, Denver, Colorado 80218 (FAX: 303-837 -2962). Vol. 64, No.6, December 1995

vaginal bleeding during the only period of gestation when the maintenance of the pregnancy depends primarily on an adequate supply of maternal gonadal hormones (e.g., the first 8 weeks of gestation) suggests that adolescents who conceive within 3 years of menarche may be less reproductively mature than their gynecologic ally older peers (3, 4). In this study we seek corroborative evidence of the reproductive immaturity of adolescents who conceive within 3 years of menarche. We hypothesize that among pregnant adolescents the length of the follicular phase of the menstrual cycle antedating conception is related inversely to the gynecological age of the mother at conception. MATERIALS AND METHODS Subjects

The data were collected as part of the Rochester Study of Adolescent Pregnancy. This was a 3-year

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prospective study of the relationship among maternal age, weight gain, and infant outcome in 140 consecutively enrolled, poor, black 12 to 19 year olds. Details of the study design and study population have been published (3-6). In this analysis we examine the cohort of 66 young women with reliable pregnancy dating. Subjects were excluded if they were unsure of the date of their last menstrual period (LMP; were unable to report both the month and the day of their LMP with certainty; n = 44) and/or if the difference between the expected date of confinement (EDC) based on the stated LMP and the EDC based on ultrasound (US) studies exceeded 30 days (n = 30). There were no significant differences in the menarcheal, chronological, or gynecological ages of the 66 study subjects who were included in this analysis and the 74 who were excluded because of inadequate or inaccurate dating information. Bone age determinations were performed on 93 of the study subjects (5); the results were not significantly different for the 46 included and 47 excluded study subjects. The study protocol was approved by the Committee on Investigations Involving Human Subjects at the University of Rochester Medical Center. Data Collection

The data were collected prospectively. Details of the procedures for data collection have been published previously (3-6). The EDC was calculated in two ways: EDC by LMP (EDC LMP); calculated from the date ofthe mother's LMP using Naegele's rule (7) and EDC by US (EDC us ); calculated from US measurements of fetal length, limb length, and head size (7). On average the 66 US studies were performed at 17.7 ± 6.0 weeks gestation; 75% of the studies were performed at $20 weeks gestation and 3% were performed at ~28 weeks gestation. The timing of the US studies was unrelated to the chronological, gynecological, or bone age of the study subjects (r = -0.08, r = 0.01, and r = 0.06, respectively). The difference between the actual and the expected length of the follicular phase of the menstrual cycle antedating conception was defined as EDC us - EDC LMP • The follicular phase was classified as prolonged (one in which ovulation occurred later than expected) if EDC us - EDC LMP > O. The follicular phase was classified as shortened (one in which ovulation occurred earlier than expected) if EDC us - EDC LMP $ o. Maternal age was defined in three ways; each definition was treated both continuously and categorically: [1] chronological age at conception: the difference in years between the date of the LMP and 1110

the mother's date of birth. For categorical analyses, chronological age was dichotomized; study subjects who conceived before their 16th birthday were classified as chronologically younger adolescents (6). [2] Gynecological age at conception; the difference between the mother's chronological age at conception an her age at menarche. For categorical analyses gynecological age was dichotomized; study subjects who conceived within 3 years of menarche were classified as reproductively immature (3-5). [3] Bone age at delivery; determined for 46 of the study subjects from a roentgenogram of the left hand and wrist. The roentgenograms were interpreted by one pediatric radiologist using the standards of Greulich and Pyle (5, 8). For categorical calculations bone age was dichotomized; study subjects who had open epiphyses at delivery (bone age < 18 years) were classified as skeletally immature (5). Birth weight was measured within 1 hour of delivery; the infants were weighed naked to the nearest fa- of a gram on a balance scale. Gestational age was calculated from the date of the mothers' LMP using Naegele's rule and verified by US and Dubowitz examinations (6). A low-birth-weight infant was defined as an infant weighing <2,500 grams, a preterm infant was defined as an infant born before the 37th week of gestation, and a small-for-gestational age infant was defined as an infant weighing less than the 10th percentile for gestational age (6). On average the 66 infants weighed 3,100 ± 669 grams at birth (mean ± SD); 8 were low birth weight, 7 were preterm, and 6 were small-for-gestational age. Because infant birth weight, gestational age, and weight-for-gestational age were unrelated to any of the measures of maternal age, the timing of the US examination, or the difference between EDC us and EDC LMP , neither undergrown nor preterm infants were excluded from the analyses. Data Analysis

Summary statistics were used to describe the study population. Comparisons between the duration ofthe follicular phase ofthe menstrual cycle and the three definitions of maternal age were conducted with Pearson correlations, t-tests, and X 2 analyses. Relationships between continuous variables were examined with Pearson correlations. Analyses were performed with the Statistical Package for the Social Sciences (9).

RESULTS The difference between the actual and the expected length of the follicular phase of the menstrual

Stevens-Simon and McAnarney Reproductive immaturity in pregnant teens

Fertility and Sterility

cycle antedating conception (EDC us - EDC LMP ) ranged from -26 to 22.5 days (mean ± SD: 0.9 ± 10.1 days). The difference between EDC us and EDC LMP exceeded zero (EDC us - EDC LMP > 0) and the follicular phase was classified as a prolonged one in which ovulation occurred later than expected in 37 cases. The difference between EDC us and EDC LMP was less than or equal to zero (EDC us - EDC LMP oS 0) and the follicular phase was classified as a shortened one in which ovulation occurred earlier than expected in 29 cases. Chronological age at conception ranged from 12.7 to 19.9 years (mean ± SD: 16.8 ± 1.7 years); 18 (27%) of the study subjects were classified as younger adolescents ( < 16 years of age at conception). Gynecological age at conception ranged from 0.8 to 8.9 years (4.7 ± 1.8 years); 11 (16.6%) of the study subjects were classified as reproductively immature (conception within 3 years of menarche). Bone age at delivery ranged from 15 to 18 years (17.0 ± 0.9 years); 32 (69.6%) of the study subjects were classified as skeletally immature (bone age < 18 years). Among subjects who had longer than expected follicular phases (and by inference had experienced late ovulation) Pearson correlations revealed a statistically significant inverse relationship between gynecological age and the duration of the follicular phase of the menstrual cycle (r = -0.4; P = 0.01). Within this subgroup of the study population further analyses revealed a statistically significant difference in the duration of the follicular phase of the menstrual cycle antedating conception among the less reproductively mature girls (those who conceived within 3 years of menarche) and more reproductively mature girls (15.6 ± 7.3 days compared with 6.2 ± 6.0 days; P = 0.003). This relationship was not effected by the timing of the US studies and was not evident among study subjects who had shorter than expected follicular phases (and by inference had experienced early ovulation). Within this latter subgroup of the study population the duration of the follicular phase of the menstrual cycle antedating conception was not significantly different among the less reproductively mature girls (those who conceived within 3 years of menarche) and more reproductively mature girls (9.0 ± 7.6 days compared with 7.0 ± 6.7 days). The duration of the follicular phase of the menstrual cycle antedating conception was unrelated to either chronological age or bone age. DISCUSSION

Studies of nulliparous adolescent females indicate that there is a progressive decrease in the length of the follicular phase ofthe menstrual cycle during the first 3 to 5 postmenarcheal years (1, 2). The results of Vol. 64, No.6, December 1995

this study suggest that this also may be true among parous adolescents. We found that when the follicular phase of the menstrual cycle antedating conception was longer than expected (and by inference when ovulation occurs later than expected) the duration of that follicular phase is significantly longer among young women who conceived within 3 years of menarche than it is among young women who conceived 2::3 years after menarche (15.6 ± 7.3 days compared with 6.2 ± 6.0 days; P = 0.003). Our finding that the duration of that follicular phase of the menstrual cycle antedating conceptions was not related significantly to either maternal chronological or bone age is consistent with the results of prior studies showing that, during adolescence, gynecological age is a more accurate index of reproductive maturity than are chronological and bone age (3, 4, 10). We recognize that US studies that are performed during the third trimester of pregnancy yield an estimate of the date of confinement that has a confidence interval of 3 weeks. However, we do not think that this threatens the validity of our findings because there was no relationship between the timing of the US studies and either the gynecological age of the study participant or the difference between EDC us and EDC LMP • Thus, US errors, were they to have occurred, would have taken place randomly within the study population. Similarly, even though it was learned at delivery that some ofthe fetuses included in the study were born prematurely and/or growth retarded, they were not excluded from the analyses because there was no relationship between infant size or maturity at birth and the gynecological age of the study participant, the timing of the US studies, or the difference between EDC us and EDC LMP • Thus, errors introduced by fetal growth delays, were they to have occurred, would have taken place randomly within the study population. Although it seems unlikely that random errors introduced by inaccuracies in US dating and/or fetal growth delays would produce the consistent finding reported in this manuscript, it would have been preferable to obtain first trimester USs. This would have limited the inaccuracy of US dating and obviated concerns about intrauterine growth retardation but would have been difficult, as most adolescents, particularly young adolescents, do not enter prenatal care during the first trimester of pregnancy (11, 12). Thus we believe that the results ofthis study should be added to the growing body of data that suggests that some adolescents conceive before establishing a fully mature adult ovulatory pattern (3, 4, 10). Further studies are needed to determine how reproductive maturity effects the outcomes of adolescent pregnancies (3-5,11). To this end the difference between EDC us

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r' and EDC LMP may prove to be a useful index of reproductive maturity. Acknowledgments. The authors thank Mrs. Carole Berger for her help and support and also the entire Rochester Adolescent Maternity Project staff for their assistance.

REFERENCES 1. Treloar AE, Boynton RE, Behn BG, Brown BW. Variation of the human menstrual cycle through reproductive life. Int J Fertil 1967; 12:77 -128. 2. Apter D, Viinikka L, Vihko R. Hormonal pattern of adolescent menstrual cycles. J Clin Endocrinol Metab 1978;47:944-54. 3. Stevens-Simon C, Roghmann KJ, McAnarney ER. Early vaginal bleeding, late prenatal care, and misdating in adolescent pregnancy. Pediatrics 1991;87:835-40. 4. Stevens-Simon C, Roghmann KJ, McAnarney ER. First trimester vaginal bleeding and pre term delivery in pregnant adolescents. Pediatrics 1991;87:951-2.

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5. Stevens-Simon C, McAnarney ER. Skeletal maturity and growth of adolescent mothers: relation to pregnancy outcome. J Adolesc Health 1993; 14:428-32. 6. Stevens-Simon C, Roghmann KJ, McAnarney ER. Weight gain in adolescent pregnancy. Part I. Relationship to maternal age and infant birth weight. Pediatrics 1993;92:805-9. 7. Cunningham FG, MacDonald PC, Gant NF, editors. Williams obstetrics. 18th ed. Norwalk (CT): Appleton and Lange, 1989. 8. Greulich WW, Pyle SI. Radiology atlas of skeletal development of the hand and wrist. 2nd ed. Stanford (CA): Stanford University Press, 1959. 9. Nie NH, Hull CH, Jenkins JG. Statistical package for the social sciences. 3rd ed. New York: McGraw-Hill, 1989. 10. Zlatnik F J, Burmeister L. Low "gynecologic age": an obstetric risk factor. Am J Obstet Gynecol 1977; 128:183-6. 11. Stevens-Simon C, White M. Adolescent pregnancy. Pediatr Ann 1991;20:322-31. 12. Committee to Study the Prevention of Low Birthweight, Division of Health Promotion and Disease Prevention. Institute of Medicine. Preventing low birthweight. Washington, DC: National Academy Press, 1985.

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