Obesity and age at menarche
2011; Elsevier BV; Volume: 95; Issue: 8 Linguagem: Inglês
10.1016/j.fertnstert.2011.02.020
ISSN1556-5653
AutoresAnshu Shrestha, Jørn Olsen, Cecilia Høst Ramlau‐Hansen, Bodil Hammer Bech, Ellen A. Nøhr,
Tópico(s)Hypothalamic control of reproductive hormones
ResumoA cohort study of 3,169 girls born in April 1984–April 1987 in Odense and Aalborg, Denmark, was performed to examine whether maternal prepregnancy body mass index (BMI) accounted for daughter’s age of menarche (AOM) and, if so, whether it accounted for part or all of the association between daughter’s BMI and AOM. Multiple regression analyses adjusted for covariates indicated a weak inverse association between maternal BMI and AOM and a much stronger inverse association between offspring BMI and AOM independent of maternal BMI. A cohort study of 3,169 girls born in April 1984–April 1987 in Odense and Aalborg, Denmark, was performed to examine whether maternal prepregnancy body mass index (BMI) accounted for daughter’s age of menarche (AOM) and, if so, whether it accounted for part or all of the association between daughter’s BMI and AOM. Multiple regression analyses adjusted for covariates indicated a weak inverse association between maternal BMI and AOM and a much stronger inverse association between offspring BMI and AOM independent of maternal BMI. Increasing obesity prevalence is one of the main global health concerns of today, because it is associated with numerous health problems, including infertility, subfecundity, diabetes, hypertension, cardiovascular diseases, and cancer (1Pi-Sunyer X. The medical risks of obesity.Postgrad Med. 2009; 121: 21-33Crossref PubMed Scopus (655) Google Scholar, 2Ramlau-Hansen C.H. Thulstrup A.M. Nohr E.A. Bonde J.P. Sørensen T.I. Olsen J. Subfecundity in obese and overweight couples.Hum Reprod. 2007; 22: 1634-1637Crossref PubMed Scopus (316) Google Scholar, 3Rich-Edwards J.W. Goldman M.B. Willet W.C. Hunter D.J. Stampfer M.J. Colditz G.A. et al.Adolescent body mass index and infertility caused by ovulatory disorder.Am J Obstet Gynecol. 1994; 171: 171-177Abstract Full Text PDF PubMed Scopus (418) Google Scholar, 4Hassan M.A. Killick S.R. Negative lifestyle is associated with a significant reduction in fecundity.Fertil Steril. 2004; 81: 384-392Abstract Full Text Full Text PDF PubMed Scopus (278) Google Scholar). Obesity in pregnancy has been linked to increased risk of pregnancy and birth complications (5Pasquali R. Pelusi C. Genghini S. Cacciari M. Gambineri A. Obesity and reproductive disorders in women.Hum Reprod Update. 2003; 9: 359-372Crossref PubMed Scopus (364) Google Scholar, 6Lashen H. Fear K. Sturdee D.W. Obesity is associated with increased risk of first trimester and recurrent miscarriage: matched case-control study.Hum Reprod. 2004; 19: 1644-1646Crossref PubMed Scopus (399) Google Scholar, 7Metwally M. Ong K.J. Ledger W.L. Li T.C. Does high body mass index increase the risk of miscarriage after spontaneous and assisted conception? A meta-analysis of the evidence.Fertil Steril. 2008; 90: 714-726Abstract Full Text Full Text PDF PubMed Scopus (341) Google Scholar, 8Nohr E.A. Timpson N.J. Andersen C.S. Smith G.D. Olsen J. Sørensen T.I.A. Severe obesity in young women and reproductive health: the Danish National Birth Cohort.PLoS ONE. 2009; 4: e8444Crossref PubMed Scopus (73) Google Scholar), and adipose tissue is involved in production and storage of sex hormones, such as estrogen and testosterone (9Maseguer A. Puche C. Cabero A. Sex steroid biosynthesis in white adipose tissue.Horm Metab Res. 2002; 34: 731-736Crossref PubMed Scopus (68) Google Scholar). Some studies indicate that prenatal exposure to excess estrogen and estrogen-like chemicals interferes with development of male reproductive organs, predisposes to cervical and vaginal cancer in female offspring, and may reduce sperm quality in male offspring (10Fernandez M.F. Olmos B. Granada A. Lopez-Espinosa M.J. Molina-Molina J.M. Fernandez J.M. Cruz M. et al.Human exposure to endocrine-disrupting chemicals and prenatal risk factors for cryptorchidism and hypospadias: a nested case-control study.Environ Health Perspect. 2007; 115: 8-14Crossref PubMed Scopus (185) Google Scholar, 11Bornstein J. Adam E. Adler-Storthz K. Kaufman R.H. Development of cervical and vaginal squamous cell neoplasia as a late consequence of in utero exposure to diethylstilbestrol.Obstet Gynecol Surv. 1988; 43: 15-21Crossref PubMed Scopus (29) Google Scholar, 12Ramlau-Hansen C.H. Nohr E.A. Thulstrup A.M. Bonde J.P. Storgaard L. Olsen J. Is maternal obesity related to semen quality in the male offspring? A pilot study.Hum Reprod. 2007; 22: 2758-2762Crossref PubMed Scopus (38) Google Scholar).High prepubertal body mass index (BMI) is associated with earlier age of menarche (AOM) (13Tam C.S. de Zegher F. Garnett S.P. Baur L.A. Cowell C.T. Opposing influences of prenatal and postnatal growth on the timing of menarche.J Clin Endocrinol Metab. 2006; 91: 4369-4373Crossref PubMed Scopus (101) Google Scholar, 14Buyken A.E. Karaolis-Danckert N. Remer T. Association of prepubertal body composition in healthy girls and boys with the timing of early and late pubertal markers.Am J Clin Nutr. 2009; 89: 221-230Crossref PubMed Scopus (102) Google Scholar), which may be related to hormonal activity in fat tissue, a shared genetic background, or prenatal programming activated by a high maternal BMI. Because obese mothers often have obese daughters (15Bjelland M. Lien N. Bergh I.H. Grydeland M. Anderssen S.A. Klepp K.I. et al.Overweight and waist circumference among Norwegian 11-year-olds and associations with reported parental overweight and waist circumference: the HEIA study.Scand J Public Health. 2010; 38: 19-27Crossref PubMed Scopus (24) Google Scholar, 16Eisenman J.C. Sarzynski M.A. Tucker J. Heelan K.A. Maternal prepregnancy overweight and offspring fatness and blood pressure: role of physical activity.Pediatr Exerc Sci. 2010; 22: 369-378PubMed Google Scholar, 17Salsberry P.J. Reagan P.B. Taking the long view: the prenatal environment and early adolescent overweight.Res Nurs Health. 2007; 30: 297-307Crossref PubMed Scopus (40) Google Scholar) , the link between daughters’ BMI and AOM could be confounded by maternal BMI at the time of pregnancy. The causal link between child BMI and AOM may occur in utero rather than in puberty. Therefore, we studied whether increased prepregnancy maternal weight was associated with timing of menarche in female offspring and, if so, whether it accounted for some or all of the association observed between offspring BMI and AOM.This study included data collected from a pregnancy cohort in two Danish cities, Aalborg and Odense, recruited between April 1984 and April 1987 as part of the health campaign “Healthy Habits for Two.” The women (n = 13,815) received a questionnaire during a routine visit to their midwives at the ∼36th week of pregnancy. Those who chose to participate returned the completed questionnaire via mail. The participating women (n = 11,980; ∼87% of all eligible) provided information about their health and lifestyles, including diet, smoking habits, and alcohol use during pregnancy (18Olsen J. Frische G. Poulsen A.O. Kirchheiner H. Changing smoking, drinking, and eating behaviour among pregnant women in Denmark. Evaluation of a health campaign in a local region.Scand J Soc Med. 1989; 17: 277-280PubMed Google Scholar). Prepregnancy height and weight were reported to their doctors at the first routine antenatal visit when their current height and weight were being measured, to reduce reporting bias. The records were later retrieved for the study purposes. Additional demographic and obstetric information were collected from the medical forms at child birth.In 2005, a total of 4,669 girls (out of 5,427 liveborn singleton girls) who were still alive and living in Denmark were contacted to complete an online survey that included questions on menarcheal age. All participants (3,382, 72%) were first asked whether they had reached menarche. If affirmed, they were asked to provide the month and the year when they reached their menarche. Of the total participants, 3,169 (94%) provided their age at menarche at least in years, and they made up the study population; another ten (0.3%) had not reached menarche yet. Among the 3,169 participants, about one-half (n = 1,634) provided information about both year and month. The months of menarche were converted into years and added to the year to form a continuous outcome variable. Maternal prepregnancy BMI was calculated by dividing prepregnancy weight in kilograms by their height in meters squared. Two offspring BMIs were calculated similarly, with heights and weights reported by: 1) mothers in 2002 (offspring ages 14–18 years); and 2) offspring in 2005 at ages 17–21 years. We examined both offspring BMIs as main exposure because only about two-thirds of the mothers provided the data. All BMIs were categorized into underweight (<18.5 kg/m2), normal (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (≥30 kg/m2), based on the World Health Organization criteria (19World Health Organization (WHO). Obesity: preventing and managing the global epidemic. Report of a WHO consultation (WHO technical report series 894) 2000. Geneva, Switzerland. Available at: http://whqlibdoc.who.int/trs/WHO_TRS_894.pdf. Accessed October 9, 2010.Google Scholar), for subgroup analyses.Multiple linear regression analyses were conducted to examine the association between maternal prepregnancy BMI and AOM. If maternal BMI programs AOM, we would expect an association between maternal BMI and AOM also in daughters with normal-to-low BMI (<25 kg/m2). If, on the other hand, the association is driven by daughter’s BMI, we would expect to see an association between daughter’s BMI and AOM even when their mothers had normal-to-low BMI. We therefore analyzed these associations in the full dataset and in subsamples restricted to either mothers or daughters with normal/low BMI. All regression analyses were conducted with the subsets that provided AOM in either only years or both months and years and finally with the full sample (i.e., AOM in at least years). All analyses included the following covariates chosen a priori based on literature reviews (20Rubin C. Maisonet M. Kieszak S. Monteilh C. Holmes A. Flanders D. et al.Timing of maturation and predictors of menarche in girls enrolled in a contemporary British cohort.Paediatr Perinat Epidemiol. 2009; 23: 492-504Crossref PubMed Scopus (88) Google Scholar, 21Baum 2nd, C.L. Ruhm C.J. Age, socioeconomic status and obesity growth.J Health Econ. 2009; 28: 635-648Crossref PubMed Scopus (147) Google Scholar, 22Sarlio-Lahteenkorva S. Lissau I. Lahelma E. The social patterning of relative body weight and obesity in Denmark and Finland.Eur J Public Health. 2005; 16: 36-40Crossref PubMed Scopus (22) Google Scholar, 23Laurier D. Guiguet M. Chau N.P. Wells J.A. Valleron A.J. Prevalence of obesity: a comparative survey in France, the United Kingdom and the United States.Int J Obes Relat Metab Disord. 1992; 16: 565-572PubMed Google Scholar) and guided by directed acyclic graphs (DAGs): maternal age at childbirth, maternal education (elementary school, school leaving certificate, upper secondary education), marital status (married, cohabiting, single), and maternal smoking during pregnancy (no smoking, stopped smoking by 36th week of pregnancy, smoked one to nine cigarettes/day in late pregnancy, smoked ten or more cigarettes/day in late pregnancy). We also examined for interaction between maternal and offspring BMI (P=.6) and between maternal BMI and three levels of pregnancy smoking (P values 0.4–0.8). All analyses were conducted by using SAS software, version 9.2 (24SASSAS 9.2. SAS Institute, Cary, North Carolina2008Google Scholar). The study was approved by the University of California, Los Angeles, internal review board and the Danish Data Protection Agency.The demographic characteristics across the subsets with AOM in both months and years and in only years were fairly similar. The mean AOMs were 13.3 and 12.9 years while prepregnancy BMI was 21.7 and 21.8 kg/m2, respectively, in the two subsets. The majority of mothers (89%, 87%) and offspring (86%, 84%) were underweight or normal weight (BMI <25 kg/m2) across the subsets. Many mothers reported having smoked at some point during the pregnancy (40%, 44%), and the majority of them (85%, 87%) were still smoking in late pregnancy (at the ∼36th week of gestation).In the subset with detailed timing of AOM, every unit increase in maternal BMI corresponded with an acceleration in AOM by 8.1 days (95% confidence interval [CI] −16.2 to 0.0) in the offspring, whereas every unit increase in offspring BMI corresponded with a larger acceleration in AOM (−32.4 days [95% CI −41.9 to −23.0] and −18.9 days [95% CI −26.0 to −11.9] for maternal reported and self-reported BMI, respectively; Table 1). When maternal and offspring BMI were mutually adjusted, it had little impact on the association between offspring BMI and AOM, but the association between maternal BMI and AOM notably attenuated (Table 1). When the analyses were restricted to mothers with a prepregnancy BMI <25 kg/m2 (underweight/normal weight), the offspring BMI showed a strong inverse association with AOM (−22.2 days [95% CI −30.6 to −13.7]), whereas the analysis restricted to daughters with BMI <25 kg/m2 indicated only a small statistically nonsignificant inverse association between AOM and maternal BMI (−3.6 days [95% CI −13.5 to 6.3]). In the subset where the participants provided only the year of menarche, all the associations were similar to the former subset except for the subgroup analysis of offspring with self-reported BMI <25 kg/m2, where the association did not attenuate (Table 1).Table 1Adjusted age of menarche according to maternal prepregnancy body mass index and/or offspring body mass index.aAll regression models were adjusted for the following covariates: maternal education, marital status, maternal age at childbirth, and maternal smoking during pregnancy. Mothers reported their daughters’ adolescent BMI in 2002 and daughters self-reported their BMI in 2005.Multiple regression modelbRegression coefficient: change in age of menarche in days for every unit increase in the exposure variable of interest compared.Exposure variableChange in AOM, d (95% CI)cSample size for each model: N1, N2, N3.Subset with AOM in months and years (N1)Subset with AOM in only years (N2)Sample with AOM in at least years (N3)Models where maternal and offspring BMI were not mutually adjusted (1493, 1,378, 2,871)Maternal prepregnancy BMI−8.1 (−16.2, 0.0)−7.0 (−15.0, 1.0)−7.6 (−13.3, −1.8) (1,203, 1,030, 2,233)Offspring BMI (reported by mother)−32.4 (−41.9, −23.0)−31.2 (−41.3, −21.1)−33.2 (−40.1, −26.2) (1,531, 1,400, 2,931)Offspring BMI (self-report)−18.9 (−26.0, −11.9)−22.0 (−28.9, −15.2)−20.8 (−25.7, −15.8)Models mutually adjusted for maternal and offspring BMI (1,134, 955, 2,089)Maternal prepregnancy BMI1.4 (−8.6, 11.5)2.7 (−7.4, 12.8)2.9 (−4.3, 10.1)Offspring BMI (reported by mother)−32.8 (−42.7, −22.9)−29.1 (−40.3, −17.9)−32.7 (−40.2, −25.3) (1,435, 1,306, 2,741)Maternal prepregnancy BMI−0.7 (−9.4, 7.9)−0.4 (−9.0, 8.3)−0.5 (−6.7, 5.7)Offspring BMI (self-report)−19.8 (−27.3, −12.2)−20.4 (−28.0, −12.8)−20.5 (−25.9, −15.1)Subgroup of offspring (BMI <25 kg/m2) BMI reported by mother (1,031, 882, 1913)Maternal prepregnancy BMI−8.4 (−19.4, 2.6)−8.5 (−19.7, 2.8)−8.2 (−16.1, −0.2) Self-reported BMI (1,229, 1,098, 2,327)Maternal prepregnancy BMI−3.6 (−13.5, 6.3)−9.2 (−19.2, 0.7)−6.4 (−13.5, 0.7)Subgroup of mothers (BMI <25 kg/m2) (1,013, 848, 1,861)Offspring BMI (reported by mother)−35.5 (−46.3, −24.7)−38.3 (−50.4, −26.3)−37.9 (−46.0, −29.8) (1,283, 1,150, 2,433)Offspring BMI (self-report)−22.2 (−30.6, −13.7)−28.0 (−36.5, −19.5)−25.3 (−31.4, −19.3)Note: AOM = age of menarche; BMI = body mass, index (kg/m2).a All regression models were adjusted for the following covariates: maternal education, marital status, maternal age at childbirth, and maternal smoking during pregnancy. Mothers reported their daughters’ adolescent BMI in 2002 and daughters self-reported their BMI in 2005.b Regression coefficient: change in age of menarche in days for every unit increase in the exposure variable of interest compared.c Sample size for each model: N1, N2, N3. Open table in a new tab We found no strong support for a programming effect of maternal prepregnancy BMI on AOM, but a small effect cannot be ruled out. Whereas the results indicate that daughter’s BMI plays an important role in accelerating AOM independent of the mother’s prepregnancy BMI.Some studies have linked polycystic ovary syndrome (PCOS) and obesity in mothers as well as prenatal exposure to androgen with obesity and PCOS in female offspring later in life (25Cresswell J.L. Barker D.J. Osmond C. Egger P. Phillips D.I. Fraser R.B. Fetal growth, length of gestation, and polycystic ovaries in adult life.Lancet. 1997; 350: 1131-1135Abstract Full Text Full Text PDF PubMed Scopus (191) Google Scholar, 26Abbott D.H. Dumesic D.A. Eisner J.R. Colman R.J. Kemnitz J.W. Insights into the development of PCOS from studies of prenatally androgenized female rhesus monkeys.Trends Endocrinol Metab. 1998; 9: 62-67Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar, 27Eisner J.R. Dumesic D.A. Kemnitz J.W. Abbott D.H. Timing of prenatal androgen excess determines differential impairment in insulin secretion and action in adult female rhesus monkeys.J Clin Endocrinol Metab. 2000; 85: 1206-1210Crossref PubMed Scopus (159) Google Scholar, 28Padmanabhan V. Evans N. Taylor J.A. Robinson J.E. Prenatal exposure to androgen leads to the development of cystic ovaries in the sheep.Biol Reprod. 1997; 56: 194PubMed Google Scholar). Similarly, studies have linked prenatal exposure to excess estrogen or estrogen-like chemicals (e.g., diethystillbestrol, xenoestrogen) with malformation of male reproductive organs and cancer in female reproductive organs (10Fernandez M.F. Olmos B. Granada A. Lopez-Espinosa M.J. Molina-Molina J.M. Fernandez J.M. Cruz M. et al.Human exposure to endocrine-disrupting chemicals and prenatal risk factors for cryptorchidism and hypospadias: a nested case-control study.Environ Health Perspect. 2007; 115: 8-14Crossref PubMed Scopus (185) Google Scholar, 11Bornstein J. Adam E. Adler-Storthz K. Kaufman R.H. Development of cervical and vaginal squamous cell neoplasia as a late consequence of in utero exposure to diethylstilbestrol.Obstet Gynecol Surv. 1988; 43: 15-21Crossref PubMed Scopus (29) Google Scholar, 12Ramlau-Hansen C.H. Nohr E.A. Thulstrup A.M. Bonde J.P. Storgaard L. Olsen J. Is maternal obesity related to semen quality in the male offspring? A pilot study.Hum Reprod. 2007; 22: 2758-2762Crossref PubMed Scopus (38) Google Scholar). Such findings suggest fetal programming of ovarian function. In two recent studies, an inverse association was observed between maternal prepregnancy BMI and AOM in daughters (20Rubin C. Maisonet M. Kieszak S. Monteilh C. Holmes A. Flanders D. et al.Timing of maturation and predictors of menarche in girls enrolled in a contemporary British cohort.Paediatr Perinat Epidemiol. 2009; 23: 492-504Crossref PubMed Scopus (88) Google Scholar, 29Keim S.A. Branum A.M. Klebanoff M.A. Zemel B.S. Maternal body mass index and daughters’ age at menarche.Epidemiology. 2009; 20: 677-681Crossref PubMed Scopus (50) Google Scholar). In one study, the association remained even after adjusting for the child BMI measured at age 7 years (29Keim S.A. Branum A.M. Klebanoff M.A. Zemel B.S. Maternal body mass index and daughters’ age at menarche.Epidemiology. 2009; 20: 677-681Crossref PubMed Scopus (50) Google Scholar). In the present study, we found inverse association between offspring BMI and early AOM, with slightly stronger association for the BMI reported by mothers, which may support the importance of prepubertal BMI. The maternal reports are closer to this time frame (14-18 years). A high childhood BMI often persists into adulthood (30Venn A.J. Thomson R.J. Schmidt M.D. Cleland V.J. Curry B.A. Gennat H.C. et al.Overweight and obesity from childhood to adulthood: a follow-up of participants in the 1985 Australian Schools Health and Fitness Survey.Med J Aust. 2007; 186: 458-460PubMed Google Scholar, 31Singh A.S. Mulder C. Twisk J.W. van Mechelen W. Chinapaw M.J. Tracking of childhood overweight into adulthood: a systematic review of the literature.Obes Rev. 2008; 9: 474-488Crossref PubMed Scopus (1690) Google Scholar, 32Kindblom J.M. Lorentzon M. Hellqvist A. Lonn L. Brandberg J. Nilsson S. et al.BMI changes during childhood and adolescence as predictors of amount of adult subcutaneous and visceral adipose tissue in men: the GOOD study.Diabetes. 2009; 58: 867-874Crossref PubMed Scopus (45) Google Scholar), and it is plausible that the offspring BMIs correlate well with their prepubertal BMIs.The main advantage of the present study is the longitudinal data collection, which provides temporal divides between prenatal exposures, postnatal exposures, and outcome measures. Moreover, the prenatal exposures were measured when the mothers were pregnant, making differential recall bias unlikely. Limitations of the study include lack of data on prepubertal BMI, maternal AOM, and complete AOM data for all participants.In summary, our findings did not support maternal BMI accounting for the strong association between child BMI and AOM. Given the continuing obesity epidemic that starts in childhood, we expect a continuing decline in AOM in many countries worldwide. Increasing obesity prevalence is one of the main global health concerns of today, because it is associated with numerous health problems, including infertility, subfecundity, diabetes, hypertension, cardiovascular diseases, and cancer (1Pi-Sunyer X. The medical risks of obesity.Postgrad Med. 2009; 121: 21-33Crossref PubMed Scopus (655) Google Scholar, 2Ramlau-Hansen C.H. Thulstrup A.M. Nohr E.A. Bonde J.P. Sørensen T.I. Olsen J. Subfecundity in obese and overweight couples.Hum Reprod. 2007; 22: 1634-1637Crossref PubMed Scopus (316) Google Scholar, 3Rich-Edwards J.W. Goldman M.B. Willet W.C. Hunter D.J. Stampfer M.J. Colditz G.A. et al.Adolescent body mass index and infertility caused by ovulatory disorder.Am J Obstet Gynecol. 1994; 171: 171-177Abstract Full Text PDF PubMed Scopus (418) Google Scholar, 4Hassan M.A. Killick S.R. Negative lifestyle is associated with a significant reduction in fecundity.Fertil Steril. 2004; 81: 384-392Abstract Full Text Full Text PDF PubMed Scopus (278) Google Scholar). Obesity in pregnancy has been linked to increased risk of pregnancy and birth complications (5Pasquali R. Pelusi C. Genghini S. Cacciari M. Gambineri A. Obesity and reproductive disorders in women.Hum Reprod Update. 2003; 9: 359-372Crossref PubMed Scopus (364) Google Scholar, 6Lashen H. Fear K. Sturdee D.W. Obesity is associated with increased risk of first trimester and recurrent miscarriage: matched case-control study.Hum Reprod. 2004; 19: 1644-1646Crossref PubMed Scopus (399) Google Scholar, 7Metwally M. Ong K.J. Ledger W.L. Li T.C. Does high body mass index increase the risk of miscarriage after spontaneous and assisted conception? A meta-analysis of the evidence.Fertil Steril. 2008; 90: 714-726Abstract Full Text Full Text PDF PubMed Scopus (341) Google Scholar, 8Nohr E.A. Timpson N.J. Andersen C.S. Smith G.D. Olsen J. Sørensen T.I.A. Severe obesity in young women and reproductive health: the Danish National Birth Cohort.PLoS ONE. 2009; 4: e8444Crossref PubMed Scopus (73) Google Scholar), and adipose tissue is involved in production and storage of sex hormones, such as estrogen and testosterone (9Maseguer A. Puche C. Cabero A. Sex steroid biosynthesis in white adipose tissue.Horm Metab Res. 2002; 34: 731-736Crossref PubMed Scopus (68) Google Scholar). Some studies indicate that prenatal exposure to excess estrogen and estrogen-like chemicals interferes with development of male reproductive organs, predisposes to cervical and vaginal cancer in female offspring, and may reduce sperm quality in male offspring (10Fernandez M.F. Olmos B. Granada A. Lopez-Espinosa M.J. Molina-Molina J.M. Fernandez J.M. Cruz M. et al.Human exposure to endocrine-disrupting chemicals and prenatal risk factors for cryptorchidism and hypospadias: a nested case-control study.Environ Health Perspect. 2007; 115: 8-14Crossref PubMed Scopus (185) Google Scholar, 11Bornstein J. Adam E. Adler-Storthz K. Kaufman R.H. Development of cervical and vaginal squamous cell neoplasia as a late consequence of in utero exposure to diethylstilbestrol.Obstet Gynecol Surv. 1988; 43: 15-21Crossref PubMed Scopus (29) Google Scholar, 12Ramlau-Hansen C.H. Nohr E.A. Thulstrup A.M. Bonde J.P. Storgaard L. Olsen J. Is maternal obesity related to semen quality in the male offspring? A pilot study.Hum Reprod. 2007; 22: 2758-2762Crossref PubMed Scopus (38) Google Scholar). High prepubertal body mass index (BMI) is associated with earlier age of menarche (AOM) (13Tam C.S. de Zegher F. Garnett S.P. Baur L.A. Cowell C.T. Opposing influences of prenatal and postnatal growth on the timing of menarche.J Clin Endocrinol Metab. 2006; 91: 4369-4373Crossref PubMed Scopus (101) Google Scholar, 14Buyken A.E. Karaolis-Danckert N. Remer T. Association of prepubertal body composition in healthy girls and boys with the timing of early and late pubertal markers.Am J Clin Nutr. 2009; 89: 221-230Crossref PubMed Scopus (102) Google Scholar), which may be related to hormonal activity in fat tissue, a shared genetic background, or prenatal programming activated by a high maternal BMI. Because obese mothers often have obese daughters (15Bjelland M. Lien N. Bergh I.H. Grydeland M. Anderssen S.A. Klepp K.I. et al.Overweight and waist circumference among Norwegian 11-year-olds and associations with reported parental overweight and waist circumference: the HEIA study.Scand J Public Health. 2010; 38: 19-27Crossref PubMed Scopus (24) Google Scholar, 16Eisenman J.C. Sarzynski M.A. Tucker J. Heelan K.A. Maternal prepregnancy overweight and offspring fatness and blood pressure: role of physical activity.Pediatr Exerc Sci. 2010; 22: 369-378PubMed Google Scholar, 17Salsberry P.J. Reagan P.B. Taking the long view: the prenatal environment and early adolescent overweight.Res Nurs Health. 2007; 30: 297-307Crossref PubMed Scopus (40) Google Scholar) , the link between daughters’ BMI and AOM could be confounded by maternal BMI at the time of pregnancy. The causal link between child BMI and AOM may occur in utero rather than in puberty. Therefore, we studied whether increased prepregnancy maternal weight was associated with timing of menarche in female offspring and, if so, whether it accounted for some or all of the association observed between offspring BMI and AOM. This study included data collected from a pregnancy cohort in two Danish cities, Aalborg and Odense, recruited between April 1984 and April 1987 as part of the health campaign “Healthy Habits for Two.” The women (n = 13,815) received a questionnaire during a routine visit to their midwives at the ∼36th week of pregnancy. Those who chose to participate returned the completed questionnaire via mail. The participating women (n = 11,980; ∼87% of all eligible) provided information about their health and lifestyles, including diet, smoking habits, and alcohol use during pregnancy (18Olsen J. Frische G. Poulsen A.O. Kirchheiner H. Changing smoking, drinking, and eating behaviour among pregnant women in Denmark. Evaluation of a health campaign in a local region.Scand J Soc Med. 1989; 17: 277-280PubMed Google Scholar). Prepregnancy height and weight were reported to their doctors at the first routine antenatal visit when their current height and weight were being measured, to reduce reporting bias. The records were later retrieved for the study purposes. Additional demographic and obstetric information were collected from the medical forms at child birth. In 2005, a total of 4,669 girls (out of 5,427 liveborn singleton girls) who were still alive and living in Denmark were contacted to complete an online survey that included questions on menarcheal age. All participants (3,382, 72%) were first asked whether they had reached menarche. If affirmed, they were asked to provide the month and the year when they reached their menarche. Of the total participants, 3,169 (94%) provided their age at menarche at least in years, and they made up the study population; another ten (0.3%) had not reached menarche yet. Among the 3,169 participants, about one-half (n = 1,634) provided information about both year and month. The months of menarche were converted into years and added to the year to form a continuous outcome variable. Maternal prepregnancy BMI was calculated by dividing prepregnancy weight in kilograms by their height in meters squared. Two offspring BMIs were calculated similarly, with heights and weights reported by: 1) mothers in 2002 (offspring ages 14–18 years); and 2) offspring in 2005 at ages 17–21 years. We examined both offspring BMIs as main exposure because only about two-thirds of the mothers provided the data. All BMIs were categorized into underweight (<18.5 kg/m2), normal (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (≥30 kg/m2), based on the World Health Organization criteria (19World Health Organization (WHO). Obesity: preventing and managing the global epidemic. Report of a WHO consultation (WHO technical report series 894) 2000. Geneva, Switzerland. Available at: http://whqlibdoc.who.int/trs/WHO_TRS_894.pdf. Accessed October 9, 2010.Google Scholar), for subgroup analyses. Multiple linear regression analyses were conducted to examine the association between maternal prepregnancy BMI and AOM. If maternal BMI programs AOM, we would expect an association between maternal BMI and AOM also in daughters with normal-to-low BMI (<25 kg/m2). If, on the other hand, the association is driven by daughter’s BMI, we would expect to see an association between daughter’s BMI and AOM even when their mothers had normal-to-low BMI. We therefore analyzed these associations in the full dataset and in subsamples restricted to either mothers or daughters with normal/low BMI. All regression analyses were conducted with the subsets that provided AOM in either only years or both months and years and finally with the full sample (i.e., AOM in at least years). All analyses included the following covariates chosen a priori based on literature reviews (20Rubin C. Maisonet M. Kieszak S. Monteilh C. Holmes A. Flanders D. et al.Timing of maturation and predictors of menarche in girls enrolled in a contemporary British cohort.Paediatr Perinat Epidemiol. 2009; 23: 492-504Crossref PubMed Scopus (88) Google Scholar, 21Baum 2nd, C.L. Ruhm C.J. Age, socioeconomic status and obesity growth.J Health Econ. 2009; 28: 635-648Crossref PubMed Scopus (147) Google Scholar, 22Sarlio-Lahteenkorva S. Lissau I. Lahelma E. The social patterning of relative body weight and obesity in Denmark and Finland.Eur J Public Health. 2005; 16: 36-40Crossref PubMed Scopus (22) Google Scholar, 23Laurier D. Guiguet M. Chau N.P. Wells J.A. Valleron A.J. Prevalence of obesity: a comparative survey in France, the United Kingdom and the United States.Int J Obes Relat Metab Disord. 1992; 16: 565-572PubMed Google Scholar) and guided by directed acyclic graphs (DAGs): maternal age at childbirth, maternal education (elementary school, school leaving certificate, upper secondary education), marital status (married, cohabiting, single), and maternal smoking during pregnancy (no smoking, stopped smoking by 36th week of pregnancy, smoked one to nine cigarettes/day in late pregnancy, smoked ten or more cigarettes/day in late pregnancy). We also examined for interaction between maternal and offspring BMI (P=.6) and between maternal BMI and three levels of pregnancy smoking (P values 0.4–0.8). All analyses were conducted by using SAS software, version 9.2 (24SASSAS 9.2. SAS Institute, Cary, North Carolina2008Google Scholar). The study was approved by the University of California, Los Angeles, internal review board and the Danish Data Protection Agency. The demographic characteristics across the subsets with AOM in both months and years and in only years were fairly similar. The mean AOMs were 13.3 and 12.9 years while prepregnancy BMI was 21.7 and 21.8 kg/m2, respectively, in the two subsets. The majority of mothers (89%, 87%) and offspring (86%, 84%) were underweight or normal weight (BMI <25 kg/m2) across the subsets. Many mothers reported having smoked at some point during the pregnancy (40%, 44%), and the majority of them (85%, 87%) were still smoking in late pregnancy (at the ∼36th week of gestation). In the subset with detailed timing of AOM, every unit increase in maternal BMI corresponded with an acceleration in AOM by 8.1 days (95% confidence interval [CI] −16.2 to 0.0) in the offspring, whereas every unit increase in offspring BMI corresponded with a larger acceleration in AOM (−32.4 days [95% CI −41.9 to −23.0] and −18.9 days [95% CI −26.0 to −11.9] for maternal reported and self-reported BMI, respectively; Table 1). When maternal and offspring BMI were mutually adjusted, it had little impact on the association between offspring BMI and AOM, but the association between maternal BMI and AOM notably attenuated (Table 1). When the analyses were restricted to mothers with a prepregnancy BMI <25 kg/m2 (underweight/normal weight), the offspring BMI showed a strong inverse association with AOM (−22.2 days [95% CI −30.6 to −13.7]), whereas the analysis restricted to daughters with BMI <25 kg/m2 indicated only a small statistically nonsignificant inverse association between AOM and maternal BMI (−3.6 days [95% CI −13.5 to 6.3]). In the subset where the participants provided only the year of menarche, all the associations were similar to the former subset except for the subgroup analysis of offspring with self-reported BMI <25 kg/m2, where the association did not attenuate (Table 1). Note: AOM = age of menarche; BMI = body mass, index (kg/m2). We found no strong support for a programming effect of maternal prepregnancy BMI on AOM, but a small effect cannot be ruled out. Whereas the results indicate that daughter’s BMI plays an important role in accelerating AOM independent of the mother’s prepregnancy BMI. Some studies have linked polycystic ovary syndrome (PCOS) and obesity in mothers as well as prenatal exposure to androgen with obesity and PCOS in female offspring later in life (25Cresswell J.L. Barker D.J. Osmond C. Egger P. Phillips D.I. Fraser R.B. Fetal growth, length of gestation, and polycystic ovaries in adult life.Lancet. 1997; 350: 1131-1135Abstract Full Text Full Text PDF PubMed Scopus (191) Google Scholar, 26Abbott D.H. Dumesic D.A. Eisner J.R. Colman R.J. Kemnitz J.W. Insights into the development of PCOS from studies of prenatally androgenized female rhesus monkeys.Trends Endocrinol Metab. 1998; 9: 62-67Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar, 27Eisner J.R. Dumesic D.A. Kemnitz J.W. Abbott D.H. Timing of prenatal androgen excess determines differential impairment in insulin secretion and action in adult female rhesus monkeys.J Clin Endocrinol Metab. 2000; 85: 1206-1210Crossref PubMed Scopus (159) Google Scholar, 28Padmanabhan V. Evans N. Taylor J.A. Robinson J.E. Prenatal exposure to androgen leads to the development of cystic ovaries in the sheep.Biol Reprod. 1997; 56: 194PubMed Google Scholar). Similarly, studies have linked prenatal exposure to excess estrogen or estrogen-like chemicals (e.g., diethystillbestrol, xenoestrogen) with malformation of male reproductive organs and cancer in female reproductive organs (10Fernandez M.F. Olmos B. Granada A. Lopez-Espinosa M.J. Molina-Molina J.M. Fernandez J.M. Cruz M. et al.Human exposure to endocrine-disrupting chemicals and prenatal risk factors for cryptorchidism and hypospadias: a nested case-control study.Environ Health Perspect. 2007; 115: 8-14Crossref PubMed Scopus (185) Google Scholar, 11Bornstein J. Adam E. Adler-Storthz K. Kaufman R.H. Development of cervical and vaginal squamous cell neoplasia as a late consequence of in utero exposure to diethylstilbestrol.Obstet Gynecol Surv. 1988; 43: 15-21Crossref PubMed Scopus (29) Google Scholar, 12Ramlau-Hansen C.H. Nohr E.A. Thulstrup A.M. Bonde J.P. Storgaard L. Olsen J. Is maternal obesity related to semen quality in the male offspring? A pilot study.Hum Reprod. 2007; 22: 2758-2762Crossref PubMed Scopus (38) Google Scholar). Such findings suggest fetal programming of ovarian function. In two recent studies, an inverse association was observed between maternal prepregnancy BMI and AOM in daughters (20Rubin C. Maisonet M. Kieszak S. Monteilh C. Holmes A. Flanders D. et al.Timing of maturation and predictors of menarche in girls enrolled in a contemporary British cohort.Paediatr Perinat Epidemiol. 2009; 23: 492-504Crossref PubMed Scopus (88) Google Scholar, 29Keim S.A. Branum A.M. Klebanoff M.A. Zemel B.S. Maternal body mass index and daughters’ age at menarche.Epidemiology. 2009; 20: 677-681Crossref PubMed Scopus (50) Google Scholar). In one study, the association remained even after adjusting for the child BMI measured at age 7 years (29Keim S.A. Branum A.M. Klebanoff M.A. Zemel B.S. Maternal body mass index and daughters’ age at menarche.Epidemiology. 2009; 20: 677-681Crossref PubMed Scopus (50) Google Scholar). In the present study, we found inverse association between offspring BMI and early AOM, with slightly stronger association for the BMI reported by mothers, which may support the importance of prepubertal BMI. The maternal reports are closer to this time frame (14-18 years). A high childhood BMI often persists into adulthood (30Venn A.J. Thomson R.J. Schmidt M.D. Cleland V.J. Curry B.A. Gennat H.C. et al.Overweight and obesity from childhood to adulthood: a follow-up of participants in the 1985 Australian Schools Health and Fitness Survey.Med J Aust. 2007; 186: 458-460PubMed Google Scholar, 31Singh A.S. Mulder C. Twisk J.W. van Mechelen W. Chinapaw M.J. Tracking of childhood overweight into adulthood: a systematic review of the literature.Obes Rev. 2008; 9: 474-488Crossref PubMed Scopus (1690) Google Scholar, 32Kindblom J.M. Lorentzon M. Hellqvist A. Lonn L. Brandberg J. Nilsson S. et al.BMI changes during childhood and adolescence as predictors of amount of adult subcutaneous and visceral adipose tissue in men: the GOOD study.Diabetes. 2009; 58: 867-874Crossref PubMed Scopus (45) Google Scholar), and it is plausible that the offspring BMIs correlate well with their prepubertal BMIs. The main advantage of the present study is the longitudinal data collection, which provides temporal divides between prenatal exposures, postnatal exposures, and outcome measures. Moreover, the prenatal exposures were measured when the mothers were pregnant, making differential recall bias unlikely. Limitations of the study include lack of data on prepubertal BMI, maternal AOM, and complete AOM data for all participants. In summary, our findings did not support maternal BMI accounting for the strong association between child BMI and AOM. Given the continuing obesity epidemic that starts in childhood, we expect a continuing decline in AOM in many countries worldwide. The authors are grateful to the Institute of Public Health, Aarhus University, for providing the data for this study.
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