Anshu Shrestha

Smoking and alcohol use during pregnancy and age of menarche in daughters

BACKGROUND We assessed whether exposure to prenatal smoking or alcohol accelerates age of menarche (AOM) in offspring. METHODS We studied a Danish cohort of 3169 singleton females born in April 1984-April 1987. Linear regressions were conducted to examine associations between prenatal smoking or alcohol exposure and offsprings AOM on: (i) the daughters who provided data on both month and the year of menarche (n= 1634) and (ii) the entire sample that provided at least the year of menarche (n= 3169). We also examined associations between only pre-pregnancy smoking or childhood exposure to smoking and AOM. The full model was adjusted for maternal pre-pregnancy body mass index, maternal age at childbirth, parental socio-economic status, parity, consumption of milk products during pregnancy and marital status. RESULTS Among those who provided both year and month, AOM was accelerated by 2.8 months (95% CI in months: -5.3, -0.4) among those exposed to 10+ cigarettes/day throughout pregnancy and by 4.1 months (95% CI in months: -7.7, -0.5) among those with mothers who quit smoking sometime during pregnancy, compared with the unexposed group after adjustment for covariates. Similar, but much weaker, associations were observed among girls whose mothers smoked 1-9 cigarettes/day throughout pregnancy or whose fathers smoked compared with their unexposed counterparts after adjustment for covariates [-0.8 months (95% CI: -2.6, 1.0)]. No associations were observed between AOM and only pre-pregnancy smoking or only childhood exposure or prenatal alcohol exposure. CONCLUSIONS Our study indicates that heavy smoking throughout the pregnancy may be important in prenatal programming of AOM.

Obesity and age at menarche

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 daughters age of menarche (AOM) and, if so, whether it accounted for part or all of the association between daughters 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.

Early life factors and risk of childhood rhabdomyosarcoma

Although little is known about etiology of childhood rhabdomyosarcoma (RMS), early life factors are suspected in the etiology. We explored this hypothesis using linked data from the California Cancer Registry and the California birth rolls. Incident cases were 359 children <6-year-old (218 embryonal, 81 alveolar, 60 others) diagnosed in 1988–2008. Controls (205, 173), frequency matched on birth year (1986–2007), were randomly selected from the birth rolls. We examined association of birth characteristics such as birth weight, size for gestational age, and timing of prenatal care with all-type RMS, embryonal, and alveolar subtypes. Crude and adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression. In contrast to a previous study, we observed statistically non-significant association for embryonal subtype among high birth weight (4000–5250 g) children for term births [OR (95% CI): 1.28 (0.85, 1.92)] and all births adjusted for gestational age [OR (95% CI): 1.21 (0.81, 1.81)]. On the other hand, statistically significant 1.7-fold increased risk of alveolar subtype (95% CI: 1.02, 2.87) was observed among children with late or no prenatal care and a 1.3-fold increased risk of all RMS subtypes among children of fathers ≥35 years old at child birth (95% CI: 1.00, 1.75), independent of all covariates. Our finding of positive association on male sex for all RMS types is consistent with previous studies. While we did not find a convincingly positive association between high birth weight and RMS, our findings on prenatal care supports the hypothesis that prenatal environment modifies risk for childhood RMS.

Maternal cigarette smoking during pregnancy and pubertal development in sons. A follow‐up study of a birth cohort

Epidemiological studies have raised concern about the reproductive consequences of prenatal cigarette smoking exposure, possibly affecting semen quality and onset of pubertal development of the offspring. The aim of this study was to further investigate pubertal development in young men exposed to cigarette smoking in foetal life. In a Danish pregnancy cohort, information on maternal smoking during pregnancy was available from questionnaires administered in 1984–1987, and information on pubertal development, assessed by age at first nocturnal emission, acne, voice break and regular shaving, was obtained from a follow‐up questionnaire administered in 2005 to the young men (age: 18–21). We found no significant association between prenatal cigarette smoking exposure and earlier onset of puberty, but we did observe a tendency towards earlier age of first nocturnal emission, acne and voice break, indicating an accelerated age of pubertal development. Men exposed to ≥15 cigarettes/day had 3.1 months (95% CI: −6.4; 0.2) earlier age at acne and 2.2 months (95% CI: −7.3; 3.0) earlier age at first nocturnal emission, 1.2 months (95% CI: −4.6; 2.2) earlier age at voice break, however, 1.3 months (95% CI: −1.6; 4.3) later age at regular shaving, compared with unexposed men. Prenatal cigarette smoking exposure may induce an earlier age at onset of puberty in young men, but larger studies with prospectively collected data on pubertal development are needed to explore this hypothesis further.

Parental age at childbirth and age of menarche in the offspring

BACKGROUND Early age of menarche (AOM) is associated with serious health problems including breast cancer and heart disease. Rising parental age at childbirth is associated with some adverse health outcomes in the offspring, but whether early menarche is one of them is not known. METHODS We studied a Danish cohort of singleton females (n = 3168) born in 1984-1987. Prenatal data were collected from mothers around 36th week of pregnancy (self-administered questionnaire), although the menarcheal age was collected from daughters aged 17-21 years in 2005 (Web-based questionnaire). We assessed each parental age association in separate linear regression models adjusted for covariates (socioeconomic status, parity, maternal pre-pregnancy BMI, marital status, maternal smoking and daughters self-reported BMI), then included both ages in a third model. RESULTS Each year increase in maternal age showed a 9 day earlier onset of menarche in daughters [95% confidence interval (CI): -15.98, -2.90] and a 5 day earlier onset for each year increase in paternal age [95% CI: -10.85, 0.00], after adjusting for covariates. However, these associations attenuated when adjusted for the other parent [change in AOM in days: (i) maternal: -8.49 (95% CI: -17.09, 0.12), (ii) paternal: -1.14 (95% CI: -8.13, 5.84)]. CONCLUSIONS We found no significant association between parental age and AOM, but the small sample of advance aged parents (over 30 years) limits the information we have. Future studies with a larger sample or a sample with over-representation of older parents will be of value.

Abstract 665: Association between early life factors and childhood rhabdomyosarcoma

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Background: Rhabdomyosarcoma (RMS) is the most common type of soft-tissue sarcoma among 0-19 year olds, with the incidence rate highest among children of ages 0-4. Since, childhood cancers tend to have relatively shorter lag time between exposure and disease, early childhood cancer such as RMS could be due to exposures during pregnancy or early infancy. Very little is known about environmental factors that may increase the susceptibility to RMS. Two major subtypes\_embryonal and alveolar\_have been linked with overexpression of the gene encoding insulin-like growth factor 2 (IFG2), which is also associated with fetal overgrowth syndrome. A couple of studies have suggested accelerated fetal growth as a risk factor, but needs to be confirmed. We examined associations between fetal growth measures and all RMS, and separately for the two major subtypes. We also examined other prenatal/perinatal factors including prenatal care, parental age, and parity. Methods: We conducted a population based case-control study in California by linking California Cancer registry and birth certificate data. Incident cases in children 0-5 ages (overall n=359, embryonal RMS=218, alveolar RMS=81) diagnosed in 1988-2008 and controls, frequency matched on birth year (1986-2007, n=205,230) were included. Logistic regression was applied to examine the associations of interest in crude and adjusted models. Results: The point estimates in adjusted models suggested an increased risk for embryonal RMS for all fetal growth measures employed, i.e., high birthweight (4000-5250 gms) at term births only, for high birth weight (4000-5250 gms) adjusted for gestational age, and large for gestational age births (OR (95%CI): 1.28 (0.85, 1.92); 1.21 (0.81, 1.81); 1.13 (0.73, 1.75) respectively), but not for alveolar RMS or overall RMS cases. We found increased risk for alveolar RMS among those with prenatal care starting after the first trimester or no care at all compared to prenatal care in the first trimester (OR(95%CI): 1.68 (1.01, 2.80)). Findings for other factors including higher risk among male and higher parental age at child birth were consistent with findings from existing studies. Conclusion: We did not find a convincingly positive association between fetal growth and RMS, although our data suggested small risk increases particularly for embryonal RMS. However, our findings on starting time of prenatal care and parental age at childbirth further support the notion that the early fetal/embryonic environment may be important for developing RMS in early childhood. Larger studies examining well-measured early life environment that may cause genetic and epigenetic alteration observed in RMS cases are needed to improve our understanding of the RMS etiology. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 665. doi:1538-7445.AM2012-665