Birth size and age at menarche: a twin perspective.

STUDY QUESTION: Do birthweight (BW) and co-twin sex influence the age at menarche in twins? SUMMARY ANSWER: BW, but not co-twin sex, was associated with age at menarche in twins. However, BW was not associated with age at menarche after controlling for genetics and shared rearing environment. WHAT IS KNOWN ALREADY: Nutritional deprivation during critical developmental periods can trigger long-term effects on health. A small size at birth has been associated with early age at menarche in singletons. However, the relative influence of genetics and environmental factors on this association remains unresolved. STUDY DESIGN, SIZE, DURATION: In total, 2505 twin pairs were included in this cohort study. PARTICIPANTS/MATERIALS, SETTING,
METHODS: All participants were recruited from the Danish Twin Register. Data on the age at menarche were collected by questionnaire and combined with data on BW, birth length (BL) and gestational age (GA) from the Danish Medical Birth register. The BW for GA standard deviation score (BW-SDS) was calculated. MAIN RESULTS AND THE ROLE OF CHANCE: BW-SDS [hazard ratio (HR) 0.96; 95% confidence interval (CI): 0.93-0.00], P = 0.04], but not BW, BL or GA (P ≥ 0.15), was positively associated with age at menarche in all twins after adjustment for zygosity and year of birth. However, BW-SDS was not associated with menarcheal age within twin pairs (HR 1.01; 95% CI: 0.91-1.12, P = 0.88). No differences were found in the age at menarche or birth size between twin girls from same sex and twin girls from opposite-sex pregnancies. Heritability of menarcheal age and BW were estimated to be 0.61 (95% CI: 0.38-0.84) and 0.27 (95% CI: 0.18-0.38), respectively. Both BW and menarcheal age were influenced by genetic and environmental factors. LIMITATIONS, REASONS FOR CAUTION: A limitation of this study is recall bias on the age at menarche. It is also not clear how these results should be extrapolated to the non-twin population. WIDER IMPLICATIONS OF THE
FINDINGS: lower BW for GA is associated with earlier age at menarche in twin girls. However, the lack of within-pair differences in menarcheal age between even markedly BW-discordant twins indicates that this association is governed by environmental or genetic factors shared by both twins. Thus, within-pair differences in intrauterine nutritional factors leading to discordant growth do not seem to influence timing of menarche. STUDY FUNDING/COMPETING INTEREST(S): The authors have nothing to declare. Departmental funds were used to support all authors during the study period and preparation.