Associations of maternal anthropometrics with newborn anogenital distance and the 2:4 digit ratio.

study questionAre maternal anthropometrics associated with anogenital distance (AGD) and 2:4 digit ratio (2:4D) in newborns? SUMMARY ANSWER: Select maternal anthropometrics indicative of obesity or increased adiposity are associated with elongated AGD in daughters. WHAT IS KNOWN ALREADY: Excessive maternal weight or adiposity before or in early pregnancy may impact child reproductive, and other hormonally mediated, development. AGD and 2:4D are proposed markers of in utero reproductive development. STUDY DESIGN, SIZE, DURATION: This study includes 450 mother/newborn dyads participating in the Illinois Kids Development Study (I-KIDS), a prospective pregnancy cohort from Champaign-Urbana, IL, USA. Participants included in the current study enrolled between 2013 and 2018. PARTICIPANTS/MATERIALS, SETTING,

methodsMost mothers in this study were college-educated (82%) and non-Hispanic White (80%), and 55% were under- or normal weight before pregnancy. Pregnant women aged 18-40 years reported pre-pregnancy weight and height to calculate pre-pregnancy BMI. At 8-15 weeks gestation, we measured waist and hip circumference, and evaluated weight, % body fat, visceral fat level, % muscle and BMI using bioelectrical impedance analysis. Within 24 h of birth, we measured newborn 2nd and 4th left/right digits to calculate the 2:4D. In daughters, we measured AGDAF (anus to fourchette) and AGDAC (anus to clitoris). In sons, we measured AGDAS (anus to scrotum) and AGDAP (anus to base of the penis). MAIN RESULTS AND THE ROLE OF CHANCE: Select maternal anthropometrics were positively associated with AGD in newborn daughters, but not sons. For example, AGDAC was 0.73 mm (95% CI: 0.15, 1.32) longer for every interquartile range (IQR) increase in pre-pregnancy BMI and 0.88 mm (95% CI: 0.18, 1.58) longer for every IQR increase in hip circumference, whereas AGDAF was 0.51 mm (95% CI: 0.03, 1.00) and 0.56 mm (95% CI: 0.03, 1.09) longer for every IQR increase in hip and waist circumference, respectively. Quartile analyses generally supported linear associations, but additional strong associations emerged in Q4 (versus Q1) of maternal % body fat and visceral fat levels with AGDAC. In quartile analyses, we observed only a few modest associations of maternal anthropometrics with 2:4D, which differed by hand (left versus right) and newborn sex. Although there is always the possibility of spurious findings, the associations for both measures of female AGD were consistent across multiple maternal anthropometric measures, which strengthens our conclusions. LIMITATIONS, REASONS FOR CAUTION: Our study sample was racially and ethnically homogenous, educated and relatively healthy, so our study may not be generalizable to other populations. Additionally, we may not have been powered to identify some sex-specific associations, especially for 2:4D. WIDER IMPLICATIONS OF THE

findingsIncreased maternal weight and adiposity before and in early pregnancy may lengthen the female AGD, which warrants further investigation. STUDY FUNDING/COMPETING INTEREST(S): This publication was made possible by the National Institute for Environmental Health Sciences (NIH/NIEHS) grants ES024795 and ES022848, the National Institute of Child Health and Human Development grant R03HD100775, the U.S. Environmental Protection Agency grant RD83543401 and National Institute of Health Office of the Director grant OD023272. Its contents are solely the responsibility of the grantee and do not necessarily represent the official views of the US EPA or NIH. Furthermore, the US EPA does not endorse the purchase of any commercial products or services mentioned in the publication. This project was also supported by the USDA National Institute of Food and Agriculture and Michigan AgBioResearch. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.