Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, USA.
Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA.
Hum Reprod. 2022 Aug 25;37(9):2154-2166. doi: 10.1093/humrep/deac143.
Are maternal anthropometrics associated with anogenital distance (AGD) and 2:4 digit ratio (2:4D) in newborns?
Select maternal anthropometrics indicative of obesity or increased adiposity are associated with elongated AGD in daughters.
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, METHODS: Most 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).
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.
Increased 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.
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母体人体测量学与新生儿的肛门生殖器距离（AGD）和 2:4 指长比（2:4D）有关吗？
表明肥胖或脂肪增加的母体人体测量学与女儿的 AGD 延长有关。
母亲在怀孕前或怀孕初期体重或肥胖过多可能会影响儿童生殖和其他受荷尔蒙调节的发育。AGD 和 2:4D 是宫内生殖发育的拟议标志物。
研究设计、规模、持续时间：本研究包括来自美国伊利诺伊州香槟市的伊利诺伊州儿童发展研究（I-KIDS）的 450 对母婴对，这是一项前瞻性的妊娠队列研究。参与者于 2013 年至 2018 年期间入组。
参与者/材料、地点、方法：本研究中的大多数母亲受过大学教育（82%），是非西班牙裔白人（80%），55%的母亲在怀孕前体重不足或正常。孕妇在 18-40 岁时报告怀孕前的体重和身高，以计算怀孕前的 BMI。在怀孕 8-15 周时，我们测量了腰围和臀围，并使用生物电阻抗分析评估了体重、体脂肪百分比、内脏脂肪水平、肌肉百分比和 BMI。在新生儿出生后 24 小时内，我们测量了新生儿的第二和第四左/右手指数，以计算 2:4D。在女儿中，我们测量了 AGDAF（肛门至四叉）和 AGDAC（肛门至阴蒂）。在儿子中，我们测量了 AGDAS（肛门至阴囊）和 AGDAP（肛门至阴茎基部）。
母体人体测量学的某些指标与新生儿女儿的 AGD 呈正相关，但与儿子无关。例如，AGDAC 每增加一个四分位距（IQR），与孕前 BMI 增加 0.73mm（95%CI：0.15，1.32）相关，而与臀围增加 0.88mm（95%CI：0.18，1.58）相关，而 AGDAF 每增加一个 IQR，与腰围增加 0.51mm（95%CI：0.03，1.00）和 0.56mm（95%CI：0.03，1.09）相关。母体体脂肪百分比和内脏脂肪水平的四分位分析一般支持线性关联，但在母体 %脂肪和内脏脂肪水平的 Q4（与 Q1 相比）与 AGDAC 之间存在额外的强关联。在四分位分析中，我们仅观察到母体人体测量学与 2:4D 之间存在一些适度的关联，这些关联因手（左手与右手）和新生儿性别而异。尽管总是存在虚假发现的可能性，但女性 AGD 的两种测量值的关联在多个母体人体测量指标中是一致的，这加强了我们的结论。
局限性、谨慎的原因：我们的研究样本在种族和民族上是同质的，受教育程度和健康状况相对较好，因此我们的研究结果可能不适用于其他人群。此外，我们可能没有足够的能力来确定某些性别特异性关联，特别是对于 2:4D。
母亲在怀孕前和怀孕初期体重和肥胖增加可能会使女性的 AGD 延长，这需要进一步研究。
研究资助/利益冲突：本文的发表得到了美国国立环境卫生科学研究所（NIH/NIEHS）拨款 ES024795 和 ES022848、美国国立儿童健康与人类发育研究所拨款 R03HD100775、美国环境保护署拨款 RD83543401 和美国国立卫生研究院主任办公室拨款 OD023272 的支持。其内容完全由受赠方负责，并不一定代表美国 EPA 或 NIH 的官方观点。此外，美国 EPA 不认可购买出版物中提到的任何商业产品或服务。该项目还得到了美国农业部国家食品和农业研究所和密歇根州农业生物研究的支持。作者声明没有利益冲突。
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