Wijesiriwardhana Prabhavi, Habtewold Tesfa Dejenie, Wang Guisong, Gleason Jessica L, Wapner Ronald J, Grantz Katherine L, Tekola-Ayele Fasil
Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892-7004, USA.
The Prospective Group (TPG), Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892-7004, USA.
Sci Rep. 2025 Jul 31;15(1):27915. doi: 10.1038/s41598-025-10415-1.
Low birthweight is more common among children born to nulliparas (women with no prior pregnancy lasting ≥20 weeks of gestation) compared to those born to multiparas (women with one or more prior pregnancies lasting ≥20 weeks). We investigated whether parity modifies the association of maternal genetic risk score (mGRS) of maternal birthweight-reducing genetic variants with fetal size and weekly growth pace (i.e., change in fetal size over a 1-week gestational age interval) at gestational weeks 10-40 in two multi-ancestral cohorts of pregnant women. mGRS, derived from previously identified birthweight-reducing maternal variants was tested for association with fetal size and weekly growth pace using linear regression adjusted for fetal sex and top 10 genetic principal components. Among nulliparas, but not among multiparas, higher birthweight-reducing mGRS was associated with lower fetal size and slower weekly growth pace as measured by fetal weight, humerus and femur lengths, and abdominal and head circumferences beginning from gestational week 11. The findings suggest that the maternal genetic factors target major physiological changes at the first pregnancy that get less profound with multi-parity. Considering parity as a biological variable may facilitate the precision of identifying sensitive intrauterine periods and interventions for pregnancy outcomes using genomics.
与经产妇（有一次或多次妊娠持续时间≥20周的女性）所生的孩子相比，低出生体重在初产妇（无先前妊娠持续时间≥20周的女性）所生的孩子中更为常见。我们在两个多祖先孕妇队列中研究了胎次是否会改变母亲出生体重降低遗传变异的母亲遗传风险评分（mGRS）与孕10至40周时胎儿大小和每周生长速度（即胎儿大小在1周胎龄间隔内的变化）之间的关联。使用针对胎儿性别和前10个遗传主成分进行调整的线性回归，对源自先前确定的降低出生体重的母亲变异的mGRS进行了与胎儿大小和每周生长速度的关联测试。在初产妇中，而不是经产妇中，从孕11周开始，较高的降低出生体重的mGRS与较低的胎儿大小和较慢的每周生长速度相关，胎儿大小通过胎儿体重、肱骨和股骨长度以及腹围和头围来衡量。研究结果表明，母亲遗传因素针对首次怀孕时的主要生理变化，而多胎妊娠时这些变化则不那么明显。将胎次视为一个生物学变量可能有助于提高使用基因组学识别敏感宫内时期和妊娠结局干预措施的准确性。
