Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, (Haartmaninkatu 3), P.O BOX 21, 00014, Helsinki, Finland.
Clinical Medicine Research Unit, MRC Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland.
BMC Pregnancy Childbirth. 2024 Jan 24;24(1):78. doi: 10.1186/s12884-024-06274-9.
A substantial proportion of maternal pregnancy complications, adverse birth outcomes and neurodevelopmental delay in children may be attributable to high maternal pre-pregnancy Body Mass Index (BMI). However, BMI alone is insufficient for the identification of all at-risk mothers and children as many women with non-obesity(< 30 kg/m) or normal weight(18.5-24.99 kg/m) and their children may suffer from adversities. Evidence suggests that BMI-related metabolic changes during pregnancy may predict adverse mother-child outcomes better than maternal anthropometric BMI.
In a cohort of 425 mother-child dyads, we identified maternal BMI-defined metabolome based on associations of 95 metabolic measures measured three times during pregnancy with maternal pre-pregnancy BMI. We then examined whether maternal BMI-defined metabolome performed better than anthropometric BMI in predicting gestational diabetes, hypertensive disorders, gestational weight gain (GWG), Caesarian section delivery, child gestational age and weight at birth, preterm birth, admission to neonatal intensive care unit (NICU), and childhood neurodevelopment. Based on metabolic measures with the highest contributions to BMI-defined metabolome, including inflammatory and glycolysis-related measures, fatty acids, fluid balance, ketone bodies, lipids and amino acids, we created a set of maternal high BMI-related polymetabolic risk scores (PMRSs), and in an independent replication cohort of 489 mother-child dyads tested their performance in predicting the same set of mother-child outcomes in comparison to anthropometric BMI.
BMI-defined metabolome predicted all of the studied mother-child outcomes and improved their prediction over anthropometric BMI, except for gestational hypertension and GWG. BMI-related PMRSs predicted gestational diabetes, preeclampsia, Caesarian section delivery, admission to NICU, lower gestational age at birth, lower cognitive development score of the child, and improved their prediction over anthropometric BMI. BMI-related PMRSs predicted gestational diabetes, preeclampsia, Caesarean section delivery, NICU admission and child's lower gestational age at birth even at the levels of maternal non-obesity and normal weight.
Maternal BMI-defined metabolome improves the prediction of pregnancy complications, birth outcomes, and neurodevelopment in children over anthropometric BMI. The novel, BMI-related PMRSs generated based on the BMI-defined metabolome have the potential to become biomarkers identifying at-risk mothers and their children for timely targeted interventions even at the level of maternal non-obesity and normal weight.
大量的孕产妇妊娠并发症、不良分娩结局和儿童神经发育迟缓可归因于孕妇孕前体重指数（BMI）较高。然而，仅 BMI 不足以识别所有高危孕妇和儿童，因为许多非肥胖（<30kg/m2）或正常体重（18.5-24.99kg/m2）的妇女及其子女可能会遭受不良影响。有证据表明，妊娠期间与 BMI 相关的代谢变化可能比母体人体测量学 BMI 更好地预测母婴不良结局。
在一个由 425 对母婴对子组成的队列中，我们根据 95 种代谢物在妊娠期间与孕妇孕前 BMI 的三次关联，确定了基于母体 BMI 的代谢组。然后，我们研究了母体 BMI 定义的代谢组在预测妊娠糖尿病、高血压疾病、妊娠体重增加（GWG）、剖宫产分娩、胎儿孕龄和出生体重、早产、新生儿重症监护病房（NICU）入院以及儿童神经发育方面是否优于人体测量学 BMI。基于对 BMI 定义的代谢组有最高贡献的代谢物，包括炎症和糖酵解相关指标、脂肪酸、液体平衡、酮体、脂质和氨基酸，我们创建了一组母体高 BMI 相关的多代谢风险评分（PMRS），并在一个由 489 对母婴对子组成的独立复制队列中，比较了它们在预测相同的母婴结局方面的表现，与人体测量学 BMI 相比。
BMI 定义的代谢组预测了所有研究的母婴结局，并提高了对人体测量学 BMI 的预测，除了妊娠高血压和 GWG。BMI 相关的 PMRS 预测了妊娠糖尿病、子痫前期、剖宫产分娩、NICU 入院、出生时较低的胎龄、儿童认知发育评分较低，并提高了对人体测量学 BMI 的预测。即使在孕妇非肥胖和正常体重水平，BMI 相关的 PMRS 也预测了妊娠糖尿病、子痫前期、剖宫产分娩、NICU 入院和儿童出生时较低的胎龄。
母体 BMI 定义的代谢组改善了人体测量学 BMI 对妊娠并发症、分娩结局和儿童神经发育的预测。基于 BMI 定义的代谢组生成的新型 BMI 相关 PMRS 具有成为生物标志物的潜力，即使在母体非肥胖和正常体重水平，也可以识别高危孕妇及其子女，并及时进行有针对性的干预。
