Effect of common pregnancy and perinatal complications on offspring metabolic traits across the life course: a multi-cohort study

Abstract

Background Common pregnancy and perinatal complications are associated with offspring cardiometabolic risk factors. These complications may influence multiple metabolic traits in the offspring and these associations might differ with offspring age. Methods We used data from eight population-based cohort studies to examine and compare associations of pre-eclampsia (PE), gestational hypertension (GH), gestational diabetes (GD), preterm birth (PTB), small (SGA) and large (LGA) for gestational age (vs. appropriate size for gestational age (AGA)) with up to 167 plasma/serum-based nuclear magnetic resonance-derived metabolic traits encompassing lipids, lipoproteins, fatty acids, amino acids, ketones, glycerides/phospholipids, glycolysis, fluid balance, and inflammation. Confounder-adjusted regression models were used to examine associations (adjusted for maternal education, parity age at pregnancy, ethnicity, pre/early pregnancy body mass index and smoking, and offspring sex and age at metabolic trait assessment), and results were combined using meta-analysis by five age categories representing different periods of the offspring life course: neonates (cord blood), infancy (mean ages: 1.1–1.6 years), childhood (4.2–7.5 years); adolescence (12.0–16.0 years), and adulthood (22.0–67.8 years). Results Offspring numbers for each age category/analysis varied from 8925 adults (441 PTB) to 1181 infants (135 GD); 48.4% to 60.0% were females. Pregnancy complications (PE, GH, GD) were each associated with up to three metabolic traits in neonates (P≤0.001) with some evidence of persistence to older ages. PTB and SGA were associated with 32 and 12 metabolic traits in neonates respectively, which included an adjusted standardised mean difference of −0.89 standard deviation (SD) units for albumin with PTB (95% CI: −1.10 to −0.69, P=1.3×10−17) and −0.41 SD for total lipids in medium HDL with SGA (95% CI: −0.56 to −0.25, P=2.6×10−7), with some evidence of persistence to older ages. LGA was inversely associated with 19 metabolic traits including lower levels of cholesterol, lipoproteins, fatty acids, and amino acids, with associations emerging in adolescence, (e.g. −0.11 SD total fatty acids, 95% CI: −0.18 to −0.05, P=0.0009), and attenuating with older age across adulthood. Conclusions These reassuring findings suggest little evidence of wide-spread and long-term impact of common pregnancy and perinatal complications on offspring metabolic traits, with most associations only observed for newborns rather than older ages, and for perinatal rather than pregnancy complications.

Perinatal Factors and its Association with Cardiometabolic Profile in Schoolchildren

“…Complications during pregnancy can have long-lasting effects on the health of the child, several risk factors like the obstetric complications as preterm labor and their long-term maternal effects serve as indicators for an elevated risk of acute cardiovascular complications during delivery and pose a long-term risk for CVD for both the mother and the offspring [28,29]. These complications can impact various metabolic traits in the offspring, its fetal growth and development [30]. In our research, the offspring of mothers without complications during pregnancy exhibited higher levels of CRF, suggesting better physical development and overall cardiorespiratory health.…”

Social inequalities in pregnancy metabolic profile: findings from the multi-ethnic Born in Bradford cohort study

“…A SEP by ethnicity (i.e., White European, or South Asian) interaction term was included in all models to investigate ethnic differences in associations between SEP and metabolic traits. All metabolic traits were standardised (by ethnicity group to mean=0, SD=1) to aid comparison of results between different metabolic traits 25 . In sensitivity analysis, we repeated the LCA and regression modelling separately in White European and South Asian women and separately in the White 10 British and Pakistani women (the two biggest groups within the White European and South Asian ethnic groups).…”

Social inequalities in pregnancy metabolic profile: findings from the multi-ethnic Born in Bradford cohort study

“…Ethnic differences in the associations between SEP and metabolic traits were examined by including an interaction term between SEP and ethnicity (i.e., White European, or South Asian) in all models. All metabolic traits were standardised (to mean = 0, SD = 1) to aid comparison of results for different metabolic traits [ 26 ]. Standardisation was done separately by ethnicity because we have previously found differences in pregnancy metabolic traits between White European and South Asians in this cohort [ 14 ].…”