Pre-pregnancy and gestational cardiometabolic disorders and risk of preterm birth and infant mortality.

Background: Cardiometabolic disorders (CMDs) are common in pregnancy and can harm the offspring's health. While prior studies have explored clustered cardiometabolic risks in pregnancy, most have focused on a limited number of conditions or a single period. We aimed to examine the associations of individual, multiple, and separate and combined patterns of six pre-pregnancy and gestational CMDs with preterm birth and infant mortality. Methods: Using data from US National Vital Statistics System (2014-2020), we analysed pre-pregnancy CMDs (body mass index, diabetes, hypertension) and gestational CMDs (gestational weight gain, gestational diabetes, hypertensive disorders). We estimated the prevalence and time trends in CMDs using Joinpoint regression models and examined associations with preterm birth and infant mortality using multivariable logistic regression. Results: Among 24 447 869 mother-infant pairs, 1 932 716 (7.9%) were preterm births and 108 891 (0.5%) were infant deaths. Prevalence rates of most multi-CMD patterns increased significantly. There was a dose-response association between the number of pre-pregnancy and gestational CMDs and the risk of preterm birth and infant mortality (P for trend <0.001). Co-occurring pre-pregnancy diabetes and hypertension showed the strongest associations with preterm birth (odds ratio (OR) = 10.52; 95% CI = 9.71-11.40) and infant mortality (OR = 3.93; 95% CI = 2.99-5.18). Co-occurring inadequate gestational weight gain, gestational diabetes and hypertensive disorders showed the strongest association with preterm birth (OR = 4.57; 95% CI = 4.46-4.68). Specific combinations of pre-pregnancy and gestational CMD patterns such as pre-pregnancy diabetes and developed additional gestational hypertensive disorders experienced highest risk of preterm birth (OR = 18.80; 95% CI = 17.38-20.35). Conclusions: Increasing prevalence of multiple CMDs was associated with higher risks of preterm birth and infant mortality, emphasising the need for enhanced prevention and management of cardiometabolic health before and during pregnancy.