Association of multiple pregnancies with risk of preterm birth in the United States: a retrospective cohort study.

Background: The elevated risks of adverse fetal and neonatal outcomes in multiple pregnancies (MPs) are predominantly driven by complications linked to preterm birth (PTB). However, studies on the association between MPs and PTB are limited. Furthermore, the impact of varying degrees of MPs on the likelihood of PTB is unclear, making it challenging to assess the PTB risk degree associated with different types of MPs. This uncertainty can consequently affect prenatal and perinatal management planning and fetal health. In this study, we aimed at examining the association between MPs and the risk of PTB in a large population-based study in the United States (US). Methods: This retrospective cohort study examined nationwide birth certificate data from the US National Vital Statistics System (NVSS) between 2016 and 2021. A total of 22,669,736 mothers who had live births and for whom data on the number of fetuses and gestational age at birth were available were included in this study. The exposure was MPs, including the twin, triplet, quadruplet, or more pregnancy. The main outcome was PTB, which is defined as birth before 37 weeks' gestation. The important covariates included maternal age and education, race or ethnicity, marital status, pre-pregnancy body mass index (BMI), smoking during pregnancy, previous history of PTB and cesarean, pre-pregnancy diabetes and hypertension, gestational diabetes and hypertension or pre-eclampsia, eclampsia, infertility treatment, prenatal care, and maternal sexually transmitted infections. The association between MPs and PTB was estimated through logistic regression. Results: This study enrolled in 22,669,736 mothers {mean [standard deviation (SD)] age, 29.05 (5.8) years; the Hispanic, 5,365,989 (23.7%); the non-Hispanic White, 11,680,688 mothers (51.5%); the non-Hispanic Black, 3,269,219 (14.4%) as, and the non-Hispanic Asian 1,418,537 (6.3%)}. Among the mothers, 732,289 (3.2%) were twin pregnancy, 19,573 (0.1%) were triplet pregnancy, and 1,066 (<0.1%) were quadruplet or higher pregnancy. Among the newborns, the PTB accounted for 11.8% (2,683,587 cases), of which 10.2% (2,242,028 cases) were single births, 57.6% (422,097 cases) were twin births, 94.2% (18,446 cases) were triplets, and 95.3% (1,016 cases) were quadruplets or more. After adjustment for all the covariates in this study, the adjusted odds ratio (OR) of PTB was 12.03 [95% confidence interval (CI): 11.97-12.10] for twin, 139.08 (95% CI: 130.43-148.30) for triplet, 161.17 (95% CI: 118.80-218.65) for quadruplet or higher, and 12.51 (95% CI: 12.44-12.58) for any kinds of MPs comparing mothers with these conditions and those without. Conclusions: This study found that MPs were associated with increased risk of PTB, with the risk magnifying as the number of fetuses increases, which may help us to accurately judge the risk degree of PTB in different type of MPs, and provide reference value for the formulation of prenatal and perinatal management planning.