Family history is a predictor of current preterm birth

Abstract

Background: Reliable prediction of spontaneous preterm birth remains limited, particularly for nulliparous and multiparous women without a personal history of preterm birth. Although previous preterm birth is a risk factor for recurrent preterm birth, most spontaneous preterm births occur in women with no previous history of preterm birth.

Objective: This study aimed to determine whether patients' self-reported maternal family history of preterm births among siblings and across 3 generations was an independent risk factor for spontaneous preterm births after controlling for potential confounders.

Study design: This was a retrospective analysis of a prospectively acquired cohort using a comprehensive single, academic center database of deliveries from August 2011 to July 2017. The objective of the current analysis was to evaluate the risk of preterm birth among women with and without a family history of preterm birth. All subjects in the database were directly queried regarding familial history across 3 generations, inclusive of obstetrical morbidities. Index subjects with probable indicated preterm birth (eg, concurrent diagnosis of preeclampsia; hemolysis, elevated liver enzymes, and low platelet count; or placenta previa or placenta accreta) were excluded, as were nonsingleton pregnancies. Univariate and multivariate analyses with logistic regression were used to determine significance and adjusted relative risk.

Results: In this study, 23,816 deliveries were included, with 2345 (9.9%) born prematurely (<37 weeks' gestation). Across all subjects, preterm birth was significantly associated with a maternal family history of preterm birth by any definition (adjusted relative risk, 1.44; P<.001), and the fraction of preterm birth occurring in women with a positive family history increased with decreasing gestational age at which the index subjects of preterm birth occurred. For nulliparous women, a history in the subject's sister posed the greatest risk (adjusted relative risk, 2.25; P=.003), whereas for multiparous women with no previous preterm birth, overall family history was most informative (P=.003). Interestingly, a personal history of the index subject herself being born preterm presented the greatest individual risk factor (adjusted relative risk, 1.94; P=.004).

Conclusion: Spontaneous preterm birth in the current pregnancy was significantly associated with a maternal family history of preterm birth among female relatives within 3 generations and notably sisters. The risk persisted among gravidae without a previous preterm birth, demonstrating the capacity for familial history to independently predict risk of spontaneous preterm birth even in the context of a negative personal history. This study provides evidence that self-reported maternal family history is relevant in a US population cohort and across more distant generations than has previously been reported.

Keywords: family history; heritability; preterm birth risk; spontaneous preterm birth.