Population-based estimate of sibling risk for preterm birth, preterm premature rupture of membranes, placental abruption and pre-eclampsia

Jevon Plunkett¹^,4^,5 , Ingrid Borecki³^,4^,5 , Thomas Morgan¹^,4 , David Stamilio²^,4 and Louis J Muglia¹^,2^,4^,5

¹Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA

²Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri 63110, USA

³Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri 63110, USA

⁴Center for Preterm Birth Research, Washington University School of Medicine, St. Louis, Missouri 63110, USA

⁵Human and Statistical Genetics Program, Washington University School of Medicine, St. Louis, Missouri 63110, USA

author email corresponding author email

BMC Genetics 2008, 9:44doi:10.1186/1471-2156-9-44


Published:	8 July 2008

Abstract

Background

Adverse pregnancy outcomes, such as preterm birth, preeclampsia and placental abruption, are common, with acute and long-term complications for both the mother and infant. Etiologies underlying such adverse outcomes are not well understood. As maternal and fetal genetic factors may influence these outcomes, we estimated the magnitude of familial aggregation as one index of possible heritable contributions.

Using the Missouri Department of Health's maternally-linked birth certificate database, we performed a retrospective population-based cohort study of births (1989–1997), designating an individual born from an affected pregnancy as the proband for each outcome studied. We estimated the increased risk to siblings compared to the population risk, using the sibling risk ratio, λ_s, and sibling-sibling odds ratio (sib-sib OR), for the adverse pregnancy outcomes of preterm birth, preterm premature rupture of membranes (PPROM), placental abruption, and pre-eclampsia.

Results

Risk to siblings of an affected individual was elevated above the population prevalence of a given disorder, as indicated by λ_S(λ_S(95% CI): 4.3 (4.0–4.6), 8.2 (6.5–9.9), 4.0 (2.6–5.3), and 4.5 (4.4–4.8), for preterm birth, PPROM, placental abruption, and pre-eclampsia, respectively). Risk to siblings of an affected individual was similarly elevated above that of siblings of unaffected individuals, as indicated by the sib-sib OR (sib-sib OR adjusted for known risk factors (95% CI): 4.2 (3.9–4.5), 9.6 (7.6–12.2), 3.8 (2.6–5.5), 8.1 (7.5–8.8) for preterm birth, PPROM, placental abruption, and pre-eclampsia, respectively).

Conclusion

These results suggest that the adverse pregnancy outcomes of preterm birth, PPROM, placental abruption, and pre-eclampsia aggregate in families, which may be explained in part by genetics.