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Maternal and Fetal Genetic Contributions to Postterm Birth: Familial Clustering in a Population-Based Sample of 475,429 Swedish Births

Oberg, Anna S.; Frisell, Thomas; Svensson, Anna C.; Iliadou, Anastasia N.

Obstetrical & Gynecological Survey:
doi: 10.1097/OGX.0b013e31829b7ea2
Obstetrics: Physiology & Pathophysiology of Pregnancy, Labor, and the Puerperium

Pregnancies lasting longer than 293 days (42 weeks and beyond) are considered postterm, which carry greater risks for maternal and fetal complications. The etiology of postterm pregnancy is largely unknown, but women of older age, those with higher body mass index, those who are nulliparous, and those carrying a male fetus are at higher risk. This population-based study was undertaken to examine the familial clustering of postterm birth, to determine whether potential clustering could be explained by familial sharing of risk factors, and to quantify the genetic and environmental contributions to postterm birth.

Parent-offspring relations were identified from 2 Swedish national registries. Postterm births were identified as births occurring after 42 completed weeks (>42 + 0). The study also examined a cutoff of 41 completed weeks (>41 + 0). All men and women who had at least 2 live births with the same partner in Sweden between 1992 and 2004 and their full siblings who fulfilled the same criterion were included. The study population included 358,420 births, representing full siblings and their first cousins. For individuals who had children with more than 1 partner, the first 2 births with separate fathers (or mothers) were selected, yielding 54,810 births with the same father but different mothers and 62,688 births with the same mother but different fathers (half-siblings). The complete sample contained 475,918 births. The 3 types of family relationships in the offspring generation were full siblings, half-siblings, and cousins. Full- and half-siblings had 3 unique within-person patterns in the parental generation: intact couples, mothers with new partner, and fathers with new partner. Cousins also had 3 unique within-sibling relations in the parental generation, being related as sisters, brothers, or sister-brother pairs.

Twenty-one percent and 5.5% of all live births occurred after 41 and 42 completed weeks of gestation, respectively. Maternal age, prepregnancy body mass index, education level, primiparity, and carrying a male fetus were positively associated with odds of postterm birth. The highest odds increase of postterm birth was seen when couples with previous postterm birth (odds ratio [OR], 4.4; 95% confidence interval [CI], 4.1–4.6) were compared with couples with no previous postterm birth. Changing partners between pregnancies attenuated the odds increase slightly for women (OR, 3.4; 95% CI, 2.9–3.9) but not for men (OR, 1.1; 95% CI, 0.9–1.4). Recurrence of postterm birth in intact couples could be due to fetal, maternal genetic, or shared environment; recurrence after partner change may indicate maternal and paternal influences via genes or unique environment, respectively. Sisters of women with a postterm birth also had increased odds of delivering postterm compared with sisters of women without a postterm birth (OR, 1.8; 95% CI, 1.6–2.0). The corresponding OR increases in brother pairs and brother-sister pairs were 1.1 (95% CI, 1.0–1.3) and 1.2 (95% CI, 1.1–1.3), respectively. The odds increases in men who changed partners or among brother pairs were significant (OR, 1.2; 95% CI, 1.1–1.3; and OR, 1.1; 95% CI, 1.1–1.2, respectively). More clustering in sister pairs compared with brother pairs and brother-sister pairs indicated a maternal influence on the risk of postterm birth through genes or a maternal-specific environment shared by sisters. Clustering in brother-sister pairs could indicate some influence from a shared sibling environment or genetics transmitted from both mother and father; clustering in brother pairs reflects shared brother environment or paternal genetic influence. Fetal genetic effects explained 26% (95% CI, 13%–35%) and maternal genetic effects explained 21% (95% CI, 16%–26%) of the variation in postterm birth. Maternal environment explained only 2% of the variation (95% CI, 0%–7%).

Nearly half of the variation in postterm birth could be attributed to genetic effects. The familial recurrence of postterm birth was largely attributed to genetic effects and not to shared environment. Identification of pregnancies at risk to become postterm could be important for clinical decision making about monitoring and timing of labor induction.

Author Information

Department of Medical Epidemiology and Biostatistics (A.S.O., T.F., A.N.I.), Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (A.S.O.), Harvard School of Public Health, Boston, MA; and Department of Public Health Sciences, Karolinska Institutet; and Centre for Epidemiology and Community Medicine, Stockholm County Council (A.C.S.), Stockholm, Sweden

© 2013 by Lippincott Williams & Wilkins.