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The Heritability of Preterm Delivery

From the ¹Department of Obstetrics, Gynecology, and Women's Health and the Pacific Research Center for Early Human Development; University of Hawai'i, John A. Burns School of Medicine, Honolulu, Hawai'i; and ²Taueret Laboratories LLC, Salt Lake City, Utah.

OBJECTIVE: To study the heritability of preterm delivery.

METHODS: Women who delivered a singleton infant at less than 36 weeks of gestation were asked about their family history. Twenty-eight families were identified in which the proband had at least five first- or second-degree relatives with preterm delivery. An extensive genealogy database (GenDB) was constructed using more than 9,000 genealogy sources in the public domain (records before 1929). GenDB documents the relationships between more than 17.5 million ancestors and 3.5 million descendants of approximately 10,000 individuals who moved to Utah in the mid 1800s. This database was searched for the names, birth dates, and birthplaces of the four grandparents for each of the 28 probands. Pairwise coefficients of kinship were determined for the 93 preterm delivery grandparents identified, and for sets of 100 individuals born in the 1920s who were randomly selected from the population database.

RESULTS: Probands had a mean of 3.3 grandparents included in this database. The average coefficient of kinship for controls was 1.5 x 10⁶ (standard deviation = 0.6 x 10⁶). This measure agrees with previous calculations for the Utah population. The coefficient of kinship for familial preterm delivery grandparents was more than 50 standard deviations higher (3.4 x 10⁵ [P < .001]).

CONCLUSION: This study confirms the familial nature of preterm delivery. On average, gravidae randomly selected from our population are 23rd degree relatives, while these preterm delivery probands are eighth-degree relatives. A genome-wide scan using these affected families is underway.

LEVEL OF EVIDENCE: II-3

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