Pre-term births are a leading cause of neonatal morbidity and mortality in the U.S., where they occur in about 12% to 13% of all pregnancies and about 17% to 18% of pregnancies among African-American women. Family history is a known risk factor of pre-term birth, suggesting that genetics might affect the likelihood of pre-term birth. The disparity in pre-term birth rates between African-American and white women also suggests that genetic variants contribute to pre-term birth susceptibility. However, it is highly unlikely that a single gene mutation causes this complex event, according to the researchers. The study attempts to further understanding of the genetic predisposition for pre-term birth and investigate the high rate among African-American women through a large-scale gene association analysis focusing on an African-American population.
Digna Velez of the Miami Institute of Human Genomics and the Department of Human Genetics at the University of Miami and colleagues analyzed maternal and fetal DNA from birth events among African-American women ages 18 to 40, who were recruited between September 2003 and December 2006 at Centennial Medical Center in Nashville, Tenn. The study included 76 African-American women who experienced pre-term birth with no rupture of membranes and 191 African-American women in the control group, as well as 65 fetal cases and 183 fetal controls. Pre-term birth was defined as having two contractions per 10 minutes followed by delivery at less than 36 weeks’ gestation, and controls were identified by normal labor and delivery after at least 37 weeks’ gestation. The researchers used questionnaires and medical records to obtain demographic and clinical data about the women, and also performed single locus association and haplotype analyses on 1,432 single nucleotide polymorphisms from 130 candidate genes to identify genetic factors associated with spontaneous pre-term birth.
The researchers observed significant differences between cases and controls for gestational age, birthweight, one-minute Apgar scores and five-minute Apgar scores. There were no differences between cases and controls for other demographic factors, including socioeconomic measures. In addition, the researchers identified 96 single nucleotide polymorphisms with statistically significant associations for either allelic or genotypic tests among maternal samples and 126 among fetal samples. They found the most significant associations in the maternal interleukin (IL)-15 and the fetal IL-2 receptor. Overall, fetal samples had more significant allelic associations with pre-term birth than did maternal samples. The researchers also determined that the largest number of significant associations with pre-term birth occurred in genes related to infection and inflammation.
The data collected in the study indicate that “no single gene” accounts for pre-term birth, “but rather locus heterogeneity appears to exist for multiple genes from this pathway.” In addition, the “unexpectedly large number of associations” found between fetal genotypes and pre-term birth suggests “that the fetal genetic contribution to pre-term birth exceeds the maternal contribution” among African-Americans, the researchers write. They continue that the study’s finding that infection- and inflammation-related pathways have the most significant association with pre-term birth among African-American women is “very promising,” particularly because it is “consistent with documented elevated rates of infection” among African-American women. The researchers recommend further study on this topic to determine whether the type of infection is an important factor.
Source: American Journal of Obstetrics and Gynecology, February 2009.