Parental human leukocyte antigen genes linked to preterm delivery

The transmission of Human Leukocyte Antigen (HLA) genes may play a significant role in the risk of preterm delivery, according to a study in the September issue of Obstetrics and Gynecology.

Researchers from Kaiser Permanente's Division of Research, Northern California and Children's Hospital Oakland Research Institute concluded that the passing on of parentally shared HLA genes (also know as alleles) from parents to their offspring led to a more than five-fold increased risk of preterm delivery.

"The implication of the study to infant mortality is simple because preterm delivery is the leading cause of infant mortality and morbidity. Unfortunately, the causes of preterm delivery are still largely unknown despite decades of research, and as a result, the rate of preterm delivery has not declined," said De-Kun Li, MD, PhD, senior research scientist at Kaiser Permanente's Division of Research and the study's lead author. "Finding a cause of preterm delivery and reducing its incidence would consequently reduce mortality and morbidity."

This population-based family study was conducted with participating children and their parents at Kaiser Permanente's Northern California Region. A total of 234 participants from 78 families with early preterm deliveries (35 weeks or less) and 60 participants from 20 families with full-term births were included in the study. Cheek cells were collected from first-born preterm cases and their parents to determine HLA-B and DRB1 gene type and the transmission of parental alleles to the offspring. The focus of the study was to determine whether parentally shared HLA alleles are more likely than expected to be transmitted to preterm children.

Compared to offspring who did not receive any parentally shared HLA alleles, offspring who received the alleles from both parents had more than a five-fold increased risk of preterm delivery. Offspring who received the HLA allele from the mother only, but not from the father also had increased risk of preterm delivery, while offspring who received the HLA allele from the father only, but not from the mother did not have increased risk.

This is the first time that parental HLA makeup has been linked to preterm delivery. Dr. Li, when asked why parentally shared HLA alleles and its transmission to offspring would lead to preterm delivery, said, "Although our study did not directly examine them, the underlying mechanisms of the finding could be immunologic. There is increasing evidence that successful pregnancy requires healthy immunological interaction between parents and between mother and the fetus. HLA alleles control immune response. Abnormal immune response due to HLA mismatch among mother, father and the fetus could lead to unsuccessful pregnancy."

The findings could have broad implications for prenatal testing; said Dr. Li, noting that the results will need confirmation by future studies. "We may find a way to detect in advance which fetuses are at high risk of preterm delivery by testing parental HLA types (a simple procedure) and fetal HLA types if necessary. Once those high-risk pregnancies are identified, targeted monitoring could be more effectively implemented to prevent preterm delivery from occurring."