Researchers have discovered how one genetic and one sexual risk factor can combine to increase the risk of preeclampsia, according to a study published in the Journal of Reproductive Immunology.

Elizabeth Triche and colleagues at Brown University say their findings suggest there could be new ways for couples to plan pregnancy with improved awareness of the disorder, as well as improved management of the risks.

Preeclampsia is a common condition that can occur during pregnancy, most typically during the postpartum period. It is defined by a sudden sharp rise in blood pressure; swelling to the face, hands and feet; and albuminuria – excess of the protein albumin that leaks into the urine.

If preeclampsia remains untreated, it can develop into eclampsia – a life-threatening condition that can cause convulsions, coma and even death.

According to the Preeclampsia Foundation, the disorder is estimated to account for 76,000 maternal deaths and 500,000 infant deaths worldwide every year.

Previous research has suggested that preeclampsia may stem from the mother’s immune response to pregnancy. From this, the research team set out to study two potential risk factors. These were:

  • The level of similarity between the mother and father, or mother and fetus with five human leukocyte antigen (HLA) genes linked to immune system compatibility, and
  • The degree of vagina exposure the mother has had to the father’s semen prior to pregnancy.

For the study, the researchers analyzed these risk factors using data of 118 women who had developed preeclampsia, alongside 106 women who did not have the disorder. All data was taken from the Study of Pregnancy Hypertension in Iowa (SOPHIA).

Results of the analysis revealed that women who had relatively limited exposure to the father’s semen prior to pregnancy, and who highly matched the class I group of HLA genes, had a 4.5 times higher risk of developing preeclampsia, compared with women who had higher exposure to the father’s semen and lower gene matching.

Elizabeth Triche, assistant professor of epidemiology at the School of Public Health at Brown University, explained the findings to Medical News Today:

The study suggests that maternal-fetal sharing of HLA alleles increases the likelihood of preeclampsia, and that these associations depend on the level of exposure to the paternal seminal fluid prior to pregnancy.

For mothers who have low cumulative exposure to paternal seminal fluid prior to pregnancy, increased sharing of Class 1 alleles increases the likelihood of preeclampsia over 4-fold.”

Prof. Triche says that the underlying biology of these findings appear to link to the way the mother’s immune system views the “foreign genes,” first when they are introduced by the father’s sperm and then in the fetus.

“At the maternal-fetal interface it appears that for a successful pregnancy to occur, it’s likely the mother has to recognize it as foreign and develop a tolerance,” she adds.

However, the study also presented another finding. Mothers who had higher exposure to the father’s semen and a similarity to the fetus for the Class 2 gene, HLA-DQB1, showed a smaller but significant increased risk of developing preeclampsia.

“With higher levels of seminal fluid exposure, Class 2 sharing appears to be more important, particularly HLA-DQB1 sharing,” Prof. Triche told Medical News Today.

Prof. Triche says that if the findings of this study are confirmed, it is possible that HLA testing could be helpful in advising couples about the best methods for decreasing their risk of preeclampsia:

For couples planning pregnancy, we may advise those with greater probability of maternal-fetal sharing of Class 1 HLA genes to decrease use of barrier contraception and increase vaginal sexual intercourse prior to conception in order to decrease risk.

For those with Class 2 sharing, however, it may be that barrier contraceptive use prior to pregnancy is preferable. And other lifestyle factors may influence the risk of preeclampsia, including maintaining a healthy BMI, and physical activity.”

She warns, however, that if women are not planning to get pregnant, they should continue to use barrier contraceptives to reduce other health risks, such as sexually transmitted diseases.

The researchers say that moving forward, they would like to replicate these findings and learn more about the role of HLA in pregnancy outcomes.

“We are currently looking at specific HLA types and their joint role in risk of preeclampsia. We would also like to study HLA by gene interactions in both mothers and babies,” says Prof. Triche.

Medical News Today recently reported on a new test created by UK researchers that could predict the risk of preeclampsia.