Maternal–fetal HLA sharing and preeclampsia: variation in effects by seminal fluid exposure in a case–control study of nulliparous women in Iowa

Abstract

Whereas histocompatibility is critical for transplantation, HLA histoincompatibility is associated with successful pregnancy. Literature on HLA sharing and preeclampsia has been inconsistent; most studies focused on maternal–paternal rather than maternal–fetal sharing. This study examines whether maternal–fetal histocompatibility is associated with preeclampsia, and whether effects vary by semen exposure history. This case–control study of nulliparous women was designed to examine associations among HLA sharing, semen exposure, and preeclampsia. 258 preeclampsia cases and 182 normotensive controls met the eligibility criteria. HLA typing for mother and baby was performed for HLA-A, -B, -C, -DRB1, and -DQB1. We further restricted our study sample to 224 mother–baby pairs who had complete HLA typing for all five genes. Seminal fluid exposure indexes incorporated information on type of practice, frequency, contraceptive use (for vaginal exposure) and ingestion practices (for oral exposure). Multivariate models were adjusted for BMI and education. HLA-A matching, Class I matching, and combined Class I and II matching were associated with increased odds of preeclampsia. Among women with low semen exposure, effects of Class I matching were amplified (HLA-A matching, OR=6.27, 95%CI=1.04, 37.97; Class I matching, OR=4.49 per one-match increase, 95%CI=1.89, 14.50). With moderate to high semen exposure, Class II matching effects predominated (HLA-DQB1, OR=3.22, 95%CI=1.04, 9.99; Class II, OR=1.76 per one-match increase, 95%CI=1.05, 2.98; and total matches, OR=1.45 per one-match increase, 95%CI=1.02, 2.06). We found consistent evidence that maternal–fetal HLA sharing was associated with preeclampsia in a pattern influenced by prior vaginal exposure to paternal seminal fluid.

Physical Activity During Pregnancy and Subsequent Risk of Preeclampsia and Gestational Hypertension: A Case Control Study

“…A detailed description of this study has been described elsewhere. 18,19 Briefly, primiparous mothers who delivered a live birth from August 2002 to May 2005 and resided in one of 42 Iowa counties were identified from electronic birth certificates. Women who had an indication of hypertension during pregnancy on the birth certificate were selected for recruitment as possible cases.…”

“…Multivariable multinomial logistic regression was used in order to adjust for potential confounders; however, only variables that produced at least a 10 percent change in main effect risk estimates were retained in the final models. The covariates examined as potential confounders included: BMI (continuous), maternal age at delivery (continuous), education (categorical), preconception smoking (yes/no), smoking during pregnancy (nonsmoker, 1 st trimester only, and 2 nd /3 rd trimester), paternal seminal fluid exposure 19 , and HLA sharing 18 . Continuous measures of PA variables were analyzed as such, as well as in tertiles or quartiles based on the distribution in the normotensive control subjects.…”

The potential impact of the fetal genotype on maternal blood pressure during pregnancy

“…This may be especially apparent when there is a fetal/maternal mismatch in HLA genes as observed in a study of paternally transmitted HLA-GÃ0106, which was associated with preeclampsia in multigravida pregnancies [63], consistent with the idea that preeclampsia has an immunological basis. Alternatively, HLA-sharing between the mother and fetus, particularly of HLA class I and II molecules, has also been shown to be associated with preeclampsia [79]. Whether it is a fetal/ maternal mismatch or HLA-sharing that is important for the development of preeclampsia, or even both with respect to different HLA genes, a role is suggested for the fetal HLA genotype in the process of modulating preeclampsia risk and therefore maternal blood pressure.…”

Risk of recurrent preterm birth among women according to change in partner

“…(13) Recent work demonstrating an increased risk of preeclampsia among women with low cumulative exposure to paternal seminal fluid supports such an immune-based mechanism. (14, 15) Additionally, paternal human leukocyte antigen (HLA) sharing has been suggested to have an influence on risk of preterm birth. (8, 15) Other mechanisms may be psychosocial such as increased level of stress, reduced support, or change in financial status or social capital.…”

“…(14, 15) Additionally, paternal human leukocyte antigen (HLA) sharing has been suggested to have an influence on risk of preterm birth. (8, 15) Other mechanisms may be psychosocial such as increased level of stress, reduced support, or change in financial status or social capital. (3)…”