Population-based biomarker screening and the development of severe preeclampsia in California

Abstract

Objective To examine the relationship between second trimester maternal serum biomarkers and the development of early- and late-onset severe preeclampsia in euploid pregnancies. Study Design Included were 136,139 pregnancies participating in second trimester prenatal screening through the California Prenatal Screening Program with live births in 2006 through 2008. We identified severe preeclampsia diagnoses from hospital discharge records. We used log binomial regression to examine the association between abnormal second trimester maternal serum biomarkers and the development of severe preeclampsia. Results Approximately 0.9% of all women (n= 1,208) in our sample developed severe preeclampsia; 329 before 34 weeks gestation and 879 at or after 34 weeks. High levels of alpha fetoprotein (AFP), human gonadotropin (hCG) and inhibin (INH) (multiple of the median (MoM) ≥ 95th percentile), and low estriol (uE3) (MoM ≤ 5th percentile), were associated with severe preeclampsia (RRs 2.5 – 11.7). Biomarkers were more predictive of early-onset severe preeclampsia (RRs 3.8 – 11.7). One in 9.5 pregnancies with combined high AFP, INH and low uE3 developed severe early-onset preeclampsia compared to one in 680.5 pregnancies without any abnormal biomarkers. Conclusions The risk of developing severe preeclampsia increases for women with high second trimester AFP, hCG, INH and/or low uE3; this is especially true for early-onset severe preeclampsia. When abnormal biomarkers co-occur, risk dramatically increases. Although the screening value of second trimester biomarkers is low, abnormal biomarkers, especially when occurring in combination, appear to indicate placental dysfunction associated with the development of severe preeclampsia.

Fetal Sex-Dependent Associations Between Gestational Hormone Concentrations and Adverse Birth Outcomes: A Cohort Study

“…Women with preeclampsia had lower progesterone and estriol concentrations over the study period than women with normal pregnancies, but only when the fetus was female. We also observed increased odds of preeclampsia to be associated with higher prog/e3, but this relationship was not fetal sex-speci c. In accordance with our ndings, other studies have shown that progesterone concentrations in the third trimester (29-40 weeks gestation) [21] and estriol concentrations in the second trimester [57] were lower among women with preeclampsia than women with normal pregnancies. Carrying a female fetus has previously been demonstrated as an independent risk factor for developing preeclampsia [58,59].…”

Foetal oestrogens and autism

“…With regard to clinical studies in humans, low oestriol in maternal serum during the second trimester of pregnancy significantly increases the likelihood of autism in the foetus, as demonstrated in a large study of n = 2586 autistic pregnancies [32]. This study may have been confounded by a variety of pregnancy complications, such as pre-eclampsia [33] and being small for gestational age [34], since these are also more frequent in autism [35][36][37]. Thus, further study of prenatal oestrogenic activity, particularly in foetal circulation, is warranted.…”

Fetal sex differences in human chorionic gonadotropin fluctuate by maternal race, age, weight and by gestational age

“…hCG was put into widespread use over three decades based on its predictive power in estimating risk of fetal defects such as Down’s syndrome 18 . It later was observed that it can be useful in predictions of non-genetic, adverse pregnancy outcomes such as preterm labor, 19 preeclampsia 20 and placental abruption 21 . Lower second trimester hCG was correlated with increased risk of cryptorchidism in male infants as compared with normal controls 22 .…”