Abstract
Preeclampsia is a major cause of perinatal mortality and disease affecting 5–10% of all pregnancies worldwide, but its etiology remains poorly understood despite considerable research effort. Parent-offspring conflict theory suggests that such hypertensive disorders of pregnancy may have evolved through the ability of fetal genes to increase maternal blood pressure as this enhances general nutrient supply. However, such mechanisms for inducing hypertension in pregnancy would need to incur sufficient offspring health benefits to compensate for the obvious risks for maternal and fetal health towards the end of pregnancy in order to explain why these disorders have not been removed by natural selection in our hunter-gatherer ancestors. We analyzed >750,000 live births in the Danish National Patient Registry and all registered medical diagnoses for up to 30 years after birth. We show that offspring exposed to pregnancy-induced hypertension (PIH) in trimester 1 had significantly reduced overall later-life disease risks, but increased risks when PIH exposure started or developed as preeclampsia in later trimesters. Similar patterns were found for first-year mortality. These results suggest that early PIH leading to improved postpartum survival and health represents a balanced compromise between the reproductive interests of parents and offspring, whereas later onset of PIH may reflect an unbalanced parent-offspring conflict at the detriment of maternal and offspring health.
Highlights
Relative to the great apes, humans have long pregnancies and relatively high perinatal risks for mother and offspring
Using Cox regression that adjusted for potentially confounding effects, we estimated the risk of infant mortality and diseases after birth, depending on the occurrence of maternal pregnancy-induced hypertension (PIH) by trimester needed to code for its presence as this diagnosis predominantly occurred in trimester 3
If PIH occurred in trimester 3, risk of infant mortality was doubled (hazard or risk ratio (RR) = 2.06, 95% CI = 1.37–3.09, P,0.001, Fig. 2C), similar to the increased mortality risk experienced when more severe forms occur
Summary
Relative to the great apes, humans have long pregnancies and relatively high perinatal risks for mother and offspring. The theory maintains that there is an interval of fetal-provisioning where the maternal and paternal interests are not aligned because the father of the focal fetus has a probability of less than 100% of fathering the focal mother’s child, owing to serial monogamy or varying degrees of promiscuity [12] This implies that paternal genes expressed in the placenta have been under consistent selection to express phenotypes that somehow increase maternal blood pressure as this would generally enhance fetal resource provisioning via the mother-infant circulation interface [15,16]. The capacity of maternal blood supply (i.e. veins and arteries that connect fetal-maternal tissues, Fig. 1) is largely determined early in pregnancy (first 20–22 weeks) when placental invasion of the endometrium and modification of the spiral arteries takes place [12] This suggests that the effects of PIH on maternal-fetal interactions and offspring health may vary depending on its occurrence and timing throughout pregnancy, yet no study has investigated this before. We examine these relationships by utilizing the national health registries in Denmark, which provided us with data on .1.8 million births from 1977–2007 and diseases diagnosed within .5 million people from 1977–2009
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