No abstract

There are many published studies about the epigenetic effects of the prenatal and infant periods on health outcomes. However, there is very little knowledge regarding the effects of the intrapartum period (labor and birth) on health and epigenetic remodeling. Although the intrapartum period is relatively short compared to the complete perinatal period, there is emerging evidence that this time frame may be a critical formative phase for the human genome. Given the debates from the National Institutes of Health and World Health Organization regarding routine childbirth procedures, it is essential to establish the state of the science concerning normal intrapartum epigenetic physiology. EPIIC (Epigenetic Impact of Childbirth) is an international, interdisciplinary research collaboration with expertise in the fields of genetics, physiology, developmental biology, epidemiology, medicine, midwifery, and nursing. We hypothesize that events during the intrapartum period – specifically the use of synthetic oxytocin, antibiotics, and cesarean section – affect the epigenetic remodeling processes and subsequent health of the mother and offspring. The rationale for this hypothesis is based on recent evidence and current best practice.

It is generally accepted that preeclampsia results from reduction in perfusion to the uteroplacental unit leading to maternal hypertension and fetal growth restriction. Placental insufficiency creates an environment of fetal undernutriton, predisposing the fetus to the development of adult disease. In this study, we characterized the development and perpetuation of hypertension in two generations of male and female offspring subjected to an environment of fetal undernutrition via reduced uteroplacental perfusion pressure. Further, we examined vascular responses of resistance arteries in these animals to determine the influence of placental insufficiency on the development and perpetuation of hypertension. Experimental dams underwent a surgical procedure to reduce uteroplacental perfusion pressure, with resulting offspring comprising the first generation (F1). One male and one female from each of the F1 experimental litters served as breeders of the second generation (F2). Weekly systolic blood pressure measurements were obtained from 4 to 24 wk in control, F1, and F2 offspring. Vascular responsiveness to the vasoconstrictors phenylephrine and potassium chloride and the vasorelaxants acetylcholine and sodium nitroprusside was determined in the three offspring groups at 6, 9, and 12 wk of age. Our findings indicate that placental insufficiency during a critical developmental window in late gestation leads to hypertension in juvenile Sprague-Dawley rat offspring and is perpetuated in a second generation of offspring in a gender-specific manner. Further, exposure to placental insufficiency during late gestation leads to developmental alterations characterized by vascular hyperresponsiveness, perpetuated to a second generation of offspring in the absence of persistent environmental stimuli, contributing to hypertension.

The COVID-19 pandemic has led to disruptions in health care in the perinatal period and women's childbirth experiences. Organizations that represent health care professionals have responded with general practice guidelines for pregnant women, but limited attention has been devoted to mental health in the perinatal period during a pandemic. Evidence suggests that in this context, significant psychological distress may have the potential for long-term psychological harm for mothers and infants. For infants, this risk may extend into early childhood. In this commentary, we present recommendations for practice, research, and policy related to mental health in the perinatal period. These recommendations include the use of a trauma-informed framework to promote social support and infant attachment, use of technology and telehealth, and assessment for mental health needs and experiences of violence.

Evidence continues to implicate reduced placental perfusion as the cause of preeclampsia, initiating a sequence of events leading to altered vascular function and hypertension. The present study was designed to determine the influence of reduced uteroplacental perfusion pressure (RUPP) on the responsiveness of uterine arcuate resistance arteries. A condition of RUPP was surgically induced in pregnant Sprague-Dawley rats on Gestational Day 14. On Gestational Day 20, uterine arcuate arteries were mounted on a small-vessel wire myograph and challenged with incremental concentrations of vasoconstrictors and vasorelaxants for measurement of isometric tension. Compared to the sham-operated controls, uterine arteries from the RUPP group demonstrated an increased maximal tension in response to phenylephrine (P < 0.01); potassium chloride at 30 mM (P < 0.05), 60 mM (P < 0.01), and 120 mM (P < 0.01); and angiotensin II (P < 0.05). In arteries from the RUPP and sham-operated control groups, endothelium-dependent relaxation in response to acetylcholine (P < 0.05) and calcium ionophore (A23187; P < 0.05) was significantly reduced in the RUPP group compared to the sham-operated controls. Fetal growth indices, including litter size, fetal weight, and placental weight, were significantly reduced in the RUPP group compared to sham-operated controls, which is consistent with significant growth restriction. Data suggest that RUPP promotes hyperresponsiveness and impaired endothelium-dependent relaxation in uterine arcuate arteries, leading to intrauterine fetal growth restriction.