Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, Florida.
Department of Pharmacodynamics, University of Florida College of Pharmacy, Gainesville, Florida.
Am J Physiol Regul Integr Comp Physiol. 2022 Aug 1;323(2):R193-R203. doi: 10.1152/ajpregu.00041.2022. Epub 2022 Jun 7.
Maternal stress in pregnancy is thought to be a contributing factor in adverse pregnancy outcomes, including stillbirth and prematurity. Previous studies in our laboratory have shown that chronic elevation in maternal cortisol concentration in ewes (by maternal infusion of 1 mg/kg/day) during the late gestation increased the incidence of stillbirth and altered fetal heart rate and blood pressure at birth. We designed the current study to test the effect of chronically elevated maternal cortisol on fetal cardiac adaption from in utero life to ex utero life. The combined risk of stillbirth or prematurity was significantly greater in the pregnancies with maternal hypercortisolemia; in this cohort, 40% of the lambs of cortisol-infused ewes died in utero or at birth compared with 25% of lambs of control ewes, and 24% of lambs of cortisol-infused ewes were born preterm, whereas no lamb was born preterm in the control group. Compared with control lambs, the lambs of cortisol-infused ewes born at full term exhibited a significant increase in mean aortic pressure just before birth and a significant decrease in mean aortic pressure that was evident during the first 9 h after birth. The QT interval was decreased before birth and increased immediately after birth in the newborns of cortisol-treated ewes compared with control lambs. These findings suggest that excess in utero corticosteroid exposure adversely affects fetal cardiac adaptation to extrauterine life and that chronic maternal stress or hypersecretion of corticosteroids may contribute to adverse obstetric outcomes.
母体在妊娠期间的压力被认为是不良妊娠结局的一个促成因素，包括死产和早产。我们实验室之前的研究表明，在妊娠晚期，通过给母羊输注 1mg/kg/天的皮质醇，使母体皮质醇浓度持续升高，增加了死产的发生率，并改变了出生时的胎儿心率和血压。我们设计了当前的研究来测试母体皮质醇持续升高对胎儿心脏从宫内生活到宫外生活的适应的影响。在母体高皮质醇血症的妊娠中，死产或早产的综合风险显著增加；在这组中，皮质醇输注母羊的羔羊中有 40%在宫内或出生时死亡，而对照组母羊的羔羊中有 25%，皮质醇输注母羊的羔羊中有 24%早产，而对照组中没有羔羊早产。与对照组羔羊相比，足月出生的皮质醇输注母羊的平均主动脉压在出生前显著升高，出生后 9 小时内的平均主动脉压显著降低。与对照组羔羊相比，皮质醇处理母羊的新生儿出生前 QT 间期缩短，出生后立即增加。这些发现表明，宫内皮质醇暴露过多会对胎儿心脏适应宫外生活产生不利影响，而母体慢性应激或皮质醇分泌过多可能导致不良的产科结局。
