Chenodeoxycholic acid (CDCA) treatment during pregnancy in women with cerebrotendinous xanthomatosis (CTX): Lessons learned from 19 pregnancies.

Purpose: Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive bile acid synthesis disorder. Biallelic pathogenic variants in CYP27A1, encoding for sterol 27-hydroxylase, impair cholic acid (CA) and chenodeoxycholic acid (CDCA) synthesis and lead to accumulation of cholestanol and C bile alcohols. Treatment with CDCA decreases the accumulation of these harmful metabolites and slows disease progression.

Post-Cesarean Opioid Use after Implementation of Enhanced Recovery after Surgery Protocol.

Objective: This study aimed to evaluate whether implementation of an enhanced recovery after surgery (ERAS) protocol is associated with lower maternal opioid use after cesarean delivery (CD).

Study Design: We performed a pre- and postimplementation (PRE and POST, respectively) study of an ERAS protocol for cesarean deliveries. ERAS is a multimodal, multidisciplinary perioperative approach.

Fetal Growth Restriction Induced by Transient Uterine Ischemia-Reperfusion: Differential Responses in Different Mouse Strains.

We characterized fetal and placental growth and uterine and placental inflammation in pregnant C3H/HeOuJ and C57BL/6J mice (strains with different sensitivities to metabolic and circulatory pathologies), using different uterine ischemia/reperfusion (I/R) protocols, to establish and refine a murine model of I/R-induced fetal growth restriction (FGR). Pregnant C3H/HeOuJ mice on gestation day 15 were subjected to unilateral uterine I/R by (1) total blood flow restriction (TFR) by occlusion of the right ovarian and uterine arteries for 30 minutes, (2) partial flow restriction (PFR) by occlusion of only the right ovarian artery for 30 minutes, or (3) sham surgery. Pregnant C57BL/6J mice were treated the same, but on gestation day 14 and with TFR for only 5 minutes due to high sensitivity of C57BL/6J mice to I/R.

Endothelin Receptor A Antagonism Prevents Damage to Glycogen-Rich Placental Cells Following Uterine Ischemia-Reperfusion in the Rat.

Fetal growth restriction (FGR) is a common cause of perinatal morbidity and mortality. Suboptimal uteroplacental perfusion is the most commonly identified cause of FGR, and ischemic lesions are often observed in placentas from pregnancies complicated by FGR. Ischemia followed by reperfusion is a strong stimulus to the production of the vasoconstrictor endothelin 1 (ET-1) which has been implicated in several models of FGR.

Endothelin Receptor A Antagonism and Fetal Growth in Endothelial Nitric Oxide Synthase Gene Knockout Maternal and Fetal Mice.

Fetal growth restriction (FGR) is commonly associated with perinatal morbidity and mortality. Nitric oxide (NO) deficiency increases endothelin-1 (ET-1) production, and this increased ET-1 may contribute to the pathophysiology of NO deficiency-induced FGR. Using an endothelial NO synthase knockout mouse model of FGR, we sought to determine (a) the relative importance of maternal versus conceptus (fetal and placental) NO deficiency and (b) the contribution of ET-1 to the pathogenesis of FGR in this model.

Unilateral uterine ischemia/reperfusion-induced bilateral fetal loss and fetal growth restriction in a murine model require intact complement component 5.

The role of complement in ischemia/reperfusion-induced fetal growth restriction and fetal loss is unknown. C5-deficient or wild type timed-pregnant mice were subjected to unilateral uterine ischemia/reperfusion on gestation day 13, either by (1) partial flow restriction by right ovarian artery clamping for 30 min, or (2) total flow restriction by clamping both ovarian and uterine arteries for 5 min. Ischemia/reperfusion-challenged pregnancy outcomes were compared to sham-operated controls 5 days later.

The significance of endothelin in platelet-activating factor-induced fetal growth restriction.

The significance of endothelin-1 (ET-1) in platelet-activating factor (PAF)-induced fetal growth restriction (FGR) was evaluated in timed-pregnant rats receiving intravenous carbamyl-PAF (c-PAF; 0.5, 1.0, or 2.

Endothelin receptor antagonist has limited access to the fetal compartment during chronic maternal administration late in pregnancy.

Aims: Endothelin receptor A (ET(A)) antagonism normalizes fetal growth in several models of rodent fetal growth restriction (FGR). Our aims were to determine the levels of ET(A) antagonist in maternal and fetal plasma following chronic maternal administration, and to determine its impact on pregnancy outcome, survival and growth of rat pups.

Main Methods: Timed pregnant rats were treated with one of two endothelin receptor antagonists or vehicle, from gestation day 14-21 (term=22 days).

Pathophysiology of chronic nitric oxide synthase inhibition-induced fetal growth restriction in the rat.

Objective: To evaluate the pathophysiology of chronic nitric oxide synthase (NOS) inhibition-induced fetal growth restriction (FGR) in the rat.

Methods: Timed-pregnant rats received L-NAME (2.5 mg/kg/h) with or without endothelin (ET-1) receptor A (ETA) antagonist from day 14 to 21 of gestation.

Impact of endothelin A receptor antagonist selectivity in chronic nitric oxide synthase inhibition-induced fetal growth restriction in the rat.

Objective: Endothelin receptor A (ETA) antagonism improves fetal and placental growth and placental perfusion on days 1 and 4, but not day 7 of a 7-day infusion of a nitric oxide synthase (NOS) inhibitor. Our purpose was to evaluate the significance of the degree of ETA antagonist selectivity on uteroplacental perfusion and fetal growth on day 7 of chronic NOS inhibition.

Methods: Timed-pregnant rats were treated with the NOS inhibitor nitro-L-arginine methyl ester (L-NAME, 2.

The fetal response to chronic placental insufficiency.

Fetal growth restriction is most commonly caused by failure of the placenta to meet the increasing demands for oxygen and substrate of the developing fetus, resulting in common fetal compensatory responses. Understanding these responses is helpful in developing a management strategy that will optimize pregnancy outcome.

Altered endothelin receptor binding in response to nitric oxide synthase inhibition in the pregnant rat.

The authors evaluate the expression of endothelin-1 (ET-1) and its receptors in the uterus and placenta during maternal nitric oxide synthase (NOS) inhibition. Timed-pregnant rats received L-NAME (2.5 mg/kg/h) or saline from day 14 to 21 of gestation.

Expression of endothelin 1 and its receptors in the hypoxic pregnant rat.

Endothelin 1 (EDN1) plays a primary role in the pathophysiology of hypoxia-induced fetal growth restriction in the rat. In this study we evaluated the effects of chronic maternal hypoxia on the expression of endothelin and its receptors and on receptor binding activity in the uterus and placenta of the rat, in order to elucidate their roles in hypoxia-induced fetal growth restriction. Timed-pregnant Sprague-Dawley rats were maintained in either a normoxic or a normobaric hypoxic (12% O(2)) atmosphere from Gestational Days 18-21.

Endothelin and platelet-activating factor: significance in the pathophysiology of ischemia/reperfusion-induced fetal growth restriction in the rat.

Objective: The objective of the study was to evaluate the role of endothelin-1 and platelet-activating factor in ischemia/reperfusion-induced fetal growth restriction in the rat.

Study Design: On day 17 of gestation, the right uterine and ovarian arteries were occluded for 30 minutes in experimental but not sham-operated rats. All rats received endothelin receptor A antagonist, A-127722 (10 mg/kg per day), platelet-activating factor antagonist, WEB-2086 (1 mg/kg), or vehicle.

Endothelin and the regulation of uterine and placental perfusion in hypoxia-induced fetal growth restriction.

Objective: Normal placental function is dependent on maintenance of uteroplacental perfusion. Endothelin, a potent vasoconstrictor, is produced in and is active in the uteroplacental vasculature. The purpose of this study was to determine the role of endothelin in the regulation of uteroplacental perfusion under normal conditions, and in hypoxia-induced fetal growth restriction.

Infusion of exogenous platelet-activating factor produces intrauterine growth restriction in the rat.

Objective: To determine the impact of exogenous platelet-activating factor (PAF) on pregnancy outcome in the rat.

Methods: Carbamyl-PAF (0.05, 0.

Prematurity in multiple gestations: identification of patients who are at low risk.

Objective: The purpose of this study was to evaluate a strategy for the identification of patients with multiple gestations who are at low risk for preterm delivery.

Study Design: A prospective observational study among patients with twin and triplet gestations. At 20 and 24 weeks of gestation, screening for bacterial vaginosis and fetal fibronectin was performed, followed by digital and sonographic assessment of the cervix.