Impact of Intrauterine Balloon Aortic Valvuloplasty on Gestational Outcome in a Fetal Goat Model

Abstract

Objective: Intrauterine balloon aortic valvuloplasty (IUBAV) has been used to correct critical aortic valve stenosis. Evaluation of the intervention-related risk is necessary. The purpose of this study was to establish an experimental goat model for ultrasound-guided IUBAV intervention and investigate the immediate and long-term effects of IUBAV on the fetus, gestational outcome and mother’s safety. Study Design: Fifteen pregnant goats with twin gestation in the 2nd and 3rd trimester were anesthetized to establish the surgical procedure. One fetus of the twins received IUBAV intervention, the other served as a control. The data were collected at three time points: immediately before and after IUBAV, and 24 h after birth. Critical organs including the heart, brain, lung and liver from the fetuses/newborns were collected after IUBAV or 24 h after birth. Results: IUBAV intervention immediately induced a significant decrease of pH and Ca²⁺, as well as an increase of blood glucose and lactic acid levels (p < 0.05). IUBAV also caused an increase in stress hormones (epinephrine 1-fold, norepinephrine 4-fold, and cortisol 1-fold; p < 0.05). Following the operation, all of the mother goats recovered, but in 60% (6/10) preterm delivery occurred. Neither pathological changes in fetal critical organs nor a significant difference in metabolism or growth parameters were detected between IUBAV and control kids. Conclusions: Ultrasound-guided IUBAV intervention induced a strong but transient stress response in the operated fetus, which did not result in irreversible histological changes in the fetus or the mother, but may disrupt the continuation of normal gestation in the long term. Preterm delivery is the major risk in this goat IUBAV model.

Protective effects of indomethacin and dexamethasone in a goat model with intrauterine balloon aortic valvuloplasty

“…Our previous study [15] revealed that fetal NE level was remarkably increased following IUBAV. Since NE has various effects on hemodynamics, we further determined whether IDM/DXS treatment could change the level and acting time of fetal serum NE after IUBAV operation.…”

“…Although the technical feasibility has been achieved in animal models as well as in clinical patients [13,25-28], the selection of the right patients in consideration of the long-term outcome of the fetus is still controversial. Our recent study [15] indicated that the IUBAV operation itself causes significant stress responses in fetuses of a goat model, which may in turn disrupt the normal course of gestation. Therefore, we extended our study to determine whether the combinatorial application of contraction inhibitor, indomethacin, and stress inhibitor, dexamethasone, could improve the gestational outcome.…”

“…The goats were prepared as previously reported [15]. Briefly, pregnant goats were fasted for 36 hours, forbidden from drinking for 12 hours and anesthetized using Atropine (i.m., 0.03–0.05 mg/kg), Ketamine (i.m., 10 mg/kg), diazepam (i.v.p., 0.5–1 mg/kg) and infusion of 2.5% chloralhydrate (35–50gtt/min).…”

“…However, even with successful intervention, fetal impairments induced by the novel approach are still unclear [7,13]. Recently, we established an experimental goat model of IUBAV and evaluated the operation-induced fetal metabolic and hemodynamic change, stress response, histological change in critical organs, as well as mother’s safety and gestation outcomes in the fetal and mother goats [15]. We found that the IUBAV operation had significant and immediate impact on the fetus and induced a strong stress response, which might not cause pathological changes in critical organs, but might disrupt the continuation of normal gestation in the long term.…”