The Hemodynamic Effects of Antenatal Indomethacin and a β-Sympathomimetic Agent on the Fetus and the Newborn: A Randomized Study

Abstract

ABSTRACT. To study the effect of antenatal indomethacin or nylidrin hydrochloride treatment on the fetal and neonatal ductus arteriosus and tricuspid valve function, 84 pregnant women with threatened premature birth between 22.9 and 34.0 wk gestation and 94 of their offspring born at 24.7 to 41.6 wk of gestation were studied by Doppler echocardiography. Forty-six women were treated with indomethacin and 38 with nylidrin. Both peak systolic and peak diastolic velocities in the ductus increased after administration of indomethacin and exceeded the corresponding velocities in the fetuses of the nylidrin group ( p = 0.0001). Ductal constriction occurred in 42 of 49 fetuses treated with indomethacin (86%). Tricuspid valve regurgitation (TR) was evident in 11 of 49 fetuses treated with indomethacin (22%). The mean gestational age of the fetuses with TR (30.0 wk) tended to be higher than those without TR (28.3 wk, p = 0.056). In the nylidrin group, no fetus had ductal constriction or TR. A significant increase in peak systolic velocity ( r = 0.54, p = 0.0001) and in peak diastolic velocity ( r = 0.46, p = 0.0001) in the ductus with advancing gestational age was demonstrated in the indomethacin group; however, in the nylidrin group, there was a less remarkable increase in peak systolic velocity ( r = 0.35, p = 0.04) and no increase in peak diastolic velocity ( r = 0.02, p = 0.93). In infants born at or before 35 wk gestation, incidences of both spontaneous closure and indomethacin-induced closure of ductus were similar in both study groups (p > 0.1). Ductal reopening tended to occur more frequently after indomethacin (17%) than after nylidrin (0%) administration ( p = 0.15). These findings indicate that: 1) the fetal ductus becomes more reactive to indomethacin with increasing gestational age; 2) TR tends to occur in fetuses with advanced gestational age; and 3) prenatal exposure of indomethacin does not decrease the need for patent ductus arteriosus treatment in premature infants. (Pediatr Res 33: 615-619, 1993) Abbreviations PDA, patent ductus arteriosus PDV, peak diastolic velocity PSV, peak systolic velocity RDS, respiratory distress syndrome TR, tricuspid valve regurgitation

Clinical Features of the Complete Closure of the Ductus Arteriosus Prenatally

“…14 The constriction of the DA in utero is considered to often be associated with the maternal administration of prostaglandin synthase inhibitors, such as indomethacin or other NSAIDs. 15 Moreover, most reports state that the premature constriction of the DA occurs mainly in the third trimester. Eronen et al demonstrated that the sensitivity of the DA to indomethacin increases with gestational age.…”

Indomethacin decreases furosemide-induced natriuresis and diuresis on the neonatal kidney

“…Indomethacin has been successfully used for the pharmacological closure of patent ductus arteriosus in low-birthweight neonates [13,14]. This treatment is complicated by renal dysfunction of variable severity, ranging from transient oliguria to acute renal failure [15].…”

Functional pulmonary valve regurgitation in the fetus

“…Indomethacin, as a tocolytic agent in preterm labor and in the therapy of polyhydramnios, as well as betamethasone, as an agent to reduce the incidence of respiratory distress syndrome and infant mortality in premature infants, are accompanied by a reversible partial constriction of the ductus arteriosus 16,[23][24][25][26][27][28] . However, two of our patients with pulmonary valve regurgitation were exposed to maternal medication (valproic acid and thiamazole), but the medication is thought to be without an influence on the fetal ductus arteriosus.…”