Possible association between maternal indomethacin therapy and primary pulmonary hypertension of the newborn

Manchester, David K.; Margolis, Harold S.; Sheldon, Roger E.

doi:10.1016/0002-9378(76)90640-2

Cited by 204 publications

(45 citation statements)

References 9 publications

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“…Many pregnant women continue to use aspirin-containing drugs as analgesics, antipyretics, and anti-inflammatory agents. It has been reported by others that indomethacin may interfere with normal circulatory adjustments at birth in man (22), as we would predict could be possible from our experiments on goats and sheep. Obviously, many women ingest nonsteroidal anti-inflammatory agents and deliver healthy, normal babies.…”

Section: Discussionsupporting

confidence: 77%

The Onset of Breathing at Birth Stimulates Pulmonary Vascular Prostacyclin Synthesis

1984

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Section: Discussionsupporting

confidence: 77%

The Onset of Breathing at Birth Stimulates Pulmonary Vascular Prostacyclin Synthesis

1984

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“…There are reports of pulmonary hypertension in newborn infants after administration of indomethacin (17,18). In the present study, no significant difference in the incidence of pulmonary hypertension between the groups could be found; in three premature infants (two in the indomethacin group and one in the nylidrin group), pulmonary hypertension was associated with severe RDS.…”

Section: Ductal Jlow Velocities In Fetusescontrasting

confidence: 62%

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

Eronen

1993

Pediatr Res

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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

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“…Administration of indomethacin or other prostaglandin synthetase inhibitors to pregnant animals causes ductal constriction and elevation of pulmonary artery pressure in the fetus (17,18). Indomethacin has been implicated in causing intrauterine ductal occlusion and PPHN in human neonates (19). Levin et al (20), using a unique method of quantitative analysis of the injected pulmonary vasculature, showed increased medial wall thickness of fifth generation pulmonary arteries in two human neonates who died of PPHN after maternal ingestion of prostaglandin synthetase inhibitors (indomethacin, acetylsalicylic acid).…”

Section: Resultsmentioning

confidence: 99%

Ligating the Ductus Arteriosus before birth Remodels the Pulmonary Vasculature of the Lamb

Wild¹,

Nickerson²,

Morin

1989

Pediatr Res

110

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ABSTRACT. The clinical syndrome of persistent pulmonary hypertension of the newborn includes a developmentally abnormal pulmonary microvasculature which contains excessive amounts of muscle and which cannot adapt to air breathing in the perinatal period. Surgical ligation of the ductus arteriosus of the fetal lamb has produced a physiologic model of pulmonary hypertension of the newborn. The aim of the present investigation is to determine whether surgical ligation of the ductus arteriosus in fetal sheep produces anatomic changes in the pulmonary blood vessels. The pulmonary vasculature of seven neonatal lambs that underwent surgical ligation of the ductus arteriosus from 6 to 17 d before birth was compared to that of five control lambs with a patent ductus arteriosus without fetal surgery and three control lambs with a patent ductus arteriosus that underwent sham surgery. Quantitative microscopic analysis of the barium gelatin-filled peripheral pulmonary vascular bed revealed an increase in thc proportion of partially and fully muscularized pulmonary arteries a t the level of the terminal bronchiole and within the acinus (p < 0.0001). This finding demonstrates that medial muscle develops in areas of the distal pulmonary vascular bed where it is normally absent. Periadventitial fibrosis surrounding intraacinar pulmonary arteries was also present. No change in the number of small intraacinar arteries was detected. This structural remodeling of the peripheral pulmonary vascular bed was initiated in utero by ductus arteriosus occlusion. Prenatal closure of the ductus arteriosus for 6 to 17 d in fetal lambs produces anatomic changes in small pulmonary arteries of the newborn lamb. These anatomic changes are similar to pathologic alterations reported in human neonates dying with idiopathic persistent pulmonary hypertension of the newborn. The clinical syndrome of idiopathic PPHN is characterized morphologically by the abnormal presence of muscle in the walls of the smallest pulmonary artery branches (1). The etiology of PPHN occurring in the absence of primary cardiac, pulmonary,

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Possible association between maternal indomethacin therapy and primary pulmonary hypertension of the newborn

Cited by 204 publications

References 9 publications

The Onset of Breathing at Birth Stimulates Pulmonary Vascular Prostacyclin Synthesis

The Onset of Breathing at Birth Stimulates Pulmonary Vascular Prostacyclin Synthesis

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

Ligating the Ductus Arteriosus before birth Remodels the Pulmonary Vasculature of the Lamb

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