Constriction of the fetal ductus arteriosus after administration of indomethacin to the pregnant ewe

doi:10.1016/S0022-3476(79)80043-8

The Journal of Pediatrics

Volume 94, Issue 4, April 1979, Pages 647-650

https://doi.org/10.1016/S0022-3476(79)80043-8 Get rights and content

The prostaglandin synthetase inhibitor indomethacin was given orally or intravenously to pregnant ewes.This resulted in the fetal pulmonary to systemic arterial mean blood pressure difference across the ductus arteriosus rising significantly, presumably secondary to constriction of the ductus arteriosus. The pressure difference was due to pulmonary arterial hypertension, and not due to a fall in systemic arterial mean blood pressure. Fetal arterial blood gas tensions and pH values were normal throughout. In five experiments the pressure difference could be promptly but temporarily reversed by the administration of PGE₁ into the fetal inferior vena cava. Indomethacin was present in fetal blood, and maternal plasma prostaglandin levels were suppressed. Indomethacin administration during pregnancy causes constriction of the fetal ductus arteriosus and fetal pulmonary arterial hypertension which, if severe, may cause rapid fetal death. It is possible that this mechanism may be one cause of persistent pulmonary hypertension or tricuspid insufficiency or both in the newborn infant.

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The article is primarily focused on PPHN and a detailed description of impaired pathophysiology and management of CDH is out of the scope of this article. Other causes of PPHN include constriction of the fetal ductus arteriosus in utero, which can occur after exposure of fetus to nonsteroidal anti-inflammatory drugs or selective serotonin reuptake inhibitors during late gestation.15–17 There is a sixfold increase in the prevalence of PPHN after exposure to these medications during the third trimester.17
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La fermeture anténatale du canal artériel est un événement exceptionnel qui peut conduire à une insuffisance cardiaque fœtale et se traduire à la naissance par des signes d'hypertension artérielle pulmonaire. Nous rapportons ici un cas de fermeture anténatale du canal artériel secondaire à une intoxication volontaire maternelle par acide niflumique à 32 semaines d'aménorrhée (SA). Le diagnostic échocardiographique anténatal précoce et l'apparition de signes de retentissement cardiaque fœtal ont motivé l'extraction fœtale. L'issue a été favorable malgré une hypoxémie réfractaire. Ce nouveau cas souligne la toxicité potentielle de l'acide niflumique pendant la grossesse et l'intérêt de la surveillance échographique anténatale régulière en cas d'exposition.
Antenatal closure of the ductus arteriosus is an uncommon event that has been considered as a risk factor for development of congestive heart failure and persistent pulmonary hypertension of the newborn. We report here on a case of antenatal ductus arteriosus closure due to niflumic acid maternal intoxication at 32 weeks of gestation. Fetal extraction was performed few days later because of echographic signs of congestive heart failure. The child survived after 3 days of severe persistent pulmonary hypertension. This case emphasizes the potential risk of niflumic acid during pregnancy and the need of antenatal echographic monitoring for optimal management.
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^**: Supported by the American Heart Association Grant-In-Aid 76-878.

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Constriction of the fetal ductus arteriosus after administration of indomethacin to the pregnant ewe**

Prostaglandins

Am J Obstet Gynecol

J Pediatr

Am J Obstet Gynecol

J Pediatr

Am J Obstet Gynecol

J Pediatr

Prostaglandins

The pharmacological basis of therapeutics