Intrauterine Closure of the Ductus Arteriosus: Implications for the Neonatologist

ABSTRACT

Intrauterine closure of the fetal ductus arteriosus is a rare but serious condition. It can lead to congestive heart failure, fetal hydrops, and fetal death. No intrauterine intervention is currently available to treat this condition. Postnatally, it can present as pulmonary hypertension and can be associated with high mortality and morbidity. Postnatal therapies aimed at pulmonary hypertension or with medications that maintain the patency of the ductus arteriosus are variably successful. We present the neonatal course of a full-term neonate with severe pulmonary hypertension and intrauterine closure of the ductus arteriosus who survived to early infancy.

KEYWORDS

Ductus arteriosus - congestive heart failure - pulmonary hypertension - fetal hydrops - prostaglandins

REFERENCES

• 1 Hofstadler G, Tulzer G, Altmann R et al.. Spontaneous closure of the human fetal ductus arteriosus–a cause of fetal congestive heart failure.  Am J Obstet Gynecol. 1996;  174 879-883
• 2 Clyman R I. Ductus arteriosus: current theories of prenatal and postnatal regulation.  Semin Perinatol. 1987;  11 64-71
• 3 Mielke G, Gonser M. Closure of the human fetal ductus arteriosus.  Am J Obstet Gynecol. 1997;  176 495-496
• 4 Trivedi D B, Sugimoto Y, Loftin C D. Attenuated cyclooxygenase-2 expression contributes to patent ductus arteriosus in preterm mice.  Pediatr Res. 2006;  60 669-674 , Epub 2006 Oct 25
• 5 Reese J, Anderson J D, Brown N et al.. Inhibition of cyclooxygenase isoforms in late- but not midgestation decreases contractility of the ductus arteriosus and prevents postnatal closure in mice.  Am J Physiol Regul Integr Comp Physiol. 2006;  291 R1717-R1723 , Epub 2006 Jul 20
• 6 Bouissou A, Glorieux I, Dulac Y et al.. Antenatal closure of ductus arteriosus following maternal intoxication by niflumic acid.  Arch Pediatr. 2006;  13 48-50 , Epub 2005 Nov 17
• 7 Simbi K A, Secchieri S, Rinaldo M et al.. In utero ductal closure following near-term maternal self-medication with nimesulide and acetaminophen.  J Obstet Gynaecol. 2002;  22 440-441
• 8 Clyman R I, Roman C. The effects of caffeine on the preterm sheep ductus arteriosus.  Pediatr Res. 2007;  62 167-169
• 9 Ivey K N, Srivastava D. The paradoxical patent ductus arteriosus.  J Clin Invest. 2006;  116 2863-2865
• 10 Clyman R I, Campbell D. Indomethacin therapy for patent ductus arteriosus: when is prophylaxis not prophylactic?.  J Pediatr. 1987;  111 718-722
• 11 Saenger J S, Mayer D C, D'Angelo L J et al.. Ductus-dependent fetal cardiac defects contraindicate indomethacin tocolysis.  J Perinatol. 1992;  12 41-47
• 12 Rheinlaender C, Weber S C, Sarioglu N et al.. Changing expression of cyclooxygenases and prostaglandin receptor EP4 during development of the human ductus arteriosus.  Pediatr Res. 2006;  60 270-275 , Epub 2006 Jul 20
• 13 Momma K, Takeushi H. Constriction of fetal ductus arteriosus by non-steroidal anti-inflammatory drugs.  Prostaglandins. 1983;  26 631-643
• 14 Auer M, Brezinka C, Eller P et al.. Prenatal diagnosis of intrauterine premature closure of the ductus arteriosus following maternal diclofenac application.  Ultrasound Obstet Gynecol. 2004;  23 513-516
• 15 Suarez V R, Thompson L L, Jain V et al.. The effect of in utero exposure to indomethacin on the need for surgical closure of a patent ductus arteriosus in the neonate.  Am J Obstet Gynecol. 2002;  187 886-888
• 16 Yokoyama U, Minamisawa S, Ouan H et al.. Chronic activation of the prostaglandin receptor EP4 promotes hyaluronan-mediated neointimal formation in the ductus arteriosus.  J Clin Invest. 2006;  116 3026-3034
• 17 Kajino H, Taniquchi T, Fujieda K, Ushikubi F, Muramatsu I. An EP4 receptor agonist prevents indomethacin-induced closure of rat ductus arteriosus in vivo.  Pediatr Res. 2004;  56 586-590 , Epub 2004 Aug 4
• 18 Wasserstrum N, Huhta J C, Mari G et al.. Betamethasone and the human fetal ductus arteriosus.  Obstet Gynecol. 1989;  74 897-900
• 19 Resnik E, Herron J, Keck M et al.. Chronic intrauterine pulmonary hypertension selectively modifies pulmonary artery smooth muscle cell gene expression.  Am J Physiol Lung Cell Mol Physiol. 2006;  290 L426-L433
• 20 van den Hoff M J, Deprez R S, Ruijter J M et al.. Increased cardiac workload by closure of the ductus arteriosus leads to hypertrophy and apoptosis rather than to hyperplasia in the late fetal period.  Naunyn Schmiedebergs Arch Pharmacol. 2004;  370 193-202 , Epub 2004 Aug 31
• 21 Abman S H, Accurso F J. Acute effects of partial compression of ductus arteriosus on fetal pulmonary circulation.  Am J Physiol. 1989;  257(2 Pt 2) H626-H634
• 22 Huhta J C, Moise K J, Fisher D J et al.. Detection and quantitation of constriction of the fetal ductus arteriosus by Doppler echocardiography.  Circulation. 1987;  75 406-412
• 23 Belik J, Halayko A J, Rao K et al.. Fetal ductus arteriosus ligation. Pulmonary vascular smooth muscle biochemical and mechanical changes.  Circ Res. 1993;  72 588-596
• 24 Downing G J, Thibeault D W. Pulmonary vasculature changes associated with idiopathic closure of the ductus arteriosus and hydrops fetalis.  Pediatr Cardiol. 1994;  15 71-75
• 25 Toyoshima K, Momma K, Imamura S et al.. In vivo dilatation of the postnatal ductus arteriosus by atrial natriuretic peptide in the rat.  Neonatology. 2007;  92 139-144 , Epub 2007 Apr 4
• 26 Kajimoto H, Hashimoto K, Bonnet S N et al.. Oxygen activates the Rho/Rho-kinase pathway and induces RhoB and ROCK-1 expression in human and rabbit ductus arteriosus by increasing mitochondria-derived reactive oxygen species: a newly recognized mechanism for sustaining ductal constriction.  Circulation. 2007;  115 1777-1788 , Epub 2007 Mar 12