Case Report: Persistent Pulmonary Hypertension of the Newborn and Narrowing of the Ductus Arteriosus After Topical Use of Non-Steroidal Anti-Inflammatory During Pregnancy

Background: The use of non-steroidal anti-inflammatory drugs (NSAIDs) during the third trimester of pregnancy can cause premature constriction of the ductus arteriosus. This report describes a case of in utero narrowing of the ductus arteriosus (DA) diagnosed postnatally in a baby with Persistent Pulmonary Hypertension of the Newborn (PPHN), after maternal use of Diclofenac-Epolamine 140 mg patch during the second and third trimester. Case Presentation: A fetal ultrasounds revealed an enlarged hypertrophic right ventricle at 32 weeks of gestation. Detailed questioning of the mother highlighted that topical Diclofenac (FLECTOR®) had been used at 26 and at 31 weeks of gestation. An echocardiography performed 8 h postnatally showed supra-systemic pulmonary hypertension, a restrictive ductus arteriosus and a dilated right ventricle. The newborn was treated by inhaled nitric oxide and oral Sildenafil and was discharged from hospital on day 24. He had a complete normalization of his pulmonary vascular resistance on day 48. Conclusion: This case illustrates the potential fetal and neonatal complications associated with maternal topical Diclofenac medication during pregnancy resulting in antenatal closure of the DA.

[1]  C. Schaefer,et al.  Risk estimation of fetal adverse effects after short-term second trimester exposure to non-steroidal anti-inflammatory drugs: a literature review , 2019, European Journal of Clinical Pharmacology.

[2]  S. Narasimha Murthy,et al.  Effect of Mild Hyperthermia on Transdermal Absorption of Nicotine from Patches , 2019, AAPS PharmSciTech.

[3]  M. Lane,et al.  Formulation of diclofenac for dermal delivery. , 2014, International journal of pharmaceutics.

[4]  S. Busato,et al.  Prenatal Effects of Maternal Consumption of Polyphenol-Rich Foods in Late Pregnancy upon Fetal Ductus Arteriosus , 2013, Birth defects research. Part C, Embryo today : reviews.

[5]  P. Tourneux,et al.  Pathophysiology of persistent pulmonary hypertension of the newborn: impact of the perinatal environment. , 2013, Archives of cardiovascular diseases.

[6]  Y. Taketani,et al.  Prediction and evaluation of fetal toxicity induced by NSAIDs using transplacental kinetic parameters obtained from human placental perfusion studies. , 2012, British journal of clinical pharmacology.

[7]  M. Migita,et al.  Idiopathic severe constriction of the fetal ductus arteriosus: a possible underestimated pathophysiology , 2011, European Journal of Pediatrics.

[8]  B. Eyskens,et al.  Premature foetal closure of the arterial duct: clinical presentations and outcome. , 2009, European heart journal.

[9]  G. Ehrlich,et al.  Review of the pharmaceutical properties and clinical effects of the topical NSAID formulation, diclofenac epolamine , 2008 .

[10]  M. Prausnitz,et al.  The effect of heat on skin permeability. , 2008, International journal of pharmaceutics.

[11]  R. Clyman Mechanisms Regulating the Ductus Arteriosus , 2006, Neonatology.

[12]  M. Torloni,et al.  Reversible constriction of the fetal ductus arteriosus after maternal use of topical diclofenac and methyl salicylate , 2006, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[13]  L. Storme,et al.  Pulmonary vascular effects of sildenafil on the development of chronic pulmonary hypertension in the ovine fetus. , 2005, American journal of physiology. Lung cellular and molecular physiology.

[14]  C. Brezinka,et al.  Prenatal diagnosis of intrauterine premature closure of the ductus arteriosus following maternal diclofenac application , 2004, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[15]  J. Manica,et al.  Intrauterine ductus arteriosus constriction: analysis of a historic cohort of 20 cases. , 2003, Arquivos brasileiros de cardiologia.

[16]  Y. Sawada,et al.  H(+)-linked transport of salicylic acid, an NSAID, in the human trophoblast cell line BeWo. , 2002, American journal of physiology. Cell physiology.

[17]  J. Domenech,et al.  In vitro based index of topical anti-inflammatory activity to compare a series of NSAIDs. , 2001, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[18]  T. Lau,et al.  A study on placental transfer of diclofenac in first trimester of human pregnancy. , 2000, Human reproduction.

[19]  J C Huhta,et al.  Role of the pulmonary circulation in the distribution of human fetal cardiac output during the second half of pregnancy. , 1996, Circulation.

[20]  A. Leviton,et al.  Persistent pulmonary hypertension of the newborn and smoking and aspirin and nonsteroidal antiinflammatory drug consumption during pregnancy. , 1996, Pediatrics.

[21]  J. Evans,et al.  Topical non-steroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study , 1995, BMJ.

[22]  K. Moise,et al.  Prostaglandin synthetase inhibitors in pregnancy. , 1993, Obstetrical & gynecological survey.

[23]  K. Momma,et al.  Constriction of fetal ductus arteriosus by non-steroidal anti-inflammatory drugs:study of additional 34 drugs. , 1984, Prostaglandins.

[24]  B. Whittle PROSTAGLANDIN SYNTHETASE INHIBITORS , 1979, Acta obstetricia et gynecologica Scandinavica. Supplement.

[25]  L. Storme,et al.  Chronic hypertension impairs flow-induced vasodilation and augments the myogenic response in fetal lung. , 2002, American journal of physiology. Lung cellular and molecular physiology.