title: When the right (Drug) should be left: Prenatal drug exposure and heterotaxy syndrome.
abstract: BACKGROUND
  Recent studies reported an association between prenatal propylthiouracil exposure and birth defects, including abnormal arrangement across the left-right body axis, suggesting an association with heterotaxy syndrome.
  
  
  METHODS
  This case-control and case-finding study used data from 1981 to 2013 from the EUROCAT birth defect registry in the Northern Netherlands. First, we explored prenatal exposures in heterotaxy syndrome (cases) and Down syndrome (controls). Second, we describe the specific birth defects in offspring of mothers using propylthiouracil (PTU) prenatally.
  
  
  RESULTS
  A total of 66 cases with heterotaxy syndrome (incidence 12.1 per 100,000 pregnancies) and 783 controls with Down syndrome (143.3 per 100,000 pregnancies) were studied. No differences in intoxication use during pregnancy were found between cases and controls, including smoking (28.0% vs. 22.7%; p = 0.40), alcohol (14.0% vs. 26.9%; p = 0.052), and recreational drugs (0 vs. 0.3%; p = 1.00). We found an association between heterotaxy syndrome and prenatal drug exposure to follitropin-alfa (5.6% vs. 1.1%; p = 0.04), and drugs used in nicotine dependence (3.7% vs. 0.2%; p = 0.02). Five mothers used PTU during pregnancy and gave birth to a child with trisomy 18, renal abnormalities, or hypospadias and cardiac defects.
  
  
  CONCLUSIONS
  This study identified follitropin-alfa and drugs used in nicotine dependence as possible teratogens of heterotaxy syndrome. Our data suggest the possibility that there is an increased risk of birth defects (including renal, urological, and cardiac abnormalities) in children born among mothers taking PTU prenatally, but not for heterotaxy syndrome. Birth Defects Research (Part A) 106:573-579, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pediatrics and Clinical Genetics, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.|Department of Pediatrics, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
authors.forename: Nicole R
authors.initials: NR
authors.lastname: van Veenendaal
authors.affiliation: Eurocat Northern Netherlands, Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Cynthia D J
authors.initials: CD
authors.lastname: Kusters
authors.affiliation: Department of Anatomy, Embryology and Physiology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Roelof-Jan
authors.initials: RJ
authors.lastname: Oostra
authors.affiliation: Eurocat Northern Netherlands, Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jorieke E H
authors.initials: JE
authors.lastname: Bergman
authors.affiliation: Department of Pediatrics and Clinical Genetics, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Jan-Maarten
authors.initials: JM
authors.lastname: Cobben
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects; D016022:Case-Control Studies; D004314:Down Syndrome / Q000139:chemically induced / Q000453:epidemiology; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage / Q000009:adverse effects*; D059446:Heterotaxy Syndrome / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D013287:Illicit Drugs / Q000009:adverse effects; D009426:Netherlands / Q000453:epidemiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000453:epidemiology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012042:Registries; D012907:Smoking / Q000009:adverse effects
chemical_list: D043373:Follicle Stimulating Hormone, Human; D013287:Illicit Drugs; D011994:Recombinant Proteins; C571801:follitropin alfa
keywords: heterotaxy syndrome; pregnancy; prenatal drug exposure; propylthiouracil; teratology