title: Maternal butalbital use and selected defects in the national birth defects prevention study.
abstract: BACKGROUND
  Butalbital is a barbiturate contained in combination products with caffeine and an analgesic prescribed for the treatment of migraine and tension-type headaches. Controversy exists as to whether butalbital should continue to be prescribed in the United States because of the potential for abuse, overuse headache, and withdrawal syndromes. Butalbital crosses the placenta but there is limited information about potential teratogenicity.
  
  
  OBJECTIVE
  To evaluate associations between butalbital and a wide range of specific birth defects.
  
  
  METHODS
  The National Birth Defects Prevention Study is an ongoing, case-control study of nonsyndromic, major birth defects conducted in 10 states. The detailed case classification and large number of cases in the National Birth Defects Prevention Study allowed us to examine the association between maternal self-reported butalbital use and specific birth defects. We conducted an analysis of 8373 unaffected controls and 21,090 case infants with estimated dates of delivery between 1997 and 2007; included were birth defects with 250 or more cases. An exploratory analysis examined groups with 100 to 249 cases.
  
  
  RESULTS
  Seventy-three case mothers and 15 control mothers reported periconceptional butalbital use. Of 30 specific defect groups evaluated, adjusted odds ratios for maternal periconceptional butalbital use were statistically significant for 3 congenital heart defects: tetralogy of Fallot (adjusted odds ratio = 3.04; 95% confidence interval = 1.07-8.62), pulmonary valve stenosis (adjusted odds ratio = 5.73; 95% confidence interval = 2.25-14.62), and secundum-type atrial septal defect (adjusted odds ratio = 3.06; 95% confidence interval = 1.07-8.79). In the exploratory analysis, an elevated odds ratio was detected for 1 congenital heart defect, single ventricle.
  
  
  CONCLUSIONS
  We observed relationships between maternal periconceptional butalbital use and certain congenital heart defects. These associations have not been reported before, and some may be spurious. Butalbital use was rare and despite the large size of the National Birth Defects Prevention Study, the number of exposed case and control infants was small. However, if confirmed in additional studies, our findings will be useful in weighing the risks and benefits of butalbital for the treatment of migraine and tension-type headaches.
authors.affiliation: Congenital Malformations Registry, New York State Department of Health, Albany, NY, USA; School of Public Health, University at Albany, Rensselaer, NY, USA.
authors.forename: Marilyn L
authors.initials: ML
authors.lastname: Browne
authors.forename: Alissa R
authors.initials: AR
authors.lastname: Van Zutphen
authors.forename: Lorenzo D
authors.initials: LD
authors.lastname: Botto
authors.forename: Carol
authors.initials: C
authors.lastname: Louik
authors.forename: Sandra
authors.initials: S
authors.lastname: Richardson
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Druschel
mesh_terms: D000293:Adolescent; D000328:Adult; D001463:Barbiturates / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D000013:Congenital Abnormalities; D005260:Female; D006330:Heart Defects, Congenital / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D007231:Infant, Newborn; D011159:Population Surveillance / Q000379:methods; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D057566:Self Report / Q000592:standards; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D001463:Barbiturates; C004470:butalbital
keywords: birth defect; butalbital; headache; migraine