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Use of opioid analgesics in early pregnancy associated with birth defects

Clinical Question:
Is exposure to prescription opioid analgesics in early pregnancy associated with birth defects?

Bottom Line:
There is an association between a woman's exposure to opioid analgesics in early pregnancy and heart defects and spina bifida in her children. The findings were also suggestive of increased risk for hydrocephaly, glaucoma, and gastroschisis. The study results could have been affected by recall bias; that is, mothers of children with birth defects may be more likely to remember taking medications around the time of conception. (LOE = 3b)

Broussard CS, Rasmussen SA, Reefhuis J, et al, for the National Birth Defects Prevention Study. Maternal treatment with opioid analgesics and risk for birth defects. Am J Obstet Gynecol 2011;204(4):314.e1-14.  [PMID:21345403]

Study Design:



The authors analyzed data from the National Birth Defects Prevention Study, a population-based case-control study with sites in 10 states. They included data about infants born from October 1997 through December 2005 to assess associations between birth defects and maternal exposure to opioid analgesics between 1 month prior to conception through 3 months' gestation. Mothers were interviewed between 6 months and 2 years after date of delivery. Prescribed opioids considered at any dose or duration were: codeine (34.5%), hydrocodone (34.5%), oxycodone (14.4%), meperidine (12.9%), propoxyphene, morphine tramadol, methadone, hydromorphone, fentanyl, and pentazocine. The authors excluded participants with missing data, pre-existing diabetes, or illicit drug use at any time during the pregnancy. The final sample included 17,449 infants with birth defects and 6701 control infants. The authors conducted multivariable logistic regression analyses to estimate odds ratios (ORs). The primary analysis included 7724 infants with one or more of 15 types of congenital heart defects (OR = 1.4; 95% CI, 1.1-1.7). Significant associations were demonstrated for specific congenital heart defects: conoventricular septal defects, atrial septal defects, hypoplastic heart syndrome, tetrology of Fallot, and pulmonary valve stenosis. The associations were not dose dependent. The researchers also found a significant association with spina bifida, but not other neural tube defects (OR = 2.0; 1.3-3.2). Exploratory analyses showed associations for hydrocephaly, glaucoma or other anterior chamber eye defects, and gastroschisis. Limiting the analysis to women who reported exposure to opioids between 1 month and 2 months of gestation produced similar results, with the strongest association for hypoplastic left heart syndrome (OR = 3.7; 2.1-6.6).


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