Maternal drug use, fertility problems, and infant craniostenosis.
OBJECTIVE
To test the hypothesis that maternal drug use or treatment for infertility is related to the occurrence of infant craniostenosis.


METHODS
Maternal drug use and infertility treatment were studied in 398 cases of craniostenosis, identified from various Swedish health registers. Exposure information was ascertained in early pregnancy, and comparisons after adjustment for some confounders were made with all infants born. In order to validate some findings, data from the Central-East France Registry were studied for first trimester drug exposure in 235 infants, and use of ovarian stimulation in 315 infants with craniostenosis.


RESULTS
A statistically significant association between maternal use of anticonvulsants and infant craniostenosis was found (risk ratio [Swedish data], 6.9; 95% confidence interval, 1.10 to 7.94). With the Swedish data, an association was found with three nitrosatable drugs (risk ratio, 3.4; 95% confidence interval, 1.10 to 7.94), previously associated with the occurrence of craniostenosis, but this was based on only five exposures, and no such exposure occurred in the French data set. No association with subfertility (odds ratio, 0.72; 95% confidence interval, 0.60 to 1.86) or infertility treatment (odds ratio, 1.06; 95% confidence interval, 0.60 to 1.87) was found in the Swedish data and no statistically significant increase in the use of ovulation stimulation in the French data.


CONCLUSIONS
A strong association was found between the maternal use of anticonvulsants and infant craniostenosis, and a tentative association was found with the use of nitrofurantoin and two other nitrosatable drugs. There was no association with maternal subfertility or infertility treatment.
Källén
Bengt
B
Tornblad Institute, University of Lund, Lund, Sweden. embryol@embryol.lu.se
Robert-Gnansia
Elisabeth
E
D000328:Adult; D018926:Anti-Allergic Agents / Q000009:adverse effects; D014151:Anti-Anxiety Agents / Q000009:adverse effects; D000892:Anti-Infective Agents, Urinary / Q000009:adverse effects; D000927:Anticonvulsants / Q000009:adverse effects; D002707:Chlordiazepoxide / Q000009:adverse effects; D002744:Chlorpheniramine / Q000009:adverse effects; D003398:Craniosynostoses / Q000139:chemically induced*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005300:Fertility Agents, Female / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D007247:Infertility, Female / Q000188:drug therapy*; D008875:Middle Aged; D009582:Nitrofurantoin / Q000009:adverse effects; D010062:Ovulation Induction / Q000009:adverse effects; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors
D018926:Anti-Allergic Agents; D014151:Anti-Anxiety Agents; D000892:Anti-Infective Agents, Urinary; D000927:Anticonvulsants; D005300:Fertility Agents, Female; D002744:Chlorpheniramine; D002707:Chlordiazepoxide; D009582:Nitrofurantoin