Antiherpetic Medication Use and the Risk of Gastroschisis: Findings from the National Birth Defects Prevention Study, 1997–2007

Abstract

Background Previous studies examining the teratogenic effects of antiherpetic medications have found no associations for birth defects overall but have not examined the risk of specific birth defects. Methods The National Birth Defects Prevention Study ascertains population-based cases with birth defects and live-born controls without birth defects in ten states across the United States for the purpose of identifying potential teratogenic risk factors. Mothers of cases and controls are interviewed within two years of their estimated date of delivery about demographic, medical and behavioral factors before and during pregnancy. This analysis examined the possible association between use of antiherpetic medications (acyclovir, valacyclovir or famciclovir) during early pregnancy and gastroschisis, a birth defect of the abdominal wall. Results The mothers of 1.1% (n=10) of 941 gastroschisis cases and 0.3% (n=27) of 8339 controls reported antiherpetic medication use during the month before conception through the third month of pregnancy. The adjusted odds ratios for such use in relation to gastroschisis were 4.68 (95% confidence interval [1.65, 13.28]) and 4.68 [1.15, 19.03] among women with and without self-reported genital herpes, respectively, when compared to women without antiherpetic use or herpes. Among women reporting no antiherpetic medication use, the odds ratio for self-reported genital herpes in relation to gastroschisis was 3.00 [1.58, 5.68]. Conclusions Our study raises the possibility of an increased risk of gastroschisis due to either antiherpetic medication use during early pregnancy or the underlying genital herpes infection for which it was indicated.

Maternal factors associated with the occurrence of gastroschisis

“…While our findings across a number of other factors are in agreement with associations previously reported in the literature-namely with respect to parity [Feldkamp et al, 2008;Duong et al, 2012], education [Jenkins et al, 2014], rural versus urban residence [Salihu et al, 2003], smoking [Siega-Riz et al, 2009;Hackshaw et al, 2011;Khodr et al, 2013;Jenkins et al, 2014], drug abuse [Elliott et al, 2009], maternal nativity [Salemi et al, 2009], and infection [Feldkamp et al, 2008;Elliott et al, 2009;Ahrens et al, 2013;Yazdy et al, 2014]-our findings suggest that these risks may differ somewhat by age grouping. Like others [Salihu et al, 2003;Siega-Riz et al, 2009;Jenkins et al, 2014], before consideration of factors by age grouping, we found that Hispanic women were at increased risk of gastroschisis compared to non-Hispanic white women.…”

“…While others have also observed a relationship between gastroschisis, sexually transmitted diseases, and urinary tract infections [Feldkamp et al, 2008;Elliott et al, 2009;Ahrens et al, 2013;Yazdy et al, 2014], our findings suggest an age-related pattern with respect to the importance of a particular type of infection. Of particular note with respect to age-related patterns is our observation regarding reported infection.…”

A machine learning approach to investigate potential risk factors for gastroschisis in California

“…We observed higher odds of delivering an infant with gastroschisis with acetaminophen use in the beginning of pregnancy among women younger than 20 but after adjustment for other variables such as urinary tract infection the odds were attenuated. Associations between maternal use of various medications and gastroschisis have been studied previously (Ahrens et al, ; Alwan, Reefhuis, Rasmussen, Olney, & Friedman, ; Draper et al, ; Feldkamp, Meyer, Krikov, & Botto, ; Interrante et al, ; Lin et al, ; Polen, Rasmussen, Riehle‐Colarusso, & Reefhuis, ; Waller et al, ; Werler et al, ; Werler, Sheehan, & Mitchell, ). However, acetaminophen was the only important predictor we identified of the medications included in our analysis.…”

Maternal genitourinary infections and risk of birth defects in the National Birth Defects Prevention Study

“…The treatments for GUIs vary widely, so it seems unlikely that one medication is responsible for the range of significant associations observed. Studies exploring risk of medications used to treat GUIs, including antibiotics and antiherpetic medications, have been inconsistent (Ahrens et al, 2013;Ailes et al, 2016;Andersen et al, 2013;Hansen et al, 2016;Pasternak & Hviid, 2010;Reiff-Eldridge et al, 2000). We did not explore medications in this analysis.…”