Acetaminophen use in pregnancy and risk of birth defects: findings from the National Birth Defects Prevention Study.

Division of Medical Genetics, Department of Pediatrics, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
Obstetrics and Gynecology (Impact Factor: 5.18). 01/2010; 115(1):109-15. DOI: 10.1097/AOG.0b013e3181c52616
Source: PubMed


To investigate whether exposure during the first trimester of pregnancy to single-ingredient acetaminophen increases the risk of major birth defects.
Data from the National Birth Defects Prevention Study, a population-based, case-control study, were used. Women who delivered between January 1, 1997, and December 31, 2004, and participated in the telephone interview were included. Type and timing of acetaminophen use were assigned based on maternal report. Women reporting first-trimester acetaminophen use in a combination product were excluded, resulting in a total of 11,610 children in the case group and 4,500 children in the control group for analysis.
The prevalence of first-trimester single-ingredient-acetaminophen use was common: 46.9% (n=5,440) among women in the case group and 45.8% (n=2,059) among women in the control group (P=.21). Overall, acetaminophen was not associated with an increased risk of any birth defect. Among women reporting a first-trimester infection and fever, use of acetaminophen was associated with a statistically significantly decreased odds ratio (OR) for anencephaly or craniorachischisis (adjusted OR 0.35, 95% confidence interval [CI] 0.08-0.80), encephalocele (adjusted OR 0.17, 95% CI 0.03-0.87), anotia or microtia (adjusted OR 0.25, 95% CI 0.07-0.86), cleft lip with or without cleft palate (adjusted OR 0.44, 95% CI 0.26-0.75), and gastroschisis (adjusted OR 0.41, 95% CI 0.18-0.94).
Single-ingredient-acetaminophen use during the first trimester does not appear to increase the risk of major birth defects. It may decrease the risk of selected malformations when used for a febrile illness.

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    • "This literature search yielded 33 studies with medication usage rates for 14 out of 17 countries with autism prevalence rates. Two studies were excluded because they were subsets of two included studies to yield a total of 31 studies [44,45]. If multiple studies were identified for a country a summary usage rate was calculated using the weighted average by study population size. "
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    ABSTRACT: Background Autism and Autism Spectrum Disorder (ASD) are complex neurodevelopmental disorders. Susceptibility is believed to be the interaction of genetic heritability and environmental factors. The synchronous rises in autism/ASD prevalence and paracetamol (acetaminophen) use, as well as biologic plausibility have led to the hypothesis that paracetamol exposure may increase autism/ASD risk. Methods To explore the relationship of antenatal paracetamol exposure to ASD, population weighted average autism prevalence rates and paracetamol usage rates were compared. To explore the relationship of early neonatal paracetamol exposure to autism/ASD, population weighted average male autism prevalence rates for all available countries and U.S. states were compared to male circumcision rates – a procedure for which paracetamol has been widely prescribed since the mid-1990s. Prevalence studies were extracted from the U.S. Centers for Disease Control and Prevention Summary of Autism/ASD Prevalence Studies database. Maternal paracetamol usage and circumcision rates were identified by searches on Pub Med. Results Using all available country-level data (n = 8) for the period 1984 to 2005, prenatal use of paracetamol was correlated with autism/ASD prevalence (r = 0.80). For studies including boys born after 1995, there was a strong correlation between country-level (n = 9) autism/ASD prevalence in males and a country’s circumcision rate (r = 0.98). A very similar pattern was seen among U.S. states and when comparing the 3 main racial/ethnic groups in the U.S. The country-level correlation between autism/ASD prevalence in males and paracetamol was considerably weaker before 1995 when the drug became widely used during circumcision. Conclusions This ecological analysis identified country-level correlations between indicators of prenatal and perinatal paracetamol exposure and autism/ASD. State level correlation was also identified for the indicator of perinatal paracetamol exposure and autism/ASD. Like all ecological analyses, these data cannot provide strong evidence of causality. However, biologic plausibility is provided by a growing body of experimental and clinical evidence linking paracetamol metabolism to pathways shown to be important in autism and related developmental abnormalities. Taken together, these ecological findings and mechanistic evidence suggest the need for formal study of the role of paracetamol in autism.
    Environmental Health 05/2013; 12(1):41. DOI:10.1186/1476-069X-12-41 · 3.37 Impact Factor
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    • "Moreover, using HEALTHY design, twenty-nine birth defects were significantly associated with acetaminophen exposure. These results disagree with a recent study conducted by the NBDPS (National Births Defects Prevention Study, USA) that showed that single-ingredient acetaminophen use during the first trimester of pregnancy does not appear to increase the risk for major birth defects [32]. Whereas acetaminophen has no proven teratogenic effect [33], the HEALTHY design in our study increased the number of false-positive associations compared to SICK and OECA designs. "
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    PLoS ONE 10/2012; 7(10):e46626. DOI:10.1371/journal.pone.0046626 · 3.23 Impact Factor
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    • "Acetaminophen was also widely used during the pandemic to treat fever, and since the pandemic, additional data have become available regarding risks to the embryo or fetus after use of acetaminophen during pregnancy . In 2010, Feldkamp et al. reported data from the National Birth Defects Prevention Study that showed no increased risks with maternal acetaminophen exposure for each of over 50 birth defects (Feldkamp et al., 2010). Before the pandemic, some studies had shown an association between maternal acetaminophen use and asthma in childhood (Shaheen et al., 2002; Koniman et al., 2007; Persky et al., 2008; Rebordosa et al., 2008; Garcia-Marcos et al., 2009), although not all studies had identified an association (Kang et al., 2009). "
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    ABSTRACT: Anniversaries of the identification of three human teratogens (i.e., rubella virus in 1941, thalidomide in 1961, and diethylstilbestrol in 1971) occurred in 2011. These experiences highlight the critical role that scientists with an interest in teratology play in the identification of teratogenic exposures as the basis for developing strategies for prevention of those exposures and the adverse outcomes associated with them. However, an equally important responsibility for teratologists is to evaluate whether medications and vaccines are safe for use during pregnancy so informed decisions about disease treatment and prevention during pregnancy can be made. Several recent studies have examined the safety of medications during pregnancy, including antiviral medications used to treat herpes simplex and zoster, proton pump inhibitors used to treat gastroesophageal reflux, and newer-generation antiepileptic medications used to treat seizures and other conditions. Despite the large numbers of pregnant women included in these studies and the relatively reassuring results, the question of whether these medications are teratogens remains. In addition, certain vaccines are recommended during pregnancy to prevent infections in mothers and infants, but clinical trials to test these vaccines typically exclude pregnant women; thus, evaluation of their safety depends on observational studies. For pregnant women to receive optimal care, we need to define the data needed to determine whether a medication or vaccine is "safe" for use during pregnancy. In the absence of adequate, well-controlled data, it will often be necessary to weigh the benefits of medications or vaccines with potential risks to the embryo or fetus.
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