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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    • "Other studies have reported associations between peri-conceptual use of codeine and the incidence of neural tube defects[18]and neuroblastoma[19]. Co-administration of codeine with paracetamol is unlikely to explain the higher rate of congenital abnormalities , because paracetamol per se is not associated with an increase in birth abnormalities[20,21]. The worrying associations between use of codeine and birth defects are, however, tempered by a recent Norwegian cohort study that failed to identify an association between use of codeine in pregnancy and an increased rate of congenital malfor- mations[22]. "

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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.
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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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    ABSTRACT: Different approaches have been used in case-control studies to estimate maternal exposure to medications and the risk of birth defects. However, the performance of these approaches and how they affect the odds ratio (OR) estimates have not been evaluated using birth-defect surveillance programmes. The aim of this study was to evaluate the scope and limitations of three case-control approaches to assess the teratogenic risk of birth defects in mothers exposed to antiepileptic medications, insulin, or acetaminophen.
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