Acetaminophen Use During Pregnancy, Behavioral Problems, and Hyperkinetic Disorders
ABSTRACT IMPORTANCE Acetaminophen (paracetamol) is the most commonly used medication for pain and fever during pregnancy in many countries. Research data suggest that acetaminophen is a hormone disruptor, and abnormal hormonal exposures in pregnancy may influence fetal brain development. OBJECTIVE To evaluate whether prenatal exposure to acetaminophen increases the risk for developing attention-deficit/hyperactivity disorder (ADHD)-like behavioral problems or hyperkinetic disorders (HKDs) in children. DESIGN, SETTING, AND PARTICIPANTS We studied 64 322 live-born children and mothers enrolled in the Danish National Birth Cohort during 1996-2002. EXPOSURES Acetaminophen use during pregnancy was assessed prospectively via 3 computer-assisted telephone interviews during pregnancy and 6 months after child birth. MAIN OUTCOMES AND MEASURES To ascertain outcome information we used (1) parental reports of behavioral problems in children 7 years of age using the Strengths and Difficulties Questionnaire; (2) retrieved HKD diagnoses from the Danish National Hospital Registry or the Danish Psychiatric Central Registry prior to 2011; and (3) identified ADHD prescriptions (mainly Ritalin) for children from the Danish Prescription Registry. We estimated hazard ratios for receiving an HKD diagnosis or using ADHD medications and risk ratios for behavioral problems in children after prenatal exposure to acetaminophen. RESULTS More than half of all mothers reported acetaminophen use while pregnant. Children whose mothers used acetaminophen during pregnancy were at higher risk for receiving a hospital diagnosis of HKD (hazard ratio = 1.37; 95% CI, 1.19-1.59), use of ADHD medications (hazard ratio = 1.29; 95% CI, 1.15-1.44), or having ADHD-like behaviors at age 7 years (risk ratio = 1.13; 95% CI, 1.01-1.27). Stronger associations were observed with use in more than 1 trimester during pregnancy, and exposure response trends were found with increasing frequency of acetaminophen use during gestation for all outcomes (ie, HKD diagnosis, ADHD medication use, and ADHD-like behaviors; P trend < .001). Results did not appear to be confounded by maternal inflammation, infection during pregnancy, the mother's mental health problems, or other potential confounders we evaluated. CONCLUSIONS AND RELEVANCE Maternal acetaminophen use during pregnancy is associated with a higher risk for HKDs and ADHD-like behaviors in children. Because the exposure and outcome are frequent, these results are of public health relevance but further investigations are needed.
SourceAvailable from: Ragnhild Eek Brandlistuen
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ABSTRACT: In a letter to the editor of Basic & Clinical Pharmacology & Toxicology, Per Damkier et al.1 criticise recent studies linking paracetamol exposure in pregnancy with adverse neurodevelopmental outcomes. They state that the recent findings on associations between prolonged prenatal paracetamol exposure and adverse child developmental outcomes rely primarily on questionnaire-based outcomes such as the Ages and Stages Questionnaire (ASQ)2 which they claim to be invalid and uninterpretable.This article is protected by copyright. All rights reserved.Basic & Clinical Pharmacology & Toxicology 10/2014; 116(1). DOI:10.1111/bcpt.12339 · 2.18 Impact Factor
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ABSTRACT: The intake of several substances by pregnant women could be hazardous to the fetus and mother health: many substances can cross the placenta and reach the fetal compartment, causing adverse outcomes. Consequently, to accurately measure the presence of xenobiotics in fetal matrices, sensitive and specific bioanalytical methods are necessary: this would allow to assess fetal exposure to substances which, although licit, can be dangerous for the fetal and child’s growth. The aim of this study was to develop and validate a liquid chromatography tandem mass spectrometry method for the simultaneous determination and quantitation of caffeine and acetaminophen in amniotic fluid. Amniotic fluid is a quite complex biological matrix and, as such, it requires a purification step prior to analysis. The extraction method has been optimized by comparing three different commercially available SPE cartridges (SupelTM Select HLB, Phenomenex Strata C18-E, and Agilent ABS Elut-NEXUS), and a liquid/liquid extraction with acetonitrile. A reverse-phase HPLC with a C18 column and gradient elution program was used. MS detection was carried out in MRM mode. Quantitation was performed using the internal standard method. Validation parameters were very satisfactory. The high selectivity and sensitivity of the method (LOQ < 9.5 ng/ml, and LOD < 3.3 ng/ml) allow to determine target analytes even in small amounts. Precision, matrix effect, and stability were also evaluated. The whole validated method has finally been applied to the analysis of 194 real samples of human amniotic fluid obtained from pregnant women (15-21 weeks of gestation) in order to monitor the effective intake of target analytes: 96% of examined women consumed caffeine during pregnancy while a lower percentage (20%) showed acetaminophen intake. The whole procedure is simple and easy to perform with minimal sample preparation and short analysis time.Analytical methods 11/2014; 7(2). DOI:10.1039/C4AY02577F · 1.94 Impact Factor
Journal of Allergy and Clinical Immunology 12/2014; 135(2). DOI:10.1016/j.jaci.2014.10.030 · 11.25 Impact Factor