Maternal Acetaminophen Use Research Articles

Association Between Prenatal Acetaminophen Exposure and Future Risk of Attention Deficit/Hyperactivity Disorder in Children.

To evaluate the effect of prenatal acetaminophen exposure on the future development of attention deficit/hyperactivity disorder (ADHD) in children. Literature searches of MEDLINE (1975 to June 2015), International Pharmaceutical Abstracts (1975 to June 2015), and Cochrane Database (publications through June 2015) for prospective clinical trials assessing the relationship of prenatal acetaminophen exposure and the development of attention deficit disorders or hyperactivity. Studies comparing self-reported maternal acetaminophen use during pregnancy to development of ADHD or ADHD-like behaviors in offspring between the ages of 3 and 12 years. Four studies examining the effects of prenatal acetaminophen exposure on subsequent ADHD behaviors were identified. Of these, one early study found no link to ADHD behaviors while the other studies found statistically significant correlations with the most prominent being a study finding a higher risk for using ADHD medications (hazard ratio = 1.29; 95% CI, 1.15-1.44) or having ADHD-like behaviors at age 7 years as determined by the Strengths and Difficulties Questionnaire (risk ratio = 1.13; 95% CI, 1.01-1.27) in children whose mothers used acetaminophen during pregnancy. While there does appear to be a mild correlation between prenatal acetaminophen use and the development of ADHD symptoms in children, current data do not provide sufficient evidence that prenatal acetaminophen exposure leads to development of ADHD symptoms late in life. Acetaminophen is a preferred option for pain management during pregnancy when compared with other medications such as nonsteroidal anti-inflammatory drugs or opioids for pyretic or pain relief.

Case-control analysis of maternal prenatal analgesic use and cardiovascular malformations: Baltimore–Washington Infant Study

We sought to assess maternal prenatal use of analgesics and risk of cardiovascular malformations (CVM) in the offspring. Data from the Baltimore-Washington Infant Study, a population-based case-control investigation of CVM, were used to examine selected isolated CVM diagnoses and maternal analgesic use during the periconceptional period (3 months before and after conception). We compared case and control infants on frequency of maternal use of analgesics and estimated adjusted odds ratios (adjORs) and 95% confidence intervals (CI) with logistic regression models for specific CVM phenotypes. Frequency of periconceptional use of any analgesic was 52% among control mothers and 53% among case mothers. Analyses by CVM diagnoses identified an association of tetralogy of Fallot with maternal acetaminophen use (adjOR, 1.6; 95% CI, 1.1-2.3) and dextrotransposition of the great arteries with intact ventricular septum with maternal nonsteroidal antiinflammatory drug use (adjOR, 3.2; 95% CI, 1.2-8.7). Analgesic use during the periconceptional period was not associated with CVM in the aggregate or with most phenotypes of CVM examined. Associations with 2 phenotypes of CVM may have occurred by chance. These findings warrant corroboration and further study, including further evaluation of the observed associations, the dose of analgesic taken, more specific timing of analgesic use, and indications for use.

Infant acetaminophen use associates with early asthmatic symptoms independently of respiratory tract infections: The Copenhagen Prospective Study on Asthma in Childhood 2000 (COPSAC2000) cohort

Infant acetaminophen use associates with early asthmatic symptoms independently of respiratory tract infections: The Copenhagen Prospective Study on Asthma in Childhood 2000 (COPSAC2000) cohort

Accuracy of Cryptorchidism Diagnoses and Corrective Surgical Treatment Registration in the Danish National Patient Registry

In recent years several Danish studies of the etiology, time trends and long-term health consequences of cryptorchidism have relied on diagnoses and surgical treatments registered in the National Patient Registry. We evaluated the diagnostic accuracy of these registry data. According to the Danish National Patient Registry, 16,168 males were diagnosed with cryptorchidism and 9,244 surgical treatments for cryptorchidism were performed between January 1, 1995 and October 10, 2009. We randomly selected 500 diagnosed cases, of which 284 had been managed surgically. We requested the medical records from the departments making the diagnoses and performing the surgery. We successfully retrieved medical records for 452 diagnosed cases (90%) and 249 operations (88%). Overall positive predictive value of a registry diagnosis of cryptorchidism was 80% (95% CI 77-84) using the testicular position described by the physician performing the clinical examination as the gold standard. Similarly the positive predictive value of the surgical treatment registration was 99% (95% CI 98-100) using the type of procedure performed. The data on cryptorchidism in the Danish National Patient Registry are quite accurate. In etiological research the limited misclassification will in most cases only slightly attenuate estimates of the true relative association. Thus, the registry has the potential to serve as a valuable research tool, although caution should be exercised when studying time trends or geographical differences.

770: Toll-like receptor gene family expression on maternal neutrophils is down-regulated in normal and preeclamptic pregnancies

are provided in table. There was no significant effect of acetaminophen on either fetal breathing or body movements when the data was expressed as number of activity episodes, total activity time, percent of activity time, or activity rate. In addition, there was no effect of acetaminophen when fetal breathing and body movements were combined into a single composite activity score. There were no differences in the proportion of fetuses demonstrating breathing or movement sufficient to achieve a normal biophysical profile score for that parameter, nor was their a difference in time required to achieve a normal score. CONCLUSION: Acetaminophen does not impact fetal breathing or body movements in humans when given at normally prescribed doses. Thus, assessment of fetal well-being using biophysical parameters should not be effected by maternal acetaminophen use.

Maternal Use of Acetaminophen, Ibuprofen, and Acetylsalicylic Acid During Pregnancy and Risk of Cryptorchidism

Cyclooxygenase (COX) inhibitors-acetaminophen, ibuprofen and acetylsalicylic acid-have endocrine-disruptive properties in the rainbow trout. In humans, aspirin blocks the androgen response to human chorionic gonadotropin (hCG), and, because hCG-stimulated androgen production in utero is crucial for normal testicular descent, exposure to COX inhibitors at vulnerable times during gestation may impair testicular descent. We examined whether prenatal exposure to acetaminophen, ibuprofen, and acetylsalicylic acid was associated with increased occurrence of cryptorchidism. Our study used data on 47,400 live-born singleton sons of mothers enrolled in the Danish National Birth Cohort during 1996-2002. Cryptorchidism was identified in 980 boys during childhood, of whom 565 underwent orchiopexy. The use of acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy was assessed in 3 computer-assisted telephone interviews and 1 self-administered questionnaire. We estimated adjusted hazard ratios (HRs) of cryptorchidism by Cox regression analysis. Exposure to acetaminophen during both the first and second trimesters was associated with increased occurrence of cryptorchidism (HR = 1.33 [95% confidence interval = 1.00-1.77]). Exposure for more than 4 weeks within the postulated time-window of programming testicular descent (gestational weeks 8-14) was associated with a HR of 1.38 (1.05-1.83) for cryptorchidism. Exposure to ibuprofen and acetylsalicylic acid was not associated with cryptorchidism. Maternal intake of acetaminophen for more than 4 weeks during pregnancy, especially during the first and second trimesters, may moderately increase the occurrence of cryptorchidism.

Prenatal exposure to acetaminophen and respiratory symptoms in the first year of life

Prevalence of asthma in developed countries increased between the 1970s and the 1990s. One factor that might contribute to the trends in asthma is the increased use of acetaminophen vs aspirin in children and pregnant women. To examine relationships between in utero exposure to acetaminophen and incidence of respiratory symptoms in the first year of life. A total of 345 women were recruited in the first trimester of pregnancy and followed up with their children through the first year of life. Use of acetaminophen in pregnancy was determined by questionnaire and related to incidence of respiratory symptoms. Use of acetaminophen in middle to late but not early pregnancy was significantly related to wheezing (odd ratio, 1.8; 95% confidence interval, 1.1-3.0) and to wheezing that disturbed sleep (odds ratio, 2.1; 95% confidence interval, 1.1-3.8) in the first year of life after control for potential confounders. This study suggests that use of acetaminophen in middle to late but not early pregnancy may be related to respiratory symptoms in the first year of life. Additional follow-up will examine relationships of maternal and early childhood use of acetaminophen with incidence of asthma at ages 3 to 5 years, when asthma diagnosis is more firmly established.

P05.19: Constriction and complete occlusion of the ductus arteriosus associated with maternal use of acetaminophen

Objectives: 1) To establish normograms (using predicted interval formulas) of fetal pulmonary artery diameters and ratios as a function of fetal biometric parameters (FBP). Study design: Cross sectional study: Fetuses with the following criteria following fetal echocardiography were recruited for this study: 1) known gestational age based on LMP or early ultrasound, 2) unremarkable fetal echocardiogram study, 3) full fetal biometry, 4) singleton gestation, and 5) no major anomalies. Data of the following pulmonary artery (PA) parameters were taken if measured in each fetus at least three times: 1) Main PA (MPA) diameter, 2) Right branch PA diameter, 3) Left branch PA diameter and 4) Ascending Aorta. The following ratios were calculated: MPA/RPA, RPA/LPA, MPA/LPA and MPA/AO. Pearson coefficients (P) were calculated for each parameter versus the following FBP: 1) Biparietal diameter, 2) Head circumference, 3) Abdominal circumference (AC), 4) Femur length (FL), 5) Estimated fetal weight and 6) Calculated fetal gestational age (CFGA) based on biparietal diameter and femur length. Predicted interval normograms (95%tile confidence intervals) were developed using SPSS for fetal pulmonary artery diameters and ratios. Results: One hundred and fifty-five fetuses have been enrolled in this study. Gestational age range was 124–272 days. PA diameters were well correlated to all the FPB (all P > 0.85), suggesting a stable linear relationship. Arterial diameter ratios were stable across the gestational age range studied and appeared independent of FPB. Conclusions: Normograms (based on Predicted Intervals, 95% CI) for fetal PA diameters and ratios are established for a variety of FBP. In the absence of known gestational age, these normograms of fetal pulmonary artery diameters can be used reliably as a basis of comparison.

Maternal use of acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), and muscular ventricular septal defects.

Muscular ventricular septal defects (mVSDs) are the most common congenital heart defects. Previous studies have suggested maternal use of acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs), and/or fever as risk factors. We evaluated the association between mVSDs and maternal use of acetaminophen or NSAIDs adjusting for fever. Infants with nonsyndromic mVSDs (cases) and without birth defects (controls), with gestational age > or =37 weeks and their mothers were enrolled in the National Birth Defects Prevention Study. Two exposure periods were defined: the first trimester of pregnancy, and one month before pregnancy through delivery. Mothers reporting fever or medication use at least once during either period were considered exposed. Adjusted odds ratios and 95% confidence intervals were estimated independently for each exposure period. The analysis included 168 cases and 692 controls. Two case groups were evaluated: all mVSD infants (n = 168) (including those with associated minor cardiac defects or noncardiac defects), and infants with isolated mVSDs (n = 133). Mothers of cases were less likely to be African-American than Caucasian (OR, 0.36; 95% CI, 0.18, 0.73). Approximately equal numbers of case mothers and control mothers (10.4 versus 9.7%, respectively) reported at least one febrile episode during the first trimester. Neither acetaminophen nor NSAID exposure was significantly associated with mVSDs. This was true for both case groups and both exposure periods. Significant associations were not detected between the occurrence of mVSDs and maternal use of NSAIDs or acetaminophen adjusting for maternal fever, nor were they detected between maternal fever and mVSDs.

Aspirin and acetaminophen use by pregnant women and subsequent child IQ and attention decrements.

In a longitudinal prospective study of 1,529 women pregnant in 1974-1975, aspirin and acetaminophen were the two medications most frequently taken during the first half of pregnancy (46 and 41%, respectively). In a selected cohort of 421 offspring of these women, examined at 4 years of age, maternal aspirin use during the first half of pregnancy was significantly related to IQ and attention decrements in the exposed children. Multiple regression analyses were used to statistically adjust for a variety of potentially confounding factors including demographic characteristics, child characteristics, other exposures, and lifestyle/environmental variables. Continuous dose-response and step-function parameterizations of aspirin exposure were both statistically significant and not clearly distinguishable from each other. The estimated aspirin effect is significantly greater for girls than boys. Aspirin effects on offspring function were found in the absence of effects on physical size both at birth and at 4 years. Maternal acetaminophen use was not significantly related to child IQ or attention. As this exploratory research originated from observations of a data set gathered for other purposes, it would be desirable to have these findings replicated in other studies. Further follow-up of the children at a later age is planned.