Pain reliever in pregnancy link to child behavioural problems

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Using the common pain-relieving medication acetaminophen during pregnancy was associated with increased risk for multiple behavioural problems in children, including a 42% higher incidence of hyperactivity, found a University of Bristol study.

Using the common pain-relieving medication acetaminophen during pregnancy was associated with increased risk for multiple behavioural problems in children, according to research.

Acetaminophen is generally considered safe in pregnancy and is used by a many pregnant women for pain and fever.

Dr Evie Stergiakouli, of the University of Bristol, UK, and co-authors analysed data for 7,796 mothers enrolled in the Avon Longitudinal Study of Parents and Children between 1991 and 1992 along with their children and partners. The authors examined associations between behavioural problems in children and their mothers’ prenatal and postnatal acetaminophen use, as well as acetaminophen use by their partners.

Questionnaires assessed acetaminophen use at 18 and 32 weeks during pregnancy and when children were 5 years old. Behavioural problems in children reported by mothers were assessed by questionnaire when children were 7 years old.

At 18 weeks of pregnancy, 4,415 mothers (53%) reported using acetaminophen and 3,381 mothers (42%) reported using acetaminophen at 32 weeks. There were 6,916 mothers (89%) and 3,454 partners (84%) who used acetaminophen post-natally.

The study reports 5% of children had behavioural problems.

Study results suggest prenatal use of acetaminophen by mothers at 18 and 32 weeks of pregnancy was associated with increased risk of conduct problems and hyperactivity symptoms in children, and maternal acetaminophen use at 32 weeks of pregnancy also was associated with higher risk for emotional symptoms and total difficulties in children.

Postnatal maternal acetaminophen use and acetaminophen use by partners were not associated with behavioural problems. Because the associations were not observed in these instances, the authors suggest that this may indicate that behavioural difficulties in children might not be explained by unmeasured behavioural or social factors linked to acetaminophen use.

Study limitations include a lack of information on dosage or duration of acetaminophen use.

“Children exposed to acetaminophen use prenatally are at increased risk of multiple behavioural difficulties. … Our findings suggest that the association between acetaminophen use during pregnancy and offspring behavioural problems in childhood may be due to an intrauterine mechanism. Further studies are required to elucidate mechanisms behind this association as well as to test alternatives to a causal explanation. Given the widespread use of acetaminophen among pregnant women, this can have important implications on public health advice,” the authors write.

But the authors also caution: “However, the risk of not treating fever or pain during pregnancy should be carefully weighed against any potential harm of acetaminophen to the offspring.”

Abstract
Importance: Acetaminophen (paracetamol) is used by a large proportion of pregnant women. Research suggests that acetaminophen use in pregnancy is associated with abnormal fetal neurodevelopment. However, it is possible that this association might be confounded by unmeasured behavioral factors linked to acetaminophen use.
Objective: To examine associations between offspring behavioral problems and (1) maternal prenatal acetaminophen use, (2) maternal postnatal acetaminophen use, and (3) partner’s acetaminophen use.
Design, Setting, and Participants: From February 2015 to March 2016, we collected and analyzed data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective birth cohort. We studied 7796 mothers enrolled in ALSPAC between 1991 and 1992 along with their children and partners.
Exposures: Acetaminophen use was assessed by questionnaire completion at 18 and 32 weeks of pregnancy and when the child was 61 months old.
Main Outcomes and Measures: Maternal reports of behavioral problems using the Strengths and Difficulties Questionnaire (SDQ) when the children were 7 years old. We estimated risk ratios for behavioral problems in children after prenatal, postnatal, and partner’s exposure to acetaminophen and mutually adjusted each association.
Results: Maternal prenatal acetaminophen use at 18 (n = 4415; 53%) and 32 weeks of pregnancy (n = 3381; 42%) was associated with higher odds of having conduct problems (risk ratio [RR], 1.42; 95% CI, 1.25-1.62) and hyperactivity symptoms (RR, 1.31; 95% CI, 1.16-1.49), while maternal acetaminophen use at 32 weeks was also associated with higher odds of having emotional symptoms (RR, 1.29; 95% CI, 1.09-1.53) and total difficulties (RR, 1.46; 95% CI, 1.21-1.77). This was not the case for maternal postnatal (n = 6916; 89%) or partner’s (n = 3454; 84%) acetaminophen use. We found the associations between maternal prenatal acetaminophen use and all the SDQ domains unchanged even after adjusting for maternal postnatal or partner’s acetaminophen use.
Conclusions and Relevance: Children exposed to acetaminophen prenatally are at increased risk of multiple behavioral difficulties, and the associations do not appear to be explained by unmeasured behavioral or social factors linked to acetaminophen use insofar as they are not observed for postnatal or partner’s acetaminophen use. Although these results could have implications for public health advice, further studies are required to replicate the findings and to understand mechanisms.

Authors
Evie Stergiakouli; Anita Thapar; George Davey Smith

JAMA material
JAMA Pediatrics abstract


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