OTC painkiller use during pregnancy tied to adverse infant outcomes

Use of over-the-counter (OTC) painkillers during pregnancy is associated with an increased risk of adverse neonatal outcomes, suggests a large retrospective study presented at ESHRE 2021.

“[Our findings] indicate that healthcare guidance for pregnant women [regarding the use of common painkillers] should be reassessed,” said lead author Dr Aikaterini Zafeiri from the University of Aberdeen in Aberdeen, UK.

In the retrospective cohort study, data from 151,141 singleton pregnancies in the Aberdeen Maternity and Neonatal Databank were analysed. Exposure to five common painkillers, including aspirin, paracetamol, and non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac, ibuprofen, and naproxen, either alone or in combination during pregnancy was extracted from medical records. [ESHRE 2021, abstract P-732]

Overall, the researchers found that almost one out of three women (29 percent) in the cohort had used OTC analgesics during pregnancy. Moreover, there is a trend towards increasing use over the 30 years of study period, with the prevalence of analgesic use doubled to 60 percent in the last 7 years of study period.

In addition, a large proportion of the women who reported using analgesics during pregnancy had done so during the first 12 weeks after conception (84 percent), rather than using analgesics in late pregnancy or after labour.  

“A high percentage of pregnant women use OTC analgesics during pregnancy globally,” noted Zafeiri. “Some of these compounds such as paracetamol are considered safe to use, while contraindications exist for others, such as NSAIDs use beyond gestational week 30.”

“[However,] current evidence regarding the safety of use during pregnancy in humans has been largely conflicting,” noted the researchers, who pointed out that many of the studies were limited by small cohorts, short duration of study, or residual cofounding bias.

In the retrospective cohort, exposure to any of the five analgesics, either as a single agent or in combination, was associated with increased risk of adverse neonatal outcomes. These included neural tube defects (adjusted odds ratio [OR], 1.64), admission to a neonatal unit (aOR, 1.57), neonatal death (aOR, 1.56), premature delivery (aOR, 1.50), and APGAR score of <7 at 5 minutes (aOR, 1.48).

Other outcomes that were adversely affected included stillbirth (aOR, 1.33), infant birthweight <2.5kg (aOR, 1.28), hypospadias (aOR, 1.27), APGAR score of <7 at 1 minute (aOR, 1.18), and birth weight of >4kg (aOR, 1.09).

When the analgesic was analysed individually as a class, the associations between paracetamol use alone during pregnancy with neural tube defects, high birth weight, and hypospadias were not significant.

By contrast, exposure to diclofenac during pregnancy was, instead, associated with significantly reduced risk of stillbirth (aOR, 0.59, 95 percent confidence interval [CI], 0.41–0.87). The protective effect, according to the researchers, may be due to the stronger anti-inflammatory properties of diclofenac than the other NSAIDs.

Given the rampant availability of information on these drugs through the internet — which may be inaccurate, the ease of access to these common painkillers raises safety concerns, said Zafeiri. “This is especially when misinformed or partially-informed self-medication decisions are taken during pregnancy.”