Pre-pregnancy acetaminophen use tied to increased adverse birth outcomes risk

The use of acetaminophen 3 months prior to pregnancy was associated with an increased risk of adverse birth outcomes, such as low birth weight (LBW), preterm birth (PTB), and small-for-gestational-age (SGA), according to a recent study.

Using data from the Ontario Birth Study (OBS), the researchers conducted a prospective study involving 1,200 women (mean age 33.8 years, mean BMI 23.2 kg/m²) who gave birth between January 2013 and June 2017 at Mount Sinai Hospital in Ontario, Canada. Information on acetaminophen use and other lifestyle factors across the three periods of pregnancy were documented in a questionnaire, and was categorized into pre-pregnancy (3 months before pregnancy), early pregnancy (first 12–16 weeks), and mid-to-late pregnancy (completion of the first questionnaire and 28–32 weeks of gestation). [Pediatric Research 2019;doi:10.1038/s41390-019-0726-8]

After adjusting for potential confounders, children born to mothers who were exposed to acetaminophen for ≥1/week pre-pregnancy were at an increased risk of being LBW (<2,500 g; adjusted risk ratio [adjRR], 2.16, 95 percent confidence interval [CI], 1.02–4.54), SGA* (adjRR, 1.84, 95 percent CI, 1.14–2.98), or PTB** (adjRR, 1.86, 95 percent CI, 0.96–3.63), which was not statistically significant.

An increased risk of SGA was also observed among children of mothers who consumed acetaminophen <1/week pre-pregnancy (RR, 1.46, 95 percent CI, 1.02–2.11).

However, the researchers found no associations between acetaminophen intake during early or mid-to-late pregnancy and risk of adverse birth outcomes.

With regard to the frequency of acetaminophen use, women who were only exposed to acetaminophen during pre-pregnancy or early pregnancy demonstrated an increased risk of their infants being born SGA (RR, 1.54, 95 percent CI, 1.02–2.34).

“[Of note,] we were … able to incorporate information on frequency of acetaminophen use, to detect a dose response relationship between maternal acetaminophen use during the pre-pregnancy period and the offspring being born SGA. In addition, we limited the possibility of confounding by other pain medications by adjusting for the use of other commonly used pain medications including NSAIDs,” noted the researchers.

On the other hand, those who used acetaminophen across the three pregnancy periods showed no increased risk of PTB (RR, 1.29, 95 percent CI, 0.58–2.88), LBW (RR, 1.18, 95 percent CI, 0.47–2.95), or SGA (RR, 0.80, 95 percent CI, 0.41–1.53).

“[W]e found that maternal acetaminophen use in the 3 months prior to pregnancy is associated with an increased risk of adverse birth outcomes,” the researchers highlighted. “As data on longer-term outcomes in the OBS cohort are not yet available, PTB, LBW, and SGA serve as intermediary outcomes that have been implicated in later negative developmental outcomes. Follow-up of offspring in the OBS cohort is ongoing and future studies to investigate child developmental outcomes are planned.”

“To our knowledge, acetaminophen remains the safest analgesic for use during pregnancy as per the current literature. However, further research is warranted to evaluate and validate our results, and to investigate the effects of pre-conception acetaminophen use,” said the researchers, noting that “the results … should not be overstated so as to not unnecessarily burden pregnant women and those planning for pregnancy.”

*SGA: Defined as a birthweight of <10^th centile for gestational age, relative to a Canadian reference population