Maternal opioid use in pregnancy linked to childhood hospitalizations

Children whose mothers received opioid prescriptions during pregnancy have a higher rate of hospital admission in childhood than unexposed children, including unexposed siblings, according to a new study published October 13^th in the open access journal PLOS Medicine by Dong Keon Yon of Kyung Hee University College of Medicine, South Korea, and colleagues.

Over recent decades, opioid prescriptions and doses have risen in clinical practice, and a considerable proportion of pregnant women are exposed to these drugs. In the U.S., for example, data has shown that 14-22% of women filled a prescription for opioids during pregnancy. Prenatal opioid exposure may disrupt infant development and immune system function, but prior studies have had limitations such as confounding factors, limited sample sizes, or restricted follow-up durations.

In the new study, researchers used nationwide health insurance data on mothers and children in South Korea, following a cohort of 2,928,186 children born between 2010 and 2017 for up to 14 years. Children were classified as prenatally exposed to opioids if their mothers received two or more opioid prescriptions during pregnancy, and were compared both with unexposed children and with their own siblings.

Children with prenatal opioid exposure had a 28% higher rate of hospital admission than unexposed children (adjusted incidence rate ratio 1.28, 95% CI 1.28-1.29). The association was smaller but still significant when comparing siblings (aIRR 1.08, 95% CI 1.07-1.10). The effect was also dose-dependent, with higher maternal opioid doses associated with higher admission rates (aIRR 1.19 for low-dose exposure versus 1.40 for high-dose exposure). The elevated admission rates spanned several causes, including infections and respiratory, gastrointestinal and genitourinary conditions, with the association strongest up to five years of age.

"These findings suggest the need for additional postnatal health checks for those born to mothers with opioid prescriptions during pregnancy," the authors write. "However, these findings should be interpreted with caution, as the study relied on electronic health records, which may not reflect actual use of medication, and unmeasured factors shared within families may still partly explain the observed associations."

Dong Keon Yon, MD, PhD (co-corresponding author) states, "In a nationwide cohort of nearly three million Korean children, those whose mothers received two or more opioid prescriptions during pregnancy had about a 28% higher rate of hospital admission, most notably for infections and respiratory illness in the first years of life. The risk rose with higher opioid doses and longer prescriptions, which points to a possible biological effect-but when we compared siblings within the same family, the association shrank considerably, so shared family factors clearly explain part of what we see."

Because opioids in South Korea are obtained almost entirely by prescription, our data let us examine prescribed opioid exposure in pregnancy unusually cleanly, and following nearly three million children for up to 14 years gave us the statistical power to look at dose, timing, and specific causes of admission separately. The consistency of the pattern across all of these analyses is what makes the finding hard to dismiss." 

Jiseung Kang, PhD, co-corresponding author

Hyeon Jin Kim, MS (joint first author) states, "Our message is not that pregnant women should never receive opioids-for some, pain relief is essential. It is that opioids in pregnancy should be prescribed at the lowest effective dose for the shortest time, and that children born after such exposure may benefit from closer routine health checks, particularly in infancy when the risk was highest."

Yesol Yim (joint first author) notes, "What surprised us most was how quickly the association faded as children grew older. The excess risk was clearest in the first year of life and had largely disappeared after age five. That pattern suggests a window of vulnerability in early infancy rather than a lifelong effect-and it is a window in which pediatric follow-up can make a real difference."