Opioid Medicines in Pregnancy and Children's Later Hospital Stays: What Nearly Three Million Korean Children Tell Us

A plain-language guide to Kim and colleagues' nationwide South Korean birth cohort study (PLoS Medicine, 2026), and why its brother-and-sister comparison matters for families

A large study from South Korea followed nearly three million children. Those whose mothers filled two or more opioid pain or cough medicine prescriptions within the same three-month stretch of pregnancy were admitted to hospital somewhat more often, mainly in early childhood and mostly for infections. Comparing brothers and sisters shrank the difference a lot, suggesting family factors explain much of it; the study shows a link, not proof of cause.

Many women need medicine for pain or a stubborn cough at some point in pregnancy. Some of those medicines are opioids, a family of strong pain relievers and cough suppressants that includes codeine, tramadol and morphine. It is natural for parents to wonder whether a medicine taken months before birth could affect a child's health as they grow, and doctors want honest answers too. A team of Korean researchers led by Kim and colleagues set out to measure one practical part of that question: how often children whose mothers were prescribed opioids in pregnancy later needed a hospital stay [1].

What families and doctors knew before this study

Opioids have been at the centre of a worldwide public health crisis: in 2017 an estimated 40.5 million people around the world were dependent on them [2]. In South Korea, the number of opioid prescriptions per 1,000 people rose from about 348 in 2009 to about 531 in 2019, mostly for milder opioids [3]. Pregnancy is no exception: in a 2019 survey across 34 areas of the United States, about 7 in every 100 women (6.6%) said they had used prescription opioid pain relievers while pregnant [4]. In Korea, Kim and colleagues cite an estimate from their earlier research that about 7 in every 100 babies (6.9%) were exposed through a mother's prescription [1][5].

For a long time, the main worries were birth defects and withdrawal. A careful review by the US Centers for Disease Control and Prevention found mixed results on birth defects and concluded that uncertainty remained [6]. A later study of very large American insurance records found no large increase in most types of birth defect after opioids in early pregnancy, though a small rise in cleft lip or palate could not be ruled out [7]. Withdrawal, a condition in which a newborn becomes unsettled and unwell after opioid exposure before birth comes to an end, turned out to be uncommon after prescribed pain relievers: about 6 in every 1,000 births to mothers who filled opioid prescriptions in one large American study [8]. That picture is quite different from babies whose mothers have opioid addiction, a group that faces other challenges [9].

Researchers then began asking about longer-term health. The same Korean team had found that a small link between opioid prescriptions in pregnancy and later childhood behavioural or mental health conditions disappeared when brothers and sisters were compared with each other [5]. Laboratory studies of newborns' blood suggested that opioid exposure before birth might change parts of the immune system, the body's defence against germs [10], and a study from Western Australia linked opioid exposure in pregnancy to more infections and asthma in childhood, though it included only a small number of exposed babies [11]. A Canadian study had looked at mothers taking opioids after birth and found no rise in babies returning to hospital within a month [12], but very few studies had looked at hospital stays across childhood after opioid prescriptions during pregnancy, and almost none had compared brothers and sisters.

How the Korean study worked

South Korea's national health insurance covers about 98 out of every 100 people, so its records allowed the researchers to link mothers with their children across the entire country [1]. They studied 2,928,186 children born between 2010 and 2017 and followed their hospital stays until the end of 2023, for up to 14 years. No one was given a medicine as part of the study; the researchers looked back at prescriptions doctors had already written.

A child counted as "exposed" if the mother filled at least two prescriptions for any of six opioids (codeine, dihydrocodeine, fentanyl, morphine, oxycodone or tramadol) within the same three-month stretch of pregnancy, called a trimester. That applied to 118,671 children, about 4 in every 100. Babies who needed a hospital stay in their first month, and children with certain serious long-term illnesses, were left out, so the study looks at hospital stays from one month of age onward.

Because mothers who need opioids may differ in many ways from those who do not, the researchers used two strategies to make fair comparisons. First, they matched each exposed child with up to five unexposed children who were similar in things like the mother's age, income, earlier health and the baby's birth details. Second, and most importantly, they compared brothers and sisters: 122,948 children from 57,509 families in which one child had been exposed and another had not. Siblings share parents, a home, and often the same germs and the same habits around seeking care, so this comparison strips away many family influences that ordinary matching cannot reach.

What the researchers found, in everyday numbers

In the matched comparison, for every 1,000 exposed children followed for a year, there were about 242 hospital stays, compared with about 183 among similar unexposed children [1]. After the researchers allowed for the remaining differences between the two groups, that worked out to about 28% more. Some children had more than one stay, so these are counts of stays rather than of children.

The brother-and-sister comparison told a gentler story. There, the figures were about 234 versus 217 stays per 1,000 children per year, a difference of about 8%. Put simply, the gap shrank from about 59 extra stays to about 17 extra stays per 1,000 children each year once family was taken into account.

Two other patterns stood out. The link was strongest in the youngest age group the researchers looked at (0 to 1 years), smaller at ages two to five, and no longer clear from about age six onward. And within families, the difference showed up mainly with heavier use: higher total doses, prescriptions lasting 12 days or more, three or more prescriptions, or use across more than one trimester. When mothers had a lower total dose or just two prescriptions, brothers and sisters had essentially the same number of hospital stays. Infections were the most common reason children were admitted, and they accounted for much of the difference.

Why the brother-and-sister comparison matters so much

Imagine two families. In one, the mother has a long-standing back problem and a busy household where colds pass from child to child. In the other, there are fewer such pressures. Children in the first family might be admitted more often for many reasons that have nothing to do with a medicine. Comparing siblings within one family holds many of those shared circumstances steady. Because the difference fell from 28% to 8% when siblings were compared, it seems that a large part of the original difference came from family circumstances rather than the medicine itself [1]. Experts who study this kind of design also point out that it has its own blind spots, so even the smaller figure is not proof that the medicine caused the extra stays [13].

What this means for your family

If you were prescribed an opioid during pregnancy, this study is not a reason for alarm. The difference it found was moderate against similar children from other families and small between brothers and sisters, and for lower-dose courses or just two prescriptions there was essentially no difference between brothers and sisters. Please do not stop or change any prescribed medicine on your own; talk with your doctor or midwife, because treating real pain or illness also matters for you and your baby, as the study's authors note [1].

It does help to tell your baby's doctors which medicines you took during pregnancy, for how long and roughly when. The researchers suggest that children whose mothers received opioid prescriptions should have regular child health check-ups, especially in the first year. In everyday terms that means keeping up with routine baby visits and seeking care when your child seems unwell, as any parent would. For the prescribing side, the authors point to a US guideline on long-term pain treatment in adults, which encourages doctors to consider non-opioid options first, agree clear goals before starting and review treatment regularly [14].

What the study cannot tell us

This was an observational study, meaning it looked for patterns in records rather than testing a medicine in a trial. A prescription does not prove the medicine was taken. Visits to a family doctor or emergency department were not counted, only hospital stays. Korea has very little illegal opioid use, so the results may not apply everywhere. And no baby in the study was identified as having opioid withdrawal, so it tells us nothing about that condition [1].

What researchers are working on next

Scientists would like to compare mothers treated with opioids against mothers with the same condition treated in other ways, to separate the effect of the medicine from the illness itself. They also want to follow babies' immune systems over time [10] and repeat this kind of study in other countries.

The bottom line

In this nationwide study, children whose mothers were prescribed opioids in pregnancy had somewhat more hospital stays, mostly for infections and mostly when they were very young [1]. Within families the difference was small and appeared mainly with heavier or longer use. For most families, the sensible response is simple: share your medication history with your baby's doctors and keep up with routine care.

References

  1. Kim HJ, Yim Y, Nehs CJ, et al. Maternal opioid prescriptions and subsequent risk of hospital admission in offspring in South Korea: A nationwide birth cohort study. PLoS Med. 2026;23(10):e1004829. doi:10.1371/journal.pmed.1004829 ↩
  2. Degenhardt L, Grebely J, Stone J, et al. Global patterns of opioid use and dependence: harms to populations, interventions, and future action. Lancet. 2019;394(10208):1560-1579. doi:10.1016/S0140-6736(19)32229-932229-9) ↩
  3. Cho NR, Chang YJ, Lee D, Kim JR, Ko DS, Choi JJ. Trends in opioid prescribing practices in South Korea, 2009-2019: Are we safe from an opioid epidemic? PLoS One. 2021;16(5):e0250972. doi:10.1371/journal.pone.0250972 ↩
  4. Ko JY, D'Angelo DV, Haight SC, et al. Vital Signs: Prescription Opioid Pain Reliever Use During Pregnancy - 34 U.S. Jurisdictions, 2019. MMWR Morb Mortal Wkly Rep. 2020;69(28):897-903. doi:10.15585/mmwr.mm6928a1 ↩
  5. Kang J, Kim HJ, Kim T, et al. Prenatal opioid exposure and subsequent risk of neuropsychiatric disorders in children: nationwide birth cohort study in South Korea. BMJ. 2024;385:e077664. doi:10.1136/bmj-2023-077664 ↩
  6. Lind JN, Interrante JD, Ailes EC, et al. Maternal Use of Opioids During Pregnancy and Congenital Malformations: A Systematic Review. Pediatrics. 2017;139(6):e20164131. doi:10.1542/peds.2016-4131 ↩
  7. Bateman BT, Hernandez-Diaz S, Straub L, et al. Association of first trimester prescription opioid use with congenital malformations in the offspring: population based cohort study. BMJ. 2021;372:n102. doi:10.1136/bmj.n102 ↩
  8. Desai RJ, Huybrechts KF, Hernandez-Diaz S, et al. Exposure to prescription opioid analgesics in utero and risk of neonatal abstinence syndrome: population based cohort study. BMJ. 2015;350:h2102. doi:10.1136/bmj.h2102 ↩
  9. Grossarth S, Osmundson SS, Wiese AD, et al. Maternal Opioid Use Disorder and the Risk of Postneonatal Infant Mortality. JAMA Pediatr. 2023;177(7):675-683. doi:10.1001/jamapediatrics.2023.1047 ↩
  10. Miller NW, Seman BG, Akers SM, et al. The impact of opioid exposure during pregnancy on the human neonatal immune profile. Pediatr Res. 2022;92(6):1566-1574. doi:10.1038/s41390-022-02014-x ↩
  11. Kelty E, Rae K, Jantzie LL, Wyrwoll CS, Preen DB. Prenatal Opioid Exposure and Immune-Related Conditions in Children. JAMA Netw Open. 2024;7(1):e2351933. doi:10.1001/jamanetworkopen.2023.51933 ↩
  12. Zipursky JS, Gomes T, Everett K, et al. Maternal opioid treatment after delivery and risk of adverse infant outcomes: population based cohort study. BMJ. 2023;380:e074005. doi:10.1136/bmj-2022-074005 ↩
  13. Frisell T, Öberg S, Kuja-Halkola R, Sjölander A. Sibling comparison designs: bias from non-shared confounders and measurement error. Epidemiology. 2012;23(5):713-720. doi:10.1097/EDE.0b013e31825fa230 ↩
  14. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain--United States, 2016. JAMA. 2016;315(15):1624-1645. doi:10.1001/jama.2016.1464 ↩