Opioids in Pregnancy and the Folds of a Newborn's Brain: What a Large Brain-Scan Study Found

A plain-language guide to the 2026 OBOE study by Wu and colleagues, which scanned 259 full-term babies in the United States, and what its results do and do not mean for families

A large US study scanned the brains of 259 full-term newborns and found that babies exposed to opioids before birth had, on average, slightly shallower brain folds and a slightly smaller brain surface than babies who were not exposed. The differences were small, the study cannot show that opioids caused them, and it did not look at how the children learn or behave. Researchers are following the same children as they grow.

Why researchers wanted to look at babies' brains

Many families today have a baby who was exposed to opioids during pregnancy. Opioids are a group of medicines and drugs that include prescription pain relievers, heroin and fentanyl, as well as methadone and buprenorphine, two medicines used to treat opioid addiction (also called opioid use disorder) during pregnancy. Parents in this situation often worry most about one question: has this affected my baby's brain? This article explains what a careful new study can, and cannot, tell them.

How families and doctors have faced this question until now

The number of affected families has grown quickly. The research team behind the new study, drawing on national hospital records, describe a 131% increase in pregnant women with opioid use disorder in the United States between 2010 and 2017 [1][2]. Over the same years, the number of babies diagnosed with withdrawal after birth rose from about 4 to about 7 in every 1,000 births in hospital [2]. Opioid use in pregnancy is not limited to addiction: in a 2019 survey covering 34 areas of the United States, about 7 in every 100 women who answered (6.6%) said they had used a prescription opioid pain reliever while pregnant [3].

For a long time, the main concern doctors and nurses focused on was withdrawal. A baby who has been exposed to opioids in the womb can become unsettled after birth when the supply suddenly stops, with symptoms such as crying, poor sleep and feeding problems. This is called neonatal abstinence syndrome, and teams have long used scoring charts and, when needed, medicine such as morphine to treat it [4]. Withdrawal passes, but families and researchers wanted to know about the longer term. Studies following children found some differences in development. In New Zealand, 100 children exposed to methadone scored lower on average in movement, thinking and language at age 2 than 110 other children, but much of the gap was linked to the child's home and family circumstances after birth rather than to the medicine alone [5]. A review combining 7 studies also found more attention and hyperactivity symptoms in exposed children [6].

Brain scans added another piece. Small studies in Norway scanned older children and teenagers who had been exposed before birth and found that, on average, some parts of their brains were smaller [7][8][9]. But because these children were scanned many years after birth, nobody could tell whether the differences came from the exposure before birth or from everything that happened afterwards. Studies in newborns were very small, with as few as 16 babies [10]. In 2025 the same research team reported that, among 173 exposed newborns and 96 unexposed newborns, the exposed babies had slightly smaller brain volumes on average [11]. What nobody had measured after birth in opioid-exposed babies was the brain's folding.

Why the folds of the brain matter

The outer layer of the brain, called the cortex, is the part we use for thinking, moving, feeling and sensing. To fit a large cortex inside the skull, it folds into ridges and grooves, a little like crumpling a sheet of paper to fit it into a small box. This folding happens very fast in the last three months of pregnancy [12], and a large study of scans around the time of birth found an extra burst of folding just after birth [13]. Scanning babies in their first weeks of life therefore captures a busy period of development, before months of life outside the womb have had their effect. Before this study, only one very small study had looked at folding, using scans of 29 unborn babies, and it found less folding in the opioid-exposed group [14].

How the new study was done

The new study comes from the Outcomes of Babies With Opioid Exposure (OBOE) study, part of a US research programme called Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) [1][15]. It took place at four sites in the United States; the authors thank hospital teams at Case Western Reserve University in Cleveland, Cincinnati Children's Hospital Medical Center, the University of Alabama at Birmingham and Children's Hospital of Philadelphia, and the brain scans were analysed at Children's National Hospital in Washington, DC. Families joined between August 2020 and December 2023 [1].

This was an observational study, which means the researchers did not give anyone any medicine. They simply compared two groups: 164 babies whose mothers had used opioids in the middle or later months of pregnancy, and 95 babies with no known opioid exposure, born at the same hospitals. All 259 babies were born at full term (37 weeks of pregnancy or later) and did not need a breathing machine or pressure support in intensive care. Most exposed mothers were taking buprenorphine (about 68 in every 100) or methadone (about 26 in every 100), and many had also used other substances, such as nicotine or cannabis [1].

Each baby had an MRI scan, a type of scan that uses magnets and radio waves instead of X-rays, during natural sleep and without any sedating medicine, a few weeks after birth. Computer software then measured three things in each of the brain's four main regions: how deep the grooves were (called sulcal depth), how much surface the cortex covered (surface area), and how folded it was overall (the gyrification index). The researchers adjusted for differences between the groups, such as the baby's age at the scan, sex and birth weight, and the mother's age, smoking and education [1].

What the researchers found

On average, the exposed babies had slightly shallower grooves in the front and upper-middle parts of the brain and a slightly smaller cortical surface in all four regions. Groove depth differed by about one or two tenths of a millimetre, less than the thickness of a fingernail. For the whole brain, the surface area of the exposed babies was about 2,185 square millimetres smaller, on a total of about 28,500 square millimetres in the unexposed babies, a little under 8% (our own rough calculation). How folded the brain was overall (the gyrification index) did not differ between the two groups [1]. In other words, the amount of folding looked similar, but the surface was, on average, a little smaller.

The researchers also looked at smaller groups. Compared with unexposed babies, the 37 babies exposed to methadone showed somewhat larger differences than the 108 babies exposed to buprenorphine, and babies exposed to opioids plus other substances showed differences in more brain regions than babies exposed to opioids alone. However, when the methadone and buprenorphine groups were compared directly with each other, there was no statistically clear difference, and the same was true for opioids alone versus opioids plus other substances [1]. These patterns are interesting ideas to test, not proof that one medicine is worse than the other.

What this means for your family

If your baby was exposed to opioids before birth, these results describe averages across a large group. They cannot predict how any individual child will develop, and the study did not measure learning, behaviour or development at all. These differences were found with special research software that compares groups, not by a doctor looking at a single scan, and the study does not suggest that exposed babies need a scan.

Please do not stop or change a prescribed medicine such as methadone or buprenorphine because of this study. Treatment decisions in pregnancy should always be made with your care team. Earlier research found that babies whose mothers took buprenorphine needed less withdrawal medicine and shorter hospital stays than babies whose mothers took methadone, in a carefully controlled study at eight sites in several countries [16], and a very large US study of health records found that they were less likely to develop withdrawal (52 in every 100 babies compared with 69 in every 100) [17]. The right choice depends on each woman's situation and is a decision for her and her care team.

There is also real reason for hope. The New Zealand study found that a large share of later differences was linked to a child's home and family life [5], which is something families and support services can influence. Stress during pregnancy has itself been linked to differences in how a baby's brain folds [18], so support for parents' wellbeing matters too. Regular check-ups of your child's development, help to stop smoking, and early support if any concerns arise are practical steps that make a difference.

What the study cannot tell us

Because this was an observational study, it cannot prove that opioids caused the differences. Families in the two groups differed in other ways: for example, 77 in every 100 exposed mothers smoked, compared with 23 in every 100 mothers in the other group [1]. Even with careful adjustments, other factors such as stress, money worries or access to care may play a part. Some mothers in the comparison group also took other medicines, such as antidepressants, which may have their own small links with brain shape [19]. The study did not know how much medicine was taken or for how long, and it included only healthy babies born at full term.

What researchers are working on next

The OBOE team is following the same children with more brain scans and developmental check-ups until they are 2 years old [15]. A related study from the same group has also looked at other brain areas linked to emotion and memory [20]. The key question is whether these early differences have any effect on how children grow, learn and behave, and what kinds of support help most. Families interested in related topics can read In[Neo]Sight's articles on Eat, Sleep, Console care for opioid withdrawal and on cannabis exposure in pregnancy.

The bottom line

In this large study, babies exposed to opioids before birth had, on average, slightly shallower brain grooves and a slightly smaller brain surface, while the overall amount of folding did not differ [1]. The study does not show cause, does not predict any single child's future, and is not a reason to change prescribed treatment. Follow-up of these children will tell us much more.

References

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