A Mother's Medicine Dose Did Not Predict How Hard Withdrawal Was for Her Baby

Explaining Townsel and colleagues' 2026 study of umbilical cord drug levels in newborns whose mothers were treated with methadone or buprenorphine

Many pregnant women treated with methadone or buprenorphine worry that their dose decides how much withdrawal their newborn will have. A 2026 US study of 94 babies measured the medicine in each baby's umbilical cord and found that neither the mother's dose nor the cord level predicted severe withdrawal. Severe withdrawal was less common after buprenorphine than after methadone.

If you are expecting a baby while being treated for opioid use disorder, or are caring for a newborn after such a pregnancy, you may have asked yourself whether taking less medicine would have made things easier for your baby. It is a natural question, and a loving one. This article explains what one new study found, what it means, and what it cannot yet tell us [1].

Why babies can go through withdrawal after birth

Opioid use disorder is a medical condition in which a person's body and brain have come to depend on opioids, a family of drugs that includes heroin, fentanyl and some prescription painkillers. In pregnancy it is usually treated with a steady, prescribed medicine, most often methadone or buprenorphine. These medicines are often called MOUD, short for medications for opioid use disorder.

Because these medicines reach the baby during pregnancy, many babies are born used to them. After birth that supply stops, and a baby may become irritable and unsettled, have feeding or tummy troubles, and show other signs that the nervous system is out of balance. Doctors call this neonatal opioid withdrawal syndrome, or NOWS [1]. It is uncomfortable and needs careful, standard care, but it is a well-known condition that newborn teams are used to looking after.

How families and doctors have faced this question until now

NOWS became much more common during the 2010s. In the United States, the number of babies diagnosed with withdrawal almost doubled between 2010 and 2017, from about 4 to about 7 in every 1000 births in hospital [2]. Doctors still strongly support MOUD in pregnancy because it protects mothers. A large study of pregnancies in Pennsylvania found that each extra week of treatment was linked to a lower chance of the mother having an overdose and a higher chance of her staying in treatment after the birth, even though the babies were more likely to have withdrawal [3]. The American Academy of Pediatrics, a national organisation of children's doctors, has published guidance on how to assess, treat and support these babies, and has pointed out that their care still varies [4].

Researchers have also compared the two main medicines. In a carefully designed study of 175 pregnant women at eight sites in several countries, in which neither the women nor their doctors knew which medicine each woman was taking, babies born to mothers on buprenorphine needed much less morphine for withdrawal and went home after about 10 days instead of about 17 and a half [5]. A later study of thousands of pregnancies covered by US public health insurance found withdrawal in about 52 of every 100 babies after buprenorphine and about 69 of every 100 after methadone [6]. A review that pooled many studies also found buprenorphine compared well on other measures, such as being born too early and birth weight [7].

The question of dose was less clear. When researchers pooled many studies of methadone, they did not find a clear difference in withdrawal between mothers on higher and lower doses [8]. But a few very small laboratory studies, one of only 19 umbilical cords [9] and another of just five placentas [10], hinted that the amount of medicine reaching the baby might help predict how severe withdrawal would be. Some experts suggested that the amount of exposure before birth was probably the main reason some babies have a harder time than others [11]. Many families were left with the impression that a lower dose meant an easier start for the baby.

What the researchers did

A team led by Dr Courtney Townsel, with colleagues at the University of Maryland, Yale University and Washington University in St Louis, studied mothers and babies from several US hospitals between July 2016 and December 2025 [1]. The paper does not name the hospitals or say how many there were. This was an observational study, which means the researchers watched what happened in normal care rather than assigning mothers to one medicine or the other. It drew on a larger research project set up by the same team to follow pregnancies treated with MOUD [12].

All the mothers had taken methadone or buprenorphine steadily for at least 30 days before giving birth, and all babies were born at 34 weeks of pregnancy or later. Right after each birth, a small piece of the umbilical cord was saved and frozen. A laboratory then measured how much medicine, and how much of the substances the body breaks it down into, was in the cord. The cord was chosen because it holds a record of what reached the baby during roughly the last three months of pregnancy, more steadily than a single blood or urine test.

Each hospital checked babies for withdrawal using its usual method. Some used a scoring system called the Finnegan score, in which staff add up points for a list of withdrawal signs. Others used Eat, Sleep, Console, an approach that asks whether the baby can feed well, sleep and be comforted. The researchers counted withdrawal as "severe" if a baby needed medicine for it, had high Finnegan scores, or could not meet the Eat, Sleep, Console goals.

What they found

The study included 92 pregnancies and 94 babies: 54 babies whose mothers took methadone and 40 whose mothers took buprenorphine [1].

For methadone, the mother's dose and the amount in the cord went closely together: higher doses meant more methadone in the cord. That was not clearly the case for buprenorphine.

The key finding is the next one. Babies with severe withdrawal did not have more medicine in their cords than babies with milder withdrawal, and their mothers were not on higher doses. For buprenorphine, mothers in both groups were on the same typical dose, 16 mg. For methadone, the typical doses were similar too, 127.5 mg for mothers of babies with severe withdrawal and 120 mg for the others, a difference small enough to be due to chance.

The type of medicine did make a difference. Severe withdrawal happened in 30 of the 54 methadone babies, a little over half, and in 11 of the 40 buprenorphine babies, a little over one in four. Fewer buprenorphine babies needed medicine for withdrawal (4 of 40, compared with 18 of 54 after methadone), and the typical hospital stay was 5 days rather than 8.

What this means for families

The most important message is about the mother's dose. The researchers concluded that their results do not support lowering a mother's dose to prevent severe withdrawal in her baby, and that doses should be set to keep the mother well and stable, which lowers her risk of relapse and overdose [1]. A healthy, stable mother is one of the best things a baby can have.

If your baby has withdrawal, it does not mean you took "too much". In this study, how hard withdrawal was for each baby was not explained by the mother's dose or by how much medicine reached the baby. The researchers think other things matter, such as how the placenta handles the medicine, how the baby's own body processes it, and the baby's genes [1][11]. Other medicines taken in pregnancy, such as some medicines for anxiety (benzodiazepines), certain nerve-pain medicines and antidepressants, can also make withdrawal more likely, so it helps to tell the care team about everything you take [13].

The finding that withdrawal was less common after buprenorphine fits earlier research, but it does not mean a mother who is doing well on methadone should switch. The researchers point out that the choice of medicine often reflects how stable a mother is, so the difference may not be caused by the medicine alone. Any change in treatment should be talked through with the mother's own doctors.

How babies are cared for also matters. A large study at 26 US hospitals, the ESC-NOW trial (a test of the Eat, Sleep, Console approach), found that the Eat, Sleep, Console approach helped babies be ready to go home after about 8 days instead of about 15 [14], and a newer study in 23 US hospitals, the OPTimize NOW trial (a test of as-needed withdrawal medicine), found that giving withdrawal medicine only when a baby's symptoms called for it helped many babies cared for with Eat, Sleep, Console be ready to go home sooner [15]. You can read more about Eat, Sleep, Console and as-needed dosing on In[Neo]Sight. Parents can help a great deal by holding, feeding and comforting their baby.

What the study cannot tell us yet

This was a fairly small study. Most families were White and had public health insurance, all babies were born at 34 weeks or later, and hospitals measured withdrawal in different ways. Because the mothers were not randomly assigned to a medicine, the study cannot prove that methadone itself caused the extra withdrawal. A small study can also miss a small effect of dose [1].

What researchers are working on next

Researchers want to understand why some babies have a harder time than others, looking at the placenta, the baby's genes and the way the baby's body breaks down medicine. Larger studies, using the same way of measuring withdrawal in every hospital, should give clearer answers. For now, the message from this study is reassuring: a mother staying well on her treatment is the priority, and her dose did not predict how hard withdrawal would be for her baby.

References

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  2. Hirai AH, Ko JY, Owens PL, Stocks C, Patrick SW. Neonatal Abstinence Syndrome and Maternal Opioid-Related Diagnoses in the US, 2010-2017. JAMA. 2021;325(2):146-155. doi:10.1001/jama.2020.24991 ↩
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  6. Suarez EA, Huybrechts KF, Straub L, et al. Buprenorphine versus Methadone for Opioid Use Disorder in Pregnancy. N Engl J Med. 2022;387(22):2033-2044. doi:10.1056/NEJMoa2203318 ↩
  7. Zedler BK, Mann AL, Kim MM, et al. Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta-analysis of safety in the mother, fetus and child. Addiction. 2016;111(12):2115-2128. doi:10.1111/add.13462 ↩
  8. Cleary BJ, Donnelly J, Strawbridge J, et al. Methadone dose and neonatal abstinence syndrome-systematic review and meta-analysis. Addiction. 2010;105(12):2071-2084. doi:10.1111/j.1360-0443.2010.03120.x ↩
  9. de Castro A, Jones HE, Johnson RE, Gray TR, Shakleya DM, Huestis MA. Methadone, cocaine, opiates, and metabolite disposition in umbilical cord and correlations to maternal methadone dose and neonatal outcomes. Ther Drug Monit. 2011;33(4):443-452. doi:10.1097/FTD.0b013e31822724f0 ↩
  10. Concheiro M, Jones HE, Johnson RE, Choo R, Shakleya DM, Huestis MA. Maternal buprenorphine dose, placenta buprenorphine, and metabolite concentrations and neonatal outcomes. Ther Drug Monit. 2010;32(2):206-215. doi:10.1097/FTD.0b013e3181d0bd68 ↩
  11. van Hoogdalem MW, Wexelblatt SL, Akinbi HT, Vinks AA, Mizuno T. A review of pregnancy-induced changes in opioid pharmacokinetics, placental transfer, and fetal exposure: Towards fetomaternal physiologically-based pharmacokinetic modeling to improve the treatment of neonatal opioid withdrawal syndrome. Pharmacol Ther. 2022;234:108045. doi:10.1016/j.pharmthera.2021.108045 ↩
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