#445 - [Journal Club] - 📌 Can symptom-based dosing cut hospitalization time for babies with neonatal opioid withdrawal syndrome?

One infant is diagnosed with neonatal opioid withdrawal syndrome every 27 minutes, and rates are rising. In this episode of Journal Club, Ben and Daphna review the Optimized NOW randomized clinical trial, a landmark multicenter study published in JAMA. The trial compared symptom-based dosing,  a single opioid dose given when a withdrawal threshold is met against the traditional scheduled opioid taper in infants managed with Eat Sleep Console. The results are striking: symptom-based dosing reduced time to medical readiness for discharge by nearly two and a half days, and 65% of pharmacologically treated infants avoided scheduled opioid dosing entirely. Could this be the evidence-based approach that finally reshapes how we treat NOWS pharmacologically?

----

Symptom-Based Dosing for Neonatal Opioid Withdrawal: The OPTimize NOW Randomized Clinical Trial. Devlin LA et al HEAL Evaluation of Limited Pharmacotherapies for Neonatal Opioid Withdrawal Syndrome (HELP for NOWS) Consortium.JAMA. 2026 Apr 25:e265782. doi: 10.1001/jama.2026.5782. Online ahead of print. PMID: 42033722

Transcript

Ben Courchia (00:00.936) Hello everybody, welcome back to The Incubator Podcast. We're back today for Journal Club. What's up?

Daphna Yasova Barbeau (00:10.722) So intense this intro this morning.

Ben Courchia (00:13.832) It's the mood of the day. We're trying to catch up. This is the first Journal Club since we came back from PAS. It's been a rough ride. People have encouraged us to share some of our mental state, so...

Daphna Yasova Barbeau (00:29.602) We had to catch up a little bit. Yeah.

Ben Courchia (00:42.906) It's very difficult when you come back from a conference. There's that ambiguity — the schedule allowed you to go, but you come back tired, you have shifts waiting for you, and you're not allowed to complain. Nobody wants to be that person who comes back from the conference exhausted.

Daphna Yasova Barbeau (01:06.966) Yeah, the people who didn't get to go have been working.

Ben Courchia (01:09.702) They don't want to hear that you're tired from your escapade to Massachusetts. You just have to take it on the chin and be miserable alone. But we both got to go — we got to commiserate during sign out.

Daphna Yasova Barbeau (01:22.892) Travel is harder than it used to be. Are we showing our age? We're almost in mid-career now. PAS is just a whirlwind. A big thank you to everybody who came to chat with us — even if not to be on the podcast — just to come and tell us about your experience, give us some ideas, chat with other listeners, get some swag. That was so much fun, but it was three full days of being on. So we're back.

Ben Courchia (02:08.828) We're back, and we're going to try to continue to partner with PAS in some way. We're having ongoing conversations, and there's no hesitation from anybody — but it is a first for everyone. PAS has never partnered with a podcast before, so we're just trying to make sure we do this carefully and correctly.

Daphna Yasova Barbeau (02:45.070) I was just going to say — we've always learned from the community. If you've been listening to the PAS coverage or any of our conference coverage and you like it, think it could be different, or have an idea, please share with us about that experience on the receiving end.

Ben Courchia (02:58.534) Yeah, absolutely. And I think that's a good segue, because the paper I'm reviewing today is a big study published in JAMA.

Daphna Yasova Barbeau (03:16.620) Did you want to do some announcements first, or did you just want to get going?

Ben Courchia (03:20.902) We'll do them tomorrow. Three minutes in — that's enough banter for today. Tomorrow there will be some big announcements. Stay tuned. We'll trickle them throughout the week. Back to my paper.

Daphna Yasova Barbeau (03:40.376) Please go ahead.

Ben Courchia (03:42.248) Published in JAMA — symptom-based dosing for neonatal opioid withdrawal syndrome (NOWS), the Optimized NOW randomized clinical trial. Going forward, we're also going to start linking to the clinical trial sessions from PAS that are available online as on-demand oral abstracts. The authors recorded a presentation of their slides — you won't be watching the live talk, but it's the same content, almost like a mock lecture. Very helpful. We'll link to that so you can go check it out.

Daphna Yasova Barbeau (05:14.070) I also want to highlight the lead author, Dr. Lori Devlin. We were able to sit down with her at the PAS Incubator booth — that's episode 439, "Can We Give Fewer Opioids to Babies with Withdrawal Syndrome?" — so listeners can follow up after hearing Ben review the paper.

Ben Courchia (05:30.534) Great. So the background — a brief overview of the situation with NOWS in the US. One infant is diagnosed with NOWS approximately every 27 minutes. And the rates are going up, not down.

When managing this condition, the Finnegan-based approach focuses on detailed scoring of the signs of withdrawal. The other approach — also evidence-based — is Eat Sleep Console (ESC), which emphasizes the functional well-being of the infant: specifically eating, sleeping, and the ability to be consoled. Both care models are still present in practice, though ESC is becoming more and more the norm based on data showing reductions in hospital stay and opioid exposure.

Non-pharmacologic care is always the initial line of treatment we want to favor for babies with NOWS. However, when babies do not adequately respond to non-pharmacologic intervention, that's when medications are needed.

The two most frequently used pharmacologic approaches are: (1) the traditional scheduled opioid taper approach, where you start medication, check scores, and taper as scores improve; and (2) a newer symptom-based dosing approach, which is really what this paper is about.

With symptom-based dosing, pharmacologic treatment is provided as a single opioid dose when a specified withdrawal threshold is met. Monitoring continues, and additional doses are given only if withdrawal severity remains above or escalates back to that threshold. The authors note that with consistent application, symptom-based dosing may decrease postnatal opioid exposure and shorten the duration of hospitalization for infants whose withdrawal is adequately controlled with intermittent dosing.

To date, there had been very limited data supporting one approach over the other — mostly retrospective data and quality improvement initiatives from single centers or small regional collaboratives. Promising, but not rigorously generalizable. That led to this trial, conducted under the National Institutes of Health's Helping to End Addiction Long-term (HEAL) initiative — specifically, the Evaluation of Limited Pharmacotherapies for Neonatal Opioid Withdrawal Syndrome, known as the HELP for NOWS consortium.

The objective: to evaluate the safety, efficacy, and generalizability of symptom-based dosing compared with a traditional scheduled opioid taper for infants with NOWS at risk for pharmacologic treatment.

Ben Courchia (10:33.660) The study design is extremely rigorous. It's a multicenter, stratified, cluster randomized clinical trial — with one cluster, the Finnegan cohort, subordinate to the other, the ESC cohort. The trial was conducted at 23 US sites between March 2024 and April 2025.

To reflect current clinical practice while acknowledging the growing use of ESC, the investigators included hospitals using either ESC or Finnegan-based care, but powered the primary analysis on the ESC cohort. The goal was to test traditional scheduled taper versus symptom-based dosing specifically within that ESC context.

Enrolled infants were at least 36 weeks gestational age at birth, had documented opioid exposure during the middle or final trimester of pregnancy, and were assessed as at risk for pharmacologic treatment — meaning at least one Finnegan score ≥ 8, or at least one "yes" for difficulty with eating, sleeping, or consoling on an ESC assessment.

Infants were randomized 1:1 to one of two sequences. Sequence 1: symptom-based approach for five months, then scheduled taper for five months. Sequence 2: scheduled taper for five months, then symptom-based approach for five months. Sites cycled through both approaches. I'd encourage listeners to look at Figure 1 for the full treatment algorithms.

During the scheduled taper approach, pharmacologic management followed the site's routine algorithm without modification — including the threshold for initiation and the weaning strategy. During symptom-based dosing, the same site-specific treatment thresholds were used, but rather than initiating scheduled dosing when the threshold was met, infants received a single opioid dose equivalent to what would have been the first dose of a taper. Withdrawal severity was then monitored, and additional doses were only given if signs of withdrawal again met the threshold.

Each time the threshold was met, another as-needed dose could be given — as long as the infant had not already received three doses in the preceding 24 hours or two consecutive short-interval doses. Short-interval doses were defined as morphine every 2 hours, buprenorphine every 3 hours, or methadone every 4 hours. If either of those thresholds was crossed, the site's scheduled opioid taper was then initiated. Throughout the trial, sites used their consistent assessment method — ESC or Finnegan — and their preferred primary opioid: morphine, buprenorphine, or methadone.

Ben Courchia (14:19.144) The primary outcome was time from birth until medical readiness for discharge in the ESC cohort. Infants were considered medically ready at the time of discharge by the medical team, or when they met the study criteria — whichever came first. The criteria for medical readiness were being at least 96 hours of age and at least 48 hours from the final dose of opioid.

Secondary outcomes included receipt of pharmacologic treatment, length of hospital stay, time to medical readiness among infants who received pharmacologic treatment, number of opioid doses, days of primary opioid administration, length of opioid treatment, and receipt of secondary medications. An important secondary outcome specific to the symptom-based group was the proportion of infants who ultimately required transition to scheduled opioid dosing for persistently elevated signs of withdrawal.

Now the results. The ESC cohort included 189 infants in the symptom-based dosing group and 194 in the scheduled taper group. Maternal and infant characteristics were similar between groups.

For the primary outcome, mean time to medical readiness for discharge was significantly shorter with symptom-based dosing: 9.2 days versus 11.6 days with scheduled taper — adjusted means ratio 0.79, p = 0.02. That's a reduction of nearly two and a half days.

For secondary outcomes: the likelihood of receiving pharmacologic treatment was 0.40 in the symptom-based group versus 0.41 in the scheduled taper group — not statistically significant. Length of hospital stay was 10.9 days versus 12.1 days, a similar trend. Among infants who did receive pharmacologic treatment, mean time to medical readiness was also shorter with symptom-based dosing: 13.1 days versus 17.56 days, adjusted means ratio 0.75.

Thirty-five percent of pharmacologically treated infants in the symptom-based group required transition to scheduled dosing for persistently elevated signs of withdrawal — a number needed to treat of 1.5 to prevent one infant from receiving scheduled opioids. There were no significant differences between groups in mean opioid doses, opioid treatment days, length of treatment, or receipt of secondary medications.

Ben Courchia (18:55.826) The conclusion: in this randomized clinical trial, symptom-based dosing decreased time to medical readiness for discharge and resulted in avoidance of scheduled opioid dosing for 65% of infants cared for with Eat Sleep Console with NOWS. For infants in the ESC setting, symptom-based dosing should be considered an effective, evidence-based approach for pharmacologic treatment.

I love when trials are well-designed, because the conclusion doesn't say "we need more data." It says: this is what we should be doing. For me, it's a no-brainer. Reducing opioid exposure makes sense. The approach pairs a single dose with rigorous, ongoing assessment and the opportunity to intervene based on symptoms. And the reduction in length of stay — nearly two and a half days — is enormous. People might say it's just a couple of days, but if someone told you your child was going to be in the hospital two and a half days longer, nobody would say that's not a big deal.

Daphna Yasova Barbeau (20:00.279) In some hospitals, that's on the pediatric ward. In many hospitals, that's two and a half more days in the ICU. We've all had that experience — a baby who needed some treatment, did great, and you're just weaning, weaning, weaning. Obviously some kids don't fit that paradigm, and the study addressed that. But I think this is a new way to look at a group of babies who already needed medication beyond Eat Sleep Console — and that shift in itself was already a change from how we managed things in training. Exciting nonetheless.

Ben Courchia (20:44.368) Agreed. This is why I wanted to start here today — it's a very important study. To me, this is the type of study we'll see in the next edition of 50 Studies Every Neonatologist Should Know. These are the studies that define practice. I'm very curious to see the long-term outcomes. We know that in utero opioid exposure has negative effects on neurodevelopment, and we know that postnatal opioid exposure does as well. What we don't know is how much of the neurodevelopmental impairment we see after in utero exposure is driven by the prenatal phase versus our own treatment after birth. If we can reduce the postnatal opioid load, what improvement might we see down the road? I'm sure they'll come out with long-term data.

Daphna Yasova Barbeau (21:59.757) It's also compounded because — for systems that have adopted ESC — Eat Sleep Console doesn't stop when we start pharmacologic treatment. Before, we'd keep babies in a closed dark room. But now it's eat, sleep, and console: pick up this baby, spend time with this baby, hold this baby. I really hope we'll find that long-term outcomes are improving significantly for these kids.

Ben Courchia (22:40.070) All right. That wraps up today. See you tomorrow.

Daphna Yasova Barbeau (22:45.583) Bye.