Neonatal outcomes following in utero exposure to methadone or buprenorphine: A National Cohort Study of opioid-agonist treatment of Pregnant Women in Norway from 1996 to 2009.
PMID: 22841456
This study is a non randomized look at neonatal outcomes in Norway. It is non randomized so should be interpreted cautiously but does have some unexpected findings.
The authors recruited women in three waves: 1996 to 2003 (n = 51), 2005 to 2007 (n = 36), and 2004 to 2009 (n = 52). They only looked at women having their first child on opiate maintenance treatment and the authors believe they captured approx 65% of all women meeting this criteria in Norway from 1996-2009. [Estimating that only 210 women had first children on maintenance treatment during this 13 year period, a surprisingly low number]. The authors reviewed records, spoke with women in the third trimester and had follow up calls post partum, on average on year after delivery.
As an aside, when they compare drug testing to maternal interviews they note "self-report reveals more use of drugs than does urine drug screening"
These women were not randomly assigned. The authors note "The inclusion criteria for both medications are the same and both medications are provided by the same health professionals in any part of the country" but don't give any indication as to how local providers might decide to offer methadone vs buprenorphine. They authors tracked 90 pregnancies on methadone and 49 on buprenorphine.
Women on methadone were found to have longer histories of opiate dependence. They also had more use of other opiates in late pregnancy. Very different from our experience 90% of the women were on opiate maintenance treatment prior to conception, with a median length of 18 months. Average dose of methadone 90 mg, average buprenorphine 13 mg.
Buprenorphine babies were heavier, longer and had larger head circumferences than the
methadone-exposed newborns. Methadone babies were 2944g (6.4lbs) ± 649g (910–4624), buprenorphine babies 3254g (7.2 bls) ± 569 (973–4200). When they adjusted for presumed relevant covariants only the head size remained statistically significant. There were no differences in gestational ages or apgars. The c-section rate was 28% on methadone, only 15% on buprenorphine, but htis was not statistically significant.
There are surprising results in the NAS treatment for these babies.
There was no difference in the occurrence of NAS between these two groups. 58% of methadone babies were treated and 60% of buprenorphine babies. Our clinical experience in Seattle is very different were almost all of methadone babies have Finnegan scores requiring treatment of NAS.
The length of NAS treatment was nearly significantly different between the groups (p = 0.05); with buprenorphine-exposed neonates tending to have shorter treatment for NAS but not by much. 38.6 days of methadone babies and 27.7 days for buprenorphine babies. When they adjusted for co-variants the difference decreased and was not longer statistically significant.
The authors note the length of treatment is much longer than in the MOTHERS trial and comment "Another possible explanation for the long average treatment of NAS in our study is that most hospitals in Norway have little experience with the treatment of NAS, and
therefore are more cautious when tapering down the NAS medication of the newborn."
They did not report type of medication given for NAS or on the total medication used. In the MOTHERS randomized trial there was a striking 90% decrease in the total morphine needed for buprenorphine exposed babies.
Subgroup analysis showed that women using any drugs (opiates, benzodiazepines, cannabis and/or amphetamine) early or late in pregnancy had significantly longer NAS treatment, 40 days vs 28 days.
Finally, two neonates exposed to buprenorphine in pregnancy were born with malformations, one child with spina bifida and one child with gastroschisis. It is assumed these are not related to buprenorphine.
In conclusion: this study may not inform our practice much. These women were unusual in that almost all were on maintenance treatment before pregnancy and there was little additional drug use. They were not randomized to buprenorphine vs methadone and the authors give little clue how the patient or clinician might have assigned them. The buprenorphine babies were slightly larger. There as little difference in the NAS treatment reported.
It is interesting how both the MOTHERS trial and this report show much fewer methadone babies requiring NAS treatment than our clinical experience has show.
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