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Chronic opioid use during pregnancy linked with reduced head circumference in NAS newborns

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Add optimizing outcomes to NAS focus

At a time when more people in the United States are dying from opioid overdose than from automobile trauma, the number of newborns with NAS has virtually exploded, rising fivefold since 2000. In some states, more than 30 infants per 1,000 live births develop NAS “effectively transforming some NICUs into NAS wards,” Mark L. Hudak, MD, and Kartikeya Makker, MD, wrote in an accompanying editorial.

Among the strengths of the current study, they cited “universal dating of pregnancies by early ultrasound, multiple antenatal maternal urine drug tests for exposures in both cases and controls, and the use of a fairly robust statistical methodology to account for confounding exposures.”

Among the findings of the study were that, “compared with well-matched controls, newborns with NAS demonstrated a highly significant (nearly 1 cm) decrease in the mean head circumference. Another finding was that newborns with NAS showed proportionately greater decreases in head circumference than in birth weight,” the editorialists said.

Dr. Hadak and Dr. Makker noted that, while NAS can be challenging to manage, the acute effects of withdrawal are transient. The more important questions, they propose are: “What are the best methods to prevent NAS?” and “What, if any, are the long-term effects of fetal and neonatal opioid exposure on the developing child?”

Dr. Hudak and Dr. Makker question the practicality of closely following maternal opioid usage during pregnancy, but they do foresee value in the anticipated findings of a current study in which Dr. Towers and his associates are observing newborns with reduced fetal exposure to opioids who have not developed NAS.

“Additional evidence revealing that the reduction of maternal opioid use can protect normal fetal head and brain growth should energize discussion about refining the management of the opioid-maintained maternal-fetal dyad, with the goal not solely to prevent NAS but more importantly to optimize the outcome of the child,” they said.

Dr. Hudak and Dr. Makker are affiliated with the department of pediatrics at the University of Florida, Jacksonville. These comments are summarized from an editorial commenting on the study by Towers et al. (Pediatrics. 2019;143[1]:e20183376). Dr. Hudak and Dr. Makker said they had no relevant financial disclosures.



Newborns who develop neonatal abstinence syndrome (NAS) caused by chronic maternal opioid use during pregnancy are at risk of significantly smaller head circumference (HC), reported Craig V. Towers, MD, and his associates at the University of Tennessee Medical Center in Knoxville in Pediatrics.

In the first large prospective cohort study to compare HC in newborns being treated for NAS, a total of 858 neonates, including 429 with NAS and 429 controls, were enrolled and assessed at the University of Tennessee Medical Center, Knoxville, from April 1, 2014, to Dec. 31, 2016.

Dr. Towers and his associates found that mean HC in those neonates with NAS was significantly smaller, by 9.5 mm, than it was in controls. Of the 429 newborns with NAS, 62% had a normal HC, 30% had an HC less than the 10th percentile, and 8% had an HC less than or equal to the third percentile. Of the controls, 12% had an HC less than the 10th percentile.

The authors identified a significant 3% reduction in mean HC as well as a 2% reduction in mean birth weight. “Because newborn HC is an indirect measure of brain volume, further research is necessary to determine if this finding increases the risk for long-term neurodevelopmental delay,” they said.

Even though the newborns with NAS were found to experience greater coexposure to benzodiazepines, stimulants, marijuana, gabapentin, tobacco, and SSRIs, compared with controls, none of these coexposures was determined to be a significant risk factor for smaller head circumference at birth when individual drug exposure relationships within the newborn population alone were assessed, the researchers observed.

Dr. Towers and his associates did consider it noteworthy, however, that the majority of NAS cases included in the study were born to mothers receiving opioid agonist medication–assisted treatment (MAT), which is the recommended treatment in cases where opioid use disorder is addressed during pregnancy. Among the 429 NAS cases, the mothers of 372 (87%) were on opioid agonist MAT (320 buprenorphine and 52 methadone); the remaining 13% were born to mothers who were prescribed other opioid drugs.

There is limited data available to determine whether detoxification during pregnancy for patients with opioid use disorder (OUD) has any effect on lessening the risk of lower HC. In fact, the authors caution that detoxification during pregnancy is not recommended for managing OUD. To date, there are only a few locations in the United States and other countries offering such treatment. If the practice becomes more widespread, they cautioned, further research examining new born HC and long-term outcomes “is of paramount importance.”

Further prospective studies evaluating the effects of opioid exposure in newborns who do not develop NAS also are needed. Such data could provide clues concerning whether there is a crucial period of exposure that leads to reduced HC or whether the effects of opioid exposure are in fact cumulative. In cases where newborns are exposed as a result of maintenance MAT, through illicit use, or as a result of maternal detoxification, such studies also could assist with determining whether it is necessary to reconsider current practices for managing OUD in pregnancy.

The study was partially funded through the Blue Cross Blue Shield Research Foundation. The authors reported no relevant financial disclosures.

SOURCE: Towers CV et al. Pediatrics. 2019;143(1):e20180541.

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