Comment on “Head Ultrasound Findings in Infants with Birth Weight >1,500 g and Gestational Age >32 Weeks Exposed to Prenatal Opioids”

We recently reviewed with keen interest the study by Sakaria et al, [1] titled “Head Ultrasound Findings in Infants with Birth Weight >1,500 g and Gestational Age >32 Weeks Exposed to Prenatal Opioids,” published in your journal. This retrospective cohort study, conducted at a level III NICU, investigates head ultrasound (HUS) findings in 127 late preterm and term infants with prenatal opioid exposure, offering a valuable contribution to a sparsely researched area. The authors report a 13% incidence of abnormal HUS findings, predominantly sub-ependymal hemorrhage or grade 1 intraventricular hemorrhage, alongside rare cases of absent septum pellucidum. We commend the team for addressing this critical gap, given the rising prevalence of maternal opioid use and its implications for neonatal health. To enhance this promising work, we offer several suggestions in a spirit of collaboration.

First, we appreciate the study's focus on a specific population—infants >32 weeks gestation and >1,500 g—yet the lack of a control group limits causal inference. Incorporating matched unexposed infants could clarify whether the 13% abnormality rate exceeds expected baseline rates for this gestational age, strengthening the link to opioid exposure. This addition would contextualize findings and guide clinical decision-making regarding routine HUS screening.

Second, the distinction between opioid-only (16%) and polysubstance (84%) exposure is noted, but the analysis does not stratify HUS outcomes by exposure type. Given the potential confounding effects of polysubstance use (e.g., cocaine and methamphetamine), we suggest subgroup analyses to discern whether specific drug combinations or opioid monotherapy drive the observed abnormalities. This could refine the study's implications, especially as the authors call for correlating findings with specific exposures.

Third, the identification of absent septum pellucidum in three infants is intriguing, hinting at possible structural anomalies linked to opioid exposure. We propose expanding neuroimaging to include MRI in a subset of cases to validate HUS findings and explore subtler brain changes, such as white matter injury or cortical malformations, which HUS might miss. This could elucidate mechanisms underlying neurodevelopmental risks, a key area flagged for future study.

Last, while the study highlights abnormal HUS prevalence, it lacks data on clinical correlates or long-term outcomes. Linking these findings to neonatal symptoms (e.g., seizures and withdrawal severity) or follow-up neurodevelopmental assessments (e.g., Bayley Scales at 18–24 months) would bolster relevance. Such data could justify routine HUS by demonstrating prognostic value and addressing the study's central question.

Sakaria et al provide a compelling initial exploration of HUS findings in opioid-exposed infants, revealing a notable abnormality rate that warrants attention. We sincerely praise their efforts and encourage the inclusion of a control group, exposure-specific analyses, advanced imaging, and outcome correlations. These enhancements could elevate this study's impact, informing neonatal care protocols amid the opioid epidemic.

Authors' Contributions

S.K., R.M., and R.S. critically provided comments on methodological aspects. S.K. and R.S. have written the edited the draft.

Publication History

Received: 06 April 2025

Accepted: 19 May 2025

Accepted Manuscript online:
20 May 2025

Article published online:
04 June 2025

• Reference

• 1 Sakaria RP, Rana D, Harsono M, Cohen HL, Pourcyrous M. Head ultrasound findings in infants with birth weight >1,500 g and gestational age >32 weeks exposed to prenatal opioids. Am J Perinatol 2025; (e-pub ahead of print)