Impact of Coronavirus Disease-2019 on Hospital Care for Neonatal Opioid Withdrawal Syndrome.

OBJECTIVE: To compare prenatal exposures, hospital care processes, and hospitalization outcomes for opioid-exposed newborns before and during the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: In this multicenter retrospective analysis, data were collected from 19 Massachusetts hospitals, including 5 academic and 14 community hospitals. The pre-COVID-19 cohort was defined as births occurring during March 1, 2019-February 28, 2020, and the COVID-19 cohort was defined as births occurring during March 1, 2020-December 31, 2020. Opioid-exposed newborns born at ≥35 weeks of gestation were included. Differences in prenatal substance exposures, hospital care processes, and neonatal opioid withdrawal syndrome (NOWS) outcomes, including pharmacologic treatment for NOWS (PharmTx), length of stay (LOS), and as-needed (prn) treatment failure rates, were evaluated. RESULTS: There were 663 opioid-exposed newborns in the pre-COVID-19 group and 476 in the COVID-19 group. No between-group differences were seen in prenatal substance exposures or the need for PharmTx. Compared with the pre-COVID-19 group, in the COVID-19 group there was less rooming-in after maternal discharge (53.8% vs 63.0%; P = .001) and less care in the pediatric unit setting (23.5% vs 25.3%; P = .001), longer LOS (adjusted risk ratio, 1.04; 95% CI, 1.01-1.08), and a higher rate of breast milk receipt at discharge (aOR, 2.03; 95% CI, 1.22-3.39). Within the subset of academic centers, more infants failed prn treatment in the COVID-19 group (53.8% vs 26.5%, P = .02; aOR, 3.77; 95% CI, 0.98-14.5). CONCLUSIONS: Among the hospitals in our collaborative, hospital processes for NOWS, including care setting, rooming-in, and LOS were negatively impacted in the COVID-19 group, particularly in academic medical centers.

Neurodevelopmental Outcomes of Neonates Randomized to Morphine or Methadone for Treatment of Neonatal Abstinence Syndrome.

OBJECTIVE: To evaluate the effects of pharmacologic treatment of neonatal abstinence syndrome on neurodevelopmental outcome from a randomized, controlled trial. STUDY DESIGN: Eight sites enrolled 116 full-term newborn infants with neonatal abstinence syndrome born to mothers maintained on methadone or buprenorphine into a randomized trial of morphine vs methadone. Ninety-nine infants (85%) were evaluated at hospital discharge using the NICU Network Neurobehavioral Scale. At 18 months, 83 of 99 infants (83.8%) were evaluated with the Bayley Scales of Infant and Toddler Development-Third Edition and 77 of 99 (77.7%) with the Child Behavior Checklist (CBCL). RESULTS: Primary analyses showed no significant differences between treatment groups on the NICU Network Neurobehavioral Scale, Bayley Scales of Infant and Toddler Development-Third Edition, or CBCL. However in post hoc analyses, we found differences by atypical NICU Network Neurobehavioral Scale profile on the CBCL. Infants receiving adjunctive phenobarbital had lower Bayley Scales of Infant and Toddler Development-Third Edition scores and more behavior problems on the CBCL. In adjusted analyses, internalizing and total behavior problems were associated with use of phenobarbital (P = .03; P = .04), maternal psychological distress (measured by the Brief Symptom Inventory) (both P < .01), and infant medical problems (both P = .02). Externalizing problems were associated with maternal psychological distress (P < .01) and continued maternal substance use (P < .01). CONCLUSIONS: Infants treated with either morphine or methadone had similar short-term and longer term neurobehavioral outcomes. Neurodevelopmental outcome may be related to the need for phenobarbital, overall health of the infant, and postnatal caregiving environment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958476.

Perinatal Transmission of Hepatitis C Virus: Defining the Cascade of Care.

OBJECTIVES: The US National Viral Hepatitis Action Plan calls for major efforts to expand hepatitis C virus (HCV) diagnosis and treatment; prenatal care settings are potential venues for expanding HCV testing. We aimed to characterize the HCV diagnostic cascade for women and infants and investigate factors associated with linkage and follow-up. STUDY DESIGN: We used electronic health records for a 10-year cohort of 879 women with opioid use disorder from an obstetric clinic serving women with substance use disorders. RESULTS: Altogether, 744 women (85%) were screened for HCV; 510 (68%) were seropositive, of whom 369 (72%) had nucleic acid testing performed and of these 261 (71%) were viremic. Of 404 infants born to HCV-seropositive women, 273 (68%) were tested at least once for HCV, 180 (45%) completed the American Academy of Pediatrics-recommended perinatal HCV screening, and 5 (2.8%) were diagnosed with HCV infection and linked to care. More recent delivery date (2014-2015) was associated with maternal linkage to care (aOR, 2.5; 95% CI, 1.4-4.7). Maternal coinfection with HIV (aOR, 9.0; 95% CI, 1.1-72.8) and methadone maintenance therapy, compared with buprenorphine (aOR, 1.5; 95% CI, 0.9-2.5), were associated with higher rates of infant HCV testing. CONCLUSIONS: HCV prevalence among pregnant women with opioid use is high and infant HCV screening is imperfect. Programmatic changes to improve both mother and infant follow-up may help to bridge identified gaps in the cascade to cure.

Epigenetic variation in the mu-opioid receptor gene in infants with neonatal abstinence syndrome.

OBJECTIVE: Neonatal abstinence syndrome (NAS) from in utero opioid exposure is highly variable with genetic factors appearing to play an important role. Epigenetic changes in cytosine:guanine (CpG) dinucleotide methylation can occur after drug exposure and may help to explain NAS variability. We correlated DNA methylation levels in the mu-opioid receptor (OPRM1) promoter in opioid-exposed infants with NAS outcomes. STUDY DESIGN: DNA samples from cord blood or saliva were analyzed for 86 infants who were being treated for NAS according to institutional protocol. Methylation levels at 16 OPRM1 CpG sites were determined and correlated with NAS outcome measures, including need for treatment, treatment with ≥ 2 medications, and length of hospital stay. We adjusted for covariates and multiple genetic testing. RESULTS: Sixty-five percent of infants required treatment for NAS, and 24% required ≥ 2 medications. Hypermethylation of the OPRM1 promoter was measured at the -10 CpG in treated vs nontreated infants (adjusted difference δ = 3.2% [95% CI, 0.3-6.0%], P = .03; nonsignificant after multiple testing correction). There was hypermethylation at the -14 (δ = 4.9% [95% CI, 1.8%-8.1%], P = .003), -10 (δ = 5.0% [95% CI, 2.3-7.7%], P = .0005), and +84 (δ = 3.5% [95% CI, 0.6-6.4], P = .02) CpG sites in infants requiring ≥ 2 medications, which remained significant for -14 and -10 after multiple testing correction. CONCLUSIONS: Increased methylation within the OPRM1 promoter is associated with worse NAS outcomes, consistent with gene silencing.