Sex-Related Differences in the Severity of Neonatal Opioid Withdrawal Syndrome: A Single-Center, Retrospective Cohort Study.

OBJECTIVE: Factors associated with the development and expression of Neonatal Opioid Withdrawal Syndrome (NOWS) are poorly understood. There are conflicting data on the role of infant sex in NOWS. Some studies have suggested that infant sex predicts NOWS severity and adverse outcomes, with male infants being more vulnerable. This study aimed to analyze if infant sex is associated with the severity of NOWS among those who require pharmacologic treatment. STUDY DESIGN: This is a retrospective cohort study of term and late-preterm infants (≥35 weeks gestation) exposed to in utero opioids, born between September 2006 and August 2022, and required pharmacologic treatment for NOWS. Maternal and infant demographics were collected. Indicators of the severity of NOWS (duration of medical treatment (DOT), duration of hospitalization, maximum dose of opioid treatment, and use of secondary medications) were compared between male and female infants. Standard statistical tests and regression analysis were used to establish the differences in outcomes after accounting for confounders and baseline differences. RESULTS: Out of the 1,074 infants included in the study, 47.9% were female, and 52.1% were male. There was no significant difference in demographic and baseline clinical characteristics between groups except for anthropometry (birth weight, head circumference, and length) and Apgar score at 5 minutes. The median DOT (25 days [14, 39] vs. 23 days [13, 39], p = 0.57), length of hospital stay (31.5 days [20, 44] vs. 28 days [20, 44], p = 0.35), treatment with phenobarbital (24.7 vs. 26.3%, p = 0.56), and clonidine (3.9 vs. 3.8%, p = 0.9) were similar in both groups. The differences remained nonsignificant after adjusting for birth anthropometric measurements, gestational age, 5-minute Apgar score, small for gestational age status, and maternal exposure to benzodiazepines. CONCLUSION: In this cohort of neonates, sex-related differences were not identified to influence the severity of NOWS among those who required pharmacological treatment. KEY POINTS: · Vulnerability to NOWS is multifactorial.. · The role of infant sex in the severity of NOWS is not concrete.. · We noted that sex did not impact NOWS severity in those treated..

Acute Kidney Injury and Abnormalities on Brain Magnetic Resonance Imaging or Death in Infants with Hypoxic-Ischemic Encephalopathy: A Case-Control Study.

OBJECTIVE: This study aimed to analyze the association between acute kidney injury (AKI) and abnormalities on brain magnetic resonance imaging (MRI) or death in neonates treated with therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: This is a retrospective case-control analysis of 380 neonates born at ≥35 weeks' gestation treated with therapeutic hypothermia for HIE. Death or abnormal brain MRI using the basal ganglia watershed scoring system was compared between neonates with and without AKI. RESULTS: A total of 51 (13.4%) neonates had AKI. Infants with AKI had higher rates of the composite of death or abnormal brain MRI (74.5 vs. 38.3%; p < 0.001). Rate of death (21.6 vs. 5.5%; p < 0.001) and severe abnormalities on MRI or death (43.1 vs. 19.1%; p < 0.001) were also higher in neonates with AKI. CONCLUSION: AKI is strongly associated with abnormalities on brain MRI or death in neonates with HIE. Identification of AKI in this patient population may be helpful in guiding clinical management and predicting potential neurodevelopmental impairment. KEY POINTS: · Neonates with HIE are at increased risk for AKI.. · AKI is associated with hypoxic-ischemic injury on brain MRI or death among neonates with HIE.. · Identification of AKI in infants with HIE may help predict neurodevelopmental impairment..

Is Maternal Methadone Dose Associated with the Severity of Neonatal Abstinence Syndrome?

OBJECTIVE: The aim of the study is to assess the correlation between maternal methadone dose and severity of neonatal abstinence syndrome (NAS) in infants that required pharmacological treatment for NAS. STUDY DESIGN: This is a retrospective analysis of 574 infants ≥35 weeks' gestation exposed to methadone in utero, born between August 2006 and May 2018, and who required pharmacological therapy for NAS. Indicators of NAS severity (duration of morphine treatment, maximum morphine dose, use of phenobarbital, and length of hospitalization) were compared between infants exposed to high (≥200 mg), intermediate (100-199 mg), and low doses (<100 mg) of methadone. Logistic and linear regression models were used to adjust for the covariates. RESULTS: Median (interquartile range) duration of medical treatment with morphine was higher in infants exposed to higher doses of methadone (low dose 23 [14-37] days, intermediate dose 31 [18-45] days, and high dose 35 [20-48] days, p < 0.001). Higher methadone doses were also predictive of longer duration of hospitalization, higher maximum morphine dose, and increased likelihood of treatment with phenobarbital. The association between maternal methadone dose and the severity of NAS persisted in multivariable regression models. CONCLUSION: Infants exposed to higher methadone doses displayed more severe NAS, as indicated by longer durations of treatment, higher maximum morphine dose, longer duration of hospitalization, and increased likelihood of phenobarbital use. KEY POINTS: · Methadone maintenance therapy is used during pregnancy to control maternal withdrawal symptoms.. · Relationship between maternal methadone dose and severity of NAS is not adequately investigated.. · Increased doses of methadone during pregnancy correlate with increased severity of NAS..

Use of a Modified Early-Onset Sepsis Risk Calculator for Neonates Exposed to Chorioamnionitis.

OBJECTIVE: To validate the recently modified Kaiser Permanente early-onset sepsis (EOS) calculator with a higher baseline incidence in chorioamnionitis exposed neonates. STUDY DESIGN: This is a retrospective study of chorioamnionitis-exposed neonates born at ≥35 weeks of gestation with a known EOS incidence of 4.3/1000. The risk and management categories were calculated using the calculator with an incidence of 4/1000. The results were compared with a previous analysis of the same cohort that used an EOS incidence of 0.5/1000. RESULTS: In our sample, the EOS calculator recommends at least a blood culture in 834 of 896 (93.1%) and empiric antibiotics in 533 of 896 (59.5%) chorioamnionitis-exposed neonates when using an EOS incidence of 4/1000. This captures 5 of 5 neonates (100%) with EOS. When using a baseline EOS incidence of 0.5/1000, the calculator recommends at least a blood culture in only 289 of 896 (32.2%) and empiric antibiotics in only 209 of 896 (23.3%) neonates, but fails to recommend empiric antibiotics in 2 of 5 neonates with EOS (40%). CONCLUSIONS: When using an EOS risk of 4 of 1000 in infants exposed to mothers with chorioamnionitis, the EOS calculator has the ability to capture an increased number of neonates with culture-positive EOS. However, this change also leads to nearly a 3-fold increase in the use of empiric antibiotics and an evaluation with blood culture in almost all infants born to mothers with chorioamnionitis.

Infants Born to Mothers with Clinical Chorioamnionitis: A Cross-Sectional Survey on the Use of Early-Onset Sepsis Risk Calculator and Prolonged Use of Antibiotics.

OBJECTIVE: To evaluate variations in practice for the management of neonates born to mothers with clinical chorioamnionitis. METHODS: This was a prospective cross-sectional survey consisting of 10 multiple choice questionnaires distributed to 2,900 members of the Perinatal Section of American Academy of Pediatrics. Variations in responses were assessed and compared between the various groups. RESULTS: A total of 682 members (23.5%) completed the survey; 169 (24.8%) indicated that they use the neonatal early-onset sepsis (EOS) risk calculator for the management of neonates born to mothers with clinical chorioamnionitis. More respondents from the western region of United States and level III units are using the EOS risk calculator compared with the south and level II units. Approximately 44% of the respondents indicated that they will not stop antibiotics at 48 to 72 hours in asymptomatic neonates born to mothers with chorioamnionitis with negative blood culture if the complete blood count (CBC) and C-reactive protein (CRP) are abnormal. CONCLUSION: A large number of practitioners are using the neonatal EOS risk calculator for neonates born to mothers with chorioamnionitis. Despite a clear guideline from the Committee on Fetus and Newborn, almost 44% will treat healthy-appearing neonates born to mothers with chorioamnionitis with a prolonged course of antibiotics solely for abnormal CBC or CRP.

Apgar Scores at 10 Minutes and Outcomes in Term and Late Preterm Neonates with Hypoxic-Ischemic Encephalopathy in the Cooling Era.

OBJECTIVE: To determine the short-term outcomes (abnormal brain magnetic resonance imaging [MRI]/death) in infants born with a 10-minute Apgar score of 0 who received therapeutic hypothermia and compare them with infants with higher scores. STUDY DESIGN: This is a retrospective review of 293 neonates (gestational age ≥ 35 weeks) born between November 2006 and October 2015 admitted with hypoxic-ischemic encephalopathy who received therapeutic hypothermia. Results of brain MRIs were assessed by the basal ganglia/watershed scoring system. Short-term outcomes were compared between infants with Apgar scores of 0, 1 to 4, and ≥5 at 10 minutes. RESULTS: Eight of 17 infants (47%) with an Apgar of 0 at 10 minutes survived, having 4 (24%) without abnormalities on the brain MRI and 7 (41%) without severe abnormalities. There was no significant difference in the combined outcomes of "death/abnormal MRI" and "death/severe abnormalities on the MRI" between infants with Apgar scores of 0 and 1 to 4. Follow-up data were available for six of eight surviving infants, and none had moderate or severe neurodevelopmental impairment. CONCLUSION: In the cooling era, 47% of infants with no audible heart rate at 10 minutes and who were admitted to the neonatal intensive care unit survived; 24% without abnormalities on the brain MRI and 41% without severe abnormalities.

Utility of Early-Onset Sepsis Risk Calculator for Neonates Born to Mothers with Chorioamnionitis.

OBJECTIVES: To evaluate the performance of the early-onset sepsis (EOS) risk calculator in a cohort of neonates born to mothers with clinical chorioamnionitis, and to compare the diagnostic utility of the EOS calculator, clinical signs, and laboratory evaluations for correctly identifying EOS in this cohort. STUDY DESIGN: This was a retrospective study of neonates born at ≥35 weeks of gestation to mothers with chorioamnionitis. The risk and management categories for all neonates were calculated using the EOS calculator, and these results were analyzed and compared with laboratory data and clinical signs. RESULTS: Of the 1159 neonates born to mothers with chorioamnionitis, 5 (0.43%) had culture-proven EOS. Data for calculation of EOS risk were available for 896 neonates, including the 5 neonates with culture-proven EOS. The management recommendation based on the calculator was no empiric antibiotic treatment for 67% of the neonates, including 2 of the 5 with EOS. All neonates with culture-proven EOS had abnormal complete blood counts and C-reactive protein levels at 6-12 hours. Three of the 5 neonates with EOS had clinical signs of sepsis. CONCLUSIONS: The risk of EOS in neonates born to mothers with chorioamnionitis is low. The use of an EOS calculator may reduce the use of empiric antibiotics in chorioamnionitis-exposed neonates, but in our cohort, some neonates with culture-confirmed EOS would have been missed. A larger study is needed to evaluate whether limiting antibiotics to chorioamnionitis-exposed neonates with clinical and/or laboratory signs of infection can safely decrease antibiotic use.

Buprenorphine vs. morphine: impact on neonatal opioid withdrawal syndrome (NOWS) outcomes in a single center retrospective study.

OBJECTIVES: To compare clinical outcomes for infants with neonatal opioid withdrawal syndrome (NOWS) treated with buprenorphine or morphine. STUDY DESIGN: Retrospective study of infants born ≥35 weeks' gestation and admitted to the NICU for NOWS treatment between 2011 and 2022. Length of treatment, length of stay in the hospital, and the need for secondary medications were compared between buprenorphine and morphine treated neonates. Multiple regression analysis was performed, adjusting for baseline differences and confounders. RESULTS: 417 neonates were treated with morphine and 232 with buprenorphine. The buprenorphine group had shorter treatment days [-10.8 days; 95% CI: -8.08 to -13.53] and shorter hospital stay [-11.8 days; 95% CI: -8.83 to -14.78]. The buprenorphine group was no more likely to receive phenobarbital or clonidine (26% vs. 29%). CONCLUSION: In this large single-center study, buprenorphine was associated with shorter lengths of treatment and hospital stay in the treatment of NOWS compared to morphine.

Growth failure in infants with neonatal abstinence syndrome in the neonatal intensive care unit.

OBJECTIVE: To assess if infants with neonatal abstinence syndrome (NAS) are smaller at birth and have decreased growth parameters between birth and discharge from the neonatal intensive care unit (NICU). METHODS: Retrospective data analysis of term/late-preterm neonates with NAS at a single-center NICU between September 2006 and May 2018. Growth parameters (weight, length, HC) were measured at birth and discharge. Z scores and percentiles were calculated using WHO standard growth curves. RESULTS: A total of 864 infants ≥35 weeks were admitted for NAS. At birth, median percentiles were weight 30%, HC 23%, and length 37%; these decreased significantly (p < 0.001) at discharge to 12%, 6.5%, and 13%, respectively. The percentage of infants <3rd percentile increased significantly (p < 0.001) in all growth parameters from birth to discharge. CONCLUSION: Infants with NAS are smaller at birth and have significant growth retardation in all growth parameters at discharge. An ongoing long-term growth follow-up study will discern the impact of growth restriction in NAS infants.

A comparison of Triple I classification with neonatal early-onset sepsis calculator recommendations in neonates born to mothers with clinical chorioamnionitis.

OBJECTIVE: To compare the early-onset sepsis (EOS) calculator recommendations for infants born to mothers with clinical chorioamnionitis with those made by the Triple I classification. STUDY DESIGN: Retrospective analysis of chorioamnionitis-exposed neonates ≥35 weeks. EOS risk was calculated with baseline risks of 0.5/1000 and 4/1000. Mothers were retrospectively categorized using the Triple I classification. Calculator recommendations were compared with the Triple I classification recommendations. RESULTS: We included 687 chorioamnionitis-exposed neonates. With a baseline risk of 0.5/1000, the calculator recommended no evaluation in 68.4% of infants of mothers with confirmed Triple I. With a baseline risk of 4/1000, 62.3% of infants of mothers with confirmed Triple I and 57.1% of infants born to mothers who did not meet fever criteria would have received evaluation. CONCLUSIONS: The EOS calculator with either baseline risk does not recommend evaluation in a large number of infants born to mothers with confirmed Triple I.

Maternal breast milk feeding and length of treatment in infants with neonatal abstinence syndrome.

OBJECTIVE: The objective of this study is to assess whether infants with neonatal abstinence syndrome (NAS), who receive maternal breast milk (BM), have shorter pharmacological treatment durations and lengths of stay compared with formula-fed infants. STUDY DESIGN: Retrospective data analysis from Optum Neonatal Database for infants born between 1 January 2010 and 21 November 2016, who received treatment for NAS. Clinical characteristics and outcomes were compared between infants who received any amount of BM and those exclusively formula-fed. RESULT: Infants (1738) were analyzed. Median length of pharmacological treatment was significantly lower in infants who received any BM (14 days) compared with "no BM" group (17 days, p = 0.04). Similarly, median length of hospitalization was significantly reduced in "any BM" group (19 days vs. 20 days), which remained significant after adjustment for confounders (p = 0.01). There was no difference in hospital re-admission rates. CONCLUSION: Feeding any BM to infants with NAS was associated with both decreased lengths of pharmacological treatment and hospital stay compared with exclusively formula-fed infants.