Effect of Early vs Late Inguinal Hernia Repair on Serious Adverse Event Rates in Preterm Infants: A Randomized Clinical Trial.

Importance: Inguinal hernia repair in preterm infants is common and is associated with considerable morbidity. Whether the inguinal hernia should be repaired prior to or after discharge from the neonatal intensive care unit is controversial. Objective: To evaluate the safety of early vs late surgical repair for preterm infants with an inguinal hernia. Design, Setting, and Participants: A multicenter randomized clinical trial including preterm infants with inguinal hernia diagnosed during initial hospitalization was conducted between September 2013 and April 2021 at 39 US hospitals. Follow-up was completed on January 3, 2023. Interventions: In the early repair strategy, infants underwent inguinal hernia repair before neonatal intensive care unit discharge. In the late repair strategy, hernia repair was planned after discharge from the neonatal intensive care unit and when the infants were older than 55 weeks' postmenstrual age. Main Outcomes and Measures: The primary outcome was occurrence of any prespecified serious adverse event during the 10-month observation period (determined by a blinded adjudication committee). The secondary outcomes included the total number of days in the hospital during the 10-month observation period. Results: Among the 338 randomized infants (172 in the early repair group and 166 in the late repair group), 320 underwent operative repair (86% were male; 2% were Asian, 30% were Black, 16% were Hispanic, 59% were White, and race and ethnicity were unknown in 9% and 4%, respectively; the mean gestational age at birth was 26.6 weeks [SD, 2.8 weeks]; the mean postnatal age at enrollment was 12 weeks [SD, 5 weeks]). Among 308 infants (91%) with complete data (159 in the early repair group and 149 in the late repair group), 44 (28%) in the early repair group vs 27 (18%) in the late repair group had at least 1 serious adverse event (risk difference, -7.9% [95% credible interval, -16.9% to 0%]; 97% bayesian posterior probability of benefit with late repair). The median number of days in the hospital during the 10-month observation period was 19.0 days (IQR, 9.8 to 35.0 days) in the early repair group vs 16.0 days (IQR, 7.0 to 38.0 days) in the late repair group (82% posterior probability of benefit with late repair). In the prespecified subgroup analyses, the probability that late repair reduced the number of infants with at least 1 serious adverse event was higher in infants with a gestational age younger than 28 weeks and in those with bronchopulmonary dysplasia (99% probability of benefit in each subgroup). Conclusions and Relevance: Among preterm infants with inguinal hernia, the late repair strategy resulted in fewer infants having at least 1 serious adverse event. These findings support delaying inguinal hernia repair until after initial discharge from the neonatal intensive care unit. Trial Registration: ClinicalTrials.gov Identifier: NCT01678638.

Multi-Omics Analysis on Neurodevelopment in Preterm Neonates: A Protocol Paper.

BACKGROUND: The gut microbiome is an important determinant of health and disease in preterm infants. OBJECTIVES: The objective of this article was to share our current protocol for other neonatal intensive care units to potentially expand their existing protocols, aiming to characterize the relationship between the intestinal microbiome and health outcomes in preterm infants. METHODS: This prospective, longitudinal study planned to recruit 160 preterm infants born <32 weeks gestational age or weighing <1,500 g and admitted to one of two Level III/IV neonatal intensive care units. During the neonatal intensive care unit period, the primary measures included events of early life pain/stress, gut microbiome, host genetic variations, and neurobehavioral assessment. During follow-up visits, gut microbiome; pain sensitivity; and medical, growth, and developmental outcomes at 4, 8-12, and 18-24 months corrected age were measured. DISCUSSION: As of February 14, 2020, 214 preterm infants have been recruited. We hypothesize that infants who experience greater levels of pain/stress will have altered gut microbiome, including potential adverse outcomes such as necrotizing enterocolitis and host genetic variations, feeding intolerance, and/or neurodevelopmental impairments. These will differ from the intestinal microbiome of preterm infants who do not develop these adverse outcomes. To test this hypothesis, we will determine how alterations in the intestinal microbiome affect the risk of developing necrotizing enterocolitis, feeding intolerance, and neurodevelopmental impairments in preterm infants. In addition, we will examine the interaction between the intestinal microbiome and host genetics in the regulation of intestinal health and neurodevelopmental outcomes.

Individualized versus standard diet fortification for growth and development in preterm infants receiving human milk.

BACKGROUND: Human milk as compared to formula reduces morbidity in preterm infants but requires fortification to meet their nutritional needs and to reduce the risk of extrauterine growth failure. Standard fortification methods are not individualized to the infant and assume that breast milk is uniform in nutritional content. Strategies for individualizing fortification are available; however it is not known whether these are safe, or if they improve outcomes in preterm infants. OBJECTIVES: To determine whether individualizing fortification of breast milk feeds in response to infant blood urea nitrogen (adjustable fortification) or to breast milk macronutrient content as measured with a milk analyzer (targeted fortification) reduces mortality and morbidity and promotes growth and development compared to standard, non-individualized fortification for preterm infants receiving human milk at < 37 weeks' gestation or at birth weight < 2500 grams. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 9), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), on September 20, 2019. We also searched clinical trials databases and the reference lists of retrieved articles for pertinent randomized controlled trials (RCTs) and quasi-randomized trials. SELECTION CRITERIA: We considered randomized, quasi-randomized, and cluster-randomized controlled trials of preterm infants fed exclusively breast milk that compared a standard non-individualized fortification strategy to individualized fortification using a targeted or adjustable strategy. We considered studies that examined any use of fortification in eligible infants for a minimum duration of two weeks, initiated at any time during enteral feeding, and providing any regimen of human milk feeding. DATA COLLECTION AND ANALYSIS: Data were collected using the standard methods of Cochrane Neonatal. Two review authors evaluated the quality of the studies and extracted data. We reported analyses of continuous data using mean differences (MDs), and dichotomous data using risk ratios (RRs). We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: Data were extracted from seven RCTs, resulting in eight publications (521 total participants were enrolled among these studies), with duration of study interventions ranging from two to seven weeks. As compared to standard non-individualized fortification, individualized (targeted or adjustable) fortification of enteral feeds probably increased weight gain during the intervention (typical mean difference [MD] 1.88 g/kg/d, 95% confidence interval [CI] 1.26 to 2.50; 6 studies, 345 participants), may have increased length gain during the intervention (typical MD 0.43 mm/d, 95% CI 0.32 to 0.53; 5 studies, 242 participants), and may have increased head circumference gain during the intervention (typical MD 0.14 mm/d, 95% CI 0.06 to 0.23; 5 studies, 242 participants). Compared to standard non-individualized fortification, targeted fortification probably increased weight gain during the intervention (typical MD 1.87 g/kg/d, 95% CI 1.15 to 2.58; 4 studies, 269 participants) and may have increased length gain during the intervention (typical MD 0.45 mm/d, 95% CI 0.32 to 0.57; 3 studies, 166 participants). Adjustable fortification probably increased weight gain during the intervention (typical MD 2.86 g/kg/d, 95% CI 1.69 to 4.03; 3 studies, 96 participants), probably increased gain in length during the intervention (typical MD 0.54 mm/d, 95% CI 0.38 to 0.7; 3 studies, 96 participants), and increased gain in head circumference during the intervention (typical MD 0.36 mm/d, 95% CI 0.21 to 0.5; 3 studies, 96 participants). We are uncertain whether there are differences between individualized versus standard fortification strategies in the incidence of in-hospital mortality, bronchopulmonary dysplasia, necrotizing enterocolitis, culture-proven late-onset bacterial sepsis, retinopathy of prematurity, osteopenia, length of hospital stay, or post-hospital discharge growth. No study reported severe neurodevelopmental disability as an outcome. One study that was published after our literature search was completed is awaiting classification. AUTHORS' CONCLUSIONS: We found moderate- to low-certainty evidence suggesting that individualized (either targeted or adjustable) fortification of enteral feeds in very low birth weight infants increases growth velocity of weight, length, and head circumference during the intervention compared with standard non-individualized fortification. Evidence showing important in-hospital and post-discharge clinical outcomes was sparse and of very low certainty, precluding inferences regarding safety or clinical benefits beyond short-term growth.

Delayed Achievement of Oral Feedings Is Associated with Adverse Neurodevelopmental Outcomes at 18 to 26 Months Follow-up in Preterm Infants.

OBJECTIVE: This study aimed to compare neurodevelopmental outcomes in preterm infants at 18 to 26 months corrected age (CA) who did versus did not achieve full oral feedings at 40 weeks postmenstrual age (PMA). STUDY DESIGN: This retrospective study included infants born between 2010 and 2015 with gestational age <32 weeks and followed between 18 and 26 months CA. Achievement of full oral feedings was defined as oral intake >130 mL/kg/d for >72 hours by 40 weeks PMA. Incidence of cognitive, language, or motor delay, or cerebral palsy at 18 to 26 months CA was compared in multivariable analyses for infants in the two feeding groups. RESULTS: Of 372 included infants, those achieving full oral feedings had lower incidence of any adverse neurodevelopmental outcome (p < 0.001) compared with those who did not achieve full oral feedings. In multivariable analyses, achievement of full oral feedings by 40 weeks PMA was associated with decreased odds of cognitive, language, and motor delays, cerebral palsy, and any adverse neurodevelopmental outcome at follow-up. CONCLUSION: Achievement of full oral feedings by 40 weeks PMA was associated with better adjusted neurodevelopmental outcomes at 18 to 26 months CA. Inability to fully feed orally at 40 weeks PMA may be a simple, clinically useful marker for risk of adverse neurodevelopmental outcomes.

Trends and variation in management and outcomes of very low-birth-weight infants with patent ductus arteriosus.

BACKGROUND: We examined recent trends and interhospital variation in use of indomethacin, ibuprofen, and surgical ligation for patent ductus arteriosus (PDA) in very-low-birth-weight (VLBW) infants. METHODS: Included in this retrospective study of the Pediatric Hospital Information System database were 13,853 VLBW infants from 19 US children's hospitals, admitted at age < 3 d between 1 January 2005 and 31 December 2014. PDA management and in-hospital outcomes were examined for trends and variation. RESULTS: PDA was diagnosed in 5,719 (42%) VLBW infants. Cyclooxygenase inhibitors and/or ligation were used in 74% of infants with PDA overall, however studied hospitals varied greatly in PDA management. Odds of any cyclooxygenase inhibitor or surgical treatment for PDA decreased 11% per year during the study period. This was temporally associated with improved survival but also with increasing bronchopulmonary dysplasia, periventricular leukomalacia, retinopathy of prematurity, and acute renal failure in unadjusted analyses. There was no detectable correlation between hospital-specific changes in PDA management and hospital-specific changes in outcomes of preterm birth during the study period. CONCLUSION: Use of cyclooxygenase inhibitors and ligation for PDA in VLBW infants decreased over a 10-y period at the studied hospitals. Further evidence is needed to assess the impact of this change in PDA management.

Treatment of Patent Ductus Arteriosus with Cyclo-oxygenase Inhibitors beyond 2 Weeks of Age in Very Low Birth Weight Infants.

Background Cyclo-oxygenase inhibitors (COX-I) treatment of patent ductus arteriosus (PDA) in very low birth weight (VLBW) infants during the early postnatal period is well established, but their use beyond early postnatal period is not well studied. Objective The objective of this study was to determine the effectiveness of postnatal COX-I for PDA treatment beyond 2 weeks of age in VLBW infants. Study Design A retrospective cohort of VLBW infants admitted to two tertiary NICUs between 1990 and 2008 were studied. Infants with symptomatic PDA were treated with COX-I and infants with failed medical treatment were candidates for surgical ligation. Effectiveness of COX-I treatment, measured by the need for surgical ligation, was compared between early (day of life [DOL] < 14, early treatment group [ETG]) and late (DOL ≥ 14, late treatment group [LTG]) treatment groups. Results Of the 1,289 infants with PDA, 1,082 (84%) were treated with COX-I; 1,046 (97%) infants were in ETG and 36 (3%) in LTG. PDA ligation rates after COX-I treatment were 15% in ETG and 14% in LTG (p-value: not significant). There were no significant differences in demographics or morbidities between the two groups. Conclusions In VLBW infants, late treatment of PDA with COX-I was as effective as early treatment. Trial of late COX-I treatment is warranted for symptomatic PDA before surgical treatment.

Effect of maternal voice on proportion of oral feeding in preterm infants.

OBJECTIVE: To determine the impact of maternal voice exposure on oral feeding in preterm infants. STUDY DESIGN: Prospective, unblinded, 2-center intervention study of infants born 28 0/7-34 6/7 weeks gestation. Infants were exposed twice daily to maternal voice for 20 min before attempting oral feeding. Feedings were divided into groups consisting of Baseline, Intervention, and Follow-up feeds. The study was registered at clinicaltrials.gov (NCT05181020). RESULT: 29/37 (78%) mother-infant dyads consented for the study. 25 infants with 2051 feedings were included. Compared to the preceding Baseline, Intervention feeds were associated with an adjusted 7.1 percentage-point increase in oral intake (p = 0.036) and in post-hoc analysis a 71% increased likelihood of having the highest feeding readiness score (p = 0.003). CONCLUSION: Exposure to maternal voice prior to enteral feeding is feasible and was associated with significantly improved oral feeding proportions in preterm infants. CLINICAL TRIAL REGISTRY: clinicaltrials.gov (NCT05181020).

Health disparities in preterm births.

Introduction: Black African American (B/AA) women have a 2-fold to 3-fold elevated risk compared with non-Hispanic White (W) women for preterm birth. Further, preterm birth is the leading cause of mortality among B/AA infants, and among survivors, preterm infant adverse health outcomes occur disproportionately in B/AA infants. Racial inequities in maternal and infant health continue to pose a public health crisis despite the discovery >100 years ago. The purpose of this study was to expand on reported preterm infant outcome disparities. A life-course approach, accumulation of lifelong stress, including discrimination, may explain social factors causing preterm birth rate and outcome inequities in B/AA mothers. Methods: Anthropometric measures and clinical treatment information for 197 consented participants were milled from electronic health records across 4 years. The Neonatal Infant Stressor Scale was used to tally acute and chronic painful/stressful procedures. Neurobehavioral differences were investigated using the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale. Results: B/AA mothers gave birth to preterm infants earlier than W mothers. NICU hospitalization stays were extended more than 2 weeks for the significantly smaller B/AA preterm infants in comparison to the age-matched W preterm infants. A higher number of chronic lifesaving procedures with demonstrated altered stress response patterns were recorded for B/AA preterm infants. Discussion: This cross-sectional analysis of preterm birth rates and preterm infant developmental and neurodevelopmental outcomes are presented in the context of NICU stress and pain, with attendant implications for infant mortality and future health disparities. Preterm birth rate and outcome inequities further support the need to develop interventions and policies that will reduce the impact of discrimination and improve social determinants of health for Black, Indigenous, and other People of Color.

Nurses' experiences of caring for preterm infants in pain: A meta-ethnography.

Objective: Preterm infants are subjected to numerous painful procedures during their neonatal intensive care unit (NICU) hospitalization. Despite advancements in pain alleviation, nurses remain challenged to provide timely and effective pain management for preterm infants. Greater understanding of the lived experience of nurses caring for preterm infants in pain could provide novel insights to improve pain management for this vulnerable population. The aim of this meta-ethnography was to synthesize and interpret qualitative findings of nurses' experiences of taking care of preterm infants in pain. Methods: An extensive literature search in PubMed, CINAHL, PsycINFO, Scopus, BIOSIS and ProQuest Dissertation and Theses Database was conducted, including studies within the past 10 years. Two nursing researchers conducted data extraction and analysis independently. Inclusion criteria were applied to search for qualitative studies of nurse participants who worked in the NICU taking care of preterm infants. Studies published in a language other than English, articles that did not include qualitative data and qualitative data that could not be extracted from the findings or did not discuss nurses' experiences were excluded. Critical Appraisal Skills Programme was used for literature quality evaluation. Results: Eight studies remained after further screening according to inclusion and exclusion criteria. These eight studies were conducted from 2013 to 2018 and totally enrolled 205 nurses from Iran, Canada, the United States, Finland, Sweden, Switzerland, and Australia. Five themes emerged on the nurses' perspectives of taking care of preterm infants in pain: 1) They sense the neonatal pain; 2) Adverse consequences of unrelieved pain; 3) Barriers of managing pain; 4) Concerns of available approaches for pain relief; 5) Failure to work with parents. Conclusions: This meta-ethnography identified nurses' understanding of pain in preterm infants that can be assessed, and they acknowledged that unrelieved pain could cause developmental deficits in infants. The barriers are lack of training and support on pain assessment and intervention in preterm infants. Optimizing workload and environment, developing age-specified pain assessment and intervention, receiving emotional support and training, and building up a rapport with parents are urgent needs for nurses to provide better care to infants having pain.

Optimizing High-risk Infant Follow-up in Nonresearch-based Paradigms: The New England Follow-up Network.

OBJECTIVES: To establish the first regional quality improvement collaborative solely dedicated to follow-through care of high-risk infants after Neonatal intensive care unit (NICU) discharge and to characterize extremely low birth weight (ELBW) follow-up in New England. METHODS: Eleven of 14 follow-up programs in New England partnered with the Vermont Oxford Network (VON) ELBW project for an initial data collection project. We collected information about the health status and developmental outcomes of infants born ≤1,000 g or younger than 28 weeks 2014-2016 at the 18-24 months corrected for gestational age (CGA) follow-up visit. VON collected and compiled the data. RESULTS: Of 993 eligible infants, 516 (52.0%) had follow-up visits. The rehospitalization rate was 33.9%, mostly respiratory illness. Ninety-six children (19.3%) had weight less than 10th percentile and 44 (8.9%) had weight less than third percentile at 18-24 months. Only 170 (61.4%) children had recommended hearing screening after NICU discharge. Forty-six (9.1%) had cerebral palsy; 81 of the 441 infants that completed all 3 sections of the Bayley Scales of Infant Development, third edition (18.4%) had any composite score less than 70. Over half of the social and demographic data were missing. CONCLUSION: Most quality initiatives in neonatology stop at NICU discharge. This first project by the New England Follow-up Network showed a low rate for clinical follow-up. It demonstrated many opportunities to improve postdischarge follow-through specific to NICU-based care. Future projects will aim to improve the quality of follow-through services through collaborative learning, data sharing, and comparative outcomes.

Comparison of Types of Breast Milk Fortification at Discharge from the Neonatal Intensive Care Unit and Breast Milk Feeding Rates and Growth at 4 Months Corrected Age.

Background: Effects of breast milk (BM) enhancement on long-term BM feeding in preterm infants discharged from the neonatal intensive care unit (NICU) have not been examined previously. This study compares any BM feeding rates at 4 months corrected age (CA) in preterm infants discharged from the NICU on BM enhancement by fortification of expressed BM with infant formula additives (BM-F) versus BM supplemented with infant formula feeds (BM-S). Subjects and Methods: We compared infants born between January 1, 2013, and December 31, 2017, with gestational age <32 weeks or birth weight <1500 g, discharged home on BM-F or BM-S from two NICUs and followed at 4 months CA. Multivariate logistic regression with propensity scoring estimated the adjusted associations between nutrition at discharge and any BM feeding at 4 months CA. Results: Two hundred eighty-five infants were followed at 4 months CA. Infants discharged on BM-F were more likely to have mothers with multiple gestation, private insurance and not Caucasian, initiate feeds of human milk, be discharged from NICU-1, and receive any BM at 4 months CA (p < 0.03). No significant difference in growth parameters <10th percentile at 4 months CA was observed between the two groups. After adjusting for confounding factors, discharge from the NICU on BM-F was significantly associated with BM feeding at 4 months CA (odds ratio: 3.89, 95% confidence interval 1.66-9.14, p = 0.002). Conclusion: In this observational study, preterm infants receiving BM fortified with formula powder additives at discharge from the NICU had better BM feeding outcomes without poor growth at 4 months CA relative to those infants receiving BM supplemented with infant formula feeds.

Clinical and nutritional outcomes of two liquid human milk fortifiers for premature infants.

BACKGROUND: In preterm infants fortification of human milk with human milk fortifiers (HMF) to optimize nutrition and growth is standard practice. We compared clinical, nutrition and growth outcomes in infants receiving two types of liquid HMF (LHMF). METHODS: Clinical, nutrition and growth outcomes were compared between infants admitted to a level IV NICU, and born with birth weight less than or equal to 1800 grams, between 10/1/2014-12/31/2014 and received human milk with acidified LHMF (ALHMF) and between 1/1/2015-4/31/2015 and received human milk with heat treated LHMF (HTLHMF). RESULTS: Of the 85 qualifying infants, 67 received human milk and LHMF. ALHMF group had significantly higher incidence of metabolic acidosis and lower bicarbonate and base excess levels relative to infants receiving HTLHMF (P < 0.001). There were no significant differences by LHMF status in other clinical outcomes and nutrition and growth outcomes. In multivariate analyses, ALHMF use was associated with metabolic acidosis, and lower base excess and bicarbonate levels. CONCLUSION: In our study, the clinical, nutrition and growth outcomes between the two LHMF groups were similar. However, use of ALHMF in preterm infants was associated with increased incidence of metabolic acidosis in our cohort. Further randomized control trials are warranted to evaluate these findings.

Clinical presentation and treatment of transfusion-associated babesiosis in premature infants.

We review here 7 cases of neonatal transfusion-associated babesiosis at a NICU in the northeast United States. Transfusion from 2 infected units of blood resulted in the 7 cases described. The clinical presentation was highly variable in this cohort; the extremely low birth weight neonates were the most severely affected. Antibiotic therapy was effective in neonates with mild and asymptomatic infection; however, double-volume exchange blood transfusion with prolonged multidrug treatment was required for the 2 most severe cases. The risk of Babesia microti infection is not eliminated through current blood-bank practices. Neonatologists in endemic areas should have a high index of suspicion for babesiosis in premature infants exposed to blood transfusions.

Neurodevelopmental and growth outcomes of extremely low birth weight infants who are transferred from neonatal intensive care units to level I or II nurseries.

OBJECTIVE: Transfer of clinically stable infants to level I and II nurseries alleviates demands on NICUs and allows better use of beds and resources. This study compared growth, neurodevelopmental impairments, postdischarge rehospitalization and deaths, and compliance for follow-up assessment at 18 to 22 months' corrected age of extremely low birth weight infants who transferred to level I and II nurseries with those who continued to receive care to discharge in a NICU. METHODS: A retrospective analysis of prospectively collected data from the National Institute of Child Health and Human Development Neonatal Research Network was performed. Between January 1998 and June 2002, 4896 infants born with birth weights of 401 to 1000 g and cared for in 19 National Institute of Child Health and Human Development Neonatal Research Network centers were included. The sample consisted of 4392 survivors who received continuing care in the NICU to discharge home and 504 infants who were transferred to level I and II nurseries before discharge home. Demographics, perinatal characteristics, growth, and neurodevelopmental impairments were compared. Bivariate and logistic regression analyses were performed. RESULTS: Transfer of infants to level I and II nurseries was associated significantly with white race, private insurance, outborn status, and lower neonatal morbidities and compliance for follow-up compared with the NICU group. After adjusting for known covariates, transfer to level I and II nurseries was not associated with neurodevelopmental impairments or death; however, it was associated with increased postdischarge rehospitalization. CONCLUSIONS: Extremely low birth weight infants who are transferred to level I and II nurseries have similar growth and neurodevelopmental outcomes to infants who are discharged from a NICU. They are, however, more likely to be readmitted to the hospital and are less compliant for follow-up. Establishment of consistent guidelines for comprehensive discharge planning for level I and II nurseries may improve follow-up compliance and reduce rehospitalization rates among these infants who are transferred.

A retrospective study of length of hospital stay in infants treated for neonatal abstinence syndrome with methadone versus oral morphine preparations.

PURPOSE: Length of hospital stay (LOS) of infants treated for neonatal abstinence syndrome (NAS) with methadone was compared to LOS of those treated with an oral morphine preparation (OMP, neonatal morphine solution, or deodorized tincture of opium). METHODS: A retrospective review of medical records of infants treated for NAS due to in utero exposure to methadone and/or illicit drugs such as heroin or morphine was performed for birthweight, neonatal abstinence scores, infant and maternal illicit drug exposure history, maternal methadone dose (if any), and details of treatment. Length of stay was the primary outcome measure. RESULTS: Forty-six infants met the inclusion criteria. The median LOS of infants treated with methadone versus OMP was not significant (P > 0.05). Prolonged LOS was associated with larger pharmacological treatment doses required to control withdrawal symptoms, larger maternal methadone dose, and increased birthweight. After adjusting for these factors, exposure to opioids in utero, maternal nicotine use, hospital of treatment, severity of withdrawal symptoms, and foster care placement were not significantly associated with LOS in univariate or multivariate analyses. CONCLUSIONS: These results suggest that infants treated with OMP or methadone have similar LOS. Longer LOS is associated with both higher maternal methadone doses and higher opioid treatment dose requirements after birth. The potential effect of maternal methadone dose on neonatal LOS should be considered when treating expectant mothers on methadone maintenance therapy.