A Flipped Classroom Pilot in Neonatal Mechanical Ventilation.

Background: Pediatric residents frequently manage critically ill neonates but have limited systematic training in mechanical ventilation (MV). Competing demands, varying learner levels, and topic complexity contribute to inconsistent education. A blended learning approach may be ideally suited to achieve meaningful learning but has not been described for this topic and learner. Objective: To design, implement, and evaluate a flipped classroom for pediatric residents in neonatal MV. Methods: We used Kern's six-step framework for curricular development to create a flipped classroom curriculum in neonatal MV. Individual prework included interaction with six prerecorded animated whiteboard videos, while in-person learning occurred in small groups at the bedside of a ventilated infant. A mixed-methods evaluation included surveys, quantitative knowledge test scores (before, immediately after, and six months after course completion), and qualitative analysis of participant focus groups. Results: Twenty-six learners participated in the curriculum. Mean knowledge test scores rose and were sustained after course completion (51% baseline, 82% immediate posttest, 90% retention; P < 0.001). Learners identified various design elements, technology affordances, and instructor factors as meaningful, and they identified unexpected impacts of the curriculum beyond knowledge acquisition, including effects on professional identities, interdisciplinary communication skills, and contribution to the culture of safety. Conclusion: This curriculum aligned with resident roles, was meaningful to learners, and led to long-term increases in knowledge scores and access to quality education; flipped classroom design using meaningful learning theory and leveraging animated whiteboard technology may be a useful strategy for other highly complex topics in graduate medical education.

Social Determinants of Health and Redirection of Care for Infants Born Extremely Preterm.

Importance: Redirection of care refers to withdrawal, withholding, or limiting escalation of treatment. Whether maternal social determinants of health are associated with redirection of care discussions merits understanding. Objective: To examine associations between maternal social determinants of health and redirection of care discussions for infants born extremely preterm. Design, Setting, and Participants: This is a retrospective analysis of a prospective cohort of infants born at less than 29 weeks' gestation between April 2011 and December 2020 at 19 National Institute of Child Health and Human Development Neonatal Research Network centers in the US. Follow-up occurred between January 2013 and October 2023. Included infants received active treatment at birth and had mothers who identified as Black or White. Race was limited to Black and White based on service disparities between these groups and limited sample size for other races. Maternal social determinant of health exposures were education level (high school nongraduate or graduate), insurance type (public/none or private), race (Black or White), and ethnicity (Hispanic or non-Hispanic). Main Outcomes and Measures: The primary outcome was documented discussion about redirection of infant care. Secondary outcomes included subsequent redirection of care occurrence and, for those born at less than 27 weeks' gestation, death and neurodevelopmental impairment at 22 to 26 months' corrected age. Results: Of the 15 629 infants (mean [SD] gestational age, 26 [2] weeks; 7961 [51%] male) from 13 643 mothers, 2324 (15%) had documented redirection of care discussions. In unadjusted comparisons, there was no significant difference in the percentage of infants with redirection of care discussions by race (Black, 1004/6793 [15%]; White, 1320/8836 [15%]) or ethnicity (Hispanic, 291/2105 [14%]; non-Hispanic, 2020/13 408 [15%]). However, after controlling for maternal and neonatal factors, infants whose mothers identified as Black or as Hispanic were less likely to have documented redirection of care discussions than infants whose mothers identified as White (Black vs White adjusted odds ratio [aOR], 0.84; 95% CI, 0.75-0.96) or as non-Hispanic (Hispanic vs non-Hispanic aOR, 0.72; 95% CI, 0.60-0.87). Redirection of care discussion occurrence did not differ by maternal education level or insurance type. Conclusions and Relevance: For infants born extremely preterm, redirection of care discussions occurred less often for Black and Hispanic infants than for White and non-Hispanic infants. It is important to explore the possible reasons underlying these differences.

Early-Life Outcomes in Relation to Social Determinants of Health for Children Born Extremely Preterm.

OBJECTIVE: To characterize the relationships between social determinants of health (SDOH) and outcomes for children born extremely preterm. STUDY DESIGN: This is a cohort study of infants born at 22-26 weeks of gestation in National Institute of Child Health and Human Development Neonatal Research Network centers (2006-2017) who survived to discharge. Infants were classified by 3 maternal SDOH: education, insurance, and race. Outcomes included postmenstrual age (PMA) at discharge, readmission, neurodevelopmental impairment (NDI), and death postdischarge. Regression analyses adjusted for center, perinatal characteristics, neonatal morbidity, ethnicity, and 2 SDOH (eg, group comparisons by education adjusted for insurance and race). RESULTS: Of 7438 children, 5442 (73%) had at least 1 risk-associated SDOH. PMA at discharge was older (adjusted mean difference 0.37 weeks, 95% CL 0.06, 0.68) and readmission more likely (aOR 1.27, 95% CL 1.12, 1.43) for infants whose mothers had public/no insurance vs private. Neither PMA at discharge nor readmission varied by education or race. NDI was twice as likely (aOR 2.36, 95% CL 1.86, 3.00) and death 5 times as likely (aOR 5.22, 95% CL 2.54, 10.73) for infants with 3 risk-associated SDOH compared with those with none. CONCLUSIONS: Children born to mothers with public/no insurance were older at discharge and more likely to be readmitted than those born to privately insured mothers. NDI and death postdischarge were more common among children exposed to multiple risk-associated SDOH at birth compared with those not exposed. Addressing disparities due to maternal education, insurance coverage, and systemic racism are potential intervention targets to improve outcomes for children born preterm.

Copeptin levels in hospitalized infants and children with suspected vasopressin-dependent disorders: a case series.

OBJECTIVES: There have been recent advances assessing copeptin levels in adults with suspected disorders of vasopressin release. Very limited data exits on copeptin levels in children and infants, especially in a critically-ill hospitalized population where hyper- and hypo-natremia are very common. Our objective is to describe the institutional experience assessing copeptin levels in hospitalized infants and children with hyper- or hypo-natremia. METHODS: We performed a single-center retrospective case series of all infants, children, and adolescents who had an ultrasensitive plasma copeptin level obtained between 2019-2021. RESULTS: A total of 29 critically ill patients (6 infants) were identified with 38 % of patients having copeptin levels after neurosurgical procedures for tumors or trauma. Approximately 13/17 children with hypernatremia had central diabetes insipidus (central diabetes insipidus) to diagnose CDI, A copeptin level ≤ 4.9 pmol/L resulted in an 88 % sensitivity (95 % CI 47-99 %), and 66 % specificity (95 % CI 30-93 %). Amongst those with hyponatremia levels were more variable, 8/12 children had syndrome of inappropriate antidiuresis (SIAD) with copeptin levels ranging 4.7-72.6 pmol/L. CONCLUSIONS: While difficult to conclude due to multiple limitations, this case series highlights that typical copeptin cutoffs used to diagnose DI in adults in an ambulatory setting may also translate to a critically-ill pediatric population. Large prospective studies are needed to confirm this observation. In addition, postoperative copeptin levels could potentially be utilized as an additional marker to predict permanent from transient DI, but much larger studies are needed. Further work is needed to establish normative copeptin levels in infants and patients with SIAD.

Poor Neonatal Adaptation After Antidepressant Exposure During the Third Trimester in a Geographically Defined Cohort.

Objective: To examine the associations between antidepressant exposure during the third trimester of pregnancy, including individual drugs, drug doses, and antidepressant combinations, and the risk of poor neonatal adaptation (PNA). Patients and Methods: The Rochester Epidemiology Project medical records-linkage system was used to study infants exposed to selective serotonin reuptake inhibitors (SSRIs; n=1014), bupropion, (n=118), serotonin-norepinephrine reuptake inhibitors (n=80), antidepressant combinations (n=20), or other antidepressants (n=22) during the third trimester (April 11, 2000-December 31, 2013). Poor neonatal adaptation was defined based on a review of medical records. Poisson regression was used to examine the risk of PNA with serotonergic antidepressant and drug combinations compared with that with bupropion monotherapy as well as with high- vs standard-dose antidepressants. When possible, analyses were performed using propensity score (PS) weighting. Results: Forty-four infants were confirmed cases of PNA. Serotonin-norepinephrine reuptake inhibitor monotherapy, antidepressant combinations, and paroxetine monotherapy were associated with a significantly higher risk of PNA than bupropion monotherapy in unweighted analyses. High-dose SSRI exposure was associated with a significantly increased risk of PNA in unadjusted (relative risk, 2.61; 95% confidence interval, 1.35-5.04) and PS-weighted models (relative risk, 2.29; 95% confidence interval, 1.17-4.48) compared with standard-dose SSRI exposure. The risk of PNA was significantly higher with high-dose paroxetine and sertraline than with standard doses in the PS-weighted analyses. The other risk factors for PNA included maternal anxiety disorders. Conclusion: Although the frequency of PNA in this cohort was low (3%-4%), the risk of PNA was increased in infants exposed to serotonergic antidepressants, particularly with SSRIs at higher doses, during the third trimester of pregnancy compared with that in infants exposed to standard doses. Potential risk factors for PNA also included third-trimester use of paroxetine (especially at higher doses) and maternal anxiety.

Relationships between retinopathy of prematurity without ophthalmologic intervention and neurodevelopment and vision at 2 years.

BACKGROUND: Severe retinopathy of prematurity (ROP) is associated with adverse outcomes. Relationships between milder ROP and outcomes have not been defined. We hypothesized that children with ROP stage ≤3 who did not receive ophthalmologic intervention would have worse motor, cognitive, and language skills and more vision abnormalities than children without ROP. METHODS: This was a secondary analysis of a randomized trial evaluating the effects of myo-inositol on ROP in the NICHD Neonatal Research Network. Primary outcomes were Bayley Scales of Infant Development composite scores; secondary outcomes included behavioral difficulties and ophthalmologic measures. Outcomes were compared using adjusted linear or modified Poisson models. RESULTS: Of 506 children, 173 (34%) had no ROP, 262 (52%) had ROP stage ≤3 without intervention, and 71 (14%) had ROP with intervention. There was no difference in motor, cognitive, or language scores between children with ROP stage ≤3 without intervention and children without ROP. Children with ROP stage ≤3 without intervention had a higher rate of strabismus compared to children without ROP (p = 0.040). CONCLUSION: Children with ROP stage ≤3 without intervention did not have adverse neurodevelopmental outcomes at 2 years' corrected age compared to children without ROP but did have an increased incidence of strabismus. IMPACT: This study addresses a gap in the literature regarding the relationship between milder forms of retinopathy of prematurity (ROP) that regress without intervention and neurodevelopment and vision outcomes. Children with a history of ROP stage ≤3 without intervention have similar neurodevelopmental outcomes at 2 years' corrected age as children born extremely preterm without a history of ROP and better outcomes than children with a history of ROP with ophthalmologic intervention. Counseling about likely neurodevelopment and vision outcomes for children born extremely preterm with a history of ROP may be tailored based on the severity of ROP. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: Inositol to Reduce Retinopathy of Prematurity Trial: NCT01954082.

Sociodemographic factors and family use of remote infant viewing in neonatal intensive care.

OBJECTIVE: We aimed to determine whether the use of remote infant viewing (RIV) in a neonatal intensive care unit (NICU) differed based on maternal sociodemographic factors. METHODS: The number of RIV camera views and view duration were obtained for NICU patients between 10/01/2019 and 3/31/2021 and standardized relative to patient days. Maternal sociodemographic and neonatal characteristics were obtained from institutional databases. RESULTS: Families in which mothers were unmarried (aOR 1.42, 95% CI 1.03-1.95), did not require an interpreter (aOR 2.86, 95% CI 1.54-5.32), were multiparous (aOR 1.56, 95% CI 1.16-2.10), delivered prior to 37 weeks' gestation (aOR 1.57, 95% CI 1.17-2.12), or resided ≥50 miles from the NICU (aOR 1.38, 95% CI 1.02-1.87) were significantly more likely to use RIV. CONCLUSION: Family use of RIV in the NICU varied by multiple sociodemographic factors. Further investigation to understand and to address potential equity gaps revealed or created by RIV are warranted.

Family Use of Remote Infant Viewing in the Neonatal Intensive Care Unit: Impact of the COVID-19 Pandemic and Patient Room Type.

Background: Remote infant viewing (RIV) uses a bedside camera to allow families to view a livestream video of their neonate 24/7 from anywhere with internet access. Objective: The aim of this study was to evaluate family use of RIV for infants in the neonatal intensive care unit (NICU) during the COVID-19 pandemic and whether RIV use varied by patient room type. Study Design: Use of RIV was evaluated for NICU patients between October 1, 2019, and March 31, 2021. The date, time, and duration of every RIV were exported from the RIV database and linked to the patient's room type. Results: Among 980 patients, 721 (73.6%) were viewed using RIV. The median (interquartile range) number of views per patient-days was 12.5 (5.4-26.0). Based on monthly aggregate data, the proportion of patients with at least one RIV increased during the pandemic from 71.6% in April 2020 to 94.3% in March 2021 (p < 0.001). The monthly number of views and view duration per patient-days also increased (p = 0.003; p = 0.029, respectively). When evaluating patient-level data by room type, the median number of views per patient-days was higher for open-bay than single-family rooms (13.5 vs. 10.5; p < 0.001) and median view duration (minutes) per patient-days was longer (21.8 vs. 12.1; p < 0.001). Conclusions: Use of RIV in the NICU increased during the COVID-19 pandemic. RIV was used more frequently and for longer duration by families with newborns in an open-bay room. RIV allows families to observe their newborn when visitor restrictions are in place or when in-person visits may be less private or do not allow for physical distancing.

Incidence of and Neurodevelopmental Outcomes After Late-Onset Meningitis Among Children Born Extremely Preterm.

Importance: Late-onset meningitis (LOM) has been associated with adverse neurodevelopmental outcomes in children born extremely preterm. Objective: To report the incidence of LOM during birth hospitalization and neurodevelopmental outcomes at 18 to 26 months' corrected age. Design, Setting, and Participants: This cohort study is a secondary analysis of a multicenter prospective cohort of children born at 22 to 26 weeks' gestation between 2003 and 2017 with follow-up from 2004 to 2021. The study was conducted at 25 Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers. Exposures: Culture-confirmed LOM. Main Outcomes and Measures: Incidence and microbiology of LOM (2003-2017); lumbar puncture (LP) performance in late-onset sepsis (LOS) evaluations (2011-2017); composite outcome of death or neurodevelopmental impairment (NDI; 2004-2021). Results: Among 13 372 infants (median [IQR] gestational age, 25.4 [24.4-26.1] weeks; 6864 [51%] boys), LOM was diagnosed in 167 (1%); LOS without LOM in 4564 (34%); and neither LOS nor LOM in 8641 (65%). The observed incidence of LOM decreased from 2% (95% CI, 1%-3%) in 2003 to 0.4% (95% CI, 0.7%-1.0%) in 2017 (P < .001). LP performance in LOS evaluations decreased from 36% (95% CI, 33%-40%) in 2011 to 24% (95% CI, 21%-27%) in 2017 (P < .001). Among infants with culture-confirmed LOS, LP performance decreased from 58% (95% CI, 51%-65%) to 45% (95% CI, 38%-51%; P = .008). LP performance varied by center among all LOS evaluations (10%-59%, P < .001) and among those with culture-confirmed LOS (23%-79%, P < .001). LOM occurred in the absence of concurrent LOS in 27 of 167 cases (16%). The most common LOM isolates were coagulase-negative Staphylococcus (98 [59%]), Candida albicans (38 [23%]), and Escherichia coli (27 [16%]). Death or NDI occurred in 22 of 46 children (48%) with LOM due to coagulase-negative Staphylococcus, 43 of 67 (64%) due to all other bacterial pathogens, and 26 of 33 (79%) due to fungal pathogens. The adjusted relative risk of death or NDI was increased among children with LOM (aOR, 1.53; 95% CI, 1.04-2.25) and among those with LOS without LOM (aOR, 1.41; 95% CI, 1.29-1.54) compared with children with neither infection. Conclusions and Relevance: In this cohort study, LP was performed with decreasing frequency, and the observed incidence of LOM also decreased. Both LOM and LOS were associated with increased risk of death or NDI; risk varied by LOM pathogen. The full association of LOM with outcomes of children born extremely preterm may be underestimated by current diagnostic practices.

Evaluation and Management of Noncardiac Comorbidities in Children With Congenital Heart Disease.

Outcomes for patients with neonatal heart disease are affected by numerous noncardiac and genetic factors. These can include neonatal concerns, such as prematurity and low birth weight, and congenital anomalies, such as airway, pulmonary, gastrointestinal, and genitourinary anomalies, and genetic syndromes. This section will serve as a summary of these issues and how they may affect the evaluation and management of a neonate with heart disease. These noncardiac factors are heavily influenced by conditions common to neonatologists, making a strong argument for multidisciplinary care with neonatologists, cardiologists, surgeons, anesthesiologists, and cardiovascular intensivists. Through this section and this project, we aim to facilitate a comprehensive approach to the care of neonates with congenital heart disease.

Refining interpretation of transcutaneous bilirubin measurement in newborns born late preterm.

BACKGROUND: Transcutaneous bilirubin (TCB) monitoring is widely used for jaundice screening in the newborn period. Limited data exists on adjusting TCB for bias in late preterm infants. The objective of this study was to determine the median bias between transcutaneous bilirubin and total serum bilirubin levels in newborns born at 35-36 weeks' gestation. METHODS: This was a retrospective cohort study of late preterm infants born at 35-0/7 to 36-6/7 weeks' gestation who were admitted to a level III neonatal intensive care unit from May 2018 to February 2020. Transcutaneous and total serum bilirubin levels were assessed within 2 h of each other during the first 60 h of life. Bland-Altman plots were used to evaluate transcutaneous bilirubin bias. Bilirubin risk stratification based on age (in hours) was done using an adaptation of the Bhutani nomogram for transcutaneous, adjusted transcutaneous, and total serum bilirubin measurements. RESULTS: The median bias between transcutaneous and total serum bilirubin bias was 2.4 mg/dL (IQR 1.7-3.4, 95% CI 2.2-2.7). The kappa statistic demonstrated slight agreement between the unadjusted transcutaneous bilirubin and total serum bilirubin (k = 0.033, p = 0.194. The kappa statistic demonstrated fair agreement between an adjusted transcutaneous bilirubin (subtract 1 mg/dL) and total serum bilirubin (k = 0.298, p < 0.0001) and moderate agreement between another adjusted transcutaneous bilirubin (subtract 2 mg/dL) and total serum bilirubin (k = 0.430, p < 0.0001). CONCLUSION: In a single center study of late preterm infants, transcutaneous bilirubin systematically overestimated the total serum bilirubin level. Subtracting 1 mg/dL from the transcutaneous bilirubin identified infants with total serum bilirubin levels in the high or high intermediate risk range. Adjusting the transcutaneous bilirubin prior to risk stratification may reduce unnecessary blood draws for total serum bilirubin. Studies of racially and ethnically diverse newborns using various transcutaneous bilirubin meters are needed prior to broad application of the adjusted transcutaneous bilirubin approach.

Online clinical tool to estimate risk of bronchopulmonary dysplasia in extremely preterm infants.

OBJECTIVE: Develop an online estimator that accurately predicts bronchopulmonary dysplasia (BPD) severity or death using readily-available demographic and clinical data. DESIGN: Retrospective analysis of data entered into a prospective registry. SETTING: Infants cared for at centres of the United States Neonatal Research Network between 2011 and 2017. PATIENTS: Infants 501-1250 g birth weight and 23 0/7-28 6/7 weeks' gestation. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Separate multinomial regression models for postnatal days 1, 3, 7, 14 and 28 were developed to estimate the individual probabilities of death or BPD severity (no BPD, grade 1 BPD, grade 2 BPD, grade 3 BPD) defined according to the mode of respiratory support administered at 36 weeks' postmenstrual age. RESULTS: Among 9181 included infants, birth weight was most predictive of death or BPD severity on postnatal day 1, while mode of respiratory support was the most predictive factor on days 3, 7, 14 and 28. The predictive accuracy of the models increased at each time period from postnatal day 1 (C-statistic: 0.674) to postnatal day 28 (C-statistic 0.741). We used these results to develop a web-based model that provides predicted estimates for BPD by postnatal day. CONCLUSION: The probability of BPD or death in extremely preterm infants can be estimated with reasonable accuracy using a limited amount of readily available clinical information. This tool may aid clinical prognostication, future research, and center-specific quality improvement surrounding BPD prevention. TRIAL REGISTRATION NUMBER: NCT00063063.

Association of outborn versus inborn birth status on the in-hospital outcomes of neonates treated with therapeutic hypothermia: A propensity score-weighted cohort study.

OBJECTIVE: To compare the risk of in-hospital mortality and morbidity between outborn and inborn neonates treated with whole body hypothermia. METHODS: The association of outborn birth status with in-hospital mortality and morbidity, prior to NICU discharge or transfer, was assessed in a large historical cohort of neonates who had therapeutic hypothermia initiated on the day of birth. The cohort was restricted to neonates born at ≥35 weeks gestational age from 2007 to 2018. Since the sample was non-random, inverse probability weighting (IPW) derived from propensity scores was used to reduce imbalance in baseline maternal and neonatal characteristics between outborn and inborn neonates. Cox proportional hazards regression was used to assess the association between outborn status and in-hospital mortality. RESULTS: There were 4447 neonates included in the study (2463 outborn). Outborn status was not significantly associated with an increased risk of in-hospital mortality in the unadjusted cohort (HR = 1.17, 95% CI 0.97-1.42, p = 0.10) or IPW cohort (HR = 1.09, 95% CI 0.95-1.26, p = 0.22). However, in the IPW cohort, outborn neonates were significantly more likely to have seizures (28% vs 24%, p = 0.006), anticonvulsant exposure (46% vs 41%, p = 0.002), and gastrostomy tube placement (5.8% vs 3.8%, p = 0.009) during their newborn hospitalization. CONCLUSION: Outborn status was not significantly associated with increased in-hospital mortality among neonates treated with whole body hypothermia. However, outborn neonates were more likely to have seizures, receive anticonvulsant treatment, and undergo gastrostomy tube placement. Further study is needed to better understand the etiologies of these outcome disparities and potential implications for long-term neurodevelopmental outcomes.

Profound Hypotonia and Respiratory Failure due to Suspected Nemaline Myopathy in a Preterm Infant.

Congenital myopathies, such as nemaline myopathy, may present with hypotonia and respiratory failure in the neonatal period. Respiratory function can be further compromised in affected infants by the development of chylous effusions. We present the case of a preterm male infant born at 32 6/7 weeks' gestation, who was profoundly hypotonic and required intubation at birth. His clinical course progressed from acute to chronic respiratory failure with mechanical ventilation dependence. He developed bilateral chylous pleural effusions during the newborn period. Whole exome sequencing identified an ACTA1 gene mutation leading to the presumed diagnosis of nemaline myopathy. This case highlights the need to include congenital myopathies in the differential for a preterm newborn with hypotonia and respiratory failure.

The relationship of neurodevelopmental impairment to concurrent early childhood outcomes of extremely preterm infants.

OBJECTIVE: Determine how neurodevelopmental impairment (NDI) relates to concurrent outcomes for children born extremely preterm. STUDY DESIGN: Retrospective cohort study children born 22 0/7-26 6/7 weeks' gestation at NICHD Neonatal Research Network hospitals. Outcomes were ascertained at 18-22 months' corrected age. RESULT: Of 6562 children, 2618 (40%) died and 441 (7%) had no follow-up. Among the remaining 3483 children, 825 (24%), 1576 (45%), 657 (19%), and 425 (12%) had no, potential/mild, moderate, and severe NDI, respectively. Rehospitalization, respiratory medications, surgery, and medical support services were associated with greater NDI severity but affected >10% of children without NDI. Rehospitalization occurred in 40% of children with no NDI (mean (SD): 1.7 (1.3) episodes). CONCLUSION: Medical, functional, and social outcomes at 18-22 months' corrected age were associated with NDI; however, many children without NDI were affected. These data should contribute to counseling families and the design of studies for childhood outcomes beyond NDI.

Long-term outcome of brain structure in female preterm infants: possible associations of liberal versus restrictive red blood cell transfusions.

BACKGROUND: Preterm infants who receive differential red blood cell (RBC) transfusions at birth may show brain structure differences across development, including abnormalities in white matter (WM) structure and organization. This study investigated long-term outcomes of brain structure in female infants born preterm, at an average age of 13 years old, who received red blood cell (RBC) transfusions in the neonatal period according to a liberal or restrictive approach. Results from this study will increase understanding of the effects of transfusion on the developing brain. STUDY DESIGN AND METHODS: This follow-up study included female preterm infants who participated in a clinical trial and had been randomized at birth to either a liberal or restrictive hematocrit threshold. Brain structures were measured in childhood using structural magnetic resonance imaging (MRI) scans. Due to the low number of females in the restrictive transfusion group at follow-up, additional females were recruited for inclusion. Main outcome measures included cerebral and subcortical brain region volumes. RESULTS: Total intracranial volume was significantly decreased in females who were randomized to higher average hematocrit levels at birth. Infants in the liberal transfusion group had proportionately smaller volumes in all measures of regional cerebral WM and subcortical brain volumes, reaching significance for temporal lobe WM and caudate volumes. CONCLUSION: Female premature infants who received a liberal transfusion threshold at birth had decreased WM volumes, which suggests the potential long-term neurodevelopmental risks associated with liberal transfusion practices.