The Journal of Pediatrics

BACKGROUND AND OBJECTIVESex chromosome trisomies (SCT), including XXY, XYY, and XXX syndromes, have been historically underdiagnosed. Noninvasive prenatal cell-free DNA screening has significantly increased identification of these conditions, leading to a need for pediatric care for a growing population of newborns with SCT. Our goal was to analyze and compare perinatal features, medical diagnoses, and physical features in infants with prenatal identification of SCT conditions through the first year of life. METHODSThe eXtraordinarY Babies Study is an ongoing, prospective natural history study of prenatally identified children with SCT conducted by interdisciplinary teams in Colorado and Delaware. Participants were enrolled prior to 12 months of age and had pregnancy, birth, medical histories, and physical exams completed by board-certified pediatricians at 2, 6, and/or 12-month visits. Descriptive statistics were followed by comparisons between SCT groups using t-tests or ANOVA, Fisher exact, and correlations between medical features with alpha of 0.05. Relative risks were calculated compared to general population rates. RESULTS327 infants were included in the analysis (XXY=195, XXX=79, XYY=53). Major congenital anomalies were rare (1.7%). Relative risk compared to general population was elevated for breastfeeding difficulties (51.7%;RR 2.7), positional torticollis (28.2%;RR 7.2), eczema (48.0%;RR 3.5), food allergies (19.3%;RR 2.4), constipation requiring intervention (33.9%;RR 7.6), small cardiac septal defects (7.7%;RR 17.2), and structural renal abnormalities (4.4%;RR 9.7). Inpatient hospitalization was required for 12.4%, with 59.5% of hospitalizations attributable to respiratory infections. DISCUSSIONThese findings of medical conditions with a higher prevalence can inform anticipatory guidance and medical management for pediatricians caring for infants with SCT. Article SummaryMedical findings in largest cohort of prenatally identified infants with XXY, Trisomy X, and XYY from birth to 12 months and implications for pediatric care. Whats Known on This SubjectOne in [~]500 individuals have an extra X or Y chromosome, or sex chromosome trisomy (SCT). Prenatal screening is now routinely identifying SCT, however there are few studies to guide perinatal and infant care for these individuals. What This Study AddsThis prospective observational study presents medical features for 327 infants with prenatally identified SCT from birth through the first year of life. Results identify where proactive screenings and/or interventions may be warranted for infants with SCT.

AbstractO_ST_ABSBackgroundC_ST_ABSThe increasing clinical use of combining structural MRI (sMRI) with General Movements Assessment (GMA) or Hammersmith Infant Neurological Exam (HINE) before five months corrected age (CA) for early diagnosis of cerebral palsy (CP) lacks sufficient prognostic data for children with CP, especially those with Gross Motor Function Classification System (GMFCS) I. ObjectiveEvaluate the predictive value of sMRI, GMA, and HINE individually and in combination for early CP diagnosis and assess accuracy across varying GMFCS levels in a regional cohort of preterm infants. MethodsWe performed sMRI between 39-44 weeks postmenstrual age and GMA and HINE between 12-18 weeks CA in 395 preterm infants born at [&le;]32 weeks gestation across five NICUs in Greater Cincinnati. Brain abnormalities on sMRI included white matter injuries, cortical and deep gray matter lesions, or extensive cerebellar hemorrhage. Absent fidgety movements constituted abnormal GMA; abnormal HINEs were scores <56. The primary outcome was CP diagnosis at 22-26 months CA, classified by the GMFCS. We calculated sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios for individual tests and combinations. ResultsOf 338 (86%) infants with complete follow-up, 48 (14.2%) showed sMRI abnormalities, 15 (4.6%) had abnormal GMA, and 69 (20.9%) had abnormal HINE. Thirty-nine children (11.5%) developed CP at age 2, of which 28 had GMFCS level I and 11 had GMFCS >II. The combination of sMRI and GMA achieved 100% specificity but only 22% sensitivity while the combination of abnormal sMRI and HINE demonstrated sensitivity of 32% and specificity of 98% for prediction of CP. Individual or combined tests showed far higher sensitivity (78-100%) for predicting CP in children with GMFCS levels II-V. ConclusionsThe combination of sMRI with GMA or HINE demonstrated high specificity but low sensitivity for early CP diagnosis in a regional cohort of preterm infants. This approach appears effective for early detection of CP levels II-V but not for level I cases, the most prevalent type, underscoring the need for continued developmental follow-up for all very preterm infants and need for more sensitive diagnostic tools for early detection of CP. Key PointsO_ST_ABSQuestionsC_ST_ABSWhat is the individual and combined prognostic accuracy of sMRI, GMA, and HINE for early diagnosis of CP in preterm infants? FindingsIn our prospective, regional study of preterm infants born at [&le;]32 weeks gestation, we found that combining brain abnormalities on sMRI with abnormal GMA achieved 100% specificity but 22% sensitivity for diagnosing CP. Individual or combined tests showed far higher sensitivity (78-100%) for predicting CP in children with GMFCS levels II-V. Both individual and combined tests were poor predictors of GMFCS level I CP, the most common type. MeaningWhile sMRI combined with GMA or HINE is effective for diagnosing CP with GMFCS levels II-V, this approach falls short for children with GMFCS level I.

BackgroundChildren born very preterm (< 32 weeks gestational age), are at risk for poor growth and adverse neurodevelopmental outcomes. Poor outcomes in preterm children have been attributed to the aversive sounds and relative speech paucity of the neonatal intensive care unit (NICU). Experimental studies that directly expose preterm infants to speech sounds in the NICU find significant improvements in health factors relevant for neurodevelopment. Few studies have examined whether natural variations in the speech environment of the NICU are related to short-term health outcomes in preterm infants. Such data are important for optimizing the sound environment of the NICU. ObjectiveExamine relations between the NICU speech environment and rate of weight gain during hospitalization, an important determinant of physical health and neurodevelopmental outcomes for preterm infants. MethodsParticipants were infants born very preterm (n = 20). The speech environment of each infant was assessed at 32-36 weeks postmenstrual age using a speech-counting device known as a Starling. Speech rates were averaged for each infant over the 4-week period. Average rates of weight gain (g/kg/day) were ascertained over the same period. Calories were derived from charted intake (kcals/kg/day). Linear regressions examined associations between weight gain and both caloric intake and speech counts. Control analyses explored whether effects remained after controlling for family visitation, time in incubator, and health acuity. ResultsInfants who received more calories gained more weight, accounting for more than 30% of the variance. Importantly, speech counts accounted for nearly 29% additional variance (p < .001). These effects were not reduced when controlling for family visitation, time in incubator, or health acuity. ConclusionsEnhancing speech exposure in the NICU may be beneficial for physical growth. NICU infant care plans should consider opportunities to increase speech exposure.

Objective To examine group differences and continuity in caregiving environments of infants born preterm from Spanish- and English-speaking families. Study Design We conducted a prospective cohort study of Spanish- (n = 17) and English-speaking (n = 23) families of infants born preterm (< 32 weeks gestation). Caregiver-infant engagement was assessed neonatally via hospital visitation and skin-to-skin (STS) care, and at home via child-directed adult word counts/hour (CD-AWC/hour) from all-day audio recordings. Result No significant group differences were observed in family visitation, neonatal STS care, or in-home verbal engagement, although STS care rates varied considerably, especially within Spanish-speaking families. Across both groups, greater STS care was associated with higher CD-AWC/hour at home. Conclusion Spanish- and English-speaking families showed comparable patterns of caregiver-infant engagement, as a group, however, many Spanish-speaking families engaged in less STS than English-speaking families. STS care predicted caregiver-infant verbal engagement at home, highlighting continuity from hospital to home.

ObjectiveTo evaluate whether combining abdominal ultrasound with radiography improves diagnostic accuracy and surgical risk prediction in neonates with suspected necrotising enterocolitis (NEC) compared with radiography alone. Design, setting, patientsProspective cohort study conducted in two tertiary neonatal intensive care units. Sixty-seven neonates with suspected NEC underwent concurrent abdominal radiography and ultrasound assessments. Imaging studies were independently reviewed by masked investigators using pre-specified criteria to classify each study as reassuring or non-reassuring. Main outcome measuresThe primary outcome was the need for surgical intervention. Imaging data were analysed using unsupervised k-means clustering (k = 2); logistic regression - testing associations with surgery and Principal component analysis (PCA) - to identify imaging features most contributing to group separation. ResultsUltrasounds were reassuring in all cases subsequently diagnosed with non-NEC, i.e feeding intolerance, whereas most radiographs in this group were non-reassuring. Clustering based on radiographs alone did not significantly discriminate surgical risk (58.8% vs 39.4%; p = 0.11). Combined model (radiograph + ultrasound) produced two distinct clusters with significantly different surgical rates (78.3% vs 34.1%; OR 6.96, 95% CI 2.29-24.58). PCA highlighted complex ascites, absent peristalsis, and abnormal bowel perfusion as key discriminating features. ConclusionIn suspected NEC, combining ultrasound with radiography significantly improves surgical risk stratification compared with radiography alone. A reassuring ultrasound reliably identified infants with feeding intolerance, suggesting potential to reduce unnecessary transfers and treatments. Larger multicentre studies are needed to validate these findings and inform development of a unified multimodal imaging score for NEC diagnosis. Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSO_LINEC is an acquired intestinal disease mainly affecting preterm infants with the potential risk of serious life-long co-morbidities. C_LIO_LIPlain abdominal radiography remains the standard initial investigation for suspected NEC but provides limited information on bowel perfusion and viability. C_LIO_LIEmerging evidence supports the role of bowel ultrasound in NEC, in assessing bowel wall thickness, perfusion, peristalsis, and intra-abdominal fluid collections. C_LI What this study addsO_LIUsing a multi-modal imaging approach (combining ultrasound and radiography) improved surgical risk stratification in neonates with suspected NEC compared with using radiography alone. C_LIO_LIA reassuring ultrasound may identify benign conditions initially suspected as early NEC, supporting earlier de-escalation of care. C_LIO_LIThe study findings lay the foundation for a standardised imaging-based score combining radiograph and ultrasound findings in cases with suspected NEC, to better guide diagnosis and predict the need for surgical intervention. C_LI

Background and objectivesSex chromosome trisomy (SCT) is a common chromosomal abnormality associated with increased risks for early developmental delays and neurodevelopmental disorders later in childhood. Our objective was to quantify the spectrum of early developmental milestones in SCT. We hypothesized later milestone achievement in SCT than the general population. MethodsData were collected as part of the eXtraordinarY Babies Study, a prospective natural history of developmental and health trajectories in a prenatally identified sample of infants with SCT. Parent reported, clinician-validated, early motor and language milestones were collected at 2, 6, 12, 18, 24, and 36-months. Age distributions of milestone achievement were compared with normative data. ResultsIn all SCT conditions, compared with normative data, there was increased variability and a later median age of skill development across multiple gross motor and expressive language milestones. Results also show a significant amount of overlap with the general pediatric population, suggesting that for many children with prenatally identified SCT, early milestones present within, or close to, the expected timeline. ConclusionsAs increasing numbers of infants with prenatal SCT diagnoses present at pediatric practices, we provide an evidence-based schedule of milestone achievement in SCT as a tool for pediatricians and families. Detailed data on SCT milestones can support clinical interpretation of milestone achievement. Increased variability and later median age of milestone acquisition in SCT compared to norms support consideration of all infants with SCT as high risk.

Background and ObjectivesHyperlactatemia is common in hospitalized infants. Machine learning was applied to clinical and laboratory characteristics in hospitalized infants with hyperlactatemia to identify predictors of inborn error of energy metabolism (IEEM). MethodsRetrospective cohort study of hospitalized infants aged 0-90 days (2012-2020) with a lactate [&ge;] 5 mmol/L. Final diagnosis was discretized to IEEM, cardiac, hypoxia, infectious and other. Random forest and XGBoost models were tuned and compared using cross-validation, and a final model was evaluated on an independent test set to determine ability to predict IEEM. ResultsAmong 1000 infants, median lactate was 8 mmol/L. The overall mortality rate was 30%, (N=291) and was 51% (N=21) among infants with an IEEM (N=41). Lactate was significantly higher in infants with an IEEM (12.6 mmol/L; IQR: 5-27 mmol/L). Machine learning analysis including plasma amino acid and acylcarnitine values yielded an area under the ROC curve (AUC-ROC) of 0.81 in a held-out test set, and was significantly better than lactate alone in a comparable population (AUC-ROC 0.81 vs. 0.56, p=0.027). ConclusionsRapid diagnosis of IEEM vs. other causes is essential for neonatal hyperlactatemia prognostication. Machine learning has high diagnostic utility, serving as a framework for computer-aided interpretation of complex diagnostic data.

Preterm infants are at high risk for systemic inflammatory disorders, including sepsis, meningitis, bronchopulmonary dysplasia, and necrotizing enterocolitis (NEC). The developing brain of the premature newborn is especially susceptible to the cascade of inflammatory mediators elaborated in these conditions that cross the blood-brain barrier. NEC, a severe and potentially fatal condition of the gut that occurs in premature newborns, is a prime example of how an inflammatory reaction, perhaps initially localized, can become generalized and cause systemic harm. One such result is brain injury, especially to the cerebral white matter, which may lead to neurodevelopmental abnormality and dysregulated behavior. Numerous studies have documented an association between necrotizing enterocolitis and neurodevelopmental impairment (NDI), but to date, the brain and behavioral deficits associated with neonatal NEC are not fully understood. We performed a comprehensive systematic review and meta-analysis of existing literature to characterize brain injury and behavioral alterations associated with NEC. 7153 peer-reviewed published manuscripts were screened by two independent reviewers and evidence quality was assessed using GRADE criteria. Of these papers, 62 satisfied the criteria for our review (i.e., no case reports, meta-analyses, systematic reviews, or animal studies). Data from 32 papers using Bayley Scales of Infant and Toddler Development to assess infant outcomes were included in the meta-analysis. Our findings support neonatal necrotizing enterocolitis having deleterious effects on brain and behavioral development and impact on cognitive function, risk of cerebral palsy and motor impairment, educational achievement, behavior, and neuroanatomy. We discuss herein findings of both short-term outcomes (1-3 years) and long-term outcomes (until 13 years). Our meta-analysis also indicates that NEC has a moderate effect size on infant development, with consistent impairment across mental, cognitive, language and motor domains. WHAT DO THE FINDINGS OF THIS REVIEW MEAN?In this review, we describe several short-term and long-term neurodevelopmental outcomes of preterm infants with NEC. These findings suggest that infants with NEC should be monitored with close developmental follow-up so that individuals can receive appropriate testing that may prompt therapies and qualify them to receive early intervention services. HOW UP TO DATE IS THIS REVIEW?The review authors searched for studies published up to 2021. Abstracts with no data available were excluded, so this review does not consider any new findings published from 2022-2024.

ObjectiveIn preterm infants, lower birthweight correlates with a higher risk of neonatal complications. Understanding the factors influencing birthweight in these infants is important as it may guide future antenatal and perinatal care. Genetic variants account for at least one-quarter of variation in birthweight in term-born infants, but the genetic contribution to birthweight in preterm infants is not well understood. We aimed to compare genetic score associations with birthweight in a well-powered sample of preterm infants with those in term-born infants. Study designWe used linear regression to test the association between birth weight and fetal genetic scores for birthweight (BW-GS) in a total of 1,416 preterm, singleton and 15,253 term, singleton infants. Analyses, adjusted for ancestry principal components were performed within each of 4 datasets and meta-analysed. ResultsIn term-born infants: a 1 SD higher BW-GS was associated with a 1.20 (95% CI 1.10-1.29) SD higher birthweight. In preterm infants, there was also strong evidence of association, but with a smaller effect size (0.76SD (0.41-1.11) higher birthweight per 1-SD higher BW-GS). In preterms, when stratifying by gestational duration, we found that the associations strengthened with increasing gestational duration. ConclusionsGenetic scores composed of variants identified in term-born infants also influenced birthweight in preterm infants. However, the associations had smaller effects in preterms and were weaker at earlier gestations. This suggests that while many of the same genetic factors influence birthweight in preterm and term-born infants, other factors (environmental, placental, different genetic) may be more important in preterms. Future well-powered studies are required to investigate this.

BackgroundLittle is known about preterm infant feeding and growth in the outpatient community setting and there are no standardized post-hospital discharge feeding guidelines. ObjectiveTo describe the post-neonatal intensive care unit (NICU) discharge growth trajectories of very preterm (<32 weeks gestational age (GA)) and moderately preterm (32-34 6/7 weeks GA) infants managed by community pediatric providers and to determine the association between post-discharge feeding type and growth Z-scores and z-score changes through 12 months corrected age (CA). MethodsVery preterm infants (n=104) and moderately preterm infants (n=109) born 2010-2014 and followed in hospital-affiliated community health clinics were enrolled in a single-center retrospective cohort study. Infant home feeding type and anthropometry were abstracted from outpatient medical chart review, and repeated measures analysis of variance calculated adjusted growth z-scores and z-score differences between 4 and 12 months CA. Linear regression models tested the relationship between type of home feeding at 4 months CA and anthropometry at 12 months CA. ResultsBy 12 months CA, 5% of very preterm and 10% of moderately preterm infants were overweight. Moderately preterm infants on nutrient-enriched vs. standard term feeds had lower length z-scores at 12 months CA (-0.04 vs. 0.37, P=.03). Feeding type at 4 months CA predicted 12 month CA body mass index z-scores for very preterm infants ({beta}=-0.66(-1.28, -0.04)). ConclusionCommunity pediatric providers may manage preterm infant post-NICU discharge feeding in the context of growth. Further research is needed to explore modifiable drivers of obesity risk in preterm infants to optimize infant development.

ImportanceSocioeconomic status impacts pregnancy outcomes and child development after NICU discharge for infants born prematurely, but has not been well studied for outcomes during the NICU stay. The Area Deprivation Index (ADI) is a validated measure of neighborhood disadvantage that uses Census data on income, education, employment, and housing quality. ObjectiveIn NICUs in different US regions, determine if ADI predicts NICU mortality and morbidity in extremely premature infants. DesignWe conducted a retrospective cohort study. SettingFour level IV neonatal intensive care units (NICU) in different US geographic regions: Northeast, Mid-Atlantic, Midwest, and South. ParticipantsNon-Hispanic White and Black extremely premature infants (gestational age <29 weeks) and admitted to a study NICU from 2012-2020. ExposuresADI, race, BW, sex, and outborn status (admitted after transfer from an outside birth hospital). Main Outcomes and MeasuresWe converted addresses to census blocks, identified by 12-digit Federal Information Processing Series (FIPS) codes, to link residences to the national ADI percentile of study participants. We analyzed the relationship between ADI and NICU mortality using Bayesian logistic regression adjusted for race, BW, outborn status, and sex. Predictors were considered significant if the 95% Credible Intervals excluded zero. We also analyzed the effect of ADI on NICU morbidities of late-onset sepsis, necrotizing enterocolitis, and severe intraventricular hemorrhage. ResultsWe studied 2,765 infants. In univariate analysis, infants with higher ADI were more likely to be Black, suffer from short-term morbidities, and die before NICU discharge. ADI did not correlate with BW (r = -0.05) or sex. Black infants also had higher mortality and lower BW. In a multivariable model, lower BW, higher ADI, and male sex were statistically significant risk factors, while Black race and outborn status were not. Using these methods, ADI was also identified as a risk factor for NICU morbidities. Conclusions and RelevanceAmong extremely preterm infants admitted to four NICUs in different US geographic regions, ADI was a risk factor for mortality and morbidity after adjusting for multiple covariates. These findings have implications for public health measures to improve prenatal and NICU care for patients from disadvantaged areas. Key PointsO_ST_ABSQuestionC_ST_ABSIs socioeconomic deprivation at the neighborhood level, measured by an Area Deprivation Index (ADI), an independent risk factor for NICU mortality and morbidity among extremely premature infants? FindingsIn a cohort of 2,765 extremely premature infants (gestational age <29 weeks) admitted to four Level IV NICUs in different US regions, national ADI percentile correlated with risk of NICU mortality and morbidities after adjusting for multiple covariates. MeaningThese findings have implications for public health measures to improve prenatal and NICU care for patients from disadvantaged areas.

ObjectiveTo examine the association of admission NICU strain with neonatal mortality and morbidity. Study Design2008-2021 South Carolina cohort using linked vital statistics and discharge data of 22-44 weeks GA infants, born at hospitals with [&ge;] level 2 unit and [&ge;]5 births of infants <34 weeks GA/year. The exposure was tertiles of admission NICU strain, defined as the sum of infants <44 weeks GA with a congenital anomaly plus all infants born <33 weeks GA at midnight on the day of birth. We used Poisson generalized linear mixed models to examine the association of exposure to strain with the primary outcome of a composite of mortality and term and preterm morbidities adjusting for patient and hospital characteristics. ResultsWe studied 64,647 infants from 30 hospitals. High strain was associated with increased risk of mortality and morbidity adjusting for patient/hospital factors (aIRR 1.07, 95% CI 1.01 - 1.12). ConclusionNICU strain is associated with increased adverse outcomes.

ObjectivesTo characterize early developmental trajectories of selective motor control (SMC) in very preterm infants and examine associations with later cerebral palsy (CP) diagnosis and gross motor function. MethodsVery preterm infants (<32 weeks gestation) were recorded every 2-4 weeks until 5 months post-term age (PTA). SMC was scored from 352 videos (n=47 infants; 12 with CP) using BabyOSCAR, a validated observational tool. Linear mixed models examined SMC trajectories by CP diagnosis and Gross Motor Function Classification System (GMFCS) level. ROC curves tested the ability of early SMC change (40-45 weeks) to predict CP. ResultsSMC scores increased over time, but infants with CP showed slower gains. Between 41-63 weeks, group differences emerged and widened (p<0.001). Change in BabyOSCAR score from 40-45 weeks predicted CP with 92% sensitivity and 100% specificity (AUC=0.98). GMFCS groups showed distinct trajectories, with children classified as GMFCS III-V changing scores less. Infants with unilateral CP showed increasing asymmetry from 42 weeks PTA. ConclusionsSMC develops rapidly after term age but is altered in infants with CP, particularly among those later classified as GMFCS III-V. Early trajectories may reflect emerging corticospinal connectivity and offer a clinically useful marker of functional motor outcomes.

AimTo examine the effects of an early home-based 8-week crawling intervention performed by trained therapists on the motor and general development of very premature infants during the first year of life. MethodsAt term-equivalent age, immediately following discharge from the Neonatal Intensive Care Unit (NICU), we randomly allocated 44 premature infants born before 32 weeks gestation without major brain damage to one of three conditions in our intervention study: crawling on a mini-skateboard, the Crawliskate (Crawli), prone positioning control (Mattress), or standard care (Control). The Crawli and Mattress groups received 5 min daily at-home training administered by trained therapists for 8 consecutive weeks upon discharge from the NICU. The outcomes of greatest interest included gross motor development (Bayley-III) at 2, 6, 9, and 12 months (primary outcome) corrected age (CA), mature crawling at 9 months CA and general development at 9 and 12 months CA [Ages and Stages Questionnaires-3 (ASQ-3)]. ResultsA 3 (Condition) x 4 (Age) repeated measures ANOVA revealed that Crawli group infants had significantly higher Bayley-III gross motor development scores than Mattress and Control group infants. Crawli group infants also scored significantly higher on groups of Bayley-III items related to specific motor skills than infants in the other groups, including crawling at 9 months CA (p<0.05). Separate one-way ANOVAs at each of the four ages tested revealed the Crawli group had significantly higher gross motor development scores than the Mattress group (p<.001) but not the Control group (p<.08) at 2 months CA, than the Mattress and Control groups at 6 months CA (p<.05), and than the Control group at 9 and 12 months CA (p<.05). The Mattress and Control groups did not differ significantly at any age. A 3 (Condition) x 2 (Age) repeated measures ANOVA revealed that the Crawli group scored significantly higher than the Control group for the ASQ-3 total score (p<.01) and communication score (p<.05) and significantly higher for the fine motor score than the Control (p<.01) and Mattress (p<.05) groups. We found additional significant differences in favor of the Crawli group for other dimensions of the ASQ-3 in separate one-way ANOVAs at 9 and 12 months CA. Interpretation Early crawling training on a Crawliskate provides an effective way to promote motor and general development in very premature infants. The Crawli groups significantly higher scores on the crawling items at 9 months CA provide clear evidence for a link between newborn crawling and more mature crawling later in development. What this paper addsO_LIVery premature infants can propel themselves on a mini-skateboard using crawling movements at term equivalent age C_LIO_LIEight weeks of daily, at-home early crawling training immediately following discharge from the NICU facilitates the acquisition of mature crawling in premature infants C_LIO_LIEight weeks of early crawling training positively influences motor development in premature infants C_LIO_LIEight weeks of early crawling training positively influences general development in premature infants C_LIO_LIEarly daily at-home crawling is a promising intervention for premature infants at heightened risk for motor delays and disabilities, potentially feasible for parents to conduct C_LI Data sharing statementThe data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

ObjectiveTo examine differences in infant-directed talk activities (e.g., reading) before and after introduction of a NICU book cart. Study DesignWe retrospectively analyzed medical record data of infants born <32 weeks gestational age (n = 147) whose NICU stay occurred in the year before or after book cart implementation (6/1/2022). Talk rates and frequencies were calculated from clinically charted family and staff talk data; talk amounts were compared across pre- and post-book cart cohorts, adjusting for covariates. ResultsCohorts displayed equivalent clinical/demographic variables, except for higher bronchopulmonary dysplasia rates in the post-book cart cohort. Post-book cart family and staff engaged in more talk than those in the pre-book cart cohort, with staff showing higher talk rates and frequencies than family across both cohorts. ConclusionFamily and staff with access to a NICU book cart engaged in more talk, suggesting a strategy to support infant speech exposure.

ObjectivesTo evaluate the impact of undernutrition in school-aged children born with type III esophageal atresia (EA), and to determine its potential risk factors, including their respiratory history and status assessed by pulmonary function tests. MethodsRetrospective multicentre cohort study encompassing patients born between 2008 and 2013 with type III EA included in a national registry. Baseline data, surgical history and outcomes of patients with or without undernutrition (body mass index (BMI) z-score < -2 SD) at the age of 6-9 years were compared. ResultsOf the 212 patients included in the study, 20 (9.4%) presented with undernutrition, with a mean BMI z-score of -2.5 +/- 0.4. At birth, 13 (65%) of them where preterm, twice as high as in the control group (34.9%, p = 0.013), but adjusted neonatal weights and associated malformations did not differ between groups. Surgical management of EA and other intestinal malformations, including gastrostomy and fundoplication, were comparable between groups, except for hernia/cryptorchidism occurrence (20% vs 5.2%, p = 0.03). On spirometry, 15 (75%) of these patients demonstrated restriction, as compared to 38% of normal weight patients (p=0.002), and 60% of them required pulmonary treatments (vs 32%, p=0.02). Multivariate analysis identified birth in a level 3 maternity (odds ratio OR=6.0), hernia/cryptorchidism surgery (OR=5.2), a restrictive syndrome (OR=3.3) and pulmonary crisis treatment use (OR=2.7) as risk factors for undernutrition. ConclusionsIn contrast to intestinal and esophageal surgeries, the respiratory status appears to be significantly associated with nutritional outcomes in children born with type III EA. Clinical trialNCT04136795. What is known- Undernutrition remains common in children operated on for esophageal atresia. - There are associations between prematurity and undernutrition in children with esophageal atresia. What is new- Undernutrition is associated with a restrictive ventilatory pattern and with the use of pulmonary crisis treatments in school-aged children with type III esophageal atresia; - On the contrary, in this population, associated malformative conditions including the digestive tract and esophageal surgeries secondary to esophageal repair do not predispose children to undernutrition.

ImportanceHuman milk is beneficial for preterm newborns, and pasteurized donor human milk (PDHM) is increasingly used when mothers own milk (MM) is insufficient. However, PDHM has been associated with suboptimal growth outcomes. ObjectiveTo quantify the comparative clinical effectiveness of PDHM, MM, and formula in supporting daily weight gain and growth outcomes during the birth hospitalization. DesignRetrospective cohort study of infants born before 34 weeks gestation between 2016 and 2024 SettingFive newborn nurseries across the Mass General Brigham healthcare system (Boston, MA), including one Level IV, one Level III, and three Level II newborn units. ParticipantsA total of 2,635 preterm infants born before 34 weeks gestation between 2016 and late 2024 were included in the daily weight gain analysis, contributing 40,007 days of eligible enteral intake data for evaluation of in-hospital growth outcomes. For the analysis examining the association between PDHM use and discharge weight, 2,719 infants met eligibility criteria. ExposuresPDHM, MM, formula Main Outcomes and MeasuresThe primary outcome was daily weight gain (g/kg/day). The secondary outcome was the change in weight Z-score from birth to discharge. ResultsIn adjusted analyses, an equal volume of PDHM was associated with 74% of the daily weight gain achieved with MM (p < 0.0001, 95% CI 70%-77%), and formula with 115% of MM (p < 0.0001, 95% CI 111%-119%). During the birth hospitalization, infants in the highest quartile of PDHM exposure had a significantly greater decline in weight-for-age Z-score compared with those with no exposure (-0.09, p = 0.005), while no differences were observed in the lower quartiles. Conclusions and RelevanceGrowth outcomes varied by PDHM exposure, with a significant decline observed only in the highest quartile, while lower exposure levels showed no significant effect. Formula-fed infants were observed to have greater weight gain than either PDHM or MM. These results highlight the need for close growth monitoring and timely nutritional adjustments in preterm infants, particularly when PDHM is the primary source of enteral nutrition. QuestionHow does pasteurized donor human milk (PDHM) compare with mothers own milk (MM) and formula in supporting in-hospital growth among preterm infants born at or before 34 weeks gestation? FindingsIn this multicenter retrospective cohort study involving > 2500 preterm infants contributing over 40,000 infant-days of enteral data, PDHM correlated with significantly reduced daily weight gain compared with MM, whereas formula supported greater weight gain than either human milk source. At discharge, infants with the highest quartile of PDHM exposure showed a greater reduction in weight-for-age Z-score than infants with no PDHM exposure. No association was observed in the lower quartiles. MeaningOur findings underscore the need for close growth monitoring and potentially greater nutritional supplementation in relation to PDHM exposure.

BackgroundNeurodevelopmental impairments are common in children with congenital heart disease. The Cardiac Neurodevelopmental Outcome Collaborative and Pediatric Cardiac Critical Care Consortium registry linkage allows for the analysis of associations between neurodevelopmental, medical, and sociodemographic variables in a large contemporary cohort. MethodsChildren with congenital heart disease who required surgery with cardiopulmonary bypass at <12 months of age and completed a neurodevelopmental assessment between 11-30 months of age from 2019-2022 were included. Multivariable regression modeling was performed to identify differences in Cognitive, Language, and Motor standard scores from the Bayley Scales of Infant and Toddler Development-III/4 based on congenital cardiac diagnosis, clinical risk factors, and social drivers of health. ResultsPrimary analyses included 942 assessments from 868 children completed at 25 sites. Across cardiac diagnostic groups, those with genetic diagnoses (n=116 assessments) scored >1 standard deviation lower on all Bayley indices than those without (P<0.001 for each). For those without genetic diagnoses, there were differences between cardiac diagnostic groups (P<0.001) in both Cognitive and Motor indices; participants with transposition of the great arteries exhibited the highest scores compared with other cardiac diagnoses. Lower birth weight, male sex, older age at initial surgery, longer hospital length of stay, more cardiac catheterizations, and lower primary caregiver education were independently associated with worse performance in all indices. ConclusionsFindings from this multicenter cohort demonstrate variation in neurodevelopmental outcomes according to cardiac diagnosis. Regardless of cardiac diagnosis, the presence of a genetic diagnosis is associated with lower neurodevelopmental scores. Heterogeneous outcomes reinforce the importance of surveillance for all infants undergoing heart surgery in the first year of life. Clinical Perspective What is new?O_LIWhile genetic diagnoses confer the highest risk of developmental delays and disorders in patients with CHD, cardiac diagnosis also impacts early neurodevelopmental outcomes in non-syndromic patients. C_LIO_LIIn non-syndromic patients, those with transposition of the great arteries exhibit higher scores on early ND testing than other common CHD subtypes, while those with single ventricle physiology and atrioventricular septal defects exhibit lower scores. C_LIO_LIOlder age at surgery and greater number of interventional cardiac catheterizations may represent newly identified risk factors for adverse early ND outcomes in infants with CHD. C_LI What are the clinical implications?O_LIData from the CNOC registry emphasizes the importance of ND follow-up for all infants undergoing cardiac surgery, including those with simpler CHD subtypes. C_LIO_LIThe improved outcomes we observed in patients with transposition of the great arteries suggest advances in routine clinical management, including early surgery, may have had a neuroprotective influence. C_LI

Background and ObjectivesPreterm infants (<34 weeks gestation) experience high rates of morbidity and mortality before hospital discharge. Genetic disorders substantially contribute to morbidity and mortality in related populations. The prevalence and clinical impact of genetic disorders is unknown in this population. We sought to determine the prevalence of commonly diagnosed genetic disorders in preterm infants, and to determine the association of disorders with morbidity and mortality. MethodsThis was a retrospective multicenter cohort study of infants born from 23 to 33 weeks gestation between 2000 and 2020. Genetic disorders were abstracted from diagnoses present in electronic health records. We excluded infants transferred from or to other health care facilities prior to discharge or death when analyzing clinical outcomes. We determined the adjusted odds of pre-discharge morbidity or mortality after adjusting for known risk factors. ResultsOf 320,582 infants, 4196 (1.3%) had genetic disorders. Infants with trisomy 13, 18, 21, or cystic fibrosis had greater adjusted odds of severe morbidity or mortality. Of the 17,427 infants who died, 566 (3.2%) had genetic disorders. Of the 65,968 infants with a severe morbidity, 1319 (2.0%) had genetic disorders. Conclusions Genetic disorders are prevalent in preterm infants, especially those with life-threatening morbidities. Clinicians should consider genetic testing for preterm infants with severe morbidity and maintain a higher index of suspicion for life-threatening morbidities in preterm infants with genetic disorders. Prospective genomic research is needed to clarify the prevalence of genetic disorders in this population, and the contribution of genetic disorders to preterm birth and subsequent morbidity and mortality. Article SummaryGenetic disorders were found in 1.3% of preterm infants and at a higher rate (2.0%) in infants who died or developed severe morbidity. Whats Known on This SubjectPrevious research described the prevalence and associated short-term morbidity and mortality of trisomy 13, 18, and 21 in preterm infants. The prevalence of other commonly diagnosed genetic disorders and associated short-term morbidity and mortality in preterm infants is unknown. What This Study AddsIn a multicenter, retrospective cohort of 320,582 preterm (<34 weeks gestation) infants, we found that 1.3% had genetic disorders diagnosed through standard care. Multiple disorders were associated with increased adjusted odds of morbidities or mortality prior to hospital discharge. Contributors Statement PageSelin S. Everett conceptualized and designed the study, conducted analyses, drafted the initial manuscript, and critically reviewed and revised the manuscript. Dr. Thomas Hays conceptualized and designed the study, drafted the initial manuscript, and critically reviewed and revised the manuscript. Miles Bomback conceptualized and designed the study and critically reviewed and revised the manuscript. Drs. Veeral N. Tolia and Reese H. Clark coordinated and supervised data collection and critically reviewed and revised the manuscript. Dr. Rakesh Sahni conceptualized and designed the study and critically reviewed and revised the manuscript. Dr. Alex Lyford conducted analyses and critically reviewed and revised the manuscript. Dr. Ronald J. Wapner reviewed and critically revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

ObjectivePreterm infants born small, vs. appropriate for gestational age (SGA, AGA) are at greater risk for morbidity and mortality. The contribution of genetic disorders to preterm SGA birth, morbidity, and mortality is unknown. We sought to determine the association between genetic disorders and preterm SGA birth, and the association between genetic disorders and morbidity or mortality within preterm SGA infants. We hypothesized that genetic disorders were significantly associated with both. Study DesignThis was a retrospective multicenter cohort study of 409 339 infants, born 23-33 weeks gestation between 2000 and 2020. The odds of preterm SGA (vs AGA) birth, and the odds of severe morbidity or mortality within SGA preterm infants were determined for infants with genetic disorders, after adjusting for known risk factors. ResultsGenetic disorders were present in 3.0 and 1.3% of SGA and AGA preterm infants respectively; genetic disorders conferred an aOR (95% CI) of 2.06 (1.92, 2.21) of SGA birth. Genetic disorders were present in 4.3 of preterm SGA infants with morbidity or mortality and 2.1% of preterm SGA infants that did not experience morbidity or mortality. Genetic disorders conferred an aOR (95% CI) of 2.12 (2.66, 3.08) of morbidity or mortality. ConclusionsGenetic disorders are strongly associated with preterm SGA birth, morbidity, and mortality. Clinicians should consider genetic testing of preterm SGA infants, particularly in the setting of other comorbidities or anomalies. Prospective, genomic research is needed to clarify the contribution of genetic disorders to disease in this population.