Child Fatality Review.

Understanding why children die is necessary to implement strategies to prevent future deaths and improve the health of any community. Child fatality review teams (CFRTs) have existed since the 1970s and provide a necessary framework to ensure that proper questions are asked about a child's death. CFRTs provide a vital function in a community to ensure that preventable causes of deaths are identified. Pediatricians are necessary members of CFRTs because they provide medical expertise and context around a child's death. All CFRTs should have pediatric physician representation, and results from team meetings should inform public policy at all levels of government. Pediatricians should be supported in their efforts to be present on CFRTs, and they should use data from team meetings to help advocate for implementing prevention strategies.

Examining early intervention referral patterns in neonatal intensive care unit follow up clinics using telemedicine during COVID-19.

BACKGROUND: Neonatal intensive care unit (NICU) follow up programs are in place to ensure infant health and development are monitored after discharge. The COVID-19 Public Health Epidemic (PHE) negatively impacted the ability to conduct in-person NICU follow up visits. AIMS: This study examines using telemedicine in NICU follow up clinics and compares the rates of referral for further medical and/or educational developmental evaluation. A second objective of the study examines if telemedicine can be implemented in the future to ensure access to families while maintaining high levels of caregiver satisfaction. METHOD: Data were obtained retrospectively from clinical records from one state's NICU follow-up program. Patterns of referral for further developmental evaluation and caregiver satisfaction prior to the COVID-19 PHE and during the first year of the COVID-19 PHE were examined. A total of 658 NICU follow up visits (384 in-person and 274 telemedicine) were included. RESULTS: Chi Square analyses revealed significantly more medically related referrals were made during telemedicine visits compared to in-person visits, χ2 (1) = 5.55, p .05. There were no significant differences between the clinic types in the number of educationally based referrals made, χ2 (1) = 0.028, p > .05. CONCLUSION: The rates of referral for further evaluation made from in-person and telemedicine clinics were comparable, and caregivers were highly satisfied with telemedicine clinic visits. NICU follow up via a virtual platform saves time, money and is equally effective or better in identifying the need for referral for further evaluation.

The Relationship Between Neonatal Surgery, Postpartum Depression, and Infant Clinical Course.

OBJECTIVE: Postpartum depression (PPD) affects 10-15% of mothers in the general population, and studies show increased incidence for mothers of infants with serious health conditions. This study investigates incidence of PPD in mothers of surgical patients in the neonatal intensive care unit (NICU) and characterizes these patients' clinical and neurodevelopmental outcomes. METHODS: This retrospective cohort study analyzed Nebraska's Tracking Infant Progress Statewide (TIPS) database and referring hospital medical records from February 2013 to June 2018. Upon NICU discharge, children were referred to the TIPS program, with scheduled follow-up appointments at approximately 6 months corrected age. All patients seen in NICU follow-up clinic with recorded scores for maternal Edinburgh postnatal depression screen (EPDS) were eligible except infants with congenital heart disease as this cohort was previously studied. Patients were stratified into groups based on presence or absence of a general surgical procedure within the first 6 months of life and positive (≥ 10) or negative (< 10) EPDS score. Statistical analyses assessed for significant differences between groups regarding gestational age, birth weight, maternal age, length of NICU stay (LOS), number of days on a ventilator, payment method, ethnicity, developmental testing, and rate of referral for early intervention services. RESULTS: Of 436 patients, 83 were surgical patients (16 with positive EPDS; 19.3% incidence), and 353 were non-surgical patients (44 with positive EPDS; 12.5% incidence). Statistical analysis showed no significant relationship between neonatal surgery and positive EPDS (χ2 = 2.6, p = 0.1). While the surgical cohort had longer LOS and days on ventilator, maternal EPDS did not predict these factors. In the surgical cohort, mothers of children not independent on oral feeding at discharge were more likely to screen positive for depression (7/14, 50% vs. 7/61, 11%; p < 0.05). CONCLUSION: Mothers of surgical patients are not significantly more likely to screen positive for post-partum depression compared to other NICU mothers. This underscores the importance of routine screening for PPD in mothers of both surgical and non-surgical NICU patients in order to identify parents and children at risk.

Rare and de novo variants in 827 congenital diaphragmatic hernia probands implicate LONP1 as candidate risk gene.

Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly that is often accompanied by other anomalies. Although the role of genetics in the pathogenesis of CDH has been established, only a small number of disease-associated genes have been identified. To further investigate the genetics of CDH, we analyzed de novo coding variants in 827 proband-parent trios and confirmed an overall significant enrichment of damaging de novo variants, especially in constrained genes. We identified LONP1 (lon peptidase 1, mitochondrial) and ALYREF (Aly/REF export factor) as candidate CDH-associated genes on the basis of de novo variants at a false discovery rate below 0.05. We also performed ultra-rare variant association analyses in 748 affected individuals and 11,220 ancestry-matched population control individuals and identified LONP1 as a risk gene contributing to CDH through both de novo and ultra-rare inherited largely heterozygous variants clustered in the core of the domains and segregating with CDH in affected familial individuals. Approximately 3% of our CDH cohort who are heterozygous with ultra-rare predicted damaging variants in LONP1 have a range of clinical phenotypes, including other anomalies in some individuals and higher mortality and requirement for extracorporeal membrane oxygenation. Mice with lung epithelium-specific deletion of Lonp1 die immediately after birth, most likely because of the observed severe reduction of lung growth, a known contributor to the high mortality in humans. Our findings of both de novo and inherited rare variants in the same gene may have implications in the design and analysis for other genetic studies of congenital anomalies.

Postural control may drive the development of other domains in infancy.

BACKGROUND: To examine differences in sitting posture in infants at low- and high-risk for autism spectrum disorder and to establish the relationship between sitting postural control and other developmental domains. METHODS: A total of 19 infants participated in the study. Eight infants at high-risk and 11 infants at low-risk for autism spectrum disorder. Sitting posture at 6 months was evaluated using a force platform while center of pressure data were acquired. We utilized traditional tools of center of pressure analysis, such as range, median frequency and frequency dispersion, as well as non-linear tools such as Sample Entropy for both the medial-lateral and anterior-posterior directions. At 12 months we used the Mullen Scales of Early Learning, the Communication and Symbolic Behavior Scales Developmental Profile™ and the Ages and Stages Questionnaire, the personal-social subscale. FINDINGS: At 6 months none of the postural control measures showed statistically significant differences between groups. Infants at high-risk presented significantly lower scores in all behavioral domains than infants at low-risk at 12 months with fair effect sizes. Certain measures of postural control at 6 months could predict language and visual reception behavior at 12 months. INTERPRETATION: Infants at high-risk for autism spectrum disorder present with delays in social, communication and language behavior as well as altered postural control in the first year of life. The present data support the possibility that motor skills and specifically postural control may drive the development in other domains.

Variations in Criteria for Eligibility Determination for Early Intervention Services with a Focus on Eligibility for Children with Neonatal Complications.

OBJECTIVE: The purpose of this policy review is to describe data on eligibility determination practices for early intervention (EI) services across the United States as they particularly relate to eligibility determination for children seen in neonatal follow-up clinics. METHOD: Policy information was gathered from posted information on state EI websites and confirmed through follow-up phone calls. Information collected included definition of delay, approved measures for developmental assessment, and inclusion criteria for medically at-risk status based on birth weight, prematurity, and/or neonatal abstinence syndrome/prenatal exposure. RESULTS: States varied widely across enrollment practices and policies. Forty percent of states defined eligibility based on percent delay (vs SD). Thirty-five states had criteria for enrollment based on birth weight and/or prematurity, and 19 states specifically allowed enrollment for an infant with neonatal abstinence syndrome. CONCLUSION: Providers working in neonatal follow-up clinics should be carefully educated about the eligibility criteria and approved tests for assessing development in the states in which they practice, recognizing that there is obvious and significant variability across states.

Sitting Matters! Differences Between Sitters and Nonsitters at 6 Months' Adjusted Age in Infants At-Risk and Born Preterm.

PURPOSE: Sitting delays in infants born preterm compound cognitive and language deficits. This retrospective study examines differences in prematurity-related risk and compares developmental outcomes between sitters and nonsitters at 6 months' adjusted age. METHODS: A total of 105 graduates of the neonatal intensive care unit met inclusion criteria. Infant demographic and medical risk profiles and 6-month Bayley Scales of Infant Development-3rd edition (BSID-III) cognitive and language scores were retrieved. Infants who sat with hands free greater than 60 seconds were classified as "sitters." RESULTS: Sixty-nine percent of the sample were nonsitters and were born earlier, had lower birth weights, were chronologically older at follow-up, and spent more days with respiratory support. BSID-III scores were significantly higher in sitters but did not differ by gender, multiple birth, head ultrasound results, payment type, or race/ethnicity. CONCLUSION: Sitting abilities at 6 months' adjusted age are associated with prematurity risk factors. Cognitive and language scores differ significantly between sitters and nonsitters.

Fat-soluble vitamins A and E and health disparities in a cohort of pregnant women at delivery.

The objective of the present study was to evaluate intakes and serum levels of vitamin A, vitamin E, and related compounds in a cohort of maternal-infant pairs in the Midwestern USA in relation to measures of health disparities. Concentrations of carotenoids and tocopherols in maternal serum were measured using HPLC and measures of socio-economic status, including food security and food desert residence, were obtained in 180 mothers upon admission to a Midwestern Academic Medical Center labour and delivery unit. The Kruskal-Wallis and independent-samples t tests were used to compare measures between groups; logistic regression models were used to adjust for relevant confounders. P < 0·05 was considered statistically significant. The odds of vitamin A insufficiency/deficiency were 2·17 times higher for non-whites when compared with whites (95 % CI 1·16, 4·05; P = 0·01) after adjustment for relevant confounders. Similarly, the odds of being vitamin E deficient were 3·52 times higher for non-whites (95 % CI 1·51, 8·10; P = 0·003). Those with public health insurance had lower serum lutein concentrations compared with those with private health insurance (P = 0·05), and living in a food desert was associated with lower serum concentrations of ß-carotene (P = 0·02), after adjustment for confounders. Subjects with low/marginal food security had higher serum levels of lutein and ß-cryptoxanthin compared with those with high food security (P = 0·004 and 0·02 for lutein and ß-cryptoxanthin). Diet quality may be a public health concern in economically disadvantaged populations of industrialised societies leading to nutritional disadvantages as well.

A definition of gentle ventilation in congenital diaphragmatic hernia: a survey of neonatologists and pediatric surgeons.

Ventilation practices have changed significantly since the initial reports in the mid 1980 of successful use of permissive hypercapnia and spontaneous ventilation [often called gentle ventilation (GV)] in infants with congenital diaphragmatic hernia (CDH). However, there has been little standardization of these practices or of the physiologic limits that define GV. We sought to ascertain among Diaphragmatic Hernia Research and Exploration; Advancing Molecular Science (DHREAMS) centers' GV practices in the neonatal management of CDH. Pediatric surgeons and neonatologists from DHREAMS centers completed an online survey on GV practices in infants with CDH. The survey gathered data on how individuals defined GV including ventilator settings, blood gas parameters and other factors of respiratory management. A total of 87 respondents, from 12 DHREAMS centers completed the survey for an individual response rate of 53% and a 92% center response rate. Approximately 99% of the respondents defined GV as accepting higher carbon dioxide (PCO2) and 60% of the respondents also defined GV as accepting a lower pH. There was less consensus about the use of sedation and neuromuscular blocking agents in GV, both within and across the centers. Acceptable pH and PCO2 levels are broader than the goal ranges. Despite a lack of formal standardization, the results suggest that GV practice is consistently defined as the use of permissive hypercapnia with mild respiratory acidosis and less consistently with the use of sedation and neuromuscular blocking agents. GV is the reported practice of surveyed neonatologists and pediatric surgeons in the respiratory management of infants with CDH.

Neurodevelopmental outcomes of tracheoesophageal fistulas.

PURPOSE: The purpose of this study was to perform a retrospective review of tracheoesophageal fistula (TEF) patients who followed up in a state-sponsored program to assess neurodevelopmental outcomes. METHODS: Records were reviewed retrospectively of children who underwent TEF repair between August 2001 and June 2014. Children discharged from the neonatal intensive care unit were referred to the state-sponsored Developmental Tracking Infant Progress Statewide (TIPS) program. We reviewed TIPS assessments performed before age 24months and noted referral for early school intervention services. Poor outcomes were defined as scores of "failure" on the screening assessment or referral for enrollment in early intervention services by 24months. Children with TEF were compared with case-matched nonsyndromic children of similar gestational age and birth weight. RESULTS: Seventy-eight children underwent TEF repair. Thirty-eight followed up with TIPS. Survival was 93.6%. Predictors of hospital survival were Waterston classification (p=0.001), birth weight (p=0.027), and ventilator days (p=0.013). LOS was the only significant predictor of referral for early intervention services (p=0.0092) in multivariate analysis. There was a borderline significant difference in referral rate between children with TEF and controls. 52.6% of TEF patients were referred, while 34.2% of controls were referred (p=0.071). CONCLUSION: More than half of TEF patients experience neurodevelopmental delays requiring referral for early intervention (53%).

Effect of community size on eligibility for early intervention for infants with a neonatal intensive care experience.

PURPOSE: To determine if population density (rural vs urban) in a child's home community influenced the decision of eligibility for early intervention (EI) services. METHODS: The sample included 356 infants with a gestational age of <31 weeks referred from a statewide child find program for an evaluation for EI services. A binary logistic regression analysis was completed to determine which variables predicted acceptance into EI services. FINDINGS: Infants less than 31 weeks gestation residing in rural areas were more likely to be eligible for EI services than premature infants (ie, <31 weeks gestation) with similar birth characteristics from urban areas. A binary logistic regression analysis revealed an odds ratio for eligibility for EI services among children living in rural areas compared to those living in urban areas was 3.007 (95% CI, 1.497 to 6.040). Additionally, the odds ratio for eligibility for males as compared to females was 1.908 (95% CI, 1.017 to 3.578). Participants who lived in a rural area and were male were more likely to be eligible for EI services than those who lived in urban locations and were female. CONCLUSIONS: Factors such as community support, experience with high-risk populations, and differences in interpreting eligibility criteria may influence the differences found between the rural and urban populations. Analysis of intervention cost versus effectiveness will be needed to determine whether the system as adopted in the rural versus urban environment is more appropriate for the provision of EI services.

Developmental outcomes of children with congenital diaphragmatic hernia: a multicenter prospective study.

PURPOSE: To determine developmental outcomes and associated factors in patients with congenital diaphragmatic hernia (CDH) at 2 years of age. METHODS: This is a multicenter prospective study of a CDH birth cohort. Clinical and socioeconomic data were collected. Bayley Scales of Infant Development (BSID-III) and Vineland Adaptive Behavior Scales (VABS-II) were performed at 2 years of age. RESULTS: BSID-III and VABS-II assessments were completed on 48 and 49 children, respectively. The BSID-III mean cognitive, language, and motor scores were significantly below the norm mean with average scores of 93 ± 15, 95 ± 16, and 95 ± 11. Ten percent (5/47) scored more than 2 standard deviations below the norm on one or more domains. VABS-II scores were similar to BSID-III scores with mean communication, daily living skills, social, motor, adaptive behavior scores of 97 ± 14, 94 ± 16, 93 ± 13, 97 ± 10, and 94 ± 14. For the BSID-III, supplemental oxygen at 28 days, a prenatal diagnosis, need for extracorporeal membrane oxygenation (ECMO) and exclusive tube feeds at time of discharge were associated with lower scores. At 2 years of age, history of hospital readmission and need for tube feeds were associated with lower scores. Lower socioeconomic status correlated with lower developmental scores when adjusted for significant health factors. CONCLUSION: CDH patients on average have lower developmental scores at 2 years of age compared to the norm. A need for ECMO, oxygen at 28 days of life, ongoing health issues and lower socioeconomic status are factors associated with developmental delays.

Long-term neurodevelopmental outcomes in children born with gastroschisis: the tiebreaker.

PURPOSE: We evaluated 2-year neurodevelopmental outcomes in children with gastroschisis. METHODS: We reviewed the records of children with gastroschisis treated between August 2001 and July 2008. Children discharged from the neonatal intensive care unit were referred to the state-sponsored Developmental Tracking Infant Progress Statewide (TIPS) program. We reviewed TIPS assessments performed before age 2 years. School districts evaluated children referred by TIPS and determined their eligibility for early intervention services. Poor outcomes were defined as scores of "failure" or "moderate/high risk" on the screening assessment or enrollment in early intervention services by 2 years. Children with gastroschisis were compared with case-matched nonsurgical, nonsyndromic children of similar gestational age and birth weight. RESULTS: One hundred five children were born with gastroschisis, and 46 were followed up with TIPS. There was no statistically significant difference in performance on screening assessments or in the rate of enrollment in early intervention services between the gastroschisis children and controls. CONCLUSIONS: Children born with gastroschisis have similar 2-year neurodevelopmental outcomes as nonsurgical, nonsyndromic neonatal intensive care unit children of similar gestational age and birth weight. Both groups of children have a higher rate of enrollment in early intervention than their healthy peers. These data suggest that neurodevelopmental outcomes in gastroschisis children are delayed secondary to prematurity rather than the presence of the surgical disease.

Bayley Scales of Infant Development Screening Test-Gross Motor Subtest: efficacy in determining need for services.

PURPOSE: To identify the efficacy of the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), Screening Test-Gross Motor Subtest (GMS) in identifying infants who are accepted for early intervention services. METHODS: This retrospective study included 93 infants with a neonatal intensive care experience who participated in a 6-month developmental assessment follow-up visit. All infants were examined using the BSID-III Screening Test-GMS and the Alberta Infant Motor Scale. A binary logical regression analysis was used to determine the best predictors of acceptance status in this sample. RESULTS: The BSID-III Screening Test-GMS accounted for a significant portion of the variance in acceptance status. CONCLUSION: The results suggest that the BSID-III Screening Test-GMS has great applicability for transdisciplinary/interdisciplinary teams as it effectively identified children who were eligible for early intervention.

Neurodevelopmental outcomes in infants after surgery for congenital heart disease: a comparison of single-ventricle vs. two-ventricle physiology.

INTRODUCTION: The neurodevelopmental outcome of children with repaired congenital heart defect has risen in importance with improved survival. This study compares neurodevelopmental outcomes of children who had CHD with single ventricle physiology with those who had CHD with two-ventricle physiology. PATIENTS AND METHODS: Participants included 112 infants discharged from the NICU between February 1999 to August 2006. The 12 infants who had a known genetic defect were excluded. Of the 100 infants 26 had single ventricle physiology and 74 had CHD with two-ventricle physiology. The children were seen in a follow-up clinic and growth parameters and standardized instruments were used to evaluate development. The referral rate to early intervention services was also compared. RESULTS: The number of functional ventricles did not significantly differentiate growth parameters at 6-8 months of age. Early cognitive outcomes were relatively unimpaired in both the groups (single ventricle vs. two ventricle physiology). Early motor outcomes were worse in (p < 0.05) CHD with single ventricle physiology. The rate of referral for early intervention services was high in both groups compared to the average rate of referral in the state, but there was not a significant difference between the CHD groups. CONCLUSION: Significant differences noted on motor outcomes at the 6-8 month visit were no longer apparent in later visits. Referral to early intervention services is high in both the groups. These findings are important to those caring for infants with CHD because many of these patients may need referral for early intervention.

The effect of hydrocortisone on neurodevelopmental outcome in premature infants less than 29 weeks' gestation.

The use of postnatal dexamethasone in premature newborns can be associated with a deleterious neurodevelopmental outcome. The effect of hydrocortisone on developmental outcome in these patients is less clear. We therefore sought to examine the effect of hydrocortisone on early developmental outcome in premature newborns. We retrospectively examined the effect of hydrocortisone on developmental outcome during the first 2 years of life in premature infants <29 weeks' gestation at birth. Even though hydrocortisone was used in infants with a greater risk for poor outcome, its use, unless prolonged >7 days, was generally not associated with a worse developmental outcome or higher rate of referral for early intervention. A short course of hydrocortisone in sick premature newborns does not appear to have a deleterious effect on developmental outcome.

Effects of postnatal dexamethasone exposure on the developmental outcome of premature infants.

Extremely low birth weight premature infants are at risk for poor neurodevelopmental outcome. Postnatal dexamethasone has often been used in premature infants to prevent or treat bronchopulmonary dysplasia, and this drug is thought by some to affect neurodevelopmental outcome. We retrospectively examined the effect of this steroid on early neurodevelopment. Dexamethasone exposure was associated with an adverse outcome and was a stronger predictor of outcome than other accepted risk factors. If used, dexamethasone should be used in these high-risk infants for as short a period as possible.

Postterm closure of the cavum septi pellucidi and developmental outcome in premature infants.

The authors report the natural history of closure of the cavum Septi pellucidi in premature infants 26 to 27 weeks postconception at birth and compare the developmental outcome in these infants who had closure by 42 weeks postconception to those who still had a cavum septum pellucidi visualized on ultrasound at approximately term (35-42 weeks). Of 72 patients, 35 patients still had a cavum septum pellucidi visualized on the last ultrasound done between 35 and 42 weeks postconception, and the developmental outcome of these patients was no different from those with earlier closure. The authors conclude that persistence of a cavum septi pellucidi through term is not an independent risk factor for developmental delay.

Ontogeny and physiology of the cavum septum pellucidum in premature infants.

We report the natural history of the closure of the cavum septum pellucidum in 47 premature infants. In this study, a cavum septum pellucidum was present in all patients at 25 to 26 weeks' postconceptual age, in keeping with previous reports. The data from this study suggest that premature delivery does not change the natural history of the normal closure of the cavum septum pellucidum in most infants by 36 to 40 weeks' postconceptual age. Although not statistically significant, there is a suggestion from these data that higher grades of intraventricular hemorrhage are more frequently associated with loss (early closure) of the cavum septum pellucidum. One particularly illustrative case with a grade 4 intraventricular hemorrhage and subsequent hydrocephalus suggests that increases in pressure and volume in the lateral ventricles can cause the laminae of the septum pellucidum to approximate and appear to fuse earlier than expected. However, the fact that the cavum septum pellucidum reappeared in this case after ventricular pressure was decreased (postventricular shunt) suggests that approximation is not the sole factor in definitive fusion of the laminae of the septum pellucidum.