Spatiotemporal dynamics of cortical somatosensory network in typically developing children.

Sense of touch is essential for our interactions with external objects and fine control of hand actions. Despite extensive research on human somatosensory processing, it is still elusive how involved brain regions interact as a dynamic network in processing tactile information. Few studies probed temporal dynamics of somatosensory information flow and reported inconsistent results. Here, we examined cortical somatosensory processing through magnetic source imaging and cortico-cortical coupling dynamics. We recorded magnetoencephalography signals from typically developing children during unilateral pneumatic stimulation. Neural activities underlying somatosensory evoked fields were mapped with dynamic statistical parametric mapping, assessed with spatiotemporal activation analysis, and modeled by Granger causality. Unilateral pneumatic stimulation evoked prominent and consistent activations in the contralateral primary and secondary somatosensory areas but weaker and less consistent activations in the ipsilateral primary and secondary somatosensory areas. Activations in the contralateral primary motor cortex and supramarginal gyrus were also consistently observed. Spatiotemporal activation and Granger causality analysis revealed initial serial information flow from contralateral primary to supramarginal gyrus, contralateral primary motor cortex, and contralateral secondary and later dynamic and parallel information flows between the consistently activated contralateral cortical areas. Our study reveals the spatiotemporal dynamics of cortical somatosensory processing in the normal developing brain.

Discharge Best Practices of High-Risk Infants From Regional Children's Hospital NICUs.

OBJECTIVES: Lack of discharge preparedness after NICU hospitalization is associated with risk of readmission and parental stress. Complex infants cared for at regional children's hospital NICUs would benefit from a systematic approach to transition home. Our objective was to identify potential best practices for NICU discharge and examine priorities for incorporating these best practices in regional children's hospital NICUs. METHODS: We used techniques from quality improvement, including fish bone and key driver diagrams, yielding 52 potential best practice statements for discharge preparation. Using the modified Delphi method, we surveyed stakeholders on their level of agreement for the statement to be included in the final guideline regarding discharge processes and parental education. Consensus was defined as 85% agreement among respondents. To identify implementation feasibility and understand unit-level priorities, a prioritization and feasibility assessment survey was used to rank the top best practices and performed gap analyses for the first prioritized intervention. RESULTS: Fifty of the 52 statements met the predefined criteria for consensus. The prioritization survey of potential best practice statements named assessment of families' social determinants of health with a standardized tool as the top priority among respondents. Conducting gap analyses enabled an understanding of current practice, barriers, and affordances, allowing for implementation planning. CONCLUSIONS: This multicenter and interdisciplinary expert panel reached a consensus on multiple potential best practices for complex discharge preparation from regional children's hospital NICUs. Better support for families navigating the complex NICU discharge process has the potential to improve infant health outcomes.

Health Care Disparities in High-Risk Neonates.

Long-standing health disparities in maternal reproductive health, infant morbidity and mortality, and long-term developmental outcomes are rooted in a foundation of structural racism. Social determinants of health profoundly affect reproductive health outcomes of Black and Hispanic women disproportionately; they have higher rates of death during pregnancy and preterm birth. Their infants are also more likely to be cared for in poorer quality neonatal intensive care units (NICUs), receive poorer quality of NICU care, and are less likely to be referred to an appropriate high-risk NICU follow-up program. Interventions that mitigate the impact of racism will help to eliminate health disparities.

Association of Hospital Resource Utilization With Neurodevelopmental Outcomes in Neonates With Hypoxic-Ischemic Encephalopathy.

Importance: Intercenter variation exists in the management of hypoxic-ischemic encephalopathy (HIE). It is unclear whether increased resource utilization translates into improved neurodevelopmental outcomes. Objective: To determine if higher resource utilization during the first 4 days of age, quantified by hospital costs, is associated with survival without neurodevelopmental impairment (NDI) among infants with HIE. Design, Setting, and Participants: Retrospective cohort analysis of neonates with HIE who underwent therapeutic hypothermia (TH) at US children's hospitals participating in the Children's Hospitals Neonatal Database between 2010 and 2016. Data were analyzed from December 2021 to December 2022. Exposures: Infants who survived to 4 days of age and had neurodevelopmental outcomes assessed at greater than 11 months of age were divided into 2 groups: (1) death or NDI and (2) survived without NDI. Resource utilization was defined as costs of hospitalization including neonatal neurocritical care (NNCC). Data were linked with Pediatric Health Information Systems to quantify standardized costs by terciles. Main Outcomes and Measures: The main outcome was death or NDI. Characteristics, outcomes, hospitalization, and NNCC costs were compared. Results: Among the 381 patients who were included, median (IQR) gestational age was 39 (38-40) weeks; maternal race included 79 (20.7%) Black mothers, 237 (62.2%) White mothers, and 58 (15.2%) mothers with other race; 80 (21%) died, 64 (17%) survived with NDI (combined death or NDI group: 144 patients [38%]), and 237 (62%) survived without NDI. The combined death or NDI group had a higher rate of infants with Apgar score at 10 minutes less than or equal to 5 (65.3% [94 of 144] vs 39.7% [94 of 237]; P < .001) and a lower rate of infants with mild or moderate HIE (36.1% [52 of 144] vs 82.3% [195 of 237]; P < .001) compared with the survived without NDI group. Compared with low-cost centers, there was no association between high- or medium-hospitalization cost centers and death or NDI. High- and medium-EEG cost centers had lower odds of death or NDI compared with low-cost centers (high vs low: OR, 0.30 [95% CI, 0.16-0.57]; medium vs low: OR, 0.29 [95% CI, 0.13-0.62]). High- and medium-laboratory cost centers had higher odds of death or NDI compared with low-cost centers (high vs low: OR, 2.35 [95% CI, 1.19-4.66]; medium vs low: OR, 1.93 [95% CI, 1.07-3.47]). High-antiseizure medication cost centers had higher odds of death or NDI compared with low-cost centers (high vs. low: OR, 3.72 [95% CI, 1.51-9.18]; medium vs low: OR, 1.56 [95% CI, 0.71-3.42]). Conclusions and Relevance: Hospitalization costs during the first 4 days of age in neonates with HIE treated with TH were not associated with neurodevelopmental outcomes. Higher EEG costs were associated with lower odds of death or NDI yet higher laboratory and antiseizure medication costs were not. These findings serve as first steps toward identifying aspects of NNCC that are associated with outcomes.

Aberrant somatosensory phase synchronization in children with hemiplegic cerebral palsy.

Children with hemiplegic cerebral palsy (HCP) often show disturbances of somatosensation. Despite extensive evidence of somatosensory deficits, neurophysiological alterations associated with somatosensory deficits in children with HCP have not been elucidated. Here, we aim to assess phase synchrony within and between contralateral primary (S1) and secondary (S2) somatosensory areas in children with HCP. Intra-regional and inter-regional phase synchronizations within and between S1 and S2 were estimated from somatosensory evoked fields (SEFs) in response to passive pneumatic stimulation of contralateral upper extremities and recorded with pediatric magnetoencephalography (MEG) in children with HCP and typically developing (TD) children. We found aberrant phase synchronizations within S1 and between S1 and S2 in both hemispheres in children with HCP. Specifically, the less-affected (LA) hemisphere demonstrated diminished phase synchronizations after the stimulus onset up to ~120 ms compared to the more-affected (MA) hemisphere and the dominant hemisphere of TD children, while the MA hemisphere showed enhanced phase synchronizations after ~100 ms compared to the LA hemisphere and the TD dominant hemisphere. Our findings indicate abnormal somatosensory functional connectivity in both hemispheres of children with HCP.

Predictive Models of Neurodevelopmental Outcomes After Neonatal Hypoxic-Ischemic Encephalopathy.

OBJECTIVES: To develop predictive models for death or neurodevelopmental impairment (NDI) after neonatal hypoxic-ischemic encephalopathy (HIE) from data readily available at the time of NICU admission ("early") or discharge ("cumulative"). METHODS: In this retrospective cohort analysis, we used data from the Children's Hospitals Neonatal Consortium Database (2010-2016). Infants born at ≥35 weeks' gestation and treated with therapeutic hypothermia for HIE at 11 participating sites were included; infants without Bayley Scales of Infant Development scores documented after 11 months of age were excluded. The primary outcome was death or NDI. Multivariable models were generated with 80% of the cohort; validation was performed in the remaining 20%. RESULTS: The primary outcome occurred in 242 of 486 infants; 180 died and 62 infants surviving to follow-up had NDI. HIE severity, epinephrine administration in the delivery room, and respiratory support and fraction of inspired oxygen of 0.21 at admission were significant in the early model. Severity of EEG findings was combined with HIE severity for the cumulative model, and additional significant variables included the use of steroids for blood pressure management and significant brain injury on MRI. Discovery models revealed areas under the curve of 0.852 for the early model and of 0.861 for the cumulative model, and both models performed well in the validation cohort (goodness-of-fit χ2: P = .24 and .06, respectively). CONCLUSIONS: Establishing reliable predictive models will enable clinicians to more accurately evaluate HIE severity and may allow for more targeted early therapies for those at highest risk of death or NDI.

Abnormal Nutritive Sucking as an Indicator of Neonatal Brain Injury.

A term neonate is born with the ability to suck; this neuronal network is already formed and functional by 28 weeks gestational age and continues to evolve into adulthood. Because of the necessity of acquiring nutrition, the complexity of the neuronal network needed to suck, and neuroplasticity in infancy, the skill of sucking has the unique ability to give insight into areas of the brain that may be damaged either during or before birth. Interpretation of the behaviors during sucking shows promise in guiding therapies and how to potentially repair the damage early in life, when neuroplasticity is high. Sucking requires coordinated suck-swallow-breathe actions and is classified into two basic types, nutritive and non-nutritive. Each type of suck has particular characteristics that can be measured and used to learn about the infant's neuronal circuitry. Basic sucking and swallowing are present in embryos and further develop to incorporate breathing ex utero. Due to the rhythmic nature of the suck-swallow-breathe process, these motor functions are controlled by central pattern generators. The coordination of swallowing, breathing, and sucking is an enormously complex sensorimotor process. Because of this complexity, brain injury before birth can have an effect on these sucking patterns. Clinical assessments allow evaluators to score the oral-motor pattern, however, they remain ultimately subjective. Thus, clinicians are in need of objective measures to identify the specific area of deficit in the sucking pattern of each infant to tailor therapies to their specific needs. Therapeutic approaches involve pacifiers, cheek/chin support, tactile, oral kinesthetic, auditory, vestibular, and/or visual sensorimotor inputs. These therapies are performed to train the infant to suck appropriately using these subjective assessments along with the experience of the therapist (usually a speech therapist), but newer, more objective measures are coming along. Recent studies have correlated pathological sucking patterns with neuroimaging data to get a map of the affected brain regions to better inform therapies. The purpose of this review is to provide a broad scope synopsis of the research field of infant nutritive and non-nutritive feeding, their underlying neurophysiology, and relationship of abnormal activity with brain injury in preterm and term infants.

Extracorporeal membrane oxygenation and bloodstream infection in congenital diaphragmatic hernia.

OBJECTIVE: To characterize the risk of bloodstream (BSI) and urinary tract infection (UTI) and describe antibiotic use in infants with congenital diaphragmatic hernia (CDH) requiring extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: The Children's Hospitals Neonatal Database was queried for infants with CDH and ECMO treatment from 2010 to 2016. The outcomes included BSI, UTI, and antimicrobial medication. Member institutions completed a survey on infection practices. RESULT: Eighteen of the 338 patients identified (5.3%) had ≥1 BSI during their ECMO course. The likelihood of BSI increased with time: 1.2/1000 ECMO days; 0.6% (2/315) in the first week and rising to 14.6/1000; 8.6% (5/58) after 21 days (p = 0.002). More than 95% of patients received antibiotics each week on ECMO. CONCLUSIONS: Confirmed BSI is rare in infants with CDH treated with ECMO in the first week, but increases with the duration of ECMO. Use of antibiotics was extensive and did not correspond to infection frequency.

Predicting Risk of Infection in Infants with Congenital Diaphragmatic Hernia.

OBJECTIVE: To predict incident bloodstream infection and urinary tract infection (UTI) in infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: We conducted a retrospective analysis using the Children's Hospital Neonatal Database during 2010-2016. Infants with CDH admitted at 22 participating regional neonatal intensive care units were included; patients repaired or discharged to home prior to admission/referral were excluded. The primary outcome was death or the occurrence of bloodstream infection or UTI prior to discharge. Factors associated with this outcome were used to develop a multivariable equation using 80% of the cohort. Validation was performed in the remaining 20% of infants. RESULTS: Median gestation and postnatal age at referral in this cohort (n = 1085) were 38 weeks and 3.1 hours, respectively. The primary outcome occurred in 395 patients (36%); and was associated with low birth weight, low Apgar, low admission pH, renal and associated anomalies, patch repair, and extracorporeal membrane oxygenation (P < .001 for all; area under receiver operating curve = 0.824; goodness of fit χ2 = 0.52). After omitting death from the outcome measure, admission pH, patch repair of CDH, and duration of central line placement were significantly associated with incident bloodstream infection or UTI. CONCLUSIONS: Infants with CDH are at high risk of infection which was predicted by clinical factors. Early identification and low threshold for sepsis evaluations in high-risk infants may attenuate acquisition and the consequences of these infections.

Newborn intensive care survivors: a review and a plan for collaboration in Texas.

BACKGROUND: Neonatal intensive care is a remarkable success story with dramatic improvements in survival rates for preterm newborns. Significant efforts and resources are invested to improve mortality and morbidity but much remains to be learned about the short and long-term effects of neonatal intensive care unit (NICU) interventions. Published guidelines recommend that infants discharged from the NICU be in an organized follow-up program that tracks medical and neurodevelopmental outcomes. Yet, there are no standardized guidelines for provision of follow-up services for high-risk infants. The National Institute of Child Health and Human Development Neonatal Research Network and the Vermont Oxford Network have made strides toward standardizing practices and conducting outcomes research, but only include a subset of developmental follow-up programs with a focus on extremely preterm infants. Several studies have been conducted to gain a better understanding of current practices in developmental follow-up. Some of the major themes in these studies are the lack of personnel and funding to provide comprehensive follow-up care; feeding difficulties as a primary issue for NICU survivors, families, and programs; wide variability in referral and follow-up care practices; and calls for standardized, systematic developmental surveillance to improve outcomes. FINDINGS: We convened a one-day summit to discuss developmental follow-up practices in Texas involving four academic and three nonacademic centers. All seven centers described variable age and weight criteria for follow-up of NICU patients and a unique set of developmental practices, including duration of follow-up, types and timing of developmental assessments administered, education and communication with families and other health care providers, and referrals for services. Needs identified by the centers focused on two main themes: resources and comprehensive care. Participants identified key challenges for developmental follow-up, generated recommendations to address these challenges, and outlined components of a quality program. CONCLUSIONS: The long-term goal is to ensure that all children maximize their potential; a goal supported through quality, comprehensive developmental follow-up care and outcomes research to continuously improve evidence-based practices. We aim to contribute to this goal through a statewide working group collaborating on research to standardize practices and inform policies that truly benefit children and their families.

Postnatal weight gain in preterm infants with severe bronchopulmonary dysplasia.

OBJECTIVES: To characterize postnatal growth failure (PGF), defined as weight < 10th percentile for postmenstrual age (PMA) in preterm (≤ 27 weeks' gestation) infants with severe bronchopulmonary dysplasia (sBPD) at specified time points during hospitalization, and to compare these in subgroups of infants who died/underwent tracheostomy and others. STUDY DESIGN: Retrospective review of data from the multicenter Children's Hospital Neonatal Database (CHND). RESULTS: Our cohort (n = 375) had a mean ± standard deviation gestation of 25 ± 1.2 weeks and birth weight of 744 ± 196 g. At birth, 20% of infants were small for gestational age (SGA); age at referral to the CHND neonatal intensive care unit (NICU) was 46 ± 50 days. PGF rates at admission and at 36, 40, 44, and 48 weeks' PMA were 33, 53, 67, 66, and 79% of infants, respectively. Tube feedings were administered to > 70% and parenteral nutrition to a third of infants between 36 and 44 weeks' PMA. At discharge, 34% of infants required tube feedings and 50% had PGF. A significantly greater (38 versus 17%) proportion of infants who died/underwent tracheostomy (n = 69) were SGA, compared with those who did not (n = 306; p < 0.01). CONCLUSIONS: Infants with sBPD commonly had progressive PGF during their NICU hospitalization. Fetal growth restriction may be a marker of adverse outcomes in this population.

Death or neurodevelopmental impairment at 18 to 22 months corrected age in a randomized trial of early dexamethasone to prevent death or chronic lung disease in extremely low birth weight infants.

OBJECTIVE: To evaluate the incidence of death or neurodevelopmental impairment (NDI) at 18-22 months corrected age in subjects enrolled in a trial of early dexamethasone treatment to prevent death or chronic lung disease in extremely low birth weight infants. STUDY DESIGN: Evaluation of infants at 18-22 months corrected age included anthropomorphic measurements, a standard neurological examination, and the Bayley Scales of Infant Development-II, including the Mental Developmental Index and the Psychomotor Developmental Index. NDI was defined as moderate or severe cerebral palsy, Mental Developmental Index or Psychomotor Developmental Index <70, blindness, or hearing impairment. RESULTS: Death or NDI at 18-22 months corrected age was similar in the dexamethasone and placebo groups (65% vs 66%, P = .99 among those with known outcome). The proportion of survivors with NDI was also similar, as were mean values for weight, length, and head circumference and the proportion of infants with poor growth (50% vs 41%, P = .42 for weight less than 10th percentile); 49% of infants in the placebo group received treatment with corticosteroid compared with 32% in the dexamethasone group (P = .02). CONCLUSION: The risk of death or NDI and rate of poor growth were high but similar in the dexamethasone and placebo groups. The lack of a discernible effect of early dexamethasone on neurodevelopmental outcome may be due to frequent clinical corticosteroid use in the placebo group.

Impact of prenatal evaluation and protocol-based perinatal management on congenital diaphragmatic hernia outcomes.

BACKGROUND/PURPOSE: Although intuitive, the benefit of prenatal evaluation and multidisciplinary perinatal management for fetuses with congenital diaphragmatic hernia (CDH) is unproven. We compared the outcome of prenatally diagnosed patients with CDH whose perinatal management was by a predefined protocol with those who were diagnosed postnatally and managed by the same team. We hypothesized that patients with CDH undergoing prenatal evaluation with perinatal planning would demonstrate improved outcome. METHODS: Retrospective chart review of all patients with Bochdalek-type CDH at a single institution between 2004 and 2009 was performed. Patients were stratified by history of perinatal management, and data were analyzed by Fisher's Exact test and Student's t test. RESULTS: Of 116 patients, 71 fetuses presented in the prenatal period and delivered at our facility (PRE), whereas 45 infants were either outborn or postnatally diagnosed (POST). There were more high-risk patients in the PRE group compared with the POST group as indicated by higher rates of liver herniation (63% vs 36%, P = .03), need for patch repair (57% vs 27%, P = .004), and extracorporeal membrane oxygenation use (35% vs 18%, P = .05). Despite differences in risk, there was no difference in 6-month survival between groups (73% vs 73%). CONCLUSIONS: Patients with CDH diagnosed prenatally are a higher risk group. Prenatal evaluation and multidisciplinary perinatal management allows for improved outcome in these patients.

Neurodevelopmental outcomes of premature infants with severe respiratory failure enrolled in a randomized controlled trial of inhaled nitric oxide.

OBJECTIVES: We hypothesized that inhaled nitric oxide (iNO) would not decrease death or neurodevelopmental impairment (NDI) in infants enrolled in the National Institute of Child Health and Human Development Preemie iNO Trial (PiNO) trial, nor improve neurodevelopmental outcomes in the follow-up group. STUDY DESIGN: Infants <34 weeks of age, weighing <1500 g, with severe respiratory failure were enrolled in the multicenter, randomized, controlled trial. NDI at 18 to 22 months corrected age was defined as: moderate to severe cerebral palsy (CP; Mental Developmental Index or Psychomotor score Developmental Index <70), blindness, or deafness. RESULTS: Of 420 patients enrolled, 109 who received iNO (52%) and 98 who received placebo (47%) died. The follow-up rate in survivors was 90%. iNO did not reduce death or NDI (78% versus 73%; relative risk [RR], 1.07; 95% CI, 0.95-1.19), or NDI or Mental Developmental Index <70 in the follow-up group. Moderate-severe CP was slightly higher with iNO (RR, 2.41; 95% CI, 1.01-5.75), as was death or CP in infants weighing <1000 g (RR, 1.22; 95% CI, 1.05-1.43). CONCLUSIONS: In this extremely ill cohort, iNO did not reduce death or NDI or improve neurodevelopmental outcomes. Routine iNO use in premature infants should be limited to research settings until further data are available.

Real-time polymerase chain reaction for the rapid detection of group B streptococcal colonization in neonates.

BACKGROUND: Group B streptococcal (GBS) infection remains a leading cause of neonatal sepsis. Currently, the management guidelines of neonates born to women with unknown GBS status at delivery are unclear. In this cohort, who undergo at least a 48-hour observation, a rapid method of detection of GBS colonization would allow targeted evaluation and treatment, as well as prevent delayed discharge. OBJECTIVE: The goal of this research was to evaluate the validity of rapid fluorescent real-time polymerase chain reaction in comparison with standard culture to detect GBS colonization in infants born to women whose GBS status is unknown at delivery. DESIGN/METHODS: Neonates at >32 weeks' gestation born to women whose GBS status was unknown at delivery were included. Samples were obtained from the ear, nose, rectum, and gastric aspirate for immediate culture and real-time polymerase chain reaction after DNA extraction using the LightCycler. Melting point curves were generated, and confirmatory agar gel electrophoresis was performed. RESULTS: The study population (n = 94) had a mean +/- SD gestational age of 38 +/- 2 weeks and birth weight of 3002 +/- 548 g. The rates of GBS colonization by culture were 17% and 51% by real-time polymerase chain reaction. The 4 surface sites had comparable rates of GBS. The overall sensitivities, specificities, and positive and negative predictive values of real-time polymerase chain reaction were: 90%, 80.3%, 28%, and 98.9%. CONCLUSIONS: Real-time polymerase chain reaction resulted in a threefold higher rate of detection of GBS colonization and had an excellent negative predictive value in a cohort of neonates with unknown maternal GBS status at delivery. Thus, real-time polymerase chain reaction would be a useful clinical tool in the management of those infants potentially at risk for invasive GBS infection and would allow earlier discharge for those found to be not at risk.