Neurodevelopmental Outcomes Research Articles

Prediction of Cerebral Palsy and Other Motor Developmental Trajectories in High-Risk Neonate Using the Rapid Neurodevelopmental Assessment (RNDA)

Background: Cerebral Palsy (CP) is a prevalent motor disability affecting children globally, emphasizing the need for early identification and intervention. The Rapid Neurodevelopmental Assessment (RNDA) offers a comprehensive approach to predict CP and other motor developmental trajectories in high-risk neonates. Objective: This longitudinal cohort study aims to evaluate the effectiveness of RNDA in predicting CP and motor developmental trajectories. Method: Seventy term neonates from Dhaka Shishu (Children) Hospital were included, with neurodevelopmental assessments conducted using RNDA. Assessments were performed at 3 months and 6-9 months, with CP evaluation at 12 months using clinical examinations. Results: Prolonged labor (44.3%) and delayed cry after birth (31.4%) were common among the study patients (n=70), with varying modes of delivery including normal vaginal delivery (50.0%), vaginal delivery with complications (12.9%), and lower uterine cesarean section (37.1%). Muscle tone, primitive reflexes, gross and fine motor skills, epilepsy, and microcephaly were evaluated across visits to identify impending CP. Significant associations were found between hypertonicity, primitive reflex impairment, gross motor impairment, and fine motor impairment with impending CP across visits, particularly in the 3rd visit (p<0.05). Sensitivity, specificity, accuracy, and predictive values varied across parameters and visits, with fine motor skills and gross motor skills showing the highest sensitivity in the 3rd visit (86.4% and 100.0%, respectively). Additionally, abnormal EEG, USG of the brain, and MRI findings were significantly associated with impending CP, with USG of the brain demonstrating the highest sensitivity (93.3%) and MRI showing the highest specificity (70.0%). Conclusion: RNDA emerges as a valuable tool for early prediction of CP and motor developmental trajectories in high-risk neonates. Early identification through RNDA facilitates timely interventions, optimizing long-term neurodevelopmental outcomes.

Neonatal dysglycemia: a review of dysglycemia in relation to brain health and neurodevelopmental outcomes.

Neonatal dysglycemia has been a longstanding interest of research in neonatology. Adverse outcomes from hypoglycemia were recognized early but are still being characterized. Premature infants additionally introduced and led the reflection on the importance of neonatal hyperglycemia. Cohorts of infants following neonatal encephalopathy provided further information about the impacts of hypoglycemia and, more recently, highlighted hyperglycemia as a central concern for this population. Innovative studies exposed the challenges of management of neonatal glycemic levels with a "u-shape" relationship between dysglycemia and adverse neurological outcomes. Lately, glycemic lability has been recognized as a key factor in adverse neurodevelopmental outcomes. Research and new technologies, such as MRI and continuous glucose monitoring, offered novel insight into neonatal dysglycemia. Combining clinical, physiological, and epidemiological data allowed the foundation of safe operational definitions, including initiation of treatment, to delineate neonatal hypoglycemia as ≤47 mg/dL, and >150-180 mg/dL for neonatal hyperglycemia. However, questions remain about the appropriate management of neonatal dysglycemia to optimize neurodevelopmental outcomes. Research collaborations and clinical trials with long-term follow-up and advanced use of evolving technologies will be necessary to continue to progress the fascinating world of neonatal dysglycemia and neurodevelopment outcomes. IMPACT STATEMENT: Safe operational definitions guide the initiation of treatment of neonatal hypoglycemia and hyperglycemia. Innovative studies exposed the challenges of neonatal glycemia management with a "u-shaped" relationship between dysglycemia and adverse neurological outcomes. The importance of glycemic lability is also being recognized. However, questions remain about the optimal management of neonatal dysglycemia to optimize neurodevelopmental outcomes. Research collaborations and clinical trials with long-term follow-up and advanced use of evolving technologies will be necessary to progress the fascinating world of neonatal dysglycemia and neurodevelopment outcomes.

Possible associations between prenatal exposure to environmental pollutants and neurodevelopmental outcome in children

This study aimed to evaluate associations between prenatal and childhood exposure to phthalates and prenatal exposure to polychlorinated biphenyls (PCBs) and the development of 4-year-old children. Urinary metabolites of five phthalates were measured in women upon delivery, as well as serum concentrations of four PCB congeners. Postnatal phthalate metabolites were measured from children's urine obtained at the time of developmental assessment. The primary outcome was cognitive function as evaluated by the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) administered at 4 years. Secondary outcomes were motor function and response to sensory stimuli as evaluated by the Developmental Coordination Disorder Questionnaire (DCDQ) and Short Sensory Profile (SSP) that the mothers filled out, respectively. The study included 57 mother-child pairs. Higher maternal phthalate metabolite concentrations were inversely associated with WPPSI-III scores among boys and not among girls. After using linear regression models and controlling for confounding variables, we found that higher levels of monobenzyl phthalate (MBzP) were the ones associated with lower WPPSI-III scores (p=0.004, 95 %CI [-14.18; −3.16]), lower DCDQ scores (p=0.007, 95 %CI [-6.08; −1.17] and lower SSP scores (p=0.004, 95 %CI [-7.47; −1.79]). No association was found between child urinary phthalate metabolite concentrations or maternal PCB blood concentrations and developmental function. These findings indicate that higher prenatal phthalate metabolite levels may be associated with deficits in neurologic development of young boys.

Identifying novel data-driven subgroups in congenital heart disease using multi-modal measures of brain structure

Individuals with congenital heart disease (CHD) have an increased risk of neurodevelopmental impairments. Given the hypothesized complexity linking genomics, atypical brain structure, cardiac diagnoses and their management, and neurodevelopmental outcomes, unsupervised methods may provide unique insight into neurodevelopmental variability in CHD. Using data from the Pediatric Cardiac Genomics Consortium Brain and Genes study, we identified data-driven subgroups of individuals with CHD from measures of brain structure. Using structural magnetic resonance imaging (MRI; N = 93; cortical thickness, cortical volume, and subcortical volume), we identified subgroups that differed primarily on cardiac anatomic lesion and language ability. In contrast, using diffusion MRI (N = 88; white matter connectivity strength), we identified subgroups that were characterized by differences in associations with rare genetic variants and visual-motor function. This work provides insight into the differential impacts of cardiac lesions and genomic variation on brain growth and architecture in patients with CHD, with potentially distinct effects on neurodevelopmental outcomes.

P-756 Neurodevelopmental outcomes at school-age after conception with hysterosalpingography using iodinated contrast media - follow-up of the nationwide multicentre H2Oil trial

Abstract Study question How does conception <6 months after hysterosalpingography (HSG) with iodinated contrast media affect the neurodevelopment of the offspring compared to naturally-conceived peers at a school-age? Summary answer Children conceived <6 months after HSG with iodinated contrast media perform lower on intelligence tests and information processing and attention control compared to naturally-conceived peers. What is known already Tubal patency in subfertile women is commonly assessed using hysterosalpingography (HSG), but the potential risks of exposure to high iodine content in contrast media used remains unknown. Exposure to iodine excess can cause transient reduction in thyroid hormone synthesis due to the Wolff-Chaikoff effect. Thyroid hormone sufficiency in early pregnancy is vital for children’s neurodevelopment. When conception occurs shortly after HSG with iodinated contrast, a temporary reduction of maternal and/or foetal thyroid hormone supply could jeopardize children’s neurodevelopment. Study design, size, duration We evaluated neurodevelopmental outcomes of 6–9-year-old children conceived <6 months after HSG with oil-based (iodine content: 480mg/ml) or water-based contrast (iodine content: 240-300mg/ml) in a nationwide randomised controlled trial (H2Oil trial; Netherlands; 2012-2014; NCT05168228). Naturally-conceived children (n = 44) with similar age, sex and parental education were used as a comparison group (NTR9574). We also compared children conceived <4w, 4-12w, >12w after HSG with those conceived naturally. The study took place January 2022 until November 2023. Participants/materials, setting, methods We contacted 140 mothers from the H2Oil trial, 69 children conceived <6m after HSG participated, and parallelly we recruited 44 naturally-conceived children. Primary outcomes were intelligence (Wechsler’s Intelligence Scale for Children V), behavioural functioning (SDQ and SWAN, administered to parents and teachers), and academic performance. Secondary outcomes were neurocognitive function assessed by a battery of computerized tests. We used linear regression adjusted for age, sex, and parental education and applied FDR correction. Main results and the role of chance Compared to naturally conceived children, children conceived <6m after HSG had lower performance on intelligence tests (-6.81; 95%CI-10.97 to -2.65; p = 0.02) and the neurocognitive domain Processing & Control (-0.52; 95%CI-0.84 to -0.19; p = 0.02), with functions relating to information processing speed and consistency affected. No differences were found for other neurocognitive domains, behaviour or academic performance. Considering time between HSG and conception, intelligence scores were lower for children conceived <4w after HSG compared to naturally-conceived peers (-11.47; 95%CI-17.98 to -4.95; p = 0.03), while no significant differences were found for the groups of children conceived 4-12 weeks after HSG (-7.17; 95%CI -12.28 to -2.06; p = 0.10) or > 12 weeks after HSG (-4.20; 95%CI -9.33 to 0.94; p = 0.52). The findings of this study warrant replication in larger independent samples in order to evaluate the long-term neurodevelopment of children conceived after HSG with iodinated contrast media. Limitations, reasons for caution We aimed to recruit 64 children for each group, but our study was not sufficiently powered for small- and medium-sized differences. We did not collect information on the thyroid or iodine status of the mothers following HSG, and there is limited knowledge about pharmacokinetics of iodinated contrast media in humans. Wider implications of the findings Replication studies with are needed to further evaluate the safety of iodinated contrast media use periconception, including their effects on thyroid function and children’s neurodevelopment. Closer monitoring and treatment of thyroid dysfunction in the months following HSG may be warranted. Trial registration number NCT05168228

Regional variations in morbidity and mortality among neonates with intraventricular hemorrhage: a national database analysis.

Intraventricular hemorrhage (IVH) often affects newborns of low gestational age and low birth weight, requires critical care for neonates, and is linked to long-term neurodevelopmental outcomes. Assessing regional differences in the U.S. in care for neonatal IVH and subsequent outcomes can shed light on ways to mitigate socioeconomic disparities. Using the 2016-2019 National Inpatient Sample (NIS), patients with a primary diagnosis of IVH were identified using ICD-10-CM codes. A retrospective cohort study was conducted with patients stratified by hospital region. Demographics, comorbidities, presentation, intraoperative variables, and inpatient outcomes were assessed. Multivariate logistic regression analyses were used to identify the impact of insurance status on extended LOS (defined as > 75th percentile of LOS), exorbitant cost (defined as > 75th percentile of cost), and mortality. Included in this study were 1630 newborns with IVH. A larger portion of patients in the South and Midwest were Black, compared to the Northeast and West (Northeast: 12.2% vs Midwest: 30.2% vs South: 22.8% vs West: 5.8%, p < 0.001), while a greater percentage of patients in the West and South were Hispanic (Northeast: 7.3% vs Midwest: 9.5% vs South: 22.8% vs West: 36.2%, p < 0.001). LOS was similar among all regions. Factors associated with prolonged LOS included hydrocephalus and CSF diversions. Median total cost of admission was highest in the West, while the South was associated with decreased odds of exorbitant cost. LOS was associated with exorbitant cost, and large bed-volume hospital, VLBW, and permanent CSF shunt were associated with mortality. Demographic variables, but not presenting or intraoperative variables, differed among regions, pointing to possible geographic health disparities. The West had the highest total cost of admission, while the South was associated with reduced odds of exorbitant admission costs.

Has the COVID-19 pandemic negatively impacted children's development? An assessment of the neurodevelopment of premature babies born during the pandemic.

Pandemics, such as COVID-19, have the potential to adversely affect children's development due to a variety of negative factors at the level of children, families, and services. In this study the effect of the pandemic on the cognitive, language and motor development of premature babies who are among the most vulnerable group, were evaluated. The study included 236 premature infants who were followed at Hacettepe University Department of Developmental Pediatrics. The Bayley-Third Edition Developmental Assessment (Bayley III) was used to evaluate the neurodevelopment of 152 premature infants from the pre-pandemic group and 84 from the post-pandemic group at the corrected age of 18-24 months. The perinatal and sociodemographic risks were also evaluated. No difference in Bayley III scores (cognitive, language, and motor) was found between the pre- and post-pandemic groups. Furthermore, the multivariate covariance analysis displayed that regardless of the pandemic, infants with higher maternal education consistently scored higher in the cognitive, language, and motor domains; and the motor area scores of infants with moderate perinatal risk were also significantly higher than infants with high perinatal risk. It is crucial to monitor the development of vulnerable children who encounter developmental risks, such as premature babies. Fortunately, no significant effect was encountered during the COVID-19 pandemic. However, this does not underweigh the need for close supervision in extraordinary circumstances. Additionally, it should be noted that severe postnatal comorbidities, perinatal risks, and social factors, such as maternal education level, interact to influence the neurodevelopmental outcomes of preterm infants.

Mortality and neurodevelopmental outcomes at 2years' corrected age of very preterm infants with necrotising enterocolitis or spontaneous intestinal perforation: The EPIPAGE-2 cohort study.

The primary objective was to evaluate the impact of necrotising enterocolitis (NEC) and spontaneous intestinal perforation (SIP) on mortality and neurodevelopmental outcomes at 2years' corrected age (CA) in infants born before 32weeks' gestation (WG). We studied neurodevelopment at 2years' CA of infants with NEC or SIP who were born before 32 WG from the EPIPAGE-2 cohort study. The primary outcome was death or the presence of moderate-to-severe motor or sensory disability defined by moderate-to-severe cerebral palsy or hearing or visual disability. The secondary outcome was developmental delay defined by a score < 2 SDs below the mean for any of the five domains of the Ages and Stages Questionnaire. At 2years' CA, 46% of infants with SIP, 34% of infants with NEC, and 14% of control infants died or had a moderate-to-severe sensorimotor disability (p < 0.01). This difference was mainly due to an increase in in-hospital mortality in the infants with SIP or NEC. Developmental delay at 2years' CA was more frequent for infants with SIP than controls (70.8% vs 44.0%, p = 0.02) but was similar for infants with NEC and controls (49.3% vs 44.0%, p = 0.5). On multivariate analysis, the likelihood of developmental delay was associated with SIP (adjusted odds ratio = 3.0, 95% CI 1.0-9.1) but not NEC as compared with controls. NEC and SIP significantly increased the risk of death or sensorimotor disability at 2years' CA. SIP was also associated with risk of developmental delay at 2years' CA.

Comparison of “IN-REC-SUR-E” and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial)

BackgroundSurfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration.MethodsIn this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks).Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR).DiscussionThis trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life.Trial registrationClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Association of germinal matrix hemorrhage volume with neurodevelopment and hydrocephalus.

The objective of this study was to evaluate whether volumetric measurements on early cranial ultrasound (CUS) in high-grade germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) are associated with hydrocephalus and neurodevelopmental metrics. A retrospective case series analysis of infants with high-grade GMH-IVH admitted to the St. Louis Children's Hospital neonatal intensive care unit between 2007 and 2015 who underwent neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) at 2 years of corrected age was performed. GMH volume, periventricular hemorrhagic infarction volume, and frontotemporal horn ratio were obtained from direct review of neonatal CUS studies. Univariate and multivariable regression models were used to evaluate the association between hemorrhage volumes and hydrocephalus requiring permanent CSF diversion with ventricular shunt or endoscopic third ventriculostomy with or without choroid plexus cauterization and composite Bayley-III cognitive, language, and motor scores. Forty-three infants (29 males, mean gestational age 25 weeks) met the inclusion criteria. The mean age at time of the CUS with the largest hemorrhage volume or first diagnosis of highest grade was 6.2 days. Nineteen patients underwent treatment for hydrocephalus with permanent CSF diversion. In multivariable analyses, larger GMH volume was associated with worse estimated Bayley-III cognitive (left-sided GMH volume: p = 0.048, total GMH volume: p = 0.023) and motor (left-sided GMH volume: p = 0.010; total GMH volume: p = 0.014) scores. Larger periventricular hemorrhagic infarction volume was associated with worse estimated Bayley-III motor scores (each side p < 0.04). Larger left-sided (OR 2.55, 95% CI 1.10-5.88; p = 0.028) and total (OR 1.35, 95% CI 1.01-1.79; p = 0.041) GMH volumes correlated with hydrocephalus. There was no relationship between early ventricular volume and hydrocephalus or neurodevelopmental outcomes. Location-specific hemorrhage volume on early CUS may be prognostic for neurodevelopmental and hydrocephalus outcomes in high-grade GMH-IVH.

What are the neurodevelopmental outcomes of children with asymptomatic congenital cytomegalovirus infection at birth? A systematic literature review.

Congenital cytomegalovirus (cCMV) is among the most common congenital infections globally. Of 85%-90% cCMV-infected infants without symptoms at birth, 10%-15% develop sequelae, most commonly sensorineural hearing loss (SNHL); their childhood neurodevelopmental outcomes are less well understood. Embase and MEDLINE were searched for publications from 16th September 2016 to 9th February 2024 to identify studies reporting primary data on neurodevelopmental outcomes in children with asymptomatic cCMV (AcCMV), measured using assessment tools or as evaluated by the study investigators, clinicians, educators, or parents. The Newcastle-Ottawa scale was applied to studies to assess risk of bias. Of 28 studies from 18 mostly high-income countries, there were 5-109 children with AcCMV per study and 6/28 had a mean or median age at last follow-up of ≥5years. Children with AcCMV had better neurodevelopmental outcomes than children with symptomatic cCMV in 16/19 studies. Of 9/28 studies comparing AcCMV with CMV-uninfected children, six reported similar outcomes whilst three reported differences limited to measures of full-scale intelligence and receptive vocabulary among children with AcCMV and SNHL, or more generally in motor impairment. Common limitations of studies for our question were a lack of cCMV-uninfected controls, heterogeneous definitions of AcCMV, lack of focus on neurodevelopment, selection bias and inadequate follow-up. There was little evidence of children with AcCMV having worse neurodevelopmental outcomes than CMV-uninfected children, but this conclusion is limited by study characteristics and quality; findings highlight the need for well-designed and standardised approaches to investigate long-term sequelae.

Epidemiology and outcome of infantile spasms in Denmark in 1996–2019

PurposeTo investigate the treatment of infantile epileptic spasm syndrome (IESS) in Denmark. MethodsNational retrospective cohort study of all patients born 1996–2019 who had a diagnosis of IESS in the National Patient Registry. Medical records were reviewed to evaluate the diagnosis. Patients were included if semiology was compatible with IESS, or if unclear semiology if there was an abnormal EEG or EEG with hypsarrhythmia. ResultsNumber of cases with a register based IESS diagnosis was 538. Medical records were unavailable in 48 and 164 did not fulfil the inclusion criteria. Thereby the cohort consisted of 326 children. Mean age at onset of IESS was 5.9 months and mean lead time to treatment was 26.6 days (SD= 63.5). Consistent with the Danish treatment guidelines most patients received vigabatrin as first treatment. In the cohort 44.7 % of patients solely received vigabatrin, whereas combined vigabatrin and corticosteroid was given to 28.3 % (either hydrocortisone or prednisolone). Other anti-seizure medication was given to 28.4 % within 90 days of IESS onset. Aetiology was prenatal (40.3 %), perinatal (10.5 %), postnatal (3.7 %), with unknown timing (10.2 %) or with unknown aetiology (33.5 %). The cohort was followed to a mean age of 8.2 years. At latest follow-up severe neurodevelopmental outcome was seen in 44.2 % and 76.4 % still had epilepsy. The incidence of IESS was 22 per 100.000 live births. ConclusionIn Denmark treatment algorithm is based on start of treatment with vigabatrin. A total of 44.7 % became seizure free by vigabatrin. Neurodevelopmental outcome was severe. A national incidence could be established.

Effect of cannabidiol as a neuroprotective agent on neurodevelopmental impairment in rats with neonatal hypoxia

ObjectiveThis study aims to investigate the neuroprotective effects of cannabidiol (CBD) on neurodevelopmental impairments in rats subjected to neonatal hypoxia, specifically examining its potential to mitigate motor and sensory deficits without the confounding effects of ischemia. MethodsNeonatal Sprague-Dawley rats were allocated to one of four groups: Control, Control-CBD, Hypoxia, and Hypoxia-CBD. Hypoxia was induced on postnatal days 0 and 1. CBD (50 mg/kg) was administered orally for 14 days starting at postnatal day 0. Neurodevelopmental outcomes were assessed using the Neurodevelopmental Reflex Testing in Neonatal Rat Pups scale and the Revised Neurobehavioral Severity Scale for rodents. Statistical analyses were conducted using two-way and one-way ANOVA, with Tukey’s post-hoc tests for group comparisons. ResultsPup weights were recorded on specified postnatal days, with no significant differences observed across the groups (p = 0.1834). Significant neurological impairments due to hypoxia were noted in the Control group compared to the Hypoxia group, particularly in hindlimb grasping on postnatal day 3 (p = 0.0025), posture on postnatal day 12 (p = 0.0073), and in general balance and sound reflex on postnatal day 20 (p = 0.0016 and p = 0.0068, respectively). Additionally, a statistically significant improvement in posture was observed in the Hypoxia-CBD group compared to the Hypoxia group alone (p = 0.0024). ConclusionOur findings indicate that CBD possesses neuroprotective properties that significantly counteract the neurodevelopmental impairments induced by neonatal hypoxia in rats. This study not only supports the therapeutic potential of CBD in managing conditions characterized by neurodevelopmental challenges due to hypoxia but also underscores the necessity for further investigation into the specific molecular mechanisms driving CBD’s neuroprotective effects. Further research is essential to explore CBD’s clinical applications and its potential role in treating human neurodevelopmental disorders.

The effects of buprenorphine and morphine during pregnancy: Impact of exposure length on maternal brain, behavior, and offspring neurodevelopment

The escalating incidence of opioid-related issues among pregnant women in the United States underscores the critical necessity to understand the effects of opioid use and Medication for Opioid Use Disorders (MOUDs) during pregnancy. This research employed a translational rodent model to examine the impact of gestational exposure to buprenorphine (BUP) or morphine on maternal behaviors and offspring well-being. Female rats received BUP or morphine before conception, representing established use, with exposure continuing until postnatal day 2 or discontinued on gestational day 19 to mimic treatment cessation before birth. Maternal behaviors – including care, pup retrieval, and preference – as well as hunting behaviors and brain neurotransmitter levels were assessed. Offspring were evaluated for mortality, weight, length, milk bands, surface righting latency, withdrawal symptoms, and brain neurotransmitter levels. Our results reveal that regardless of exposure length (i.e., continued or discontinued), BUP resulted in reduced maternal care in contrast to morphine-exposed and control dams. Opioid exposure altered brain monoamine levels in the dams and offspring, and was associated with increased neonatal mortality, reduced offspring weight, and elevated withdrawal symptoms compared to controls. These findings underscore BUP's potential disruption of maternal care, contributing to increased pup mortality and altered neurodevelopmental outcomes in the offspring. This study calls for more comprehensive research into prenatal BUP exposure effects on the maternal brain and infant development with the aim to mitigate adverse outcomes in humans exposed to opioids during pregnancy.

Artificial Intelligence Applications in Neonatal Critical Care: A Scoping Review

Background: The development of artificial intelligence (AI) approaches impacted drug discovery, medical imaging, customized diagnostics, and therapeutics. Medicine will be transformed by AI. One such area of medicine where AI is significantly improving care is neonatology. Objective: The objective of this scoping review is to explore the applications of AI in neonatal critical care and its outcome. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a scoping review was conducted utilizing the Web of Science, MEDLINE (PubMed), and Scopus databases. The search was limited to full-text publications on AI applications in neonatal critical care that were published between January 1, 2019, and December 31, 2023. Articles specifically addressing the application of AI in neonatal care have been considered within the scope of this review. At least three reviewers had independently executed the screening, data abstraction, and exploration. Results: Database searches yielded 631 articles, of which 11 met the inclusion criteria. The research encompassed extensive AI applications in neonatal critical care, employed for prognosis, diagnosis, and therapy strategizing. Artificial neural networks, machine learning, deep learning, and shallow hybrid neural networks were the commonly utilized AI techniques (neonatal critical care). These methods were applied to screen for inborn metabolic abnormalities, predict various outcomes, including death and sepsis, identify diseases such as sepsis, and assess neurodevelopmental outcomes in preterm newborns, helping plan several medical treatments. The included research demonstrated encouraging outcomes when using AI in neonatal critical care. Conclusions: AI-driven electronic arrangements upgrade neonatal basic care by improving risk forecast, promising critical commitments to future health care. Be that as it may, careful appraisal, evidence-based considers, and determination of safety, ethics, and information straightforwardness issues are essential before implementation. Acceptance by administrative bodies and the therapeutic community pivots on tending to these concerns.

Precision Medicine: Trends In Perinatal Gynecology

The Kurjak Antenatal Neurodevelopmental Test (KANET) has revolutionized prenatal care and fetal neurology by providing a non-invasive method to assess fetal neurodevelopment using fourdimensional ultrasound (4D US). Over the past ten years, KANET has been widely implemented across various clinical settings, enabling the early detection of neurodevelopmental disorders. This early identifi cation is crucial for timely intervention and improved long-term outcomes. KANET standardizes the assessment of fetal neurological function, off ering a structured and objective approach that enhances our understanding of fetal behavior and its implications for postnatal development. While KANET demonstrates high specifi city and a low false-negative rate, its sensitivity in detecting specifi c conditions like cerebral palsy (CP) remains limited. The test’s widespread use has not only informed clinical management strategies but also promoted further research into prenatal neurodevelopment and potential prenatal interventions. Recent studies highlight diff erences in fetal behavior in pregnancies complicated by gestational diabetes, suggesting the potential for KANET to inform future neurodevelopmental outcomes. Continued research and refi nement of KANET are essential to enhance its predictive accuracy and ensure comprehensive postnatal follow-up.

Severe brain injury and trends of gestational‐age‐related neurodevelopmental outcomes in infants born very preterm: A population cohort study

AbstractAimTo investigate the impact of severe neonatal brain injury (SNBI) on gestational age‐related trends in neurodevelopmental impairment (NDI) outcome in infants born very preterm.MethodA population‐based cohort study recruited 1091 infants born at a gestational age of less than 31 weeks between 2011 and 2020. The trends in neonatal morbidities, mortality, and 24‐month NDI severity (no/mild, moderate, severe) by epoch (2011–2015, 2016–2020) and gestational age (22–25 weeks, 26–28 weeks, 29–30 weeks) were determined in infants with and without SNBI inclusion.ResultsThere was increased antenatal steroid use and higher maternal education and socioeconomic status over time. The rates of neonatal morbidities and mortality had no temporal changes. Among 825 infants with follow‐up, those in the 22 to 25 weeks gestational age group had declining trends in cerebral palsy and severe cognitive impairment, with decreased rates of severe NDI from 19% to 8% across epochs, particularly in those without SNBI (from 16% to 2%). Relative to its occurrence in epoch 2011 to 2015, risk of severe NDI was significantly reduced in epoch 2016 to 2020 (adjusted relative risk 0.39, 95% confidence interval 0.16–0.96) for infants born at 22 to 25 weeks gestational age, and the risk dropped even lower in these infants without SNBI (0.12, 0.02–0.84).InterpretationInfants born at 22 to 25 weeks gestational age had decreased rates of severe NDI in the decade between 2011 and 2020, particularly those without SNBI. The improvement might be attributed to better perinatal/neonatal and after‐discharge care.

Implementation of a Standardized Feeding Protocol in a Level III Neonatal Intensive Care Unit

Introduction: The nutritional management of preterm infants in the Neonatal Intensive Care Unit (NICU) can be challenging and can often lead to extrauterine growth restriction (EUGR). A new feeding protocol was recently established and implemented at Ascension St. John’s NICU. Objectives: 1.) To determine the association of a standardized feeding protocol in the NICU and feeding intolerance, as well as growth outcomes and the number of days on parenteral nutrition; and 2.) To determine the association of a standardized feeding protocol and the development of necrotizing enterocolitis and central line associated infections. Methods: This study was a historical cohort study done by retrospective chart review. The pre-feeding protocol period included infants &lt;32 weeks gestation and &lt;1500g who were in the NICU between 1/1/2018 to 12/31/2020. The post-feeding protocol period was from 1/1/2021 to 11/15/2023. Data were recorded on demographics; and measurements at birth, 34 weeks postmenstrual age, and at discharge. Nutritional milestones and clinical outcomes were collected. Statistical analysis was done using Student’s t-test, the chi-squared test, the Mann-Whitney U test and repeated measures analysis of variance. Results: A total of 243 infants were included: 158 pre-implementation and 85 post-implementation of protocol. The mean gestational age was 27.7 ± 2.3 weeks, 61.7% of infants were black and 53.5% were female; there were no significant differences by time period. Results show no statistically significant difference in growth outcomes, days when infants received nothing by mouth; necrotizing enterocolitis, or sepsis. There was a delay in fortification and reaching full feeds, longer parental nutrition and central line days, and higher number of central line associated infections in the post-implementation period. Rates of intraventricular hemorrhage, retinopathy of prematurity and pulmonary outcomes were improving. Conclusions: The data suggest that implementation of a standardized feeding protocol can improve short term morbidities in high-risk neonates. Future studies are needed to optimize feeding protocols with the goal of improving growth, nutrition, and neurodevelopmental outcomes of this high-risk population.

Fetal Growth Velocity-A Breakthrough in Intrauterine Growth Assessment?

The pursuit of assessing fetal well-being in obstetrical practice remains a central tenet, propelling ongoing endeavors to explore innovative markers and diagnostic methodologies aimed at prognosing potential perinatal adversities. Deviations from standard patterns of intrauterine growth, whether exhibiting excessive or insufficient trajectories, stand as pivotal indices hinting at underlying pathophysiological processes or heightened concurrent medical conditions. Initiatives like the Delphi consensus and the INTERGROWTH-21st project strive to refine diagnostic criteria and establish international standards for fetal growth assessment. This article aims to present the current knowledge regarding the assessment of abnormal growth, including novel methods such as growth velocity. Integrating fetal growth velocity assessment into perinatal care protocols holds promise in enhancing diagnostic precision. Growth velocity, involving changes in fetal size over a given period, offers insights into distinguishing between constitutional and pathological growth abnormalities. Various methodologies and models have been proposed to evaluate growth velocity, with notable advancements in understanding fetal growth patterns across different trimesters. It is believed that accelerated and reduced growth velocity may be a sensible parameter in the detection of fetal growth restriction (FGR), small-for-gestational-age (SGA) fetuses, large-for-gestational-age (LGA) fetuses and macrosomic fetuses as well as appropriate-for-gestational age (AGA) fetuses that encounter problems with growth continuation. Recent studies found that changes in growth velocity reflect the risk of adverse perinatal outcomes (APOs). Future directions in fetal health research aim to elucidate the long-term consequences of abnormal fetal growth velocity on neurodevelopmental outcomes, highlighting the critical role of early assessment and intervention.

Green spaces and respiratory, cardiometabolic, and neurodevelopmental outcomes: An individual-participant data meta-analysis of >35.000 European children

Studies evaluating the benefits and risks of green spaces on children’s health are scarce. The present study aimed to examine the associations between exposure to green spaces during pregnancy and early childhood with respiratory, cardiometabolic, and neurodevelopmental outcomes in school-age children. We performed an Individual-Participant Data (IPD) meta-analysis involving 35,000 children from ten European birth cohorts across eight countries. For each participant, we calculated residential Normalized Difference Vegetation Index (NDVI) within a 300 m buffer and the linear distance to green spaces (meters) during prenatal life and childhood. Multiple harmonized health outcomes were selected: asthma and wheezing, lung function, body mass index, diastolic and systolic blood pressure, non-verbal intelligence, internalizing and externalizing problems, and ADHD symptoms. We conducted a two-stage IPD meta-analysis and evaluated effect modification by socioeconomic status (SES) and sex. Between-study heterogeneity was assessed via random-effects meta-regression. Residential surrounding green spaces in childhood, not pregnancy, was associated with improved lung function, particularly higher FEV1 (β = 0.06; 95 %CI: 0.03, 0.09 I2 = 4.03 %, p < 0.001) and FVC (β = 0.07; 95 %CI: 0.04, 0.09 I2 = 0 %, p < 0.001) with a stronger association observed in females (p < 0.001). This association remained robust after multiple testing correction and did not change notably after adjusting for ambient air pollution. Increased distance to green spaces showed an association with lower FVC (β = −0.04; 95 %CI: −0.07, −0.02, I2 = 4.8, p = 0.001), with a stronger effect in children from higher SES backgrounds (p < 0.001). No consistent associations were found between green spaces and asthma, wheezing, cardiometabolic, or neurodevelopmental outcomes, with direction of effect varying across cohorts. Wheezing and neurodevelopmental outcomes showed high between-study heterogeneity, and the age at outcome assessment was only associated with heterogeneity in internalizing problems.. This large European meta-analysis suggests that childhood exposure to green spaces may lead to better lung function. Associations with other respiratory outcomes and selected cardiometabolic and neurodevelopmental outcomes remain inconclusive.