Poor Neurodevelopmental Outcomes Research Articles

Neurodevelopmental Outcome in Infants of Gestational Diabetic Mother in a Tertiary Care Hospital, Dhaka, Bangladesh

Background: Diabetes Mellitus (DM) is one of the most common metabolic complications of pregnancy, with negative influences on maternal and fetal health. Infants of Diabetic Mothers (IDMs) are prone to develop both early and late complications. Evidences shows that diabetes in pregnancy have strong association with long-term adverse effects on brain development in babies born to mothers with gestational diabetes mellitus. Very few studies were done in this subcontinent regarding association of gestational diabetes mellitus and infant’s neurodevelopmental outcome. This study will help to find out this associations and thus to reduce poor neurodevelopmental outcome in infants of diabetic mothers by early detection and providing proper early childhood stimulation. Objective: To assess the neurodevelopmental outcome of infants born to mother with gestational diabetes mellitus. Methodology: This prospective observational study was conducted in the department of Neonatology and Institute of Pediatric Neurodisorder and Autism (IPNA), BSMMU, from March 2022 to September 2023. Neonates (N= 52) born at or after 34 weeks of gestation and born to gestational diabetic mother were enrolled in this study. Consent was taken from guardians. The newborns fulfilling the inclusion criteria were followed up for neurodevelopmental assessment at their 9 months of age by clinical psychologists assigned from Institute of Pediatric Neurodisorder and Autism (IPNA), BSMMU, who were blinded about infant’s diagnosis. Bayley scales of infant and toddler development (BSID III) was used for developmental assessment. In the Bayley III, cognitive development, expressive and receptive language and fine and gross motor development all were evaluated at 9 months of age. All data were recorded in a preformed questionnaire and analyzed by Statistical Package for Social Sciences (SPSS), version 25. Results: According to inclusion and exclusion criteria 58 newborn were enrolled and their blood samples were sent at 24 to 48 hours of age to see the laboratory parameters of metabolic and hematological profile. Among them 6 patients lost to follow up, so 52 infants were followed up for neurodevelopmental outcome at 9 months of age. Among the baseline characteristics of mother and neonate 48% mother needed drugs for glycemic control, while others were on dietary modification and 75% of the mothers had good glycemic control. Most of the neonate were born at term and were age appropriate, 18 patients needed NICU admission. Among the neonatal laboratory parameters hyperbilirubinemia was most common (30.8%) and hypoglycemia was second most common found in 15.4% of newborns. The most common morbidity was sepsis (17.3%). Overall adverse neurodevelopmental outcome was found among 14 (26.9%) neonate and 38 (73.1%) neonates had favorable outcome. Use of drugs and poor maternal glycemic control were found statistically significant in between adverse and favorable groups. (p-value- 0.041 and 0.000). Among the neonatal clinical parameters only hypoglycemia was found statistically significant in between these two groups. (p-value- 0.014) Multivariate logistic regression among these predictive factors showed only maternal poor glycemic control was significantly associated with adverse neurodevelopmental outcome (p-value=0.001). Conclusion: Maternal gestational diabetes can adversely affect on their infants neurodevelopment. Among the adverse outcome of three domains language delay was most common. Neonatal hypoglycemia, maternal poor glycemic control and use of drugs for GDM are significant predictors of adverse neurodevelopmental outcome in infants of gestational diabetic mother. Among them maternal poor glycemic control was significantly associated with adverse neurodevelopmental outcome.

Enhancement of Family-Centred Care Is Associated with a Reduction in Postmenstrual Age at Discharge in Preterm Infants

Background/Objectives: Long hospitalisation has been recognized as an independent risk factor for poor neurodevelopmental outcomes of preterm infants. Systematic training and early inclusion of parents in their preterm infant’s care is a strategy to shorten the length of hospital stay. We implemented an enhanced stepwise family-centred care program and assessed its effects on postmenstrual age (PMA) at discharge and parental satisfaction. Methods: This prospective single-centre longitudinal cohort study was carried out in a German level III neonatal unit from October 2020 to May 2023. Five consecutive 6-month cohorts (1 baseline and 4 intervention cohorts, 169 infants and their caregivers) were analysed. Results: Mean PMA at discharge did not change in the total cohort but declined significantly in patients without neonatal morbidities from baseline to cohort 4 (37.2 ± 1.4 to 36.1 ± 1.6 weeks; p = 0.036). Concomitantly, discharge with tube feeding raised from 2.4% to 74.1% (p < 0.001) and discharge with home monitoring raised from 9.8% to 74.1% (p < 0.001), while unplanned readmissions remained unchanged (p = 0.44). Parental satisfaction with time point of discharge increased non-significantly from baseline to cohort 4 (75.8% vs. 95.7%; Chi2 0.22). Conclusions: Discharge of preterm infants at a significantly lower PMA is feasible through enhancement of family-centred care and is very well accepted by parents.

Neurodevelopmental outcome in preterm infants

Background and objectives. Preterm is defined as babies born alive before 37 weeks of pregnancy are completed. It is one of the world's critical health problems because it may be a significant cause of long-term neurodevelopmental disability. The purpose of this work was to evaluate the impact of premature birth and brain injuries on neurological development and to identify problems as soon as possible in order to prevent or minimize sequelae as much as possible. Materials and methods. Between June 2022 and July 2024, 374 infants were examined at “Prof. Dr. Panait Sarbu” Clinical Hospital of Obstetrics and Gynecology. Each baby's gross and fine motor development was assessed, cognitive acquisitions were evaluated using an adapted Denver Developmental Screening Test, and where needed, physical therapy, head ultrasound/MRI, EEG, or genetic tests were recommended. Results. From the 374 infants evaluated (M/F: 142/232), 72 were excluded considering the normal term of birth. Of the other 302, 23 did not present for follow-up checks after one or two appointments, and 54 completed all evaluations up to 21-24 months (the study is ongoing). 5/54 had poor neurodevelopmental outcomes, almost all due to very preterm birth. From the remaining 225 babies, with a few exceptions with variable neurological damage (13/225), no motor or cognitive development abnormalities have been observed in the evaluations carried out so far. Conclusions. In our cohort, almost all babies who completed or did not the follow-up program had normal development (261/279), but in some cases, prematurity, brain lesions, or genetic causes remain associated with a poor long-term outcome. Establishing a follow-up system for premature infants is necessary because early management during the period of higher brain plasticity may prevent neurological complications and improve the quality of life.

Parenting stress in infancy was associated with neurodevelopment in 24-month-old children with congenital heart disease.

Having a child with congenital heart disease (CHD) is stressful for parents, but research on the impact this stress can have on child development has been lacking. We investigated the associations between parenting stress when children were infants and neurodevelopmental outcomes in toddlers with CHD. This study was carried out at the Neurocardiac Clinic at the Sainte-Justine University Hospital in Montréal, Canada. Patients born from 2012 to 2019 and followed up to 24 months of age were recruited. Parenting stress levels were measured when the child was 4-6 months and 24 months and the child's neurodevelopment was assessed at 24 months. Multiple linear regressions analyses were carried out. We studied 100 children (56% boys) with CHD. Most of the parenting stress scores were below the clinical threshold. However, they accounted for a significant part of the variance in the children's cognitive (15%-16%), receptive language (14%-15%) and gross motor outcomes (15%-18%). They had no impact on the children's expressive language or fine motor outcomes. Higher parenting stress was associated with poorer neurodevelopmental outcomes in toddlers with CHD. Early screening of parenting stress in CHD clinics is necessary to provide individualised intervention for parents and optimise neurodevelopmental outcomes in children.

PRECIOUS study (PREterm Caesarean/vaginal birth and IVH/OUtcomeS): does mode of birth reduce the risk of death or brain injury in very preterm babies? A cohort and emulated target trial protocol

IntroductionVery preterm babies are at risk of poor neurodevelopmental outcomes and death. Intraventricular haemorrhage (IVH) after birth is the most prevalent cause of this. Birth by caesarean section may protect...

The Conundrum of Mechanics Versus Genetics in Congenital Hydrocephalus and Its Implications for Fetal Therapy Approaches: A Scoping Review.

Recent advances in gene therapy, particularly for single-gene disorders (SGDs), have led to significant progress in developing innovative precision medicine approaches that hold promise for treating conditions such as primary hydrocephalus (CH), which is characterized by increased cerebrospinal fluid (CSF) volumes and cerebral ventricular dilation as a result of impaired brain development, often due to genetic causes. CH is a significant contributor to childhood morbidity and mortality and a driver of healthcare costs. In many cases, prenatal ultrasound can readily identify ventriculomegaly as early as 14-20weeks of gestation, with severe cases showing poor neurodevelopmental outcomes. Postnatal surgical approaches, such as ventriculoperitoneal shunts, do not address the underlying genetic causes, have high complication rates, and result in a marginal improvement of neurocognitive deficits. Prenatal somatic cell gene therapy (PSCGT) promises a novel approach to conditions such as CH by targeting genetic mutations in utero, potentially improving long-term outcomes. To better understand the pathophysiology, genetic basis, and molecular pathomechanisms of CH, we conducted a scoping review of the literature that identified over 160 published genes linked to CH. Mutations in L1CAM, TRIM71, MPDZ, and CCDC88C play a critical role in neural stem cell development, subventricular zone architecture, and the maintenance of the neural stem cell niche, driving the development of CH. Early prenatal interventions targeting these genes could curb the development of the expected CH phenotype, improve neurodevelopmental outcomes, and possibly limit the need for surgical approaches. However, further research is needed to establish robust genotype-phenotype correlations and develop safe and effective PSCGT strategies for CH.

The role of early aggressive nutrition on growth of very preterm or very low birth weight infants

Background Very preterm infants (<32 weeks gestational age) are at high risk of poor neurodevelopmental outcomes. Early aggressive parenteral nutrition (protein ³ 2g/kg/day) can reduce the incidence of malnutrition in very preterm infants. At present, Fatmawati General Hospital does not have a standard nutritional protocol for preterm infant. Objective To determine the difference in growth (days to regain birth weight and growth velocity) of very preterm (<32 weeks gestational age) or very low birth weight (VLBW) (<1500g) infants who were born and hospitalized in the Neonatal Unit of Fatmawati General Hospital, Jakarta, before and after applying early aggressive parenteral nutrition using a nutrition protocol from Cipto Mangunkusumo Hospital, Jakarta. Methods A quasi-experimental study was conducted on 23 very preterm or VLBW infants in the Neonatal Unit of Fatmawati General Hospital, from July to November 2019. Control group data were taken from medical records of very preterm or VLBW babies discharged from our unit from January 2018 – to June 2019 and compared to those of the intervention group. Results The intervention group regained their birth weight significantly faster than the control group [mean 7.43 (SD 3.5) vs. 16.73 (SD 5.1) days, respectively; (P=0.00)]. Mean growth velocity was also significantly higher in the intervention group than in the control group [14.6 (SD 6.0) vs. 8.9 (SD 6.9) gram/kg/day, respectively; (P=0.002)]. Conclusion Provision of early aggressive parenteral nutrition reduces the time to regain birth weight and leads to higher growth velocity in very preterm/VLBW infants.

Apnoea suppresses brain activity in infants

Abstract Apnoea—the cessation of breathing—is commonly observed in premature infants. These events can reduce cerebral oxygenation and are associated with poorer neurodevelopmental outcomes. However, relatively little is known about how apnoea and shorter pauses in breathing impact brain function in infants, which will provide greater mechanistic understanding of how apnoea affects brain development. We analysed simultaneous recordings of respiration, electroencephalography (EEG), heart rate, and peripheral oxygen saturation in 124 recordings from 118 infants (post-menstrual age: 38.6 ± 2.7 weeks [mean ± standard deviation]) during apnoeas (pauses in breathing greater than 15 seconds) and shorter breathing pauses between 5 and 15 seconds. EEG amplitude significantly decreased during both apnoeas and short breathing pauses compared with normal breathing periods. Change in EEG amplitude was significantly associated with change in heart rate during apnoea and short breathing pauses and, during apnoeas only, with oxygen saturation change. No associations were found between EEG amplitude changes and apnoea/pause duration, post-menstrual age, or sleep state. As apnoeas often occur in premature infants, frequent disruption to brain activity may impact neural development and result in long-term neurodevelopmental consequences.

Neurodevelopment Outcome among Preterm Infants Admitted in Neonatal Intensive Care Unit

Introduction: With increasing the survival rates of premature babies, the management of long term complications, especially neurodevelopmental disorder is becoming an important issue for a better life. Aims: To assess the factors associated with adverse neurodevelopment outcome among preterm infants admitted in Neonatal Intensive Care Unit (NICU). Methods and Material: This prospective cohort study was conducted in Department of Neonatology, BSMMU, Dhaka, Bangladesh. Premature infants (<34 weeks) discharged from the NICU were enrolled and followed up for neurodevelopmental assessment at 6 months of age. Prenatal, perinatal, and postnatal features of the babies were recorded. The Bayley-III scale was used to assess the composite scores. Continuous variables were analyzed using an independent t-test and categorical variables with chi-square test. Logistic regression analysis was performed to find out the relationship of risk factors with neurodevelopmental scores. Results: A total 47 patients were analysed at 6 months of age using Bayley scale III. Mean birth weight and gestational age was 1595.11 ± 377.17g and 32.43 ± 1.48 weeks respectively. Mean cognitive, motor and language score were 80.79±14.51, 82.87±14.53 and 82.98±13.72 respectively. Despite the fact that all mean scores were normal, 27.7% of infants in cognition, 23.4% in motor, and 31.9% in language had a BSID-III value < 70. Variables like gestational age < 30 weeks, birth weight <1500 grams, and convulsion have been linked to poor neurodevelopmental outcomes. However, regression analysis revealed none of them were significant. Conclusions: In our study, at six months of age, the cognitive, language, and motor scores of preterm newborns (less than 34 weeks of gestation) were within normal limits. Of the newborns, we observed that 27.7% had cognitive delay and 31.9% experienced language delay. J Dhaka Med Coll. 2022; 31(2) : 251-257

Effects of pain, sedation and analgesia on neonatal brain injury and brain development

Critically ill newborns experience numerous painful procedures as part of lifesaving care in the Neonatal Intensive Care Unit. However, painful exposures in the neonatal period have been associated with alterations in brain maturation and poorer neurodevelopmental outcomes in childhood. The most frequently used medications for pain and sedation in the NICU are opioids, benzodiazepines and sucrose; these have also been associated with abnormalities in brain maturation and neurodevelopment making it challenging to know what the best approach is to treat neonatal pain. This article provides clinicians with an overview of how neonatal exposure to pain as well as analgesic and sedative medications impact brain maturation and neurodevelopmental outcomes in critically ill infants. We also highlight areas in need of future research to develop standardized neonatal pain monitoring and management strategies.

Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medication: Practice Guideline From the AAN, AES, and SMFM.

This practice guideline provides updated evidence-based conclusions and recommendations regarding the effects of antiseizure medications (ASMs) and folic acid supplementation on the prevalence of major congenital malformations (MCMs), adverse perinatal outcomes, and neurodevelopmental outcomes in children born to people with epilepsy of childbearing potential (PWECP). A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies through August 2022. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. The following are some of the major recommendations. When treating PWECP, clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, at the earliest possible opportunity preconceptionally. Clinicians must minimize the occurrence of convulsive seizures in PWECP during pregnancy to minimize potential risks to the birth parent and to the fetus. Once a PWECP is already pregnant, clinicians should exercise caution in attempting to remove or replace an ASM that is effective in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures. Clinicians must consider using lamotrigine, levetiracetam, or oxcarbazepine in PWECP when appropriate based on the patient's epilepsy syndrome, likelihood of achieving seizure control, and comorbidities, to minimize the risk of MCMs. Clinicians must avoid the use of valproic acid in PWECP to minimize the risk of MCMs or neural tube defects (NTDs), if clinically feasible. Clinicians should avoid the use of valproic acid or topiramate in PWECP to minimize the risk of offspring being born small for gestational age, if clinically feasible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ, in children born to PWECP, clinicians must avoid the use of valproic acid in PWECP, if clinically feasible. Clinicians should prescribe at least 0.4 mg of folic acid supplementation daily preconceptionally and during pregnancy to any PWECP treated with an ASM to decrease the risk of NTDs and possibly improve neurodevelopmental outcomes in the offspring.

Brain health in preterm infants: importance of early-life pain and analgesia exposure.

"Everyday" exposures in the neonatal period, such as pain, may impact brain health in preterm infants. Specifically, greater exposure to painful procedures in the initial weeks after birth have been related to abnormalities in brain maturation and growth and poorer neurodevelopmental outcomes in preterm infants. Despite an increasing focus on the importance of treating pain in preterm infants, there is a lack of consensus of optimal approaches to managing pain in this population. This may be due to recent findings suggesting that commonly used analgesic and sedative medications in preterm infants may also have adverse effects of brain maturation and neurodevelopmental outcomes. This review provides an overview of potential impacts of pain and analgesia exposure on preterm brain health while highlighting research areas in need of additional investigations for the development of optimal pain management strategies in this population.

Postnatal Growth Assessment and Prediction of Neurodevelopment and Long-Term Growth in Very Low Birth Weight Infants: A Nationwide Cohort Study in Korea.

Background/Objectives: Extrauterine growth restriction (EUGR) is associated with high mortality and an increased incidence of poor neurodevelopmental outcomes in preterm infants. In this study, we aimed to compare the Intergrowth-21ST (IG-21ST) and Fenton charts in predicting long-term neurodevelopmental and anthropometric outcomes of very low birth weight (VLBW) infants. Methods: Data were collected from 2649 VLBW infants registered in the Korean Neonatal Network born between 240/7 and 316/7 weeks of gestational age from January 2013 to December 2017. Follow-up assessments were conducted at 18-24 months of age, corrected for prematurity. Multiple logistic regression analysis was performed to evaluate the association between EUGR and long-term outcomes. Results: Among the 2649 VLBW infants, 60.0% (1606/2649) and 36.9% (977/2649) were diagnosed as having EUGR defined by the Fenton chart (EUGRF) and by the IG-21ST chart (EUGRIG), respectively. The EUGRIG group exhibited a higher proportion of infants with cerebral palsy, neurodevelopmental impairment (NDI), and growth failure. In multiple logistic regression analysis, adjusted for risk factors for long-term outcome, the EUGRIG group showed higher risk of cerebral palsy (adjusted odds ratio [aOR], 1.66; 95% confidence interval [CI], 1.04-2.65), NDI (aOR, 2.09; 95% CI, 1.71-2.55), and growth failure (aOR, 1.57; 95% CI, 1.16-2.13). Infants with EUGRF tended to develop NDI (aOR, 1.29; 95%CI, 1.03-1.63) and experience growth failure (aOR, 2.44; 95% CI, 1.77-3.40). Conclusions: The IG-21ST chart demonstrated a more effective prediction of long-term neurodevelopmental outcomes, whereas the Fenton chart may be more suitable for predicting growth failure at 18-24 months.

Postnatal Brain Trajectories and Maternal Intelligence Predict Childhood Outcomes in Complex CHD.

Objective: To determine whether early structural brain trajectories predict early childhood neurodevelopmental deficits in complex CHD patients and to assess relative cumulative risk profiles of clinical, genetic, and demographic risk factors across early development. Study Design: Term neonates with complex CHDs were recruited at Texas Children's Hospital from 2005-2011. Ninety-five participants underwent three structural MRI scans and three neurodevelopmental assessments. Brain region volumes and white matter tract fractional anisotropy and radial diffusivity were used to calculate trajectories: perioperative, postsurgical, and overall. Gross cognitive, language, and visuo-motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development and with the Wechsler Preschool and Primary Scale of Intelligence and Beery-Buktenica Developmental Test of Visual-Motor Integration. Multi-variable models incorporated risk factors. Results: Reduced overall period volumetric trajectories predicted poor language outcomes: brainstem ((β, 95% CI) 0.0977, 0.0382-0.1571; p = 0.0022) and white matter (0.0023, 0.0001-0.0046; p = 0.0397) at 5 years; brainstem (0.0711, 0.0157-0.1265; p = 0.0134) and deep grey matter (0.0085, 0.0011-0.0160; p = 0.0258) at 3 years. Maternal IQ was the strongest contributor to language variance, increasing from 37% at 1 year, 62% at 3 years, and 81% at 5 years. Genetic abnormality's contribution to variance decreased from 41% at 1 year to 25% at 3 years and was insignificant at 5 years. Conclusion: Reduced postnatal subcortical-cerebral white matter trajectories predicted poor early childhood neurodevelopmental outcomes, despite high contribution of maternal IQ. Maternal IQ was cumulative over time, exceeding the influence of known cardiac and genetic factors in complex CHD, underscoring the importance of heritable and parent-based environmental factors.

Negative central activity in extremely preterm newborns: EEG characterization and relationship with brain injuries and neurodevelopmental outcome

ObjectiveTo characterize Negative Central Activity (NCA), an overlooked electroencephalographic activity of preterm newborns and investigate its relationship with brain injuries, dysfunction, and neurodevelopmental outcome. Methods109 preterm infants (23–28 weeks) were retrospectively included. NCA were selected at the negative peak on EEG. Individual averaged NCA were automatically characterized. Brain structural data were collected from cranial ultrasounds (cUS). The neurodevelopmental outcome at two years of age was assessed by the Denver Developmental Screening Test-II. ResultsThirty-six (33%) children showed NCA: 6,721 NCA were selected, a median of 75 (interquartile range, 25/157.3) per EEG. NCA showed a triphasic morphology, with a mean amplitude and duration of the negative component of 24.6–40.0 µV and 222.7–257.3 ms. The presence of NCA on EEG was associated with higher intraventricular haemorrhage (IVH) grade on the first (P = 0.016) and worst neonatal cUS (P < 0.001) and poorer neurodevelopmental outcome (P < 0.001). ConclusionsNCA is an abnormal EEG feature of extremely preterm newborns that may correspond to the functional neural impact of a vascular pathology. SignificanceThe NCA relationships with an adverse outcome and the presence/severity of IVH argue for considering NCA in the assessment of pathological processes in the developing brain network and for early outcome prediction.

272 Integrative Genomics Implicates Primary Impact on Cortical Development in Spina Bifida

INTRODUCTION: Spina bifida is one of the most common malformation of the central nervous system that is associated with poor neurodevelopmental outcomes. Altered neurodevelopment in spina bifida has been attributed to venting of CSF through the neural tube defect. Despite correction of the spinal defect, some patients still develop hydrocephalus with poor neurodevelopmental outcomes, suggesting incomplete understanding of disease pathogenesis. Recent human genetic efforts have identified candidate genes that confer spina bifida risk, however, the mechanisms linking gene mutations to altered neurodevelopment remain poorly understood. METHODS: We curated a list of 439 genes that confer risk to spina bifida from a whole-genome sequencing study of 310 individuals. We then mapped the spatiotemporal and cell-type specific expression of these risk genes onto bulk and single-cell RNA sequencing data of normally developing human brains covering the entire lifespan of human development. RESULTS: We found that spina bifida risk genes are enriched at post-conception weeks 5-6 and 25-38 in the developing human brain. After birth, spina bifida risk genes are enriched at postnatal months 6-10 and then after 60 years of age. At the cell type level, spina bifida risk genes are enriched in proliferative neuroprogenitor cells and microglia in the prenatal human cortex. CONCLUSIONS: Our analyses show that spina bifida risk genes are expressed in the developing human brain, suggesting a primary impact on brain development that is independent from the open caudal end of the neural tube defect. The finding that spina bifida risk genes continue to be expressed postnatally suggests a window for therapeutic intervention to optimize neurodevelopmental outcomes after birth in at least a subset of patients.

Association of in utero HIV exposure with child brain structure and language development: a South African birth cohort study

BackgroundThere is a growing population of children with in utero HIV exposure who are at risk of poor neurodevelopmental outcomes despite avoiding HIV infection. However, the underlying neurobiological pathways are not understood and neuroimaging studies are lacking. We aimed to investigate the cortical brain structure of children who are HIV-exposed and uninfected (HEU) compared to HIV-unexposed (HU) children and to examine the relationship with neurodevelopment.MethodsThe Drakenstein Child Health birth cohort study enrolled pregnant women from a high HIV prevalence area in South Africa with longitudinal follow-up of mother–child pairs. High-resolution magnetic resonance imaging scans from 162 children (70 HEU; 92 HU) were acquired at 2–3 years of age. All HEU children were born to mothers taking antiretroviral therapy. Measures of brain structure (cortical thickness and surface area) in the prefrontal cortex regions were extracted from T1-weighted images and compared between groups using multivariate analysis of variance and linear regression. Child development, assessed using the Bayley Scales of Infant and Toddler Development-III, was correlated with cortical structure, and mediation analyses were performed.ResultsAnalyses demonstrated an association between HIV exposure and cortical thickness across the prefrontal cortex (p = 0.035). Children who were HEU had thicker cortices in prefrontal regions, with significantly greater cortical thickness in the medial orbitofrontal cortex (mOFC) bilaterally compared to HU children (3.21 mm versus 3.14 mm, p = 0.009, adjusted effect size 0.44 [95% CI 0.12 to 0.75]). Estimates held across multiple sensitivity analyses. There were no group differences in cortical surface area. Language scores, which were lower in HEU versus HU children (81.82 versus 86.25, p = 0.011, effect size − 0.44 [95% CI − 0.78 to − 0.09]), negatively correlated with prefrontal cortical thickness in both groups. Cortical thickness in the mOFC mediated the relationship between HIV exposure and poor language outcomes (Sobel test p = 0.032).ConclusionsIn this cohort study, exposure to HIV during pregnancy was associated with altered cortical structure in early life. Our findings indicate that differences in cortical thickness development in the prefrontal region in children who are HEU may be a pathway leading to language impairment. Longitudinal studies are needed to determine the lasting impact.

Maternal Blood Adipokines and Their Association with Fetal Growth: A Meta-Analysis of the Current Literature.

Background: Assessing fetal growth constitutes a fundamental aim within the realm of prenatal care. Impaired prenatal growth increases the risk of perinatal mortality, morbidity, and poor newborn outcomes. Growth restriction increases the risk of premature birth problems, as well as the risk of poor neurodevelopmental outcomes and future non-communicable disorders such as hypertension and metabolic syndrome as adults. The objective of this systematic review is to accumulate current literature evidence to assess the patterns of serum adipokine levels among women with growth-restricted fetuses and assess their potential alterations in those high-risk pregnancies. Methods: Medline, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception until 31 March 2023. All observational studies reporting serum adipokine values among women with appropriately grown and growth-restricted fetuses were held eligible. Results: The current systematic review encompassed a total of 20 studies, incorporating a patient population of 1850 individuals. Maternal blood leptin emerged as the adipokine most investigated, as evidenced by 13 studies encompassing a collective sample size of 1081 patients, all of which explored its potential correlation with intrauterine growth restriction. Elevated levels of leptin were detected in fetuses with intrauterine growth restriction, although the observed difference did not reach statistical significance. Furthermore, regarding adiponectin, the meta-analysis conducted indicated that there were not any statistically significant differences observed in the mean values of adiponectin. The available data on the remaining three adipokines were extremely limited, making it difficult for any solid conclusions to be extracted. Conclusions: Though limited and inconsistent, the existing data suggest that fetal growth restriction is not linked to leptin, adiponectin, visfatin, resistin, or RBP4. More substantial prospective studies are needed to comprehend the importance of established and novel adipokines.

Early IGF-1 receptor inhibition in mice mimics preterm human brain disorders and reveals a therapeutic target.

Besides recent advances in neonatal care, preterm newborns still develop sex-biased behavioral alterations. Preterms fail to receive placental insulin-like growth factor-1 (IGF-1), a major fetal growth hormone in utero, and low IGF-1 serum levels correlate with preterm poor neurodevelopmental outcomes. Here, we mimicked IGF-1 deficiency of preterm newborns in mice by perinatal administration of an IGF-1 receptor antagonist. This resulted in sex-biased brain microstructural, functional, and behavioral alterations, resembling those of ex-preterm children, which we characterized performing parallel mouse/human behavioral tests. Pharmacological enhancement of GABAergic tonic inhibition by the U.S. Food and Drug Administration-approved drug ganaxolone rescued functional/behavioral alterations in mice. Establishing an unprecedented mouse model of prematurity, our work dissects the mechanisms at the core of abnormal behaviors and identifies a readily translatable therapeutic strategy for preterm brain disorders.

Language brain responses and neurodevelopmental outcome in preschoolers with congenital heart disease: A fNIRS study

Neurodevelopmental disabilities affect up to 50% of survivors of congenital heart disease (CHD). Language difficulties are frequently identified during preschool period and can lead to academic, social, behavioral, and emotional difficulties. Structural brain alterations are associated with poorer neurodevelopmental outcomes in patients with CHD during infancy, childhood, and adolescence. However, evidence is lacking about the functional brain activity in children with CHD and its relationship with neurodevelopment. This study therefore aimed to characterize brain responses during a passive story-listening task in 3-year-old children with CHD, and to investigate the relationship between functional brain patterns of language processing and neurodevelopmental outcomes. To do so, we assessed hemodynamic concentration changes, using functional near-infrared spectroscopy (fNIRS), and neurodevelopmental outcomes, using the Wechsler Preschool and Primary Scale of Intelligence – 4th Edition (WPPSI-IV), in children with CHD (n = 19) and healthy controls (n = 23). Compared to their healthy peers, children with CHD had significantly lower scores on the Verbal comprehension index (VCI), the Vocabulary acquisition index (VAI), the General ability index (GAI), and the Information and the Picture Naming subtests of the WPPSI-IV. During the passive story-listening task, healthy controls showed significant hemodynamic brain responses in the temporal and the temporal posterior regions, with stronger activation in the temporal posterior than in the temporal regions. In contrast, children with CHD showed reduced activation in the temporal posterior regions compared to controls, with no difference of activation between regions. Reduced brain responses in the temporal posterior regions were also correlated with lower neurodevelopmental outcomes in both groups. This is the first study that reveals reduced brain functional responses in preschoolers with CHD during a receptive language task. It also suggests that the temporal posterior activation could be a potential brain marker of cognitive development. These findings provide support for the feasibility of identifying brain correlates of neurodevelopmental vulnerabilities in children with CHD.