Neurodevelopmental Outcome Of Infants 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.

Investigating the impact of severe maternal SARS-CoV-2 infection on infant DNA methylation and neurodevelopment.

Maternal infections during pregnancy can increase the risk to offspring of developing a neurodevelopmental disorder. Given the global prevalence and severity of infection with Severe Acute Respiratory Syndrome related Coronavirus 2 (SARS-CoV-2), the objective of this study was to determine if in utero exposure to severe maternal SARS-CoV-2 infection alters infant neurodevelopmental outcomes at 12 months and to identify potential biological markers of adverse infant outcomes. Mother-infant dyads exposed to severe SARS-CoV-2 infection (requiring hospitalization) during pregnancy and age and sociodemographic matched control dyads were recruited from Monash Medical Centre, Australia in 2021/22 and prospectively assessed over 12 months. Maternal serum cytokine levels and Edinburgh Postnatal Depression Scale (EPDS) scores were assessed at birth. DNA methylation was assessed from infant buccal swabs at birth (Illumina EPIC BeadChip). Infant neurodevelopmental outcomes at 12 months were assessed using the Ages and Stages Questionnaire (ASQ-3). Mothers exposed to severe SARS-CoV-2 exhibited elevated serum IL-6 and IL-17A and higher EPDS scores than controls at birth. Infants exposed to severe SARS-CoV-2 in utero demonstrated over 3000 significant differentially methylated sites within their genomes compared to non-exposed (adjusted p-value < 0.05), including genes highly relevant to ASD and synaptic pathways. At 12 months, severe SARS-CoV-2 exposed infants scored lower on the ASQ-3 than non-exposed infants, and communication and problem-solving scores negatively correlated with maternal IL-6 levels at birth. DNA methylation changes therefore unveil potential mechanisms linking infection exposure to delayed neurodevelopment and maternal serum IL-6 levels may be a potential biomarker of child developmental delay. Mothers exposed to severe SARS-CoV-2 infections show elevated pro-inflammatory cytokines. Infants exposed in utero to severe SARS-CoV-2 infection show altered DNA methylation at birth and delayed development at 12 months of age. Created in Biorender.com.

Maternal pre-pregnancy weight and infant spontaneous movement: is there an association?

Abstract Introduction Maternal pre-pregnancy overweight status might create a chronic systemic inflammatory environment for the foetus, impairing neurons development. The Motor Optimality Score-Revised (MOS-R) is an established tool to assess infant spontaneous movement at 3-5 months helping predict later neurodevelopmental outcomes in infants, including language, minor neurological dysfunction or learning difficulties at school age. The aim of our study was to investigate if maternal BMI together with other characteristics were potentially associated with MOS-R score at 3-5 months in a sample of newborns representative of physiologic full-term pregnancies. Methods 128 mother-children couples were enrolled in the Hospital of Modena, Italy. Mothers’ socio-demographic characteristics and BMI pre and during pregnancy were collected. MOS-R was assessed in infants within 9-18 weeks post term age (Median 13, IQR 12-14). Descriptive statistics, bivariate associations and multivariate analysis were performed. Results In our sample, 94.5% of infants (44% females) had a MOS-R≥25 (optimal score), 3.9% a MOS-R between 23-24 and 1.6% a MOS-R&amp;lt;23. In bivariate analyses pre-pregnancy BMI≥25 and weight gain higher than recommended during pregnancy were associated with MOS-R&amp;lt;25 (p &amp;lt; 0.05); being unemployed before and during pregnancy and having pregnancy during COVID lockdown were associated with reduced “age adequate movement repertoire” subcategory (p &amp;lt; 0.05). In multivariate analysis, pre-pregnancy BMI≥25 remained the only factor significantly associated with lower scores (p &amp;lt; 0.05). Discussion Our sample of healthy infants showed a typical range of spontaneous movements reflecting neural integrity. However, lower MOS-R scores were associated with pre-pregnancy overweight. This finding reinforce the importance of enhancing public health actions targeted at keeping a weight in the normal range to protect from a large number of unhealthy conditions both the mother and the offspring. Key messages • Pre-pregnancy weight appears associated with infant spontaneous movement in 3-5 months infants. • Public health actions targeted at keeping female weight in the normal range must be strengthen.

Neurodevelopmental outcomes of infants after in utero exposure to SARS-CoV-2 or mRNA-COVID-19 vaccine compared with unexposed infants: a COVI-PREG prospective cohort study

ObjectivesData are lacking regarding the long-term consequences of SARS-CoV-2 and COVID-19 mRNA vaccine on infants exposed in utero. We aimed to evaluate the neurodevelopment of infants exposed prenatally to SARS-CoV-2 or mRNA-COVID-19 vaccine during pregnancy at 12 months after birth. MethodsInfants born to mothers exposed to SARS-CoV-2 or mRNA-COVID-19 vaccine during pregnancy, or unexposed to either the virus or the vaccine were enrolled from 2021 to 2023. Infants with prenatal exposure to the virus or vaccine were compared with infants without prenatal exposure to the virus and/or vaccine. Parents received a neurodevelopmental questionnaire (ages and stages questionnaire third edition) at 12 months after birth assessing five subdomains: communication, gross motor, fine motor, problem-solving, and personal social development. A low score was defined as <2 standard deviations below the normative mean in at least one of the subdomains. ResultsA total of 330 infants were included (76 in the SARS-CoV-2 group, 153 in the mRNA-COVID-19 vaccine group, and 101 in the reference group). In utero exposure to the SARS-CoV-2 or mRNA-COVID-19 vaccine was not associated with an increased risk of a low score for at least one subdomain compared with the reference group. The crude ORs were 1.16 (95% CI, 0.59–2.28) and 1.04 (95% CI, 0.58–1.86), respectively. Results remained consistent in the multivariate analysis, showing no increased risk of a low score for at least one subdomain for infants exposed to the SARS-CoV-2 or mRNA-COVID-19 vaccine, compared with the reference group. The adjusted ORs were 1.74 (95% CI, 0.76–3.99) and 0.76 (95% CI, 0.39–1.49), respectively. DiscussionIn utero exposure to SARS-CoV-2 or mRNA-COVID-19 vaccine was not associated with an increased risk of a low score for at least one ages and stages questionnaire third edition subdomain at 12 months after birth. Additional studies are needed to confirm our results, especially longer-term evaluation of infant development.

Anesthesia and Sedation Exposure and Neurodevelopmental Outcomes in Infants Undergoing Congenital Cardiac Surgery: A Retrospective Cohort Study

Anesthesia and Sedation Exposure and Neurodevelopmental Outcomes in Infants Undergoing Congenital Cardiac Surgery: A Retrospective Cohort Study

Mapping brain development against neurological disorder using contrastive sharing

Cerebral palsy (CP) is a neurological disorder caused by cerebral ischemia and hypoxia during fetal brain development. Early intervention in CP patients has a favorable impact on medications and therapy; however, challenges are associated with early age development, potential recovery, and neuroimaging sensitivity. Previously, the main focus was given on early diagnosis, brain injury characterization, and neurodevelopmental outcomes in infants; however, it is inevitable to study the brain developmental patterns in health controls (HC) and CP children. This study elaborates on the effects of aging on the brains of infants with HC and CP, age ranging from a few months and 17 years using deep learning (DL). The introduced DL-based models, namely SCT-DL and MCT-DL, trained on single contrast MRI (SC-MRI) and coupling of multi-contrast (MC-MRI) to learn vulnerable brain regions associated to brain development. The proposed models are equipped with fully-convolutional-based attention mechanism leveraging average pooling operation, directly passing salient features, parallel partial computing unit, specialized parameter sharing module, fusion, and spatial-channel attention with traversal placement to learn and associate brain development accurately. In addition, the study reports optimal SC-MRI and MC-MRI deeply associated with CP vulnerabilities and association to brain development. The SCT-DL outperformed the counterpart models with accumulative MAE = 1.73 (C11C denotes HC and P denotes CP.= 1.61 and P = 1.63) underlying T1-w, where the MCT-DL is the improved version of SCT-DL and the prediction accuracy reached to MAE = 1.08 (C = 1.01 and P = 1.12) over the coupling of T1-w⊕Sagittal. The trained models result in unmatching and distinct learning patterns for healthy and CP patients. Notably, the age-wise brain development-based results deduce a significance in age association at an early age (around two years) and poor at a later age. The study findings will assist neurodevelopmental processing and clinical practices in radiomics without concerning infants’ uncooperative movement or MRI artifacts.

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.

A combination of phospholipids and long chain polyunsaturated fatty acids supports neurodevelopmental outcomes in infants: a randomized, double-blind, controlled clinical trial

A combination of phospholipids and long chain polyunsaturated fatty acids supports neurodevelopmental outcomes in infants: a randomized, double-blind, controlled clinical trial

Dolphin CONTINUE: a multi-center randomized controlled trial to assess the effect of a nutritional intervention on brain development and long-term outcome in infants born before 30 weeks of gestation

BackgroundPreterm born infants are at risk for brain injury and subsequent developmental delay. Treatment options are limited, but optimizing postnatal nutrition may improve brain- and neurodevelopment in these infants. In pre-clinical animal models, combined supplementation of docosahexaenoic acid (DHA), choline, and uridine-5-monophosphate (UMP) have shown to support neuronal membrane formation. In two randomized controlled pilot trials, supplementation with the investigational product was associated with clinically meaningful improvements in cognitive, attention, and language scores. The present study aims to assess the effect of a similar nutritional intervention on brain development and subsequent neurodevelopmental outcome in infants born very and extremely preterm.MethodsThis is a randomized, placebo-controlled, double-blinded, parallel-group, multi-center trial. A total of 130 infants, born at less than 30 weeks of gestation, will be randomized to receive a test or control product between term-equivalent age and 12 months corrected age (CA). The test product is a nutrient blend containing DHA, choline, and UMP amongst others. The control product contains only fractions of the active components. Both products are isocaloric powder supplements which can be added to milk and solid feeds. The primary outcome parameter is white matter integrity at three months CA, assessed using diffusion-tensor imaging (DTI) on MRI scanning. Secondary outcome parameters include volumetric brain development, cortical thickness, cortical folding, the metabolic and biochemical status of the brain, and product safety. Additionally, language, cognitive, motor, and behavioral development will be assessed at 12 and 24 months CA, using the Bayley Scales of Infant Development III and digital questionnaires (Dutch version of the Communicative Development Inventories (N-CDI), Ages and Stages Questionnaire 4 (ASQ-4), and Parent Report of Children’s Abilities – Revised (PARCA-R)).DiscussionThe investigated nutritional intervention is hypothesized to promote brain development and subsequent neurodevelopmental outcome in preterm born infants who have an inherent risk of developmental delay. Moreover, this innovative study may give rise to new treatment possibilities and improvements in routine clinical care.Trial registrationWHO International Clinical Trials Registry: NL-OMON56181 (registration assigned October 28, 2021).

Infant neurodevelopment during the COVID-19 pandemic: Associations with maternal pandemic-related experiences, parenting stress, and self-efficacy

BackgroundAlthough pandemic-related experiences have been linked to the psychological well-being of mothers, the effects of the COVID-19 pandemic on infant neurodevelopmental outcomes have not been sufficiently studied. AimsTo assess whether maternal COVID-19-related experiences (i.e., COVID-19-related health, risk, resource worries, and feelings of grief), parenting stress, and maternal self-efficacy are associated with infant neurodevelopment as measured by the Ages and Stages Questionnaire, Third Edition (ASQ-3) maternal report when infants were between 8 to 10 months of age. Furthermore, this study examined the moderating effect of maternal self-efficacy between maternal COVID-19-related experiences and infant neurodevelopment. MethodsThis cross-sectional study included 122 women who were drawn from the Perinatal Experiences and COVID-19 Effects (PEACE) Study, with online surveys administered between November 2020 and August 2022. ResultsAfter controlling for maternal anxiety and depression symptoms and demographic factors, hierarchical regression analysis indicated that parenting stress showed no effect on ASQ-3 scores. However, more adverse COVID-19-related experiences and higher levels of maternal self-efficacy were associated with better infant neurodevelopment. Moreover, there was a significant interaction effect between maternal self-efficacy and COVID-19-related experiences on infant neurodevelopment. For mothers with moderate to high levels of self-efficacy, more adverse COVID-19-related experiences were associated with better infant neurodevelopment. For mothers with low levels of self-efficacy, more adverse COVID-19-related experiences were associated with poorer developmental outcomes in infants. ConclusionsUnder adverse conditions, confidence in caregiving may afford more optimal infant neurodevelopment. Interventions aimed at fostering maternal self-efficacy and addressing specific stressors can be valuable in promoting positive developmental trajectories for infants born during the pandemic.

The predictive value of MRI scores for neurodevelopmental outcome in infants with neonatal encephalopathy.

MRI scoring systems are utilized to quantify brain injury and predict outcome in infants with neonatal encephalopathy (NE). Our aim was to evaluate the predictive accuracy of total scores, white matter (WM) and grey matter (GM) subscores of Barkovich and Weeke scoring systems for neurodevelopmental outcome at 2 years of age in infants receiving therapeutic hypothermia for NE. Data of 162 infants were analyzed in this retrospective cohort study. DeLong tests were used to compare areas under the curve of corresponding items of the two scoring systems. LASSO logistic regression was carried out to evaluate the association between MRI scores and adverse composite (death or severe disabilities), motor and cognitive outcomes (Bayley developmental index <70). Weeke scores predicted each outcome measure with greater accuracy than the corresponding items of Barkovich system (DeLong tests p < 0.03). Total scores, GM and cerebellum involvement were associated with increased odds for adverse outcomes, in contrast to WM injury, after adjustment to 5' Apgar score, first postnatal lactate and aEEG normalization within 48 h. A more detailed scoring system had better predictive value for adverse outcome. GM injury graded on both scoring systems was an independent predictor of each outcome measure. A more detailed MRI scoring system had a better predictive value for motor, cognitive and composite outcomes. While hypoxic-ischemic brain injuries in the deep grey matter and cerebellum were predictive of adverse outcome, white matter injury including cortical involvement was not associated with any of the outcome measures at 2 years of age. Structured MRI evaluation based on validated scores may aid future clinical research, as well as inform parents and caregivers to optimize care beyond the neonatal period.

Growth and Neurodevelopmental Outcomes of Preterm Infants Born < 26 Weeks Gestation before and after Implementation of a Nutrition-Care Bundle.

This study aimed to assess the impact of a nutrition-care bundle on growth and neurodevelopmental outcomes of micro-preterm infants born in a level III neonatal intensive care unit (NICU) by two years corrected age. A nutrition-care bundle emphasizing the prompt initiation of parenteral nutrition at birth, initiation of enteral feeds within 6 h after birth, and early addition of human milk fortifiers was implemented in 2015 for infants born < 26 weeks gestation. This before-and-after study evaluated growth and neurodevelopmental outcomes in infants born between 2012-2013 (before-nutrition-bundle, BNB) and 2016-2017 (after-nutrition-bundle, ANB). A total of 145 infants were included in the study. Infants in the ANB group (n = 73) were smaller (birthweight and gestational age), and there were more male infants and multiples included compared to the BNB group (n = 72). Enteral feeds and fortifiers started earlier in the ANB group. Growth velocity and weight z-score changes were similar in both groups during NICU stay and post-discharge. Systemic steroid use, but not cohort, was linked to lower Bayley scores across all domains. Implementing a nutrition-care bundle was not consistently associated with improved weight gain and neurodevelopmental outcomes in the micro-preterm infant population, possibly due to ongoing high-quality nutritional care by the clinical team.

Long-term outcomes of very low birth weight infants with intraventricular hemorrhage: a nationwide population study from 2011 to 2019.

Advancements in neonatal care have increased preterm infant survival but paradoxically raised intraventricular hemorrhage (IVH) rates. This study explores IVH prevalence and long-term outcomes of very low birth weight (VLBW) infants in Korea over a decade. Using Korean National Health Insurance data (NHIS,2010-2019), we identified3372 VLBW infants with IVH among 4,129,808 live births.Health-related claims data, encompassing diagnostic codes, diagnostic test costs, and administered procedures were sourced from the NHIS database.The results of the developmental assessments are categorized into four groups based on standard deviation (SD) scores.Neonatal characteristics and complications were compared amongthe groups. Logistic regression models were employed to identify significant changes in the incidence of complications and to calculate odds ratios with corresponding 95% confidence intervals for each risk factor associated with mortality and morbidity in IVH.Long-term growth and developmentwere compared between the two groups(years2010-2013 and 2014-2017). IVH prevalence was 12% in VLBW and 16% in extremely low birth weight (ELBW) infants. Over the past decade, IVH rates increased significantly in ELBW infants (P = 0.0113), while mortality decreased (P = 0.0225). Major improvements in certain neurodevelopmental outcomes and reductions in early morbidities have been observed among VLBW infants with IVH. Ten percent of the population received surgical treatments such as external ventricular drainage (EVD) or a ventriculoperitoneal (VP) shunt, with the choice of treatment methods remaining consistent over time. The IVH with surgical intervention group exhibited higher incidences of delayed development, cerebral palsy, seizure disorder, and growth failure (height, weight, and head circumference) up to 72months of age (P < 0.0001). Surgical treatments were also significantly associated with abnormal developmental screening test results. The neurodevelopmental outcomes of infants with IVH, especially those subjected tosurgical treatments, continue to be a matter of concern. It is imperative to prioritize specialized care for patients receiving surgical treatments and closely monitor their growth and development after discharge to improve developmental prognosis. Supplementary file2 (MP4 77987 kb).

Stability of the Motor Optimality Score Revised (MOS-R) in medically complex infants

BackgroundThe Motor Optimality Score-Revised (MOS-R) is a clinical test of infant spontaneous movement at 3–5 months of age and has been associated with neurodevelopmental outcomes in infants with medical complexity. However the stability of the MOS-R tested at different developmental ages is not yet known. AimTo determine if the repeated scoring of the MOS-R remained consistent when tested at two developmental ages in young infants. Study designIn this prospective cohort study, infants were tested twice with the MOS-R between 12 and 13 weeks corrected age (CA) and 14–16 weeks CA. Bland Altman Plots were used to calculate agreement between the scores. Infants were grouped as having higher or lower medical complexity. MOS-R threshold scores were analyzed to assess changes over time within each group using Fisher's exact test. Subjects85 infants with history of hospitalization in a neonatal intensive care unit (NICU). ResultsThe MOS-R scores had a high agreement with negligible bias (0.058) between timepoints (95 % CI -1.10, 1.22). Using a MOS-R cut point of 19, infants with higher medical complexity were more likely to change groups between timepoints than infants with lower medical complexity (p = 0.008), but this was not significantly different using cut points of 20 or 21. ConclusionThe MOS-R scores were stable when measured repeatedly in infants who were hospitalized in a NICU. Infants with high medical complexity had less stable MOS-R scores using certain cut points than infants with lower medical complexity.

Pre-pregnancy maternal obesity and infant neurodevelopmental outcomes in Latino infants.

This study explores the impact of maternal pre-pregnancy BMI on infant neurodevelopment at 24 months in low-income Latino families. It also investigates whether infant diet mediates this relationship. Latino mother-infant pairs (n = 163) were enrolled at 1 month post partum and were followed for 2 years, with assessments at 6-month intervals. Maternal pre-pregnancy anthropometrics were self-reported at baseline, and child neurodevelopment was assessed at 24 months using the Bayley Scales of Infant Development. Diet quality of infants was measured using the Healthy Eating Index (HEI)-2015 and HEI-Toddlers-2020 scores at multiple time points. Mediation and regression models that adjust for maternal factors were used to examine the associations. Pre-pregnancy BMI showed significant negative associations with child cognitive scores (β = -0.1, 95% CI: -0.2 to -0.06, p < 0.001) and language scores (β = -0.1, 95% CI: -0.2 to -0.03, p = 0.01) at 24 months. Infant HEI-2015 scores at 24 months partly mediated these associations, explaining 23% and 30% of the total effect on cognitive and language subscales, respectively. No specific dietary components in infants mediated the relationship, except for the total HEI-2015 score. Managing maternal obesity pre-pregnancy is crucial for improving infant neurodevelopmental outcomes, especially in low-income Latino families. Promoting healthy weight and enhancing infant diet quality can enhance neurodevelopment in these populations.

Evaluation of three-year neurodevelopmental outcomes in infants prenatally exposed to substance use

IntroductionPrenatal exposure to substance use is associated with long-term deficits in the neurodevelopment of children. The objective was to investigate the association between cognitive, motor, and language neurodevelopment at three years of age in infants prenatally exposed to substance use. Material and methodsA prospective matched case-control study was conducted. Biomarkers of fetal exposure were measured in meconium samples. The Bayley Scales of Infant and Toddler Development (BSID-III) were used to calculate neurodevelopment scores. Results32 non-exposed and 32 exposed infants were evaluated, of which 16 were exposed to cannabis, 8 to ethanol, 2 to cocaine and 6 to more than one substance. Normal BSID-III scores ≥85 in all domains, were detected in 23 exposed infants to any substance and 29 infants non-exposed. Neurodevelopmental delay was detected in the language domain, specifically in male infants exposed to cannabis. Two infants exposed to cannabis had a severe developmental delay (score<70). Infants exposed to any substance obtained significantly lower total scores than control infants in all domains. Infants exposed to cannabis obtained significantly lower composite scores in the cognitive and motor domains. Infants exposed to more than one substance had lower scores in motor skills. By gender, only males exposed obtained significantly lower composite scores than non-exposed males in the cognitive domain. ConclusionsThe most common and severe neurodevelopmental delay at 36 months was detected in the domain of language in male infants prenatally exposed to cannabis. Neurodevelopmental disorders detected can enable an early intervention and plan therapeutic strategies.

How effective are musical and vocal interventions to improve neurodevelopmental outcomes in infants born preterm? ACochrane Review summary with commentary.

How effective are musical and vocal interventions to improve neurodevelopmental outcomes in infants born preterm? ACochrane Review summary with commentary.

Pain/Stress, Mitochondrial Dysfunction, and Neurodevelopment in Preterm Infants

Introduction: Preterm infants experience tremendous early life pain/stress during their neonatal intensive care unit (NICU) hospitalization, which impacts their neurodevelopmental outcomes. Mitochondrial function/dysfunction may interface between perinatal stress events and neurodevelopment. Nevertheless, the specific proteins or pathways linking mitochondrial functions to pain-induced neurodevelopmental outcomes in infants remain unidentified. Our study aims to investigate the associations among pain/stress, proteins associated with mitochondrial function/dysfunction, and neurobehavioral responses in preterm infants. Methods: We conducted a prospective cohort study, enrolling 33 preterm infants between September 2017 and July 2022 at two affiliated NICUs located in Hartford and Farmington, CT. NICU Network Neurobehavioral Scale (NNNS) datasets were evaluated to explore potential association with neurobehavioral outcomes. The daily pain/stress experienced by infant’s during their NICU stay was documented. At 36–38 weeks post-menstrual age (PMA), neurobehavioral outcomes were evaluated using the NNNS and buccal swabs were collected for further analysis. Mass spectrometry-based proteomics was conducted on epithelial cells obtained from buccal swabs to evaluate protein expression level. Lasso statistical methods were conducted to study the association between protein abundance and infants’ NNNS summary scores. Multiple linear regression and Gene Ontology (GO) enrichment analyses were performed to examine how clinical characteristics and neurodevelopmental outcomes may be associated with protein levels and underlying molecular pathways. Results: During NICU hospitalization, preterm premature rupture of membrane (PPROM) was negatively associated with neurobehavioral outcomes. The protein functions including leptin receptor binding activity, glutathione disulfide oxidoreductase activity and response to oxidative stress, lipid metabolism, and phosphate and proton transmembrane transporter activity were negatively associated with neurobehavioral outcomes; in contrast, cytoskeletal regulation, epithelial barrier, and protection function were found to be associated with the optimal neurodevelopmental outcomes. In addition, mitochondrial function-associated proteins including SPRR2A, PAIP1, S100A3, MT-CO2, PiC, GLRX, PHB2, and BNIPL-2 demonstrated positive association with favorable neurodevelopmental outcomes, while proteins of ABLIM1, UNC45A, keratins, MUC1, and CYB5B showed positive association with adverse neurodevelopmental outcomes. Conclusion: Mitochondrial function-related proteins were observed to be associated with early life pain/stress and neurodevelopmental outcomes in infants. Large-scale studies with longitudinal datasets are warranted. Buccal proteins could be used to predict potential neurobehavioral outcomes.

Rule-based deep learning method for prognosis of neonatal hypoxic-ischemic encephalopathy by using susceptibility weighted image analysis.

Susceptibility weighted imaging (SWI) of neonatal hypoxic-ischemic brain injury can provide assistance in the prognosis of neonatal hypoxic-ischemic encephalopathy (HIE). We propose a convolutional neural network model to classify SWI images with HIE. Due to the lack of a large dataset, transfer learning method with fine-tuning a pre-trained ResNet 50 is introduced. We randomly select 11 datasets from patients with normal neurology outcomes (n = 31) and patients with abnormal neurology outcomes (n = 11) at 24 months of age to avoid bias in classification due to any imbalance in the data. We develop a rule-based system to improve the classification performance, with an accuracy of 0.93 ± 0.09. We also compute heatmaps produced by the Grad-CAM technique to analyze which areas of SWI images contributed more to the classification patients with abnormal neurology outcome. Such regions that are important in the classification accuracy can interpret the relationship between the brain regions affected by hypoxic-ischemic and neurodevelopmental outcomes of infants with HIE at the age of 2 years.

Effect of Nicotinamide Mononucleotide Concentration in Human Milk on Neurodevelopmental Outcome: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

(1) Background: Breast milk is the only source of nutrition for breastfed infants, but few studies have examined the relationship between breast milk micronutrients and infant neurodevelopmental outcome in exclusively breastfed infants. The aim of this study was to characterize the association between nicotinamide adenine dinucleotide (NAD)-related compounds in the breast milk of Japanese subjects and infant neurodevelopmental outcome. (2) Methods: A total of 150 mother-child pairs were randomly selected from the three-generation cohort of the Tohoku Medical Megabank in Japan. Infants were exclusively breastfed for up to 6 months. Breast milk was collected at 1 month postpartum, and the quantity of NAD-related substances in the breast milk was quantified. The mothers also completed developmental questionnaires at 6, 12, and 24 months. The relationship between the concentration of NAD-related substances in breast milk and developmental indicators was evaluated via ordinal logistic regression analysis. (3) Results: Nicotinamide mononucleotide (NMN) was quantified as the major NAD precursor in breast milk. The median amount of NMN in the breast milk was 9.2 μM. The NMN concentration in breast milk was the only NAD-related substance in breast milk that showed a significant positive correlation with neurodevelopmental outcome in infants at 24 months. (4) Conclusions: The results suggest that NMN in human milk may be an important nutrient for early childhood development.