Search Results (78)

Background: Very preterm infants are at increased risk of impairment. The objective was to explore the effect of immediate parent–infant skin-to-skin contact at very preterm birth on cognition, motor, social, and language development during the two first years. Methods: The Immediate Parent-Infant Skin-To-Skin Study (IPISTOSS) was a clinical trial with inclusions between April 2018 to June 2021, in three Scandinavian neonatal intensive care units. Infants were randomised at gestational age 28 + 0 to 32 + 6 weeks plus days, to immediate and continuous skin-to-skin contact at birth or conventional care, during the first six hours of life. Results: At three months, 42 infants underwent a General Movement Assessment. At four and 12 months, 69 and 62 infants, respectively, were assessed with the Alberta Motor Infant Scale. At 24 months, language and cognition were tested in 62 infants with the Bayley Scales of Infant and Toddler Development, third edition. Parents completed the Modified Checklist for Autism in Toddlers for 57 infants. There were no significant differences in motor development, cognition, or autism spectrum disorders. A significant difference in language scores in favour of immediate skin-to-skin contact, was found, when adjusted for fathers’ education, mothers’ education, and infants’ sex, Beta (95% CI): 32.00 (7.57, 56.43) p = 0.01, 11.51 (8.94, 55.06) p = 0.007, and 32.00 (7.85, 56.15) p = 0.01, respectively. Conclusions: Skin-to-skin contact immediately at birth did not enhance cognition, motor, or social development during the first two years of life but may have been important for language skills. Our findings support the World Health Organisation guidelines recommending iSSC for preterm born infants in all settings. Full article

Objective: To comprehensively evaluate the interaction between diet quality and multivitamin intake during pregnancy on offspring neurodevelopment. Methods: This analysis was grounded in mother-child dyads from the 3D Cohort Study in Quebec, Canada. Among the 2366 participants initially enrolled in the 3D study, 1535 women successfully completed the 3-day food record during 20–24 weeks of gestation. A Canadian adaptation of the Healthy Eating Index (HEI-C) 2010 was used to quantify diet quality. The total HEI-C score was dichotomized into low and high diet quality by median split. Cognitive and motor development in childhood were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Language abilities were measured using the toddler short-form version of the MacArthur–Bates Communicative Development Inventories (MCDI) questionnaire, administered in either English or French. After excluding participants with missing covariate data, cognitive, motor, and language development scores at 2 years of age were available for 1066, 1040, and 981 children, respectively. Multiple linear regression models were employed to calculate adjusted effect estimates. The interaction on an additive scale was assessed by incorporating a product term into the linear regression model. Results: Statistically significant interactions were detected between diet quality and multivitamin intake in relation to the cognitive and language development outcomes of the offspring (interaction p-values were 0.018 and 0.023, respectively). The lowest cognitive and language scores were observed in the group of women who neither took multivitamins nor maintained a high-quality diet. Among women not taking multivitamins, a high-quality diet was associated with improved offspring cognitive and language scores (mean difference [95% CI] = 4.2 [0.1, 8.2], p = 0.04; and 11.3 [3.1, 19.5], p = 0.01, respectively). However, among women taking multivitamins, no such associations were identified. Conversely, in participants with a low-quality diet, multivitamin intake was associated with a 3.0-point increase in cognitive composite scores (95% CI: 0.3, 5.8, p = 0.03), but this was not the case for those with a high-quality diet. No statistically significant interactions were observed between maternal diet quality and multivitamin intake for motor development outcomes. Conclusions: Adequate nutritional supply during pregnancy, achieved either through a high-quality diet or multivitamin supplementation, is fundamental for the neurodevelopment of children. Full article

Background/Objectives: Preterm infants are at high risk of extrauterine growth restriction and suboptimal neurological development due to cumulative nutrient deficits. Standard fortification (SF) of human milk does not account for individual macronutrient variability, potentially leading to inadequate intake. Target fortification (TFO) adjusts supplementation based on the measured macronutrient content, aimed at providing macronutrient intake aligned with ESPGHAN (European Society for Paediatric Gastroenterology, Hepatology and Nutrition) recommendations and optimize growth and development. This study aims to evaluate the effects of TFO compared to SF on growth, body composition, and neurological outcomes at 18 months corrected age. Methods: In this double-blind, randomized controlled trial, preterm infants (<30 weeks gestation) received either SF or TFO for at least three weeks. Macronutrient levels in breast milk were analyzed three times per week, with modular adjustments in the TFO group. Growth parameters, body composition at 36 weeks postmenstrual age, and Bayley Scales of Infant and Toddler Development III (BSID-III) scores at 18 months corrected age were assessed (n = 69). Results: TFO significantly increased protein, fat, and carbohydrate intake compared to SF, leading to higher weight gain (2514 ± 289 g vs. 2283 ± 332 g, p < 0.01) and growth velocity (21.7 ± 2.3 g/kg/d vs. 19.2 ± 2.2 g/kg/d, p < 0.001). In infants whose mother’s milk had low protein levels, fat-free mass was significantly higher with TFO compared to SF. BSID-III scores were higher in the TFO group across cognitive, language, and motor domains, with significant improvements in expressive language scores in infants whose mother’s milk had high protein levels (p < 0.05). The number of preterm infants with a motor BSID-III score of ≤70 was significantly lower in the TFO group compared to the SF group (0 vs. 3, p < 0.05). Conclusions: TFO enhanced growth and body composition and may support better neurological outcomes in preterm infants. While most BSID-III differences were not statistically significant, the data suggest that TFO may reduce the risk of developmental delays. Larger, multicenter trials are needed to confirm these findings. Full article

Background/Objectives: Optimal feeding regimens for preterm neonates, including the role of multi-nutrient fortification, are unknown, leading to large practice variation in comparing different feeding regimens that include fortification and their impact on outcomes for preterm infants. Methods: Using a network meta-analyses design, two reviewers independently extracted data. A Cochrane CENTRAL, Medline, Embase, and CINAHL search was conducted for all studies published up to 27 June 2023. Randomized clinical trials of feeding regimens for preterm infants that included multi-nutrient fortification were included. Outcomes were mortality, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), sepsis, periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), time to full enteral feeds, and the Bayley II MDI developmental score. Results: Fifty-nine studies were included. For mortality, NEC, and time to reach full enteral feeds, the top-ranked treatment class was the mother’s own milk with donor milk and a human-milk-based fortifier. For ROP and BPD, the top-ranked treatment class was mother’s own milk with a phosphorus fortifier. For sepsis, the top-ranked treatment class was mother’s own milk with formula. For PVL, the top-ranked treatment classes were mother’s own milk and mother’s own milk with donor milk and a bovine fortifier in the two disconnected networks. For the Bayley II MDI score, the top-ranked treatment class was mother’s own milk with formula and bovine fortification. Conclusions: Treatment rankings are consistent with the underlying hypothesis that increased mother’s own milk intake appears to be associated with better clinical outcomes. This review provides the first global view of interventions and highlights insufficient high-quality evidence to support or refute one fortification feeding regimen over another. Full article

Background/Objectives: Follow-up studies in very preterm infants are common, but fewer studies are situated in low- or middle-income countries. In a prospective cohort study, we explored longitudinal motor performance trajectories and influencing factors, including an early motor intervention program. Very preterm infants (gestational age < 32 weeks and/or very-low-birth-weight < 1500 g) in the middle-income country of Suriname were included. Methods: We assessed 149 (49.7% boys) infants (mean gestational age 29⁺⁶, mean birth weight 1271 g) at 3, 12, and 24 months with the Bayley Scales of Infant and Toddler Development for fine motor (FM), gross motor (GM), and composite scores (CSs). Influencing perinatal and environmental factors were explored. Delayed-scoring infants were referred to a motor intervention program. Data were analyzed using mixed-model linear regression. Results: The Bayley mean FM and GM scores decreased between 3 and 12 months and stabilized at 24 months. The mean CS at 3, 12, and 24 months was 102.3, 92.7, and 92.2, respectively. The latter two were significantly below the reference values (100, SD 15, p < 0.01). Birth weight z-scores significantly influenced FM (p = 0.013) and CS (p = 0.009); a lower birth weight was associated with initially lower scores and a smaller decline over time than a higher birth weight. The motor intervention program (n = 54) showed no significant interaction effects at all time points after correction for frequency of interventions (no; 1–5; >5 interventions). Conclusions: Motor performance was normal at 3 months and delayed at 12 and 24 months. Birth weight, but not the early intervention program, influenced longitudinal motor trajectories. We recommend follow-up of motor performance and suggest adding the Prechtl General Movement assessment at 3 months of age. The clinical implementation of the early motor invention program needs additional studies to reach an adequate training level. Full article

Objectives: Previous studies have assessed the effect of docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (ARA, 20:4n-6)-supplemented infant formula on brain development and cognitive function in infants. However, the results have been inconsistent. The aim of this systematic review and meta-analysis was to assess the effect of DHA and ARA supplementation on cognitive function in infants from randomized controlled trials (RCTs). Methods: We systematically searched and identified relevant literature from the PubMed, Web of Science, and Embase databases up to July 2024. Standard methods were applied to assess publication bias, sensitivity analysis, and heterogeneity among the included studies. A total of nine RCTs were included in the study, which comprised 1039 subjects. Results: Meta-analysis showed significantly positive effects of DHA and ARA supplementation on cognitive development in infants (Standardized Mean Difference (SMD): 0.21; 95% CI: 0.03, 0.38). No significant difference was found in Mental Development Index (MDI) score (Weighted Mean Difference (WMD): 0.20; 95% CI: −0.03, 0.43) and Psychomotor Development Index (PDI) score (WMD: 0.12; 95% CI: −0.11, 0.35) in Bayley Scales of Infant and Toddler Development compared with the control group. In subgroup analysis, when DHA/ARA was 0.5–1, PDI had a significant difference (WMD: 0.48; 95% CI: 0.03, 0.93) compared with the control group, with no significant difference between heterogeneity (I² = 46.4%, p = 0.155). In comparison to the control group, significant differences were observed in MDI when DHA/ARA levels were between 0.5 and 1 (WMD: 0.55; 95% CI: 0.07, 1.02), with no significant difference between heterogeneity (I² = 51.6%, p = 0.127). Conclusion: When the DHA /ARA was 0.5–1 can significantly improve the cognitive function in infants. Full article

Preclinical studies have shown that progenitor cells (PCs) are mobilized toward injured tissues to ameliorate damage and contribute to regeneration. The exogenous therapeutic administration of PCs in children affected by neonatal encephalopathy (NE) is a promising, yet underreported, topic. In this prospective study, we investigated whether endogenous circulating progenitor cells (CPCs) are involved in intrinsic regeneration mechanisms following neonatal brain injury. Thirteen full-term infants with moderate/severe NE, eleven with perinatal stress, and twelve controls were enrolled. Blood samples were collected on days 1, 3, 9, 18, and 45, as well as at 8 and 24 months of life, and were analyzed with a focus on Endothelial Progenitor Cells, Haematopoietic Stem Cells, and Very Small Embryonic-Like Stem Cells, in addition to chemotactic factors (erythropoietin, IGF-1, and SDF-1). Correlations between CPCs, chemotactic factors, and brain injury were assessed using serum levels of brain injury biomarkers (S100B and neuron-specific enolase), brain MRIs, and Bayley III developmental scores. Increased brain injury biomarkers were followed by the upregulation of SDF-1 receptor and erythropoietin and, finally, by elevated CPCs. These findings suggest a potential endogenous regenerative effort, primarily observed in the moderate encephalopathy group, but this is suppressed in cases of severe brain injury. Mimicking and enhancing endogenous regeneration pathways in cases of failure—regarding cell type and timeframe—could provide a novel therapeutic model. Full article

Background/Objectives: Infant FreeSurfer was introduced to address robust quantification and segmentation in the infant brain. The purpose of this study is to develop a new model for predicting the long-term neurodevelopmental outcomes of very low birth weight preterm infants using automated volumetry extracted from term-equivalent age (TEA) brain MRIs, diffusion tensor imaging, and clinical information. Methods: Preterm infants hospitalized at Severance Children’s Hospital, born between January 2012 and December 2019, were consecutively enrolled. Inclusion criteria included infants with birth weights under 1500 g who underwent both TEA MRI and Bayley Scales of Infant and Toddler Development, Second Edition (BSID-II), assessments at 18–24 months of corrected age (CA). Brain volumetric information was derived from Infant FreeSurfer using 3D T1WI of TEA MRI. Mean and standard deviation of fractional anisotropy of posterior limb of internal capsules were measured. Demographic information and comorbidities were used as clinical information. Study cohorts were split into training and test sets with a 7:3 ratio. Random forest and logistic regression models were developed to predict low Psychomotor Development Index (PDI < 85) and low Mental Development Index (MDI < 85), respectively. Performance metrics, including the area under the receiver operating curve (AUROC), accuracy, sensitivity, precision, and F1 score, were evaluated in the test set. Results: A total of 150 patient data were analyzed. For predicting low PDI, the random forest classifier was employed. The AUROC values for models using clinical variables, MR volumetry, and both clinical variables and MR volumetry were 0.8435, 0.7281, and 0.9297, respectively. To predict low MDI, a logistic regression model was chosen. The AUROC values for models using clinical variables, MR volumetry, and both clinical variables and MR volumetry were 0.7483, 0.7052, and 0.7755, respectively. The model incorporating both clinical variables and MR volumetry exhibited the highest AUROC values for both PDI and MDI prediction. Conclusions: This study presents a promising new prediction model utilizing an automated volumetry algorithm to distinguish long-term psychomotor developmental outcomes in preterm infants. Further research and validation are required for its clinical application. Full article

Background: Preventing neurodevelopmental impairment after extremely preterm birth remains challenging. While breast milk feeding is linked to better neurodevelopment, the underlying mechanisms are unclear. This study explored the association between individual human milk oligosaccharides (HMO) and neurodevelopment at two years of age in extremely preterm children. Methods: Milk samples from mothers of 76 extremely preterm infants collected at two weeks after birth were analyzed for 15 dominant HMOs. Register data from examination and Bayley-III neurodevelopmental assessment at two years’ corrected age was retrieved and categorized into levels of impairment. An exploratory analysis examined associations between the HMO composition and neurodevelopment. Results: Bioinformatic volcano plots revealed associations between specific HMOs and outcomes: 3FL with less neurodevelopmental impairment, LSTb with higher Bayley-III cognitive scores, and LSTa with worse neurodevelopmental impairment outcomes. Spearman correlations indicated LSTa was linked to more neurodevelopmental impairment (p = 0.018), lower language (p = 0.009), and motor (p = 0.02) scores, whereas 3FL correlated with less neurodevelopmental impairment (p = 0.02). Dichotomized analysis showed LSTa was associated with more neurodevelopmental impairment and lower language scores (p < 0.05), 3FL with milder neurodevelopmental impairment (p < 0.05), and LSTb with better cognitive (p < 0.01) and language (p < 0.05) scores. No significant associations were found for HMO diversity, total sialic acid content, or secretor/Lewis patterns. Conclusions: In this explorative hypothesis-generating study, certain HMOs appeared to be associated with both potentially beneficial and adverse neurodevelopmental outcomes in extremely preterm infants. However, these findings should be interpreted with caution, as they do not constitute evidence but rather serve as a preliminary foundation for future hypothesis-driven research. Full article

Background: The percentage of preterm infants requiring surgery before 44 weeks of postmenstrual age (PMA) varies between 19% and 36%. The potential impact of general anesthesia on the vulnerable developing brain of preterm infants remains unknown. Methods: A systematic review and meta-analysis on the impact of general anesthesia on brain integrity and neurodevelopmental outcomes in preterm infants undergoing surgery before 44 weeks PMA was conducted. Studies were identified via a PubMed, EMBASE (Ovid), and Cochrane CENTRAL search conducted from inception until 8 March 2023, following PRISMA guidelines. Brain abnormality was assessed using MRI-based brain volume and abnormality scores. Neurodevelopment was evaluated through Bayley Infant and Toddler Development (BSID) or Wechsler Preschool and Primary Scale of Intelligence (WPPSI) tests. Quality was assessed via the Cochrane ROBINS-I tool and GRADE. Results: Our systematic search identified 2883 records, leading to the inclusion of 12 observational studies. Very low-quality evidence suggests that preterm infants exposed to anesthesia were more likely to show postoperative brain abnormalities on MRI (OR 2.01, 95%CI 1.24–3.25, p = 0.005). They had lower neurodevelopmental scores on the BSID II and III (psychomotor developmental index: mean difference (MD) −10.98; 95%CI −12.04 to −9.91; p < 0.001 and cognitive composite score: (MD) −10.11; 95%CI −11.06 to −9.16; p < 0.001 at two years of age compared to preterm infants not exposed to anesthesia. Conclusion: Exposure to surgery and anesthesia before term age is associated with brain abnormalities and neurodevelopmental delay at two years, but conclusions are limited by low evidence quality, uncontrolled confounders, and the methodological biases of the included studies; thus further robust studies are required (PROSPERO:CRD42021255907). Full article

Background/Objectives: While studies in rat pups suggest that early zinc exposure is critical for optimal brain structure and function, associations of prenatal zinc intake with measures of brain development in infants are unknown. This study aimed to assess the associations of maternal zinc intake during pregnancy with MRI measures of brain tissue microstructure and neurodevelopmental outcomes, as well as to determine whether MRI measures of the brain mediated the relationship between maternal zinc intake and neurodevelopmental indices. Methods: Forty-one adolescent mothers were recruited for a longitudinal study during pregnancy. Maternal zinc intake was assessed during the third trimester of pregnancy using a 24 h dietary recall. Infant MRI scans were acquired at 3 weeks postpartum using a 3.0 Tesla scanner to measure fractional anisotropy (FA) and mean diffusivity (MD). Cognitive, language, and motor skills were assessed at 4, 14, and 24 months postpartum using the Bayley Scales of Infant Development. Results: Greater prenatal zinc intake was associated with reduced FA in cortical gray matter, particularly in the frontal lobe [medial superior frontal gyrus; β (95% CI) = −1.0 (−1.5, −0.5)], in developing white matter, and in subcortical gray matter nuclei. Greater prenatal zinc intake was associated with reduced MD in cortical gray matter and developing white matter [superior longitudinal fasciculus; −4.4 (−7.1, −1.7)]. Greater maternal zinc intake also was associated with higher cognitive development scores at 14 [0.1 (0.0, 0.1)] and 24 [0.1 (0.0, 0.2)] months of age; MRI indices of FA and MD did not mediate this relationship. Conclusions: Maternal prenatal zinc intake was associated with more favorable measures of brain tissue microstructural maturation and cognitive development during infancy. Full article

Prenatal lead (Pb) and manganese (Mn) exposure can impair neurodevelopment, targeting the central nervous system. This study investigated the effects of prenatal exposure to Pb and Mn on neurodevelopment in children at 18 months of age, using data from 607 Italian mother–child pairs enrolled in the Northern Adriatic Cohort II (NAC-II). All children born at term (≥37 weeks) were assessed with the Bayley Scales of Infant and Toddler Development, third edition. Cord blood concentrations of Mn and Pb were categorized as low or high exposures based on the 75th percentile of their distribution. Sociodemographic and lifestyle information was collected via questionnaires. Using simple and multiple linear regressions, the study examined the relationship between the cognitive composite score (COGN) and Mn and Pb co-exposure, including their interaction. Stratified regressions explored how Mn exposure influenced the effect of Pb, in the whole cohort and by the child’s sex. Beta coefficients (β) and the 90% confidence interval (90% CI) were estimated. Boys showed an interaction effect between Mn and Pb, with a reduction in COGN (β = −5.78, 90% CI: −11.17; −0.40), further described as a negative effect of high Pb on cognition when Mn exposure was also high (β = −6.98, 90% CI: −10.93; −3.04). No clear effects were observed in girls or the entire cohort at these levels of exposure. The findings highlight the harmful impact of combined prenatal Pb and Mn exposure on cognitive development in boys. Full article

Introduction and Aim: Propranolol is an effective treatment option for infantile hemangiomas, but there is still insufficient information about neurodevelopmental side effects of propranolol. In our study, the neurodevelopmental levels of infantile hemangioma patients receiving propranolol treatment were examined using the Bayley-III test. Method: In our single-center, cross-sectional study, patients were recruited between 1 January 2020 and 31 December 2023. In total, 40 children (n1) diagnosed with hemangioma who received propranolol treatment and 31 children (n2) who were only under observation were included. A control group of 31 healthy children (n3) matched for age and gender was also included. The demographic, clinical, perinatal, and postnatal characteristics of the total 102 children were recorded from their medical records. Neurodevelopmental levels were assessed with the Bayley-III test. The significance level was set at (p < 0.05). Results: The Bayley-III test composite and percentile scores were used to evaluate the neurodevelopmental levels. Significant differences in motor functions were found between the treated and untreated groups compared to the healthy control group (p = 0.006 and p = 0.006). However, no significant differences were found in cognitive, language, and social-emotional skills. Cognitive, language, and motor functions were associated with maternal education level, and additionally, cognitive functions were also associated with paternal education level. Conclusions: Propranolol has a relatively safer side effect profile, and therefore, it has been described as a safe agent. In our study, no significant effect of propranolol on neurodevelopment was observed. The difference in motor skills shown was mainly between the healthy control group (n3) and the treated and untreated group (n1 and n2), which led to the conclusion that the relevant difference could be due to factors other than propranolol itself. Full article

This study aimed to explore whether early developmental abilities are related to future executive function (EF) in children with motor delays. Fourteen children with motor delays (Mean age = 10.76, SD = 2.55) were included from a larger study. Object interaction and developmental outcomes (Bayley-III) were evaluated at baseline and 3, 6, and 12 months post-baseline. Bayley-III and EF assessments (Minnesota Executive Function Scale) were conducted at 36 months post-baseline. Children with high EF demonstrated advanced early bimanual, visual–bimanual, receptive language, expressive language, and fine motor skills compared to children with low EF. Significant positive correlations between later Bayley-III and EF scores were found for cognitive, expressive language, and fine motor scores. These preliminary results suggest that early developmental skills support the emergence of EF in children with motor delays. Full article