Search Results (33)

Background/Objectives: Preterm infants are at risk for developmental delays due to immature brain development and increased sensitivity to environmental stress. Genetic factors, such as polymorphisms in *OXTR* rs2268490, *COMT* rs4818, and *GRIN2B*, may influence these vulnerabilities and affect neurodevelopment. Methods: We recruited 91 preterm infants (<35 weeks gestation) admitted to the NICU at Hanyang University Seoul Hospital between January 2020 and December 2022. Brain MRIs were conducted at term-equivalent age, and DNA samples were analyzed for SNPs. Neurodevelopmental assessments were performed at 18 months corrected age using the Korean Developmental Screening Test (K-DST) and Bayley Scales of Infant Development, Third Edition (BSID-III). Results: Carriers of the minor alleles in *OXTR* rs2268490 showed significantly lower language and adaptive behavior, and *COMT* rs4818, rs740603 showed significantly lower social–emotional scores on BSID-III. *OXTR* rs2268490 was also associated with altered brain network metrics, including decreased small-worldness (p = 0.012) and increased global (p = 0.038) and local efficiency (p = 0.042). Conclusions: Polymorphisms in the *OXTR* genes are associated with differences in brain network organization and neurodevelopmental outcomes in preterm infants. These variants may influence how environmental factors affect early brain development, highlighting the importance of genetic screening and early intervention. Full article

Background/Objectives: Overweight and obesity during pregnancy are metabolic risk factors that may compromise offspring brain development. The first 1000 days of life represent a critical window in which neurodevelopmental trajectories are shaped by intrauterine and early-life exposures. The 6- and 12-month milestones are key checkpoints where deviations may emerge, and interventions are most effective. This study evaluated the association between maternal pregestational weight status and infant neurodevelopment at 6 and 12 months of age. Methods: Mother and infant pairs from the OBESO perinatal cohort in Mexico City were included. Women in the first trimester of pregnancy were classified as normal weight and overweight/obesity according to their pregestational body mass index (pBMI), calculated from self-reported pre-pregnancy weight. Infant neurodevelopment was assessed at 6 and 12 months using the Bayley Scales of Infant Development III, Third Edition (BSID-III). Descriptive, bivariate and multiple linear regression analyses with mixed effects correction were conducted. Results: Among 97 mother–infant pairs, infants of mothers with overweight/obesity had lower language and socio-emotional scores at 12 months. Higher maternal pBMI was correlated with lower motor scores at 6 and 12 months, and with lower language scores at 12 months. Longitudinal analysis showed that maternal overweight/obesity was associated with a significant decline in language development from 6 to 12 months. (p = 0.002). Conclusions: Maternal pregestational overweight or obesity may negatively influence early neurodevelopment, particularly affecting language and cognitive domains during the first year of life. These early deficits could reflect alterations in intrauterine programming associated with maternal metabolic status. Full article

Background: Preterm birth is associated with increased risk for neurodevelopmental disorders. Although standardized tools such as the Bayley Scales of Infant and Toddler Development—Third Edition (BSID-III) are widely used for early developmental assessment, parent-report measures may offer complementary and cost-effective alternatives. The Developmental Profile 3 (DP-3) is a parent questionnaire with potential utility in preterm follow-up programs. Objective: To compare developmental outcomes of preterm infants at 12 months corrected age assessed using the BSID-III and the DP-3 questionnaires and to evaluate the agreement between these tools across cognitive, language-communication, motor, and social-emotional domains. Methods: Fifty-five preterm infants (mean GA = 30.3 weeks; mean BW = 1388 g) were assessed using both the BSID-III (administered by professionals) and the DP-3 (completed by parents) at 12 months corrected age. Mean scores were computed for each domain, and infants were assigned to the corresponding descriptive categories. The agreement between BSID-III and DP-3 scores was statistically evaluated. Results: Both instruments identified similar developmental trends, with motor development emerging as the most vulnerable domain for preterm infants. DP-3 scores were higher than BSID-III scores in virtually all domains, and absolute intraclass correlation coefficients showed a generally moderate agreement between measurements. The BSID-III identified significantly more infants at risk in the cognitive and social-emotional areas compared to the DP-3. Conclusions: The DP-3 showed fair convergence with the BSID-III, supporting its use as a complementary tool in preterm follow-up. Extending follow-up assessments into later developmental stages will be essential to more accurately determine the predictive validity of the DP-3. 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: 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: The balance of omega-6/omega-3 (n-6/n-3) is crucial for proper brain function as they have opposite physiological roles. Objectives: To analyze the association between maternal serum ratios of n-6/n-3 in the first and third trimesters of pregnancy and the neurodevelopment of their children in the early days after birth in the population of Northern Spain’s Mediterranean region. Methods: Longitudinal study in which 336 mother–child pairs participated. Mother serum concentrations of long-chain polyunsaturated fatty acids (LCPUFAs), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) were determined. Sociodemographic, clinical, lifestyle habits, and obstetrical variables were collected. The Bayley Scales of Infant and Toddler Development (BSID-III) was used to assess infant neurodevelopment. Multiple linear regression models adjusting for confounding factors were performed. Results: In the third trimester, a higher maternal n-6/n-3 ratio was negatively associated with infant motor development (β = −0.124, p = 0.023). Similarly, higher ARA/DHA ratios were negatively associated with total motor (β = −2.005, p = 0.002) and fine motor development (β = −0.389, p = 0.001). No significant associations were observed in the first trimester nor for the ARA/EPA ratio in the third trimester. Conclusions: Our findings indicate that an elevated n-6/n-3 ratio and ARA/DHA ratio in the third trimester of pregnancy are associated with poorer motor development outcomes in infants. These results highlight the importance of optimizing maternal fatty acid balance during pregnancy to support fetal neurodevelopment, suggesting a need for further research to verify these associations and elucidate underlying mechanisms. Full article

Background: Research in typically and some atypically developing populations showed associations between early motor and communication development, documenting how postural development can support communicative advancements. However, these relations have scarcely been investigated in the preterm population. Aims: The present study aimed to describe motor (gross and fine motor) and communication (receptive and expressive) skills of very preterm infants at six months of corrected age and their associations, focusing on sitting posture achievement and early vocal production. Methods: Seventy very preterm infants (≤32 weeks) with no major brain injuries were assessed with the BSID-III for gross and fine motor skills, receptive and expressive language skills, and cognitive skills and were categorized as mastering (sitters), partially mastering (emerging sitters), or not mastering (non sitters) unsupported sitting. The proportional duration of sitting postures (caregiver supported, arms supported, and unsupported) in an observative section was coded with the Interact software (version 20.8.3.0). Frequency per minute of vocal utterances (vocalizations, babbling, and total) during a parent–infant play interaction was coded with the CHILDES software v11. Results: Correlational analyses showed significant positive associations between motor composite score and language scores (composite and expressive scaled) and between gross motor and expressive language scaled scores but a negative association between arms supported sitting duration and vocal utterances. In addition, ANCOVAs showed that sitters had significantly higher BSID-III expressive language scaled scores and vocal utterances than non sitters and emerging sitters. Conclusions: These findings brought new evidence linking early motor and vocal development in very preterm infants, emphasizing the importance of using observational tools alongside standardized ones to identify developmental delays and plan tailored intervention programmes. Full article

The emergence of symbolic gestures is a solid milestone in early childhood development. Interventions that intentionally promote them have contributed to children’s language, cognitive, and socioemotional development. However, these studies have mainly been conducted in the USA with middle-SES families, and such research has considerably decreased in recent years. This study aimed to assess the effects of an intentional intervention for promoting symbolic gestures in the expressive and comprehensive language of Chilean children who were aged 18 months. Sixty-nine highly psychosocially at-risk children were assessed at 5–9 months and then at 18 months. Teachers from half of the nurseries involved in the study received the intervention. The assessment included a report on the children’s gestural vocabulary, the CDI, and the language scale of BSID-III. The results showed that the children in the intervention group had a significantly greater gestural vocabulary at 18 months and they performed better in their expressive language than the children in the control group did. Additionally, this study aimed to analyze if this intervention affected children differentially in consideration of their language development (adequate and at-risk). The results showed that children with adequate development improved their language when they received the intervention, but those from the at-risk group did not. The implications of these results for the design of interventions at an early age are discussed while considering children from different sociocultural backgrounds and with different language development. Full article

Omega-3 Long-Chain Polyunsaturated Fatty Acids (n-3 LCPUFAs) play a key role in early neurodevelopment, but evidence from observational and clinical studies remains inconsistent. This study investigates the association between maternal n-3 LCPUFA, Docosahexaenoic Acid (DHA), and eicosapentaenoic acid (EPA) concentrations during pregnancy and infant development functioning at 40 days. This study includes 348 mother–infant pairs. Maternal serum concentrations were assessed in the first and third trimesters alongside sociodemographic, clinical, nutritional, psychological, and obstetrical data. At 40 days, the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) was administered. An adjusted analysis revealed that lower first-trimester n-3 LCPUFA and DHA concentrations are associated with better infant motor development. These results underscore the potential significance of the maternal n-3 LCPUFA status in early pregnancy for influencing fetal neurodevelopment. However, the complexity of these associations necessitates further investigation, emphasizing the urgent need for additional studies to comprehensively elucidate the nuanced interplay between the maternal n-3 LCPUFA status and infant neurodevelopment. Full article

Metabolic bone disease (MBD) predominantly affects preterm infants, particularly very-low-birth-weight (VLBW) infants weighing <1500 g. However, there are limited reports on MBD and neurodevelopmental outcomes. This study aimed to analyze the risk factors for MBD and understand its impact on neurodevelopmental outcomes at 2 years of corrected age. Overall, 749 VLBW infants weighing <1350 g at birth were enrolled. Exclusion criteria were major congenital abnormalities, chromosomal abnormalities, and loss of follow-up on the Bayley Scales of Infant Development, Third Edition (BSID-III) test at 24 months of corrected age. Infants were retrospectively assessed by a trained case manager using the BSID-III test at 6, 12, and 24 months old. Infants were categorized as with or without MBD according to radiographic signs. Of those enrolled, 97 VLBW infants were diagnosed with MBD, compared to 362 VLBW infants without MBD. The proportion of infants that completed three follow-ups was 86%. At the assessment at 2 years of age, infants with MBD had lower and more significant differences in motor, language, and cognitive composites. MBD is associated with poor neurodevelopmental outcomes in cognitive, motor, and language composites for VLBW infants at 24 months of corrected age. Full article

Background: Severe maternal iodine deficiency has profound consequences for the developing brain; however, the impact of mild to moderate deficiency is less clear, and findings from observational studies have been mixed. Aim: The purpose of this study is to assess the relationship between maternal iodine status in early pregnancy and infant neurological development in an Irish maternal–infant cohort. Methods: Maternal–infant dyads of the Improved Pregnancy Outcomes by Early Detection (IMPROvED) and the Cork Nutrition and Development (COMBINE) cohorts (n 456) were followed during pregnancy and from birth to 2 years of age. Participants completed detailed a clinical and questionnaire-based assessments (including Bayley’s Scale of Infant Development (BSID-III) at 24 months; n 295). Maternal urinary iodine concentration (UIC) was quantified at 15 weeks of gestation by the Sandell–Kolthoff (S-K) method, and urinary creatinine (Cr) was quantified by the Jaffe rate method using the RX Monaco Clinical Chemistry Analyser (Randox Laboratories Ltd.). Statistical analysis was performed using IBM SPSS Version 27 (IBM Corp., Armonk, NY, USA). Results: The median (IQR) maternal age at delivery was 32 (5) years, and the median (IQR) BMI at 15 weeks of gestation was 25.1 (5.0) kg/m². Three-quarters completed third-level education, 95% were in a relationship and 7% were smokers. Median (IQR) UIC was 118 (132) µg/L, and 65% had UIC < 150 µg/L. At 24 months, median (IQR) cognitive, language and motor composite scores were 105 (15), 103 (20) and 103 (14), respectively. Cognitive, language and motor developmental delay was indicated in 6.0, 7.8 and 0.4% of children, respectively. Though a slightly higher prevalence of developmental language delay was observed among infants of mothers with UI:Cr < 150 µg/g for language (11 versus 6%) and a combined cognitive/language outcome (10 versus 4%), when adjusted for education, marital status, gestational age and birthweight, UI:Cr was not associated with language delay (aOR (95% CI): 1.7 (0.6, 4.7)). Among non-users of iodine supplements (29% of sample; median (IQR) UIC: 84 (96) µg/L; 75% < 150 µg/L), for every 10 µg/L increase in UIC, we observed a 23% and 19% reduction in odds of cognitive and language delay, respectively (aOR (95% CI): 0.77 (0.71, 0.97), p = 0.029; 0.81 (0.66, 0.99), p = 0.035). Our findings highlight the importance of sufficient iodine status in early pregnancy. Full article

(1) Background: Cerebral MRI plays a significant role in assessing the extent of brain injury in neonates with neonatal encephalopathy after perinatal asphyxia. Over the last decades, several MRI scoring systems were developed to enhance the predictive accuracy of MRI. The aim of this study was to validate the correlation of four established MRI scoring systems with cognitive long-term outcomes in cooled asphyxiated newborns. (2) Methods: Forty neonates with neonatal encephalopathy treated with therapeutic hypothermia were included in this retrospective study. The MRI scans from the second week of life were scored using four existing MRI scoring systems (Barkovich, NICHD, Rutherford, and Weeke). The patients’ outcome was assessed with the Bayley Scales of Infant Development (BSID-III) at the age of 2 years. To evaluate the correlation between the MRI scoring system with the cognitive scores of BSID-III, the correlation coefficient was calculated for each scoring system. (3) Results: All four MRI scoring systems showed a significant correlation with the cognitive scores of BSID-III. The strongest correlation was found between the Weeke Score (r² = 0.43), followed by the Rutherford score (r² = 0.39), the NICHD score (r² = 0.22), and the Barkovich score (r² = 0.17). (4) Conclusion: Our study confirms previously published results in an independent cohort and indicates that the Weeke and Rutherford scores have the strongest correlation with the cognitive score of BSID-III in cooled asphyxiated newborns. Full article

One of the biggest threats to early childhood development in Africa is poor maternal mental health. The present study reports on the relationships between clinical diagnoses of persistent maternal mental health disorders (at 3- and/or 6- and 18-month post-term age) and toddler neurodevelopment at 18 months of age. Eighty-three mother–toddler dyads from low socio-economic status settings in Cape Town, South Africa, were included. At the 3-, 6- and 18-month postnatal visits, clinician-administered structured diagnostic assessments were carried out according to the Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) criteria. Toddler neurodevelopment at 18 months corrected age was assessed with the Bayley Scales of Infant and Toddler Development (BSID-III). No significant differences (p > 0.05) were found between toddlers with exposure to persistent mood or psychotic disorders in the different BSID-III domains compared to toddlers with no exposure. Toddlers exposed to persistent comorbid anxiety and mood disorders scored significantly higher on the cognitive (p = 0.049), motor (p = 0.013) and language (p = 0.041) domains and attained significantly higher fine motor (p = 0.043) and gross motor (p = 0.041) scaled scores compared to toddlers with no maternal mental health disorder exposure. Future investigations should focus on the role of protective factors to explain the pathways through which maternal mental health status is associated with positive toddler neurodevelopmental outcomes. Full article

Mucolipidosis type II (MLII), an ultra-rare lysosomal storage disorder, manifests as a fatal multi-systemic disease. Mental inhibition and progressive neurodegeneration are commonly reported disease manifestations. Nevertheless, longitudinal data on neurocognitive testing and neuroimaging lack in current literature. This study aimed to provide details on central nervous system manifestations in MLII. All MLII patients with at least one standardized developmental assessment performed between 2005 and 2022 were included by retrospective chart review. A multiple mixed linear regression model was applied. Eleven patients with a median age of 34.0 months (range 1.6–159.6) underwent 32 neurocognitive and 28 adaptive behaviour assessments as well as 14 brain magnetic resonance imagings. The scales used were mainly BSID-III (42%) and VABS-II (47%). Neurocognitive testing (per patient: mean 2.9, standard deviation (SD) 2.0) performed over 0–52.1 months (median 12.1) revealed profound impairment with a mean developmental quotient of 36.7% (SD 20.4) at last assessment. The patients showed sustained development; on average, they gained 0.28 age-equivalent score points per month (confidence interval 0.17–0.38). Apart from common (63%) cervical spinal stenosis, neuroimaging revealed unspecific, non-progressive abnormalities (i.e., mild brain atrophy, white matter lesions). In summary, MLII is associated with profound developmental impairment, but not with neurodegeneration and neurocognitive decline. Full article

Young children’s mastery motivation and neurodevelopmental evaluation can contribute to overall early assessment for early intervention evaluation. At present, children born preterm (<37 weeks gestation) and with a low birth weight (LBW; <2500 g) are at increased risk of experiencing developmental delays and more nuanced cognitive and language challenges. The main objective of this exploratory study was to examine the connection between preterm children’s mastery motivation and their neurodevelopment, as well as to determine whether assessing mastery motivation can enhance assessment practices for early intervention (EI) programs. Parents of children born preterm completed the revised Dimensions of Mastery Motivation Questionnaire (DMQ18). Neurodevelopment was measured on the Bayley Scales of Infant and Toddler Development (BSID-III). Results revealed significant correlations between DMQ18 and BSID-III measures. Multivariate analysis showed that infants and toddlers born with a very low birth weight (VLBW; <1500 g) scored significantly lower on the infant DMQ18 and the BSID-III measures. Regression analyses revealed that birth weight and home environment were significant predictors of the children’s eligibility for EI programs. Infants’ social persistence with other children, gross motor persistence, and mastery pleasure, as well as toddlers’ objective cognitive persistence, social persistence with adults, gross motor persistence, mastery pleasure, and negative reaction to frustration, were important markers for evidenced-based practices in EI programs. This study demonstrates the utility of the DMQ18 as a contributory assessment measure and the importance of birth weight and home environment in predicting EI enrollment. Full article