Multisensory stimulation for promoting development and preventing morbidity in preterm infants.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of multisensory stimulation compared to any single sensory intervention or standard care for physical and neurological development in preterm infants.

Introduction of Solid Foods in Preterm Infants and Its Impact on Growth in the First Year of Life-A Prospective Observational Study.

The aim of this study was to investigate whether age at introduction of solid foods in preterm infants influences growth in the first year of life. This was a prospective observational study in very low birth weight infants stratified to an early (<17 weeks corrected age) or a late (≥17 weeks corrected age) feeding group according to the individual timing of weaning. In total, 115 infants were assigned to the early group, and 82 were assigned to the late group. Mean birth weight and gestational age were comparable between groups (early: 926 g, 26 + 6 weeks; late: 881 g, 26 + 5 weeks). Mean age at weaning was 13.2 weeks corrected age in the early group and 20.4 weeks corrected age in the late group. At 12 months corrected age, anthropometric parameters showed no significant differences between groups (early vs. late, mean length 75.0 vs. 74.1 cm, weight 9.2 vs. 8.9 kg, head circumference 45.5 vs. 45.0 cm). A machine learning model showed no effect of age at weaning on length and length z-scores at 12 months corrected age. Infants with comorbidities had significantly lower anthropometric z-scores compared to infants without comorbidities. Therefore, regardless of growth considerations, we recommend weaning preterm infants according to their neurological abilities.

Outcome of creating clustering nursing care and healing environment on premature infants' behavioural outcomes.

We conducted a quasi-experimental study in two neonatal intensive care units (NICUs) from January to July 2021, focusing on the effects of clustering nursing care and creating a healing environment on premature infants' behavioural outcomes. The study included 106 infants, with 53 in both the study and control groups. Significant improvements were observed in organisation state/sleep and responsiveness/interaction domains in the study group, along with shorter hospital stays and greater weight gain on discharge. These findings highlight the positive impact of targeted interventions on premature infants' developmental outcomes, emphasising the need for comprehensive care strategies in NICU settings.

Cumulative sucrose exposure for repeated procedural pain in preterm neonates and neurodevelopment at 18 months of corrected age: a prospective observational longitudinal study.

INTRODUCTION: Oral sucrose is repeatedly administered to neonates in the neonatal intensive care unit (NICU) to treat pain from commonly performed procedures; however, there is limited evidence on its long-term cumulative effect on neurodevelopment. We examined the association between total sucrose volumes administered to preterm neonates for pain mitigation in the NICU and their neurodevelopment at 18 months of corrected age (CA). METHODS: A prospective longitudinal single-arm observational study that enrolled hospitalised preterm neonates <32 weeks of gestational age at birth and <10 days of life was conducted in four level III NICUs in Canada. Neonates received 0.1 mL of 24% sucrose 2 min prior to all commonly performed painful procedures during their NICU stay. Neurodevelopment was assessed at 18 months of CA using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Multiple neonatal and maternal factors known to affect development were adjusted for in the generalised linear model analysis. RESULTS: 172 preterm neonates were enrolled and 118 were included in the analysis at 18 months of CA. The total mean sucrose volume administered/neonate/NICU stay was 5.96 (±5.6) mL, and the mean Bayley-III composite scores were: cognitive 91 (±17), language 86 (±18) and motor 88 (±18). There was no association between Bayley-III scores and the total sucrose volume: cognitive (p=0.57), language (p=0.42) and motor (p=0.70). CONCLUSION: Cumulative sucrose exposure for repeated procedural pain in preterm neonates was neither associated with a delay in neurodevelopment nor neuroprotective effects at 18 months of CA. If sucrose is used, we suggest the minimally effective dose combined with other non-pharmacological interventions with demonstrated effectiveness such as skin-to-skin contact, non-nutritive sucking, facilitated tucking and swaddling. TRIAL REGISTRATION NUMBER: NCT02725814.

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

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

Factors influencing on gross motor skills in infants: Implications for walking development.

BACKGROUND: This longitudinal study aimed to explore the impact of containers on gross motor percentile from 8 to 13 months corrected age during the walking development in moderate to late preterm infants. METHODS: Sixty preterm infants were enrolled in this study, and their monthly assessment the gross motor percentile using the Alberta Infant Motor Scale. Monthly parent interviews focused on collecting information about container characteristics. RESULTS: Infants exhibited fluctuating percentiles in gross motor development, averaging 37.81 (SD = 21.9; SEM = 1.4). The gross motor skills percentiles varied between 2 and 86 points across the six assessments. Factors significantly associated with gross motor development percentiles were a large container size (Coef. = 15.29; p < 0.001*) and a container with a soft floor surface (Coef. = 3.64; p = 0.042*). CONCLUSION: Healthy preterm infants exhibited minimal instability in gross motor development and attained walking independently by 13 months. Placing preterm infants in a baby container during their first year should prioritize a wide space and a soft floor surface to enhance gross motor development.

Sensitivity and specificity of the Neonatal Visual Assessment to predict motor and cognitive outcomes in infants born very preterm.

BACKGROUND: Very preterm infants are at increased risk of neurodevelopmental impairments. The Neonatal Visual Assessment (NVA) assesses visual function and outcomes and has been used to assess early neurodevelopmental outcomes. This study aimed to compare NVA results of very preterm and term-born infants and to calculate the sensitivity and specificity of the NVA at term equivalent age (TEA) and three months corrected age (CA) to predict motor and cognitive outcomes at 12 months CA in very preterm infants. METHODS: This prospective observational cohort study recruited infants born before 31 weeks gestation and a healthy term-born control group. The NVA was assessed at TEA and three months CA, and neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development, Third Edition; Neurosensory Motor Developmental Assessment; Alberta Infant Motor Scale) were performed at 12 months CA. The sensitivity and specificity of the NVA to predict outcomes were calculated based on a previously published optimality score. RESULTS: 248 preterm (54 % male) and 46 term-born infants (48 % male) were analysed. The mean NVA scores of preterm and term-born infants were significantly different at TEA (preterm 3.1±2.1; term-born 1.2±1.7, p < 0.001). The NVA had moderate sensitivity (59-78 %) and low specificity (25-27 %) at TEA, and low sensitivity (21-28 %) and high specificity (86-87 %) at three months CA for the prediction of preterm infants' outcomes at 12 months CA. CONCLUSION: The NVA at TEA and three months CA was not a strong predictor of motor and cognitive impairments in this contemporary cohort of very preterm infants.

A Systematic Review over the Effect of Early Infant Diet on Neurodevelopment: Insights from Neuroimaging.

The optimization of infant neuronal development through nutrition is an increasingly studied area. While human milk consumption during infancy is thought to give a slight cognitive advantage throughout early childhood in comparison to commercial formula, the biological underpinnings of this process are less well-known and debated in the literature. This systematic review seeks to quantitatively analyze whether early diet affects infant neurodevelopment as measured by various neuroimaging modalities and techniques. Results presented suggest that human milk does have a slight positive impact on the structural development of the infant brain-and that this impact is larger in preterm infants. Other diets with distinct macronutrient compositions were also considered, although these had more conflicting results.

Real-time predictive model of extrauterine growth retardation in preterm infants with gestational age less than 32 weeks.

The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0-95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants.

Nutritional Strategies for Preterm Neonates and Preterm Neonates Undergoing Surgery: New Insights for Practice and Wrong Beliefs to Uproot.

The nutrition of preterm infants remains contaminated by wrong beliefs that reflect inexactitudes and perpetuate old practices. In this narrative review, we report current evidence in preterm neonates and in preterm neonates undergoing surgery. Convictions that necrotizing enterocolitis is reduced by the delay in introducing enteral feeding, a slow advancement in enteral feeds, and the systematic control of residual gastric volumes, should be abandoned. On the contrary, these practices prolong the time to reach full enteral feeding. The length of parenteral nutrition should be as short as possible to reduce the infectious risk. Intrauterine growth restriction, hemodynamic and respiratory instability, and patent ductus arteriosus should be considered in advancing enteral feeds, but they must not translate into prolonged fasting, which can be equally dangerous. Clinicians should also keep in mind the risk of refeeding syndrome in case of high amino acid intake and inadequate electrolyte supply, closely monitoring them. Conversely, when preterm infants undergo surgery, nutritional strategies are still based on retrospective studies and opinions rather than on randomized controlled trials. Finally, this review also highlights how the use of adequately fortified human milk is strongly recommended, as it offers unique benefits for immune and gastrointestinal health and neurodevelopmental outcomes.

Impact of COVID-19 pandemic on neurodevelopmental outcomes of premature infants: a retrospective national cohort study.

OBJECTIVE: To compare the neurodevelopmental outcomes of preterm infants before and during the COVID-19 pandemic. DESIGN: Premature infants born in 2018 were assigned to the pre-pandemic group, while those born in 2019 were assigned to the during-pandemic group. SETTING: Nationwide cohort study. PATIENTS: Very low birthweight premature infants registered in the Taiwan Premature Infant Follow-up Network database. INTERVENTIONS: Anti-epidemic measures, including quarantine and isolation protocols, social distancing, the closure of public spaces and restrictions on travel and gatherings during COVID-19 pandemic. MAIN OUTCOME MEASURES: Outcomes were measured by Bayley Scales of Infant and Toddler Development Third Edition at corrected ages of 6, 12 and 24 months old. Generalised estimating equation (GEE) was applied to incorporate all measurements into a single model. RESULTS: Among the 1939 premature infants who were enrolled, 985 developed before the pandemic, while 954 developed during the pandemic. Premature infants whose development occurred during the pandemic exhibited better cognitive composite at the corrected age of 6 months (beta=2.358; 95% CI, 1.07 to 3.65; p<0.001), and motor composite at corrected ages of 12 months (beta=1.680; 95% CI, 0.34 to 3.02; p=0.014). GEE analysis showed that infants who had grown during the pandemic achieved higher scores in cognitive composite (beta=1.416; 95% CI, 0.36 to 2.48; p=0.009). CONCLUSION: Premature infants in Taiwan who developed during the pandemic showed better neurodevelopment compared with those born before the pandemic.

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.

BACKGROUND: Preterm 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. METHODS: This 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)). DISCUSSION: The 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 REGISTRATION: WHO International Clinical Trials Registry: NL-OMON56181 (registration assigned October 28, 2021).

Kidney volume-to-birth weight ratio as an estimate of nephron endowment in extremely low birth weight preterm infants.

In humans, nephrogenesis is completed by 32-36 weeks gestation, with a highly variable total number of nephrons, ranging from 200,000 to over 2 million. Premature birth disrupts the development and maturation of the kidneys, leading to a reduction in the final number of nephrons. Due to significant genetic variability in the number of nephrons among individuals, it is crucial to identify premature infants with fewer nephrons at birth as early as possible. These infants are more susceptible to developing renal failure with advancing age compared to those with a higher nephron endowment. Bedside ultrasound, an effective and non-invasive tool, is practical for identifying newborns with a lower nephron count. However, renal volume alone cannot reliably indicate the number of nephrons due to substantial variability at birth, influenced by gestational age when nephron maturation is incomplete. This variability in kidney volumes persists as newborns grow. In this observational study we hypothesize that the relationship between renal volume and birth weight may serve as an indicator of nephron endowment in premature infants with birth weight less than 1000 g. This finding could represent the basis for defining appropriate surveillance protocols and developing targeted therapeutic approaches.

Hybrid developmental follow-up for preterm infants in Brazil: A feasibility study.

INTRODUCTION: The low attendance of families in child developmental follow-up programs for at-risk preterm children is a challenge in Brazil. OBJECTIVE: This study evaluates the feasibility of implementing a developmental follow-up program for Brazilian preterm infants in a hybrid format. METHODS: This is an observational, prospective cohort study, involving preterm infants. Longitudinal developmental test results, the participation frequency in the program, and the number of referrals to early intervention programs were used to assess feasibility. The General Movements (GMs) assessment, Alberta Infant Motor Scale (AIMS) and, Survey of Wellbeing of Young Children (SWYC) Milestones were administered via telehealth. The Bayley-III was administered in-person. RESULTS: Thirty-four preterm infants attended the follow-up until 12 months of corrected age and 18 (52.9 %) concluded all follow-up assessments. Twenty-six (76.5 %) attended all assessments via telehealth, and 26 (76.5 %) attended the in-person assessment. Eighteen (52.9 %) infants showed at least one altered result in development tests. Infants exhibiting abnormal results in the GMs assessment, motor developmental delay according to the AIMS, or developmental delay based on Balley-III were promptly referred to early intervention services. CONCLUSION: This study demonstrated high participation rate and low dropout in a developmental follow-up program employing a hybrid format. The substantial number of identified infants with developmental delay emphasizes the importance of timely detection of motor delays to referral to early intervention services.

Motor performance of Indian preterm infants as compared to the US population on the Test of Infant Motor Performance (TIMP).

PURPOSE: The study aimed at scoring Indian preterm infants at three months corrected age on the TIMP and then comparing the scores to the United States age-based population scores. METHODS: After obtaining Ethical clearance, participants meeting the inclusion criteria of 53 infants whose parents consented were screened and recruited (N = 47) at a tertiary care hospital. The TIMP was then administered at three months of corrected age. RESULTS: Data obtained from 47 infants born preterm (Male = 33, Female = 14) at three months corrected age with mean gestational age (34.4 ± 2.36 weeks) and mean birth weight (1.93 ± 0.55 kgs) was analyzed. Indian infants born preterm scored a mean of (98.17 ± 20.90) compared to the US mean of (108 ± 19), suggesting an under-performance. The average scores were lower when comparing the mean of the study group with the US-based age-matched population. CONCLUSION: Motor performance scores of Indian preterm infants were low when compared to their US counterparts. Since there exists a difference in the raw score obtained by Indian Preterm infants compared to the US-based population, it may not be appropriate to categorize the motor development of Indian infants based on the US population scores.

Interventions and their efficacy in supporting language development among preterm children aged 0-3 years - A systematic review.

BACKGROUND: Preterm children have a higher risk for linguistic delays than full-term infants but are rarely provided with language intervention at an early age. Knowledge on early language interventions targeted to preterm children is scarce, and efficacy of the interventions is rarely reported. AIM: This systematic review aims to identify interventions for preterm children aged 0-3 years with at least one language outcome. Efficacy of the interventions and quality of the study reports were evaluated. STUDY DESIGN: The article search was carried out in six databases: EBSCOhost, Scopus, ERIC, LLBA, Ovid, and Web of Science. Effect sizes (Hedges' g) were calculated for language outcomes. Quality of the study reports was assessed using the levels of evidence system by the American Speech-Language-Hearing Association. RESULTS: The 28 studies identified were divided into three groups: interventions at Neonatal Intensive Care Unit, interventions during the first year, and interventions during the second and/or third years. Most of the interventions focused on supporting child-care and general development. Of the interventions, 61 % were efficacious in supporting language development of preterm children. The most promising results regarding efficacy were interventions conducted during the second and/or third years (80 %). Quality of the reports varied from high/good (89 %) to low (11 %). CONCLUSION: The 28 existing studies provide limited evidence of the efficacy of very early interventions promoting language development of preterm children. However, especially the results for interventions conducted during the second and/or third years show promise. More studies, particularly language-focused interventions with longer follow-ups, are needed.

Impact of Nutrient Intake on Body Composition in Very Low-Birth Weight Infants Following Early Progressive Enteral Feeding.

Preterm infants have increased body adiposity at term-equivalent age and risk of adverse metabolic outcomes. The aim of the study was to define how nutrient intake may impact body composition (BC) of very low-birth weight infants fed with early progressive enteral feeding and standard fortification. Eighty-six infants with <1500 g birth weight were included in the BC study and stratified into extremely preterm (EP) and very preterm (VP) groups. Nutrient intake was calculated during the first 28 days and BC assessed by dual X-ray absorptiometry at discharge and by skinfold thickness at 12 months of corrected age (CA). Total nutrient intake did not differ between the groups. EP infants had a higher fat mass percentage at discharge than VP infants (24.8% vs. 19.4%, p < 0.001); lean mass did not differ. None of the nutrients had any impact on BC of EP infants. Protein intake did not result in a higher lean mass in either group; fat intake was a significant predictor of increased fat mass percentage in VP infants at discharge (p = 0.007) and body adiposity at 12 months of CA (p = 0.021). Nutritional needs may depend on gestational age and routine fortification should be used with caution in more mature infants.

The effects of parenteral fish oil on neurodevelopment in preterm infants: A narrative review.

OBJECTIVE: This narrative review aimed to summarize studies assessing the effects of parenteral fish oil on neurodevelopment in preterm infants. METHODS: PubMed was searched (July 1985 to October 2023). We reviewed randomized controlled trials, and observational studies assessing intravenous lipid emulsion with fish oil in preterm infants (born less than 37 weeks' gestation), that reported long-term neurodevelopmental outcomes. RESULTS: We identified four publications relating to three randomized controlled trials in addition to four cohort studies. Study designs and outcomes were heterogenous and precluded meta-analyses. Results of trials were null for a selection of neurodevelopmental outcomes, however possible benefits of parenteral fish oil supplementation for neurodevelopment was reported in three cohort studies. Certainty of the evidence is hindered by methodological limitations of available trials and observational studies. CONCLUSIONS: Further research is required to firmly establish the effects of parenteral fish oil on preterm neurodevelopment.

Association of Standardized Parenteral Nutrition with Early Neonatal Growth of Moderately Preterm Infants: A Population-Based Cohort Study.

In preterm infants, early nutrient intake during the first week of life often depends on parenteral nutrition. This study aimed to evaluate the influence of standardized parenteral nutrition using three-in-one double-chamber solutions (3-in-1 STD-PN) on early neonatal growth in a cohort of moderately preterm (MP) infants. This population-based, observational cohort study included preterm infants admitted to neonatal centers in the southeast regional perinatal network in France. During the study period, 315 MP infants with gestational ages between 320/7 and 346/7 weeks who required parenteral nutrition from birth until day-of-life 3 (DoL3) were included; 178 received 3-in-1 STD-PN solution (56.5%). Multivariate regression was used to assess the factors associated with the relative body-weight difference between days 1 and 7 (RBWD DoL1-7). Infants receiving 3-in-1 STD-PN lost 36% less body weight during the first week of life, with median RBWD DoL1-7 of -2.5% vs. -3.9% in infants receiving other PN solutions (p < 0.05). They also received higher parenteral energy and protein intakes during the overall first week, with 85% (p < 0.0001) and 27% (p < 0.0001) more energy and protein on DoL 3. After adjusting for confounding factors, RBWD DoL1-7 was significantly lower in the 3-in-1 STD-NP group than in their counterparts, with beta (standard deviation) = 2.08 (0.91), p = 0.02. The use of 3-in-1 STD-PN provided better energy and protein intake and limited early weight loss in MP infants.