Changes in the intestinal microbiome of the preterm baby associated with stopping non-invasive pressure support: a prospective cohort study.

BACKGROUND: Intestinal dysbiosis is implicated in the pathogenesis of necrotising enterocolitis and late-onset sepsis in preterm babies. The provision of non-invasive positive pressure ventilation is a common clinical intervention in preterm babies, and may be hypothesised to adversely affect intestinal bacterial growth, through increased aerophagia and induction of a hyperoxic intestinal environment; however this relationship has not been previously well characterised. METHODOLOGY: In this prospectively recruited cohort study, high-throughput 16S rRNA gene sequencing was combined with contemporaneous clinical data collection, to assess within-subject changes in microbiome development around the time of transitioning from non-invasive positive pressure respiratory support to unsupported spontaneous breathing. RESULTS: In a group of 14 preterm infants, bacterial diversity was seen to increase by 0.34 units/week (inverse Simpson index) at the point of transitioning off non-invasive positive pressure respiratory support. Correspondingly, a significant increase in anaerobic genera (Bifidobacteria spp, Veillonella spp), and a non-significant fall in Enterobacteriaceae was also seen at this time. CONCLUSIONS: Provision of non-invasive positive pressure ventilation is associated with suppression of both diversity accrual and obligate anaerobic growth in the preterm intestine. This has clinical implications in view of the widespread use of non-invasive positive pressure ventilation in preterm neonatal care (and wider adult use), and demonstrates the need for potential strategies (eg, probiotic support; reduced aerophagia) to support the development of a healthy gut microbiome during this time.

Adjusted versus Targeted Fortification in Extremely Low Birth Weight Preterm Infants: Fortin Study-A Randomized Clinical Trial.

Fortified human milk is the first choice for preterm infants. Although individualized fortification is recommended, the optimal method for this population remains uncertain. We conducted a comparative study assessing the growth effects of adjusted (AF) and targeted fortification (TF) in extremely low birth weight (ELBW) infants. This single-center, randomized, controlled clinical trial was conducted at a tertiary neonatal unit in Spain. Eligible participants were premature infants with a birthweight of <1000 g exclusively fed with human milk. A total of 38 patients were enrolled, 15 of them randomized to AF group and 23 to TF group. AF was based on blood urea nitrogen (BUN) concentration and TF on human milk analysis. The primary outcome was weight gain velocity (g/kg/day). No significant differences were found in weight gain velocity at 28 days, at 36 weeks of postmenstrual age, at discharge, nor during the intervention. Protein intake was significantly higher in the AF group (5.02 g/kg/day vs. 4.48 g/kg/day, p = 0.001). No differences were found in the lipid, carbohydrate, and energy intake; in the weight z score change between the different time points; nor in the length and head circumference growth. Both AF and TF are comparable methods of fortification and provide the appropriate growth rate in ELBW infants.

Direct breastfeeding: Predictive factors and possible effects on neurodevelopment in very preterm infants.

BACKGROUND: the importance of sucking milk directly at the mother's breast is often underestimated and many aspects of direct breastfeeding of very preterm infants are not investigated. AIM: The primary endpoint of the study was to identify maternal and infant clinical predictors of direct breastfeeding in a cohort of infants born at <32 weeks of gestation or weighing <1500 g. The secondary endpoint was to evaluate the possible effects of direct breastfeeding on infant neurodevelopment. STUDY DESIGN: Seventy-two infants born between July 2018 and December 2019 were divided into the subgroup that were directly breastfed (n = 42) and not directly breastfed (n = 30) at discharge. Maternal and infant characteristics were compared, and differences were analysed. RESULTS: Logistic regression analysis demonstrated that the percentage of maternal milk taken during hospitalization, maternal age, and weight (z-score) at discharge were positively correlated with the likelihood of direct breastfeeding at discharge. Direct breastfeeding was not correlated with the cognitive score at 24 months corrected age. CONCLUSIONS: Direct breastfeeding at discharge is more probable in infants of older mothers who receive more breastmilk and who experience greater weight gain. Direct breastfeeding is not correlated with the cognitive score at 24 months corrected age.

Circadian rhythm development in preterm infants. The role of postnatal versus postmenstrual age.

BACKGROUND, AIMS: Circadian rhythm maturation may be disturbed in premature infants undergoing neonatal intensive care. We used continuous heart rate recordings across the entire neonatal intensive care period to study circadian rhythm development in preterm infants and to evaluate the roles of postmenstrual (PMA) versus postnatal age (PNA). MATERIALS AND METHODS: The circadian rhythm was calculated using a cosine fit of heart rate. The circadian rhythm amplitudes were averaged weekly and studied relative to PMA and PNA using the linear mixed effects models, adjusting for clinical variables that could affect the heart rate. The daily circadian rhythms were used to create grand averages for PMA groups: ≤31, 32-35, and > 35 weeks, and for PNA groups: ≤30, 31-60, and > 60 days. RESULTS: Sixty-six infants were evaluated as part of an ongoing prospective study with gestational ages between 23 and 36 weeks. The PMA (1.47 × 10-2 beats per minute (bpm)/week, P = 2.07 × 10-8) and PNA (1.87 × 10-2 bpm/day; P = 1.86 × 10-6) were significantly associated with the circadian rhythm amplitude independent of covariates. Infants ≤31 weeks' PMA and ≤30 days PNA, the phase of circadian rhythm amplitude grand averages showed a peak at night and a nadir during the day. Hereafter the circadian rhythm phase reversed to that established for mature individuals. The highest circadian rhythm amplitudes present >35 weeks' PMA and > 60 days PNA. CONCLUSIONS: Our results indicate circadian rhythm matures with advancing gestation. The reversed circadian rhythm phase during the early postnatal period could be due to premature exposure to the ex-utero environment and warrant further study.

Olfactory 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 evaluate the benefits and harms of olfactory stimulation with different odorants in the NICU for promoting development and preventing morbidity in preterm infants.

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.

Enteral adequacy of the diet of low-birth-weight preterm newborns: A prospective cohort study.

OBJECTIVE: This study aimed to verify the dietary adequacy of full enteral feeding in preterm newborns (PTNB) and its relationship with birth weight (BW) during the period of hospitalization in the neonatal intensive care unit (NICU). METHODS: This is a prospective cohort study whose population were babies born at less than 37 gestational weeks and weighing less than 2500 g, admitted to a NICU. PTNB were monitored regarding their dietary evolution, considering parenteral and enteral nutrition and adequacy of diet supply in terms of volume, energy, and protein. For statistical analysis, the Statistical Package for the Social Sciences (SPSS) software was used, considering p < 0.05 as significant. RESULTS: A total of 76 PTNB were included. The mean time of using parenteral nutrition was 14 days. The mean time to reach the full enteral feeding for nutrition (FEF-N) was 29 days. However, half of the PTNB reached nutritional recommendations after this means. The time to achieve FEF-N was influenced by BW. Additionally, BW significantly influenced the length of stay in the NICU (p < 0.001). When reaching the recommended full enteral feeding for hydration (FEF-H), 60% of the sample was unable to reach the recommended energy and protein intake. CONCLUSIONS: BW influenced the time needed to reach the FEF-H and FEF-N. The lower the BW, the longer it took to achieve dietary adequacy. Despite achieving the FEF-H, most premature babies did not reach the necessary energy and protein intake at the appropriate time.

Early nutritional influences on brain regions related to processing speed in children born preterm: A secondary analysis of a randomized trial.

BACKGROUND: Processing speed is a foundational skill supporting intelligence and executive function, areas often delayed in preterm-born children. The impact of early-life nutrition on gray matter facilitating processing speed for this vulnerable population is unknown. METHODS: Magnetic resonance imaging and the Wechsler Preschool and Primary Scale of Intelligence-IV Processing Speed Index were acquired in forty 5-year-old children born preterm with very low birth weight. Macronutrient (grams per kilogram per day) and mother's milk (percentage of feeds) intakes were prospectively collected in the first postnatal month and associations between early-life nutrition and the primary outcome of brain regions supporting processing speed were investigated. RESULTS: Children had a mean (SD) gestational age of 27.8 (1.8) weeks and 45% were male. Macronutrient intakes were unrelated, but mother's milk was positively related, to greater volumes in brain regions, including total cortical gray matter, cingulate gyri, and occipital gyri. CONCLUSION: First postnatal month macronutrient intakes showed no association, but mother's milk was positively associated, with volumetric measures of total and regional cortical gray matter related to processing speed in preterm-born children. This exploratory analysis suggests early-life mother's milk supports processing speed by impacting structural underpinnings. Further research is needed on this potential strategy to improve preterm outcomes.

Association between type of feeding at hospital discharge and nutritional status of Brazilian very preterm infants: a multicenter study.

OBJECTIVES: To examine trends over time in diet and size of very preterm infants, and associations of diet with size at hospital discharge/transfer. METHODS: The authors studied 4062 surviving very preterm infants born < 32 weeks' gestational age and < 1500 g between January 2012 and December 2020 from 12 Brazilian Neonatal Intensive Care Units. Diet type at discharge/transfer was classified as exclusive human milk, exclusive formula, or mixed. Outcomes were weight and head circumference at hospital discharge and the change in each from birth to discharge. The authors used linear regression to estimate adjusted associations of diet type with infant size, overall, and stratified by fetal growth category (small vs. appropriate for gestational age). The authors also examined trends in diet and infant size at discharge over the years. RESULTS: Infants' mean gestational age at birth was 29.3 weeks, and the mean birth weight was 1136 g. Diet at discharge/transfer was exclusive human milk for 22 %, mixed for 62 %, and exclusive formula for 16 %. Infant size in weight and head circumference were substantially below the growth chart reference for all diets. Infants fed human milk and mixed diets were lighter and had smaller heads at discharge/transfer than infants fed formula only (weight z: -2.0, -1.8, and -1.5; head z: -1.3, -1.2 and -1.1 for exclusive human milk, mixed and exclusive formula respectively). CONCLUSION: Results suggest high human milk use but gaps in nutrient delivery among hospitalized Brazilian very preterm infants, with little evidence of improvement over time.

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.

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.

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.

The effect of preterm birth on thalamic development based on shape and structural covariance analysis.

Acting as a central hub in regulating brain functions, the thalamus plays a pivotal role in controlling high-order brain functions. Considering the impact of preterm birth on infant brain development, traditional studies focused on the overall development of thalamus other than its subregions. In this study, we compared the volumetric growth and shape development of the thalamic hemispheres between the infants born preterm and full-term (Left volume: P = 0.027, Left normalized volume: P < 0.0001; Right volume: P = 0.070, Right normalized volume: P < 0.0001). The ventral nucleus region, dorsomedial nucleus region, and posterior nucleus region of the thalamus exhibit higher vulnerability to alterations induced by preterm birth. The structural covariance (SC) between the thickness of thalamus and insula in preterm infants (Left: corrected P = 0.0091, Right: corrected P = 0.0119) showed significant increase as compared to full-term controls. Current findings suggest that preterm birth affects the development of the thalamus and has differential effects on its subregions. The ventral nucleus region, dorsomedial nucleus region, and posterior nucleus region of the thalamus are more susceptible to the impacts of preterm birth.

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.

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.

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.

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.

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.