Neonatal Docosahexaenoic Acid in Preterm Infants and Intelligence at 5 Years.

BACKGROUND: Docosahexaenoic acid (DHA) is a component of neural tissue. Because its accretion into the brain is greatest during the final trimester of pregnancy, infants born before 29 weeks' gestation do not receive the normal supply of DHA. The effect of this deficiency on subsequent cognitive development is not well understood. METHODS: We assessed general intelligence at 5 years in children who had been enrolled in a trial of neonatal DHA supplementation to prevent bronchopulmonary dysplasia. In the previous trial, infants born before 29 weeks' gestation had been randomly assigned in a 1:1 ratio to receive an enteral emulsion that provided 60 mg of DHA per kilogram of body weight per day or a control emulsion from the first 3 days of enteral feeds until 36 weeks of postmenstrual age or discharge home, whichever occurred first. Children from 5 of the 13 centers in the original trial were invited to undergo assessment with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) at 5 years of corrected age. The primary outcome was the full-scale intelligence quotient (FSIQ) score. Secondary outcomes included the components of WPPSI. RESULTS: A total of 1273 infants underwent randomization in the original trial; of the 656 surviving children who had undergone randomization at the centers included in this follow-up study, 480 (73%) had an FSIQ score available - 241 in the DHA group and 239 in the control group. After imputation of missing data, the mean (±SD) FSIQ scores were 95.4±17.3 in the DHA group and 91.9±19.1 in the control group (adjusted difference, 3.45; 95% confidence interval, 0.38 to 6.53; P = 0.03). The results for secondary outcomes generally did not support that obtained for the primary outcome. Adverse events were similar in the two groups. CONCLUSIONS: In infants born before 29 weeks' gestation who had been enrolled in a trial to assess the effect of DHA supplementation on bronchopulmonary dysplasia, the use of an enteral DHA emulsion until 36 weeks of postmenstrual age was associated with modestly higher FSIQ scores at 5 years of age than control feeding. (Funded by the Australian National Health and Medical Research Council and Nu-Mega Ingredients; N3RO Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820.).

Evaluation of Glymphatic System Development in Neonatal Brain via Diffusion Analysis along the Perivascular Space Index.

OBJECTIVE: Glymphatic system is a recently discovered macroscopic waste clearance system associated with numerous neurological diseases. However, little is known about glymphatic system development in neonates. We sought to evaluate diffusion along the perivascular space (ALPS) index, a proxy for glymphatic system function, in neonates and investigate its potential associations with maturation, sex, and preterm birth. METHODS: Diffusion magnetic resonance imaging (MRI) data in 418 neonates, including 92 preterm neonates (57 males) and 326 term neonates (175 males), from the Developing Human Connectome Project were used for evaluating ALPS index. Linear regression modeling was performed to assess group differences in the ALPS index according to preterm birth and sex. Pearson's and partial correlation analysis were performed to assess the association between the ALPS index and gestational age (GA) as well as postmenstrual age (PMA) at MRI. Moderation analysis was performed to assess the moderation effect of preterm birth on the relationship between the ALPS index and PMA. RESULTS: Compared to term neonates, preterm neonates exhibited lower ALPS indices (p < 0.001). The ALPS index positively correlated with PMA (p = 0.004) and GA (p < 0.001). Preterm birth (p = 0.013) had a significant moderation effect on the relationship between the ALPS index and PMA. Sex had no significant direct effect (p = 0.639) or moderation effect (p = 0.333) on ALPS index. INTERPRETATION: Glymphatic system development is a dynamic process in neonates, which can be moderated by preterm birth, the ALPS index could serve as a sensitive biomarker for monitoring this process. ANN NEUROL 2024;96:970-980.

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.

Preterm Birth Alters the Regional Development and Structural Covariance of Cerebellum at Term-Equivalent Age.

Preterm birth is associated with increased risk for a spectrum of neurodevelopmental disabilities. The cerebellum is implicated in a wide range of cognitive functions extending beyond sensorimotor control and plays an increasingly recognized role in brain development. Morphometric studies based on volume analyses have revealed impaired cerebellar development in preterm infants. However, the structural covariance between the cerebellum and cerebral cortex has not been studied during the neonatal period, and the extent to which structural covariance is affected by preterm birth remains unknown. In this study, using the structural MR images of 52 preterm infants scanned at term-equivalent age and 312 full-term controls from the Developing Human Connectome Project, we compared volumetric growth, local cerebellum shape development and cerebello-cerebral structural covariance between the two groups. We found that although there was no significant difference in the overall volume measurements between preterm and full-term infants, the shape measurements were different. Compared with the control infants, preterm infants had significantly larger thickness in the vermis and lower thickness in the lateral portions of the bilateral cerebral hemispheres. The structural covariance between the cerebellum and frontal and parietal lobes was significantly greater in preterm infants than in full-term controls. The findings in this study suggested that cerebellar development and cerebello-cerebral structural covariance may be affected by premature birth.

Nutritional intake and growth until two years of age in moderate and late preterms.

BACKGROUND AND AIM: Moderate and late preterm infants (MLPTI) (gestational age 32 0/7-36 6/7 weeks), are at risk for suboptimal growth. This study evaluated adherence to nutritional recommendations until 6 months corrected age (CA), growth until 2 years CA, and associations between nutritional intake and growth until 2 years CA. METHODS: We prospectively collected nutritional intakes from 100 MLPTI during the first week of life and at 6 weeks, 3 months, and 6 months CA. Anthropometry was assessed at birth, discharge, term age, and at 6 weeks, 3 months, 6 months, 1 year, and 2 years CA. RESULTS: On day 7, <40% reached nutritional recommendations. Thereafter, >80% reached protein recommendations until 6 months of life, but <60% reached energy recommendations. Weight z-scores increased from -0.44 at term-age to 0.59 at 3 months CA, but declined to -0.53 at 2 years CA on the TNO curves. No significant associations were found between nutritional intake and growth until 2 years CA. CONCLUSION: No associations were demonstrated between nutritional intakes and growth until 2 years CA, despite not reaching recommended intakes. Despite high efforts to optimize growth, MLPTI find their own growth curve in the first 2 years of life. IMPACT: This research is pioneering in identifying how nutrition influences growth in moderate and late preterm infants (MLPTI) up to 2 years corrected age (CA). MLPTI often do not meet the recommended protein and energy intake in their first week of life, suggesting that current guidelines might be too high. No association was demonstrated between nutritional intake and growth of MLPTI in the first 2 years of life. Initially, MLPTI show an increase in weight z-scores from term age up to 3 months CA but experience a decline in weight z-scores at 2 years CA, according to TNO growth charts.

Stability of neurodevelopmental trajectories in moderately late and early preterm children born 15 years apart.

BACKGROUND: Neurodevelopmental trajectories of preterm children may have changed due to changes in care and in society. We aimed to compare neurodevelopmental trajectories in early and moderately late preterm children, measured using the Developmental (D)-score, in two cohorts born 15 years apart. METHODS: We included early preterm and moderately late preterm children from two Dutch cohorts (LOLLIPOP, 2002-2003 and ePREM, 2016-2017). ePREM counterparts were matched to LOLLIPOP participants by gestational age and sex. D-score trajectories were summarized by a multilevel model with random intercepts and random slopes, and multigroup analyses were used to test if the intercepts and slopes differed across cohorts. RESULTS: We included 1686 preterm children (1071 moderately late preterm, 615 early preterm) from LOLLIPOP, and matched these with 1686 ePREM counterparts. The neurodevelopmental trajectories of the two cohorts were mostly similar. For early preterm children, we found no statistically significant differences. For moderately late preterm children, both the intercept (43.0 vs. 42.3, p < 0.001) and slope (23.5 vs. 23.9, p = 0.002) showed some, but only clinically minor, differences. CONCLUSION: Developmental trajectories, measured using the D-score, in the first four years of life are comparable and stable across a period of 15 years for both early and moderately late preterm children. IMPACT: Neurodevelopmental trajectories are similar for early and moderately late preterm children born 15 years apart and thus seem quite stable in time. The validated Developmental score visualizes these trajectories based on developmental milestone attainment Because of its stability over time, the Developmental score trajectory may aid clinicians in neurodevelopmental assessment of preterm children as this simplifies monitoring and interpretation, similar to a growth chart.

Postnatal growth and neurodevelopment at 2 years' corrected age in extremely low birthweight infants.

BACKGROUND: Faltering postnatal growth in preterm babies is associated with adverse neurodevelopment. However, which growth reference is most helpful for predicting neurodevelopment is unknown. We examined associations between faltering growth and developmental delay in extremely low birthweight (ELBW) infants. METHODS: We categorized faltering growth (z-score decrease ≥0.8 for weight/length, >1 for head circumference) between birth, 4 weeks, 36 weeks' postmenstrual age and 2 years' corrected age using fetal (Fenton, UK-WHO and Olsen) and healthy preterm (INTERGROWTH-21st) references. Associations between faltering growth and developmental delay were examined using binary logistic regression and area under the receiver operating curve (AUC). RESULTS: In 327 infants, Olsen charts identified the highest prevalence of faltering growth (weight 37%, length 63%, head 45%). Agreement in classification was higher amongst fetal references (kappa coefficient, ĸ = 0.46-0.94) than between INTERGROWTH-21st and fetal references (ĸ = 0.10-0.81). Faltering growth in all measures between 4-36 weeks (odds ratio, OR 2.0-4.7) compared with other time intervals (OR 1.7-2.7) were more strongly associated with developmental delay, particularly motor delay (OR 2.0-4.7). All growth references were poorly predictive of developmental delay at 2 years (AUC ≤ 0.62). CONCLUSIONS: Faltering postnatal growth in ELBW infants is associated with, but is poorly predictive of, developmental delay at 2 years. IMPACT: In babies born preterm, different growth references result in wide variation in categorization of faltering postnatal growth. Faltering growth in weight, length, and head circumference from 4 weeks to 36 weeks' postmenstrual age are associated with developmental delay at 2 years' corrected age, particularly motor delay. However, postnatal growth is a poor predictor of later developmental delay in extremely low birthweight infants irrespective of the growth reference used.

Lactoferrin intake from maternal milk during the neonatal hospitalization and early brain development among preterm infants.

BACKGROUND: Lactoferrin is an immuno-modulatory nutrient in human milk that may be neuroprotective. METHODS: In 36 infants born <32 weeks' gestation, we sampled human milk at 14 and 28 days of chronologic age and measured lactoferrin by electrochemiluminescence multiplex immunoassay. Using 3T quantitative brain magnetic resonance imaging scans obtained at term equivalent, we estimated total and regional brain volumes. We compared outcomes between infants exposed to low (bottom tertile, range 0.06-0.13 mg/mL) vs. high (top tertile, range 0.22-0.35 mg/mL) lactoferrin using median regression in models adjusted for gestational age, birth weight z-score, sex, and postmenstrual age. RESULTS: Compared to infants exposed to low lactoferrin, infants exposed to high lactoferrin had 43.9 cc (95% CI: 7.6, 80.4) larger total brain volume, 48.3 cc (95% CI: 12.1, 84.6) larger cortical gray matter, and 3.8 cc (95% CI: 0.7, 7.0) larger deep gray matter volume at term equivalent age. Other regional brain volumes were not statistically different between groups. CONCLUSION: Higher lactoferrin exposure during the neonatal hospitalization was associated with larger total brain and gray matter volumes, suggesting that lactoferrin may have potential as a dietary supplement to enhance brain growth in the neonatal intensive care unit setting. IMPACT: This study suggests that lactoferrin, a whey protein found in human milk, may be beneficial for preterm infant brain development, and therefore has potential as a dietary supplement in the neonatal intensive care unit setting.

An exploratory study of clinical factors associated with IGF-1 and IGFBP-3 in preterm infants.

BACKGROUND: Despite advances in parenteral nutrition, postnatal growth failure in very low birthweight (VLBW) preterm infants is common and associated with chronic health problems. Insulin-like growth factor 1 (IGF-1) is positively associated with improved infant growth, but factors which promote IGF-1 levels in this population have not been clearly identified. The objective of this study was to explore early factors that influence IGF-1 in VLBW preterm infants. METHODS: VLBW infants were enrolled into a prospective, randomized controlled nutrition trial (N = 87). Outcome measures included IGF-1 and IGFBP-3 levels measured at 35 weeks PMA. Linear regression analyses tested the relationships between candidate clinical predictors and levels of IGF-1 and IGFBP-3. RESULTS: Higher protein intake, longer duration of parenteral nutrition, and lower IGFBP-3 levels at 1 week of life were associated with lower IGF-1 levels at 35 weeks PMA. Neither early markers of insulin resistance nor degree of illness were associated with IGF-1 levels at 35 weeks PMA. CONCLUSION: Optimization of early nutrient intake, and attention to route of delivery, may have a lasting influence on IGF-1/IGFBP-3, and in turn, long-term health outcomes. IMPACT: In very low birthweight preterm infants, early protein intake, duration of parenteral nutrition, and insulin-like growth factor binding protein 3 (IGFBP-3) levels at 1 week of life are positively associated with insulin-like growth factor 1 (IGF-1) levels at 35 weeks postmenstrual age. Data from this study highlight the influence of early nutrition on components of the endocrine axis in preterm infants. Strategies aimed at early initiation of enteral nutrition, as well as optimizing composition of parenteral nutrition, may bolster hormones involved in promoting preterm infant growth.

Glucose-regulatory hormones and growth in very preterm infants fed fortified human milk.

BACKGROUND: Bovine colostrum (BC) contains a range of milk bioactive components, and it is unknown how human milk fortification with BC affects glucose-regulatory hormones in very preterm infants (VPIs). This study aimed to investigate the associations between hormone concentrations and fortification type, birth weight (appropriate/small for gestational age, AGA/SGA), milk intake, postnatal age, and body growth. METHODS: 225 VPIs were randomized to fortification with BC or conventional fortifier (CF). Plasma hormones were measured before, one and two weeks after start of fortification. ΔZ-scores from birth to 35 weeks postmenstrual age were calculated. RESULTS: Compared with CF, infants fortified with BC had higher plasma GLP-1, GIP, glucagon, and leptin concentrations after start of fortification. Prior to fortification, leptin concentrations were negatively associated with growth, while IGF-1 concentrations associated positively with growth during fortification. In AGA infants, hormone concentrations generally increased after one week of fortification. Relative to AGA infants, SGA infants showed reduced IGF-1 and leptin concentrations. CONCLUSION: Fortification with BC increased the plasma concentrations of several glucose-regulatory hormones. Concentrations of IGF-1 were positively, and leptin negatively, associated with growth. Glucose-regulatory hormone levels were affected by birth weight, milk intake and postnatal age, but not closely associated with growth in VPIs. IMPACT: Little is known about the variation in glucose-regulatory hormones in the early life of very preterm infants (VPIs). This study shows that the levels of glucose-regulatory hormones in plasma of VPIs are highly variable and modified by birth weight (appropriate or small for gestational age, AGA or SGA), the type of fortifier, enteral nutritional intake, and advancing postnatal age. The results confirm that IGF-1 levels are positively associated with early postnatal growth in VPIs, yet the levels of both IGF-1 and other glucose-regulatory hormones appeared to explain only a small part of the overall variation in growth rates.

Growth patterns by birth size of preterm children born at 24-29 gestational weeks for the first 3 years.

BACKGROUND: Concerns are prevalent about preterm infant long-term growth regarding plotting low on growth charts at discharge, stunting, underweight, high body fat and subsequent cardiometabolic morbidities. OBJECTIVES: To examine (a) longitudinal growth patterns of extremely and very preterm infants to 3 years corrected age (CA) (outcome), categorised by their birthweight for gestational age: small, appropriate and large for gestational age (SGA, AGA and LGA, respectively) (exposure); and (b) the ability of growth faltering (<-2 z-scores) to predict suboptimal cognitive scores at 3 years CA. METHODS: Post-discharge head, length, weight and weight-4-length growth patterns of the PreM Growth cohort study infants born <30 weeks and < 1500 g, who had dietitian and multi-disciplinary support before and after discharge, were plotted against the World Health Organization growth standard. Infants with brain injuries, necrotising enterocolitis and bronchopulmonary dysplasia were excluded. RESULTS: Of the included 405 infants, the proportions of infants with anthropometric measures > - 2 z-scores improved with age. The highest proportions <-2 z-scores for length (24.2%) and weight (24.0%) were at 36 gestational weeks. The proportion with small heads was low by 0 months CA (1.8%). By 3 years CA, only a few children plotted lower than -2 z-scores for length, weight-4-length and weight (<6%). After zero months CA, high weight-4-length and body mass index > + 2 z-scores were rare (2.1% at 3 years CA). Those born SGA had higher proportions with shorter heights (16.7% vs. 5.2%) and lower weights (27.8% vs. 3.5%) at 3 years CA compared to those born AGA. The ability of growth faltering to predict cognitive scores was limited (AUROC 0.42, 95% CI 0.39, 0.45 to 0.52, 95% CI 0.41, 0.63). CONCLUSIONS: Although children born <30 weeks gestation without major neonatal morbidities plot low on growth charts at 36 weeks CA most catch up to growth chart curves by 3 years CA.

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-life nutrition is associated with processing speed at age 5 in children born preterm with very low birth weight.

OBJECTIVE: Processing speed is suboptimal among preterm-born children which is of concern as it is a foundational skill supporting higher-level cognitive functions. The study objective was to evaluate associations between early-life nutrition and processing speed in childhood. METHODS: Macronutrient and human milk (mother's own, donor) intakes from 137 children born preterm with very low birth weight enrolled in a nutrition feeding trial were included. Processing speed was evaluated at age 5 using the Wechsler Preschool and Primary Scale of Intelligence-fourth edition Processing Speed Index. Associations between early-life nutrition and processing speed were explored through linear regression. RESULTS: Children had a mean (standard deviation [SD]) birth gestational age of 28.1 (2.5) weeks, weight of 1036 (260) g and 52% were male. The mean (SD) assessment age was 5.7 (0.2) years. Sex-dependent relationships were identified between first postnatal month protein, lipid and energy intakes and processing speed at 5 years. For females, lower protein (per 0.1 g/kg/d: -0.88, 95% confidence interval [CI]: -1.53, -0.23; p = 0.01) and energy (per 10 kcal/kg/d: -2.38, 95% CI: -4.70, -0.05; p = 0.03) intakes were related to higher processing speed scores. Mother's milk provision was positively associated (per 10% increase: 0.80, 95% CI: 0.22, 1.37; p = 0.01) and donor milk was negatively associated (per 10% increase: -1.15, 95% CI: -2.22, -0.08; p = 0.04) with processing speed scores; no sex differences were observed. CONCLUSIONS: First postnatal month nutrition was related to processing speed at age 5 in children born preterm with very low birth weight. Early-life nutrition that supports processing speed may be leveraged to improve later cognitive outcomes for this vulnerable population.

Growth charts for use at birth and in the neonatal period: Recommendations of the French Neonatal Society.

INTRODUCTION: The use of different growth charts can lead to confusion in discussions between professionals. There are obstetric charts (of fetal growth) and neonatal charts (of measurements at birth and of postnatal growth). These charts can be descriptive (derived from an unselected population) or prescriptive (derived from of a population at low risk and with optimal conditions for growth). OBJECTIVES: (1) To describe available charts for infants at birth and in the neonatal period and compare them, and (2) to recommend one or more charts for use in neonatology in France. METHODS: Bibliographic research was conducted on MEDLINE and completed by the guidelines of professional societies. RESULTS: Antenatal information about fetal growth restriction or fetuses identified as small-for-gestational-age using Intrauterine charts must be integrated into the identification of newborns at risk, but the use of Intrauterine charts to evaluate birthweight is not recommended to allow consistency with postnatal charts used in neonatal practice. Z-score variations using the updated Fenton postnatal charts are the most appropriate for the assessment of birthweight and postnatal growth for infants born preterm. These charts are sex-specific, include the three measurements (length, weight, and head circumference) and enable longitudinal follow-up of growth up to 50 weeks of corrected age and are linked to the World Health Organization charts at term. The French Audipog charts, although are individualized, accessible online and can be used in maternity units to evaluate birthweight for term infants, but do not allow the follow-up of postnatal growth, while Fenton charts may be used to evaluate birthweight and postnatal growth in the first month for hospitalized term infants. CONCLUSION: The updated Fenton charts are the neonatal charts that best suit the objectives of pediatricians in France for monitoring the growth of preterm newborns. The use of the Audipog charts at term remains an alternative in maternity wards, while Fenton charts can be used for hospitalized term newborns.

Influence of morbidity, early nutritional intake, and total energy: protein ratio on longitudinal extrauterine growth restriction of very preterm newborns at term-equivalent age: an observational study.

To evaluate the influence of early nutritional intake on the growth pattern of very preterm infants. This was an observational study including 109 newborns (< 32 weeks gestational age). Perinatal morbidities, nutritional therapy (first four weeks of life), and weight, length, and head circumference (HC) growth at term-equivalent age were evaluated. Growth restriction was defined as a difference > 1.2 SD between the birth and term age measurements. Growth restriction at term-equivalent age: 52.3% (weight), 42.9% (length), and 22% (HC). Morbidities were positively correlated with nutrition therapy and negatively correlated with the total energy provision: protein ratio. The duration of parenteral nutrition, the time to reach full enteral feedings, and the total energy provision: protein ratio were significantly correlated. Nutrient intake influenced weight, length, and HC growth, and cumulative energy deficit was significantly associated with HC growth restriction.   Conclusion: Perinatal morbidities interfere with nutritional therapy and early nutrient intake, leading to insufficient energy and energy provision: protein ratio for growth. What is Known: • The intake of macronutrients early in life, mainly protein, is important for the optimal growth of pretem infants. • The severity of morbidities and low gestational ages impact the nutritional management of preterm infants. What is New: • The number of morbidities, reflecting the severity of the neonatal clinical course, had a detrimental effect on the nutritional therapy and nutrients intake. • The inadequate energy provision per gram of protein ratio was significantly associated with growth restriction in all growth measures at the second week of life, persisting for head circumference up to the fourth week, highlighting the importance of its measurement, as it could be a precocious sign of development risk.

Impact of preterm birth on muscle mass and function: a systematic review and meta-analysis.

Individuals born preterm present lower exercise capacity. Along with the cardiopulmonary responses and activity level, muscle strength is a key determinant of exercise capacity. This systematic review aimed to summarize the current knowledge on the impact of preterm birth on skeletal muscle mass and function across the lifespan. The databases PubMed, MEDLINE, EBM, Embase, CINAHL Plus, Global Index Medicus, and Google Scholar were searched using keywords and MeSH terms related to skeletal muscle, preterm birth, and low birth weight. Two independent reviewers undertook study selection, data extraction, and quality appraisal using Covidence review management. Data were pooled to estimate the prematurity effect on muscle mass and function using the R software. From 4378 studies retrieved, 132 were full-text reviewed and 25 met the inclusion/exclusion criteria. Five studies presented a low risk of bias, and 5 had a higher risk of bias due to a lack of adjustment for confounding factors and presenting incomplete outcomes. Meta-analyses of pooled data from homogenous studies indicated a significant reduction in muscle thickness and jump test (muscle power) in individuals born preterm versus full-term with standardized mean difference and confidence interval of - 0.58 (0.27, 0.89) and - 0.45 (0.21, 0.69), respectively.    Conclusion: Overall, this systematic review summarizing the existing literature on the impact of preterm birth on skeletal muscle indicates emerging evidence that individuals born preterm, display alteration in the development of their skeletal muscle mass and function. This work also highlights a clear knowledge gap in understanding the effect of preterm birth on skeletal muscle development. What is Known: • Preterm birth, which occurs at a critical time of skeletal muscle development and maturation, impairs the development of different organs and tissues leading to a higher risk of comorbidities such as cardiovascular diseases. • Preterm birth is associated with reduced exercise capacity. What is New: • Individuals born preterm display alterations in muscle mass and function compared to individuals born at term from infancy to adulthood. • There is a need to develop preventive or curative interventions to improve skeletal muscle health in preterm-born individuals.

Association between preterm infant body composition in the first 3 months of life and preschool age: a cohort study.

Compared with full-term infants, preterm infants have fat-free mass deficit in the first months of life, which increases the risk of metabolic diseases in the future. In this cohort of children born under 32-week gestational age or less than 1500 g, we aimed to evaluate the associations of body composition at term equivalent age and in the first 3 months of life with fat-free mass and fat mass percentage at 4 to 7 years of life. Body composition assessments by air displacement plethysmography and anthropometry were performed at term, at 3 months of corrected age, and at 4 to 7 years of age. Multiple linear regression analysis was used to observe the associations between body composition at these ages. At term, fat mass percentage showed a negative association and fat-free mass a positive association with fat-free mass at 4 to 7 years. The fat-free mass at 3 months and the gain in fat-free mass between term and 3 months showed positive associations with fat-free mass at 4 to 7 years.   Conclusion: Body composition at preschool age is associated with fat-free mass in the first 3 months of life, a sensitive period for the risk of metabolic diseases. What is Known: • Preterm infants have a deficit in fat-free mass and high adiposity at term equivalent age compared to full-term infants. • Fat-free mass reflects metabolic capacity throughout life and therefore is considered a protective factor against the risk of metabolic syndrome. What is New: •Fat-free mass gain in the first 3 months of corrected age is associated with fat-free mass at preschool and school ages. •The first 3 months of life is a sensitive period to the risk of metabolic diseases.

Modeling Developmental Changes in Caffeine Clearance Considering Differences between Pre- and Postnatal Period.

Taguchi et al. reported that postmenstrual age (PMA) is a promising factor in describing and understanding the developmental change of caffeine (CAF) clearance. The aim of the present study was to quantify how developmental changes occur and to determine the effect of the length of the gestational period on CAF clearance. We performed a nonlinear mixed effect model (NONMEM) analysis and evaluated the fit of six models. A total of 115 samples were obtained from 52 patients with a mean age of 34.3 ± 18.2 d. The median values of gestational age (GA) and postnatal age (PNA) were 196 and 31 d, respectively. Serum CAF levels corrected for dose per body surface area (BSA) (C/D ratioBSA) were dependent on PMA rather than PNA, which supports the findings of a previous study. NONMEM analysis provided the following final model of oral clearance: CL/F = 0.00603∙WT∙∙0.877GA ≤ 196 L/h. This model takes into account developmental changes during prenatal and postnatal periods separately. The model successfully described the variation in clearance of CAF. Our findings suggest that the dosage of CAF in preterm infants should be determined based not only on body weight (WT) but also on both PNA and GA.

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.

Noise or sound management in the neonatal intensive care unit for preterm or very low birth weight infants.

BACKGROUND: Infants in the neonatal intensive care unit (NICU) are subjected to different types of stress, including sounds of high intensity. The sound levels in NICUs often exceed the maximum acceptable level recommended by the American Academy of Pediatrics, which is 45 decibels (dB). Hearing impairment is diagnosed in 2% to 10% of preterm infants compared to only 0.1% of the general paediatric population. Bringing sound levels under 45 dB can be achieved by lowering the sound levels in an entire unit; by treating the infant in a section of a NICU, in a 'private' room, or in incubators in which the sound levels are controlled; or by reducing sound levels at the individual level using earmuffs or earplugs. By lowering sound levels, the resulting stress can be diminished, thereby promoting growth and reducing adverse neonatal outcomes. This review is an update of one originally published in 2015 and first updated in 2020. OBJECTIVES: To determine the benefits and harms of sound reduction on the growth and long-term neurodevelopmental outcomes of neonates. SEARCH METHODS: We used standard, extensive Cochrane search methods. On 21 and 22 August 2023, a Cochrane Information Specialist searched CENTRAL, PubMed, Embase, two other databases, two trials registers, and grey literature via Google Scholar and conference abstracts from Pediatric Academic Societies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs in preterm infants (less than 32 weeks' postmenstrual age (PMA) or less than 1500 g birth weight) cared for in the resuscitation area, during transport, or once admitted to a NICU or stepdown unit. We specified three types of intervention: 1) intervention at the unit level (i.e. the entire neonatal department), 2) at the section or room level, or 3) at the individual level (e.g. hearing protection). DATA COLLECTION AND ANALYSIS: We used the standardised review methods of Cochrane Neonatal to assess the risk of bias in the studies. We used the risk ratio (RR) and risk difference (RD), with their 95% confidence intervals (CIs), for dichotomous data. We used the mean difference (MD) for continuous data. Our primary outcome was major neurodevelopmental disability. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included one RCT, which enroled 34 newborn infants randomised to the use of silicone earplugs versus no earplugs for hearing protection. It was a single-centre study conducted at the University of Texas Medical School in Houston, Texas, USA. Earplugs were positioned at the time of randomisation and worn continuously until the infants were 35 weeks' postmenstrual age (PMA) or discharged (whichever came first). Newborns in the control group received standard care. The evidence is very uncertain about the effects of silicone earplugs on the following outcomes. • Cerebral palsy (RR 3.00, 95% CI 0.15 to 61.74)and Mental Developmental Index (MDI) (Bayley II) at 18 to 22 months' corrected age (MD 14.00, 95% CI 3.13 to 24.87); no other indicators of major neurodevelopmental disability were reported. • Normal auditory functioning at discharge (RR 1.65, 95% CI 0.93 to 2.94) • All-cause mortality during hospital stay (RR 2.07, 95% CI 0.64 to 6.70; RD 0.20, 95% CI -0.09 to 0.50) • Weight (kg) at 18 to 22 months' corrected age (MD 0.31, 95% CI -1.53 to 2.16) • Height (cm) at 18 to 22 months' corrected age (MD 2.70, 95% CI -3.13 to 8.53) • Days of assisted ventilation (MD -1.44, 95% CI -23.29 to 20.41) • Days of initial hospitalisation (MD 1.36, 95% CI -31.03 to 33.75) For all outcomes, we judged the certainty of evidence as very low. We identified one ongoing RCT that will compare the effects of reduced noise levels and cycled light on visual and neural development in preterm infants. AUTHORS' CONCLUSIONS: No studies evaluated interventions to reduce sound levels below 45 dB across the whole neonatal unit or in a room within it. We found only one study that evaluated the benefits of sound reduction in the neonatal intensive care unit for hearing protection in preterm infants. The study compared the use of silicone earplugs versus no earplugs in newborns of very low birth weight (less than 1500 g). Considering the very small sample size, imprecise results, and high risk of attrition bias, the evidence based on this research is very uncertain and no conclusions can be drawn. As there is a lack of evidence to inform healthcare or policy decisions, large, well designed, well conducted, and fully reported RCTs that analyse different aspects of noise reduction in NICUs are needed. They should report both short- and long-term outcomes.