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.

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.

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.

Limite de viabilidade de prematuros extremos atendidos em um hospital universitário / Limit of viability of extremely preterm infants treated at a university hospital / Límite de viabilidad de prematuros extremos atendidos en un hospital universitario

Objetivo: descrever o perfil de recém-nascidos com prematuridade extrema e identificar fatores associados a mortalidade segundo idade gestacional e o limite de viabilidade destes. Método: estudo observacional retrospectivo, com abordagem quantitativa, realizado em um hospital universitário do estado de Minas Gerais, desenvolvido de agosto de 2021 a janeiro de 2022. A amostra foi composta por 39 prontuários de prematuros extremos nascidos vivos. Foi realizada a análise descritiva das variáveis quantitativas usando medidas como média, desvio-padrão e valores mínimo e máximo. As variáveis categóricas foram descritas a partir de suas distribuições de frequência absoluta e percentual. Resultados: a maioria das gestantes são mulheres adultos-jovens, realizaram pré-natal e parto cesárea. Dos prematuros prevalece sexo masculino, idade gestacional de 25 semanas, evoluíram para óbito a maioria destes com idade gestacional de 23 e 24 semanas. Conclusão: o limite de viabilidade nesse serviço situa-se em uma idade gestacional igual ou maior que 25 semanas.

Objective: to describe the profile of newborns with extreme prematurity and to identify factors associated with mortality according to gestational age and their limit of viability. Method: a retrospective observational study, with a quantitative approach, carried out in a university hospital in the state of Minas Gerais, developed from August 2021 to January 2022. The sample consisted of 39 records of live-born extreme preterm infants. Descriptive analysis of quantitative variables was performed using measures such as mean, standard deviation and minimum and maximum values. Categorical variables were described from their absolute and percentage frequency distributions. Results: most pregnant women are young-adult women, who underwent prenatal care and cesarean delivery. Of the preterm infants, the male sex prevails, with a gestational age of 25 weeks, most of whom died at a gestational age of 23 and 24 weeks. Conclusion: the limit of viability in this service is at a gestational age equal to or greater than 25 weeks.

Objetivo: describir el perfil de los recién nacidos con prematuridad extrema e identificar los factores asociados a la mortalidad según la edad gestacional y su límite de viabilidad. Método: estudio observacional retrospectivo, con abordaje cuantitativo, realizado en un hospital universitario del estado de Minas Gerais, desarrollado entre agosto de 2021 y enero de 2022. La muestra estuvo compuesta por 39 prontuarios de prematuros extremos nacidos vivos. El análisis descriptivo de las variables cuantitativas se realizó utilizando medidas como la media, la desviación estándar y los valores mínimo y máximo. Las variables categóricas se describieron a partir de sus distribuciones de frecuencia absoluta y porcentual. Resultados: la mayoría de las gestantes son mujeres adultas jóvenes, que realizaron control prenatal y parto por cesárea. De los prematuros prevalece el sexo masculino, con una edad gestacional de 25 semanas, la mayoría de los cuales fallecieron a las 23 y 24 semanas de edad gestacional. Conclusión: el límite de viabilidad en este servicio es a una edad gestacional igual o mayor a 25 semanas.

Birthweight and patterns of postnatal weight gain in very and extremely preterm babies in England and Wales, 2008-19: a cohort study.

BACKGROUND: Intrauterine and postnatal weight are widely regarded as biomarkers of fetal and neonatal wellbeing, but optimal weight gain following preterm birth is unknown. We aimed to describe changes over time in birthweight and postnatal weight gain in very and extremely preterm babies, in relation to major morbidity and healthy survival. METHODS: In this cohort study, we used whole-population data from the UK National Neonatal Research Database for infants below 32 weeks gestation admitted to neonatal units in England and Wales between Jan 1, 2008, and Dec 31, 2019. We used non-linear Gaussian process to estimate monthly trends, and Bayesian multilevel regression to estimate unadjusted and adjusted coefficients. We evaluated birthweight; weight change from birth to 14 days; weight at 36 weeks postmenstrual age; associated Z scores; and longitudinal weights for babies surviving to 36 weeks postmenstrual age with and without major morbidities. We adjusted birthweight for antenatal, perinatal, and demographic variables. We additionally adjusted change in weight at 14 days and weight at 36 weeks postmenstrual age, and their Z scores, for postnatal variables. FINDINGS: The cohort comprised 90 817 infants. Over the 12-year period, mean differences adjusted for antenatal, perinatal, demographic, and postnatal variables were 0 g (95% compatibility interval -7 to 7) for birthweight (-0·01 [-0·05 to 0·03] for change in associated Z score); 39 g (26 to 51) for change in weight from birth to 14 days (0·14 [0·08 to 0·19] for change in associated Z score); and 105 g (81 to 128) for weight at 36 weeks postmenstrual age (0·27 [0·21 to 0·33] for change in associated Z score). Greater weight at 36 weeks postmenstrual age was robust to additional adjustment for enteral nutritional intake. In babies surviving without major morbidity, weight velocity in all gestational age groups stabilised at around 34 weeks postmenstrual age at 16-25 g per day along parallel percentile lines. INTERPRETATION: The birthweight of very and extremely preterm babies has remained stable over 12 years. Early postnatal weight loss has decreased, and subsequent weight gain has increased, but weight at 36 weeks postmenstrual age is consistently below birth percentile. In babies without major morbidity, weight velocity follows a consistent trajectory, offering opportunity to construct novel preterm growth curves despite lack of knowledge of optimal postnatal weight gain. FUNDING: UK Medical Research Council.

Cumulative impact of multiple evidence based strategies on postnatal growth of extremely-low-birth-weight infants.

BACKGROUND: Postnatal growth failure is common in very preterm infants and is associated with worse neurodevelopmental outcome. OBJECTIVE: To evaluate the cumulative impact of multiple evidence based strategies on the postnatal growth of extremely-low-birth-weight (ELBW) infants. METHODS: We conducted a prospective observational study. Based on current literature, changes were implemented to provide optimal parenteral and enteral nutrition. Daily intakes of calories, protein, lipids and carbohydrates were calculated. The average growth velocity (GV) was calculated using 2-point exponential model and is reported as grams/kg/day. The length and head circumference gains are reported as centimeters/week. RESULTS: The mean gestational age and birth weight for 38 ELBW survivors were 27.0 ± 2.1 weeks and 752 ± 147 g respectively. The GV was 13.2 ± 2.2 g/kg/day (range 8.8-17.4) and gains in length and head circumference were 0.88 ± 0.9 (range 0.15-1.42) and 0.71 ± 0.5 (range 0.22-0.96) centimeters/week respectively. Twenty nine (76.3%) infants were small-for-gestational-age (SGA) at discharge and 23 of these (60.5% of all infants) had weight below 3rd percentile. All 11 infants who were SGA at birth were SGA at discharge as well. Of 25 appropriate-for-gestational-age (AGA) infants at birth, 16 (64%) were SGA at discharge. The number of infants with length and head circumference below 10th percentile at birth and discharge were 11 (28.9%) and 29 (76.3%) for length and 20 (52.6%) and 27 (71.1%) for head circumference. Infants with multiple morbidities and more hospital days with no enteral feeds had lower GV. CONCLUSION: All infants born SGA at birth and majority of ELBW survivors born AGA at birth had weight, length and head circumference below 10th percentile at discharge despite aggressive nutrition supplementation.

Effects of Lactobacillus reuteri supplementation on the gut microbiota in extremely preterm infants in a randomized placebo-controlled trial.

Extremely low birth weight (ELBW) infants often develop an altered gut microbiota composition, which is related to clinical complications, such as necrotizing enterocolitis and sepsis. Probiotic supplementation may reduce these complications, and modulation of the gut microbiome is a potential mechanism underlying the probiotic effectiveness. In a randomized, double-blind, placebo-controlled trial, we assessed the effect of Lactobacillus reuteri supplementation, from birth to post-menstrual week (PMW)36, on infant gut microbiota. We performed 16S amplicon sequencing in 558 stool samples from 132 ELBW preterm infants at 1 week, 2 weeks, 3 weeks, 4 weeks, PMW36, and 2 years. Probiotic supplementation results in increased bacterial diversity and increased L. reuteri abundance during the 1st month. At 1 week, probiotic supplementation also results in a lower abundance of Enterobacteriaceae and Staphylococcaceae. No effects were found at 2 years. In conclusion, probiotics may exert benefits by modulating the gut microbiota composition during the 1st month in ELBW infants.

Investigating the brain structural connectome following working memory training in children born extremely preterm or extremely low birth weight.

Children born extremely preterm (EP, <28 weeks' gestation) or extremely low birth weight (ELBW, <1,000 g) are a vulnerable population at high risk of working memory impairments. We aimed to examine changes in the brain structural connectivity networks thought to underlie working memory performance, after completion of a working memory training program (Cogmed) compared with a placebo program in EP/ELBW children. This was a double-blind, placebo-controlled randomized trial (the Improving Memory in a Preterm Randomised Intervention Trial). Children born EP/ELBW received either the Cogmed or placebo program at 7 years of age (n = 91). A subset of children had magnetic resonance imaging of the brain immediately pre- and 2 weeks post-training (Cogmed n = 28; placebo n = 27). T1 -weighted and diffusion-weighted images were used to perform graph theoretical analysis of structural connectivity networks. Changes from pre-training to post-training in structural connectivity metrics were generally similar between randomized groups. There was little evidence that changes in structural connectivity metrics were related to changes in working memory performance from pre- to post-training. Overall, our results provide little evidence that the Cogmed working memory training program has training-specific effects on structural connectivity networks in EP/ELBW children.

Changes over time in quality of life of school-aged children born extremely preterm: 1991-2005.

OBJECTIVE: To compare health-related quality of life (HRQOL) at 8 years in children born extremely preterm (EP) with contemporaneous term-born controls over three epochs: 1991-92, 1997 and 2005. DESIGN: Prospective recruitment of geographic cohorts across three distinct eras. Utilities were calculated from the parent-completed Health Utilities Index (HUI), version 2 (1991-92 and 1997 cohorts) and version 3 (2005 cohort). Differences in utilities >0.05 are clinically important. SETTING: The state of Victoria, Australia. PATIENTS: 475 EP (<28 weeks' gestation) and 570 term controls. MAIN OUTCOME MEASURES: Utilities of children born EP compared with term controls within each era, and paired differences between an EP and matched controls compared across eras. RESULTS: Overall, 86% of survivors had utility data at 8 years of age; 475 EP and 570 controls. In all eras, parent-reported utilities were lower for children born EP compared with controls (difference in medians (95% CIs); 1991-92, -0.053 (-0.071 to -0.035); 1997, -0.053 (-0.072 to -0.034); 2005, -0.082 (-0.097 to -0.068)). Mean differences (MD) between EP children and matched controls within each era were lower in the 2005 cohort compared with both the 1991-92 cohort (MD -0.054, 95% CI -0.097 to -0.010) and the 1997 cohort (MD -0.053, 95% CI -0.097 to -0.009). CONCLUSION: Children born EP in the postsurfactant era have clinically important reductions in parent-reported HRQOL compared with controls, which may be worsening over time.

Kangaroo Mother Care Reduces Noninvasive Ventilation and Total Oxygen Support Duration in Extremely Low Birth Weight Infants.

OBJECTIVE: Evidence on the safety and influence of kangaroo mother care (KMC) in extremely low birth weight infants (ELBWIs) on ventilation is lacking. STUDY DESIGN: This is a retrospective cohort study performed in 145 ELBWIs on noninvasive mechanical ventilation from a tertiary center. RESULTS: The duration of nasal intermittent positive pressure ventilation (nIPPV) and continuous positive airway pressure (CPAP) ventilation was significantly shorter in infants with KMC compared with infants without (21 vs. 13.5 days, p = 0.001 and 29.5 days vs. 20.5 days, p = 0.001, respectively). The frequency of apnea during hospital stay was fewer in KMC infants, compared with no KMC (23 vs. 20 times, p = 0.002). Multiple linear regression analysis showed that KMC was an independent protective factor for shortening nIPPV/CPAP duration (ß = -9.90, 95% confidence interval [CI] [-13.20, -6.60], p < 0.001), total supplemental oxygen support (ß = -10.52, 95% CI [-16.73, -4.30], p = 0.001), and reducing times of apneas (ß = -5.88, 95% CI [-8.56, -3.21], p < 0.001). CONCLUSION: KMC benefits ELBWIs by shortening nIPPV/CPAP ventilation duration and total supplemental oxygen support, and reducing the frequency of apneas.

Effects of Liberal vs Restrictive Transfusion Thresholds on Survival and Neurocognitive Outcomes in Extremely Low-Birth-Weight Infants: The ETTNO Randomized Clinical Trial.

Importance: Red blood cell transfusions are commonly administered to infants weighing less than 1000 g at birth. Evidence-based transfusion thresholds have not been established. Previous studies have suggested higher rates of cognitive impairment with restrictive transfusion thresholds. Objective: To compare the effect of liberal vs restrictive red blood cell transfusion strategies on death or disability. Design, Setting, and Participants: Randomized clinical trial conducted in 36 level III/IV neonatal intensive care units in Europe among 1013 infants with birth weights of 400 g to 999 g at less than 72 hours after birth; enrollment took place between July 14, 2011, and November 14, 2014, and follow-up was completed by January 15, 2018. Interventions: Infants were randomly assigned to liberal (n = 492) or restrictive (n = 521) red blood cell transfusion thresholds based on infants' postnatal age and current health state. Main Outcome and Measures: The primary outcome, measured at 24 months of corrected age, was death or disability, defined as any of cognitive deficit, cerebral palsy, or severe visual or hearing impairment. Secondary outcome measures included individual components of the primary outcome, complications of prematurity, and growth. Results: Among 1013 patients randomized (median gestational age at birth, 26.3 [interquartile range {IQR}, 24.9-27.6] weeks; 509 [50.2%] females), 928 (91.6%) completed the trial. Among infants in the liberal vs restrictive transfusion thresholds groups, respectively, incidence of any transfusion was 400/492 (81.3%) vs 315/521 (60.5%); median volume transfused was 40 mL (IQR, 16-73 mL) vs 19 mL (IQR, 0-46 mL); and weekly mean hematocrit was 3 percentage points higher with liberal thresholds. Among infants in the liberal vs restrictive thresholds groups, the primary outcome occurred in 200/450 (44.4%) vs 205/478 (42.9%), respectively, for a difference of 1.6% (95% CI, -4.8% to 7.9%; P = .72). Death by 24 months occurred in 38/460 (8.3%) vs 44/491 (9.0%), for a difference of -0.7% (95% CI, -4.3% to 2.9%; P = .70), cognitive deficit was observed in 154/410 (37.6%) vs 148/430 (34.4%), for a difference of 3.2% (95% CI, -3.3% to 9.6%; P = .47), and cerebral palsy occurred in 18/419 (4.3%) vs 25/443 (5.6%), for a difference of -1.3% (95% CI, -4.2% to 1.5%; P = .37), in the liberal vs the restrictive thresholds groups, respectively. In the liberal vs restrictive thresholds groups, necrotizing enterocolitis requiring surgical intervention occurred in 20/492 (4.1%) vs 28/518 (5.4%); bronchopulmonary dysplasia occurred in 130/458 (28.4%) vs 126/485 (26.0%); and treatment for retinopathy of prematurity was required in 41/472 (8.7%) vs 38/492 (7.7%). Growth at follow-up was also not significantly different between groups. Conclusions and Relevance: Among infants with birth weights of less than 1000 g, a strategy of liberal blood transfusions compared with restrictive transfusions did not reduce the likelihood of death or disability at 24 months of corrected age. Trial Registration: ClinicalTrials.gov Identifier: NCT01393496.

Determinants of the Very Low-Birth-Weight Infant's Intestinal Microbiome: A Systematic Review.

The intestinal microbiome is the genetic material from microorganisms residing in the intestinal tract. Very low-birth-weight infants (VLBW; birth weight ≤1500 g) are a physiologically compromised population undergoing a unique period of initial intestinal microbiome establishment. Evidence supports a connection between the intestinal microbiome and gastrointestinal illness that disproportionately affects VLBW infants. Necrotizing enterocolitis, an inflammatory and often necrotic condition of the intestine, and late-onset sepsis, a bloodstream infection occurring after 3 days of life, are thought to be associated with delayed or abnormal intestinal microbiome development. Here, we review the determinants, or factors, that influence the VLBW infant's intestinal microbiome and discuss clinical implications. PubMed, Web of Science, EMBASE, and CINAHL were systematically searched for publications addressing factors with the potential to affect the intestinal microbiome of VLBW infants. Results indicate that infant's age and weight, mode of delivery, antibiotic exposure, medication use, feeding regime, environment, and perinatal-/infant-associated factors may be important determinants of the microbiome in this vulnerable population. Clinicians have opportunities to support positive development of the VLBW infant's intestinal microbiome through antibiotic stewardship, support of human milk feeding, and hygienic care practices.

Concentrated Preterm Formula as a Liquid Human Milk Fortifier at Initiation Stage in Extremely Low Birth Weight Preterm Infants: Short Term and 2-year Follow-up Outcomes.

Human milk (HM) must be accurately fortified for extremely low birth weight (ELBW) preterm infants with human milk fortifiers (HMFs). Powdered HMF has some limitations in terms of sterilization and accuracy. A concentrated preterm formula (CPF) may serve as a safe liquid HMF to facilitate growth. Hence, we launched a quality improvement project for fortification accuracy of minute volume HM. A CPF, Similac Special Care 30 (SSC30), was newly introduced as an HMF when daily feeding reached 100 cm3/kg. CPF + HM (1:2 volume ratio), CPF + HM (1:1 volume ratio), and powdered HMF + HM (1 packet in 25 cm3) represented three fortification stages. Fortification shifted to powdered HMF while tolerable feeding reached 25 cm3/meal. The outcome was compared before (Period-I, January 2015 to June 2016, n = 37) and after the new implement (Period-II, July 2016 to December 2017, n = 36). Compared with the Period-I group, the Period-II group had significantly higher daily enteral milk intake in the first 4 weeks of life, and higher percentages of fortification in the HM-fed infants in the first 8 weeks after birth. The Period-II group also significantly increased in body weight growth in terms of z-score at term equivalent age (p = 0.04) and had better language and motor performance at 24 months old (p = 0.048 and p = 0.032, respectively). Using the liquid CPF as a strategical alternative fortification of HM might be beneficial for extremely preterm infants in terms of growth as well as neurodevelopment.

Relationships between Neonatal Nutrition and Growth to 36 Weeks' Corrected Age in ELBW Babies-Secondary Cohort Analysis from the Provide Trial.

A key modifiable factor for improving neurodevelopment in extremely low birthweight (ELBW) babies may be improving growth, especially head growth, by optimising nutrition in the early neonatal period. We aimed to investigate relationships between nutrient intakes in the 4 weeks after birth, and growth from birth to 36 weeks' corrected age (CA) in ELBW babies. We undertook a prospective cohort study of 434 participants enrolled in a randomised controlled trial (ProVIDe) in eight New Zealand and Australian neonatal intensive care units. Macronutrient intakes from birth to 4 weeks and weight, length and head circumference measurements from birth to 36 weeks' CA were collected. From birth to 36 weeks' CA, the median (IQR) z-score changes were: weight -0.48 (-1.09, 0.05); length -1.16 (-1.86, -0.43), and head circumference -0.82 (-1.51, -0.19). Changes in z-score to 4 weeks and 36 weeks' CA were correlated with protein intake. Each 1 g·Kg-1·d-1 total protein intake in week 2 was associated with 0.26 z-score increase in head circumference at 36 weeks' CA. Both nutritional intake and change in z-scores to 36 weeks' CA differed widely amongst sites. Correlations between nutrition and growth, and differences in these amongst sites, indicate there may be potential to improve growth with enhanced nutrition practices.

Growth patterns and body composition in former extremely low birth weight (ELBW) neonates until adulthood: a systematic review.

Preterm infants are obviously born lighter and shorter, with smaller head circumferences than normal birth weight term born neonates. They also have a different body composition. Compromised growth is associated with adverse health outcomes. Both growth retardation and accelerated growth are suggested to cause metabolic, cardiovascular, and renal complications. Reviews regarding growth and body composition in preterm infants often do not differentiate between birth weight and gestational age. The purpose of this systematic review is to assemble growth data, specific in extremely low birth weight children. Different databases were searched for studies regarding growth and body composition in former extremely low birth weight infants until adulthood. We compared height, weight, head circumference, body mass index, fat mass, lean mass, fat distribution, and body water to matched normal birth weight controls and the World Health Organization growth charts. Studies consistently reported that former extremely low birth weight neonates experience a period of accelerated postnatal growth, but they achieve lower anthropometric parameters than normal birth weight children. There is no consensus about differences in body composition and how to measure this.Conclusion: Although extremely low birth weight infants exhibit a period of catch-up growth, their growth remains retarded later in life. Further research is needed to investigate body composition and the associated risk of cardiovascular diseases or metabolic syndrome.What is Known:• Extremely low birth weight infants have lower anthropometric parameters and a different body composition at birth and term-corrected age than normal birth weight infants.• Former extremely low birth weight infants also have a higher risk on adverse cardiovascular health outcomes in later life.What is New:• After hospital discharge, extremely low birth weight neonates remain smaller and probably also lighter, with smaller head circumferences at each corrected age throughout childhood and adolescence when compared to normal birth weight infants or the World Health Organization growth charts. It is not clear whether extremely low birth weight infants reach a lower or similar body mass index score as normal birth weight infants.• There is a lack of (long-term) information on body composition in extremely low birth weight infants.

Exposure to placental insufficiency alters postnatal growth trajectory in extremely low birth weight infants.

Growth in the immediate postnatal period for extremely low birth weight (ELBW, birth weight < 1000 g) infants is an important topic in neonatal medicine. The goal is to ensure adequate postnatal growth and to minimize complications resulting from suboptimal growth. Past efforts have focused on postnatal nutrition as well as on minimizing comorbidities. It has not been systematically assessed whether antenatal factors play a role in postnatal growth. In this report, we conducted a retrospective study on 91 maternal-neonatal pairs. We prospectively collected maternal and neonatal demographic data, neonatal nutrition in the first 7 days of life and after enteral nutrition is fully established, comorbidity data, as well as weight data from birth to 50 weeks corrected gestational age. We developed a linear mixed-effects model to examine the role of placental insufficiency, as defined by fetal Doppler studies, in postnatal weight z-score trajectory over time in the ELBW population. We relied on Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) for model selection. Interestingly, the selected model included a quadratic term of time and a placental insufficiency-by-time interaction term. In a covariate analysis, AIC and BIC both favored a model that included calories intake in the first 7 days of life and the total duration of antibiotics as fixed-effects, but not their interaction terms with time. Overall, we demonstrated for the first time that placental insufficiency, an antenatal factor, is a major determinant of postnatal weight trajectory in the ELBW population. Prospective studies are warranted to confirm our findings.

Longitudinal Growth of Extremely Low Birth Weight Infants at 5 years.

This prospective cohort study assessed longitudinal growth of Extremely low birth weight (ELBW) infants at 5 y of age. ELBW infants discharged alive during 2009-2011 were prospectively followed till 5 y of age. Forty-five matched controls were enrolled. The weight, length, and occipitofrontal circumference were recorded and Z-scores were calculated using the WHO software. The primary outcome was the comparison of growth parameters of the ELBW cohort with controls. Forty-seven ELBW and 45 controls were assessed at 5 y. In ELBW cohort, 17 (36.2%) were underweight, 13 (27.7%) were stunted, 11 (23.4%) were wasted, and 6 (15.7%) had microcephaly at 5 y. As compared to controls, the proportion of underweight and stunting was significantly higher among ELBW infants (p < 0.001). There was no significant difference in Z-scores at 2 and 5 y. ELBW infants have significant undernutrition at 5 y of age and there is no catch-up growth beyond 2 y.

Initial and delayed thyroid-stimulating hormone elevation in extremely low-birth-weight infants.

BACKGROUND: To determine the incidence, etiology, and outcomes of thyroid-stimulating hormone (TSH) elevation in extremely low-birth-weight infants (ELBWIs). METHODS: Newborn thyroid screening data of 584 ELBWIs (birth weight, < 1000 g; gestational age, ≥ 23 weeks) were retrospectively analyzed to identify initial (≤ 2 postnatal weeks) and delayed (> 2 weeks) TSH elevations. Growth and neurodevelopmental outcomes at 2 years' corrected age (CA) were assessed according to levothyroxine replacement. RESULTS: Initial and delayed TSH elevations were detected at CAs of 27 and 30 weeks, respectively, with incidence rates of 0.9 and 7.2%, respectively. All infants with initial TSH elevations had perinatal asphyxia, and 95% of those with delayed TSH elevation were exposed to various stressors, including respiratory support, drugs, and surgery within 2 weeks before diagnosis of TSH elevation. Free thyroxine (T4) levels were simultaneously reduced in 80 and 57% of infants with initial and delayed TSH elevations, respectively. Both initial and delayed TSH elevations were transient, regardless of levothyroxine replacement. Infants receiving levothyroxine replacement therapy had significantly higher TSH elevations, significantly lower free T4 levels, and significantly reduced mortality, compared to untreated infants. However, levothyroxine replacement had no significant effect on long-term growth and neurodevelopmental outcomes. CONCLUSIONS: The timing of insult superimposition on hypothalamic-pituitary-thyroid axis maturation is a major determinant of initial or delayed TSH elevation in ELBWIs. Levothyroxine replacement did not affect growth or neurodevelopmental outcomes in this population.

Growth, Feeding Tolerance and Metabolism in Extreme Preterm Infants under an Exclusive Human Milk Diet.

BACKGROUND: For preterm infants, human milk (HM) has to be fortified to cover their enhanced nutritional requirements and establish adequate growth. Most HM fortifiers are based on bovine protein sources (BMF). An HM fortifier based on human protein sources (HMF) has become available in the last few years. The aim of this study is to investigate the impact of an HMF versus BMF on growth in extremely low birth weight (ELBW, <1000 g) infants. METHODS: This was a retrospective, controlled, multicenter cohort study in infants with a birthweight below 1000 g. The HMF group received an exclusive HM diet up to 32+0 weeks of gestation and was changed to BMF afterwards. The BMF group received HM+BMF from fortifier introduction up to 37+0 weeks. RESULTS: 192 extremely low birth weight (ELBW)-infants were included (HMF n = 96, BMF n = 96) in the study. After the introduction of fortification, growth velocity up to 32+0 weeks was significantly lower in the HMF group (16.5 g/kg/day) in comparison to the BMF group (18.9 g/kg/day, p = 0.009) whereas all other growth parameters did not differ from birth up to 37+0 weeks. Necrotizing enterocolitis (NEC) incidence was 10% in the HMF and 8% in the BMF group. CONCLUSION: Results from this study do not support the superiority of HFM over BMF in ELBW infants.

The association of early postnatal weight loss with outcome in extremely low birth weight infants.

BACKGROUND: To compare outcomes of extremely low birth weight (ELBW) infants having different weight losses in the first 3 days of life. METHODS: One hundred and twenty six ELBW infants were evaluated retrospectively for weight loss percentages on the third day of life compared to their birth weight. We examined the weight loss on the third day of life compared to the birth weight for the ELBW infants and tested its association with mortality and morbidities. The mortality was subgrouped as overall mortality and mortality in the first 7 days of life. The morbidities were patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH) and bronchopulmonary dysplasia (BPD). BPD was defined as need for supplemental oxygen at 36 weeks' postconceptional age. We grouped the infants into four quartiles according to weight loss percentage on the third day of life: Group 1 (Quartile 1), infants with weight loss of 0-3% of birth weight; Group 2 (Quartile 2); infants with weight loss of 3.1-7.5%, Group 3 (Quartile 3), infants with weight loss of 7.51-12%; and Group 4 (Quartile 4), infants with weight loss of more than 12%. The mortality and morbidities were analyzed according to these groups and other risk factors. RESULTS: Overall mortality and mortality in the first 7 days of life were significantly higher in Groups 1 (36% and 27%) and 4 (43% and 24%), compared to Groups 2 (10% and 10%) and 3 (18% and 9%), respectively. CONCLUSION: Weight loss less than 3% and more than 12% was significantly associated with an increase in mortality. There was a positive correlation between weight loss on the third day of life and IVH. CONCLUSION: Inappropriate weight loss in ELBW infants is associated with increased mortality and IVH. Appropriate weight loss can improve outcomes in this population.