Cardiometabolic health in adults born with very low birth weight-a sibling study.

BACKGROUND: Preterm survivors have increased risk for impaired cardiometabolic health. We assessed glucose regulation and cardiometabolic biomarkers in adult very low birth weight (VLBW, <1500 g) survivors, using siblings as controls. METHODS: VLBW-participants were matched with term-born, same-sex siblings. At mean age 29.2 years (SD 3.9), 74 VLBW-adults and 70 siblings underwent a 2-h 75 g oral glucose tolerance test and blood tests for assessment of cardiometabolic biomarkers. RESULTS: Of participants, 23 (31%) VLBW and 11 (16%) sibling-controls met World Health Organization criteria for impaired glucose regulation (OR adjusted for age and sex 2.5, 95% CI: 1.1 to 5.8). Adjusting for age and sex, VLBW-participants showed 9.2% higher 2-h glucose (95% CI: 0.4% to 18.8%) than their siblings. Also, fasting (13.4%, -0.3% to 29.0%) and 2-h free fatty acids (15.6%, -2.4% to 36.9%) were higher in VLBW-participants. These differences were statistically significant only after further adjusting for confounders. No statistically significant differences were found regarding other measured biomarkers, including insulin resistance, atherogenic lipid profiles or liver tests. CONCLUSIONS: VLBW-adults showed more impaired fatty acid metabolism and glucose regulation. Differences in cardiometabolic biomarkers were smaller than in previous non-sibling studies. This may partly be explained by shared familial, genetic, or environmental factors. IMPACT: At young adult age, odds for impaired glucose regulation were 3.4-fold in those born at very low birth weight, compared to same-sex term-born siblings. Taking into consideration possible unmeasured, shared familial confounders, we compared cardiometabolic markers in adults born preterm at very low birth weight with term-born siblings. Prematurity increased risk for impaired glucose regulation, unrelated to current participant characteristics, including body mass index. In contrast to previous studies, differences in insulin resistance were not apparent, suggesting that insulin resistance may partially be explained by factors shared between siblings. Also, common cardiometabolic biomarkers were similar within sibling pairs.

Self-reported executive function problems in adults born very low birthweight.

BACKGROUND: Executive function difficulties are common among children born very preterm and/or very low birthweight (<1500 g; VLBW), but little is known about whether they persist into adulthood. OBJECTIVES: Examine the nature and pattern of self-reported executive functioning at 23 and 28 years of age using data from a national cohort study of adults born VLBW and a comparison group of same-age full-term (FT) born adults. Also examined were associations between executive function difficulties and socio-economic outcomes. METHODS: All infants born VLBW in New Zealand during 1986 were prospectively included in an audit of retinopathy of prematurity (n = 413), with 250 (77% of survivors) followed to median age 28 years. A comparison group of FT adults was also recruited at age 23 and followed to 28 years (n = 100). Across both adult assessments, executive functioning was assessed using the Behaviour Rating Inventory of Executive Function-Adult Version (BRIEF-A) and analysed with semi-parametric models to examine the effects of age and group on executive function. RESULTS: At 23 and 28 years, VLBW adults had increased risk of executive function impairment compared with FT adults in behaviour regulation (relative risk [CI] 2.37, 95% confidence interval (CI)1.27, 4.45), meta-cognition (RR 6.03, 95% CI 2.18, 16.78) and global functioning (RR 3.20, 95% CI 1.40, 7.28). Impaired global executive functioning was associated with lower socio-economic status (regression estimate [b] = -0.43, 95% CI -0.59, -0.27) and a reduced likelihood of home ownership by age 28 years (RR 0.98, 95% CI 0.96, 1.00), even after controlling for sex, ethnicity and parental socio-economic backgrounds for both groups. CONCLUSION(S): VLBW-born adults continue to experience more executive function difficulties in their everyday life relative to term controls at age 28 years. These difficulties were negatively associated with their socio-economic opportunities as young adults.

Aberrant Claustrum Microstructure in Humans after Premature Birth.

Several observations suggest an impact of prematurity on the claustrum. First, the claustrum's development appears to depend on transient subplate neurons of intra-uterine brain development, which are affected by prematurity. Second, the claustrum is the most densely connected region of the mammalian forebrain relative to its volume; due to its effect on pre-oligodendrocytes, prematurity impacts white matter connections and thereby the development of sources and targets of such connections, potentially including the claustrum. Third, due to its high connection degree, the claustrum contributes to general cognitive functioning (e.g., selective attention and task switching/maintaining); general cognitive functioning, however, is at risk in prematurity. Thus, we hypothesized altered claustrum structure after premature birth, with these alterations being associated with impaired general cognitive performance in premature born persons. Using T1-weighted and diffusion-weighted magnetic resonance imaging in 70 very preterm/very low-birth-weight (VP/VLBW) born adults and 87 term-born adults, we found specifically increased mean diffusivity in the claustrum of VP/VLBW adults, associated both with low birth weight and at-trend with reduced IQ. This result demonstrates altered claustrum microstructure after premature birth. Data suggest aberrant claustrum development, which is potentially related with aberrant subplate neuron and forebrain connection development of prematurity.

Sex-typical behavior in children born preterm at very low birth weight.

BACKGROUND: Perinatal events may alter psychosexual development. We aimed to assess whether a preterm birth at very low birth weight (VLBW; <1500 g) or antenatal synthetic glucocorticoids (sGC) given to the mother are associated with altered sex-typical behavior in childhood. METHODS: Sex-typical behavior was assessed using the Pre-school Activities Inventory (PSAI) at the mean age of 4.9 years (SD 1.6) in 879 children, of whom 143 were preterm with VLBW (PT <1500 g, all exposed to sGC), 282 were preterm with birth weight ≥1500 g (PT ≥1500 g, 171 exposed to sGC), and 454 were full term (FT, 166 exposed to sGC). RESULTS: Antenatal sGC was not associated with PSAI scores in either sex. PT <1500 g boys had less male-typical PSAI scores than other boys, even in multivariate model adjusting for age, maternal age, antenatal sGC, number of brothers and sisters, and motor or cognitive impairment. PT <1500 g girls had less female-typical PSAI scores than other girls in the multivariate model. The effect size was small (d = 0.03) for both sexes. CONCLUSIONS: Preterm birth with VLBW is associated with reduced sex-typical behavior in childhood, which is in line with the previous data indicating altered psychosexual development in adults born preterm. Mechanisms underlying these observations are not fully understood. IMPACT: Preterm birth is associated with reduced rates of marriage and reproduction in adulthood, but sex-typical behavior in children born preterm has not been studied before. The results of this study indicate that preterm birth with very low birth weight <1500 g is associated with reduced sex-typical behavior in childhood in both sexes. These observations are in line with the previous data indicating altered psychosexual development in adults born preterm. Mechanisms underlying these observations are not fully understood and require further studies.

Perinatal and childhood predictors of general cognitive outcome at 28 years in a very-low-birthweight national cohort.

AIM: To determine IQ at 26 to 30 years in very-low-birthweight (VLBW) adults compared with term-born controls; and to examine the stability of IQ in VLBW individuals between 7 to 8 years and 26 to 30 years, identify perinatal and social predictors of IQ, and assess the contribution of brain volume to IQ. METHOD: At 26 to 30 years, 229 VLBW adults (71% survivors of prospectively enrolled national cohort) and 100 term-born controls were tested on the Wechsler Abbreviated Scale of Intelligence. For VLBW, IQ at 7 to 8 years, perinatal and social data were extracted from the data set, and 150 adults underwent volumetric cranial magnetic resonance imaging (MRI). RESULTS: At 26 to 30 years, the mean adjusted difference between VLBW and controls for total IQ was 9.4 (95% CI 6.5-12.4) points. In VLBW individuals the correlation between IQ scores at 7 to 8 years and 26 to 30 years was 0.78. On multiple regression analysis, parental education was the strongest predictor of verbal and total IQ at both ages. Birthweight was a strong predictor of perceptual and total IQ. In VLBW individuals with MRI scans, the addition of brain volume as a variable increased the variance explained for perceptual and total IQ. INTERPRETATION: VLBW adults have mean IQ scores 9 to 11 points below controls. Parental education and birthweight are the strongest predictors of IQ.

Passive Range-of-Motion Exercise and Bone Mineralization in Preterm Infants: A Randomized Controlled Trial.

OBJECTIVE: To assess the effect of range-of-motion exercise program on bone mineralization and somatic growth of very low birth weight (VLBW) infants. STUDY DESIGN: A total of 36 VLBW infants were randomized into 18 VLBW infants receiving range-of-motion exercise and 18 VLBW control infants receiving tactile stimulation for 4 weeks. Laboratory investigations were performed at baseline and postexercise and included serum calcium, serum phosphorus (s.PO4), magnesium, alkaline phosphatase (ALP), urinary calcium/phosphate ratio, and serum carboxy-terminal cross-linked telopeptide of type 1 collagen (CTX). Dual-energy X-ray absorptiometry was performed at the end of the exercise protocol to measure bone mineral content, bone mineral density (BMD), bone area, lean mass, and fat mass. RESULTS: The weight and the rate of weight gain were significantly higher (p < 0.001) in the exercise group compared with controls postexercise. Also, higher s.PO4, lower ALP, and lower urinary calcium/phosphate ratio were observed postexercise in the exercise group (p = 0.001, p = 0.005, and p = 0.04, respectively), whereas serum CTX showed no difference between the two groups (p = 0.254). Postexercise BMD significantly improved in the exercise group (p < 0.001) compared with controls. CONCLUSION: Although the sample size was small, we may be able to suggest favorable effects of range-of-motion exercise versus tactile stimulation on bone metabolism, BMD, and short-term growth in VLBW infants.

The role of very low birth weight and prematurity on cardiovascular disease risk and on kidney development in children: a pilot study.

BACKGROUND: Cardiovascular and renal disease are nowadays among the leading cause of morbidity and mortality in Western Countries. Low birth weight has been recently considered a key factor in determining cardiovascular disease and long-term renal disease in adulthood. METHODS: In our study we analyzed, through echocardiography, eco color Doppler of carotid arteries, ultrasound of abdominal aorta and kidneys, morphological characteristics of cardiovascular and renal system, in a group of children born preterm with very low birth weight, (birth weight<1500 grams) and in a group of children, age and sex matched, born at term with weight appropriate for gestational age. Fifteen children born very low birth weight preterm (cases), aged from 3 to 5 years, and 15, age and sex matched children, born appropriate for gestational age at term (controls) were enrolled in the study. RESULTS: The two groups were homogeneous for interventricular septum diameter, left ventricular end-systolic diameter, left atrial diameter, and ejection fraction. Left ventricular end diastolic diameter was higher in case compared to controls (P=0.04), while aortic diameter root smaller (P=0.005). E and A waves peak velocities and E/A ratio resulted lower in cases compared to controls (P=0.02, P<0.001and P<0.001, respectively). Tei index, S, e' and a' waves velocities were similar in the two groups, while E/e' ratio was higher in cases (P=0.046). Intima-media thickness and antero-posterior diameter of abdominal aorta values did not differ in cases versus controls. Longitudinal diameters of both kidneys were reduced in cases compared to controls (P<0.05). CONCLUSIONS: Although limited by the small sample size, our study highlighted an increased size of the left ventricle and altered left ventricular diastolic function in children born very low birth weight preterm, but no long-term consequences on systolic performance and vascular structure have been found. The finding of smaller kidneys in ex-preterm very low birth weight children could explain their higher susceptibility to develop renal disease in adulthood.

High-dose parenteral amino acid intake in very low birthweight infants: what is the current evidence?

PURPOSE OF REVIEW: There is uncertainty regarding optimal dosing for parenteral amino acids in preterm infants and wide variability exists in clinical practice. There is new data from clinical trials trying to address these concerns. We review the recent evidence on parenteral high-dose amino acid intake in very low birth weight (VLBW) neonates with a focus on relevant clinical outcomes. RECENT FINDINGS: Preterm infants often receive less protein than intended in the first week of life. Parenteral amino acid administration in doses that exceed requirements, however, leads to increased oxidation and higher blood urea concentrations. Amino acid doses greater than 3.5 g/kg/day have not shown to improve mortality, neonatal morbidities including sepsis, necrotizing enterocolitis, chronic lung disease, growth parameters or neurodevelopmental outcomes at 2 years of age. SUMMARY: Parenteral amino acid administration in VLBW infants should be initiated soon after birth at a dose of at least 1.5 g/kg/day to maintain anabolism. The maximum dose for parenteral amino acid should be between 2.5 and 3.5 g/kg/day, with adequate nonprotein calories and micronutrients to ensure efficient protein utilization and growth.

Effects of maturation and size on population pharmacokinetics of pentoxifylline and its metabolites in very preterm infants with suspected late-onset sepsis or necrotizing enterocolitis: a pilot study incorporating clinical outcomes.

AIMS: Infection-induced inflammation is associated with adverse long-term outcomes in preterm infants. Pentoxifylline (PTX) is a candidate for adjunct immunomodulatory therapy in preterm infants with late-onset sepsis (LOS) and necrotizing enterocolitis (NEC), but pharmacokinetic data in this population are extremely limited. This study aims to characterize the pharmacokinetic properties of intravenous PTX and its metabolites in preterm infants. METHOD: An open label pilot clinical study of intravenous PTX as an adjunct therapy in preterm infants (gestation <32 weeks) with suspected LOS or NEC was undertaken. PTX was infused for 12 h for two days (60 mg kg-1 per 12 h), and in infants with confirmed diagnosis of LOS or NEC, for 6 h for another 4 days (30 mg kg-1 per 6 h). Plasma concentrations of PTX and its principal metabolites from collected blood samples were measured using a validated LCMS assay. NONMEM was used to analyse the data using population pharmacokinetic modelling. RESULTS: The preterm infants (n = 26) had a median (range) gestation of 24.8 weeks (23.3-30.4) and birthweight of 689 g (370-1285). PTX was well tolerated and without treatment-limiting adverse effects. Changes in size (weight) and maturation were successfully modelled for PTX and metabolites. After allometric scaling, clearance increased with postmenstrual age, increasing by approximately 30% per week for PTX and M1 (lisofylline) and simulations of current dosing demonstrated a six-fold difference in exposure between 24 and 35 weeks postmenstrual age. CONCLUSIONS: The developed model can be used to explore dosing strategies based on size and maturation for preterm infants.

Head Growth and Intelligence from Birth to Adulthood in Very Preterm and Term Born Individuals.

OBJECTIVES: The aim of this study was to investigate the effects of infant and toddler head growth on intelligence scores from early childhood to adulthood in very preterm (<32 weeks gestational age; VP) and/or very low birth weight (<1500 g; VLBW) and term born individuals. METHODS: 203 VP/VLBW and 198 term comparisons were studied from birth to adulthood as part of the prospective geographically defined Bavarian Longitudinal Study (BLS). Head circumference was assessed at birth; 5, 20 months; and 4 years of age. Intelligence was assessed with standardized tests in childhood (6 and 8 years: K-ABC) and at 26 years (Wechsler Adult Intelligence Scale, WAIS). Structural equation modeling (SEM) was used to model the effect of head growth on IQ. RESULTS: On average, VP/VLBW had lower head circumference at birth (27.61 cm vs. 35.11 cm, mean difference 7.49, 95% confidence interval [7.09-7.90]) and lower adult intelligence scores (88.98 vs. 102.54, mean difference 13.56 [10.59-16.53]) than term born comparison individuals. Head circumference at birth (e.g., total effect ß=.48; p<.001 for adult IQ) and head growth in childhood predicted intelligence development from age 6 to 26 years in both VP/VLBW and term born individuals (70% of variance in adult IQ explained by full model). Effects of gestation and birth weight on intelligence were fully mediated by head circumference and growth. CONCLUSIONS: This longitudinal investigation from birth to adulthood indicates head growth as a proxy of brain development and intelligence. Repeated early head circumference assessment adds valuable information when screening for long-term neurocognitive risk. (JINS, 2019, 25, 48#x2013;56).

Renal function and blood pressure are altered in adolescents born preterm.

BACKGROUND: Preterm birth increases the risk of hypertension and kidney disease. However, it is unclear when changes in blood pressure (BP) and renal function become apparent and what role obesity and sex play. We hypothesized adolescents born preterm have higher BP and worse kidney function compared to term in an obesity- and sex-dependent manner. METHODS: Cross-sectional analysis of 14-year-olds born preterm with very low birth weight (n = 96) compared to term (n = 43). We used generalized linear models to estimate the associations among preterm birth and BP, estimated glomerular filtration rate (eGFR), and ln (x) urinary albumin-to-creatinine ratio (ACR), stratified by overweight/obesity (OWO, body mass index (BMI) ≥ 85th percentile) and sex. RESULTS: Compared to term, preterm-born adolescents had higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) (adjusted ß (aß) 3.5 mmHg, 95% CI - 0.1 to 7.2 and 3.6 mmHg, 95% CI 0.1 to 7.0), lower eGFR (ß - 8.2 mL/min/1.73 m2, 95% CI - 15.9 to - 0.4), and higher ACR (aß 0.34, 95% CI - 0.04 to 0.72). OWO modified the preterm-term difference in DBP (BMI < 85th percentile aß 5.0 mmHg, 95% CI 0.7 to 9.2 vs. OWO 0.2 mmHg, 95% CI - 5.3 to 5.6) and ACR (OWO aß 0.72, 95% CI 0.15 to 1.29 vs. BMI < 85th percentile 0.17, 95% CI - 0.31 to 0.65). Sex modified the preterm-term ACR difference (female aß 0.52, 95% CI 0.001 to 1.04 vs. male 0.18, 95% CI - 0.36 to 0.72). CONCLUSIONS: Prematurity was associated with higher BP and reduced renal function that were detectable in adolescence. OWO and sex may modify the strength of these relationships.

Joint Analysis of Cortical Area and Thickness as a Replacement for the Analysis of the Volume of the Cerebral Cortex.

Cortical surface area is an increasingly used brain morphology metric that is ontogenetically and phylogenetically distinct from cortical thickness and offers a separate index of neurodevelopment and disease. However, the various existing methods for assessment of cortical surface area from magnetic resonance images have never been systematically compared. We show that the surface area method implemented in FreeSurfer corresponds closely to the exact, but computationally more demanding, mass-conservative (pycnophylactic) method, provided that images are smoothed. Thus, the data produced by this method can be interpreted as estimates of cortical surface area, as opposed to areal expansion. In addition, focusing on the joint analysis of thickness and area, we compare an improved, analytic method for measuring cortical volume to a permutation-based nonparametric combination (NPC) method. We use the methods to analyze area, thickness and volume in young adults born preterm with very low birth weight, and show that NPC analysis is a more sensitive option for studying joint effects on area and thickness, giving equal weight to variation in both of these 2 morphological features.

Reproducibility of the assessment of myocardial function through tissue Doppler imaging in very low birth weight infants.

OBJECTIVES: This study aims to analyze the variability between two trained neonatologists when performing consecutive echocardiograms using tissue Doppler imaging (TDI) and conventional methods in very low birth weight infant (VLBWI). METHODS: Two serial echocardiograms were performed in 30 VLBWI infants. The echocardiographic parameters analyzed were tricuspid annular plane systolic excursion (TAPSE), A', E', and S' waves, and myocardial performance index acquired by TDI (MPI-TDI) of both ventricles and shortening fraction (SF). The intra-observer and inter-observer agreements and the intra-operator agreement were analyzed using quantitative and qualitative statistical methods. RESULTS: The intra-observer agreement was very good, TAPSE, and TDI-derived parameters had an intra-class correlation (ICC) > 0.8. TDI-derived velocities had a coefficient of variation (COV) < 11%, while MPI-TDI had a COV between 20%-28%. The inter-observer agreement was excellent. There was greater variability when analyzing intra-operator agreement, with the least variable parameter being TAPSE. According to PABAK, the variability presented moderately substantial agreement. CONCLUSIONS: Tricuspid annular plane systolic excursion is very reproducible between observers and operators. Measurements of TDI wave velocities are more reproducible than MPI-TDI. TDI is sufficiently reproducible in the VLBWI if adequate training is performed, and guidelines are followed to obtain standardized echocardiographic images.

Relationships of biological and environmental factors to cognition of preterm infants in the toddler and preschool periods.

One hundred and nine preterm infants were studied to examine the relative effects of biologic/neurologic factors (length of hospital stay, 18 month cognitive status) and environment (socioeconomic status) on cognition in the toddler (18 months) and preschool periods (3 years). Length of hospital stay was significantly related to toddler cognitive outcome, and less so to preschool outcome. Socioeconomic status predicted only preschool cognitive outcome and not toddler outcome. Cognitive status at 18 months significantly predicted 3 year outcome, and there was relatively little change between those periods. Together, cognitive status at 18 months and socioeconomic status significantly predicted preschool IQ, accounting for 34% of the variance. Results showed that perinatal biologic risks became less salient while socioeconomic status became increasingly important at the preschool period. Relative lack of change in cognitive status indicated the importance of early cognitive evaluation in preterm infants.

An Open-label Randomized Controlled Trial to Compare Weight Gain of Very Low Birth Weight Babies with or without Addition of Coconut Oil to Breast Milk.

Background: Nutritional guidelines involving the feeding of very low birth weight babies (VLBW) recommend addition of Human Milk Fortifiers to breast milk. Owing to financial constraints, it is a practice in low- and middle-income countries (LMIC) to add coconut oil to aid better weight gain. There are inadequate data on improvement of growth parameters with oral coconut oil supplementation of breast milk. Methods: In this randomized controlled trial, we measured growth parameters and body composition of 60 babies who received either breast milk with coconut oil or breast milk alone. Randomization was stratified according to intrauterine growth appropriate for gestational age (n = 30) and small for gestational age (n = 30). Results: There was no difference in weight gain between the two groups. The weight gain velocity was 15 ± 3.6 and 14.4 ± 3.4 g/kg/day (p value = 0.49) in the breast milk alone and in the breast milk with coconut oil group, respectively. There was no difference in increase in head circumference and length. Triceps skinfold thickness (n = 56) was similar in both groups, but subscapular skinfold thickness was significantly more in the coconut oil group. Total body fat percentage did not differ between the groups (25.2 ± 4.3 vs. 25.5 ± 4.3%, p = 0.79). Conclusion: Oral supplementation of coconut oil along with breast milk did not increase growth parameters or result in change in body composition in very low birth weight (VLBW) babies.

Neurodevelopmental Outcomes of Very Low Birth Weight Infants at 18-24 Months, Corrected Gestational Age in a Tertiary Health Centre: A Prospective Cohort Study.

OBJECTIVE: To determine the prevalence and risk factors for poor neurodevelopmental outcome in a cohort of very low birth weight (VLBW) infants. SUBJECTS AND METHODS: Four hundred and twenty-two infants of a total of 643 VLBW survivors from a teaching hospital in South India were followed up to assess their neurodevelopmental outcomes. RESULTS: Among the 422 children who completed the assessment, results of 359 children whose assessments were done between 18 and 24 months were analysed. Thirty-seven children (10.31%) had poor neurodevelopmental outcome, six children [1.67%] had cerebral palsy, one child had visual impairment and another had hearing impairment. Poor post-natal growth was independently associated with poor neurodevelopmental outcomes in the multivariate analysis (p = 0.045). Neonatal complications were not associated with the developmental outcome. CONCLUSION: Despite lower rates of neonatal complications compared with Western cohorts, significant proportion of VLBW infants had poor neurodevelopmental outcomes. Poor post-natal growth was an important determinant of the developmental outcome.

Donor Breast Milk for the Preterm Infant: Your Questions Answered!

Expressed breast milk (EBM) is the gold standard of infant nutrition, but is not always available for use for preterm infants in the NICU setting. Donor breast milk (DBM) is often a preferred alternative for preterm and very low birth weight (VLBW) infants when maternal milk is not available. This article discusses the composition of DBM, reviews its advantages compared to formula, discusses challenges related to its long-term use, and identifies strategies to utilize DBM in the context of total nutritional management of preterm and VLBW infants. We will use a framework of WHO, WHAT, WHERE, WHEN, and WHY to answer the questions: who gets DBM, why use DBM, where does DBM come from, what is in DBM, and when may DBM use be challenged.

Is Donated Breast Milk Better Than Formula for Feeding Very Low Birth Weight Infants? A Systematic Review and Meta-Analysis.

BACKGROUND: The role of donated breast milk and formula feeding in very low birth weight infants (VLBWIs) remains unclear. OBJECTIVE: The objective for this study was to evaluate the efficacy and safety of breast milk and formula for feeding VLBWIs. METHODS: A comprehensive search of PubMed databases was conducted on November 30, 2018, to identify related randomized controlled trials (RCTs). Pooled odds ratio (OR) and mean differences (MD) with 95% confidence intervals (CI) were calculated using either a fixed or random-effects model. RESULTS: Seven RCTs with a total of 876 infants were included. The formula showed more advantages in increasing infant weight (MD = -6.58, 95% CI: -11.19 to -1.98) and length (MD = -0.30, 95% CI: -0.41 to -0.20) than donated breast milk, but formula could also significantly increase the risks of necrotizing enterocolitis (OR = 0.33, 95% CI: 0.18 to 0.59) and length of hospital stay (MD = -3.78, 95% CI: -6.84 to -0.72) when compared with donated breast milk. No significant differences on the head circumference gain (MD = -0.16, 95% CI: -0.33 to 0.01), sepsis (OR = 1.21, 95% CI: 0.84 to 1.75), retinopathy of prematurity (OR = 1.22, 95% CI: 0.73 to 2.05) and mortality (OR = 0.84, 95% CI: 0.47 to 1.52) were found. LINKING EVIDENCE TO ACTION: The donated breast milk shows more advantages in reducing the incidence of NEC and length of hospital stay, but also more disadvantages in increasing the weight and length of VLBWIs and ELBWIs when compared with preterm formula feeding. Currently, there is no solid evidence demonstrating a significant advantage of donated breast milk over formula in the feeding of VLBWIs. Larger-scale RCTs with rigorous designs are needed to elucidate the feeding plans of VLBWIs.

Preterm birth leads to hyper-reactive cognitive control processing and poor white matter organization in adulthood.

Individuals born preterm with very low birth weight (VLBW; birth weight ≤ 1500 g) are at high risk for perinatal brain injuries and deviant brain development, leading to increased chances of later cognitive, emotional, and behavioral problems. Here we investigated the neuronal underpinnings of both reactive and proactive cognitive control processes in adults with VLBW. We included 32 adults born preterm with VLBW (before 37th week of gestation) and 32 term-born controls (birth weight ≥10th percentile for gestational age) between 22 and 24 years of age that have been followed prospectively since birth. Participants performed a well-validated Not-X continuous performance test (CPT) adapted for use in a mixed block- and event-related fMRI protocol. BOLD fMRI and DTI data was acquired on a 3T scanner. Performance on the Not-X CPT was highly similar between groups. However, the VLBW group demonstrated hyper-reactive cognitive control processing and disrupted white matter organization. The hyper-reactive brain activation signature in VLBW adults was associated with lower gestational age, lower fluid intelligence score, and anxiety problems. Automated Multi-Atlas Tract Extraction (AutoMATE) analyses revealed that this disruption of normal brain function was accompanied by poorer white matter organization in the anterior thalamic radiation and the cingulum, as reflected in both reduced fractional anisotropy and increased mean diffusivity. These findings show that the preterm behavioral phenotype is associated with predominantly reactive-, rather than proactive cognitive control processing, as well as white matter abnormalities, that may underlie common difficulties that many preterm born individuals experience in everyday life.

Decreased BOLD fluctuations in lateral temporal cortices of premature born adults.

Lasting volume reductions in subcortical and temporal-insular cortices after premature birth suggest altered ongoing activity in these areas. We hypothesized altered fluctuations in ongoing neural excitability and activity, as measured by slowly fluctuating blood oxygenation of resting-state functional MRI (rs-fMRI), in premature born adults, with altered fluctuations being linked with underlying brain volume reductions. To investigate this hypothesis, 94 very preterm/very low birth weight (VP/VLBW) and 92 full-term born young adults underwent structural and rs-fMRI data acquisition with voxel-based morphometry and amplitude of low-frequency fluctuations (ALFF) as main outcome measure. In VP/VLBW adults, ALFF was reduced in lateral temporal cortices, and this reduction was positively associated with lower birth weight. Regions of reduced ALFF overlapped with reduced brain volume. On the one hand, ALFF reduction remained after controlling for volume loss, supporting the functional nature of ALFF reductions. On the other hand, ALFF decreases were positively associated with underlying brain volume loss, indicating a relation between structural and functional changes. Furthermore, within the VP/VLBW group, reduced ALFF was associated with reduced IQ, indicating the behavioral relevance of ALFF decreases in temporal cortices. These results demonstrate long-term impact of premature birth on ongoing BOLD fluctuations in lateral temporal cortices, which are linked with brain volume reductions. Data suggest permanently reduced fluctuations in ongoing neural excitability and activity in structurally altered lateral temporal cortices after premature birth.