Maternal One-carbon Metabolism during the Periconceptional Period and Human Foetal Brain Growth: A Systematic Review

The maternal environment during the periconceptional period influences foetal growth and development, in part, via epigenetic mechanisms moderated by one-carbon metabolic pathways. During embryonic development, one-carbon metabolism is involved in brain development and neural programming. Derangements in one-carbon metabolism increase (i) the short-term risk of embryonic neural tube-related defects and (ii) long-term childhood behaviour, cognition, and autism spectrum disorders. Here we investigate the association between maternal one-carbon metabolism and foetal and neonatal brain growth and development. Database searching resulted in 26 articles eligible for inclusion. Maternal vitamin B6, vitamin B12, homocysteine, and choline were not associated with foetal and/or neonatal head growth. First-trimester maternal plasma folate within the normal range (> 17 nmol/L) associated with increased foetal head size and head growth, and high erythrocyte folate (1538–1813 nmol/L) with increased cerebellar growth, whereas folate deficiency (< 7 nmol/L) associated with a reduced foetal brain volume. Preconceptional folic acid supplement use and specific dietary patterns (associated with increased B vitamins and low homocysteine) increased foetal head size. Although early pregnancy maternal folate appears to be the most independent predictor of foetal brain growth, there is insufficient data to confirm the link between maternal folate and offspring risks for neurodevelopmental diseases.

Developmental Outcomes of Very Low Birth Weight Infants with Catch-up Head Growth: A Nationwide Cohort Study

This study aims to determine demographic or perinatal characteristics in premature infant according to head growth, identify clinical factors affecting growth catch-up, and find differences in developmental outcomes according to catch-up states based on Korean Neonatal Network (KNN) data. This nationwide prospective cohort study of Korean Neonatal Network (KNN) data analyzed premature infants with very low birth weight (< 1,500 g) between 2014 and 2017. A total of 253 eligible infants who had completed Bayley scales of infant and toddler development (BSID) 3rd were assigned into two groups: a catch-up (CU) group with head circumference above the 10th percentile and a no catch-up (NCU) group with head circumference below the 10th percentile at 18-24 months of corrected age (CA). Most (81.4%, 203/253) premature infants exhibited catch-up growth at 18-24 months of CA. Rates of microcephaly, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), sepsis, necrotizing enterocolitis (NEC), length of NICU stay, ventilation care, and parenteral nutrition were significantly greater in the NCU group (P < 0.05). On multiple linear regression analysis, the BPD status was the most clinical factor affecting catch-up head growth after adjusting for gestational age, birth weight, and birth head circumference (adjusted OR 4.586, 95% CI 1.960-10.729)At 18-24 months of CA, the NCU group exhibited lower developmental indices and higher rate of developmental delay than the CU group. Motor developmental delay was the most significant factor relevant to catch-up head growth and the motor development index difference between the two groups was only statistically significant after adjusting for four major neonatal morbidities: IVH, BPD, sepsis, and NEC status (adjusted OR 10.727, 95% CI 1.922-59.868). Thus, the developmental outcome of very low birth weight (VLBW) infants at 18-24 months of CA might be dependent on whether head growth was caught up. Key clinical factors determining the catch-up status were BPD and NEC status, length of parenteral nutrition, and ventilator care. Thus, measurements of head circumference at 18-24 months of CA can predict developmental delays of VLBW infants.

Head Growth and Neurodevelopment of Preterm Infants with Surgical Necrotizing Enterocolitis and Spontaneous Intestinal Perforation

Spontaneous intestinal perforation (SIP) and surgical necrotizing enterocolitis (NEC) are intestinal conditions requiring surgical intervention in preterm infants. We aimed to compare the head growth and neurodevelopment of preterm infants with SIP and surgical NEC. A retrospective single-center study was performed in preterm infants born at less than 32 weeks of gestation and who had undergone surgery for NEC or SIP. Data from the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) at 24 months of corrected age (CA) and the Korean Ages and Stages Questionnaire (K-ASQ) or Korean Developmental Screening Test (K-DST) at 36 months were collected. Among 82 eligible infants, 60 infants had surgical NEC, and 22 infants were diagnosed with SIP. Head growth was faster until CA 4 months in preterm infants with SIP than in those with surgical NEC. At 36 months, abnormal findings in the K-ASQ or K-DST were more prevalent in the NEC group than in the SIP group in the gross motor (48.2% vs. 0%, p = 0.015), fine motor (40.7% vs. 0%, p = 0.037), cognitive (55.6% vs. 12.5%, p = 0.047), and social domains (44.4% vs. 0%, p = 0.032). More studies evaluating the neurodevelopmental outcomes of preterm infants with surgical NEC and SIP are required.

Growth in extremely preterm children born in England in 1995 and 2006: the EPICure studies

ObjectivesTo determine growth outcomes at 11 years of age in children born <27 weeks of gestation in England in 2006 (EPICure2) and to compare growth from birth to 11 years of age for births<26 weeks with those in England in 1995 (EPICure).Methods200 EPICure2 children assessed at 11 years alongside 143 term-born controls. Growth measures from birth to 11 years were compared for births<26 weeks between EPICure2 (n=112) and EPICure (n=176). Growth parameter z-scores were derived from 1990 UK standards.ResultsAmong EPICure2 children, mean z-scores for height and weight were close to the population standards (0.08 and 0.18 SD, respectively) but significantly below those of controls: difference in mean (Δ) z-scores for weight −0.42 SD (95% CI −0.68 to –0.17), for height −0.45 SD (−0.70 to –0.20) and for head circumference (HC) −1.05 SD (−1.35 to –0.75); mean body mass index (BMI) z-score in EPICure2 children was 0.18 SD, not significantly different from controls (0.43 SD, p=0.065). Compared with EPICure, EPICure2 children born <26 weeks at 11 years had higher z-scores for weight (Δ 0.72 (0.47, 0.96)), height (Δ 0.55 (0.29, 0.81)) and BMI (Δ 0.56 (0.24, 0.87)), which were not fully explained by perinatal/demographic differences between eras. Weight catch-up was greater from term-age to 2.5/3 years in EPICure2 than in EPICure (1.25 SD vs 0.53 SD; p<0.001). Poor HC growth was observed in EPICure2, unchanged from EPICure.ConclusionsSince 1995, childhood growth in weight, height and BMI have improved for births <26 weeks of gestation, but there was no improvement in head growth.

Lactobacillus reuteri Colonisation of Extremely Preterm Infants in a Randomised Placebo-Controlled Trial

Lactobacillus reuteri DSM 17938 supplementation reduces morbidities in very low birth weight infants (<1500 g), while the effect on extremely low birth weight infants (ELBW, <1000 g) is still questioned. In a randomised placebo-controlled trial (ClinicalTrials.gov ID NCT01603368), head growth, but not feeding tolerance or morbidities, improved in L. reuteri-supplemented preterm ELBW infants. Here, we investigate colonisation with the probiotic strain in preterm ELBW infants who received L. reuteri DSM 17938 or a placebo from birth to postmenstrual week (PMW) 36. Quantitative PCR was used on 582 faecal DNA samples collected from 132 ELBW infants at one, two, three, and four weeks, at PMW 36, and at two years of age. Human milk oligosaccharides were measured in 31 milk samples at two weeks postpartum. At least 86% of the ELBW infants in the L. reuteri group were colonised with the probiotic strain during the neonatal period, despite low gestational age, high antibiotic pressure, and independent of infant feeding mode. Higher concentrations of lacto-N-tetraose, sialyl-lacto-N-neotetraose c, and 6′-sialyllactose in mother’s milk weakly correlated with lower L. reuteri abundance. Within the L. reuteri group, higher L. reuteri abundance weakly correlated with a shorter time to reach full enteral feeding. Female sex and L. reuteri colonisation improved head growth from birth to four weeks of age. In conclusion, L. reuteri DSM 17938 supplementation leads to successful colonisation in ELBW infants.

Head circumference trajectory in children with perinatal stroke

Background: Perinatal stroke is a leading cause of hemiparetic cerebral palsy and lifelong disability. Neurodevelopmental outcomes are difficult to predict and markers of long-term poor outcome continue to be investigated. Deceleration in growth of head circumference has been associated with worse developmental outcomes in neonatal brain injury. We hypothesized that perinatal stroke would result in decreased rates of head growth during childhood that would be associated with worse developmental outcomes. Methods: Patients with magnetic resonance imaging (MRI)–confirmed neonatal arterial ischemic stroke and arterial presumed perinatal ischemic stroke were identified from a population-based research cohort (Alberta Perinatal Stroke Project). Demographics and occipital-frontal circumference data were collected from medical records. Head growth was compared to typically developing control charts using a 2-tailed t test. The Fisher exact test was used to examine associations between Pediatric Stroke Outcome Measures (PSOM) scores and occipital-frontal head circumference. Results: Three hundred fifteen occipital-frontal head circumference measurements were collected from 102 patients (48 female, 54 male), over a median of 3.2 years (standard deviation = 5.18, range = 0-18.3). After 3 months for female patients and 1 year for male patients, occipital-frontal head circumference deviated and remained below normal growth trajectories ( P < .05) with a large effect size (Cohen d >0.8). Poor outcome (PSOM ≥ 1) was associated with smaller occipital-frontal head circumference ( P < .05). Conclusion: Head growth deceleration is observed in children with perinatal arterial ischemic stroke and is associated with poor outcome. Head circumference may be a tool to alert clinicians to the potential of abnormal neurologic outcome.

Early diet in preterm infants and later cognition: 10-year follow-up of a randomized controlled trial

Background Achieving adequate nutrition in preterm infants is challenging. The post-discharge period may be critical for influencing growth and cognitive outcomes. We studied the effects of post-discharge nutrition on childhood cognition. Methods Preterm-born children were randomized at ~36 weeks corrected age (CGA) to either preterm formula (PTF) or term formula (TF) until 6 months, or PTF until 40 weeks CGA, then TF until 6 months (crossover group). Childhood cognition was assessed using the short form Wechsler Intelligence Scale for Children III, allowing computation of full-scale intelligence quotient (FSIQ) and four-factor index scores; verbal comprehension, freedom from distractibility (FDI), perceptual organization (POI), and processing speed (PSI). Results Ninety-two children were recruited (mean 10.1 years). FSIQ did not differ by group. PTF-fed children had 10-point higher PSI (p = 0.03) compared to crossover. Faster weight gain from term to 12 weeks CGA was associated with 5-point higher FSIQ (p = 0.02) and four-point higher POI (p = 0.04). Infant head growth was positively associated with FSIQ (+3.8 points, p = 0.04) and FDI (+6 points, p = 0.003). Conclusions While there is no long-term impact of post-discharge macronutrient enrichment on childhood cognition, greater weight and head growth in specific epochs is associated with better outcomes. Further studies are needed to determine optimal early diet in preterm infants. Impact Achieving adequate nutrient intakes in preterm infants before and after hospital discharge is challenging. Nutrient intakes prior to discharge affect later cognitive and metabolic outcomes. Follow-up of a randomized controlled trial shows no cognitive benefit in later childhood from a more nutrient-dense formula compared to standard formula after hospital discharge. Growth in the first year of life is strongly correlated with childhood cognition and emphasizes the importance of nutrition in early life.