Weight shapes the intestinal microbiome in preterm infants: results of a prospective observational study

Background The intestinal microbiome in preterm infants differs markedly from term infants. It is unclear whether the microbiome develops over time according to infant specific factors. Methods We analysed (clinical) metadata - to identify the main factors influencing the microbiome composition development - and the first meconium and faecal samples til the 4th week via 16 S rRNA amplican sequencing. Results We included 41 infants (gestational age 25–30 weeks; birth weight 430-990 g. Birth via Caesarean section (CS) was associated with placental insufficiency during pregnancy and lower BW. In meconium samples and in samples from weeks 2 and 3 the abundance of Escherichia and Bacteroides (maternal faecal representatives) were associated with vaginal delivery while Staphylococcus (skin microbiome representative) was associated with CS. Secondly, irrespective of the week of sampling or the mode of birth, a transition was observed as children children gradually increased in weight from a microbiome dominated by Staphylococcus (Bacilli) towards a microbiome dominated by Enterobacteriaceae (Gammaproteobacteria). Conclusions Our data show that the mode of delivery affects the meconium microbiome composition. They also suggest that the weight of the infant at the time of sampling is a better predictor for the stage of progression of the intestinal microbiome development/maturation than postconceptional age as it less confounded by various infant-specific factors.

Weight Shapes the Intestinal Microbiome in Preterm Infants: Results of a Prospective Observational Study

Background: The intestinal microbiome in preterm infants differs markedly from term infants. It is unclear whether the microbiome develops over time according to infant specific factors. Methods: We analysed (clinical) metadata - to identify the main factors influencing the microbiome composition development - and the first meconium and feacal samples til the 4th week via 16S rRNA amplican sequencing. Results: We included 41 infants (gestational age 25-30 weeks; birth weight 430-990g. Birth via Caesarean section (CS) was associated with placental insufficiency during pregnancy and lower BW. In meconium and in weeks 2 and 3 an increased combined abundance of Escherichia and Bacteroides (maternal fecal representatives) was associated with vaginal delivery (p=0.021, p=0.0002, p=0.028, respectively) while Staphylococcus (skin microbiome representative) was associated with CS (p=0.0008, p=0.0003 p=0.046, respectively). Secondly, irrespective of the week of sampling or the mode of birth, a transition was observed as children children gradually increased in weight from a microbiome dominated by Staphylococcus (Bacilli) towards a microbiome dominated by Enterobacteriaceae (Gammaproteobacteria). Conclusions: Mode of delivery affects the meconium microbiome composition. It also suggests that the weight of the infant at the time of sampling is a better predictor for the stage of progression of the intestinal microbiome development/maturation than postconceptional age.

Improving long-term health outcomes of preterm infants: how to implement the findings of nutritional intervention studies into daily clinical practice

Preterm-born children are at risk for later neurodevelopmental problems and cardiometabolic diseases; early-life growth restriction and suboptimal neonatal nutrition have been recognized as risk factors. Prevention of these long-term sequelae has been the focus of intervention studies. High supplies of protein and energy during the first weeks of life (i.e., energy > 100 kcal kg−1 day−1 and a protein-to-energy ratio > 3 g/100 kcal) were found to improve both early growth and later neurodevelopmental outcome. Discontinuation of this high-energy diet is advised beyond 32–34 weeks postconceptional age to prevent excess fat mass and possible later cardiometabolic diseases. After discharge, nutrition with a higher protein-to-energy ratio (i.e., > 2.5–3.0 g/100 kcal) may improve growth and body composition in the short term.Conclusion: Preterm infants in their first weeks of life require a high-protein high-energy diet, starting shortly after birth. Subsequent adjustments in nutritional composition, aimed at achieving optimal body composition and minimizing the long-term cardiometabolic risks without jeopardizing the developing brain, should be guided by the growth pattern. The long-term impact of this strategy needs to be studied. What is Known:• Preterm infants are at risk for nutritional deficiencies and extrauterine growth restriction.• Extrauterine growth restriction and suboptimal nutrition are risk factors for neurodevelopmental problems and cardiometabolic disease in later life. What is New:• Postnatally, a shorter duration of high-energy nutrition may prevent excess fat mass accretion and its associated cardiometabolic risks and an early switch to a protein-enriched diet should be considered from 32-34 weeks postconceptional age.• In case of formula feeding, re-evaluate the need for the continuation of a protein-enriched diet, based on the infant’s growth pattern.

Earlier preterm birth is associated with a worse neurocognitive outcome in a rabbit model

Background Preterm birth (PTB) and particularly late preterm PTB has become a research focus for obstetricians, perinatologists, neonatologists, pediatricians and policy makers alike. Translational models are useful tools to expedite and guide clinical but presently no model exists that contextualizes the late PTB scenario. Herein we aimed to develop a rabbit model that echo’s the clinical neurocognitive phenotypes of early and late PTB. Methods Time mated rabbit does underwent caesarean delivery at a postconceptional age (PCA) of either 28 (n = 6), 29 (n = 5), 30 (n = 4) or 31 (n = 4) days, term = 31 d. Newborn rabbits were mixed and randomly allocated to be raised by cross fostering and underwent short term neurobehavioral testing on corrected post-natal day 1. Open field (OFT), spontaneous alteration (TMT) and novel object recognition (NORT) tests were subsequently performed at 4 and 8 weeks of age. Results PTB was associated with a significant gradient of short-term mortality and morbidity inversely related to the PCA. On postnatal day 1 PTB was associated with a significant sensory deficit in all groups but a clear motor insult was only noted in the PCA 29d and PCA 28d groups. Furthermore, PCA 29d and PCA 28d rabbits had a persistent neurobehavioral deficit with less exploration and hyperanxious state in the OFT, less alternation in TMT and lower discriminatory index in the NORT. While PCA 30d rabbits had some anxiety behavior and lower spontaneous alteration at 4 weeks, however at 8 weeks only mild anxiety driven behavior was observed in some of these rabbits. Conclusions In this rabbit model, delivery at PCA 29d and PCA 28d mimics the clinical phenotype of early PTB while delivery at PCA 30d resembles that of late PTB. This could serve as a model to investigate perinatal insults during the early and late preterm period.

Fifteen-minute consultation: Neonatal hypertension

Neonatal hypertension is a rare but well recognised condition, especially in newborns needing invasive monitoring in the intensive care unit. Recognition of newborns with hypertension remains challenging because of natural variability in blood pressure with postconceptional age and the lack of reference data for different gestational ages. Investigation of neonates with hypertension can be challenging in light of the myriad differing aetiologies. This may be simplified by a systematic approach to investigation. There remains a relative paucity of data to guide the use of pharmacological therapies for hypertension in neonates. Clinicians rely on empirical management protocols based on experience and expert opinion. Much of the information on dosing regimens and protocols has simply been derived from the use of antihypertensive agents in older children and in adults, despite fundamental pathophysiological differences.

New Paradigm in Abilitation of Premature Children with Perinatal Pathology — Therapeutic Stages Personalization: Cohort Study

Background. The abilitation of premature infants acquires importance due to the increased prevalence of delayed health disorders in these children. The article considers the issues of individualization of rehabilitation treatment for premature infants according to prediction of perinatal pathology outcomes, determining the individual levels of «abilitation windows» and developing personalized abilitation programs.Objective. The aim of the study was to determine individual timely sensitive ontogenesis stages («abilitation windows») for premature children with various perinatal pathology, as well as the most effective methods of rehabilitation treatment according to the maturity of the child and the type of neurosomatic deficiency.Methods. Two-stage cohort study of premature children with gestational age of 250–6–300–6 weeks was conducted. Stage 1 — retrospective analysis of «abilitation windows» in 115 premature children, development of prognostic scenarios. Stage 2 — prospective cohort study of 109 premature children, using abilitation methods in this cohort according to predicted events and estimation of abilitation efficacy. Medical interventions: familyoriented educational counseling, kinesiotherapy, physiotherapy, neuroprotectors, music therapy.Results. Information matrixes on filling ontogenetic abilitation periods have been developed, as well as age limits for «abilitation windows» have been defined on the 1st stage. Sensitive interval has been established for the use of stimulating effects in extremely immature children (postconceptional age of 34–37 weeks). The leading role of abilitation protective measures has been identified. Perinatal pathology outcomes have been analyzed in children from retrospective analysis group. Direct abilitation of premature children (from birth to 18 months) was carried out on the 2nd stage of the study according to probability forecasts. The priority of non-drug abilitation methods usage in immature children was confirmed. The need in step-by-step dynamic correction of abilitation programs was established.Conclusion. Prognostic significance of perinatal period events and individual postconceptional age in «abilitation windows» development for premature children was determined. The priority of non-drug abilitation for such patients (including family-oriented pedagogics) is established.

Periventricular Venous Infarction in an Extremely Premature Infant as the Cause of Schizencephaly

Schizencephaly is a disorder of neuronal migration which has been hypothesized to arise from vascular ischemic lesion during the early phase of neuroembryogenesis. We describe a case of a premature boy born at 23 weeks of gestation with neonatal stroke. On the first day of life cranial ultrasonography detected a grade II intraventricular hemorrhage and on day 12 periventricular venous infarction. At the postconceptional age of 40 weeks, magnetic resonance imaging revealed a gray matter–lined cleft, suggesting schizencephaly. We have evidence of the pathogenesis of schizencephaly following vascular ischemic stroke early in neurodevelopment before neuronal migration is completed.

Bovine Milk Oligosaccharides with Sialyllactose Improves Cognition in Preterm Pigs

Optimal nutrition is important after preterm birth to facilitate normal brain development. Human milk is rich in sialic acid and preterm infants may benefit from supplementing formula with sialyllactose to support neurodevelopment. Using pigs as models, we hypothesized that sialyllactose supplementation improves brain development after preterm birth. Pigs (of either sex) were delivered by cesarean section at 90% gestation and fed a milk diet supplemented with either an oligosaccharide-enriched whey with sialyllactose (n = 20) or lactose (n = 20) for 19 days. Cognitive performance was tested in a spatial T-maze. Brains were collected for ex vivo magnetic resonance imaging (MRI), gene expression, and sialic acid measurements. For reference, term piglets (n = 14) were artificially reared under identical conditions and compared with vaginally born piglets naturally reared by the sow (n = 12). A higher proportion of sialyllactose supplemented preterm pigs reached the T-maze learning criteria relative to control preterm pigs (p < 0.05), and approximated the cognition level of term reference pigs (p < 0.01). Furthermore, supplemented pigs had upregulated genes related to sialic acid metabolism, myelination, and ganglioside biosynthesis in hippocampus. Sialyllactose supplementation did not lead to higher levels of sialic acid in the hippocampus or change MRI endpoints. Contrary, these parameters were strongly influenced by postconceptional age and postnatal rearing conditions. In conclusion, oligosaccharide-enriched whey with sialyllactose improved spatial cognition, with effects on hippocampal genes related to sialic acid metabolism, myelination, and ganglioside biosynthesis in preterm pigs. Dietary sialic acid enrichment may improve brain development in infants.