Birth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potential.

The rate of caesarean section delivery (CSD) is increasing worldwide. It remains unclear whether disruption of mother-to-neonate transmission of microbiota through CSD occurs and whether it affects human physiology. Here we perform metagenomic analysis of earliest gut microbial community structures and functions. We identify differences in encoded functions between microbiomes of vaginally delivered (VD) and CSD neonates. Several functional pathways are over-represented in VD neonates, including lipopolysaccharide (LPS) biosynthesis. We link these enriched functions to individual-specific strains, which are transmitted from mothers to neonates in case of VD. The stimulation of primary human immune cells with LPS isolated from early stool samples of VD neonates results in higher levels of tumour necrosis factor (TNF-α) and interleukin 18 (IL-18). Accordingly, the observed levels of TNF-α and IL-18 in neonatal blood plasma are higher after VD. Taken together, our results support that CSD disrupts mother-to-neonate transmission of specific microbial strains, linked functional repertoires and immune-stimulatory potential during a critical window for neonatal immune system priming.

Colonization and Succession within the Human Gut Microbiome by Archaea, Bacteria, and Microeukaryotes during the First Year of Life.

Perturbations to the colonization process of the human gastrointestinal tract have been suggested to result in adverse health effects later in life. Although much research has been performed on bacterial colonization and succession, much less is known about the other two domains of life, archaea, and eukaryotes. Here we describe colonization and succession by bacteria, archaea and microeukaryotes during the first year of life (samples collected around days 1, 3, 5, 28, 150, and 365) within the gastrointestinal tract of infants delivered either vaginally or by cesarean section and using a combination of quantitative real-time PCR as well as 16S and 18S rRNA gene amplicon sequencing. Sequences from organisms belonging to all three domains of life were detectable in all of the collected meconium samples. The microeukaryotic community composition fluctuated strongly over time and early diversification was delayed in infants receiving formula milk. Cesarean section-delivered (CSD) infants experienced a delay in colonization and succession, which was observed for all three domains of life. Shifts in prokaryotic succession in CSD infants compared to vaginally delivered (VD) infants were apparent as early as days 3 and 5, which were characterized by increased relative abundances of the genera Streptococcus and Staphylococcus, and a decrease in relative abundance for the genera Bifidobacterium and Bacteroides. Generally, a depletion in Bacteroidetes was detected as early as day 5 postpartum in CSD infants, causing a significantly increased Firmicutes/Bacteroidetes ratio between days 5 and 150 when compared to VD infants. Although the delivery mode appeared to have the strongest influence on differences between the infants, other factors such as a younger gestational age or maternal antibiotics intake likely contributed to the observed patterns as well. Our findings complement previous observations of a delay in colonization and succession of CSD infants, which affects not only bacteria but also archaea and microeukaryotes. This further highlights the need for resolving bacterial, archaeal, and microeukaryotic dynamics in future longitudinal studies of microbial colonization and succession within the neonatal gastrointestinal tract.

Familial very long chain acyl-CoA dehydrogenase deficiency as a cause of neonatal sudden infant death: improved survival by prompt diagnosis.

In neonates, very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is often characterized by cardiomyopathy, hepatic encephalopathy, or severe hypoketotic hypoglycemia, or a combination thereof. The purpose of this study was to further elucidate a familial VLCAD deficiency in three patients, two of whom died in the neonatal period. We report on a family with VLCAD deficiency. Acyl-carnitine profiles were obtained from dried blood spot and/or from oxidation of (13) C-palmitate by cultured skin fibroblasts. In the index patient, VLCAD deficiency was ascertained by enzyme activity measurement in fibroblasts and by molecular analysis of ACADVL. At 30 hr of life, the proband was diagnosed with hypoglycemia (1.77 mmol/L), rhabdomyolysis (CK: 12966 IU/L) and hyperlactacidemia (10.6 mmol/L). Acylcarnitine profile performed at 31 hr of life was consistent with VLCAD deficiency and confirmed by cultured skin fibroblast enzyme activity measurement. Molecular analysis of ACADVL revealed a homozygous splice-site mutation (1077 + 2T>C). The acyl-carnitine profile obtained from the sibling's original newborn screening cards demonstrated a similar, but less pronounced abnormal profile. In the proband, the initial metabolic crisis was controlled with 10% dextrose solution and oral riboflavin followed by specific diet (Basic-F and medium chain triglyceride (MCT). This clinical report demonstrates a familial history of repeated neonatal deaths explained by VLCAD deficiency, and the clinical evolution of the latest affected, surviving sibling. It shows that very early metabolic screening is an effective approach to avoid sudden unexpected death.

Antiviral Drug-Resistance Typing Reveals Compartmentalization and Dynamics of Acyclovir-Resistant Herpes Simplex Virus Type-2 (HSV-2) in a Case of Neonatal Herpes.

A neonate suffering from herpes simplex virus type 2 disease with central nervous system involvement developed an early recurrence under acyclovir therapy. Isolates from the cerebrospinal fluid and skin lesions were acyclovir resistant, while viruses from blood and trachea were not. Acyclovir combined with foscavir followed by long-term suppressive acyclovir therapy supported normal neurological development.

The EPIBEL study: outcomes to discharge from hospital for extremely preterm infants in Belgium.

OBJECTIVE: To determine mortality and morbidity at discharge from the hospital of a large population-based cohort of infants who were born at

Indicators of fetal and infant health outcomes.

OBJECTIVE: To assess the ability of the member states of the European Union to produce the indicators recommended by the PERISTAT project on perinatal health indicators and to provide an overview of fetal and infant health outcomes for these countries according to the information now available. METHODS: We used data from the PERISTAT survey of data providers to compute PERISTAT indicators of fetal and infant health. RESULTS: National data on fetal mortality are available for all countries, but vary in their definitions. To adjust for these differences in definition, PERISTAT recommends presenting rates by gestational age and birth weight. Not all countries can provide neonatal mortality data by gestational age, birth weight or plurality, as recommended by PERISTAT. Few countries in Europe can report infant mortality rates by birth weight and gestational age. The other recommended indicators are available to varying degrees. CONCLUSIONS: This overview, which shows that Europe can produce a variety of indicators for monitoring the health of its new-borns, indicates that some key dimensions of perinatal health cannot now be measured with routine health statistics and reveals important disparities in health outcomes throughout Europe. For most indicators, the highest values are between 50 and 100% higher than the lowest values. The reasons for these variations and their importance for the surveillance of perinatal health are discussed.