Microbiome and its impact on fetal and neonatal brain development:current opinion in pediatrics

PURPOSE OF REVIEW: Emerging evidence suggests that the gut microbiota and its metabolites regulate neurodevelopment and cognitive functioning via a bi-directional communication system known as the microbiota-gut-brain axis (MGBA).RECENT FINDINGS: The MGBA influences brain development and function via the hypothalamic-pituitary axis, the vagal nerve, immune signaling, bacterial production of neurotransmitters, and microbial metabolites like short-chain fatty acids, tryptophan derivatives, and bile acids. Animal studies show fetal neurodevelopment is mediated by maternal microbiota derivatives, immune activation, and diet. Furthermore, manipulation of the microbiota during critical windows of development, like antibiotic exposure and fecal microbiota transplantation, can affect cognitive functioning and behavior in mice. Evidence from human studies, particularly in preterm infants, also suggests that a disrupted gut microbiota colonization may negatively affect neurodevelopment. Early microbial signatures were linked to favorable and adverse neurodevelopmental outcomes.SUMMARY: The link between the gut microbiota and the brain is evident. Future studies, including experimental studies, larger participant cohort studies with longitudinal analyses of microbes, their metabolites, and neurotransmitters, and randomized controlled trials are warranted to further elucidate the mechanisms of the MGBA. Identification of early, predictive microbial markers could pave the way for the development of novel early microbiota-based intervention strategies, such as targeted probiotics, and vaginal or fecal microbiota transplantation, aimed at improving infant neurodevelopment.</p

Continuous sensing and quantification of body motion in infants:A systematic review

Abnormal body motion in infants may be associated with neurodevelopmental delay or critical illness. In contrast to continuous patient monitoring of the basic vitals, the body motion of infants is only determined by discrete periodic clinical observations of caregivers, leaving the infants unattended for observation for a longer time. One step to fill this gap is to introduce and compare different sensing technologies that are suitable for continuous infant body motion quantification. Therefore, we conducted this systematic review for infant body motion quantification based on the PRISMA method (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). In this systematic review, we introduce and compare several sensing technologies with motion quantification in different clinical applications. We discuss the pros and cons of each sensing technology for motion quantification. Additionally, we highlight the clinical value and prospects of infant motion monitoring. Finally, we provide suggestions with specific needs in clinical practice, which can be referred by clinical users for their implementation. Our findings suggest that motion quantification can improve the performance of vital sign monitoring, and can provide clinical value to the diagnosis of complications in infants.</p

Continuous movement quantification in preterm infants using fiber mat:Advancing long-term monitoring in hospital settings

Movement patterns in preterm infants can offer crucial insights into their physiological state including maturational development and sleep. These patterns can also serve as early indicators for potential deteriorations, such as cerebral palsy, sepsis, and epilepsy. In this study, we investigated a novel 2-D optical fiber mat system for the automated monitoring of infant movement, thereby enhancing the efficiency and safety of neonatal care in both the neonatal intensive care unit (NICU) and neonatal medium care unit (NMCU). The 20 preterm infants admitted to both NICU and NMCU were enrolled in the study. They underwent monitoring for a duration of 2–5 h using both an optical fiber mat and a camera which provided valuable movement annotations. The signals from the fiber mat were quantified, selected, and then integrated into a consolidated movement signal. This signal was subsequently transformed into binary states, distinguishing between “movement” and “still” based on the distribution of the movement signal. The proposed fiber mat system achieved a mean [standard deviation (SD)] area under the receiver operating curve (AUC) of 0.91 (0.05), and an F-score of 0.73 (0.09), when compared with manually annotated video recordings. This study demonstrates the feasibility of continuous movement monitoring for preterm infants within hospital settings. It illustrates the promising potential to evolve into a predictive tool for monitoring patient deterioration through the fusion of physiological information in both hospital environments and within the comfort of homes

Risk Factors for Necrotizing Enterocolitis:A Prospective Multicenter Case-Control Study

BACKGROUND: The identification of independent clinical risk factors for necrotizing enterocolitis (NEC) may contribute to early selection of infants at risk, allowing for the development of targeted strategies aimed at the prevention of NEC. OBJECTIVE: The objective of this study was to identify independent risk factors contributing to the development of NEC in a large multicenter cohort. METHODS: This prospective cohort study was performed in 9 neonatal intensive care units. Infants born at a gestational age &lt;/=30 weeks were included. Demographic and clinical data were collected daily until day 28 postnatally. Factors predictive of the development of NEC were identified using univariate and multivariable analyses in a 1: 5 matched case-control cohort. RESULTS: In total, 843 infants (56 NEC cases) were included in this study. In the case-control cohort, univariate analysis identified sepsis prior to the onset of NEC and formula feeding to be associated with an increased risk of developing NEC, whereas the administration of antibiotics directly postpartum was inversely associated with NEC. In a multivariable logistic regression model, enteral feeding type and the number of days parenterally fed remained statistically significantly associated with NEC, whereas the administration of antibiotics directly after birth was associated with a lower risk of developing NEC. CONCLUSIONS: Formula feeding and prolonged (duration of) parenteral feeding were associated with an increased risk of NEC. Contrary to expectations, the initiation of treatment with antibiotics within 24 h after birth was inversely associated with NEC

Profound Pathogen-Specific Alterations in Intestinal Microbiota Composition Precede Late-Onset Sepsis in Preterm Infants:A Longitudinal, Multicenter, Case-Control Study

BACKGROUND: The role of intestinal microbiota in the pathogenesis of late-onset sepsis (LOS) in preterm infants is largely unexplored but could provide opportunities for microbiota-targeted preventive and therapeutic strategies. We hypothesized that microbiota composition changes before the onset of sepsis, with causative bacteria that are isolated later in blood culture. METHODS: This multicenter case-control study included preterm infants born under 30 weeks of gestation. Fecal samples collected from the 5 days preceding LOS diagnosis were analyzed using a molecular microbiota detection technique. LOS cases were subdivided into 3 groups: gram-negative, gram-positive, and coagulase-negative Staphylococci (CoNS). RESULTS: Forty LOS cases and 40 matched controls were included. In gram-negative LOS, the causative pathogen could be identified in at least 1 of the fecal samples collected 3 days prior to LOS onset in all cases, whereas in all matched controls, this pathogen was absent (P = .015). The abundance of these pathogens increased from 3 days before clinical onset. In gram-negative and gram-positive LOS (except CoNS) combined, the causative pathogen could be identified in at least 1 fecal sample collected 3 days prior to LOS onset in 92% of the fecal samples, whereas these pathogens were present in 33% of the control samples (P = .004). Overall, LOS (expect CoNS) could be predicted 1 day prior to clinical onset with an area under the curve of 0.78. CONCLUSIONS: Profound preclinical microbial alterations underline that gut microbiota is involved in the pathogenesis of LOS and has the potential as an early noninvasive biomarker

Association between duration of early empiric antibiotics and necrotizing enterocolitis and late-onset sepsis in preterm infants:a multicenter cohort study

The threshold to initiate empiric antibiotics for suspicion of early-onset sepsis (EOS) is low in preterm infants. Antibiotics’ effects on short-term outcomes have recently been debated. We aimed at exploring the extent of early empiric antibiotic exposure (EEAE) in preterm infants and the association between the duration of EEAE with necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) within different EEAE groups. EEAE practice for suspicion of EOS was evaluated in all included infants (gestational age 72 h). Infants with EEAE ≤ 72 h had a lower incidence of NEC compared to both infants without EEAE (adjusted odds ratio (aOR) 0.39; 95% confidence interval (CI) [0.19–0.80]; p = 0.01) and with prolonged EEAE (> 72 h) (aOR [95%CI]: 0.58 [0.35–0.96]; p = 0.03). With every additional day of EEAE, LOS incidence decreased (aOR [95%CI]: 0.90 [0.85–0.97]; p = 0.003). Conclusion: Almost 90% of preterm infants who have negative blood culture results in the first 72 h of life are exposed to EEAE under suspicion of EOS. One-fourth has prolonged EEAE. Duration of EEAE was differently associated with NEC and LOS incidence. The effects of antibiotics, and potentially induced microbial dysbiosis related to development of NEC and LOS, should further be explored.What is Known:• Preterm infants often receive antibiotics empirically directly after birth for suspicion of early-onset sepsis.• The effects of the duration of early empirical antibiotic exposure on the risk for necrotizing enterocolitis and late-onset sepsis are debated.What is New:• Almost 90% of preterm infants with a gestational age below 30 weeks are exposed to antibiotics empirically after birth despite negative culture results. In a quarter of these culture-negative infants, empirical antibiotics are prolonged.• A short course of empirical antibiotics (≤72h) is associated with decreased odds for necrotizing enterocolitis compared to both prolonged (>72h) or no empirical antibiotics after birth. Furthermore, every additional day of empirical antibiotic exposure is associated with decreased risk for late-onset sepsis in the first month of life

Preclinical detection of non-catheter related late-onset sepsis in preterm infants by fecal volatile compounds analysis : a prospective, multi-center cohort study

Background: Late onset sepsis (LOS) in preterm infants is preceded by fecal volatile organic compound (VOC) alterations, suggesting an etiological role of gut microbiota in LOS rather than being primarily caused by central venous catheters (CVC). To increase our knowledge about the involvement of the gut microbiota in LOS, we analyzed fecal samples from septic infants without a CVC. Methods: In this prospective multicenter study, fecal samples were collected daily from all infants born at ≤30 weeks gestation. Fecal VOC profiles up to 3 days prior to sepsis onset from infants with non-catheter–related LOS were compared with profiles from non-septic controls by means of High-Field Asymmetric Waveform Ion Mobility Spectrometry. Results: In total, 104 fecal samples were analyzed. Fecal VOC profiles allowed for discrimination between non-catheter–related LOS cases (n = 24) and matched controls (n = 25). Discriminative accuracy increased after focusing on center of origin (area under the curve, sensitivity, specificity; 0.95, 100%, 83%) and after focusing on LOS cases caused by Staphylococcus epidermidis (0.95, 100%, 78%), the most cultured pathogen (n = 11). Conclusions: Fecal VOC profiles of preterm LOS infants without a CVC differed from matched controls underlining the increasing notion that aberrations in gut microbiota composition and activity may play a role in LOS etiology

Detection of volatile organic compounds as potential novel biomarkers for chorioamnionitis - proof of experimental models

Background: Histologic chorioamnionitis is only diagnosed postnatally which prevents interventions. We hypothesized that volatile organic compounds (VOCs) in the amniotic fluid might be useful biomarkers for chorioamnionitis and that VOC profiles differ between amnionitis of different origins. Methods: Time-mated ewes received intra-amniotic injections of media or saline (controls), or live Ureaplasma parvum serovar 3 (Up) 14, 7 or 3d prior to c-section at day 124 gestational age (GA). 100 μg recombinant ovine IL-1α was instilled at 7, 3 or 1d prior to delivery. Headspace VOC profiles were measured from amniotic fluids at birth using ion mobility spectrometer coupled with multi-capillary columns. Results: 127 VOC peaks were identified. 27 VOCs differed between samples from controls and Up- or IL-1α induced amnionitis. The best discrimination between amnionitis by Up vs. IL-1α was reached by 2-methylpentane, with a sensitivity/specificity of 96/95% and a positive predictive value/negative predictive values of 96 and 95%. The concentration of 2-methylpentane in VOCs peaked 7d after intra-amniotic instillation of Up. Discussion: We established a novel method to study headspace VOC profiles of amniotic fluids. VOC profiles may be a useful tool to detect and to assess the duration of amnionitis induced by Up. 2-methylpentane was previously described in the exhalate of women with pre-eclampsia and might be a volatile biomarker for amnionitis. Amniotic fluids analyzed by ion mobility spectrometry coupled with multi-capillary columns may provide bedside diagnosis of amnionitis and understanding inflammatory mechanisms during pregnancy

Pregnant patient with acute abdominal pain and previous bariatric surgery

Pregnant women who previously had bariatric surgery may develop acute abdominal pain during pregnancy. Two patients, 38-year-old twin primigravida (gestational age of 24+6 weeks) and a 26-year-old woman (gestational age of 24+0 weeks), both of whom had laparoscopic gastric bypass surgery previously, developed abdominal pain. The patients both had diffuse abdominal pain in combination with normal blood tests and imaging. Patient B had undergone laparoscopy at another centre after 5 weeks of gestation for internal herniation. After referral to our multidisciplinary bariatric-obstetric-neonatal (MD-BON) team, diagnostic laparoscopy was advised as internal herniation was deemed possible. In both patients, internal herniation was indeed found in Petersen's space and jejunal mesenteric defect, which was closed using laparoscopic surgery. Both women delivered healthy offspring afterwards. The presence of an MD-BON team allows for an increased awareness of potential long-term complications associated with earlier bariatric surgery in pregnancy