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Concept: Necrotizing enterocolitis

152

In vitro human pluripotent stem cell (hPSC) derived tissues are excellent models to study certain aspects of normal human development. Current research in the field of hPSC derived tissues reveals these models to be inherently fetal-like on both a morphological and gene expression level. In this review we briefly discuss current methods for differentiating lung and intestinal tissue from hPSCs into individual 3-dimensional units called organoids. We discuss how these methods mirror what is known about in vivo signaling pathways of the developing embryo. Additionally, we will review how the inherent immaturity of these models lends them to be particularly valuable in the study of immature human tissues in the clinical setting of premature birth. Human lung organoids (HLOs) and human intestinal organoids (HIOs) not only model normal development, but can also be utilized to study several important diseases of prematurity such as respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC).

Concepts: Gene expression, Cell, Cancer, Developmental biology, Stem cell, Cellular differentiation, Pluripotency, Necrotizing enterocolitis

143

To study the value of combined measurement of intestinal fatty acid-binding protein (I-FABP) and fecal calprotectin (FC) in the diagnosis of necrotizing enterocolitis (NEC) in full-term neonates.

Concepts: Pediatrics, Necrotizing enterocolitis

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Background The preferred timing of umbilical-cord clamping in preterm infants is unclear. Methods We randomly assigned fetuses from women who were expected to deliver before 30 weeks of gestation to either immediate clamping of the umbilical cord (≤10 seconds after delivery) or delayed clamping (≥60 seconds after delivery). The primary composite outcome was death or major morbidity (defined as severe brain injury on postnatal ultrasonography, severe retinopathy of prematurity, necrotizing enterocolitis, or late-onset sepsis) by 36 weeks of postmenstrual age. Analyses were performed on an intention-to-treat basis, accounting for multiple births. Results Of 1634 fetuses that underwent randomization, 1566 were born alive before 30 weeks of gestation; of these, 782 were assigned to immediate cord clamping and 784 to delayed cord clamping. The median time between delivery and cord clamping was 5 seconds and 60 seconds in the respective groups. Complete data on the primary outcome were available for 1497 infants (95.6%). There was no significant difference in the incidence of the primary outcome between infants assigned to delayed clamping (37.0%) and those assigned to immediate clamping (37.2%) (relative risk, 1.00; 95% confidence interval, 0.88 to 1.13; P=0.96). The mortality was 6.4% in the delayed-clamping group and 9.0% in the immediate-clamping group (P=0.03 in unadjusted analyses; P=0.39 after post hoc adjustment for multiple secondary outcomes). There were no significant differences between the two groups in the incidences of chronic lung disease or other major morbidities. Conclusions Among preterm infants, delayed cord clamping did not result in a lower incidence of the combined outcome of death or major morbidity at 36 weeks of gestation than immediate cord clamping. (Funded by the Australian National Health and Medical Research Council [NHMRC] and the NHMRC Clinical Trials Centre; APTS Australian and New Zealand Clinical Trials Registry number, ACTRN12610000633088 .).

Concepts: Pregnancy, Childbirth, Epidemiology, Embryo, Fetus, Medical statistics, Statistical significance, Necrotizing enterocolitis

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Abstract Background: Provision of human milk has important implications for the health and outcomes of extremely preterm (EP) infants. This study evaluated the effects of an exclusive human milk diet on the health of EP infants during their stay in the neonatal intensive care unit. Subjects and Methods: EP infants <1,250 g birth weight received a diet consisting of either human milk fortified with a human milk protein-based fortifier (HM) (n=167) or a diet containing variable amounts of milk containing cow milk-based protein (CM) (n=93). Principal outcomes were mortality, necrotizing enterocolitis (NEC), growth, and duration of parenteral nutrition (PN). Results: Mortality (2% versus 8%, p=0.004) and NEC (5% versus 17%, p=0.002) differed significantly between the HM and CM groups, respectively. For every 10% increase in the volume of milk containing CM, the risk of sepsis increased by 22% (p<0.001). Growth rates were similar between groups. The duration of PN was 8 days less in the subgroup of infants receiving a diet containing <10% CM versus ≥10% CM (p<0.02). Conclusions: An exclusive human milk diet, devoid of CM-containing products, was associated with lower mortality and morbidity in EP infants without compromising growth and should be considered as an approach to nutritional care of these infants.

Concepts: Childbirth, Infant, Nutrition, Intensive care medicine, Milk, Cattle, Pediatrics, Necrotizing enterocolitis

28

A randomised, double-blind clinical trial was undertaken in order to assess the effectiveness of probiotics in the prevention of necrotising enterocolitis (NEC) in newborns weighing <1500 g.

Concepts: Clinical trial, Randomized controlled trial, Effectiveness, ClinicalTrials.gov, Efficacy, Pediatrics, Necrotizing enterocolitis

27

The aim was to study the effects of boric acid (BA) and 2-aminoethoxydiphenyl borate (2-APB) on oxidative stress and inflammation in an experimental necrotizing enterocolitis (NEC) rat model.

Concepts: Hydrogen, Oxidative stress, Oxidative phosphorylation, Borax, Boric acid, Necrotizing enterocolitis, Boron, Borate

27

Abstract OBJECTIVE: To assess perinatal antecedents to postpartum depression. METHODS: This was a prospective population-based, observational study of women screened for symptoms of depression using the Edinburgh Postnatal Depression Scale (EPDS) with scores > 13 referred for psychiatric evaluation. Obstetric and neonatal outcomes were analyzed using univariable and multivariable analysis for associations with postpartum depressive symptoms. RESULTS: Of 25,050 women delivered, 17,648 (71%) completed EPDS questionnaires with 1,106 (6.3%) scoring > 13. Perinatal complications most associated with EPDS scores > 13 included major malformation (adjusted OR 1.5;95%CI,1.1-2.3), neonatal death (adjusted OR 5.8; 95%CI,2.9-11.4), stillbirth (adjusted OR 9.4;95%CI,6.0-14.8), and necrotizing enterocolitis (adjusted OR 21.7;95%CI,1.9-244.3). A total of 238 (22%) women kept their psychiatric referral appointment, and 111 (47%) were diagnosed with postpartum depression. Perinatal factors were also found to be significantly associated with postpartum depression. CONCLUSIONS: Postpartum depression is significantly increased in women with adverse pregnancy outcomes, especially involving the infant.

Concepts: Pregnancy, Childbirth, Fetus, Obstetrics, Pediatrics, Bipolar disorder, Postpartum depression, Necrotizing enterocolitis

24

Necrotizing enterocolitis (NEC) is a severe inflammatory disease, mostly occurring in preterm infants. The Dutch guidelines for active treatment of extremely preterm infants changed in 2006 from 26+0 to 25+0weeks of gestation, and in 2010 to 24+0 of gestation. We aimed to gain insight into the incidence, clinical outcomes and treatment strategies, in three academic referral centers in the Netherlands over the last nine years.

Concepts: Inflammation, Netherlands, Belgium, Dutch people, Necrotizing enterocolitis, Dutch language, Afrikaner

23

Human milk (donor milk (DM) and/or maternal milk (MM)) feedings protect against late onset sepsis (LOS), necrotizing enterocolitis (NEC) and death. However, DM lacks many anti-infective components of MM. Therefore, we studied exclusive MM feedings to evaluate the full effect of human milk on infectious and other outcomes in premature infants.

Concepts: Inflammation, Childbirth, Infant, Infection, Milk, Breastfeeding, Lactation, Necrotizing enterocolitis

23

Necrotizing enterocolitis is a devastating disease afflicting premature infants, though after 50 years of investigation, the pathophysiology remains elusive. This report describes the possible etiologic factors from a historical perspective, and outlines the importance of human milk, intestinal blood flow, and intestinal blood flow changes from a developmental perspective over the last 40-50 years.

Concepts: Medicine, Childbirth, Myocardial infarction, Milk, Hematology, Infarction, Necrotizing enterocolitis, Reason