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Abstract Body

Monogenic diabetes represents a heterogeneous group of disorders resulting from defects in single genes. Defects are categorized primarily into two groups: disruption of beta cell function or a reduction in the number of beta cells. Identifying gene variants causing monogenic diabetes increases understanding of disease etiology and allows for implementation of precision therapy to improve metabolic control and quality of life. In a systematic study, we assessed the prevalence of monogenic diabetes in diabetic youth at 3.5%. We screened all antibody-negative patients using targeted high-throughput sequencing of more than 400 potential candidate genes. In this group, 41% had monogenic diabetes, with the highest percentage (100%) in infants (diagnosis at ages 0–12 months), followed by those diagnosed at ages >1–18 years (40.3%) and at >18–25 years (22.2%). The prevalence of monogenic diabetes in diabetic youth was 1.9% for GCK diabetes, 0.7% for HNF1A, 0.2% for HNF4A and ABCC8, 0.3% for KCNJ11, and 0.1% for INS. After diagnosis, we prospectively introduced precision treatment. Prospective treatment change was successful in over 50% of eligible candidates, with C-peptide over 252 pmol/L emerging as the best prognostic factor.

Abstract Body

Background: Postnatal systemic and inhaled glucocorticoid (GC) therapy in VLBW infants may have a sex-specific impact on neurological, pulmonary, and anthropometric outcome parameters.

Methods: We performed a retrospective chart analysis of all VLBW infants treated between 2010 and 2014 in our NICU. Active agent, dosing, interval, ventilator mode, and oxygenation index (FiO₂ x MAP) were recorded for each day of GC treatment. Neurological, pulmonary, and anthropometric outcome parameters were compared regarding sex.

Results: Of 552 infants, 183 received postnatal GC (77 females, 106 male, p<0.01). There were no sex-specific differences in BPD rate, mortality, cumulative dosage, and pulmonary response to GC therapy. Table 1 showes anthropometric parameters at discharge in GC treated infants.

Neurological examination at the age of 2 years (BSID [median; IQR]) after GC therapy showed a significantly worse outcome than in non-treated infants. However, no significant sex-specific differences were detectable: cognitive score of males vs. females [median; IQR]: 88 (77 – 99), vs. 86 (63 –100), motor scales = 103 (90 –107), vs. 100 (85 –109).

Conclusion: Male premature infants were treated postnatally more frequently with glucocorticoids, but with equivalent cumulative dosages. Postnatal glucocorticoid therapy seems to have a sex-specific influence on growth parameters.

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Background and aims: Human milk is better tolerated than formula in preterm infants. Insulin, present in human milk but not in formula, has been suggested as a key factor, as it seems to stimulate intestinal maturation and thereby feeding tolerance. Therefore, it might serve as supplement for formula or as additive to fortifiers. The objective of this study was to determine the milk insulin course directly following preterm (gestational age (GA) <37 weeks) and term (GA ≥37 weeks) delivery. Furthermore, we assessed the effect of maternal pre-pregnancy body-mass-index (BMI) and diurnal rhythm as they may impact the insulin concentration.

Methods: Milk was collected from 30 non-diabetic mothers (preterm, n=20; term, n=10) on at least four timepoints per day in the first five days, and once on day 10 postpartum.

Results: Milk insulin concentration declined rapidly in the first three days postpartum in both the preterm group (day 1, 723 (356-1137) pmol/L; day 3, 153 (93-302) pmol/L) and the term group (day 1, 389 (256-734) pmol/L; day 3, 159 (69-337) pmol/L). Preterm delivery did not significantly affect the milk insulin concentration (p=0.277), when adjusted for obesity. Obese mothers had a higher milk insulin concentration compared to non-obese mothers (p<0.001). Diurnal rhythm was characterized by an insulin concentration decline throughout the night (p=0.001), followed by an increase in the morning (p=0.004).

Conclusions: Milk insulin course is characterized by a rapid decline in the first three days postpartum, irrespective of GA. Besides, insulin concentration is affected by maternal pre-pregnancy BMI and diurnal rhythm.

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Background and Aim

Evidence suggests that multi-strain probiotics may be more beneficial than single-strain probiotics in preterm neonates. We aimed to assess the effects of single vs. three-strain probiotic supplementation in extremely preterm (EP) neonates.

Research method

EP neonates (Gestation <28 weeks) were randomly allocated to a single-strain (B. breve M-16V) or three-strain (B. breve M-16V, B. longum subsp. infantis M-63, B. longum subsp. longum BB536) probiotic while assuring blinding. Supplementation (3×10⁹ CFU/day) was commenced with feeds and continued till corrected gestational age 37 weeks. Sample size was powered for the primary outcome time to full feeds (TFF: 150ml/kg/day). Secondary outcomes included intestinal transit time (ITT), faecal short chain fatty acid (SCFA: acetate, butyrate, propionate) levels, necrotising enterocolitis (NEC ≥ Stage II), late onset sepsis (LOS), and mortality. Stool samples were collected before (T1) and after three weeks of supplementation (T2).

Results

173 EP neonates were randomised (Single-strain: 87; Three-strain: 86). Maternal and neonatal demographic characteristics were comparable. Median (IQR) TFF [11 (8-16) vs. 10 (8-16) days; p=0.92], median ITT (17 vs. 18 hrs; p=0.826), and faecal SCFA levels did not differ significantly between single vs. three-strain groups. Clustering showed significantly raised butyrate (single-strain) and propionate (three-strain) levels in T2 samples. Secondary outcomes including NEC≥ Stage II, all-cause mortality, and LOS were comparable.

Conclusion

Compared with single-strain, multi-strain probiotic had no significant effect on TFF in EP neonates. The long-term significance of raised butyrate (neurodevelopment, metabolic health) and propionate (allergy, asthma) needs to be studied.

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Background

Necrotizing enterocolitis (NEC) is an inflammatory intestinal disease affecting premature infants. The aim of this study was to investigate the effect of hBM-MSCs.

Methods

NEC was induced in 3-day old C57BL/6 mouse pups, through gavage feeding with infant formula, hypoxia/ischemia, oral lipopolysaccharide (LPS). Mice were allocated into five groups. The control group remained with mothers and breastfed ad libitum. The NEC experimental groups were randomized to receive either an intraperitoneal (i.p.) injection of PBS (NEC+PBS group) or two different concentrations (0.5-1x10⁶ cells) of hBM-MSCs (NEC+hBM-MSCs) or C34 (3mg/Kg/day) as TLR4 inhibitor. Mice were sacrificed 72 hours after NEC induction (Fig.1). The histological score ≥ 2 indicated the presence of NEC.

Results

Only two breastfed pups developed NEC (11.1%). Compared to the breastfed group, 66.7% of pups exposed to experimental NEC and receiving PBS alone (NEC+PBS) developed NEC (p=0.0014). Compared to pups that received PBS, pups exposed to NEC and treated with hBM-MSCs (0.5x10⁶) showed a NEC incidence of 52.2% while mice treated with hBM-MSCs (1x10⁶) did not develop any NEC at all (p=0.0002 compared to NEC+PBS). As expected, NEC did not develop in mice exposed to NEC and treated with C34 (p=0.0004, vs. NEC+PBS). Interestingly, the infusion of a higher dose of hBM-MSCs (1x10⁶) significantly decreased NEC incidence (p=0.008, vs. NEC+hBM-MSCs (0.5x10⁶)) (Fig.2).

Conclusions

hBM-MSCs reduced the incidence and severity of NEC in our model in a dose-dependent manner, probably through their immunoregulatory/anti-inflammatory activity. However, further experiments are needed to identify the molecular basis of hBM-MSCs action on NEC.

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Background and Aims: over a 40-year period, numerous adverse outcomes have been identified in very low birthweight (VLBW) preterm infants fed cow’s milk (CM)-derived products. Using meta-analyses, we developed an approach to quantifying CM-related morbidity, providing a baseline for quality improvement in neonatal nutrition.

Methods: comparative studies of CM and human milk (HM) generally explore benefits of human milk rather than safety of CM which requires different study designs. Also, the HM limb often has a high CM intake from fortifier, blunting the difference between HM and CM groups. Therefore, we conducted a search to 2019 for randomised controlled trials (RCTs) and cohort studies where we could compare a group exposed to CM products (partial or total) with a reference group fed exclusively HM (EHM), seen in studies from the pre-fortifier era and modern studies which used EHM products.

Results: the CM group had higher morbidity and mortality in random-effect meta-analyses, strictly of RCTs: 6 for proven sepsis (RR = 1.4, P=0.03: n=1113); 7 for necrotising enterocolitis (RR=2.7; P=0.001: n=1035) and 3 for death (RR=2.5, P=0.05: n=401). When also including cohort studies, adverse effects of CM were seen for severe retinopathy of prematurity (RR=2.3; P=0.02: n=2311) and bronchopulmonary dysplasia (RR=1.3, P=0.02: n=2310). Our explorations suggest these adverse effects of CM exposure are seen with similar incidence in current practice.

Conclusions: appropriate study designs show major adverse effects of CM products in VLBW infants persistently found over decades, indicating an under-estimated, unresolved yet potentially reducible safety issue in neonatology