Cardiac Mechanics Evaluation in Preschool-Aged Children with Preterm Birth History: A Speckle Tracking and 4D Echocardiography Study.

Background: The premature-born adult population is set to grow significantly, and prematurity has emerged as an important cardiovascular risk factor. We aimed to comprehensively assess cardiac mechanics and function in a cohort of ex-preterm preschoolers. Methods: Ex-preterm children (<30 weeks of gestation), aged 2 to 5 years, underwent transthoracic 2D, speckle-tracking, and 4D echocardiography. The findings were compared with 19 full-term children. Results: Our cohort of 38 children with prematurity history showed a normal morpho-functional echocardiographic assessment. However, compared to controls, the indexed 3D end-diastolic volumes of ventricular chambers were reduced (left ventricle 58.7 ± 11.2 vs. 67.2 ± 8.5 mL/m2; right ventricle 50.3 ± 10.4 vs. 57.7 ± 11 mL/m2; p = 0.02). Left ventricle global and longitudinal systolic function were worse in terms of fraction shortening (32.9% ± 6.8 vs. 36.5% ± 5.4; p = 0.05), ejection fraction (59.2% ± 4.3 vs. 62.3% ± 3.7; p = 0.003), and global longitudinal strain (-23.6% ± 2.4 vs. -25.5% ± 1.7; p = 0.003). Finally, we found a reduced left atrial strain (47.4% ± 9.7 vs. 54.9% ± 6.8; p = 0.004). Conclusions: Preschool-aged ex-preterm children exhibited smaller ventricles and subclinical impairment of left ventricle systolic and diastolic function compared to term children. Long-term follow-up is warranted to track the evolution of these findings.

Impact of macronutrients intake on glycemic homeostasis of preterm infants: evidence from continuous glucose monitoring.

Nutritional intake could influence the blood glucose profile during early life of preterm infants. We investigated the impact of macronutrient intake on glycemic homeostasis using continuous glucose monitoring (CGM). We analyzed macronutrient intake in infants born ≤ 32 weeks gestational age (GA) and/or with birth weight ≤ 1500 g. CGM was started within 48 h of birth and maintained for 5 days. Mild and severe hypoglycemia were defined as sensor glucose (SG) < 72 mg/dL and <47 mg/dL, respectively, while mild and severe hyperglycemia were SG > 144 mg/dL and >180 mg/dL. Data from 30 participants were included (age 29.9 weeks (29.1; 31.2), birthweight 1230.5 g (1040.0; 1458.6)). A reduced time in mild hypoglycemia was associated to higher amino acids intake (p = 0.011) while increased exposure to hyperglycemia was observed in the presence of higher lipids intake (p = 0.031). The birthweight was the strongest predictor of neonatal glucose profile with an inverse relationship between the time spent in hyperglycemia and birthweight (p = 0.007).  Conclusions: Macronutrient intakes influence neonatal glucose profile as described by continuous glucose monitoring. CGM might contribute to adjust nutritional intakes in preterm infants. What is Known: • Parenteral nutrition may affect glucose profile during the first days of life of preterm infants. What is New: • Continuous glucose monitoring describes the relationship between daily parenteral nutrient intakes and time spent in hypo and hyperglycemic ranges.

Glucose variability increases during minimally invasive procedures in very preterm infants.

The objective of this study is to assess the effect of neonatal procedures on glucose variability in very preterm infants. Preterm infants (≤ 32 weeks gestation and/or birthweight ≤ 1500 g) were started on continuous glucose monitoring (CGM) on day 2 of birth and monitored for 5 days. Minimally invasive (heel stick, venipunctures) and non-invasive (nappy change, parental presence) procedures were recorded. CGM data were analyzed 30 min before and after each procedure. The primary outcome was the coefficient of glucose variation (CV = SD/mean) before and after the procedure; SD and median glucose were also evaluated. We analyzed 496 procedures in 22 neonates (GA 30.5 weeks [29-31]; birthweight 1300 g [950-1476]). Median glucose did not change before and after each procedure, while CV and SD increased after heel prick (p = 0.017 and 0.030), venipuncture (p = 0.010 and 0.030), and nappy change (p < 0.001 and < 0.001), in the absence of a difference during parental presence. CONCLUSIONS: Non-invasive and minimally invasive procedures increase glucose variability in the absence of changes of mean glucose. WHAT IS KNOWN: • Minimally invasive procedures - including nappy change - may increase neonatal stress in preterm infants. WHAT IS NEW: • Continuous glucose monitoring provides a quantitative measure of neonatal stress during neonatal care procedures demonstrating an increase of glucose variability.

Neonatal Hyperglycemia and Neurodevelopmental Outcomes in Preterm Infants: A Review.

Glucose impairment is common in preterm infants but the impact of early neonatal hyperglycemia on long term neurodevelopment is still highly controversial. This review reports current evidence of the effect of hyperglycemia on neurodevelopmental outcome. It was conducted according to the PRISMA guidelines. We searched MEDLINE via PubMed; EMBASE via Ovid; the Cochrane Central Register of Controlled Trials; the Cochrane Library; ClinicalTrials.gov; and the World Health Organization's International Trials Registry and Platform. We included studies that investigated the association between hyperglycemia, defined as at least one episode of glycemia ≥8 mmol/L, and neurodevelopment outcome evaluated either through the Griffiths Mental Developmental Scales (GMDS) or the Bayley Scales of Infant Development (BSID) for the first 5 years of life, and the Wechsler Intelligence Scale for Children (WISC) and the Movement Assessment Battery for Children (MABC) for the following age category. We selected six studies, comprising 2226 infants in total and which included 1059 (48%) infants for whom neurodevelopment assessment was available. We found an association between hyperglycemia and neurological delay in the first two years of life, especially for motor functions; this result was confirmed in later childhood. The quality of evidence was poor; therefore, the negative influence of neonatal hyperglycemia on the neurological development of preterm infants must be investigated in further studies.

The Metabolome and the Gut Microbiota for the Prediction of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation: A Systematic Review.

Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal emergency in preterm neonates. Research on early predictive biomarkers is fundamental. This is a systematic review of studies applying untargeted metabolomics and gut microbiota analysis to evaluate the differences between neonates affected by NEC (Bell's stage II or III), and/or by spontaneous intestinal perforation (SIP) versus healthy controls. Five studies applying metabolomics (43 cases, 95 preterm controls) and 20 applying gut microbiota analysis (254 cases, 651 preterm controls, 22 term controls) were selected. Metabolomic studies utilized NMR spectroscopy or mass spectrometry. An early urinary alanine/histidine ratio >4 showed good sensitivity and predictive value for NEC in one study. Samples collected in proximity to NEC diagnosis demonstrated variable pathways potentially related to NEC. In studies applying untargeted gut microbiota analysis, the sequencing of the V3−V4 or V3 to V5 regions of the 16S rRNA was the most used technique. At phylum level, NEC specimens were characterized by increased relative abundance of Proteobacteria compared to controls. At genus level, pre-NEC samples were characterized by a lack or decreased abundance of Bifidobacterium. Finally, at the species level Bacteroides dorei, Clostridium perfringens and perfringens-like strains dominated early NEC specimens, whereas Clostridium butyricum, neonatale and Propionibacterium acnei those at disease diagnosis. Six studies found a lower Shannon diversity index in cases than controls. A clear separation of cases from controls emerged based on UniFrac metrics in five out of seven studies. Importantly, no studies compared NEC versus SIP. Untargeted metabolomics and gut microbiota analysis are interrelated strategies to investigate NEC pathophysiology and identify potential biomarkers. Expression of quantitative measurements, data sharing via biorepositories and validation studies are fundamental to guarantee consistent comparison of results.

Providing the Best Parenteral Nutrition before and after Surgery for NEC: Macro and Micronutrients Intakes.

Necrotizing enterocolitis (NEC) is the main gastrointestinal emergency of preterm infants for whom bowel rest and parenteral nutrition (PN) is essential. Despite the improvements in neonatal care, the incidence of NEC remains high (11% in preterm newborns with a birth weight <1500 g) and up to 20−50% of cases still require surgery. In this narrative review, we report how to optimize PN in severe NEC requiring surgery. PN should begin as soon as possible in the acute phase: close fluid monitoring is advocated to maintain volemia, however fluid overload and electrolytes abnormalities should be prevented. Macronutrients intake (protein, glucose, and lipids) should be adequately guaranteed and is essential in each phase of the disease. Composite lipid emulsion should be the first choice to reduce the risk of parenteral nutrition associated liver disease (PNALD). Vitamin and trace elements deficiency or overload are frequent in long-term PN, therefore careful monitoring should be planned starting from the recovery phase to adjust their parenteral intake. Neonatologists must be aware of the role of nutrition especially in patients requiring long-term PN to sustain growth, limiting possible adverse effects and long-term deficiencies.