Relationship between insulin-like growth factor I levels, early insulin treatment, and clinical outcomes of very low birth weight infants.

OBJECTIVES: Insulin regulates the secretion of insulin-like growth factor I (IGF-I) in the newborn, and low levels of IGF-I have been linked to neonatal morbidity. As part of the Neonatal Insulin Replacement Therapy in Europe Trial, we investigated the impact of early insulin treatment on IGF-I levels and their relationship with morbidity and growth. STUDY DESIGN: Prospective cohort analyses of data collected as part of an international randomized controlled trial. Blood samples (days 1, 3, 7, and 28), were taken for IGF-I bioassay from 283 very low birth weight infants (<1500 g). RESULTS: Early insulin treatment led to a late increase in IGF-I levels between day 7 and 28 (P = .028). In the first week of life IGF-I levels were lower in infants with early hyperglycemia; mean difference -0.10 µg/L (95% CI -0.19, -0.02, P = .02). Lower levels of IGF-I at day 28 were independently associated with an increased risk of chronic lung disease, OR 3.23 (95% CI, 1.09-9.10), and greater IGF-I levels were independently associated with better weight gain, 0.10 kg (95% CI, 0.03-0.33, P = .02). CONCLUSIONS: Early intervention with insulin is related to increased IGF-I levels at 28 days. Low IGF-I levels are associated with hyperglycemia, increased morbidity, and reduced growth. Increasing IGF-I levels may improve outcomes of very low birth weight infants.

Early insulin therapy in very-low-birth-weight infants.

BACKGROUND: Studies involving adults and children being treated in intensive care units indicate that insulin therapy and glucose control may influence survival. Hyperglycemia in very-low-birth-weight infants is also associated with morbidity and mortality. This international randomized, controlled trial aimed to determine whether early insulin replacement reduced hyperglycemia and affected outcomes in such neonates. METHODS: In this multicenter trial, we assigned 195 infants to continuous infusion of insulin at a dose of 0.05 U per kilogram of body weight per hour with 20% dextrose support and 194 to standard neonatal care on days 1 to 7. The efficacy of glucose control was assessed by continuous glucose monitoring. The primary outcome was mortality at the expected date of delivery. The study was discontinued early because of concerns about futility with regard to the primary outcome and potential harm. RESULTS: As compared with infants in the control group, infants in the early-insulin group had lower mean (+/-SD) glucose levels (6.2+/-1.4 vs. 6.7+/-2.2 mmol per liter [112+/-25 vs. 121+/-40 mg per deciliter], P=0.007). Fewer infants in the early-insulin group had hyperglycemia for more than 10% of the first week of life (21% vs. 33%, P=0.008). The early-insulin group had significantly more carbohydrate infused (51+/-13 vs. 43+/-10 kcal per kilogram per day, P<0.001) and less weight loss in the first week (standard-deviation score for change in weight, -0.55+/-0.52 vs. -0.70+/-0.47; P=0.006). More infants in the early-insulin group had episodes of hypoglycemia (defined as a blood glucose level of <2.6 mmol per liter [47 mg per deciliter] for >1 hour) (29% in the early-insulin group vs. 17% in the control group, P=0.005), and the increase in hypoglycemia was significant in infants with birth weights of more than 1 kg. There were no differences in the intention-to-treat analyses for the primary outcome (mortality at the expected date of delivery) and the secondary outcome (morbidity). In the intention-to-treat analysis, mortality at 28 days was higher in the early-insulin group than in the control group (P=0.04). CONCLUSIONS: Early insulin therapy offers little clinical benefit in very-low-birth-weight infants. It reduces hyperglycemia but may increase hypoglycemia (Current Controlled Trials number, ISRCTN78428828.)

Comprehensive Ocular Examination of Healthy Newborns in the Middle East.

Purpose: To report the prevalence of the perinatal ocular disease in healthy infants referred to a referral eye centre in the Middle East region for comprehensive ocular examinations.Methods: All healthy full-term babies born at a tertiary care women's and children hospital were referred to Moorfields Eye Hospital Centre in Abu Dhabi (MEHCAD), the United Arab Emirates for comprehensive ocular examination between January 2018 and April 2019. The examination included red-reflex testing, external, anterior and dilated posterior segment examination, and refraction.Results: Out of 6836 newborns, 4719 (69%) were not referred due to lack of national insurance (n = 3089), out of network referral (n = 1405), required ROP screening (n = 220) and identification of systemic diagnosis (n = 5). Of 2117 eligible referrals 897 (42%) babies were not examined because they either did not attend (890) or had a double booking for ROP screening (7); hence, 1220 babies (56%) were examined. Their mean age was 39 ± 16 days, and 48.8% were male, 51.2% were female. One hundred and sixty-four (13.4%) babies had an ocular abnormality in 249 (10.2%) eyes. The commonest abnormalities were nasolacrimal duct obstruction (36%) and refractive errors in 53 patients (32.3%). Congenital cataract and ptosis were present in four (0.3%) and three (0.2%) babies, respectively. The commonest retinal findings were intra-retinal haemorrhages (1.4%). Other posterior pole abnormalities included optic disc pit (0.08%) and myelinated nerve fibers (0.08%). One eye (0.08%) had a congenital macular hole.Conclusion: Comprehensive ocular examinations of healthy infants identifies a number of ocular abnormalities that would not be detected using red-reflex testing by a paediatrician or nurse.

Prevalence and determinants of hyperglycemia in very low birth weight infants: cohort analyses of the NIRTURE study.

OBJECTIVES: To investigate the prevalence and determinants of hyperglycemia in the preterm population, as part of the Neonatal Insulin Therapy in Europe (NIRTURE) Trial. STUDY DESIGN: We conducted prospective cohort analyses of continuous glucose monitoring data from control infants participating in an international randomized controlled trial. Data were collected from 188 very low birth weight infants (<1500 g). RESULTS: In the first week of life, 80% of infants had evidence of glucose levels >8 mmol/L, and 32% had glucose levels >10 mmol/L >10% of the time. Independent risk factors for hyperglycemia included increasing prematurity, small size at birth, use of inotropes, lipid infusions, and sepsis. There was a lack of association between rate of dextrose infused and risk of hyperglycemia. CONCLUSION: The prevalence of hyperglycemia in the very low birth weight infant is high, with marked variability in prevalence between infants, not simply related to rates of glucose infused, but to other potentially modifiable risk factors.

Vertical transmission of human echovirus 11 at the time of Bornholm disease in late pregnancy.

We report a case of human echovirus 11 infection in a neonate at the time of Bornholm disease in late pregnancy of the mother. Mother and baby were found to be infected with the same virus, with a combination of diagnostic virologic techniques, demonstrating likely transmission from mother to baby around the time of delivery.