Neuroimaging in infants with congenital cytomegalovirus infection and its correlation with outcome: emphasis on white matter abnormalities.

OBJECTIVE: To evaluate the association between neuroimaging and outcome in infants with congenital cytomegalovirus (cCMV), focusing on qualitative MRI and quantitative diffusion-weighted imaging of white matter abnormalities (WMAs). METHODS: Multicentre retrospective cohort study of 160 infants with cCMV (103 symptomatic). A four-grade neuroimaging scoring system was applied to cranial ultrasonography and MRI acquired at ≤3 months. WMAs were categorised as multifocal or diffuse. Temporal-pole WMAs (TPWMAs) consisted of swollen or cystic appearance. Apparent diffusion coefficient (ADC) values were obtained from frontal, parieto-occipital and temporal white matter regions. Available follow-up MRI at ≥6 months (N=14) was additionally reviewed. Neurodevelopmental assessment included motor function, cognition, behaviour, hearing, vision and epilepsy. Adverse outcome was defined as death or moderate/severe disability. RESULTS: Neuroimaging scoring was associated with outcome (p<0.001, area under the curve 0.89±0.03). Isolated WMAs (IWMAs) were present in 61 infants, and WMAs associated with other lesions in 30. Although TPWMAs and diffuse pattern often coexisted in infants with IWMAs (p<0.001), only TPWMAs were associated with adverse outcomes (OR 7.8; 95% CI 1.4 to 42.8), including severe hearing loss in 20% and hearing loss combined with other moderate/severe disabilities in 15%. Increased ADC values were associated with higher neuroimaging scores, WMAs based on visual assessment and IWMAs with TPWMAs. ADC values were not associated with outcome in infants with IWMAs. Findings suggestive of progression of WMAs on follow-up MRI included gliosis and malacia. CONCLUSIONS: Categorisation of neuroimaging severity correlates with outcome in cCMV. In infants with IWMAs, TPWMAs provide a guide to prognosis.

Randomized Trial on Echocardiography-Guided Ductus Arteriosus Treatment to Reduce Necrotizing Enterocolitis.

OBJECTIVE: Patent ductus arteriosus (PDA) approach remains controversial. We aim to evaluate whether echocardiography-guided (EchoG) PDA closure (to reduce drug exposure) and 24-h continuous ibuprofen infusion (24 h-IB) (to reduce peak concentration), compared with EchoG PDA closure plus conventional bolus (bolus-IB), reduces severe bowel adverse event rate in preterm infants with hemodynamically significant (hs) PDA. STUDY DESIGN: The study design is a multicenter, blinded, randomized controlled trial. Infants with <28 weeks of gestation underwent routine echocardiographic assessment (18-72 h of birth); infants with 28-33 weeks were screened only in cases where PDA was clinically suspected. HsPDA was considered if ductal diameter >1.5 mm and indicators of pulmonary overflow, systemic hypoperfusion, or both were present. Pharmacodynamic effect of CYP450 genotypes was also analyzed. RESULTS: One hundred forty-six infants [median gestational age 26 (25-28) weeks; median birth weight 881 (704-1,100) g] were randomized to 24 h-IB (n = 70) or bolus-IB (n = 76) study group at 86 (58-140) h from birth. Groups were comparable regarding perinatal and neonatal clinical data, but higher prevalence of male sex in the bolus-IB group was found. Neither severe bowel adverse event rate [10% (24 h-IB) and 2.6% (bolus-IB), p = 0.1] nor ductal closure rate was different between the study groups. Postnatal age and peripheral SaO2 at treatment start and pulmonary hemorrhage were associated with severe bowel events, independent of treatment group allocation. CYP2C8 genetic polymorphisms were associated with ibuprofen efficacy (p = 0.03). CONCLUSIONS: Ibuprofen intravenous continuous infusion compared with bolus infusion in preterm infants with hsPDA shows similar rates of success and does not reduce the prevalence of severe bowel events.

The impact of intrauterine and extrauterine weight gain in premature infants on later body composition.

BackgroundThe impact of intrauterine and extrauterine growth on later insulin resistance and fat mass (FM) in very low birth weight (VLBW) infants is not well established. The aim of our study was to evaluate the effects of intrauterine and early/late extrauterine growth on later insulin resistance and body composition in VLBW infants from 6 months' corrected age (CA) to 36 months.MethodsProspective measurements of body composition by dual-energy X-ray absorptiometry and insulin resistance by homeostasis model assessment insulin resistance (HOMA-IR) along with other fasting plasma biochemistries were made in 95 VLBW infants at 6, 12, 18, and 24 months' CA and 36 months' postnatal age. Mixed-effect models were used to evaluate the effects of age, sex, maturation status, and Δweight SD score on percentage FM (PFM), FM index (FMI), fat-free mass index (FFMI), and HOMA-IR.ResultsPFM and FMI were negatively associated with a decrease in weight-SD scores from birth to 36 weeks' postmenstrual age (PMA; P=0.001) and from 36 weeks' PMA to 6 months' CA (P=0.003). PFM and FMI were higher in AGA than in small for gestational age (SGA) infants. HOMA-IR was not associated with the Δweight-SD scores in either period.ConclusionsCatch-down growth in terms of weight is associated with persistently lower adiposity but not insulin resistance up to 36 months of age.

Vertically transmitted cytomegalovirus infection in newborn preterm infants.

OBJECTIVE: To determine the epidemiology of congenital and acquired cytomegalovirus (CMV) infections in preterm infants and to analyze the efficacy of breast milk freezing in decreasing the vertical transmission rate of CMV. STUDY DESIGN: During 2013 and 2014, preterm newborns who weighed ≤1500 g and were admitted to 22 Spanish neonatal units were included and screened for CMV infection according to the Spanish Neonatology Society recommendations. Each hospital treated the breast milk according to its own protocols. RESULTS: Among the 1236 preterm neonates included, 10 had a congenital infection (0.8%) and 49 had an acquired infection (4.0%) (82% demonstrated positive PCR-CMV in breast milk). The neonates who received only frozen milk presented less frequently with acquired infection (1.2%) than those fed fresh milk (5.5%) (RR=0.22; 95% CI 0.05-0.90; P=0.017). The newborns who received bank milk followed by frozen or fresh breast milk more frequently had an acquired infection (2.1% or 2.2%, respectively) than those fed only frozen breast milk. CONCLUSIONS: The incidence of congenital CMV infection in our sample is low, as described in the literature. To reduce acquired CMV infection, freezing breast milk might be an advisable procedure for preterm neonates born from seropositive mothers, either from the beginning of lactation or after a period of bank milk administration.

Fetal limb soft tissue assessment for prediction of birth weight and umbilical cord blood analytes in gestational diabetes.

OBJECTIVE: To evaluate the value of third trimester ultrasound (estimated fetal weight, cheek-to-cheek diameter, sectional Wharton's jelly area, sectional areas and fractional volumes in extremities) to predict birth weight and cord biochemical markers at birth (leptin, insulin, c-peptide, IGF1, erythropoietin and ferritin) in diabetic pregnancies. METHOD: Prospective study in 49 patients with gestational diabetes. An ultrasound was performed between 32 and 34 weeks. Clinical data were collected, and a blood sample was obtained from cord after birth. ROC curve models were evaluated for 75(th) and 90(th) birth weight percentile. Univariate and multivariate models were used to assess the association between ultrasound and neonatal outcomes. RESULTS: Sectional areas and fractional volumes showed significant differences and highest AUC values for predicting birth weight. A significant association was found for extremities measurements with total birth weight and its percentile. The only marker which showed a significant association to estimated fetal weight was erythropoietin. Sectional areas and fractional volumes related to cord leptin, erythropoietin, insulin and c-peptide. CONCLUSION: Sectional areas and fractional volumes improve the predictive value of estimated fetal weight in diabetic pregnancies. They also show a predictive association to biochemical changes in cord (leptin, insulin and erythropoietin) related to increased adiposity and risk of fetal hypoxia. © 2015 John Wiley & Sons, Ltd.

Growth in preterm infants until 36 weeks' postmenstrual age is close to target recommendations.

OBJECTIVE: To establish the determinants of weight, length and head circumference changes during their initial hospitalization in very-low-birth-weight preterm infants. SUBJECTS/METHODS: A prospective cohort study was performed. Weight z-score and percentage of target dietary intakes (TDIs) were prospectively determined daily during the first 5 weeks of life in a group of preterm infants (n = 111, birth weight <1,500 g, gestational age <34 weeks). Weight, length and head circumference at 36 weeks' postmenstrual age (PMA) were recorded. A mixed effects regression model was used to evaluate changes in weight z-score during the first 5 weeks of life. Simple Pearson correlations and stepwise logistic regression were used to determine the relationship between fetal growth, illness severity, nutritional intake and growth at 36 weeks' PMA. RESULTS: Weight z-score decreased significantly in all infants during the first 5 weeks of life from -0.92 ± 0.66 at birth to -1.89 ± 0.65 at 5 weeks. The variation of weight z-score during the first 5 weeks of life was influenced by weight z-score at birth, energy and protein intakes and gestational age. Mean energy and protein intakes were 95.5 and 86.4% of TDIs. Weight z-score fell to -2.05 ± 0.64 at 36 weeks' PMA. Birth weight z-score was significantly correlated with weight z-score at 36 weeks (R2 = 0.71; p < 0.001). Severity of illness influenced the weight z-score at 36 weeks. CONCLUSION: Despite achieving a protein and energy intake close to the described target intake, the rate of growth in our infants was lower than indicated by the intrauterine growth curve. Lower gestational age, lower birth weight and severe illness had a negative effect on growth.

Influence of prematurity and growth restriction on the adipokine profile, IGF1, and ghrelin levels in cord blood: relationship with glucose metabolism.

OBJECTIVE: To determine the influence of gestational age and fetal growth restriction on the cord blood adipokine profile, IGF1, and ghrelin levels, and their relationship with glucose metabolism. STUDY DESIGN: One hundred and ninety newborns (99 preterm and 91 full term) were studied and, according to their anthropometry at birth, classified as small (SGA) or adequate for gestational age (AGA). METHODS: Venous cord blood serum levels of IGF1, IGF binding protein 3 (IGFBP-3), adiponectin, resistin, leptin, soluble leptin receptor (sOB-R), tumoral necrosis factor-alpha, interleukin 6 (IL-6), total ghrelin, and acylated ghrelin were determined and compared between preterm and full-term, as well as between SGA and AGA, newborns. Correlations with newborn weight, gestational age, and homeostatic model assessment (HOMA) index, as an index of insulin resistance, were determined. RESULTS: Preterm newborns had higher HOMA, sOB-R, resistin, and IL-6 and lower IGF1, IGFBP-3, leptin, and adiponectin levels than full-term newborns. SGA had lower IGF1, IGFBP-3, leptin, IL-6, and adiponectin and higher sOB-R and total ghrelin than AGA newborns. Adiponectin and HOMA showed independent positive and negative correlations with gestational age respectively, but not with neonatal weight. Birth weight was correlated positively with IGF1 and leptin levels and negatively with total ghrelin ones. CONCLUSIONS: Our findings suggest that the lack of proper acquisition of adipose tissue by the fetus either due to prematurity or to fetal growth restriction is associated with changes in the cord blood adipokine profile that may contribute to the impairment of glucose metabolism.