Association of Poor Postnatal Growth with Neurodevelopmental Impairment in Infancy and Childhood: Comparing the Fetus and the Healthy Preterm Infant References.

OBJECTIVES: To compare the classification of preterm postnatal poor growth using healthy preterm vs fetal growth references and to examine associations with neurodevelopmental impairment in infancy and childhood. STUDY DESIGN: We included 613 infants born at <33 weeks of gestation. Using the INTERGROWTH-21st (healthy-preterm growth) reference and the Fenton and Olsen (fetal growth) references, we classified poor growth as a decline in z-score from birth to term-equivalent >0.8 SD (weight), >1 SD (head), and >2 SD (length). We used generalized estimating equations to estimate aOR for neurodevelopmental impairment at 18 months and 7 years of corrected age, comparing infants with and without poor growth by each reference, accounting for multiple births and covariates. RESULTS: The prevalence of poor growth was higher with INTERGROWTH-21st than with fetal references for all measurements. Agreement was higher between the Fenton and Olsen (fetal) growth references (0.72-0.81) than between INTERGROWTH-21st and fetal references (0.41-0.59). Poor growth by fetal references (but not by INTERGROWTH-21st) was associated with low neurodevelopmental scores in infancy and childhood. Poor weight gain using the Fenton reference was associated with 18-month Mental Developmental Index <85 (aOR 1.6, 95%CI: 1.1, 2.4) whereas poor weight gain by the INTERGROWTH-21st reference was not (aOR 1.0, 95%CI: 0.6, 1.7). Poor linear growth by the Olsen reference, but not INTERGROWTH-21st, was associated with 7-year verbal intelligence quotient <70 (aOR 3.5, 95%CI: 1.1, 12.7). CONCLUSIONS: Poor neonatal growth categorized using fetal references showed stronger associations with long term neurodevelopment than poor growth categorized using the INTERGROWTH-21st standards.

Direct thrombin inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in people with non-valvular atrial fibrillation.

BACKGROUND: Chronic anticoagulation with vitamin K antagonists (VKAs) prevents ischaemic stroke and systemic embolism in people with non-valvular atrial fibrillation (AF) but dose adjustment, coagulation monitoring and bleeding limits its use. Direct thrombin inhibitors (DTIs) are under investigation as potential alternatives. OBJECTIVES: To assess (1) the comparative efficacy of long-term anticoagulation using DTIs versus VKAs on vascular deaths and ischaemic events in people with non-valvular AF, and (2) the comparative safety of chronic anticoagulation using DTIs versus VKAs on (a) fatal and non-fatal major bleeding events including haemorrhagic strokes, (b) adverse events other than bleeding and ischaemic events that lead to treatment discontinuation and (c) all-cause mortality in people with non-valvular AF. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (July 2013), the Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, May 2013), MEDLINE (1950 to July 2013), EMBASE (1980 to October 2013), LILACS (1982 to October 2013) and trials registers (September 2013). We also searched the websites of clinical trials and pharmaceutical companies and handsearched the reference lists of articles and conference proceedings. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing DTIs versus VKAs for prevention of stroke and systemic embolism in people with non-valvular AF. DATA COLLECTION AND ANALYSIS: All three review authors independently performed data extraction and assessment of risk of bias. Primary analyses compared all DTIs combined versus warfarin. We performed post hoc analyses excluding ximelagatran because this drug was withdrawn from the market owing to safety concerns. MAIN RESULTS: We included eight studies involving a total of 27,557 participants with non-valvular AF and one or more risk factors for stroke; 26,601 of them were assigned to standard doses groups and included in the primary analysis. The DTIs: dabigatran 110 mg twice daily and 150 mg twice daily (three studies, 12,355 participants), AZD0837 300 mg once per day (two studies, 233 participants) and ximelagatran 36 mg twice per day (three studies, 3726 participants) were compared with the VKA warfarin (10,287 participants). Overall risk of bias and statistical heterogeneity of the studies included were low.The odds of vascular death and ischaemic events were not significantly different between all DTIs and warfarin (odds ratio (OR) 0.94, 95% confidence interval (CI) 0.85 to 1.05). Sensitivity analysis by dose of dabigatran on reduction in ischaemic events and vascular mortality indicated that dabigatran 150 mg twice daily was superior to warfarin although the effect estimate was of borderline statistical significance (OR 0.86, 95% CI 0.75 to 0.99). Sensitivity analyses by other factors did not alter the results. Fatal and non-fatal major bleeding events, including haemorrhagic strokes, were less frequent with the DTIs (OR 0.87, 95% CI 0.78 to 0.97). Adverse events that led to discontinuation of treatment were significantly more frequent with the DTIs (OR 2.18, 95% CI 1.82 to 2.61). All-cause mortality was similar between DTIs and warfarin (OR 0.91, 95% CI 0.83 to 1.01). AUTHORS' CONCLUSIONS: DTIs were as efficacious as VKAs for the composite outcome of vascular death and ischaemic events and only the dose of dabigatran 150 mg twice daily was found to be superior to warfarin. DTIs were associated with fewer major haemorrhagic events, including haemorrhagic strokes. Adverse events that led to discontinuation of treatment occurred more frequently with the DTIs. We detected no difference in death from all causes.

Parasite antigen in serum predicts the presence of viable brain parasites in patients with apparently calcified cysticercosis only.

BACKGROUND: Computed tomography (CT) remains the standard neuroimaging screening exam for neurocysticercosis, and residual brain calcifications are the commonest finding. Magnetic resonance imaging (MRI) is more sensitive than CT but is rarely available in endemic regions. Enzyme-linked immunoelectrotransfer blot (EITB) assay uses antibody detection for diagnosis confirmation; by contrast, enzyme-linked immunosorbent assay (ELISA) antigen detection (Ag-ELISA) detects circulating parasite antigen. This study evaluated whether these assays predict undetected viable cysts in patients with only calcified lesions on brain CT. METHODS: Serum samples from 39 patients with calcified neurocysticercosis and no viable parasites on CT were processed by Ag-ELISA and EITB. MRI was performed for each patient within 2 months of serologic testing. Conservatively high ELISA and EITB cutoffs were used to predict the finding of viable brain cysts on MRI. RESULTS: Using receiver operating characteristic-optimized cutoffs, 7 patients were Ag-ELISA positive, and 8 had strong antibody reactions on EITB. MRI showed viable brain cysts in 7 (18.0%) patients. Patients with positive Ag-ELISA were more likely to have viable cysts than Ag-ELISA negatives (6/7 vs 1/32; odds ratio, 186 [95% confidence interval, 1-34 470.0], P < .001; sensitivity 85.7%, specificity 96.9%, positive likelihood ratio of 27 to detect viable cysts). Similar but weaker associations were also found between a strong antibody reaction on EITB and undetected viable brain cysts. CONCLUSIONS: Antigen detection, and in a lesser degree strong antibody reactions, can predict viable neurocysticercosis. Serological diagnostic methods could identify viable lesions missed by CT in patients with apparently only calcified cysticercosis and could be considered for diagnosis workup and further therapy.

Growth and Clinical Outcomes of Very Low-Birth-Weight Infants Receiving Acidified vs Nonacidified Liquid Human Milk Fortifiers.

BACKGROUND: Liquid human milk fortifiers are used commonly in neonatal intensive care. Use of an acidified HMF (A-HMF) is associated with transient metabolic acidosis, but whether growth outcomes differ between infants fed A-HMF vs nonacidified HMF (NA-HMF) remains unknown. METHODS: Retrospective cohort study of 255 infants born at <33 weeks' gestation and ≤1500 g who were receiving ≥75% fortified human milk on day of life 14, in a level III neonatal intensive care unit (NICU) from May 2015 to December 2018. Infants born before October 2017 (n = 165) received A-HMF, whereas infants born after October 2017 (n = 90) received NA-HMF. We used logistic regression to estimate odds of metabolic acidosis (serum bicarbonate <16 mEq/L in the first 21 days of life) in infants receiving A-HMF vs NA-HMF and linear mixed models to compare the mean size at discharge (weight, length, head z-scores) by HMF type. We adjusted models for confounders and accounted for the nonindependence of multiple births. RESULTS: Median gestational age was 28.7 weeks (range, 22.6-32.9) and birth weight 1.1 kg (range, 0.4-1.5). Infants receiving A-HMF had higher adjusted odds of metabolic acidosis than infants receiving NA-HMF (adjusted odds ratio, 2.7; 95% CI, 1.2-6.2). There were no differences between groups in size z-scores at discharge. CONCLUSIONS: In human-milkfed, very-low-birthweight infants, fortification with liquid A-HMF may contribute to metabolic acidosis in the first month of life, but this practice does not appear to impair growth through NICU discharge, compared with fortification with NA-HMF.

Updates on Assessment and Monitoring of the Postnatal Growth of Preterm Infants.

Assessing and monitoring the physical growth of preterm infants is fundamental to NICU care. The goals of nutritional care are to approximate the growth and body composition of the healthy fetus and to support optimal brain development while minimizing future cardiometabolic risk. Both poor and excessive growth predict adverse long-term health outcomes. Growth curves are clinical tools used to assess the preterm infant's growth status. Several growth curves for preterm infants were developed in the past decade. To use them effectively, clinicians need to understand how each growth curve was developed; the underlying reference population; intended use; and strengths and limitations. Intrauterine growth curves are references that use size at birth to represent healthy fetal growth. These curves serve 2 purposes-to assign size classifications at birth and to monitor postnatal growth. The INTERGROWTH-21 st preterm postnatal growth standards were developed to compare the postnatal growth of preterm infants to that of healthy preterm infants rather than the fetus. Individualized weight growth curves account for the water weight loss that frequently occurs after birth. In addition, body mass index (BMI) curves are now available. In this review, we discuss the main characteristics of growth curves used for preterm infants as well as the use of percentiles, z scores, and their change over time to evaluate size and growth status. We also review the differences in body composition between preterm infants at term-equivalent age and term-born infants and the potential role of monitoring proportionality of growth using BMI curves.