Unveiling the strong positive relationship: Maternal characteristics and neonatal outcomes in the Better Outcomes in Labour Difficulty (BOLD) study - a secondary analysis validating neonatal near miss classification.

Background: The near miss concept, denoting near collisions between aircraft, originated in aeronautics, but has recently been transferred to the neonatal context as a way of evaluating the quality of health services for newborns, especially in settings with reduced child mortality. However, there is yet no consensus regarding the underlying criteria. The most common indicators used to assess health care quality include mortality (maternal and neonatal) and life-threatening conditions. Using the World Health Organization (WHO) Better Outcomes in Labour Difficulty (BOLD) prospective cohort study data set, we conducted a secondary analysis to validate the near miss concept and explore the association between maternal and neonatal outcomes. Methods: We studied 10 203 singleton mothers treated between December 2014 and November 2015 in nine Nigerian and four Ugandan hospitals. We validated the near miss concept by testing the diagnostic accuracy (sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and odds ratio (OR)) using death as the reference variable and calculating the maternal and neonatal case fatality rates. We performed ordinal and binomial logistic regression, with the independent variables being those that had P < 0.1 in the univariate analyses. We considered the significance level of 5%. Results: We validated the neonatal near miss concept using the BOLD study data. We observed maternal and neonatal case fatality rates of 70.2% and 6.5%, with an increasing severity relationship between maternal and neonatal outcomes (P < 0.05). Ordinal logistic regression showed that gestational age <37 or >41 weeks and <8 antenatal consultations were related to a higher risk of neonatal severe outcomes, while maternal age between 30 and 34 years functioned as a protective factor against severe neonatal outcomes (SNO). Binomial logistic regression showed gestational age <37(OR = 1.46; 95% confidence interval (CI) = 1.07-1.94) or >41 weeks (OR = 2.26; 95% CI = 1.55-3.20), low educational level (OR = 1.76; 95% CI = 1.12-2.69), overweight/obesity (OR = 1.23; 95% CI = 1.02-1.47), one previous cesarean section (OR = 1.90; 95% CI = 1.36-2.61), one previous abortion (OR = 1.25; 95% CI = 1.00-1.56), and previous chronic condition (OR = 1.83; 95% CI = 1.37-2.41) were risk factors for SNO. Conclusions: The neonatal near miss concept could be used as a parameter for analysis in different health systems, to ensure that measuring of neonatal severity is comparable across health care units. In this analysis, we observed a progressive association between maternal severity and the severity of the newborns' outcomes.

Maple syrup urine disease in Brazilian patients: variants and clinical phenotype heterogeneity.

BACKGROUND: Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disease caused by deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by BCKDHA, BCKDHB, DBT, and DLD genes. MSUD is predominantly caused by Variants in BCKDHA, BCKDHB, and DBT genes encoding the E1α, E1ß, and E2 subunits of BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD by identifying the point variants in BCKDHA, BCKDHB, and DBT genes in a cohort of Brazilian MSUD patients and to describe their phenotypic heterogeneity. It is a descriptive cross-sectional study with 21 MSUD patients involving molecular genotyping by Sanger sequencing. RESULTS: Eight new variants predicted as pathogenic were found between 30 variants (damaging and non-damaging) identified in the 21 patients analyzed: one in the BCKDHA gene (p.Tyr120Ter); five in the BCKDHB gene (p.Gly131Val, p.Glu146Glnfs * 13, p.Phe149Cysfs * 9, p.Cys207Phe, and p.Lys211Asn); and two in the DBT gene (p.Glu148Ter and p.Glu417Val). Seventeen pathogenic variants were previously described and five variants showed no pathogenicity according to in silico analysis. CONCLUSION: Given that most of the patients received late diagnoses, the study results do not allow us to state that the molecular features of MSUD variant phenotypes are predictive of clinical severity.

Essential and toxic elements in human milk concentrate with human milk lyophilizate: A preclinical study.

Concentrated human milk (HM-concentrate) can be obtained from the simple and inexpensive method of donated breast milk direct lyophilization. A previous study reported that HM-concentrate contains the adequate amount of main macro- and micronutrients for use as a nutritional resource for preterm infants with very low birth weight admitted to neonatal intensive care units. However, further details need to be elucidated about HM-concentrate composition, particularly its content of essential and potentially toxic trace elements. Therefore, this study aimed to determine the concentration of essential and toxic elements in human milk considered baseline (HM-baseline) and HM-concentrate, as well as to quantify changes in concentration of these elements after the HM concentration process. The concentration of Aluminum, Arsenic, Cadmium, Chromium, Iron, Mercury, Manganese, Nickel, Lead, Selenium, Tin, and Thallium was analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). Moreover, Bayesian linear mixed effect models were applied to estimate the mean difference between HM-baseline and HM-concentrate samples. After comparison (HM-concentrate versus HM-baseline), a significant increase in concentration was observed only for Manganese (0.80 µg/L; 95% CrI [0.16; 1.43]) and Selenium (6.74 µg/L; 95% CrI [4.66; 8.86]), while Lead concentration (-6.13 µg/L; 95% CrI [-8.63; -3.61]) decreased. This study provides latest and reliable information about HM composition. After milk concentration by lyophilization, there was a significant increase only in the essential elements Manganese and Selenium. The essential micronutrient content in HM-concentrate was similar or higher than that in preterm mothers' milk, which suggests it is viable for nutritional support of preterm infants. In addition, the low concentrations of potentially toxic elements in HM-concentrate indicates that it is safe for consumption by premature newborns.

DNA damage is inversely associated to blood levels of DHA and EPA fatty acids in Brazilian children and adolescents.

This study aimed to investigate the association between DNA damage and blood levels of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), retinol, beta-carotene and riboflavin in Brazilian children and adolescents. Subjects (n = 140) were healthy boys and girls aged 9 to 13 years in Ribeirão Preto (SP, Brazil). Data collection included anthropometry, assessment of energy intake and blood sampling. DNA damage was evaluated by single-cell gel electrophoresis (comet assay). Principal component analysis (PCA) was used to verify associations between blood concentrations of vitamins, polyunsaturated fatty acids and DNA damage. Multiple regression analyses, k-means cluster, and analysis of covariance (ANCOVA), adjusted for confounding variables such as age, sex, energy intake, body mass index and total cholesterol (when needed), were applied to confirm the associations. PCA explained 69.4% of the inverse relationships between DNA damage and blood levels of DHA, EPA, retinol, and beta-carotene. Results were confirmed by ANCOVA and multiple regression analyses for DHA and EPA. In conclusion, omega-3-fatty acids were inversely associated with DNA damage in Brazilian children and adolescents and may be a protective factor against the development of future diseases.

The Role of Rehabilitation Specialists in Canadian NICUs: A 21st Century Perspective.

Rehabilitation specialists are an integral part of the team in the neonatal intensive care unit (NICU). New approaches to rehabilitation practice in the NICU have evolved over the past decade that aim to promote child health and development. AIMS: The aim of this study was to describe the current roles of the occupational therapist (OT), physical therapist (PT) and speech-language pathologist (SLP) in Canadian NICUs as compared to the roles documented in an earlier national survey conducted 15 years ago. METHODS: A telephone survey was conducted across Canadian NICUs and each telephone interview was recorded by a research assistant. In total, 42 questionnaires were completed across 25 health care institutions. RESULTS: Eighty percent of the PT, 93.7% of OT and 50% of SLP provided direct services to neonates in the NICU. The results demonstrated that the therapists were involved with case discussion (85.7%), decision-making (97.6%), referrals to other services (97.6%) and discharge planning (97.6%). Splinting (87.5%) and feeding (100%) were most often carried out by OT, whereas chest physiotherapy (65%) and range of motion (100%) were predominantly provided by PT. Changes in the role of rehabilitation specialists over the last decade predominantly included enhanced collaboration with the NICU team, more frequent use of standardized outcome measures and use of interventions supported by evidence. CONCLUSION: In comparison with results of the previous survey of rehabilitation practices in Canadian NICUs, rehabilitation specialists now have more dedicated time in the NICU and more frequently use standardized measures and apply interventions that are supported by recent scientific studies.

Human milk enriched with human milk lyophilisate for feeding very low birth weight preterm infants: A preclinical experimental study focusing on fatty acid profile.

BACKGROUND: Human milk, with essential nutrients and long chain polyunsaturated fatty acids (LC-PUFAs) such as the omega 3 and 6 fatty acids is important for development of the central nervous system and the retina in very low birth weight infants (<1,500 g). However, breast milk may not be sufficient to meet these needs. The possibility of supplementing breast milk with a lyophilisate of human milk was explored in this study. The objectives of this study were to determine the total lipid content and the lipid profile of the Human Milk on Baseline (HMB) and that of the Concentrates with the Human Milk + lyophilisate (with lyophilisate of milk in the immediate period (HMCI), at 3 months (HMC3m), and at 6 months (HMC6m) of storage). METHODS: Fifty donors from the Human Milk Bank of Children's Hospital provided consent, and donated milk samples. Macronutrient (including total lipids) quantification was performed using the MIRIS® Human Milk Analyzer, and the fatty acid profile was determined by gas chromatography (CG-FID, SHIMADZU®). RESULTS: There was a higher lipid concentration in HMCI relative to HMB. The concentrations of the main fatty acids (% of total) were as follows: palmitic acid (C16:0) HMB, 22.30%; HMCI, 21.46%; HMC3m, 21.54%; and HMC6m, 21.95% (p<0.01); oleic acid (C18:1n-9) HMB, 30.41%; HMCI, 30.47%; HMC3m, 30.55%; and HMC6m, 29.79% (p = 0.46); linoleic acid (C18:2n-6) HMB, 19.62%; HMCI, 19.88%; HMC3m, 19.49%; and HMC6m, 19.45% (p = 0.58); arachidonic acid (C20:4n-6) HMB, 0.35%; HMCI, 0.16%; HMC3m, 0.13%; and HMC6m, 0.15% (p<0.01); α-linolenic acid (C18:3n-3) HMB,1.32%; HMCI, 1.37%; HMC3m, 1.34%; and 1.34% HMC6m (p = 0.14); docosahexaenoic acid (C22:6n-3) HMB, 0.10%; HMCI, 0.06%; HMC3m, 0.05%; and HMC6m, 0.06% (p<0.01). There were no significant changes in the lipid profile when stored. There was no evidence of peroxidation during storage. CONCLUSIONS: Freeze-dried human milk fortified with a human milk concentrate brings potential benefits to newborns, mainly by preserving the essential nutrients present only in breast milk; however, further clinical studies are required to evaluate the safety and efficacy of the concentrate as a standard nutritional food option for very low birth weight infants.

Gestational, perinatal, and postnatal factors that interfere with practice of exclusive breastfeeding by six months after birth.

BACKGROUND: Despite evidences indicating the superiority of breastfeeding and recent advances in the indicators of breastfeeding in Brazil, exclusive breastfeeding (EBF) during the first six months after birth continues to be an infrequent practice in the country. The objective of the present study was to determine which gestational, perinatal, and postnatal factors of the mother-baby dyad might be associated with the cessation of EBF by six months after birth. METHODS: Data were collected at the rooming-in facility of the Reference Center of Women's Health of Ribeirão Preto-Mater (CRSM-Mater) during the postpartum period (24 to 72 h after birth) from December 2012 to April 2013 and by telephone contact between the researcher and participating mothers by six months after birth. Questionnaires were applied to collect data, such as the practice of EBF in the last 24 h in the sixth month after birth. The hierarchical theoretical model was proposed and data were analyzed statistically by log-binomial regression models using SAS 9.3. RESULTS: The study involved 283 mother-baby dyads in which the mother evaluated did not present pregnancy-puerperal complications that could impede breastfeeding and confirmed the interest in breastfeeding her child. After the telephone contact in the exact sixth month after the birth of each participating baby, 84.8% of the participating mothers reported that they were no longer exclusively breastfeeding their babies. After statistical analysis, we found that there was a significant association between cessation of EBF and maternal report of previous experience with EBF for one month (0.91, 95% CI 0.81, 0.99) and six months (0.81; 95% CI 0.68, 0.94). These practices were associated with the maintenance of EBF and, even after adjustment for maternal socio-demographic variables, this association was maintained (0.85; 95% CI 0.73, 0.99). Thus, there is a greater chance of practicing and maintaining EBF by six months after birth when mother had previous experience with it. CONCLUSION: The identification of the risk variables associated with cessation of EBF by six months postpartum, such as previous experience with exclusive breastfeeding, may contribute to the effectiveness of EBF intervention and support measures during the first six months after birth.

Living related versus deceased donor liver transplantation for maple syrup urine disease.

Maple syrup urine disease (MSUD) is an inherited disorder of branched chain ketoacid (BCKA) oxidation associated with episodic and chronic brain disease. Transplantation of liver from an unrelated deceased donor restores 9-13% whole-body BCKA oxidation capacity and stabilizes MSUD. Recent reports document encouraging short-term outcomes for MSUD patients who received a liver segment from mutation heterozygous living related donors (LRDT). To investigate effects of living related versus deceased unrelated grafts, we studied four Brazilian MSUD patients treated with LRDT who were followed for a mean 19 ± 12 postoperative months, and compared metabolic and clinical outcomes to 37 classical MSUD patients treated with deceased donor transplant. Patient and graft survival for LRDT were 100%. Three of 4 MSUD livers were successfully domino transplanted into non-MSUD subjects. Following LRDT, all subjects resumed a protein-unrestricted diet as mean plasma leucine decreased from 224 ± 306 µM to 143 ± 44 µM and allo-isoleucine decreased 91%. We observed no episodes of hyperleucinemia during 80 aggregate postoperative patient-months. Mean plasma leucine:isoleucine:valine concentration ratios were ~2:1:4 after deceased donor transplant compared to ~1:1:1.5 following LRDT, resulting in differences of predicted cerebral amino acid uptake. Mutant heterozygous liver segments effectively maintain steady-state BCAA and BCKA homeostasis on an unrestricted diet and during most catabolic states, but might have different metabolic effects than grafts from unrelated deceased donors. Neither living related nor deceased donor transplant affords complete protection from metabolic intoxication, but both strategies represent viable alternatives to nutritional management.

Bioelectrical impedance vector analysis in obese women before and after bariatric surgery: changes in body composition.

OBJECTIVE: Because of the inefficacy of standard methods for the evaluation of body composition of grade III obese individuals, it is difficult to analyze the quality of weight loss after bariatric surgery in these patients. Electrical bioimpedance vector analysis and the RXc graph uses crude resistance (R) and reactance (Xc) values, like components of the Z vector, to monitor variations in body fluid and the nutritional status of obese individuals. Using bioelectrical impedance vector analysis (BIVA) and the RXc graph, the objective of the present study was to evaluate long-term changes in weight and body composition of obese women after Roux-en-Y bariatric surgery. METHODS: A study was conducted on 43 grade III obese women submitted to bariatric surgery. Anthropometric and bioimpedance (800 mA-50 kHz) data were obtained during the preoperative period and 1, 2, 3, and 4 y after surgery. BIVA was performed by plotting resistance and reactance values corrected for body height (R/H and Xc/H, Ohm/m) as bivariates on the RXc graph. BIVA software was used to plot the vectors of the RXc plane. RESULTS: Surgery promoted changes in body composition, with a reduction of fat mass and of fat-free mass. During the postoperative period, the vectors demonstrated migration to the right lower quadrant of the graph, corresponding to the classification of cachexia and water retention. CONCLUSION: Weight loss due to surgery results in an important reduction of fat-free mass characterized by the position of most individuals in the cachexia quadrant throughout the postoperative period.

Bioelectrical impedance vector analysis (BIVA) in stable preterm newborns.

OBJECTIVE: To observe the behavior of the plotted vectors on the RXc (R - resistance - and Xc - reactance corrected for body height/length) graph through bioelectrical impedance analysis (BIVA) and phase angle (PA) values in stable premature infants, considering the hypothesis that preterm infants present vector behavior on BIVA suggestive of less total body water and soft tissues, compared to reference data for term infants. METHODS: Cross-sectional study, including preterm neonates of both genders, in-patients admitted to an intermediate care unit at a tertiary care hospital. Data on delivery, diet and bioelectrical impedance (800 mA, 50 kHz) were collected. The graphs and vector analysis were performed with the BIVA software. RESULTS: A total of 108 preterm infants were studied, separated according to age (< 7 days and ≥ 7 days). Most of the premature babies were without the normal range (above the 95% tolerance intervals) existing in literature for term newborn infants and there was a tendency to dispersion of the points in the upper right quadrant, RXc plan. The PA was 4.92° (±2.18) for newborns < 7 days and 4.34° (±2.37) for newborns ≥ 7 days. CONCLUSION: Premature infants behave similarly in terms of BIVA and most of them have less absolute body water, presenting less fat free mass and fat mass in absolute values, compared to term newborn infants.

Deuterium equilibrium time in saliva of newborn infants.

UNLABELLED: There is an increasing interest about the use of stable isotopes for body composition analysis in pediatrics. To ensure the success of total body water analysis by the deuterium dilution method, it is fundamental to determine the equilibrium time (plateau) of deuterium in the body fluid studied. OBJECTIVES: We report here the equilibration time of deuterium oxide in the saliva of newborns after oral intake of the isotope. METHODS: Twenty healthy term newborn infants, 10 males and 10 females, were analyzed. Saliva was collected from each newborn before the oral administration of a 100 mg/kg dose of deuterium oxide (baseline sample) and then at 1-hour intervals for 5 hours after administration. Deuterium enrichment of saliva was determined by isotope ratio mass spectrometry according to the recommendations of the International Atomic Energy Agency. RESULTS: The plateau time of deuterium in saliva occurred 3 hours after oral administration of the stable isotope. CONCLUSION: These data are essential for further studies on the body composition of newborn infants. To the best of our knowledge, this is the first study regarding the equilibration time of deuterium in the saliva of term newborns.

Assessment of vitamin A nutritional status in newborn preterm infants.

OBJECTIVE: This study assessed the vitamin A nutritional status of preterm infants determined by the vitamin A relative dose-response test (RDR) compared with serum levels of vitamin A, retinol-binding protein (RBP), transthyretin (TTR), and retinol relations with carrier proteins. METHODS: Serum levels of retinol, RBP, and TTR and retinol/RBP, retinol/TTR, and RBP/TTR molar ratios were determined in 120 infants at 7 d and in 92 at 28 d. For the determination of the performance of the tests, the RDR was considered the reference method. The sensitivity and specificity for all possible cutoff values were determined by constructing receiver operator characteristic curves. The areas under the curves were used to estimate the overall accuracy of the tests. The best cutoff values to be used for the calculation of sensitivity and specificity were determined with 95% confidence intervals. RESULTS: RDR indicated vitamin A deficiency in 60% of the infants at 7 d and in 51.1% at 28 d. In the receiver operator characteristic curves, the best area under the curve was 0.710 obtained for serum retinol at 28 d of postnatal age and considered moderately accurate. The least inadequate cutoff level was set at 25 mg/dL, but no value was considered adequate due to low sensitivity and/or low specificity. CONCLUSION: Compared with RDR, the determination of serum levels of retinol, RBP, and TTR and their molar ratios are not adequate to assess nutritional vitamin A status in preterm infants.

[Nutritional dilemmas in extremely low birth weight infants and their effects on childhood, adolescence and adulthood]. / Dilemas nutricionais no pré-termo extremo e repercussões na infância, adolescência e vida adulta.

OBJECTIVE: To review the recent medical literature on nutrition of extremely low birth weight infants, focusing on nutritional disorders and their effects on childhood, adolescence and adulthood. SOURCES OF DATA: An extensive review of the related literature was performed using MEDLINE, the Cochrane Database of Systematic Reviews and the Best Evidence database. SUMMARY OF THE FINDINGS: There is a growing body of evidence that early nutritional practices may affect short-term growth and development outcome. In addition, these practices may play a role in determining adult health and disease. There is still much to be learned about safe and efficacious nutrient administration in preterm infants; about techniques to assess the effect of different nutritional strategies; and about the long-term effects of these regimens on development outcome, growth and disease. CONCLUSION: Despite recent progress in neonatal nutrition, there is a lack of basic and clinical research to better define the nutritional requirements of preterm infants and the best way to meet these requirements, avoiding long-term undesirable consequences.