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Early postnatal hypoferremia in low birthweight and preterm babies: A prospective cohort study in hospital-delivered Gambian neonates.

ABSTRACT: BACKGROUND:Neonates, particularly those born preterm (PTB) and with low birthweight (LBW), are especially susceptible to bacterial and fungal infections that cause an estimated 225,000 deaths annually. Iron is a vital nutrient for the most common organisms causing septicaemia. Full-term babies elicit an immediate postnatal hypoferremia assumed to have evolved as an innate defence. We tested whether PTB and LBW babies are capable of the same response. METHODS:We conducted an observational study of 152 babies who were either PTB (born ?32 to <37 weeks gestational age) and/or LBW (<2500 g) (PTB/LBW) and 278 term, normal-weight babies (FTB/NBW). Blood was sampled from the umbilical cord vein and artery, and matched venous blood samples were taken from all neonates between 6-24 h after delivery. We measured haematological, iron and inflammatory markers. FINDINGS:In both PTB/LBW and FTB/NBW babies, serum iron decreased 3-fold within 12 h of delivery compared to umbilical blood (7·5 ± 4·5 vs 23·3 ± 7·1 ng/ml, P < 0·001, n = 425). Transferrin saturation showed a similar decline with a consequent increase in unsaturated iron-binding capacity. C-reactive protein levels increased over 10-fold (P < 0·001) and hepcidin levels doubled (P < 0·001). There was no difference in any of these responses between PTB/LBW and FTB/NBW babies. INTERPRETATION:Premature or low birthweight babies are able to mount a very rapid hypoferremia that is indistinguishable from that in normal term babies. The data suggest that this is a hepcidin-mediated response triggered by acute inflammation at birth, and likely to have evolved as an innate immune response against bacterial and fungal septicaemia. TRIAL REGISTRATION:clinicaltrials.gov (NCT03353051). Registration date: November 27, 2017. FUNDING:Bill & Melinda Gates Foundation (OPP1152353).

SUBMITTER: Cross JH

PROVIDER: S-EPMC6992934 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Early postnatal hypoferremia in low birthweight and preterm babies: A prospective cohort study in hospital-delivered Gambian neonates.

Cross James H JH Jarjou Ousman O Mohammed Nuredin Ibrahim NI Rayment Gomez Santiago S Touray Bubacarr J B BJB Prentice Andrew M AM Cerami Carla C

EBioMedicine 20200122

<h4>Background</h4>Neonates, particularly those born preterm (PTB) and with low birthweight (LBW), are especially susceptible to bacterial and fungal infections that cause an estimated 225,000 deaths annually. Iron is a vital nutrient for the most common organisms causing septicaemia. Full-term babies elicit an immediate postnatal hypoferremia assumed to have evolved as an innate defence. We tested whether PTB and LBW babies are capable of the same response.<h4>Methods</h4>We conducted an observ ...[more]

PMID: 31981986

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Project description:Introduction: Fetal inflammatory response syndrome (FIRS), defined as elevated umbilical cord blood interleukin-6 (IL-6) values > 11 pg/ml, is associated with an increased risk of neonatal morbidity and mortality. The primary aim of the present study was to evaluate a potential influence of FIRS on cerebral oxygen saturation (crSO2) and fractional tissue oxygen extraction (cFTOE) during immediate postnatal transition in preterm neonates. The secondary aim was to analyze the potential influence of FIRS on cerebral injury and mortality. Methods: Secondary outcome parameters of prospective observational studies were analyzed. Preterm neonates with measured IL-6 values from umbilical cord blood and cerebral near-infrared spectroscopy (NIRS) measurements during immediate transition after birth were included. Preterm neonates with FIRS (FIRS group) were matched 1:1 for gestational age (± 1 week) to preterm neonates without FIRS (non-FIRS group). crSO2, cFTOE, arterial oxygen saturation (SpO2), heart rate (HR), and fraction of inspired oxygen (FiO2) were compared between both groups. In addition, cerebral injury and mortality were compared between both groups. Results: A total of 46 preterm neonates were included. Twenty-three neonates in the FIRS group [median gestational age 32.1 (IQR 30.3-33.0) weeks; median IL-6 19.7 (IQR 12.2-37.0) pg/ml] were compared to 23 neonates in the non-FIRS group [gestational age: 32.0 (30.4-33.1) weeks; IL-6: 5.4 (3.0-6.7) pg/ml]. cFTOE showed significantly lower values within the first 4 min and a trend toward lower values in minute 5 after birth in the FIRS group. There were no significant differences in crSO2 within the first 15 min after birth between the two groups. SpO2 was significantly lower in minutes 5 and 6 and HR was significantly lower in minutes 2 and 4 after birth in the FIRS group compared to the non-FIRS group. Survival without cerebral injury was similar in both groups. Conclusion: In preterm neonates with FIRS the crSO2 was similar despite significantly lower cFTOE values during the first minutes after birth. This observation may be a result of compromised oxygen consumption and delivery in the first minutes after birth in neonates with FIRS.

Project description:BackgroundWomen who develop diabetes during pregnancy are at higher risk of preterm birth. Here, we identified differentially expressed proteins (DEPs) in the serum of umbilical cord blood samples obtained from preterm neonates delivered by women with gestational diabetes to provide therapeutic targets for clinical drug development.Materials and methodsUmbilical cord blood was collected after delivery of preterm neonates by women with gestational diabetes and after delivery of healthy neonates by women without diabetes. DEPs in the serum samples were identified using liquid chromatography-tandem mass spectrometry. Gene Ontology (GO), cluster analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to determine the biological functions associated with these DEPs. Enzyme linked immunosorbent assay was used to confirm the key DEPs.ResultsWe found that 21 proteins were significantly upregulated, and 51 proteins were significantly downregulated in 72 DEPs in serum samples. GO analyses showed that the DEPs were mainly associated with the GO terms cellular process, biological regulation, cellular anatomical entity, and binding. KEGG signaling pathway analysis indicated that most of the upregulated DEPs were associated with the complement and coagulation cascades, Staphylococcus aureus infection, pertussis, HIF-1 signaling pathway and PPAR signaling pathway and that most of the downregulated DEPs were associated with the complement and coagulation cascades, dilated cardiomyopathy, pathways in cancer, Chagas disease, and hypertrophic cardiomyopathy. The results of KEGG pathway annotation and enrichment analyses indicated that changes in the complement and coagulation cascades may be importantly associated with preterm delivery of neonates by women with gestational diabetes. The key DEPs were confirmed by enzyme linked immunosorbent assay.ConclusionOur proteomics and bioinformatics analyses identified several key proteins and the complement and coagulation cascades pathway that warrant further investigation as potential novel therapeutic targets in preterm delivery among women with gestational diabetes.

Project description:Background: Neonatal infection is the third largest cause of death in children under five worldwide. Nutritional immunity is the process by which the host innate immune system limits nutrient availability to invading organisms. Iron is an essential micronutrient for both microbial pathogens and their mammalian hosts. Changes in iron availability and distribution have significant effects on pathogen virulence and on the immune response to infection. Our previously published data shows that, during the first 24 hours of life, full-term neonates have reduced overall serum iron. Transferrin saturation decreases rapidly from 45% in cord blood to ~20% by six hours post-delivery. Methods: To study neonatal nutritional immunity and its role in neonatal susceptibility to infection, we will conduct an observational study on 300 full-term normal birth weight (FTB+NBW), 50 preterm normal birth weight (PTB+NBW), 50 preterm low birth weight (PTB+LBW) and 50 full-term low birth weight (FTB+LBW), vaginally-delivered neonates born at Kanifing General Hospital, The Gambia. We will characterize and quantify iron-related nutritional immunity during the early neonatal period and use ex vivo sentinel bacterial growth assays to assess how differences in serum iron affect bacterial growth. Blood samples will be collected from the umbilical cord (arterial and venous) and at serial time points from the neonates over the first week of life. Discussion: Currently, little is known about nutritional immunity in neonates. In this study, we will increase understanding of how nutritional immunity may protect neonates from infection during the first critical days of life by limiting the pathogenicity and virulence of neonatal sepsis causing organisms by reducing the availability of iron. Additionally, we will investigate the hypothesis that this protective mechanism may not be activated in preterm and low birth weight neonates, potentially putting these babies at an enhanced risk of neonatal infection. Trial registration: clinicaltrials.gov ( NCT03353051) 27/11/2017.

Project description:BackgroundPreterm delivery is among the major public health problems worldwide and the leading cause of morbidity and mortality among neonates. Postnatal poor weight gain, which can contribute to mortality, can be influenced by feeding practices, medical complications and quality of care that is provided to these high-risk neonates. This study aimed to investigate the proportion and predictors of poor weight gain among preterm neonates at Muhimbili National Hospital (MNH), from September 2018 to February 2019.MethodsA hospital-based prospective cohort study involving preterm neonates with Gestation age (GA) < 37 weeks receiving care at MNH. Eligible preterm, were consecutively recruited at admission and followed up until discharge, death or end of neonatal period. Poor weight gain was defined as weight gain less than 15 g per kg per day. The risk factors associated with poor weight gain were evaluated. Predictors of poor weight gain were evaluated using a multivariate analysis. Results were considered statistically significant if P -value was < 0.05 and 95% confidence interval (CI) did not include 1.ResultsA total of 227 preterm neonates < 37 weeks GA, with male to female ratio of 1:1.2 were enrolled in the study. The overall proportion of preterm with poor weight gain was 197/227 (86.8%). Proportion of poor weight gain among the early and late preterm babies, were 100/113 (88.5%) and 97/114 (85.1%) respectively. Predictors of poor weight gain were low level of maternal education (AOR = 2.58; 95%Cl: 1.02-6.53), cup feeding as the initial method of feeding (AOR = 8.65; 95%Cl: 1.59-16.24) and delayed initiation of the first feed more than 48 h (AOR = 10.06; 95%Cl: 4.14-24.43). A previous history of preterm delivery was protective against poor weight gain (AOR = 0.33; 95% Cl: 0.11-0.79).Conclusion and recommendationPoor weight gain was a significant problem among preterm neonates receiving care at MNH. This can be addressed by emphasizing on early initiation of feed and tube feeding for neonates who are not able to breastfeed. Health education and counselling to mothers focusing on feeding practices as well as close supervision of feeding especially for mothers experiencing difficulties in feeding their preterm will potentially minimize risk of growth failure.

Project description:BackgroundTo identify preterm infants at risk for neurodevelopment impairment that might benefit from early neurorehabilitation, early prognostic biomarkers of future outcomes are needed.ObjectiveTo determine whether synthetic MRI is sensitive to age-related changes in regional tissue relaxation times in the brain of preterm born neonates when scanned at term equivalent age (TEA, 37-42 weeks), and to investigate whether severe postnatal morbidity results in prolonged regional tissue relaxation times.Materials and methodsThis retrospective study included 70 very preterm born infants scanned with conventional and synthetic MRI between January 2017 and June 2019 at TEA. Infants with severe postnatal morbidity were allocated to a high-risk group (n = 22). All other neonates were allocated to a low-risk group (n = 48). Linear regression analysis was performed to determine the relationship between relaxation times and postmenstrual age (PMA) at scan. Analysis of covariance was used to evaluate the impact of severe postnatal morbidity in the high-risk group on T1 and T2 relaxation times. Receiver operating characteristic (ROC) curves were plotted and analysed with area under the ROC curve (AUC) to evaluate the accuracy of classifying high-risk patients based on regional relaxation times.ResultsA linear age-related decrease of T1 and T2 relaxation times correlating with PMA at scan (between 37 and 42 weeks) was found in the deep gray matter, the cerebellum, the cortex, and the posterior limb of the internal capsule (PLIC) (p < .005 each), but not in the global, frontal, parietal, or central white matter. Analysis of covariance for both risk groups, adjusted for PMA, revealed significantly prolonged regional tissue relaxation times in neonates with severe postnatal morbidity, which was best illustrated in the central white matter of the centrum semiovale (T1 ? = 11.5%, T2 ? = 13.4%, p < .001) and in the PLIC (T1 ? = 9.2%, T2 ? = 6.9%, p < .001). The relaxation times in the PLIC and the central white matter predicted high-risk status with excellent accuracy (AUC range 0.82-0.86).ConclusionSynthetic MRI-based relaxometry in the brain of preterm born neonates is sensitive to age-related maturational changes close to TEA. Severe postnatal morbidity correlated with a significant delay in tissue relaxation. Synthetic MRI may provide early prognostic biomarkers for neurodevelopment impairment.

Dataset Information

Early postnatal hypoferremia in low birthweight and preterm babies: A prospective cohort study in hospital-delivered Gambian neonates.

Publications

Early postnatal hypoferremia in low birthweight and preterm babies: A prospective cohort study in hospital-delivered Gambian neonates.

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