Neonatology[JOURNAL]
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200 papers
Urinary Lactate-To-Creatinine Ratio during the First Days of Life Correlates with the Degree of Brain Damage in Premature Infants.
Zasada M, Olszewska M, Kowalik A … +5 more , Berska J, Bugajska J, Karcz P, Herman-Sucharska I, Kwinta P
Neonatology · 2025 · PMID 39657616 · Full text
INTRODUCTION: This study aimed to assess the association between the urinary lactate-to-creatinine ratio (ULCR) and brain spectroscopy (1H-MRS) findings in very low gestational age (VLGA) infants with and without preterm...
INTRODUCTION: This study aimed to assess the association between the urinary lactate-to-creatinine ratio (ULCR) and brain spectroscopy (1H-MRS) findings in very low gestational age (VLGA) infants with and without preterm brain injury. METHODS: Urine samples were collected from 54 VLGA infants during the first week of life, after 1 month of life, and at term-equivalent age (TEA). Urinary lactate was measured via highly selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a quantitative organic acid analysis kit and expressed as the ULCR. Magnetic resonance imaging and 1H-MRS were performed at TEA. The Kidokoro grading system was used to assess the Global Brain Abnormality Score (GBAS). RESULTS: VLGA infants with a GBAS moderate + severe had higher ULCRs on the 2nd and 3rd days of life (DOLs) than those with a GBAS normal or mild. Only the GBAS moderate + severe subgroup presented with a secondary increase in the ULCR on the 3rd DOL, whereas in the GBAS normal or mild, the ULCR oscillated around similar values or gradually decreased. Significant positive correlations were detected between the ULCR on the 3rd DOL and the lactate/creatinine and lactate/N-acetyl aspartate ratios measured via 1H-MRS at TEA (r = 0.308; p = 0.022 and r = 0.334; p = 0.013, respectively). CONCLUSIONS: An increased ULCR during the first 3 DOLs in patients with a GBAS moderate + severe suggest an energy catastrophe that may play a role in the development of premature brain injury. Serial measurement of the ULCR during the first DOLs may help in the early identification of premature infants at risk for moderate + severe brain damage. INTRODUCTION: This study aimed to assess the association between the urinary lactate-to-creatinine ratio (ULCR) and brain spectroscopy (1H-MRS) findings in very low gestational age (VLGA) infants with and without preterm brain injury. METHODS: Urine samples were collected from 54 VLGA infants during the first week of life, after 1 month of life, and at term-equivalent age (TEA). Urinary lactate was measured via highly selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a quantitative organic acid analysis kit and expressed as the ULCR. Magnetic resonance imaging and 1H-MRS were performed at TEA. The Kidokoro grading system was used to assess the Global Brain Abnormality Score (GBAS). RESULTS: VLGA infants with a GBAS moderate + severe had higher ULCRs on the 2nd and 3rd days of life (DOLs) than those with a GBAS normal or mild. Only the GBAS moderate + severe subgroup presented with a secondary increase in the ULCR on the 3rd DOL, whereas in the GBAS normal or mild, the ULCR oscillated around similar values or gradually decreased. Significant positive correlations were detected between the ULCR on the 3rd DOL and the lactate/creatinine and lactate/N-acetyl aspartate ratios measured via 1H-MRS at TEA (r = 0.308; p = 0.022 and r = 0.334; p = 0.013, respectively). CONCLUSIONS: An increased ULCR during the first 3 DOLs in patients with a GBAS moderate + severe suggest an energy catastrophe that may play a role in the development of premature brain injury. Serial measurement of the ULCR during the first DOLs may help in the early identification of premature infants at risk for moderate + severe brain damage.
Rationale and Approach to Evaluating Interventions for Newborn Care in Low- and Middle-Income Countries.
Harrison L, Vaivada T, Yasin R … +2 more , Das JK, Bhutta ZA
Neonatology · 2025 · PMID 39653031 · Full text
INTRODUCTION: The neonatal period is the most vulnerable time in a child's life, contributing to almost half of all deaths in children under 5 years. Many of these deaths are preventable and are mainly caused by preterm...
INTRODUCTION: The neonatal period is the most vulnerable time in a child's life, contributing to almost half of all deaths in children under 5 years. Many of these deaths are preventable and are mainly caused by preterm birth, birth asphyxia, or serious infections. Over the past decade, the evidence base for interventions to prevent and manage these causes of neonatal mortality and morbidity in low- and middle-income countries (LMICs) has expanded significantly. This growth calls for a comprehensive and systematic approach to synthesizing the available evidence. This paper describes the methodological approach taken before and during the conduct of the systematic overviews and reviews described in the online supplementary material (for all online suppl. material, see <ext-link ext-link-type="doi" xlink:href="https://doi.org/10.1159/000542754" xmlns:xlink="http://www.w3.org/1999/xlink">https://doi.org/10.1159/000542754</ext-link>). METHODS: Alongside consultation with a newborn technical advisory group, the overall evidence synthesis approach began with an extensive literature-scoping exercise to establish a universe of interventions that were relevant to neonatal health and survival and to identify the associated systematic reviews examining their effectiveness. Three main approaches were taken to synthesize the evidence based on the availability of prior evidence. New systematic reviews were conducted for topics lacking an existing comprehensive synthesis. Existing systematic reviews with search dates prior to 2020 were updated. High-quality, up-to-date systematic reviews were used without modification. In all cases, trial data from studies conducted in LMICs were sought and prioritized for analysis. CONCLUSION: A comprehensive approach to summarizing the best available evidence for newborn intervention effectiveness is described. INTRODUCTION: The neonatal period is the most vulnerable time in a child's life, contributing to almost half of all deaths in children under 5 years. Many of these deaths are preventable and are mainly caused by preterm birth, birth asphyxia, or serious infections. Over the past decade, the evidence base for interventions to prevent and manage these causes of neonatal mortality and morbidity in low- and middle-income countries (LMICs) has expanded significantly. This growth calls for a comprehensive and systematic approach to synthesizing the available evidence. This paper describes the methodological approach taken before and during the conduct of the systematic overviews and reviews described in the online supplementary material (for all online suppl. material, see <ext-link ext-link-type="doi" xlink:href="https://doi.org/10.1159/000542754" xmlns:xlink="http://www.w3.org/1999/xlink">https://doi.org/10.1159/000542754</ext-link>). METHODS: Alongside consultation with a newborn technical advisory group, the overall evidence synthesis approach began with an extensive literature-scoping exercise to establish a universe of interventions that were relevant to neonatal health and survival and to identify the associated systematic reviews examining their effectiveness. Three main approaches were taken to synthesize the evidence based on the availability of prior evidence. New systematic reviews were conducted for topics lacking an existing comprehensive synthesis. Existing systematic reviews with search dates prior to 2020 were updated. High-quality, up-to-date systematic reviews were used without modification. In all cases, trial data from studies conducted in LMICs were sought and prioritized for analysis. CONCLUSION: A comprehensive approach to summarizing the best available evidence for newborn intervention effectiveness is described.
Characterizing the Role of Left Ventricular Indices and Biventricular Interaction in Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension in Extreme Prematurity.
Gopagondanahalli KR, Sundararaghavan S, Tan TH … +9 more , Yeo KT, Vora SJ, Ng WD, Choo JTL, Ang WL, Binte Mohamad Taib NQ, Han Ying NW, Rajadurai VS, Abdul Haium AA
Neonatology · 2025 · PMID 39631380 · Publisher ↗
INTRODUCTION: Bronchopulmonary dysplasia (BPD) is a common respiratory morbidity in preterm infants. The onset of pulmonary hypertension leads to worse respiratory outcomes. The contribution of left ventricular diastolic...
INTRODUCTION: Bronchopulmonary dysplasia (BPD) is a common respiratory morbidity in preterm infants. The onset of pulmonary hypertension leads to worse respiratory outcomes. The contribution of left ventricular diastolic dysfunction in BPD-PH is well reported. We evaluated the serial left ventricular function and possible ventricular interdependence among BPD-PH. METHODS: This is a single-center, prospective observational study. Infants <28 weeks of gestation are included. RESULTS: Eighty infants were enrolled. The incidence of BPD-PH was 23%. The BPD-PH group had a high incidence of hemodynamically significant ductus arteriosus (83% vs. 56%, p < 0.018), longer oxygen days (96.2 ± 68.1 vs. 59.35 ± 52, p < 0.008), and prolonged hospital stay (133.8 ± 46 vs. 106.5 ± 38 days, p < 0.005). Serial tissue Doppler imaging showed prolonged left ventricle (LV) isovolumetric contraction time (IVCT) (31.05 ± 3.3 vs. 26.8 ± 4.4 ms, p < 0.001) and myocardial performance index (MPI) (0.43 ± 0.03 vs. 0.37 ± 0.04, p < 0.001) from 33 weeks. The changes in IVCT (35.9 ± 6.7 vs. 27.9 ± 4.5 ms, p < 0.001), isovolumetric relaxation time (IVRT) (50 ± 6.5 vs. 39.9 ± 5.8 ms, p < 0.001), and MPI (0.48 ± 0.05 vs. 0.36 ± 0.03, p < 0.001) persisted at 36 weeks. The receiver operator characteristic curve showed LV MPI >40 has 83% sensitivity and 65% specificity (AUC: 0.77, p < 0.001) in the diagnosis of PH. The BPD-PH group had a higher LV E/E' ratio (13.1 ± 4.4 vs. 11.4 ± 3.4, p < 0.02). Pearson correlation test showed a moderate positive correlation between RV MPI and LV MPI (r = 0.585, p < 0.001). CONCLUSIONS: Significant LV diastolic dysfunction was observed in BPD-PH. This is the first study to show biventricular strain and possible ventricular interdependence in BPD-PH. The prolonged LV IVRT and MPI may be a novel echocardiographic indicator of BPD-PH.
Urinary Output of Very Low Birth Weight Infants during the First Weeks of Life.
Cosgun ZC, Burgmaier K, Zeiher M … +6 more , Weber A, Klein R, Aydin A, Kribs A, Mehler K, Habbig S
Neonatology · 2025 · PMID 39616995 · Publisher ↗
INTRODUCTION: Daily urinary output (UOP) serves as important tool to identify acute kidney injury (AKI) in preterm infants. However, reference values for UOP, especially stratified for gestational age (GA), are missing....
INTRODUCTION: Daily urinary output (UOP) serves as important tool to identify acute kidney injury (AKI) in preterm infants. However, reference values for UOP, especially stratified for gestational age (GA), are missing. METHODS: This retrospective single-center study assessed UOP during the first 28 days of life in 128 very low birth weight (VLBW) infants. RESULTS: VLBW infants exhibit a highly dynamic daily UOP profile in the first 28 days of life with a maximum at day 12 with 4.78 mL/kg bodyweight/h. In the subcohort of 64 extremely low gestational age neonates (ELGANs), the highest UOP is measured during the second week of life. Infants born before 24 weeks of gestation have significantly higher UOP than more mature infants. CONCLUSION: UOP is dynamic in the postnatal period and differs significantly between GA cohorts in the subgroup of ELGANs. These data might point to an adaption of the UOP threshold for neonatal AKI in preterm infants.
Reply to Letter to the Editor by Maiwald et al. on "Less Invasive Surfactant Administration for Preterm Infants - State of the Art".
Härtel C, Kribs A, Göpel W … +2 more , Dargaville PA, Herting E
Neonatology · 2025 · PMID 39602904 · Publisher ↗
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Nutritional Management of Low Birth Weight and Preterm Infants in Low- and Low Middle-Income Countries.
Azhar M, Yasin R, Hanif S … +3 more , Bughio SA, Das JK, Bhutta ZA
Neonatology · 2025 · PMID 39591949 · Full text
INTRODUCTION: Preterm and low birth weight (LBW) infants are at an increased risk of morbidity and mortality compared with their term counterparts, with more than 20 million LBW infants born each year, the majority in lo...
INTRODUCTION: Preterm and low birth weight (LBW) infants are at an increased risk of morbidity and mortality compared with their term counterparts, with more than 20 million LBW infants born each year, the majority in lower middle-income countries (LMICs). Given the increased vulnerability and higher nutritional needs of these infants, optimizing feeding strategies may play a crucial role in improving their health outcomes. METHODS: We updated evidence of Every Newborn Series published in The Lancet 2014 by identifying relevant systematic reviews, extracting low-income country (LIC) and LMIC data, and conducting revised meta-analysis for these contexts. RESULTS: We found 15 reviews; the evidence showed that early initiation of enteral feeding reduced neonatal mortality overall, but not in LIC/LMIC settings. Breastfeeding promotion interventions increased the prevalence of early initiation of breastfeeding and exclusive breastfeeding at 3 and 6 months of age in LMIC settings. There was an increased risk of neonatal mortality with formula milk in LIC/LMIC settings. Despite contributing to greater weight gain, there was a higher risk of necrotizing enterocolitis with formula milk overall. Breast milk fortification and nutrient-enriched formula improved growth outcomes. Iron and vitamin A supplementation reduced anemia and mortality rates (LMIC), respectively. The evidence also suggested that benefits of various different micronutrient supplementation interventions such as zinc, calcium/phosphorous, and vitamin D, outweigh the risks since our review demonstrates little to no adverse effects deriving from their supplementation, particularly for a breastfed preterm and/or LBW infant. CONCLUSION: Early adequate nutritional support of preterm or LBW infant is paramount to averse adverse health outcomes, contribute to normal growth, resistance to infection, and optimal development. Breast milk feeding and micronutrient supplementation are crucial to reduce diarrhea incidence and mortality respectively while feed fortification or nutrient-enriched formula, when breast milk is not available, to enhance better growth especially in LMICs where there is higher population of growth restriction and stunting. This review also highlights need for randomized trials in LMICs at large scale to further strengthen the evidence. INTRODUCTION: Preterm and low birth weight (LBW) infants are at an increased risk of morbidity and mortality compared with their term counterparts, with more than 20 million LBW infants born each year, the majority in lower middle-income countries (LMICs). Given the increased vulnerability and higher nutritional needs of these infants, optimizing feeding strategies may play a crucial role in improving their health outcomes. METHODS: We updated evidence of Every Newborn Series published in The Lancet 2014 by identifying relevant systematic reviews, extracting low-income country (LIC) and LMIC data, and conducting revised meta-analysis for these contexts. RESULTS: We found 15 reviews; the evidence showed that early initiation of enteral feeding reduced neonatal mortality overall, but not in LIC/LMIC settings. Breastfeeding promotion interventions increased the prevalence of early initiation of breastfeeding and exclusive breastfeeding at 3 and 6 months of age in LMIC settings. There was an increased risk of neonatal mortality with formula milk in LIC/LMIC settings. Despite contributing to greater weight gain, there was a higher risk of necrotizing enterocolitis with formula milk overall. Breast milk fortification and nutrient-enriched formula improved growth outcomes. Iron and vitamin A supplementation reduced anemia and mortality rates (LMIC), respectively. The evidence also suggested that benefits of various different micronutrient supplementation interventions such as zinc, calcium/phosphorous, and vitamin D, outweigh the risks since our review demonstrates little to no adverse effects deriving from their supplementation, particularly for a breastfed preterm and/or LBW infant. CONCLUSION: Early adequate nutritional support of preterm or LBW infant is paramount to averse adverse health outcomes, contribute to normal growth, resistance to infection, and optimal development. Breast milk feeding and micronutrient supplementation are crucial to reduce diarrhea incidence and mortality respectively while feed fortification or nutrient-enriched formula, when breast milk is not available, to enhance better growth especially in LMICs where there is higher population of growth restriction and stunting. This review also highlights need for randomized trials in LMICs at large scale to further strengthen the evidence.
Antenatal Care Strategies to Improve Perinatal and Newborn Outcomes.
Yasin R, Azhar M, Allahuddin Z … +2 more , Das JK, Bhutta ZA
Neonatology · 2025 · PMID 39581186 · Full text
BACKGROUND: Antenatal care strategies (ANC) play a pivotal role in ensuring a healthy gestational period for expectant mothers and promote optimal outcomes for their babies. Implementing these interventions can contribut...
BACKGROUND: Antenatal care strategies (ANC) play a pivotal role in ensuring a healthy gestational period for expectant mothers and promote optimal outcomes for their babies. Implementing these interventions can contribute to a supportive environment for pregnant women, resulting in positive perinatal and neonatal outcomes. SUMMARY: We summarize evidence for a total of twenty-seven interventions pertaining to ANC from Every Newborn Series published in The Lancet 2014 by identifying the most recent systematic reviews, extracting data from each review, and conducting a subgroup analysis for low-income and lower-middle-income countries (LMICs) for outcomes relevant to maternal and neonatal health. Findings from our paper suggest a paucity in evidence from LMICs, and consolidated efforts are required to narrow this gap to build on more inclusive evidence on ANC. KEY MESSAGES: Evidence from LMICs suggests that antenatal multiple micronutrient supplementation when compared to iron and folic acid had a significant effect on stillbirth, small for gestational age, and low birthweight (LBW). Vitamin D supplementation reduced the risks of preterm birth and LBW. High-dose calcium supplementation, when compared to placebo in pregnancy, lowered the likelihood of developing high blood pressure, preeclampsia, and preterm birth. Antihypertensives significantly reduced the probability of developing severe hypertension, proteinuria/preeclampsia, and severe preeclampsia. Metformin for GDM reduced the risk of neonatal death or serious morbidity composite. Cervical cerclage had no effect on stillbirth, preterm birth, or perinatal and neonatal mortality. Data for anti-D administration for rhesus alloimmunization were limited to HICs. BACKGROUND: Antenatal care strategies (ANC) play a pivotal role in ensuring a healthy gestational period for expectant mothers and promote optimal outcomes for their babies. Implementing these interventions can contribute to a supportive environment for pregnant women, resulting in positive perinatal and neonatal outcomes. SUMMARY: We summarize evidence for a total of twenty-seven interventions pertaining to ANC from Every Newborn Series published in The Lancet 2014 by identifying the most recent systematic reviews, extracting data from each review, and conducting a subgroup analysis for low-income and lower-middle-income countries (LMICs) for outcomes relevant to maternal and neonatal health. Findings from our paper suggest a paucity in evidence from LMICs, and consolidated efforts are required to narrow this gap to build on more inclusive evidence on ANC. KEY MESSAGES: Evidence from LMICs suggests that antenatal multiple micronutrient supplementation when compared to iron and folic acid had a significant effect on stillbirth, small for gestational age, and low birthweight (LBW). Vitamin D supplementation reduced the risks of preterm birth and LBW. High-dose calcium supplementation, when compared to placebo in pregnancy, lowered the likelihood of developing high blood pressure, preeclampsia, and preterm birth. Antihypertensives significantly reduced the probability of developing severe hypertension, proteinuria/preeclampsia, and severe preeclampsia. Metformin for GDM reduced the risk of neonatal death or serious morbidity composite. Cervical cerclage had no effect on stillbirth, preterm birth, or perinatal and neonatal mortality. Data for anti-D administration for rhesus alloimmunization were limited to HICs.
Effectiveness of Neonatal Resuscitation Training Programs, Implementation, and Scale-Up in Low- and Middle-Income Countries.
Sihota D, Lee Him R, Dominguez G … +3 more , Harrison L, Vaivada T, Bhutta ZA
Neonatology · 2025 · PMID 39581184 · Full text
INTRODUCTION: To describe recent evidence regarding the most effective neonatal resuscitation training program and scale-up of these programs in low- and middle-income countries (LMICs), which has contributed to the upco...
INTRODUCTION: To describe recent evidence regarding the most effective neonatal resuscitation training program and scale-up of these programs in low- and middle-income countries (LMICs), which has contributed to the upcoming Lancet Global Newborn Care Series 2025, and forms part of a supplement describing an extensive synthesis on effective newborn interventions in LMICs. METHODS: We included relevant studies from Medline, Embase, CINAHL, Cochrane CENTRAL and Global Index Medicus databases on the effectiveness and scale-up of Neonatal Resuscitation Training Programs (NRTP), with searches run August 2022. Data extraction and quality assessments were completed independently and in duplicate. RESULTS: A total of 93 unique records met the eligibility criteria and were included in our analyses across the reviews. NRTPs improved most knowledge and skill-based outcomes but impact on mortality varied. Included studies identified knowledge and skill retention, standardized training protocols, and limited training opportunities for health care providers as challenges to current NRTPs. CONCLUSION: Reported knowledge, skills, and mortality outcomes were similar across NRTPs. The Helping Babies Breathe (HBB) program was found to be cost-effective in Tanzania, suggesting that the HBB program or elements thereof are low-cost and scalable in LMICs. Future research across diverse settings should evaluate the cost-effectiveness of other NRTPs. To scale-up current NRTPs, programs should focus on improving long-term retention outcomes and improving training material accessibility. INTRODUCTION: To describe recent evidence regarding the most effective neonatal resuscitation training program and scale-up of these programs in low- and middle-income countries (LMICs), which has contributed to the upcoming Lancet Global Newborn Care Series 2025, and forms part of a supplement describing an extensive synthesis on effective newborn interventions in LMICs. METHODS: We included relevant studies from Medline, Embase, CINAHL, Cochrane CENTRAL and Global Index Medicus databases on the effectiveness and scale-up of Neonatal Resuscitation Training Programs (NRTP), with searches run August 2022. Data extraction and quality assessments were completed independently and in duplicate. RESULTS: A total of 93 unique records met the eligibility criteria and were included in our analyses across the reviews. NRTPs improved most knowledge and skill-based outcomes but impact on mortality varied. Included studies identified knowledge and skill retention, standardized training protocols, and limited training opportunities for health care providers as challenges to current NRTPs. CONCLUSION: Reported knowledge, skills, and mortality outcomes were similar across NRTPs. The Helping Babies Breathe (HBB) program was found to be cost-effective in Tanzania, suggesting that the HBB program or elements thereof are low-cost and scalable in LMICs. Future research across diverse settings should evaluate the cost-effectiveness of other NRTPs. To scale-up current NRTPs, programs should focus on improving long-term retention outcomes and improving training material accessibility.
Reference Ranges for Preductal Oxygen Saturation and Heart Rate in Moderate and Late Preterm Infants with Deferred Cord Clamping.
Valles-Murcia N, Solaz-García Á, Pinilla-González A … +6 more , Torrejón-Rodríguez L, Gormaz M, Escrig-Fernández R, González-Timoneda A, Cernada M, Vento M
Neonatology · 2025 · PMID 39581183 · Publisher ↗
INTRODUCTION: Moderate and late preterm (MLPT) infants represent a substantial percentage of all preterm infants and frequently need support in the delivery room. Deferred cord clamping (DCC) improves SpO2 and heart rate...
INTRODUCTION: Moderate and late preterm (MLPT) infants represent a substantial percentage of all preterm infants and frequently need support in the delivery room. Deferred cord clamping (DCC) improves SpO2 and heart rate (HR) stabilization in term infants. However, data on MLPT infants are limited. METHODS: We performed a prospective observational study collecting SpO2 and HR by pulse oximetry in healthy MLPT infants with DDC to construct percentile graphs for the first 10 min after birth. RESULTS: A total of 96 MLPT infants were monitored for preductal SpO2 and HR, and percentiles were calculated. SpO2 mean was significantly lower for MLPT than for term infants during the first 6 min after birth, and 15% did not achieve SpO2 ≥85% in the first 5 min after birth. HR was significantly lower in MLPT infants in the first 4 min after birth; however, HR consistently remained above bradycardic values (>100 bpm). NICU admission and postnatal complications were not different between MLPT achieving SpO2 ≥85% or not. CONCLUSION: MLPT infants with DCC achieved stable SpO2 and HR significantly later, 6 min and 4 min, respectively, than term infants. In addition, 15% of MLPT infants did not achieve SpO2 ≥85% at 5 min after birth. However, admission to the NICU and clinical evolution did not differ from newborns with SpO2 ≥85% at 5 min. Larger studies including long-term follow-up are needed to assess if lower SpO2 in the first 5 min has clinical consequences in non-resuscitated MLPT.
Supportive Care for Common Conditions in Small Vulnerable Newborns and Term Infants: The Evidence.
Jiang L, Lee Him R, Sihota D … +5 more , Muralidharan O, Dominguez G, Harrison L, Vaivada T, Bhutta ZA
Neonatology · 2025 · PMID 39571565 · Publisher ↗
INTRODUCTION: Small vulnerable newborns (SVNs) are at an increased risk of early death and other morbidities. Essential interventions provided to SVN, and other high-risk newborns have been proven critical in improving t...
INTRODUCTION: Small vulnerable newborns (SVNs) are at an increased risk of early death and other morbidities. Essential interventions provided to SVN, and other high-risk newborns have been proven critical in improving their outcomes. We aimed to provide an update on the effectiveness and safety of these interventions in low- and middle-income countries (LMICs). METHOD: Following a comprehensive literature scope, we updated or reanalyzed LMIC-specific evidence for essential SVN care interventions. RESULTS: A total of 113 individual LMIC studies were identified. Most of them were of high risk of bias. Kangaroo mother care significantly reduced SVN's mortality by discharge. Early erythropoiesis stimulating agent lowered SVN's risk of receiving blood transfusion. Prophylactic oral or intravenous ibuprofen resulted in a decreased risk of patent ductus arteriosus in SVN. But it did not have a significant effect on mortality and led to a higher risk of gastrointestinal bleeding. No pooled LMIC data were available for universal screening of hyperbilirubinemia in high-risk newborns. Sunlight therapy had no effect in treating hyperbilirubinemia but increased the risk of hyperthermia. Reflective curtains with phototherapy resulted in a greater and faster decline in bilirubin than standard phototherapy in treating hyperbilirubinemia. Early child development interventions were shown to have a favorable effect on cognitive and motor scores in SVN. The evidence for family involvement and family support was limited and uncertain. CONCLUSION: We present the most updated LMIC evidence for interventions targeting SVN. Despite their effectiveness and safety in improving certain neonatal outcomes, further high-quality trials are required.
The Care of Preterm and Term Newborns with Respiratory Conditions: A Systematic Synthesis of Evidence from Low- and Middle-Income Countries.
Dominguez G, Muralidharan O, Lee Him R … +3 more , Harrison L, Vaivada T, Bhutta ZA
Neonatology · 2025 · PMID 39541964 · Full text
INTRODUCTION: Neonatal respiratory conditions are leading causes of mortality and morbidity during the neonatal period. This review evaluated 11 management interventions for respiratory distress syndrome (RDS), apnoea of...
INTRODUCTION: Neonatal respiratory conditions are leading causes of mortality and morbidity during the neonatal period. This review evaluated 11 management interventions for respiratory distress syndrome (RDS), apnoea of prematurity (AOP), meconium aspiration syndrome (MAS), transient tachypnea of the newborn (TTN), as well as bronchopulmonary dysplasia (BPD) as a potential complication from respiratory care in low- and middle-income countries (LMICs). METHODS: Two different methodological approaches were completed: (1) updating outdated reviews and pooling all LMIC studies and (2) re-analysis of LMIC studies from up-to-date reviews. Review updates were conducted between October 2022 and February 2023 and followed systematic methodology. A total of 50 studies were included across four review updates and seven review re-analyses. RESULTS: Findings indicate that bubble CPAP (RR 0.74, 95% CI: 0.58-0.96) and prophylactic CPAP (RR 0.39, 95% CI: 0.26-0.57) for RDS reduced the risk of treatment failure compared to other ventilation types or supportive care, respectively. Postnatal corticosteroids reduced BPD assessed as oxygen requirement at 36 weeks' postmenstrual age (RR 0.56, 95% CI: 0.41-0.77). All other outcomes were found to be non-significant across remaining interventions. CONCLUSIONS: Our findings indicate that prophylactic and bubble CPAP may provide some benefit by reducing treatment failure compared to other pressure sources. The safety and efficacy of other management interventions for RDS, AOP, BPD, MAS, and TTN remains uncertain given limited evaluations in LMICs. Future research should conduct adequately powered trials in underrepresented LMIC regions, investigate long-term outcomes, and evaluate cost-effectiveness. INTRODUCTION: Neonatal respiratory conditions are leading causes of mortality and morbidity during the neonatal period. This review evaluated 11 management interventions for respiratory distress syndrome (RDS), apnoea of prematurity (AOP), meconium aspiration syndrome (MAS), transient tachypnea of the newborn (TTN), as well as bronchopulmonary dysplasia (BPD) as a potential complication from respiratory care in low- and middle-income countries (LMICs). METHODS: Two different methodological approaches were completed: (1) updating outdated reviews and pooling all LMIC studies and (2) re-analysis of LMIC studies from up-to-date reviews. Review updates were conducted between October 2022 and February 2023 and followed systematic methodology. A total of 50 studies were included across four review updates and seven review re-analyses. RESULTS: Findings indicate that bubble CPAP (RR 0.74, 95% CI: 0.58-0.96) and prophylactic CPAP (RR 0.39, 95% CI: 0.26-0.57) for RDS reduced the risk of treatment failure compared to other ventilation types or supportive care, respectively. Postnatal corticosteroids reduced BPD assessed as oxygen requirement at 36 weeks' postmenstrual age (RR 0.56, 95% CI: 0.41-0.77). All other outcomes were found to be non-significant across remaining interventions. CONCLUSIONS: Our findings indicate that prophylactic and bubble CPAP may provide some benefit by reducing treatment failure compared to other pressure sources. The safety and efficacy of other management interventions for RDS, AOP, BPD, MAS, and TTN remains uncertain given limited evaluations in LMICs. Future research should conduct adequately powered trials in underrepresented LMIC regions, investigate long-term outcomes, and evaluate cost-effectiveness.
Post-Asphyxial Aftercare and Management of Neonates in Low- and Middle-Income Countries: A Systematic Evidence Synthesis.
Muralidharan O, Rehman S, Sihota D … +3 more , Harrison L, Vaivada T, Bhutta ZA
Neonatology · 2025 · PMID 39536730 · Full text
INTRODUCTION: Effective post-resuscitation care is crucial for improving outcomes in neonates post-asphyxia. This review aimed to provide a comprehensive overview of post-asphyxial aftercare strategies and forms part of...
INTRODUCTION: Effective post-resuscitation care is crucial for improving outcomes in neonates post-asphyxia. This review aimed to provide a comprehensive overview of post-asphyxial aftercare strategies and forms part of a supplement describing an extensive synthesis of effective newborn interventions in low- and middle-income countries (LMICs). METHODS: Evidence was generated by performing de novo reviews, updates to reviews via systematic searches, and reanalyses of studies conducted in LMICs from existing reviews. RESULTS: Sixty-one trials recruiting 5,046 term infants post-asphyxia were included across all intervention domains. Limited studies were available from LMICs related to fluid restriction, antiseizure medications, and early interventions to improve developmental outcomes. Our reanalysis of whole-body cooling trials in LMICs found effects on neonatal mortality and mortality or neurological disability in infancy differed significantly based on the care center and type of cooling device used. Pharmacological therapies for neuroprotection evaluated in 27 trials in middle-income countries had varied effects in neonates with encephalopathy. Majority of the trials (60%) focused on magnesium sulfate therapy and showed significant improvements in short-term mortality and morbidities. CONCLUSION: The sample sizes of included trials were relatively small, and the certainty of evidence ranged from very low to moderate. Evidence on long-term survival and neurodevelopmental outcomes was limited. Further research on promising neuroprotective therapies and factors affecting their implementation in low-resource contexts is required. To reduce the high burden related to asphyxia in LMICs, this review underscores the need for a paradigm shift toward prevention, and strategies that emphasize improving antenatal and obstetric care. INTRODUCTION: Effective post-resuscitation care is crucial for improving outcomes in neonates post-asphyxia. This review aimed to provide a comprehensive overview of post-asphyxial aftercare strategies and forms part of a supplement describing an extensive synthesis of effective newborn interventions in low- and middle-income countries (LMICs). METHODS: Evidence was generated by performing de novo reviews, updates to reviews via systematic searches, and reanalyses of studies conducted in LMICs from existing reviews. RESULTS: Sixty-one trials recruiting 5,046 term infants post-asphyxia were included across all intervention domains. Limited studies were available from LMICs related to fluid restriction, antiseizure medications, and early interventions to improve developmental outcomes. Our reanalysis of whole-body cooling trials in LMICs found effects on neonatal mortality and mortality or neurological disability in infancy differed significantly based on the care center and type of cooling device used. Pharmacological therapies for neuroprotection evaluated in 27 trials in middle-income countries had varied effects in neonates with encephalopathy. Majority of the trials (60%) focused on magnesium sulfate therapy and showed significant improvements in short-term mortality and morbidities. CONCLUSION: The sample sizes of included trials were relatively small, and the certainty of evidence ranged from very low to moderate. Evidence on long-term survival and neurodevelopmental outcomes was limited. Further research on promising neuroprotective therapies and factors affecting their implementation in low-resource contexts is required. To reduce the high burden related to asphyxia in LMICs, this review underscores the need for a paradigm shift toward prevention, and strategies that emphasize improving antenatal and obstetric care.
Intravenous Dextrose for the Treatment of Neonatal Hypoglycaemia: A Systematic Review.
Roberts LF, Lord LG, Crowther CA … +2 more , Harding JE, Lin L
Neonatology · 2025 · PMID 39536722 · Full text
INTRODUCTION: Hypoglycaemic neonates are usually admitted to neonatal intensive care for intravenous (IV) dextrose infusion if increased feeding and dextrose gel fail to restore normoglycaemia. However, the effectiveness...
INTRODUCTION: Hypoglycaemic neonates are usually admitted to neonatal intensive care for intravenous (IV) dextrose infusion if increased feeding and dextrose gel fail to restore normoglycaemia. However, the effectiveness of this intervention is uncertain. This review aimed to assess the evidence for the risks and benefits of IV dextrose for treatment of neonatal hypoglycaemia. METHODS: Four databases and three clinical trial registries were searched from inception to October 5, 2023. Randomised controlled trials (RCTs), non-randomised studies of interventions, cohort studies, and before and after studies were considered for inclusion without language or publication date restrictions. Risk of bias was assessed using Cochrane's Risk of Bias 2 tool or Risk of Bias in Non-Randomized Studies of Interventions tool. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. Meta-analysis was planned but not carried out due to insufficient data. RESULTS: Across 6 studies (two RCTs and four cohort), 711 participants were included. Evidence from one cohort study suggests IV dextrose treatment may not be associated with neurodevelopmental impairment at ≥18 months of age (no effect numbers, p > 0.2; very low certainty evidence; 60 infants). Evidence from one RCT suggests IV dextrose treatment may reduce the likelihood of repeated hypoglycaemia (risk ratio [RR]: 0.67 [95% CI: 0.20, 2.18], p = 0.5; low certainty evidence; 80 infants) compared to treatment with oral sucrose bolus. However, the risk of a hyperglycaemic episode may be increased (RR: 2.33 [95% CI: 0.65, 8.39], p = 0.19; 80 infants). CONCLUSION: More evidence is needed to clarify the benefits and risks of IV dextrose for treatment of neonatal hypoglycaemia. INTRODUCTION: Hypoglycaemic neonates are usually admitted to neonatal intensive care for intravenous (IV) dextrose infusion if increased feeding and dextrose gel fail to restore normoglycaemia. However, the effectiveness of this intervention is uncertain. This review aimed to assess the evidence for the risks and benefits of IV dextrose for treatment of neonatal hypoglycaemia. METHODS: Four databases and three clinical trial registries were searched from inception to October 5, 2023. Randomised controlled trials (RCTs), non-randomised studies of interventions, cohort studies, and before and after studies were considered for inclusion without language or publication date restrictions. Risk of bias was assessed using Cochrane's Risk of Bias 2 tool or Risk of Bias in Non-Randomized Studies of Interventions tool. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. Meta-analysis was planned but not carried out due to insufficient data. RESULTS: Across 6 studies (two RCTs and four cohort), 711 participants were included. Evidence from one cohort study suggests IV dextrose treatment may not be associated with neurodevelopmental impairment at ≥18 months of age (no effect numbers, p > 0.2; very low certainty evidence; 60 infants). Evidence from one RCT suggests IV dextrose treatment may reduce the likelihood of repeated hypoglycaemia (risk ratio [RR]: 0.67 [95% CI: 0.20, 2.18], p = 0.5; low certainty evidence; 80 infants) compared to treatment with oral sucrose bolus. However, the risk of a hyperglycaemic episode may be increased (RR: 2.33 [95% CI: 0.65, 8.39], p = 0.19; 80 infants). CONCLUSION: More evidence is needed to clarify the benefits and risks of IV dextrose for treatment of neonatal hypoglycaemia.
Prevention and Treatment of Neonatal Infections in Facility and Community Settings of Low- and Middle-Income Countries: A Descriptive Review.
Lee Him R, Rehman S, Sihota D … +13 more , Yasin R, Azhar M, Masroor T, Naseem HA, Masood L, Hanif S, Harrison L, Vaivada T, Sankar MJ, Dramowski A, Coffin SE, Hamer DH, Bhutta ZA
Neonatology · 2025 · PMID 39532080 · Full text
INTRODUCTION: We present a robust and up-to-date synthesis of evidence on the effectiveness of interventions to prevent and treat newborn infections in low- and middle-income countries (LMICs). Newborn infection preventi...
INTRODUCTION: We present a robust and up-to-date synthesis of evidence on the effectiveness of interventions to prevent and treat newborn infections in low- and middle-income countries (LMICs). Newborn infection prevention interventions included strategies to reduce antimicrobial resistance (AMR), prevention of healthcare-associated infections (HAIs), clean birth kits (CBKs), chlorhexidine cleansing, topical emollients, and probiotic and synbiotic supplementation. Interventions to treat suspected neonatal infections included prophylactic systemic antifungal agents and community-based antibiotic delivery for possible serious bacterial infections (PSBIs). METHODS: A descriptive review combining different methodological approaches was conducted. To provide the most suitable recommendations for real-world implementation, our analyses considered the impact of these interventions within three distinct health settings: facility, mixed, and community. RESULTS: In facility settings, the strongest evidence supported the implementation of multimodal stewardship interventions for AMR reduction and device-associated infection prevention bundles for HAI prevention. Emollients in preterm newborns reduced the risk of invasive infection compared to routine skin care. Probiotics in preterm newborns reduced neonatal mortality, invasive infection, and necrotizing enterocolitis (NEC) risks compared to standard care or placebo. There was insufficient evidence for synbiotics and prophylactic systemic antifungals in LMICs. In mixed settings, CBKs reduced neonatal mortality risk compared to standard care. In community settings, chlorhexidine umbilical cord cleansing reduced omphalitis risk compared to dry cord care. For the treatment of PSBIs, purely domiciliary-based antibiotic delivery reduced the risk of all-cause neonatal mortality when compared to the standard hospital referral. CONCLUSION: Strategies for preventing HAIs and reducing AMR in healthcare facilities should be multimodal, and strategy selection should consider the feasibility of integration within existing newborn care programs. Probiotics are effective for facility-based use in preterm newborns; however, the establishment of high-quality, cost-effective mass production of standardized formulations is needed. Chlorhexidine cord cleansing is effective in community settings to prevent omphalitis in contexts where unhygienic cord applications are prevalent. Community-based antibiotic delivery of simplified regimens for PSBIs is a safe alternative when hospital-based care in LMICs is not possible or is declined by parents. More randomized trial evidence is needed to establish the effectiveness of CBKs, emollients, synbiotics, and prophylactic systemic antifungals in LMICs. INTRODUCTION: We present a robust and up-to-date synthesis of evidence on the effectiveness of interventions to prevent and treat newborn infections in low- and middle-income countries (LMICs). Newborn infection prevention interventions included strategies to reduce antimicrobial resistance (AMR), prevention of healthcare-associated infections (HAIs), clean birth kits (CBKs), chlorhexidine cleansing, topical emollients, and probiotic and synbiotic supplementation. Interventions to treat suspected neonatal infections included prophylactic systemic antifungal agents and community-based antibiotic delivery for possible serious bacterial infections (PSBIs). METHODS: A descriptive review combining different methodological approaches was conducted. To provide the most suitable recommendations for real-world implementation, our analyses considered the impact of these interventions within three distinct health settings: facility, mixed, and community. RESULTS: In facility settings, the strongest evidence supported the implementation of multimodal stewardship interventions for AMR reduction and device-associated infection prevention bundles for HAI prevention. Emollients in preterm newborns reduced the risk of invasive infection compared to routine skin care. Probiotics in preterm newborns reduced neonatal mortality, invasive infection, and necrotizing enterocolitis (NEC) risks compared to standard care or placebo. There was insufficient evidence for synbiotics and prophylactic systemic antifungals in LMICs. In mixed settings, CBKs reduced neonatal mortality risk compared to standard care. In community settings, chlorhexidine umbilical cord cleansing reduced omphalitis risk compared to dry cord care. For the treatment of PSBIs, purely domiciliary-based antibiotic delivery reduced the risk of all-cause neonatal mortality when compared to the standard hospital referral. CONCLUSION: Strategies for preventing HAIs and reducing AMR in healthcare facilities should be multimodal, and strategy selection should consider the feasibility of integration within existing newborn care programs. Probiotics are effective for facility-based use in preterm newborns; however, the establishment of high-quality, cost-effective mass production of standardized formulations is needed. Chlorhexidine cord cleansing is effective in community settings to prevent omphalitis in contexts where unhygienic cord applications are prevalent. Community-based antibiotic delivery of simplified regimens for PSBIs is a safe alternative when hospital-based care in LMICs is not possible or is declined by parents. More randomized trial evidence is needed to establish the effectiveness of CBKs, emollients, synbiotics, and prophylactic systemic antifungals in LMICs.
Immediate Care for Common Conditions in Term and Preterm Neonates: The Evidence.
Jiang L, Dominguez G, Cummins A … +4 more , Muralidharan O, Harrison L, Vaivada T, Bhutta ZA
Neonatology · 2025 · PMID 39532078 · Full text
BACKGROUND: Several interventions provided to newborns at birth or within 24 h after birth have been proven critical in improving neonatal survival and other birth outcomes. We aimed to provide an update on the effective...
BACKGROUND: Several interventions provided to newborns at birth or within 24 h after birth have been proven critical in improving neonatal survival and other birth outcomes. We aimed to provide an update on the effectiveness and safety of these interventions in low- and middle-income countries (LMICs). SUMMARY: Following a comprehensive scoping of the literature, we updated or re-analyzed the LMIC-specific evidence for included topics. Ninety-four LMIC studies were identified. Delayed cord clamping with immediate neonatal care after cord clamping resulted in a lower risk of blood transfusion in newborns <32-34 gestational weeks and a lower occurrence of anemia in term newborns but did not have significant effect on neonatal mortality or other common morbidities both in preterm and term newborns. Immediate thermal care using plastic wrap/bag led to a 38% lower risk of hypothermia and a higher axillary temperature in preterm newborns without increasing the risk of hyperthermia. Kangaroo mother care initiated immediately (iKMC) or early after birth (eKMC, within 24 h) significantly reduced neonatal mortality and the occurrence of hypothermia in preterm or low-birth-weight neonates. For delayed first bath in newborns, no pooled estimate was generated due to high heterogeneity of included studies. Trials from high-income countries demonstrated anti-D's effectiveness in lowering the incidence of Rhesus D alloimmunization in subsequent pregnancy if given within 72 h postpartum. KEY MESSAGES: We generated the most updated LMIC evidence for several immediate newborn care interventions. Despite their effectiveness and safety in improving some of the neonatal outcomes, further high-quality trials are necessary. BACKGROUND: Several interventions provided to newborns at birth or within 24 h after birth have been proven critical in improving neonatal survival and other birth outcomes. We aimed to provide an update on the effectiveness and safety of these interventions in low- and middle-income countries (LMICs). SUMMARY: Following a comprehensive scoping of the literature, we updated or re-analyzed the LMIC-specific evidence for included topics. Ninety-four LMIC studies were identified. Delayed cord clamping with immediate neonatal care after cord clamping resulted in a lower risk of blood transfusion in newborns <32-34 gestational weeks and a lower occurrence of anemia in term newborns but did not have significant effect on neonatal mortality or other common morbidities both in preterm and term newborns. Immediate thermal care using plastic wrap/bag led to a 38% lower risk of hypothermia and a higher axillary temperature in preterm newborns without increasing the risk of hyperthermia. Kangaroo mother care initiated immediately (iKMC) or early after birth (eKMC, within 24 h) significantly reduced neonatal mortality and the occurrence of hypothermia in preterm or low-birth-weight neonates. For delayed first bath in newborns, no pooled estimate was generated due to high heterogeneity of included studies. Trials from high-income countries demonstrated anti-D's effectiveness in lowering the incidence of Rhesus D alloimmunization in subsequent pregnancy if given within 72 h postpartum. KEY MESSAGES: We generated the most updated LMIC evidence for several immediate newborn care interventions. Despite their effectiveness and safety in improving some of the neonatal outcomes, further high-quality trials are necessary.
Response to Härtel et al.: "Less Invasive Surfactant Administration for Preterm Infants - State of the Art".
Maiwald CA, Poets CF, Franz AR
Neonatology · 2025 · PMID 39527923 · Publisher ↗
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Neonatal Outcomes following 2 Cases of Maternal CAR-T Therapy for High-Grade B-Cell Lymphoma.
O'Reilly D, Jones C, Smith A … +9 more , Mackin D, Mc Donald L, Quinn J, O'Reilly M, Flinn AM, Leahy R, Williams D, Donnelly J, Corcoran D
Neonatology · 2025 · PMID 39510057 · Publisher ↗
INTRODUCTION: Chimeric antigen receptor T cells (CAR-Ts) targeting CD19 represent a significant advance in treatment for patients with relapsed/refractory B-cell malignancies. Although a significant minority of recipient...
INTRODUCTION: Chimeric antigen receptor T cells (CAR-Ts) targeting CD19 represent a significant advance in treatment for patients with relapsed/refractory B-cell malignancies. Although a significant minority of recipients are women during their reproductive years, there is a paucity of data regarding pregnancy and neonatal outcomes in women previously treated with CAR-T. This is important as maternal T cells are known to cross the placenta and into breastmilk during pregnancy and breastfeeding, respectively. CASE PRESENTATION: Here we present two successful pregnancies following CAR-T therapy where both neonates were initially breastfed. These represent the first cases of neonates born following CAR-T therapy comprehensively described in medical literature. CONCLUSION: Pregnancy following CAR-T therapy does not appear to be associated with adverse neonatal outcomes. Further work is required to delineate the outcomes in this population.
Association between Time with Open Ductus Arteriosus and Outcomes in Congenital Diaphragmatic Hernia.
Hari Gopal S, Tillman R, Hammond Ii JD … +4 more , Hagan JL, Gowda SH, Varghese NP, Fernandes CJ
Neonatology · 2025 · PMID 39504949 · Publisher ↗
INTRODUCTION: While a patent ductus arteriosus (PDA) helps offload the right ventricle in the acute congenital diaphragmatic hernia (CDH)-associated pulmonary hypertension, its role on long-term outcomes in CDH has not b...
INTRODUCTION: While a patent ductus arteriosus (PDA) helps offload the right ventricle in the acute congenital diaphragmatic hernia (CDH)-associated pulmonary hypertension, its role on long-term outcomes in CDH has not been investigated. Our objective was to examine associations of the PDA with long-term clinical outcomes in CDH. METHODS: A single-center retrospective descriptive study of 122 CDH patients dichotomized by duration with PDA, as ≤14 versus >14 postnatal days (PND) and ≤30 versus >30 PND. Fisher's exact test, Wilcoxon rank-sum test, and multiple linear and logistic regression analyses were used for analyses. RESULTS: In unadjusted and adjusted for CDH severity comparisons, patients with PDA >14 PND and >30 PND had a higher risk of death, longer length of stay, mechanical ventilation duration, and need for tracheostomy, diuretics, and PH medications at discharge. CONCLUSION: A PDA beyond the newborn period is associated with adverse outcomes in infants with CDH.
The Effectiveness of Regionalization of Perinatal Care and Specific Facility-Based Interventions: A Systematic Review.
Ali AA, Naseem HA, Allahuddin Z … +5 more , Yasin R, Azhar M, Hanif S, Das JK, Bhutta ZA
Neonatology · 2025 · PMID 39504943 · Full text
INTRODUCTION: Appropriate perinatal care provision and utilization is crucial to improve maternal and newborn survival and potentially meet Sustainable Development Goal 3. Ensuring availability of healthcare infrastructu...
INTRODUCTION: Appropriate perinatal care provision and utilization is crucial to improve maternal and newborn survival and potentially meet Sustainable Development Goal 3. Ensuring availability of healthcare infrastructure as well as skilled personnel can potentially help improve maternal and neonatal outcomes globally as well as in resource-limited settings. METHODS: A systematic review on effectiveness of perinatal care regionalization was updated, and a new review on facility-based interventions to improve postnatal care coverage and outcomes was conducted. The interventions were identified through literature reviews and included transport, mHealth, telemedicine, maternal education, capacity building, and incentive packages. Search was conducted in relevant databases and meta-analysis conducted on Review Manager 5.4. We conducted subgroup analysis for evidence from low- and middle-income countries (LMICs). RESULTS: Implementation of regionalization programs significantly decreased maternal mortality in LMICs (OR: 0.43; 95% CI: 0.34-0.55, 2 studies), stillbirth overall (OR: 0.70; 95% CI: 0.54-0.89, 5 studies), perinatal mortality overall (OR: 0.54; 95% CI: 0.5-0.58, 2 studies), and LMICs (OR: 0.54; 95% CI: 0.50-0.58, 1 study). Transport-related interventions significantly decreased maternal mortality overall (OR: 0.55; 95% CI: 0.40-0.74, 1 study), neonatal mortality (RR: 0.76; 95% CI: 0.66-0.88, 1 study), perinatal mortality (RR: 0.86; 95% CI: 0.77-0.95, 1 study), and improved postnatal care coverage (OR: 6.89; 95% CI: 5.15-9.21, 1 study) in LMICs. Adding maternity homes/units significantly decreased stillbirth (OR: 0.75; 95% CI: 0.61-0.93, 1 study) in LMICs. Incentives for postnatal care significantly improved infant mortality (RR: 0.79; 95% CI: 0.65-0.96, 1 study), stillbirth (OR: 0.60; 95% CI: 0.44-0.83, 1 study), and postnatal care coverage (RR: 1.13; 95% CI: 1.03-1.25, 1 study) in LMICs. Telemedicine improved postnatal care coverage significantly in LMICs (RR: 2.54; 95% CI: 1.22-5.28, 3 studies) and decreased maternal mortality (OR: 0.46; 95% CI: 0.21-0.98, 1 study) and infant mortality (OR: 0.65; 95% CI: 0.45-0.95) in LMICs. Maternal education significantly decreased neonatal mortality (RR: 0.75; 95% CI: 0.66-0.84, 2 studies), perinatal mortality (RR: 0.86; 95% CI: 0.77-0.95, 1 study), infant mortality (RR: 0.79; 95% CI: 0.65-0.96, 1 study), and stillbirth (RR: 0.61; 95% CI: 0.45-0.82, 1 study). Capacity-building interventions significantly decreased maternal mortality in LMICs (OR: 0.37; 95% CI: 0.29-0.46, 5 studies), neonatal mortality overall (OR: 0.72; 95% CI: 0.53-0.98, 4 studies) and in LMICs (OR: 0.63; 95% CI: 0.54-0.74, 3 studies, and RR: 0.61; 95% CI: 0.48-0.79, 3 studies), perinatal mortality (OR: 0.53; 95% CI: 0.45-0.62, 2 studies, and RR: 0.86; 95% CI: 0.77-0.95, 1 study), infant mortality (OR: 0.50; 95% CI: 0.43-0.59, 1 study, and RR: 0.79; 95% CI: 0.65-0.96, 1 study), under-5 mortality (RR: 0.79; 95% CI: 0.66-0.94, 1 study), and stillbirth in LMICs (OR: 0.71; 95% CI: 0.62-0.82, 4 studies), and preterm birth overall (OR: 0.39; 95% CI: 0.19-0.81, 1 study). CONCLUSION: Perinatal regionalization and facility-based interventions have a positive impact on maternal and neonatal outcomes and calls for implementation in high burden settings but a better understanding of optimal interventions is needed through comprehensive trials in diverse settings. INTRODUCTION: Appropriate perinatal care provision and utilization is crucial to improve maternal and newborn survival and potentially meet Sustainable Development Goal 3. Ensuring availability of healthcare infrastructure as well as skilled personnel can potentially help improve maternal and neonatal outcomes globally as well as in resource-limited settings. METHODS: A systematic review on effectiveness of perinatal care regionalization was updated, and a new review on facility-based interventions to improve postnatal care coverage and outcomes was conducted. The interventions were identified through literature reviews and included transport, mHealth, telemedicine, maternal education, capacity building, and incentive packages. Search was conducted in relevant databases and meta-analysis conducted on Review Manager 5.4. We conducted subgroup analysis for evidence from low- and middle-income countries (LMICs). RESULTS: Implementation of regionalization programs significantly decreased maternal mortality in LMICs (OR: 0.43; 95% CI: 0.34-0.55, 2 studies), stillbirth overall (OR: 0.70; 95% CI: 0.54-0.89, 5 studies), perinatal mortality overall (OR: 0.54; 95% CI: 0.5-0.58, 2 studies), and LMICs (OR: 0.54; 95% CI: 0.50-0.58, 1 study). Transport-related interventions significantly decreased maternal mortality overall (OR: 0.55; 95% CI: 0.40-0.74, 1 study), neonatal mortality (RR: 0.76; 95% CI: 0.66-0.88, 1 study), perinatal mortality (RR: 0.86; 95% CI: 0.77-0.95, 1 study), and improved postnatal care coverage (OR: 6.89; 95% CI: 5.15-9.21, 1 study) in LMICs. Adding maternity homes/units significantly decreased stillbirth (OR: 0.75; 95% CI: 0.61-0.93, 1 study) in LMICs. Incentives for postnatal care significantly improved infant mortality (RR: 0.79; 95% CI: 0.65-0.96, 1 study), stillbirth (OR: 0.60; 95% CI: 0.44-0.83, 1 study), and postnatal care coverage (RR: 1.13; 95% CI: 1.03-1.25, 1 study) in LMICs. Telemedicine improved postnatal care coverage significantly in LMICs (RR: 2.54; 95% CI: 1.22-5.28, 3 studies) and decreased maternal mortality (OR: 0.46; 95% CI: 0.21-0.98, 1 study) and infant mortality (OR: 0.65; 95% CI: 0.45-0.95) in LMICs. Maternal education significantly decreased neonatal mortality (RR: 0.75; 95% CI: 0.66-0.84, 2 studies), perinatal mortality (RR: 0.86; 95% CI: 0.77-0.95, 1 study), infant mortality (RR: 0.79; 95% CI: 0.65-0.96, 1 study), and stillbirth (RR: 0.61; 95% CI: 0.45-0.82, 1 study). Capacity-building interventions significantly decreased maternal mortality in LMICs (OR: 0.37; 95% CI: 0.29-0.46, 5 studies), neonatal mortality overall (OR: 0.72; 95% CI: 0.53-0.98, 4 studies) and in LMICs (OR: 0.63; 95% CI: 0.54-0.74, 3 studies, and RR: 0.61; 95% CI: 0.48-0.79, 3 studies), perinatal mortality (OR: 0.53; 95% CI: 0.45-0.62, 2 studies, and RR: 0.86; 95% CI: 0.77-0.95, 1 study), infant mortality (OR: 0.50; 95% CI: 0.43-0.59, 1 study, and RR: 0.79; 95% CI: 0.65-0.96, 1 study), under-5 mortality (RR: 0.79; 95% CI: 0.66-0.94, 1 study), and stillbirth in LMICs (OR: 0.71; 95% CI: 0.62-0.82, 4 studies), and preterm birth overall (OR: 0.39; 95% CI: 0.19-0.81, 1 study). CONCLUSION: Perinatal regionalization and facility-based interventions have a positive impact on maternal and neonatal outcomes and calls for implementation in high burden settings but a better understanding of optimal interventions is needed through comprehensive trials in diverse settings.
Neonatal Sequential Organ Failure Assessment Score Predicts Respiratory Outcomes in Preterm Newborns with Late-Onset Sepsis: A Retrospective Study.
Poggi C, Sarcina D, Miselli F … +2 more , Ciarcià M, Dani C
Neonatology · 2025 · PMID 39500295 · Publisher ↗
INTRODUCTION: Neonatal sequential organ failure assessment (nSOFA) score predicts mortality in preterm newborns. The aim of the study was to assess whether nSOFA score could predict respiratory outcomes in preterm infant...
INTRODUCTION: Neonatal sequential organ failure assessment (nSOFA) score predicts mortality in preterm newborns. The aim of the study was to assess whether nSOFA score could predict respiratory outcomes in preterm infants with late-onset sepsis (LOS). METHODS: This retrospective, observational, single-center study enrolled infants with gestational age <32 weeks born between January 2016 and June 2023 who experienced an episode of LOS during NICU stay. The primary outcome was death or bronchopulmonary dysplasia (BPD); secondary outcomes were BPD, death or mechanical ventilation (MV) on day 5 after the onset of LOS, and MV on day 5 after the onset of LOS. The nSOFA score was assessed at the onset of LOS and after 6 ± 1, 12 ± 3, and 24 ± 3 h. RESULTS: Neonatal SOFA score was significantly higher in patients who developed each outcome versus those who did not at all timings. Maximal nSOFA score during the first 24 h after onset of LOS was an independent predictive factor for death or BPD (p = 0.007), BPD (p = 0.009), and death or MV on day 5 (p = 0.009), areas under the curve (AUC) were 0.740 (95% CI: 0.656-0.828), 0.700 (95% CI: 0.602-0.800), and 0.800 (95% CI: 0.710-0.889), respectively. Maximal nSOFA score also predicted moderate to severe BPD (p = 0.019) and death or moderate to severe BPD (p < 0.001). Maximal nSOFA ≥4 was associated with odds ratio (OR) of 7.37 (95% CI: 2.42-22.44) for death or BPD, 4.86 (95% CI: 1.54-15.28) for BPD, and 7.99 (95% CI: 3.47-18.36) for death or MV on day 5. AUC of the predicting model was 0.895 (95% CI: 0.801-0.928) for BPD, 0.897 (95% CI: 0.830-0.939) for death or BPD, 0.904 (95% CI: 0.851-0.956) for MV on day 5, 0.923 (95% CI: 0.892-0.973) for death or MV on day 5. CONCLUSION: Maximal nSOFA score during the first 24 h after the onset of LOS predicts respiratory outcomes and allows identification of patients who may crucially benefit from lung-protective measures.
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