Respiratory Distress Syndrome (RDS) in Newborns with Hypoxic-Ischemic Encephalopathy (HIE).

Respiratory distress syndrome (RDS) and hypoxic-ischemic encephalopathy (HIE) are frequent causes of death and disability in neonates. This study included newborns between January 2021 and July 2022 at the University Clinic for Gynecology and Obstetrics, Skopje. Up to date criteria for HIE/RDS for term and for preterm infants as well for the severity of HIE/RDS were used in a comprehensive analysis of cranial ultrasonography, neurological status, neonatal infections, Apgar score, bradycardia and hypotension, X-ray of the lungs, FiO2, acid-base status, assisted ventilation and use of surfactant. Three groups were created: HIE with RDS (42 babies), HIE without RDS (30 babies) and RDS without HIE in 38 neonates. All newborns with severe (third) degree of HIE died. Intracranial bleeding was found in 35.7% in the first group and 30% in the second group, and in the third group in 53.3%. The need for surfactant in the HIE group with RDS is 59.5%, and in the RDS group without HIE 84.2%. DIC associated with sepsis was found in 13.1-50% in those groups. In newborns with HIE and bradycardia, the probability of having RDS was on average 3.2 times higher than in those without bradycardia. The application of the surfactant significantly improved the pH, pO2, pCO2, BE and chest X-ray in children with RDS. An Apgar score less than 6 at the fifth minute increases the risk of RDS by 3 times. The metabolic acidosis in the first 24 hours increases the risk of death by 23.6 times. The combination of HIE/ RDS significantly worsens the disease outcome. The use of scoring systems improved the early detection of high risk babies and initiation of early treatment increased the chances for survival without disabilities.

The use of late preterm antenatal corticosteroids in women with gestational diabetes : a puzzle worth solving.

BACKGROUND: To investigate the association between late preterm antenatal corticosteroid treatment and outcome in late preterm neonates born to mothers with gestational diabetes mellitus, METHODS: All patients with gestational diabetes mellitus who had a late preterm delivery at Etlik Lady Zübeyde Hospital between 2017 and 2021 were included. Women who met the inclusion criteria and were not given antenatal corticosteroid treatment during current pregnancy before 34 0/7 weeks of gestation were divided into two groups according to whether or not they received late preterm antenatal corticosteroid treatment. The two groups were compared in terms of adverse neonatal complications. The main outcomes were composite respiratory outcome and composite neonatal outcome. Logistic regression analysis was used to determine additional potential predictors of neonatal outcome. RESULTS: This retrospective cohort study included a total of 400 participants with gestational diabetes mellitus who had a late preterm delivery within the study period. Of these women, 196 (49%) received late preterm antenatal corticosteroid treatment. Main outcomes showed no difference. Decreasing gestational age at birth was identified as an independent risk factor predicting both composite respiratory outcome and composite neonatal outcome in multivariate logistic regression analysis. CONCLUSIONS: Antenatal corticosteroid treatment at or after 34 0/7 weeks of gestation in women with gestational diabetes mellitus who had a late preterm delivery was not associated with improvement in adverse neonatal outcomes. Decreasing gestational age at birth was the only independent risk factor predicting composite neonatal and composite respiratory outcomes.

Relationship between chorioamnionitis or funisitis and lung injury among preterm infants: meta-analysis involved 16 observational studies with 68,397 participants.

BACKGROUND: Chorioamnionitis (CA) can cause multiple organ injuries in premature neonates, particularly to the lungs. Different opinions exist regarding the impact of intrauterine inflammation on neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD). We aim to systematically review the relationship between CA or Funisitis (FV) and lung injury among preterm infants. METHODS: We electronically searched PubMed, EMbase, the Cochrane library, CNKI, and CMB for cohort studies from their inception to March 15, 2023. Two reviewers independently screened literature, gathered data, and did NOS scale of included studies. The meta-analysis was performed using RevMan 5.3. RESULTS: Sixteen observational studies including 68,397 patients were collected. Meta-analysis showed CA or FV increased the lung injury risk (OR = 1.43, 95%CI: 1.06-1.92). Except for histological chorioamnionitis (HCA) (OR = 0.72, 95%CI: 0.57-0.90), neither clinical chorioamnionitis (CCA) (OR = 1.86, 95%CI: 0.93-3.72) nor FV (OR = 1.23, 95%CI: 0.48-3.15) nor HCA with FV (OR = 1.85, 95%CI: 0.15-22.63) had statistical significance in NRDS incidence. As a result of stratification by grade of HCA, HCA (II) has a significant association with decreased incidence of NRDS (OR = 0.48, 95%CI: 0.35-0.65). In terms of BPD, there is a positive correlation between BPD and CA/FV (CA: OR = 3.18, 95%CI: 1.68-6.03; FV: OR = 6.36, 95%CI: 2.45-16.52). Among CA, HCA was positively associated with BPD (OR = 2.70, 95%CI: 2.38-3.07), whereas CCA was not associated with BPD (OR = 2.77, 95%CI: 0.68-11.21). HCA and moderate to severe BPD (OR = 25.38, 95%CI: 7.13-90.32) showed a positive correlation, while mild BPD (OR = 2.29, 95%CI: 0.99-5.31) did not. CONCLUSION: Currently, evidence suggests that CA or FV increases the lung injury incidence in premature infants. For different types of CA and FV, HCA can increase the incidence of BPD while decreasing the incidence of NRDS. And this "protective effect" only applies to infants under 32 weeks of age. Regarding lung injury severity, only moderate to severe cases of BPD were positively correlated with CA.

Antenatal corticosteroid administration is associated with lower risk of severe ROP in preterm twin infants.

INTRODUCTION: Robust evidence revealed the impact of antenatal corticosteroid (ACS) administration on lower mortality and short-term neonatal outcomes in singleton preterm infants. We aimed to investigate the impact of ACS therapy on morbidity and mortality in preterm twin infants. METHODS: We conducted this retrospective single-center study from to the records of twin babies of 24-30 weeks of gestation admitted to the neonatal intensive care unit. The study population was grouped based on the exposure to ACS 1-7 days before birth as received or not. Groups were compared regarding in-hospital mortality and neonatal outcomes. RESULTS: Data from 160 twin infants were analyzed. Of those, 102 (64 %) were administered ACS. The median (IQR) gestational age and birth weight of the whole cohort were 28 (27-29) weeks and 1060 (900-1240) g, respectively. ACS administration was associated with a significant decline in respiratory distress syndrome (RDS), requirement ≥2 doses of surfactant, severe intraventricular hemorrhage (IVH), early-onset sepsis (EOS), and retinopathy of prematurity (ROP) requiring treatment (p < 0.05). Logistic regression analysis revealed that gestational age (OR 0.29 95 % CI 0.14-0.62; p = 0.001), ACS administration (OR 0.14 95 % CI 0.03-0.85; p = 0.032), and time to achieve full enteral feeding (OR 1.16 95 % CI 1.03-1.31; p = 0.019) were independently associated with the risk of severe ROP. CONCLUSION: The reduction in the risk of severe ROP besides RDS, severe IVH, and EOS among preterm twins who received ACS was remarkable in our study similar to the trials conducted in preterm singletons. However, large-scale prospective observational studies are required to reveal the efficacy of ACS in preterm twins.

Insights into Risk: Exploring Retinopathy of Prematurity and Short-term Comorbidities in Moderate-to-Late Preterm Infants.

BACKGROUND: Retinopathy of prematurity (ROP) and short-term comorbidity data moderate-to-late preterm (MLP) infants in Saudi Arabia are limited. AIM: The present study mainly aimed to identify ROP incidence and severity in MLP infants. The secondary objective was to explore whether moderate preterm infants are more prone to systemic short-term comorbidities compared to late preterm infants. MATERIALS AND METHODS: This retrospective study was conducted at King Abdulaziz University Hospital, a tertiary center in Jeddah, Saudi Arabia. Two-hundred and sixty-eight MLP infants born with gestational ages (GAs) of 32 to 36 + 6 weeks were included. Births were classified as moderate preterm (GA 32 to 33 + 6 weeks) and late preterm (GA 34 to 36 + 6 weeks) and the two groups were compared with an independent t-test. RESULTS: ROP incidence was 1.5%; all cases were stage 1 and involved zone II or III. No patient had type 1 ROP requiring treatment. The short-term comorbidity incidence was high (76.1%) and included hyperbilirubinemia (n = 206, 76.7%), respiratory distress syndrome (n = 178, 66.4%), hypoglycemia (n = 32, 11.9%,), and transient tachypnea of newborn (n = 25, 9.3%). Moderate preterm infants were more likely to have lower birth weight (P < 0.001), any-stage ROP (P = 0.032), respiratory distress syndrome (P = 0.031), intraventricular hemorrhage (P = 0.038), and hyperbilirubinemia (P < 0.001) compared to the late preterm infants. CONCLUSIONS: Any-stage ROP incidence among MLP infants was low, with no type 1 ROP cases requiring treatment. Short-term comorbidity incidence was relatively high among the moderate preterm infants. Despite the low non-type 1 ROP incidence at our center, MLP infants require proper surveillance of systemic short-term comorbidities.

Infant mortality in Italy: large geographic and ethnic inequalities.

BACKGROUND: Neonatal and infant mortality rates are among the most significant indicators for assessing a country's healthcare and social development. This study examined the trends in neonatal, post-neonatal, and infant mortality in Italy from 2016 to 2020 and analysed differences between children of Italian and foreign parents based on areas of residence, as well as the leading causes of death. Special attention was given to the analysis of mortality in 2020, the first year of the Covid-19 pandemic, and its comparison with previous years. METHODS: Data from 2016 to 2020 were collected by the Italian National Institute of Statistics and extracted from two national databases, the Causes of Death register and Live births registered in the population register. Neonatal, post-neonatal, and infant mortality rates were calculated using conventional definitions. The main analyses were conducted by comparing Italian citizens to foreigners and contrasting residents of the North with those of the South. Group comparisons were made using mortality rate ratios. The main causes of death were examined, and Poisson log-linear regression models were employed to investigate the relationships between mortality rate ratios for each cause of death and citizenship, place of residence and calendar year. RESULTS: In Italy, in 2020, the neonatal mortality rate was 1.76 deaths per thousand live births and it was 55% higher in foreign children than in Italian children. Foreign children had a higher mortality rate than Italians for almost all significant causes of death. Children born in the South of Italy, both Italian and foreign, had an infant mortality rate about 70% higher than residents in the North. Regions with higher infant mortality were Calabria, Sicily, Campania, and Apulia. In the South, mortality from neonatal respiratory distress and prematurity was higher. In the first months of 2020, between March and June, the first Covid-19 wave, Italy experienced an increase in neonatal and infant mortality compared to the same period in 2016-2019, not directly related to SARS-CoV-19 infection. The primary cause was neonatal respiratory distress. CONCLUSIONS: The neonatal and infant mortality rates indicate the persistence of profound inequalities in Italy between the North and the South and between Italian and foreign children.

Construction and evaluation of neonatal respiratory failure risk prediction model for neonatal respiratory distress syndrome.

BACKGROUND: Neonatal respiratory distress syndrome (NRDS) is a common respiratory disease in preterm infants, often accompanied by respiratory failure. The aim of this study was to establish and validate a nomogram model for predicting the probability of respiratory failure in NRDS patients. METHODS: Patients diagnosed with NRDS were extracted from the MIMIC-iv database. The patients were randomly assigned to a training and a validation cohort. Univariate and stepwise Cox regression analyses were used to determine the prognostic factors of NRDS. A nomogram containing these factors was established to predict the incidence of respiratory failure in NRDS patients. The area under the receiver operating characteristic curve (AUC), receiver operating characteristic curve (ROC), calibration curves and decision curve analysis were used to determine the effectiveness of this model. RESULTS: The study included 2,705 patients with NRDS. Univariate and multivariate stepwise Cox regression analysis showed that the independent risk factors for respiratory failure in NRDS patients were gestational age, pH, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), hemoglobin, blood culture, infection, neonatal intracranial hemorrhage, Pulmonary surfactant (PS), parenteral nutrition and respiratory support. Then, the nomogram was constructed and verified. CONCLUSIONS: This study identified the independent risk factors of respiratory failure in NRDS patients and used them to construct and evaluate respiratory failure risk prediction model for NRDS. The present findings provide clinicians with the judgment of patients with respiratory failure in NRDS and help clinicians to identify and intervene in the early stage.

Global, Regional and National Trends in the Burden of Neonatal Respiratory Failure and essentials of its diagnosis and management from 1992 to 2022: a scoping review.

Neonatal respiratory failure (NRF) is an emergency which has not been examined extensively. We critically synthesized the contemporary in-hospital prevalence, mortality rate, predictors, aetiologies, diagnosis and management of NRF to better formulate measures to curb its burden. We searched MEDLINE and Google Scholar from 01/01/1992 to 31/12/2022 for relevant publications. We identified 237 papers from 58 high-income and low-and middle-income countries (LMICs). NRF prevalence ranged from 0.64 to 88.4% with some heterogeneity. The prevalence was highest in Africa, the Middle East and Asia. Globally as well as in Asia and the Americas, respiratory distress syndrome (RDS) was the leading aetiology of NRF. Neonatal sepsis was first aetiology in Africa, whereas in both Europe and the Middle East it was transient tachypnoea of the newborn. Independent predictors of NRF were prematurity, male gender, ethnicity, low/high birth weight, young/advanced maternal age, primiparity/multiparity, maternal smoking, pregestational/gestational diabetes mellitus, infectious anamneses, antepartum haemorrhage, gestational hypertensive disorders, multiple pregnancy, caesarean delivery, antenatal drugs, foetal distress, APGAR score, meconium-stained amniotic fluid and poor pregnancy follow-up. The NRF-related in-hospital mortality rate was 0.21-57.3%, highest in Africa, Asia and the Middle East. This death toll was primarily due to RDS globally and in all regions. Clinical evaluation using the Silverman-Anderson score was widely used and reliable. Initial resuscitation followed by specific management was the common clinical practice. CONCLUSION: NRF has a high burden globally, driven by RDS, especially in LIMCs where more aggressive treatment and innovations, preferably subsidized, are warranted to curb its alarming burden. WHAT IS KNOWN: • Neonatal respiratory failure is a frequent emergency associated with a significant morbidity and mortality, yet there is no comprehensive research paper summarizing its global burden. • Neonatal respiratory failure needs prompt diagnosis and treatment geared at improving neonatal survival. WHAT IS NEW: • Neonatal respiratory failure has an alarmingly high global burden largely attributed to Respiratory distress syndrome. Low resource settings are disproportionately affected by the burden of neonatal respiratory failure. • Independent preditors of neonatal respiratory failure are several but can be classified into foetal, maternal and obstetrical factors. An illustrative pedagogical algorithm is provided to facilitate diagnosis and management of neonatal respiratory failure by healthcare providers.

Intrauterine Inflammation, Excessive Fetal Growth and Respiratory Morbidities in Moderate-To-Late Preterm Neonates.

INTRODUCTION: Respiratory morbidities in neonates are often progressive and life-threatening, and its early prediction is crucial. Intrauterine inflammation is one of the key control variables of respiratory morbidities in both very preterm and term neonates; however, little is known about its effects in the remaining group of moderate-to-late preterm neonates born between 32+0 and 36+6 weeks of gestation. This study aimed to confirm whether intrauterine inflammation is associated with respiratory morbidities in moderate-to-late preterm neonates. METHODS: A single-center retrospective observational study was conducted in neonates born between 32+0 and 34+6 weeks of gestation between April 2013 and March 2018. The correlation between respiratory morbidities (defined as a requirement for invasive mechanical ventilation longer than the median duration of 3 days) and intrauterine inflammation was assessed using multivariable logistic regression analysis. RESULTS: The study population comprised 242 neonates born at 33.7 ± 0.8 weeks of gestation and weighing 1,936 ± 381 g. The multivariable model to predict the outcome comprised respiratory distress syndrome (odds ratio [OR]: 9.1; 95% confidence interval [CI]: 3.7-22.5; p < 0.001), lower gestational age (per week; OR: 0.5; 95% CI: 0.3-0.8; p < 0.005), higher birth-weight z-score (OR: 1.6; 95% CI: 1.2-2.2; p < 0.005), lower cord blood pH (per 0.10; OR: 0.5; 95% CI: 0.3-0.7; p < 0.005), and chorioamnionitis (OR: 2.8; 95% CI: 1.1-7.2; p < 0.05). CONCLUSION: Together with the incidence of respiratory distress syndrome and gestational age, chorioamnionitis and high birth-weight z-scores were associated with an increased incidence of respiratory morbidities in moderate-to-late preterm neonates. The deleterious impact of intrauterine inflammation on the lungs may be common in neonates of virtually all gestational ages. Traditional admission policy of neonatal intensive care units based on a threshold birth-weight, may leave a group of neonates without close observation despite their increased risks for respiratory morbidities.

Incidence and predictors of respiratory distress syndrome among low birth weight neonates in the first seven days in Northwest Ethiopia Comprehensive Specialized Hospitals, 2023: A retrospective follow-up study.

INTRODUCTION: Respiratory distress syndrome is a catastrophic respiratory problem among low birth weight neonates. It increases the suffering of neonates and the economic expenditure of the countries. Notably, it is a major public health issue in low-income and middle-income countries such as Ethiopia. Despite this, studies regarding respiratory distress syndrome among low birth weight neonates were limited in Ethiopia. OBJECTIVE: To assess the incidence and predictors of respiratory distress syndrome among low birth weight neonates in the first 7 days in Northwest Ethiopia Comprehensive Specialized Hospitals. METHOD: Multicentred institution-based retrospective follow-up study was conducted from 19 September 2021 to 1 January 2023, among 423 low birthweight neonates. A simple random sampling technique was used. The data were collected using a data extraction checklist from the medical registry of neonates. The collected data were entered into EPI-DATA V.4.6.0.6. and analysed using STATA V.14. The Kaplan-Meier failure curve and log-rank test were employed. Bivariable and multivariable Weibull regression was carried out to identify predictors of respiratory distress syndrome. Statistical significance was declared at a p≤0.05. RESULT: The incidence rate of respiratory distress syndrome was found to be 10.78 (95% CI 9.35 to 12.42) per 100 neonate days. Fifth minute Appearance, Pulse, Grimace, Activity, Respiration (APGAR score) <7 (AHR 1.86; 95% CI 1.18 to 2.92), multiple pregnancy (AHR 1.43; 95% CI 1.04 to 1.96), caesarean section delivery (AHR 0.62; 95% CI 0.41 to 0.93), prematurity (AHR 1.56; 95% CI 1.06 to 2.30) and birth weight <1000 g (AHR 3.14; 95% CI 1.81 to 5.40) and 1000-1499 g (AHR 2.06; 95% CI 1.42 to 2.83) were significant predictors. CONCLUSION: The incidence of respiratory distress syndrome was higher than other studies conducted on other groups of neonates. Multiple pregnancy, fifth minute APGAR score, caesarean section, prematurity, extremely low birth weight and very low birth weight were predictors of respiratory distress syndrome. However, it needs further prospective study. Therefore, the concerned stakeholders should give due attention and appropriate intervention for these predictors.

Antenatal corticosteroid therapy, delivery intervals and perinatal mortality in low-resource settings.

BACKGROUND: Uncertainty exists regarding the ideal interval between the administration of antenatal corticosteroids (ACS) and delivery. The study's objective was to assess the risks of perinatal mortality and respiratory distress syndrome (RDS) among preterm neonates whose mothers gave birth within 48 h of the administration of ACS and those whose mothers gave birth between 48 h and 7 days. METHODS: The study design was a secondary analysis of data from an observational prospective chart review study that was carried out in Tanzania in 2020. Preterm infants born to mothers who got at least one dose of ACS between 28 and 34 weeks of pregnancy were included. RESULTS: A total of 346 preterm neonates (294 singletons and 52 twins) were exposed to ACS. Compared to infants born 48 h following the first dose of ACS, those exposed to the drug between 48 h and 7 days had significantly decreased rates of perinatal mortality and RDS. Multivariable analysis revealed that infants exposed ACS between 48 h and 7 days prior to delivery had lower risk of perinatal mortality (aRR 0.30, 95% CI 0.14-0.66) and RDS (aRR 0.27, 95% CI 0.14-0.52). CONCLUSION: The first dose of ACS given between 48 h and 7 days before delivery was associated with a lower risk of perinatal mortality and RDS than when the first dose was given <48 h before delivery. To improve neonatal outcomes, healthcare providers should consider administering ACS to mothers at the appropriate time.

Preterm infants exposed to antenatal corticosteroids (ACS) have lower rates of perinatal mortality and morbidity. Uncertainty exists regarding the ideal interval between the administration of ACS and delivery. We conducted a secondary analysis of data from a study that included preterm infants born in four hospitals in Tanzania. We investigated whether there were differences in perinatal mortality and respiratory distress syndrome between preterm neonates whose mothers delivered within 48 h of receiving a partial course of ACS and those whose mothers delivered between 48 h and 7 days after a full course of ACS therapy. Participants were the preterm infants of women who received ACS between 28 and 34 weeks of gestation. Neonates exposed to ACS between 48 h and 7 days prior to delivery had significantly lower risks of perinatal mortality and respiratory distress syndrome compared to infants who were delivered <48 h after ACS administration. This finding highlights the importance of optimizing the timing of ACS administration to maximize its potential benefits and minimize risks to preterm neonates. To improve neonatal outcomes, healthcare providers should consider administering ACS to mothers at the appropriate time.

Incidence and predictors of mortality among low birth weight neonates in the first week of life admitted to the neonatal intensive care unit in Northwestern Ethiopia comprehensive specialized hospitals, 2022. Multi-center institution-based retrospective follow-up study.

BACKGROUND: Globally, a high number of neonatal mortalities occurs in the first week of life, particularly among low birth weight neonates in low-income countries, including Ethiopia. However, there is limited evidence on the early neonatal mortality of low-birth-weight neonates in Ethiopia. Therefore, this study aimed to assess incidence and predictors of mortality among low-birth-weight neonates in their first week of life admitted to the neonatal intensive care unit in Northwestern Ethiopia Comprehensive Specialized Hospitals, 2022. METHODS: A multi-center retrospective follow-up study was conducted from March 21, 2020 to March 1, 2022, among 761 early neonates with low birth weight admitted in Northwestern Ethiopia Comprehensive Specialized Hospitals. The study participants were selected using simple random sampling technique. Data were collected using a data abstraction checklist ,and checked for completeness and entered into EPI data version 4.6, then exported to STATA 14 for analysis. Kaplan Meier failure curve and log-rank test were used to estimate and compare the probability of death. Both bivariable and multivariable Weibull regression models were fitted to identify predictors of mortality. Finally, a hazard ratio with 95% CI was computed, and variables having a p-value < 0.05 were considered as a significant predictor of mortality. RESULTS: The incidence of mortality among low birth weight neonates in their first week of life was 75.63 per 1000 neonate day observation (95% CI: 66.76-85.67), preeclampsia (AHR = 1.77;95% CI:1.32-2.36s), perinatal asphyxia (AHR = 1.64; 95% CI:1.14-2.36), respiratory distress syndrome (AHR = 1.76 95% CI;1.31-2.34), necrotizing enterocolitis (AHR = 2.78 95% CI;1.79-4.32), prematurity (AHR = 1.86; 95% CI:1.30-2.67), and birth weight < 1000gram (AHR = 3.13;95% CI: 1.91-5.12) and 1000-1499 gram (AHR = 1.99; 95% CI:1.47-2.68) were predictors. CONCLUSION: The incidence of early neonatal mortality in low birth weight neonates was incredibly higher than the overall early neonatal mortality in Northwest Ethiopia (Amhara region). Preeclampsia, perinatal asphyxia, respiratory distress syndrome, necrotizing enterocolitis, prematurity, and birth weight were predictors of mortality. Therefore, stakeholders shall give early identification and emphasis on preventable and treatable predictors. Furthermore, the health care provider shall give education about the importance of breastfeeding, and Antenatal and postnatal care.

Incidence and predictors of mortality among neonates with respiratory distress syndrome admitted at West Oromia Referral Hospitals, Ethiopia, 2022. Multi-centred institution based retrospective follow-up study.

INTRODUCTION: Respiratory distress syndrome is the major cause of neonatal death. However, data on the mortality and predictors related to respiratory distress syndrome were scarce. Hence, this study aimed to assess the incidence and predictors of death among neonates admitted with respiratory distress syndrome in West Oromia Referral Hospitals, Ethiopia, 2022. METHODS: A retrospective follow-up study was conducted among 406 neonates admitted with respiratory distress syndrome at five referral hospitals from, 1 January 2019 to, 31 December 2021 in West Oromia, Ethiopia. The data were collected using a structured checklist and participants were selected using simple random sampling technique. The data were entered into Epi data version 4.6.0.2 and exported to STATA version 14 for cleaning, coding and analysis. The Kaplan-Meier curve was used to estimate survival time. The Weibull regression model was fitted to identify the predictors of mortality and variables with a P-value < 0.05 was taken as significant predictors of mortality. RESULT: Four hundred six neonates with respiratory distress syndrome were included in the analysis. The overall incidence of neonatal mortality was 59.87/1000 neonates-days observations (95%CI: 51.1-70.2) with a proportion of 152 (37.44%) (95% CI: 32.7-42.2). The median time of follow-up was 11 days (95% CI: 10-23). Very low birthweight (AHR = 4.5, 95%CI: 2.0-10.9) and low birth weight (AHR = 3.1, 95%CI: 1.4-6.6), perinatal asphyxia (AHR = 2.7, 95%CI: 1.8-4), Chorioamnionitis (AHR = 2.2, 95%CI: 1.4-3.5) and multiple pregnancies (AHR = 2.2, 95%CI: 1.4-3.4) increased the hazard of death, whereas, antenatal corticosteroid administration (AHR = 0.33, 95%CI: 0.2-0.7) was negatively associated with neonatal mortality. CONCLUSION AND RECOMMENDATION: High mortality rate of neonates with respiratory distress syndrome was observed. Chorioamnionitis, perinatal asphyxia, low birth weight and multiple pregnancies increase the, mortality hazard while administering antenatal corticosteroids decreases it. Thus, administering corticosteroids- before giving birth and special emphasis on children with Chorioaminoitis, asphyxia, low birth weight and multiple pregnancies is important for reducing neonatal mortality.

Post Antenatal Late Preterm Steroids trial: interrupted time series analysis of respiratory outcomes in twin and pregestational diabetes.

BACKGROUND: The Antenatal Late Preterm Steroids trial found that corticosteroid administration decreased respiratory complications by 20% among late preterm singleton deliveries. After the Antenatal Late Preterm Steroids trial, corticosteroid administration increased by 76% among twin pregnancies and 113% among singleton pregnancies complicated by pregestational diabetes mellitus compared with expected rates based on the pre-Antenatal Late Preterm Steroids trial trend. However, the effect of corticosteroids on twin pregnancies and pregnancies complicated by pregestational diabetes mellitus is not well studied, as the Antenatal Late Preterm Steroids trial excluded twin pregnancies and pregnancies complicated by pregestational diabetes mellitus. OBJECTIVE: This study aimed to examine the change in the incidence rate of immediate assisted ventilation use and ventilation use for more than 6 hours among 2 populations after the dissemination of the Antenatal Late Preterm Steroids trial at the population level. STUDY DESIGN: This study was a retrospective analysis of publicly available US birth certificate data. The study period was from August 1, 2014, to April 30, 2018. The dissemination period of the Antenatal Late Preterm Steroids trial was from February 2016 to October 2016. Population-based interrupted time series analyses were performed for 2 target populations: (1) twin pregnancies not complicated by pregestational diabetes mellitus and (2) singleton pregnancies complicated by pregestational diabetes mellitus. For both target populations, analyses were limited to individuals who delivered nonanomalous live neonates between 34 0/7 and 36 6/7 weeks of gestation (vaginal or cesarean delivery). As a sensitivity analysis, a total of 23 placebo tests were conducted before (5 tests) and after (18 tests) the dissemination period. RESULTS: For the analysis of late preterm twin deliveries, 191,374 individuals without pregestational diabetes mellitus were identified. For the analysis of late preterm singleton pregnancy with pregestational diabetes mellitus, 21,395 individuals were identified. After the dissemination period, the incidence rate of immediate assisted ventilation use for late preterm twin deliveries was significantly lower than the expected value based on the pre-Antenatal Late Preterm Steroids trial trend (11.6% observed vs 13.0% expected; adjusted incidence rate ratio, 0.87; 95% confidence interval, 0.78-0.97). The incidence rate of ventilation use for more than 6 hours among late preterm twin deliveries did not change significantly after the dissemination of the Antenatal Late Preterm Steroids trial. A significant increase in the incidence rate of immediate assisted ventilation use and ventilation use for more than 6 hours was found among singleton pregnancies with pregestational diabetes mellitus. However, the results of placebo tests suggested that the increase in incidence was not necessarily due to the dissemination period of the Antenatal Late Preterm Steroids trial. CONCLUSION: The dissemination of the Antenatal Late Preterm Steroids trial was associated with decreased incidence of immediate assisted ventilation use, but no change in ventilation use for more than 6 hours, among late preterm twin deliveries in the United States. In contrast, the incidence of neonatal respiratory outcomes among singleton deliveries with pregestational diabetes mellitus did not decrease after the dissemination of the Antenatal Late Preterm Steroids trial.

One vs 2 courses of antenatal corticosteroids in pregnancies at risk of preterm birth: a secondary analysis of the MACS trial.

BACKGROUND: Birth is unpredictable and many patients who receive antenatal corticosteroids for preterm birth remain pregnant. Some professional societies recommend rescue antenatal corticosteroids for those who remain pregnant ≥14 days following the initial course. OBJECTIVE: This study aimed to explore a single vs a second course of antenatal corticosteroids in terms of severe neonatal morbidity and mortality. STUDY DESIGN: This is a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth (MACS) trial. The MACS study was a randomized clinical trial conducted in 80 centers in 20 different countries from 2001 to 2006. Participants who received only 1 course of intervention (ie, either a second course of antenatal corticosteroids or placebo) were included in this study. The primary outcome was a composite of stillbirth, neonatal mortality in the first 28 days of life or before discharge, severe respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage stage III and IV, periventricular leukomalacia, and necrotizing enterocolitis. Two subgroup analyses were planned to address the effect of a second course of antenatal corticosteroids on infants born before 32 weeks or within 7 days from the intervention. Moreover, a sensitivity analysis was performed to assess the effect of intervention on singleton pregnancies. Baseline characteristics were compared between the groups using chi-square and Student t tests. Multivariable regression analysis was performed to adjust for confounding variables. RESULTS: There were 385 and 365 participants included in the antenatal corticosteroid and placebo groups, respectively. The composite primary outcome occurred in 24% and 20% of participants in the antenatal corticosteroid and placebo groups, respectively (adjusted odds ratio, 1.09; 95% confidence interval, 0.76-1.57). Moreover, severe respiratory distress syndrome rate was similar between the 2 groups (adjusted odds ratio, 0.98; 95% confidence interval, 0.65-1.48). Newborns exposed to antenatal corticosteroids were more likely to be small for gestational age (14.9% vs 10.6%; adjusted odds ratio, 1.63; 95% confidence interval, 1.07-2.47). These findings remained true among singleton pregnancies for the primary composite outcome and birthweight <10th percentile (adjusted odds ratio, 1.29 [0.82-2.01]; and adjusted odds ratio, 1.74 [1.06-2.87]; respectively). Subgroup analyses of infants born before 32 weeks or within 7 days from the intervention did not show any benefits in terms of the composite primary outcome with antenatal corticosteroids vs placebo (50.5% vs 41.8% [adjusted odds ratio, 1.16; 95% confidence interval, 0.78-1.72]; and 42.3% vs 37.1% [adjusted odds ratio, 1.02; 95% confidence interval, 0.67-1.57]; respectively). CONCLUSION: Neonatal mortality and severe morbidities, including severe respiratory distress syndrome, were not improved by a second course of antenatal corticosteroids. Policy makers need to be thoughtful when recommending a second course of antenatal corticosteroids and consider whether not only short-term but also long-term benefits can be gained from such administration.

Outcomes of singleton preterm very low birth weight infants born to mothers with pregnancy-induced hypertension.

The association between maternal pregnancy-induced hypertension (PIH) and neonatal mortality and morbidities in preterm infants has not been consistent. This study aimed to evaluate the influence of maternal PIH on mortality and morbidities in singleton infants with very low birth weight born before 30 weeks of gestational age using the Korean Neonatal Network (KNN) database. A total of 5340 singleton infants with very low birth weight were registered in the KNN registry, who were born at 23+0 to 29+6 weeks of gestational age between January 2015 and December 2020. Baseline characteristics and neonatal mortality and morbidities were compared between infants with PIH and non-PIH mothers. After adjustment for potential confounders, infants with PIH mothers had significantly higher odds of respiratory distress syndrome (OR 1.983; 95% CI 1.285-3.061, p = 0.002) and bronchopulmonary dysplasia (OR 1.458; 95% CI 1.190-1.785, p < 0.001), and severe bronchopulmonary dysplasia (OR 1.411; 95% CI 1.163-1.713, p < 0.001) than infants with non-PIH mothers, while there were no significant differences in severe intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, or death during neonatal intensive care unit admission between infants with PIH and non-PIH mothers. This study showed that preterm infants with PIH mothers had an increased risk of neonatal respiratory morbidities, including respiratory distress syndrome and bronchopulmonary dysplasia.

A randomized clinical trial of antibiotic treatment duration in preterm pre-labor rupture of membranes: 7 days vs until delivery.

BACKGROUND: Antibiotic treatment in preterm pre-labor rupture of membranes can prolong the interval from membrane rupture to delivery and improve neonatal outcomes. However, the duration of antibiotic treatment for preterm pre-labor rupture of membranes has been rarely compared in prospective studies. OBJECTIVE: This study aimed to investigate the optimal duration of antibiotic treatment for pre-labor rupture of membranes. We performed a randomized controlled trial comparing neonatal morbidity and infantile neurologic outcomes between 2 groups of patients with preterm pre-labor rupture of membranes who received antibiotic treatment for 7 days or until delivery, respectively. STUDY DESIGN: This prospective randomized study included patients who were diagnosed with preterm pre-labor rupture of membranes between 22+0 weeks and 33+6 weeks of gestation. The enrolled patients were randomly assigned to receive intravenous cefazolin (1 g dosage every 12 hours) and oral clarithromycin (500 mg dosage every 12 hours) either for 7 days or until delivery. The study protocol was registered at ClinicalTrials.gov under identifier NCT01503606. The primary outcome was a neonatal composite morbidity, and the secondary outcome was neurologic outcomes at 12 months of corrected age. We enrolled 151 patients and allocated 75 and 76 of them to the 7-day and until-delivery groups, respectively. Analysis was done by per protocol. RESULTS: After excluding cases lost to follow-up and those with protocol violations, 63 (7-day regimen) and 61 (until-delivery regimen) patients with preterm pre-labor rupture of membranes and their babies were compared. There was no significant difference in the pregnancy outcomes, including gestational age at delivery and the interval from rupture of membranes to delivery, between the 2 groups. Among the neonatal outcomes, bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, and proven neonatal sepsis did not differ between the groups. However, the rates of respiratory distress syndrome (32.8% vs 50.8%; P=.039) and composite neonatal morbidities (34.4% vs 53.9%; P=.026) were lower in the until-delivery group than in the 7-day group. This difference remained statistically significant after a multivariable analysis adjusting for maternal age, twin pregnancy, antenatal corticosteroids treatment, gestational age at delivery, interval from rupture of membranes to delivery, and clinical chorioamnionitis. Infantile neurologic outcomes were evaluated in 71.4% of the babies discharged alive and did not differ between the groups. CONCLUSION: Overall, the until-delivery regimen of cefazolin and clarithromycin in preterm pre-labor rupture of membranes led to a lower incidence of composite neonatal morbidity and respiratory distress syndrome than the 7-day regimen, and both regimens otherwise showed similar individual neonatal morbidities and infantile neurologic outcomes.

Association between vitamin D level and respiratory distress syndrome: A systematic review and meta-analysis.

BACKGROUND: Growing evidence suggests an association between the vitamin D levels and respiratory outcomes of preterm infants. The objective of this systematic review and meta-analysis was to explore whether premature neonates with a vitamin D deficiency have an increased risk of respiratory distress syndrome (RDS). METHODS: We searched PubMed, EMBASE, and the Cochrane Library up through July 20, 2021. The search terms were 'premature infant', 'vitamin D', and 'respiratory distress syndrome'. We retrieved randomized controlled trials and cohort and case-control studies. For statistical analysis, we employed the random-effects model in Comprehensive Meta-Analysis Software ver. 3.3. We employed the Newcastle-Ottawa Scales for quality assessment of the included studies. RESULTS: A total of 121 potentially relevant studies were found, of which 15 (12 cohort studies and 3 case-control studies) met the inclusion criteria; the studies included 2,051 preterm infants. We found significant associations between RDS development in such infants and vitamin D deficiency within 24 h of birth based on various criteria, thus vitamin D levels < 30 ng/mL (OR 3.478; 95% CI 1.817-6.659; p < 0.001), < 20 ng/mL (OR 4.549; 95% CI 3.007-6.881; p < 0.001), < 15 ng/mL (OR 17.267; 95% CI 1.084-275.112; p = 0.044), and < 10 ng/ml (OR 1.732; 95% CI 1.031-2.910; p = 0.038), and an even lower level of vitamin D (SMD = -0.656; 95% CI -1.029 to -0.283; p = 0.001). CONCLUSION: Although the vitamin D deficiency definitions varied and different methods were used to measure vitamin D levels, vitamin D deficiency or lower levels of vitamin D within 24 h of birth were always associated with RDS development. Monitoring of neonatal vitamin D levels or the maintenance of adequate levels may reduce the risk of RDS.

Improving the external validity of Antenatal Late Preterm Steroids trial findings.

BACKGROUND: The external validity of randomised trials can be compromised when trial participants differ from real-world populations. In the Antenatal Late Preterm Steroids (ALPS) trial of antenatal corticosteroids at late preterm ages, participants had systematically younger gestational ages than those outside the trial setting. As risk of respiratory morbidity (the primary trial outcome) is higher at younger gestations, absolute benefits of corticosteroids calculated in the trial population may overestimate real-world treatment benefits. OBJECTIVES: To estimate the real-world absolute risk reduction and number-needed-to-treat (NNT) for antenatal corticosteroids at late preterm ages, accounting for gestational age differences between the ALPS and real-world populations. METHODS: Individual participant data from the ALPS trial (which recruited 2831 women with imminent preterm birth at 34+0 to 36+5 weeks') was appended to population-based data for 15,741 women admitted for delivery between 34+0 and 36+5 weeks' from British Columbia, Canada, 2000-2013. We used logistic regression to calculate inverse odds of sampling weights for each trial participant and re-estimated treatment effects of corticosteroids on neonatal respiratory morbidity in ALPS participants, weighted to reflect the gestational age distribution of the population-based (real-world) sample. RESULTS: The real-world absolute risk reduction was estimated to be -2.2 (95% CI -4.6, 0.0) cases of respiratory morbidity per 100, compared with -2.8 (95% CI -5.3, -0.3) in original trial data. Corresponding NNTs were 46 in the real-world setting vs 35 in the trial. Our focus on absolute measures also highlighted that the benefits of antenatal corticosteroids may be meaningfully greater at 34 weeks vs. 36 weeks (e.g., risk reductions of -3.7 vs. -1.2 per 100 respectively). CONCLUSIONS: The absolute risk reductions and NNTs associated with antenatal corticosteroid administration at late preterm ages estimated in our study may be more appropriate for patient counselling as they better reflect the anticipated benefits of treatment when used in a real-world situation.

Consequences of early-onset preeclampsia on neonatal morbidity and mortality.

Preterm birth is the leading cause of perinatal morbidity and mortality in developed countries. Common reasons for indicated preterm births include pre-eclampsia. The increase in incidences of morbidity and mortality observed in neonates resulting from pregnancies complicated by preeclampsia is also due to alterations in angiogenic and pro-inflammatory factors that directly affect the neonatal health. This review was prepared with the aim of gathering the information available at PubMed/MEDLINE, in the years from 2011 to 2021, on the consequences of neonatal morbidity and mortality of early-onset preeclampsia. There is great controversy in the literature and paucity of studies. Early onset pre-eclampsia has been linked to fetal growth restriction (FGR). Most studies support its association with respiratory distress syndrome (RDS). Most studies point to an association between preeclampsia and bronchopulmonary dysplasia (BPD), with the highest risk in FGR. The association between preeclampsia, patent ductus arteriosus (PDA) and sepsis is not supported by the literature. The association to necrotizing enterocolitis (NEC) is controversial. The risk of spontaneous intestinal perforation (SIP) seems to be increased with preeclampsia. The association between intraventricular hemorrhage (IVH) and preeclampsia is controversial, however, preeclampsia seems to have a protective effect on periventricular leukomalacia (PVL). Most of the evidence points to the non-association between preeclampsia and retinopathy of prematurity (ROP). Hematological changes such as neutropenia, thrombocytopenia and increased nucleated red blood cell counts have been shown to be associated with preeclampsia. The evidence is still quite controversial regarding mortality. The early installation of preeclampsia will have direct consequences on neonatal morbidity. Gestational age at preterm birth is the main risk factor on neonatal morbidity. Obstetricians should aim to prolong the pregnancies complicated by early-onset severe preeclampsia as far as maternal conditions allow. This policy may contribute to improve the neonatal outcomes.