Antenatal Corticosteroids Research Articles

Effect of utilizing either a self-reported questionnaire or administrative data alone or in combination on the findings of a randomized controlled trial of the long-term effects of antenatal corticosteroids.

A combination of self-reported questionnaire and administrative data could potentially enhance ascertainment of outcomes and alleviate the limitations of both in follow up studies. However, it is uncertain how access to only one of these data sources to assess outcomes impact study findings. Therefore, this study aimed to determine whether the study findings would be altered if the outcomes were assessed by different data sources alone or in combination. At 50-year follow-up of participants in a randomized trial, we assessed the effect of antenatal betamethasone exposure on the diagnosis of diabetes, pre-diabetes, hyperlipidemia, hypertension, mental health disorders, and asthma using a self-reported questionnaire, administrative data, a combination of both, or any data source, with or without adjudication by an expert panel of five clinicians. Differences between relative risks derived from each data source were calculated using the Bland-Altman approach. There were 424 participants (46% of those eligible, aged 49 years, SD 1, 50% male). There were no differences in study outcomes between participants exposed to betamethasone and those exposed to placebo when the outcomes were assessed using different data sources. When compared to the study findings determined using adjudicated outcomes, the mean difference (limits of agreement) in relative risks derived from other data sources were: self-reported questionnaires 0.02 (-0.35 to 0.40), administrative data 0.06 (-0.32 to 0.44), both questionnaire and administrative data 0.01 (-0.41 to 0.43), and any data source, 0.01 (-0.08 to 0.10). Utilizing a self-reported questionnaire, administrative data, both questionnaire and administrative data, or any of these sources for assessing study outcomes had no impact on the study findings compared with when study outcomes were assessed using adjudicated outcomes.

Neurodevelopmental outcomes in extremely preterm infants with placental pathologic evidence of fetal inflammatroy response.

Neonates born with fetal inflammatory response (FIR) are at increased risk for adverse neonatal outcomes. Our objective was to determine whether FIR and its severity is associated with neurodevelopmental impairment (NDI) at 2 years of age or death among preterm infants. A retrospective cohort study of prospectively collected data of all infants born <29 weeks gestational age (GA). FIR and its severity were diagnosed according to the Amsterdam Placental Workshop Group Consensus Statement. Neurodevelopmental outcomes among all participants were quantified according to Bayley III. Mothers of infants with FIR were significantly younger (P = 0.04) and had a greater prevalence of antenatal steroid use (P < 0.01), infection during pregnancy (P = 0.01), PPROM (P < 0.01), and clinical chorioamnionitis (P < 0.01). Infants with FIR had longer duration of hospitalization (P < 0.01), days on oxygen (P < 0.01), congenital pneumonia (P = 0.03), moderate/severe bronchopulmonary dysplasia (BPD; P < 0.01). Notably, infants with FIR were not at increased risk of NDI or death (primary outcome). Those with moderate to severe FIR (≥ stage 2 FIR) were at increased risk of developing motor & language impairment or death (P < 0.01). This is the first report demonstrating an association between the severity of FIR and subsequent NDI in preterm infants born. Fetal Inflammatory Response (FIR) is not associated Neurodevelopmental Impairement (NDI) or Death in preterm infants However, there is significant relationship between moderate to severe FIR and NDI at 2 years of age in preterm infants. This is the first study demonstrating the impact of progression and severity of FIR on NDI or Death in preterm infants. These observations provide additional insight into understanding the impact of intrauterine exposure to inflammation on the NDI or death in preterm infants.

Assessing Severity and Need for Delivery in Early Onset Preeclampsia Before 32 Weeks of Gestation: a Delphi Consensus Procedure.

Preeclampsia is a potentially life-threatening hypertensive pregnancy disorder that carries an acute risk of an unfavorable outcome of the pregnancy but also has consequences for the long-term health of the mother. Women who develop the early form of pre-eclampsia before the 32nd week of pregnancy have the highest risk and are also the most difficult to treat. The severity of pre-eclampsia is not characterized uniformly in Germany, so that the indication for delivery is rather individualized. The aim of this study was to reach a consensus on parameters that could serve as criteria for describing the severity of pre-eclampsia based on the urgency of delivery. To this end, a Delphi procedure was used to present a scenario in which a woman was admitted for preeclampsia before 32 gestational weeks and after completion of antenatal steroid therapy. Clinicians specialized in maternal-fetal medicine from German-speaking countries completed five rounds of a modified Delphi questionnaire. Presented parameters were selected by the section "Hypertensive Pregnancy Diseases and Fetal Growth Restriction" of the German Society of Gynecology and Obstetrics after reviewing the literature. These included objectifiable laboratory or clinical parameters as well as subjective symptoms of the patient. In addition, nine fetal parameters were taken into account. The clinicians were asked to rate presented parameters as an indication for delivery on a Likert scale from 0 to 4 (no indication to absolute indication without delay). For each item, the predefined cut-off for group consensus was ≥70% agreement. A total of 126 experts were approached. Sixty-nine experts (54.8%) took part in the first round; of those 50 completed the entire Delphi procedure. A consensus was reached on 14 parameters to be considered rapid preparation for delivery without delay (4 points on the Likert scale). These were among others hepatic hematoma or liver capsule rupture, acute liver failure with fulminant coagulation disorder or disseminated intravascular coagulation, eclampsia, pathologic findings in imaging (e.g. cMRI) or electrocardiogram arranged for new onset of headache or retrosternal pain, respectively. Twenty-six parameters were rated as factors that should be considered in the decision without being absolute (1 to 3 points), and 13 parameters should have no influence on the decision to deliver (0 points). No consensus on severe hypertension as an indication for delivery could be reached for blood pressure values below 220/140mmHg. A consensus was reached on whether to deliver in preeclampsia typic clinical findings and symptoms. The results can serve as guidance for current clinical practice and for the definition of clinical endpoints in intervention studies. Nevertheless, the isolated criteria are a theoretical construction since the combined deterioration or summation of several factors rather than a single factor most likely influences the decision to deliver and reflect the severity of preeclampsia. Moreover, the degree of hypertension as an indication for delivery remains controversial, unless the patient suffers additionally from complaints. Future research should be enforced to incorporate long-term risks for the mother into a decision aid.

Incidence of neonatal respiratory morbidity after vaginal and caesarean delivery in the late-preterm and term period - a retrospective cohort study.

Respiratory distress syndrome is a leading cause of neonatal intensive care unit admissions for late preterm (34-36 weeks gestational age) and term infants (37-41 weeks). The risk for respiratory morbidity appears to increase after an elective caesarean delivery and might be reduced after antenatal corticosteroids. However, before considering antenatal corticosteroids for women at high risk of preterm birth after 34 weeks, the incidence of respiratory distress syndrome and the effect of delivery mode on this incidence requires further evaluation. Therefore, this study aimed to investigate the relationship between respiratory distress syndrome incidence and delivery mode in late preterm and term infants. In this retrospective cohort study, the clinical databases of the University Hospitals of Zurich and Basel were queried regarding all live births between 34 + 0 and 41 + 6 weeks. Neonatal intensive care unit admissions due to respiratory distress syndrome were determined and analysed in regard to the following delivery modes: spontaneous vaginal, operative vaginal, elective caesarean, secondary caesarean and emergency caesarean. After excluding malformations (n = 889) and incomplete or inconclusive data (n = 383), 37,110 infants out of 38,382 were evaluated. Of these, 5.34% (n = 1980) were admitted to a neonatal intensive care unit for respiratory distress syndrome. Regardless of gestational age, respiratory distress syndrome in infants after spontaneous vaginal delivery was 2.92%; for operative vaginal delivery, it was 4.02%; after elective caesarean delivery it was 8.98%; following secondary caesarean delivery, it was 8.45%, and after an emergency caesarean it was 13.3%. The risk of respiratory distress syndrome was higher after an elective caesarean compared to spontaneous vaginal delivery, with an odds ratio (OR), adjusted for gestational age, of 2.31 (95% CI 1.49-3.56) at 34 weeks, OR 5.61 (95% CI 3.39-9.3) at 35 weeks, OR 1.5 (95% CI 0.95-2.38) at 36 weeks, OR 3.28 (95% CI 1.95-5.54) at 37 weeks and OR 2.51 (95% CI 1.65-3.81) at 38 weeks. At 39 weeks, there was no significant difference between the risk of respiratory distress syndrome after an elective caesarean vs. spontaneous vaginal delivery. Over the study period, gestational age at elective caesarean delivery remained stable at 39.3 ± 1.65 weeks. The incidence of respiratory distress syndrome following an elective caesarean is up to threefold higher in infants born with less than 39 weeks gestational age compared to those born by spontaneous vaginal delivery. Therefore - and whenever possible - an elective caesarean delivery should be planned after 38 completed weeks to minimise the risk of respiratory morbidity in neonates.

Outcomes in Pregnancies Complicated with Preterm Hypertensive Disorders with and without Late Antenatal Corticosteroids.

This study aimed to determine whether administration of a late preterm (34-36 weeks) course of antenatal corticosteroids (ACS) is associated with improved short-term neonatal outcomes among pregnancies complicated with hypertensive disorders of pregnancy (HDP) who delivered in the late preterm period. A single tertiary center retrospective cohort study, including pregnant individuals with singleton fetuses who delivered between 34.0 and 36.6 weeks following an HDP diagnosis. Exclusion criteria were major fetal anomalies and treatment with ACS before 34 weeks. Cases were divided into two groups: exposed group, consisting of individuals treated with a late ACS course, and nonexposed group, receiving no ACS. The primary outcome was a composite adverse neonatal outcome, including intensive care unit admission, oxygen treatment, noninvasive positive pressure ventilation, mechanical ventilation, respiratory distress syndrome, transient tachypnea, or apnea of prematurity. Secondary neonatal outcomes included birth weight, Apgar score, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, surfactant use, hypoglycemia, hyperbilirubinemia, sepsis, and neonatal death. Multivariable regression models were used to determine adjusted odds ratio (aOR)and 95% confidence intervals (CIs). Of 7,624 preterm singleton deliveries during the study period, 438 (5.7%) were diagnosed with HDP and delivered between 34.0 and 36.6 weeks. Infants who received ACS were diagnosed more commonly with fetal growth restriction (16.0 vs. 5.6%, p < 0.01) and were delivered at an earlier gestational age (GA) (mean GA: 35.6 vs. 36.3 weeks, p < 0.01). The composite neonatal morbidity did not differ between the groups after adjustments (aOR: 0.97, 95% CI: 0.47, 1.98). Neonatal hypoglycemia and hyperbilirubinemia were more common in the exposed group than in the nonexposed group (46.9 vs. 27.4%; aOR: 2.27; 95% CI: 1.26, 4.08 and 64.2 vs. 46.5%; aOR: 2.08; 95% CI: 1.16, 3.72 respectively). In people with HDP, a course of ACS given in the late preterm period did not improve neonatal morbidity. · In people with HDP, a late preterm ACS course did not improve neonatal morbidity.. · Respiratory morbidity rate was similar between infants who received late ACS and those who did not.. · Neonatal hypoglycemia and hyperbilirubinemia were more common in infants who received late ACS..

Antibiotics and beyond: Unraveling the dynamics of bronchopulmonary dysplasia in very preterm infants.

Bronchopulmonary dysplasia (BPD) remains a significant challenge in neonatal care. Prenatal inflammation and neonatal sepsis contribute to the multifactorial nature of BPD. A potential association between empirical antibiotic therapy and BPD risk has been proposed due to microbiota dysbiosis in very low birth weight premature infants. A single centered retrospective cohort study of preterm infants (24-32 weeks gestation) from 2014 to 2021. The study compared groups that received empirical antibiotics in the first days of life and those that did not receive any antibiotic in the first days of life. The primary outcomes studied were BPD, death, and the combined outcome of BPD/death. Statistical analysis employed t-tests, Mann-Whitney U, Chi-square, and logistic regression. Of 454 preterm infants, 61.5% received antibiotics. This group had lower gestational age, birth weight, and Apgar scores. Antibiotic use was associated with higher incidence of BPD (35.5% vs. 10.3%), death (21.5% vs. 8.6%), and combined outcomes (54.5% vs. 18.3%). In multivariate analysis, antibiotic use independently associated with BPD (OR 2.58, p < 0.001) and combined outcome BPD/death (OR 2.06, p < 0.02). Antenatal corticosteroids provided protection against BPD, but not mortality. This study suggests an association between early empirical antibiotic use and BPD in preterm infants, emphasizing the need for judicious antibiotic practices in neonatal care.

Impact of hyponatremia in preeclamptic patients with severe features.

Hyponatremia, though common in women with preeclampsia, has not been well studied. Our primary objectives are to assess the clinical characteristics and emergency therapy applied to subjects diagnosed with preeclampsia. We hypothesize that hyponatremia present in preeclamptic patients with severe features is associated with greater use of emergency hypertensives, antenatal steroids, and cesarean delivery. This is a retrospective descriptive study utilizing an electronic health record database (TriNetX ®). We collected and evaluated the following data of subjects aged 15 to 54 years with preeclampsia with severe features diagnosis: demographics, diagnostic codes, medication codes, procedure codes, deaths, and laboratory results. A total of 2,901 subjects [215 (7.4%)] with a sodium level below 134 mEq/L and [2686 (92.6%)] with a sodium level above 135 mEq/L were included. A higher proportion of subjects in the below 134 sodium group received emergency antihypertensives [165 (76.7%) versus 1811 (67.4%), p = 0.01], antenatal steroids [103 (47.9%) versus 953 (35.5%), p = 0.001], and cesarean section [27 (12.6%) versus 97 (3.6%), p = <0.001]. We found that hyponatremia may be associated with emergency antihypertensive use, antenatal steroid use, and cesarean section in patients with preeclampsia with severe features. Future research is needed to determine if routine sodium levels assessed in preeclamptic subjects with severe features identify subjects at risk of receiving these treatments.

Does Preterm Prolonged Rupture of Membranes Increase the Risk of Needing Invasive Respiratory Support? A Retrospective Single-Centre Study.

(1) Background: Preterm premature rupture of membranes (PPROM) has been associated with increased perinatal morbidity, but the effect of PPROM on respiratory disease has not been previously quantified. We hypothesised that PPROM would be associated with a higher incidence of invasive ventilation. (2) Methods: A retrospective cohort study at the Neonatal Unit at King's College Hospital NHS Foundation Trust, London, UK, was conducted on infants born before 37 weeks of gestation. PPROM was defined as the rupture of membranes for >48 h. (3) Results: We reviewed 1901 infants (434 with PPROM) with a median (IQR) gestational age of 32.4 (28.7-35.0) weeks. The median (IQR) duration of rupture of membranes in the infants with PPROM was 129 (78-293) h. The incidence of invasive ventilation was 56% in the infants with PPROM and 46% in the infants without PPROM (p < 0.001). Following regression analysis, PPROM was significantly related to a higher incidence of invasive ventilation (odds ratio: 1.48; 95% CI: 1.13-1.92, adjusted p = 0.004) after adjusting for birth weight [odds ratio = 0.34; 95% CI: 0.33-0.43, adjusted p < 0.001], Apgar score at 10 min [odds ratio =0.61; 95% CI: 0.56-0.66, adjusted p < 0.001] and antenatal corticosteroid use (adjusted p = 0.939). (4) Conclusions: PPROM was associated with a 1.48-fold higher risk of needing invasive ventilation.

The Role of Corticosteroids in Prevention of Neonatal Respiratory Morbidity in Term Elective Cesarean Section A Prospective Observation Study

Abstract Background Caesarean sections continue to increase day by day in both developed and developing countries, which is associated with increased respiratory distress syndrome (RDS), the key reason for early neonatal morbidity and mortality. Objective To assess the effect of routine prophylactic corticosteroids before elective caesarean section after 37 weeks of gestational age, on neonatal respiratory morbidity. Methods A prospective observational study was conducted on all pregnant women undergoing elective caesarean sections between 37-42 weeks at Ain Shams University Maternity Hospital. Over an 8- month period (from November 2020 to June 2021), 1105 cases were divided into the exposed group (A), (N = 877) who received prophylactic dexamethasone, and 228 cases in the non-exposed group (B) who did not receive dexamethasone. Outcome measures were the incidence of transient tachypnea of the newborn, and NICU admissions due to respiratory morbidity. Data were analyzed using SPSS 22. Results Overall, there was no statistically significant difference in the incidence of TTN or RDS. No cases of TTN were found in exposed subgroup, versus 1 (0.4%) in non-exposed group (p = 0.745). The respiratory distress (RDS) in the exposed subgroup was 4 cases (16.7%) versus 18 (7.9%) in non- exposed group (p = 0.148). While the admission to the neonatal intensive care unit (NICU) due to respiratory morbidity after an elective caesarean section was 4 cases (16.7%) in the exposed subgroup versus 19 cases (8.3%) in the non-exposed group (p = 0.178). Conclusion Routine administration of prophylactic antenatal corticosteroids before elective caesarean sections at term does not reduce the risk of admission to the NICU compared to non- administration.

Short-term effects of antenatal betamethasone on fetal cardiovascular and circulation status: A quasi-experimental observational (before-after) study.

The administration of antenatal corticosteroid is a standard treatment to reduce the rate of perinatal mortality and morbidity; however, there is limited evidence regarding the potential effects of betamethasone on the constriction of the ductus arteriosus (DA). This study aimed to investigate the short-term effects of antenatal betamethasone on fetal cardiovascular and circulation status. This quasi-experimental observational (before-after) study was conducted on 32 singleton fetuses. The participants were healthy pregnant women with a diagnosis of placenta accreta spectrum who were eligible for 2 doses of betamethasone and referred to prenatal care clinic, Vali-E-Asr hospital, Tehran, Iran from January 2021-May 2022. The results of fetal echocardiography and Doppler sonography were compared before and after the administration of antenatal corticosteroid therapy. Following betamethasone injection, significant increases were observed in peak systolic and diastolic velocity of the DA without constriction of the DA (p 0.001, p = 0.002 respectively). However, no significant changes were observed in right ventricular function, tricuspid valve function, Doppler of ductus venous, and peak systolic velocity of the aortic isthmus (p 0.05). Doppler examination of the uterine, umbilical, and middle cerebral arteries also showed no significant changes (p 0.05). Considering the benefits of antenatal corticosteroid therapy, its administration seems reasonable in preterm births. The transient changes in ductal blood flow are not prohibitive.

Betamethasone treatment-to-delivery interval, retreatment, and severe intraventricular hemorrhage in infants

Antenatal corticosteroids decrease the incidence of severe intraventricular hemorrhages (grades 3,4) in preterm infants. It is unclear whether their beneficial effects on intraventricular hemorrhage wane with time (as occurs in neonatal respiratory distress) and if repeat courses can restore this effect. Prior randomized controlled trials of betamethasone retreatment found no benefit on severe intraventricular hemorrhage rates. However, the trials may have included an insufficient number of infants at risk for intraventricular hemorrhage to be able to adequately address this question. Severe intraventricular hemorrhages occur almost exclusively in infants born <28 weeks, whereas only 7% (0%-16%) of the retreatment trials' populations were <28 weeks. To determine if the risk of severe intraventricular hemorrhage in infants delivered <28 weeks increases when the betamethasone treatment-to-delivery interval increases beyond 9 days and to determine if betamethasone retreatment prior to delivery decreases the rate of hemorrhage. Observational study examining the incidence of intraventricular hemorrhage before (epoch 1) and after (epoch 2) a practice change that encouraged obstetricians to retreat pregnant women still at high risk of delivery before 28 weeks' gestation when >9 days elapsed from the first dose of betamethasone. Multivariable analyses with logistic regression using generalized estimating equations techniques were conducted to examine the rates of intraventricular hemorrhage among 410 infants <28 weeks' gestation who either delivered between 1-9 days (n=290) after the first 2-dose betamethasone course or delivered ≥10 days (and eligible for retreatment) (n=120). After adjusting for potential confounding variables, infants who delivered ≥10 days after a single betamethasone course had an increased risk of either severe intraventricular hemorrhage alone or the combined outcome severe intraventricular hemorrhage or death before 4 days (OR (95%CI): 2.8 (1.2, 6.6)) compared with infants who delivered between 1-9 days after betamethasone. Among the 120 infants who delivered ≥10 days after the first dose of betamethasone, 64 (53%) received a second/retreatment course of antenatal betamethasone. The severe intraventricular hemorrhage rate in infants whose mothers received a second/retreatment course of betamethasone was similar to the rate in infants who delivered within 1-9 days and significantly lower than in those who delivered ≥10 days without retreatment (OR (95%CI): 0.10 (0.02, 0.65). Following the change in guidelines, the rate of retreatment in infants who delivered ≥10 days after the first betamethasone course (and before 28 weeks) increased from epoch 1 to epoch 2 (25% to 87%, p<0.001) and the rate of severe intraventricular hemorrhage decreased from 22% to 0% (p<0.001). In contrast, the rate of severe intraventricular hemorrhage in infants who delivered 1-9 days after the initial betamethasone dose (who were not eligible for retreatment) did not change between epochs 1 and 2 (12% and 11%, respectively). Although betamethasone's benefits on severe intraventricular hemorrhage appear to wane after the first dose, retreatment with a second course appears to restore its beneficial effects. Encouraging earlier retreatment of women at high risk of delivery before 28 weeks was associated with a lower rate of severe intraventricular hemorrhages among infants delivering <28 weeks.

Severe brain injury and trends of gestational‐age‐related neurodevelopmental outcomes in infants born very preterm: A population cohort study

AbstractAimTo investigate the impact of severe neonatal brain injury (SNBI) on gestational age‐related trends in neurodevelopmental impairment (NDI) outcome in infants born very preterm.MethodA population‐based cohort study recruited 1091 infants born at a gestational age of less than 31 weeks between 2011 and 2020. The trends in neonatal morbidities, mortality, and 24‐month NDI severity (no/mild, moderate, severe) by epoch (2011–2015, 2016–2020) and gestational age (22–25 weeks, 26–28 weeks, 29–30 weeks) were determined in infants with and without SNBI inclusion.ResultsThere was increased antenatal steroid use and higher maternal education and socioeconomic status over time. The rates of neonatal morbidities and mortality had no temporal changes. Among 825 infants with follow‐up, those in the 22 to 25 weeks gestational age group had declining trends in cerebral palsy and severe cognitive impairment, with decreased rates of severe NDI from 19% to 8% across epochs, particularly in those without SNBI (from 16% to 2%). Relative to its occurrence in epoch 2011 to 2015, risk of severe NDI was significantly reduced in epoch 2016 to 2020 (adjusted relative risk 0.39, 95% confidence interval 0.16–0.96) for infants born at 22 to 25 weeks gestational age, and the risk dropped even lower in these infants without SNBI (0.12, 0.02–0.84).InterpretationInfants born at 22 to 25 weeks gestational age had decreased rates of severe NDI in the decade between 2011 and 2020, particularly those without SNBI. The improvement might be attributed to better perinatal/neonatal and after‐discharge care.

“To Give or Not to Give”: Evolution of Recommendations on Administering Antenatal Corticosteroids in Late Preterm or Early Term

“To Give or Not to Give”: Evolution of Recommendations on Administering Antenatal Corticosteroids in Late Preterm or Early Term

Incidence, Risk Factors, Short-term Outcomes, and Microbiome of Ventilator-associated Pneumonia in Very-low-birth-weight Infants: Experience at a Single Level III Neonatal Intensive Care Unit.

Ventilator-associated pneumonia (VAP) is a common hospital-acquired infection in neonates on invasive mechanical ventilation, resulting in high morbidity and mortality. The objective of this study is to determine the incidence, risk factors, short-term outcomes and microbiome associated with VAP in very-low-birth-weight (VLBW) infants born at <32 weeks of gestational age (GA). Retrospective study of intubated VLBW infants born at <32 weeks of GA admitted to the Los Angeles General Medical Center neonatal intensive care unit from July 2015 to July 2021 who had routine tracheal aspirate cultures obtained. Neonates were retrospectively classified into 3 groups, confirmed VAP, suspected VAP and no VAP, for comparison of risk factors, outcomes and airway microbial colonization. Eighty-seven infants met inclusion criteria with a mean GA of 26.1 ± 1 weeks and mean birth weight of 812 ± 281 g. The incidence of VAP was 7.8 per 1000 ventilator days, and the most common causative organisms were Gram-positive organisms (39%), predominantly coagulase-negative Staphylococcus. Duration of postnatal dexamethasone exposure predicted VAP compared to no VAP (coefficient, 0.31; 95% CI 0.03-0.59; P = 0.03) after adjusting for duration of intubation, surfactant use and antenatal steroid exposure. Infants with VAP had higher rate of grade 2/3 bronchopulmonary dysplasia (P = 0.03) and longer hospital stay (P = 0.04). VAP occurs at a high rate in VLBW infants who are exposed to prolonged dexamethasone use. It is predominantly caused by Gram-positive organisms.

The performance of the practices associated with the occurrence of severe intraventricular hemorrhage in the very premature infants: data analysis from the Chinese neonatal network

BackgroundThe occurrence of severe intraventricular hemorrhage (sIVH) was high in the very preterm infants (VPIs) in China. The management strategies significantly contributed to the occurrence of sIVH in VPIs. However, the status of the perinatal strategies associated with sIVH for VPIs was rarely described across the multiple neonatal intensive care units (NICUs) in China. We aim to investigate the characteristics of the perinatal strategies associated with sIVH for VPIs across the multiple NICUs in China.MethodsThis was a retrospective analysis of data from a prospective cohort of Chinese Neonatal Network (CHNN) dataset, enrolling infants born at 24+0—31+6 from 2019 to 2021. Eleven perinatal practices performed within the first 3 days of life were investigated including antenatal corticosteroids use, antenatal magnesium sulphate therapy, intubation at birth, placental transfusion, need for advanced resuscitation, initial inhaled gas of 100% FiO2 in delivery room, initial invasive respiratory support, surfactant and caffeine administration, early enteral feeding, and inotropes use. The performances of these practices across the multiple NICUs were investigated using the standard deviations of differences between expected probabilities and observations. The occurrence of sIVH were compared among the NICUs.ResultsA total of 24,226 infants from 55 NICUs with a mean (SD) gestational age of 29.5 (1.76) and mean (SD) birthweight of 1.31(0.32) were included. sIVH was detected in 5.1% of VPIs. The rate of the antenatal corticosteroids, MgSO4 therapy, and caffeine was 80.0%, 56.4%, and 31.5%, respectively. We observed significant relationships between sIVH and intubation at birth (AOR 1.52, 95% CI 1.13 to 1.75) and initial invasive respiratory support (AOR 2.47, 95% CI 2.15 to 2.83). The lower occurrence of sIVH (4.8%) was observed corresponding with the highest utility of standard antenatal care, the lowest utility of invasive practices, and early enteral feeding administration.ConclusionsThe current evidence-based practices were not performed in each VPI as expected among the studied Chinese NICUs. The higher utility of the invasive practices could be related to the occurrence of sIVH.

Factors affecting neonatal respiratory distress syndrome at Wangaya General Hospital

Introduction: The neonatal period is a crucial window at the start of life. According to the American Academy of Pediatrics, 10% of all newborns require early respiratory support. Neonates with respiratory distress syndrome have a fourfold increased risk of death. Multiple maternal and neonatal risk factors affect the incidence of respiratory distress syndrome. This study aims to identify the relationship between method of delivery, maternal illness, premature rupture of membrane, amniotic fluid, low birth weight, gestational age, asphyxia, gender, multiple gestation, and perinatal infections towards the incidence of respiratory distress syndrome in Wangaya General Hospital. Methods: This is a retrospective case-control study. Secondary data was collected from the medical record. The sample size was 56 neonates aged 0-28 days with respiratory distress and without. Univariate analysis using Chi-square and Fisher’s Exact test and multivariate analysis using logistic regression. Results: Of the 114 neonates with respiratory distress, asphyxia (p &lt; 0.001) and low birth weight (p = 0.014) were correlated with respiratory distress when analyzed using bivariate and multivariate analysis. Maternal factors analyzed in the study did not affect the incidence of respiratory distress. Conclusion: Neonatal factors of birth asphyxia and low birth weight increased the risk of development of respiratory distress syndrome, while maternal factors did not increase such risks. Limitations of the study include secondary data and a lack of analysis of other detrimental factors, such as the administration of antenatal corticosteroids.

Characterisation of ciclesonide metabolism in human placentae across gestation

IntroductionCurrent clinical management of pregnancies at risk of preterm delivery includes maternal antenatal corticosteroid (ACS) treatment. ACS activate the glucocorticoid receptor (GR) in all fetal tissues, maturing the lungs at the cost of impaired brain development, creating a need for novel treatments. The prodrug ciclesonide (CIC) activates the GR only when converted to des-CIC by specific enzymes, including acetylcholinesterase (ACHE) and carboxylesterase 1 and 2 (CES1, CES2). Importantly, the human placenta expresses ACHE and CES, and could potentially produce des-CIC, resulting in systemic fetal exposure and GR activation in all fetal tissues. We therefore investigated CES gene expression and conversion of CIC to des-CIC in human placentae collected during the second trimester (Tri2), and at preterm and term birth. MethodsDifferential expression analysis was performed in Tri2 (n = 27), preterm (n = 34), and term (n = 40) placentae using the DESeq2 R-package. Conversion of CIC to des-CIC was measured in a subset of placenta samples (Tri2 n = 7, preterm n = 26, term n = 20) using functional assays. ResultsACHE mRNA expression was higher in Tri2 male than preterm and term male placentae only, whereas CES1 mRNA expression was higher in Tri2 than preterm or term placentae of both sexes. Conversion of CIC to des-CIC did not differ between gestational ages. DiscussionConversion of CIC to des-CIC by the human placenta may preclude its use as a novel GR-agonist in threatened preterm birth. In vivo studies are required to confirm the extent to which placental activation occurs after maternal treatment.

Hypertensive Disorders of Pregnancy and Risk of Early Brain Abnormalities on Magnetic Resonance Imaging at Term among Infants Born at ≤32 Weeks’ Gestational Age

To evaluate the proximal effects of hypertensive disorders of pregnancy (HDP) on a validated measure of brain abnormalities in infants born at ≤32 weeks' gestational age (GA) using magnetic resonance imaging (MRI) at term-equivalent age. In a multisite prospective cohort study, 395 infants born at ≤32 weeks' GA, underwent 3T MRI scan between 39 through 44 weeks' postmenstrual age. A single neuroradiologist, blinded to clinical history, evaluated the standardized Kidokoro global brain abnormality score as the primary outcome. We classified infants as HDP-exposed by maternal diagnosis of chronic hypertension, gestational hypertension, preeclampsia, or eclampsia. Linear regression analysis identified the independent effects of HDP on infant brain abnormalities, adjusting for histologic chorioamnionitis, maternal smoking, antenatal steroids, magnesium sulfate, and infant sex. Mediation analyses quantified the indirect effect of HDP mediated via impaired intrauterine growth and prematurity and remaining direct effects on brain abnormalities. 170/395 infants (43%) were HDP-exposed. Adjusted multivariable analyses revealed HDP-exposed infants had 27% (95% CI 5-53%) higher brain abnormality scores than those without HDP exposure (p=0.02), primarily driven by increased white matter injury/abnormality scores (p=0.01). Mediation analyses showed HDP-induced impaired intrauterine growth significantly (p=0.02) contributed to brain abnormality scores (22% of the total effect). Maternal hypertension independently increased the risk for early brain injury and/or maturational delays in infants born at ≤32 weeks' GA with an indirect effect of 22% resulting from impaired intrauterine growth. Enhanced prevention/treatment of maternal hypertension may mitigate the risk of infant brain abnormalities and potential neurodevelopmental impairments.

Association of Antenatal Corticosteroids with Neonatal Outcomes among Very Preterm Infants Born to Mothers with Clinical Chorioamnionitis: A Multicenter Cohort Study.

The objective of this study was to assess the relationship of ACS with neonatal outcomes among very preterm infants born to mothers with clinical chorioamnionitis in China. This was a multicenter retrospective cohort study. Study participants included infants born at <32 weeks' gestation with clinical chorioamnionitis and registered in the Chinese Neonatal Network from 1 January 2019 to 31 December 2020. Infants were divided into two groups: any amount of ACS or no administration of ACS. Multivariable generalized linear models using generalized estimating equations were used to assess the association between ACS and neonatal outcomes among the study population. We identified 2193 infants eligible for this study; 1966 (89.6%) infants had received ACS therapy, and 227 (10.4%) had not received any ACS therapy. Among very preterm infants born to mothers with clinical chorioamnionitis, any ACS usage was significantly associated with decreased risks of early death (aRR 0.56, 95% CI 0.32, 0.99) and severe ROP (aRR 0.51, 95% CI 0.28, 0.93) after adjustment for maternal hypertension, gestational age at birth, Caesarean section, being inborn, and administration of systemic antibiotics to the mother within 24 h before birth. In addition, out of the 2193 infants, the placentas of 1931 infants underwent pathological examination with recorded results. Subsequently, 1490 of these cases (77.2%) were diagnosed with histological chorioamnionitis. In 1490 cases of histologic chorioamnionitis, any ACS usage was significantly related to decreased risks of overall mortality (aRR 0.52, 95% CI 0.31, 0.87), severe ROP (aRR 0.47, 95% CI 0.25, 0.97), and respiratory distress syndrome (aRR 0.52, 95% CI 0.31, 0.87). We concluded that any ACS was associated with reduced risks for neonatal early death and severe ROP among very preterm infants born to mothers with clinical chorioamnionitis.

Association of different doses of antenatal corticosteroids exposure with early major outcomes and early weight loss percentage in extremely preterm infants or extremely low birthweight infants: a multicentre cohort study

ObjectivesTo determine the dose-dependent associations between antenatal corticosteroids (ANS) exposure and the rates of major morbidities, and the early weight loss percentage (EWLP) in hospital among extremely preterm infants (EPI)...