Risk Of Severe Intraventricular Hemorrhage Research Articles

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.

Serum Neuron-Specific Enolase as a Biomarker of Neonatal Brain Injury-New Perspectives for the Identification of Preterm Neonates at High Risk for Severe Intraventricular Hemorrhage.

Neonatal brain injury (NBI) is a critical condition for preterm neonates with potential long-term adverse neurodevelopmental outcomes. This prospective longitudinal case-control study aimed at investigating the levels and prognostic value of serum neuron-specific enolase (NSE) during the first 3 days of life in preterm neonates (<34 weeks) that later developed brain injury in the form of either periventricular leukomalacia (PVL) or intraventricular hemorrhage (IVH) during their hospitalization. Participants were recruited from one neonatal intensive care unit, and on the basis of birth weight and gestational age, we matched each case (n = 29) with a neonate who had a normal head ultrasound scan (n = 29). We report that serum NSE levels during the first three days of life do not differ significantly between control and preterm neonates with NBI. Nevertheless, subgroup analysis revealed that neonates with IVH had significantly higher concentrations of serum NSE in comparison to controls and neonates with PVL on the third day of life (p = 0.014 and p = 0.033, respectively). The same pattern on the levels of NSE on the third day of life was also observed between (a) neonates with IVH and all other neonates (PVL and control; p = 0.003), (b) neonates with II-IV degree IVH and all other neonates (p = 0.003), and (c) between control and the five (n = 5) neonates that died from the case group (p = 0.023). We conclude that NSE could be an effective and useful biomarker on the third day of life for the identification of preterm neonates at high risk of developing severe forms of IVH.

457 - Duration of hypotension and risk of severe intraventricular hemorrhage in periviable infants

457 - Duration of hypotension and risk of severe intraventricular hemorrhage in periviable infants

Impact of maternal age on neonatal outcomes among very preterm infants admitted to Chinese neonatal intensive care units: a multi-center cohort study.

BackgroundThe percentage of advanced maternal age (aged over 35 years) mothers has been rising across the world, the evidence of maternal age on neonatal outcomes from low- and middle-income countries is scarce. Our objective was to evaluate the effect of maternal age on mortality and major morbidity among very preterm infants admitted to Chinese neonatal intensive care units.MethodsData from a retrospective multi-center cohort of all complete care very preterm infants admitted to 57 neonatal intensive care units that participated in the Chinese Neonatal Network from January 1st to December 31st, 2019 were analyzed. Neonatal outcomes including mortality or any major morbidity, defined as necrotizing enterocolitis stage 2 or 3, moderate & severe bronchopulmonary dysplasia, severe intraventricular hemorrhage, cystic periventricular leukomalacia, severe retinopathy of prematurity, or sepsis. A multiple logistic regression model was constructed to analyze the independent association between maternal age and neonatal outcome.ResultsAmong 7,698 eligible newborns, 80.5% of very preterm infants were born to mothers between the ages of 21 and 35 years, with 18.0% born to mothers >35 years and 1.5% born to mothers <21 years. Higher rates of maternal hypertension, maternal diabetes, cesarean deliveries, antenatal steroid usage were noted as maternal age increased. The proportion of prenatal care, cesarean section, antenatal steroid usage and inborn for very preterm infants born to mothers <21 years was lower than those of mothers of other ages. Compared to the ages of 21–35 years group, the odds of severe intraventricular hemorrhage (adjusted odd ratio: 2.00, 95% CI: 1.08–3.71) was significantly higher in the ages of 15–20 years group. Increasing maternal age was associated with higher rates of small for gestational age and lower birth weight of very preterm infants, but no correlation between advanced maternal age and very preterm infants mortality or major morbidity.ConclusionsAmong very preterm infants, increasing maternal age was associated with higher rates of small for gestational age but not neonatal mortality or major morbidity. Young maternal age may increase the risk of severe intraventricular hemorrhage of very preterm infants.

Influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of

To study the influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of <34 weeks. PubMed, Web of Science, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Data, Weipu Database, and SinoMed were searched for randomized controlled trials on umbilical cord milking versus delayed cord clamping in preterm infants with a gestational age of <34 weeks published up to November 2021. According to the inclusion and exclusion criteria, two researchers independently performed literature screening, quality evaluation, and data extraction. Review Manger 5.4 was used for Meta analysis. A total of 11 articles were included in the analysis, with 1 621 preterm infants in total, among whom there were 809 infants in the umbilical cord milking group and 812 in the delayed cord clamping group. The Meta analysis showed that compared with delayed cord clamping, umbilical cord milking increased the mean blood pressure after birth (weighted mean difference=3.61, 95%CI: 0.73-6.50, P=0.01), but it also increased the incidence rate of severe intraventricular hemorrhage (RR=1.83, 95%CI: 1.08-3.09, P=0.02). There were no significant differences between the two groups in hemoglobin, hematocrit, blood transfusion rate, proportion of infants undergoing phototherapy, bilirubin peak, and incidence rates of complications such as periventricular leukomalacia and necrotizing enterocolitis (P>0.05). Compared with delayed cord clamping, umbilical cord milking may increase the risk of severe intraventricular hemorrhage in preterm infants with a gestational age of <34 weeks; however, more high-quality large-sample randomized controlled trials are needed for further confirmation.

Association between Baseline Cortisol Serum Concentrations and the Effect of Prophylactic Hydrocortisone in Extremely Preterm Infants

To define nomograms of serum cortisol values before 24hours of postnatal life for extremely preterm infants and determine whether baseline cortisol values affect the benefit/risk ratio of prophylactic hydrocortisone to improve survival without bronchopulmonary dysplasia (BPD). We performed a predefined secondary analysis of the multicenter randomized controlled PREMILOC trial that included inborn infants delivered before 28weeks of gestation. Nomograms of baseline serum cortisol values measured in 325 enrolled patients were determined for male and female neonates and correlated to perinatal events. BPD-free survival and severe adverse events were analyzed in placebo and hydrocortisone groups according to the cortisol z score in multivariate logistic regression models. Increased cortisol levels measured before 24hours following birth were associated with a significantly higher chance of BPD-free survival only in placebo-treated infants (aOR [95% CI] 1.57 [1.08-2.27], P=.02) based on sex-specific nomograms for baseline cortisol levels. The cortisol z score for infants treated with prophylactic hydrocortisonepredicted a risk of high-grade intraventricular hemorrhage (aOR [95% CI] 1.82 [1.06-3.15], P=.03) and spontaneous intestinal perforation (aOR [95% CI] 4.81 [1.34-17.22], P=.02). We found no predictive value of baseline cortisol levels for BPD-free survival in infants born extremely preterm treated with hydrocortisone. However, high cortisol levels early after birth were associated with a greater risk of severe intraventricular hemorrhage and spontaneous intestinal perforation in infants treated with hydrocortisone and, therefore, a lower benefit/risk ratio for the treatment. EudraCT 2007-002041-20, ClinicalTrial.gov: NCT00623740.

Umbilical cord milking in preterm infants: a systematic review and meta-analysis

ObjectiveTo conduct a systematic review and meta-analysis of the efficacy and safety of umbilical cord milking in preterm infants.DesignRandomised controlled trials comparing umbilical cord milking with delayed cord clamping/immediate cord...

Survival analysis of a cohort of extremely preterm infants born in Finland during 2005–2013

Objective This study aimed to analyze the mortality of extremely preterm infants (ELGA born alive before 28 weeks) until the postconceptional age of 42 weeks, death, or home discharge, whichever came first. It was focused especially on studying the relationship between antenatal risk factors, the time of death, and the postnatal morbidities associated with mortality. Study design The original data obtained from the nationwide Finnish medical birth register of extremely preterm and low birthweight infants born during 2005–2013 were analyzed. The total population consisted of 1353 ELGA infants after the exclusion of 18 infants born with lethal congenital anomalies or genetic defects. Mortality risks were adjusted according to the length of gestation, the administration of antenatal steroids, and the delivery hospital. Results During the first 48 hours, extreme immaturity was seen to be the prominent cause of death, and intrauterine growth did not influence mortality. The ELGA population surviving for at least 48 hours (N = 1135) was submitted for mortality risk analysis. After the adjustments, small-for-gestational-age (SGA) (birth weight below −2 SD) was found to be the factor with the highest risk for demise [OR 6.2; 95% CI (3.9–10.0) p < .001]. Multiple deliveries were associated with increased risk for death [OR 1.5; 95% CI (1.0–2.1), p = .048] to a lesser extent. The main neonatal morbidities associated with the risk of mortality after 48 postnatal hours of life were severe intraventricular hemorrhage (IVH) [OR 4.4; 95% CI (3.0–6.7), p < .001], respiratory distress syndrome (RDS) [OR 2.6; 95% CI (1.3–5.0), p = .006], and necrotizing enterocolitis (NEC) [OR 2.3; 95% CI (1.5–3.4), p < .001]. The major morbidities associated with deaths among non-SGA infants were severe IVH (32.1% of all deaths), NEC (19.1%), and sepsis (8.4%). In SGA infants, severe respiratory disease (RDS, severe bronchopulmonary dysplasia, pulmonary hemorrhage, or pulmonary hypertension) was the main cause of death (60.9% of all deaths). Medical or surgical PDA treatment was not found to be associated with increased risk of death [OR 0.4; 95% CI (0.2–0.5), p < .001] compared to infants who had survived for more than 2 days. Severe preeclampsia was found to be associated with 42% of all ELGA-SGA births. After the adjustments, ELGA infants from pregnancies complicated by preeclampsia of the mother exhibited a significantly lower risk of severe IVH [OR 0.3; 95% CI (0.2–0.5), p < .001] compared to the non-preeclamptic mothers’ infants. The low incidence of severe IVH was evident regardless of fetal growth in this patient group. Conclusions SGA infants with less than 28 gestational weeks, who had survived for at least 2 days, had excessively high mortality due to severe pulmonary disease. Intrauterine growth had no influence on the risk of death, other than pulmonary causes. The infants of preeclamptic mothers exhibited an increased risk of intrauterine growth retardation; however, despite this serious complication, these infants exhibited a significant decrease in the risk for severe IVH.

Risk of Severe Intraventricular Hemorrhage in the First Week of Life in Preterm Infants Transported Before 72 Hours of Age.

Evaluate the risk of severe intraventricular hemorrhage, in the first week of life, in preterm infants undergoing early interhospital transport. Retrospective cohort study. Tertiary neonatal centers of the Trent Perinatal Network in the United Kingdom. Preterm infants less than 32 weeks gestation, who were either born within and remained at the tertiary neonatal center (inborn), or were transferred (transported) between centers in the first 72 hours of life. None. Multivariable logistic regression models adjusting for key confounders were used to calculate odds ratios for intraventricular hemorrhage with 95% CIs for comparison of inborn and transported infants. Cranial ultrasound findings on day 7 of life. Secondary analyses were performed for antenatal steroid course and gestational age subgroups. A total of 1,047 preterm infants were included in the main analysis. Transported infants (n = 391) had a significantly higher risk of severe (grade III/IV) intraventricular hemorrhage compared with inborns (n = 656) (9.7% vs 5.8%; adjusted odds ratio, 1.69; 95% CI, 1.04-2.76), especially for infants born at less than 28 weeks gestation (adjusted odds ratio, 1.83; 95% CI, 1.03-3.21). Transported infants were less likely to receive a full antenatal steroid course (47.8% vs 64.3%; p < 0.001). A full antenatal steroid course significantly decreased the risk of severe intraventricular hemorrhage irrespective of transport status (odds ratio, 0.33; 95% CI, 0.2-0.55). However, transported infants less than 28 weeks gestation remained significantly more likely to develop a severe intraventricular hemorrhage despite a full antenatal steroid course (adjusted odds ratio, 2.84; 95% CI, 1.08-7.47). Preterm infants transported in the first 72 hours of life have an increased risk of early-life severe intraventricular hemorrhage even when maternal antenatal steroids are given. The additional burden of postnatal transport could be an important component in the pathway to severe intraventricular hemorrhage. As timely in-utero transfer is not always possible, we need to focus research on improving the transport pathway to reduce this additional risk.

Predictors of severe intraventricular hemorrhage in preterm infants under 29-weeks gestation

Purpose: Preterm infants <29 weeks of gestation are at risk for severe intraventricular hemorrhage (IVH). Lower gestational age, birth weight, severe illness, as indexed by higher Score for Neonatal Acute Physiology - Perinatal Extension II (SNAPPE-II) are associated with severe IVH. The role of coagulation abnormalities on the first day after birth in severe IVH remains controversial. The present study investigated factors that predict the risk of severe IVH, including SNAPPE-II at 12 h and coagulation parameters on the first day after birth. Materials and methods: A retrospective chart review of infants < 29 weeks of gestation from January 2008 to December 2013 was performed. Prenatal and postnatal characteristics, SNAPPE-II at 12 h, coagulation parameters [prothrombin time (PT), INR, partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen] on the first day and cranial ultrasound examination records were collected. The association between clinical and laboratory variables and severe IVH was determined. A joint predictive model for the risk of severe IVH (grades 3 and 4) versus no-mild IVH (grades 0, 1, and 2) was developed using multiple regression analysis. Results: Preterm infants of gestational age < 29 weeks were included (n = 101). Fifteen (15%) infants had severe IVH. Lower gestational age (p = .006), birth weight (p = .008), African American race (p = .031) and higher SNAPPE-II at 12 h (p = .001) were associated with severe IVH. Infants with severe IVH had longer PT (p = .004), higher INR (p = .004) and lower platelet count (p = .034) than those with no-mild IVH. Stepwise logistic regression showed that only SNAPPE-II at 12 h was an independent predictor of severe IVH. For each unit increase in SNAPPE-II, the log odds of severe IVH increased by 0.045 (95% CI: [0.017, 0.073]; p = .002). A threshold of 55 on the SNAPPE-II yielded a sensitivity of 60% (9/15), a specificity of 91% (78/86), a positive predictive value (PPV) of 53% (9/17) and a negative predictive value (NPV) of 93% (78/84). All other demographic and clinical variables and coagulation abnormalities had an insignificant coefficient (p > .05) when included in a bivariate logistic model with SNAPPE-II. Conclusion: SNAPPE-II at 12 h after birth is an independent predictor of severe IVH in preterm infants with gestational age < 29 weeks.

550: Dellivery mode and intraventricular hemorrhage in early preterm infants

To assess the effects of mode of delivery on the risk of severe intraventricular hemorrhage (IVH) (grade 3 or 4) in early preterm birth. This is a retrospective study of 359 infants delivered at 22-28 weeks of gestation between January 2011 and December 2017 at a tertiary center. Study subjects were divided into vaginal delivery group (n=105) and cesarean delivery group (n=254). We also performed subgroup analysis by stratifying gestational age at delivery <26 and ≥26 weeks of gestation. Univariable and multivariable analysis were used to compare the rates of IVH and mortality between the two groups. There was no significant difference in the rate of IVH (vaginal vs. cesarean; 15.2 vs. 9.4%, P=0.275). Also, there was no difference in the rate of IVH in the neonates born <26 and ≥26 weeks of gestation (22.0 vs. 14.0%, P=0.200, 9.1 vs. 6.5%, P=0.724), respectively. Meanwhile, neonatal mortality rate was significantly lower in the cesarean delivery group (29.5% vs. 18.9%, P=0.027). However, this difference was not observed after excluding unintended non-vertex vaginal delivered cases (16.3% vs. 10.6%, P=0.144). Multiple logistic regression analysis also showed that cesarean delivery could not decrease the rate of IVH [(adjusted odds ratio (aOR) 1.695; 95% confidence interval (CI) 0.816-3.523)] and mortality (aOR; 0.613; 95% CI 0.301-1.248). Cesarean delivery in preterm births at 22-28 weeks of gestation could not decrease the rate of IVH or mortality. Therefore, mode of delivery at this early gestational period could be decided based on obstetrical indications.

Intraventricular Hemorrhage Caused by Subarachnoid Hemorrhage: Does the Severity Matter?

Aneurysm rupture might be accompanied by intraventricular hemorrhage (IVH), which is associated with poor outcome of subarachnoid hemorrhage (SAH). The aim of this study was to analyze risk factors and clinical impact of IVH severity. A total of 995 consecutive patients with SAH treated at our institution between January 2003 and June 2016 were eligible for this study. Clinical and radiologic findings were correlated with the presence and severity of IVH assessed with the original Graeb score. A total of 487 patients with SAH (48.9%) presented with IVH (mean IVH severity, 5.48 points [±3.5]). IVH severity correlated with poorer initial clinical condition (World Federation of Neurosurgical Societies grade >3; P<0.001), acute hydrocephalus (P= 0.001), and poor outcome at 6 months (modified Rankin Scale score >2; P<0.001). The location of the ruptured aneurysm in the anterior cerebral artery independently predicted the occurrence (P= 0.007) and severity of IVH (P < 0.001). In turn, aneurysm size affected only the severity of IVH (P=0.001) but not its occurrence (P= 0.153). Early complications of SAH occurring within 72 hours after the bleeding event (cerebral infarction [P= 0.043], early mortality [P= 0.001], and primary craniectomy [P= 0.043]) were independently associated with the severity of IVH. Severity of aneurysmal IVH is a strong contributor to initial severity and early complications of SAH. Patients with larger aneurysms, especially located in the anterior cerebral artery, are at particular risk of severe IVH in cases of aneurysm rupture.

Morbidities associated with patent ductus arteriosus in preterm infants. Nationwide cohort study

Purpose: To evaluate the predictive factors for the development of haemodynamically significant patent ductus arteriosus (PDA) in preterm infants and to study the morbidities associated with the treatment of PDA during the first hospitalization.Materials and methods: Data were collected from the Finnish national register of preterm infants (<32 gestational weeks) born in 2005–2013. In total, 3668 infants were included. Morbidities during the first hospitalization were analysed and compared between infants who received treatments for the closure of PDA (n = 1132) and infants who received no treatment for PDA (n = 2536). The results were adjusted for the duration of pregnancy, intrauterine growth pattern, antenatal steroids, delivery hospital and respiratory distress syndrome (RDS).Results: RDS and mechanical ventilation were independently associated with an increased risk of PDA requiring treatment. Medical and surgical treatments were associated with the risk of severe bronchopulmonary dysplasia (BPD). Primary surgical ligation was associated with an increased risk of severe intraventricular haemorrhage (IVH) and necrotizing enterocolitis (NEC). Medical treatment itself and also followed by surgical ligation was associated with lower mortality.Conclusion: The severity of lung disease rather than prematurity per se was associated with the development of PDA requiring therapy. Both medical and surgical therapies for PDA were associated with severe BPD, and primary surgical ligation was associated with NEC and severe IVH.

Association between Off-Peak Hour Birth and Neonatal Morbidity and Mortality among Very Low Birth Weight Infants

To assess the independent association between overnight or "off-peak" hour delivery and 3 neonatal morbidities strongly associated with childhood neurocognitive impairment. Retrospective population based cohort study of all infants with birth weights of 500-1499 g born without severe congenital anomalies in California or Pennsylvania between 2002 and 2009. Off-peak hour delivery was defined as birth between 12:00 a.m. and 6:59 a.m. The study outcomes were death; bronchopulmonary dysplasia, retinopathy of prematurity, and severe (grade 3 or 4) intraventricular hemorrhage among survivors; the composite of each morbidity or mortality; and the composite of death or 1 or more of the evaluated morbidities. Of 47 617 evaluated infants, 9317 (19.6%) were born during off-peak hours. The frequencies of all study outcomes were higher among infants born during off-peak compared with peak hours. After adjusting for maternal, infant, and hospital characteristics, off-peak hour delivery was associated with increased odds of severe intraventricular hemorrhage among survivors (OR 1.39, 95% CI 1.23-1.57) and the composite outcomes of death or severe intraventricular hemorrhage (OR 1.16, 95% CI 1.07-1.25) and death or major morbidity (OR 1.08, 95% CI 1.02-1.15). There was no evidence of subgroup effects based on delivery mode, birth hospital neonatal intensive care level or annual very low birth weight infant delivery volume, or weekday vs weekend off-peak hour delivery for any study outcome. Very low birth weight infants born between midnight and 7:00 a.m. are at increased risk for severe intraventricular hemorrhage and death or major neonatal morbidity.

Neonatal intubation training: the patient comes first

Premature babies that require resuscitation are highly vulnerable to poor outcomes, including death, intraventricular hemorrhage, and neurodevelopmental impairment. As a result, the early minutes of neonatal resuscitation are viewed as a “golden hour” requiring technical precision and choreographed teamwork. Sauer et al used their large database of resuscitation data to show that multiple intubation attempts, particularly in the smallest babies, dramatically increased rates of intraventricular hemorrhage. As trainees typically require more attempts while learning intubation, the data from Sauer et al also suggest that delivery room resuscitation of extremely preterm babies is a poor training environment for pediatric residents. Yet, the Accreditation Council for Graduate Medical Education continues to mandate proficiency in neonatal intubation, even as the number of opportunities fall and the stakes associated with the procedure rise. Although simulation can provide some support in learning intubation mechanics, it does not fully build competency. It is time to re-examine which trainees will truly require this skill and develop novel approaches to build expertise. In the meantime, intubation training should be confined to more mature, stable, and sedated neonates. Article page 108 ▶ Intubation Attempts Increase the Risk for Severe Intraventricular Hemorrhage in Preterm Infants—A Retrospective Cohort StudyThe Journal of PediatricsVol. 177PreviewTo evaluate whether neonates exposed to multiple intubation attempts within the first 4 days after birth have an increased incidence of intraventricular hemorrhage (IVH). Full-Text PDF

Intubation Attempts Increase the Risk for Severe Intraventricular Hemorrhage in Preterm Infants—A Retrospective Cohort Study

To evaluate whether neonates exposed to multiple intubation attempts within the first 4 days after birth have an increased incidence of intraventricular hemorrhage (IVH). This is a retrospective cohort study of infants intubated during the first 4 days after birth. Infants had birth weights (BWs) less than 1500 g and were admitted to the neonatal intensive care unit (NICU) at the University of California, San Diego, between January 1, 2005, and July 30, 2009. A subgroup analysis was done for infants with BW less than 750 g. A total of 308 infants with BW <1500 g, including 102 with a BW <750 g, were intubated within the first 4 days of life. The number of intubation attempts was significantly greater in infants with a BW <750 g who had severe IVH compared with those with mild or no IVH (OR 1.395, 95% CI 1.090-1.786, P = .008). For infants with BW <1500 g, the number of intubation attempts in the delivery room was significantly greater for infants with severe IVH (OR 1.317, 95% CI 1.052-1.649, P = .016). Increased intubation attempts were associated with increased incidence of severe IVH in infants with BW less than 750 g and in infants less than 1500 g who were intubated only in the delivery room. Prospective studies are needed to further evaluate the relationship between intubation attempts and severe IVH.

Antenatal Exposure to Indomethacin Increases the Risk of Severe Intraventricular Hemorrhage, Necrotizing Enterocolitis, and Periventricular Leukomalacia

Objective The purpose of this study was to provide an updated summary of the literature regarding the effects of tocolysis with indomethacin on neonatal outcome by systematically reviewing previously and recently reported data. Study Design All previously reported studies pertaining to indomethacin tocolysis and neonatal outcomes along with recently reported data were identified with the use of electronic databases that had been supplemented with references that were cited in original studies and review articles. Observational studies that compared neonatal outcomes among preterm infants who were exposed and not exposed to indomethacin were included in this systematic review. Data were extracted and quantitative analyses were performed on those studies that assessed the neonatal outcomes of patients that received antenatal tocolysis with indomethacin. Results Twenty-seven observational studies that met criteria for systematic review and metaanalysis were identified. These studies included 8454 infants, of whom 1731 were exposed to antenatal indomethacin and 6723 were not exposed. Relative risks with 95% confidence intervals were calculated for dichotomous outcomes with the use of random and fixed-effects models. Metaanalysis revealed no statistically significant differences in the rates of respiratory distress syndrome, patent ductus arteriosus, neonatal mortality rate, neonatal sepsis, bronchopulmonary dysplasia, or intraventricular hemorrhage (all grades). However, antenatal exposure to indomethacin was associated with an increased risk of severe intraventricular hemorrhage (grade III-IV based on Papile's criteria; relative risk, 1.29; 95% confidence interval, 1.06–1.56), necrotizing enterocolitis (relative risk, 1.36; 95% confidence interval, 1.08–1.71), and periventricular leukomalacia (relative risk, 1.59; 95% confidence interval, 1.17–2.17). Conclusion The use of indomethacin as a tocolytic agent for preterm labor is associated with an increased risk for severe intraventricular hemorrhage, necrotizing enterocolitis, and periventricular leukomalacia.

Early sodium and fluid intake and severe intraventricular hemorrhage in extremely low birth weight infants.

Hypernatremic dehydration is an important cause of intracranial hemorrhage. A possible association of intraventricular hemorrhage (IVH) with hypernatremia and/or high sodium intake has been suggested in preterm infants. To investigate the associations of early fluid and sodium intake or serum sodium concentrations with severe intraventricular hemorrhage (IVH) in extremely low birth weight (ELBW) infants, we reviewed the medical records of 169 inborn ELBW infants. Daily fluid and sodium intake, urine output, weight loss and serum sodium concentration during the first 4 days of life were obtained. Patients were divided into the severe IVH (grade 3/4) and the control (no or grade 1/2 IVH) group. The maximum serum sodium concentration and the incidence of hypernatremia did not differ between the two groups. Related to the fluid balance and sodium intake, the risk for severe IVH was strongly associated with total fluid and sodium intake during the initial four days of life. With respect to the fluids other than transfusion, severe IVH can be discriminated only by sodium intake but not by fluid intake. Large randomized controlled trials are required to clarify the causal relationship between the early sodium intake and severe IVH in ELBW infants.

Antenatal exposure to indomethacin increases the risk of severe intraventricular hemorrhage, necrotizing enterocolitis, and periventricular leukomalacia: a systematic review with metaanalysis

The purpose of this study was to provide an updated summary of the literature regarding the effects of tocolysis with indomethacin on neonatal outcome by systematically reviewing previously and recently reported data. All previously reported studies pertaining to indomethacin tocolysis and neonatal outcomes along with recently reported data were identified with the use of electronic databases that had been supplemented with references that were cited in original studies and review articles. Observational studies that compared neonatal outcomes among preterm infants who were exposed and not exposed to indomethacin were included in this systematic review. Data were extracted and quantitative analyses were performed on those studies that assessed the neonatal outcomes of patients that received antenatal tocolysis with indomethacin. Twenty-seven observational studies that met criteria for systematic review and metaanalysis were identified. These studies included 8454 infants, of whom 1731 were exposed to antenatal indomethacin and 6723 were not exposed. Relative risks with 95% confidence intervals were calculated for dichotomous outcomes with the use of random and fixed-effects models. Metaanalysis revealed no statistically significant differences in the rates of respiratory distress syndrome, patent ductus arteriosus, neonatal mortality rate, neonatal sepsis, bronchopulmonary dysplasia, or intraventricular hemorrhage (all grades). However, antenatal exposure to indomethacin was associated with an increased risk of severe intraventricular hemorrhage (grade III-IV based on Papile's criteria; relative risk, 1.29; 95% confidence interval, 1.06-1.56), necrotizing enterocolitis (relative risk, 1.36; 95% confidence interval, 1.08-1.71), and periventricular leukomalacia (relative risk, 1.59; 95% confidence interval, 1.17-2.17). The use of indomethacin as a tocolytic agent for preterm labor is associated with an increased risk for severe intraventricular hemorrhage, necrotizing enterocolitis, and periventricular leukomalacia.

A risk prediction model for severe intraventricular hemorrhage in very low birth weight infants and the effect of prophylactic indomethacin

Develop a risk prediction model for severe intraventricular hemorrhage (IVH) in very low birth weight infants (VLBWI). Prospectively collected data of infants with birth weight 500 to 1249 g born between 2001 and 2010 in centers from the Neocosur Network were used. Forward stepwise logistic regression model was employed. The model was tested in the 2011 cohort and then applied to the population of VLBWI that received prophylactic indomethacin to analyze its effect in the risk of severe IVH. Data from 6538 VLBWI were analyzed. The area under ROC curve for the model was 0.79 and 0.76 when tested in the 2011 cohort. The prophylactic indomethacin group had lower incidence of severe IVH, especially in the highest-risk groups. A model for early severe IVH prediction was developed and tested in our population. Prophylactic indomethacin was associated with a lower risk-adjusted incidence of severe IVH.