Development Of Intraventricular Hemorrhage Research Articles

Causes of intraventricular hemorrhages in extremely premature newborns and features of their early outcomes

The aim. To study the predisposing factors for the development and timing of development of intraventricular hemorrhage (IVH) in extremely premature newborns.Materials and methods. We carried out retrospective analysis of 32 case histories of children born at a gestational age of less than 32 weeks. The children were divided into three groups: group 1 (n = 13) – children death was caused by non-traumatic IVH; group 2 (n = 12) – surviving infants with IVH; group 3 (comparison group; n = 7) – premature infants without IVH. We assessed risk factors for the development of IVH, their severity, and main indicators predisposing to death in newborns of these groups.Results. Children of the group 1 had statistically significantly low values of body weight – 670 [640–860] g (р1–2 = 0.007; р1–3 = 0.012), head circumference – 23 [22–24] cm (р1–2 = 0.008; р1–3 = 0.049), gestational age – 24.5 [23.5–25.5] weeks (р1–2 = 0.002; р1–3 = 0.007). Gender differences were revealed: in the group 1, there were 92.3 % of boys, in the group 2 – 33.3 % (p1–2 = 0.008). Maternal smoking increased the risk of fatal IVH by 3.5 ± 0.15 times, polyhydramnios – by 3.3 ± 0.37 times, chorioamnionitis – by 12.8 ± 0.47 times, placenta previa – by 3.2 ± 0.15 times. In newborns of the group 1, seizures developed on the day 1 of life in 84.6 % (more often than in group 2; p = 0.00001), and shock in the first 3 hours of life was recorded in 46.1 % of cases (р1–2 = 0.034), which increased the risk of death by 4.3 ± 0.47 times. In newborns of group 1, compared with newborns of groups 2 and 3, pulmonary hypertension was more often detected (60.8 [50.1–69.2] mm Hg; p1–2 = 0.028; p1–3 = 0.047).Conclusion. Confirmed infectious diseases in the mother, clinical manifestation of convulsions, pulmonary hypertension, development of multiple organ failure and shock in extremely premature newborns increase the risk of intraventricular hemorrhage and the frequency of deaths.

Does perinatal management have the potential to reduce the risk of intraventricular hemorrhage in preterm infants?

Intraventricular hemorrhage (IVH) is an important cause of neurodevelopmental impairment in preterm infants. A number of risk factors for IVH have already been proposed; however, some controversies regarding optimal perinatal management persist. This study aimed to identify perinatal and neonatal attributes associated with IVH in a representative population of preterm infants. Perinatal data on 1,279 very preterm infants (<32 weeks of gestation) admitted to a tertiary neonatal intensive care unit were analyzed. The records were assessed using univariate analysis and logistic regression model to evaluate the risk factors for any and high-grade IVH (grade III-IV according to the classification by Papile) within the first week after birth. The incidence of any IVH was 14.3% (183/1,279); the rate of low-grade (I-II) and high-grade (III-IV) IVH was 9.0% (115/1,279) and 5.3% (68/1,279), respectively. Univariate analysis revealed multiple factors significantly associated with intraventricular hemorrhage: lower gestational age and birth weight, absence of antenatal steroids, vaginal delivery, low Apgar score at 5 min, delivery room intubation, surfactant administration, high frequency oscillation, pulmonary hypertension, pulmonary hemorrhage, tension pneumothorax, persistent ductus arteriosus, hypotension and early onset sepsis. Logistic regression confirmed lower gestational age, vaginal delivery, ductus arteriosus and early onset sepsis to be independent predictors for any IVH. Pulmonary hemorrhage, tension pneumothorax and early onset sepsis were independent risk factors for high-grade IVH. Complete course of antenatal steroids was associated with a lower risk for any (odds ratio 0.58, 95% confidence interval 0.39-0.85; P = .006) and for high-grade intraventricular hemorrhage (odds ratio 0.36, 95% confidence interval 0.20-0.65; P < .001). The use of antenatal steroids and mode of delivery are crucial in the prevention of IVH; however, our study did not confirm the protective effect of placental transfusion. Severe respiratory insufficiency and circulatory instability remain to be powerful contributors to the development of IVH. Early detection and management of perinatal infection may also help to reduce the rate of brain injury and improve neurodevelopment in high-risk newborns.

Early red blood cell transfusion and the occurrence of intraventricular hemorrhage in very preterm infants

BackgroundPreterm infants are at risk of developing both intraventricular hemorrhage (IVH) and anemia of prematurity. Several studies reported an association between early postnatal red blood cell (RBC) transfusion and IVH, however the timing and causality between these two remains unclear. AimsTo describe the temporal sequence between administration of early RBC transfusion (within the first week of life) and diagnosis of IVH in very preterm infants. Study designRetrospective single center case-series. Subjects132 very preterm infants (<32 weeks' gestation), admitted to a level III neonatal intensive care unit, studied with serial cranial ultrasound (CUS), and diagnosed with any grade of IVH. Outcome measuresNumber and timing of early RBC transfusions in relation to the timing of IVH. ResultsMedian time of IVH diagnosis was 20.5 h after birth (interquartile range [IQR], 6.25–49.00 h). Of those who received an early RBC transfusion (36 %, 47/132), only 15 % (20/132) received it before the IVH diagnosis. Infants with RBC transfusion before IVH more frequently had lower birth weight, received less fequently antenatal steroids, required more often invasive mechanical ventilation and surfactant administration, had more often hypo- and hypercapnia, and received more fluid boluses, NaHCO3, and inotropes compared to the rest. ConclusionsIn the majority of infants, IVH was already present at the time of the first RBC transfusion. Studies including pre- and post RBC transfusion CUS are needed to assess the effect of early RBC transfusions on the development of IVH in preterm neonates.

Early onset neonatal thrombocytopenia is associated with severe intraventricular hemorrhage in very preterm infants: A retrospective cohort study.

The role of platelet function in the development of intraventricular hemorrhage is still a subject of debate. In this study, we aimed to determine whether there is an association between platelet indices in the first week of life and severity of intraventricular hemorrhage in very preterm infants. Preterm infants born < 30 weeks of gestation in our hospital were retrospectively evaluated. Platelet parameters, including platelet counts, mean platelet volume, platelet distribution width, and platelet mass were retrieved at two different time points: the initial value on the first day of life and the value closest to the end of the first week of life. The infants were categorized according to the findings of cranial ultrasonography as; no intraventricular hemorrhage, mild or severe intraventricular hemorrhage. Totally, 1051 infants were evaluated. The mean gestational age and birth weight for the entire cohort were 27.9±1.6 weeks and 1058±247 g, respectively. Infants in the severe intraventricular hemorrhage group had significantly lower gestational age (p < 0.001) and birthweight (p < 0.001) compared to other two groups. Furthermore, there were significant differences in platelet count and platelet mass between the groups at two time intervals. However, logistic regression analysis revealed that only platelet count of < 100×109/L on the first postnatal day was independently associated with the severity of intraventricular hemorrhage. There is an association between platelet count of < 100×109/L on the first postnatal day and severe intraventricular hemorrhage in very preterm infants.

The role of blood pressure variability indicators combined with cerebral blood flow parameters in predicting intraventricular hemorrhage in very low birth weight preterm infants.

Hemodynamic instability is the main factor responsible for the development of intraventricular hemorrhage (IVH) in premature newborns. Herein, we evaluated the predictive ability of blood pressure variability (BPV) and anterior cerebral artery (ACA) blood flow parameters in IVH in premature infants with gestational age (GA) ≤32 weeks and birth weight (BW) ≤ 1,500 g. Preterm infants with GA ≤32 weeks and BW ≤ 1,500 g admitted to the neonatal intensive care unit (NICU) of the hospital affiliated to Yangzhou University from January 2020 to January 2023 were selected as the research subjects. All preterm infants were admitted within 1 h after birth, and systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MABP) were monitored at 1-h intervals. The difference between maximum and minimum values (max-min), standard deviation (SD), coefficient of variation (CV), and successive variation (SV) were used as BPV indicators. On the 1st, 3rd, and 7th day after birth, transcranial ultrasound examination was performed to screen for the occurrence of IVH. On the 24 ± 1 h after birth, systolic velocity (Vs), diastolic velocity (Vd), and resistance index (RI) of the ACA were measured simultaneously. Preterm infants were divided into the IVH group and non-IVH group based on the results of transcranial ultrasound examination, and the correlation between BPV indicators, ACA blood flow parameters, and development of IVH was analyzed. A total of 92 premature infants were enrolled, including 49 in the IVH group and 43 in the non-IVH group. There was no statistically significant difference in baseline characteristics such as BW, GA, sex, and perinatal medical history between the two groups of preterm infants (P > 0.05). The SBP SD (OR: 1.480, 95%CI: 1.020-2.147) and ACA-RI (OR: 3.027, 95%CI: 2.769-3.591) were independent risk factors for IVH in premature newborns. The sensitivity and specificity of combined detection of SBP SD and ACA-RI in predicting IVH were 61.2% and 79.1%, respectively. High BPV and ACA-RI are related to IVH in premature infants with GA ≤32 w and BW ≤1,500 g. Combined detection of SBP SD and ACA-RI has a certain predictive effect on early identification of IVH.

Pathogenesis and Prevention of Intraventricular Hemorrhage in Preterm Infants.

Intraventricular hemorrhage (IVH) is a serious concern for preterm infants and can predispose such infants to brain injury and poor neurodevelopmental outcomes. IVH is particularly common in preterm infants. Although advances in obstetric management and neonatal care have led to a lower mortality rate for preterm infants with IVH, the IVH-related morbidity rate in this population remains high. Therefore, the present review investigated the pathophysiology of IVH and the evidence related to interventions for prevention. The analysis of the pathophysiology of IVH was conducted with a focus on the factors associated with cerebral hemodynamics, vulnerabilities in the structure of cerebral vessels, and host or genetic predisposing factors. The findings presented in the literature indicate that fluctuations in cerebral blood flow, the presence of hemodynamic significant patent ductus arteriosus, arterial carbon dioxide tension, and impaired cerebral venous drainage; a vulnerable or fragile capillary network; and a genetic variant associated with a mechanism underlying IVH development may lead to preterm infants developing IVH. Therefore, strategies focused on antenatal management, such as routine corticosteroid administration and magnesium sulfate use; perinatal management, such as maternal transfer to a specialized center; and postnatal management, including pharmacological agent administration and circulatory management involving prevention of extreme blood pressure, hemodynamic significant patent ductus arteriosus management, and optimization of cardiac function, can lower the likelihood of IVH development in preterm infants. Incorporating neuroprotective care bundles into routine care for such infants may also reduce the likelihood of IVH development. The findings regarding the pathogenesis of IVH further indicate that cerebrovascular status and systemic hemodynamic changes must be analyzed and monitored in preterm infants and that individualized management strategies must be developed with consideration of the risk factors for and physiological status of each preterm infant.

Intraventricular hemorrhage prediction in premature neonates in the era of hemodynamics monitoring: a prospective cohort study

Unstable hemodynamics and prematurity are the main players in intraventricular hemorrhage (IVH) development. Our objective was to study 8 the use of superior vena cava flow (SVCF), left ventricular output (LVO), and right ventricular output (RVO), and anterior cerebral artery (ACA) Doppler measures in prediction of IVH in the first week of life in preterm infant ≤ 32 weeks and birth weight ≤ 1500 g. This prospective cohort study was conducted in 55NICU of Alexandria University maternity hospital. Of 147 enrolled patients, 132 infants born ≤ 32 weeks GA and birth weight ≤ 1500 g were eligible for- the study. One hundred twenty-seven infants completed the study. Infants were scanned for ACA-RI using transfontanellar ultrasound, and SVCF, LVO, and RVO using functional echocardiography in the first 24 h after birth. Patients had another two scans on DOL3 and 7 to detect IVH development. Low SVCF and high ACA-RI significantly increased the risk of IVH using logistic regression models with OR, 3.16; 95%CI, 1.19–8.39; P = 0.02 and OR, 1.64; 95%Cl, 1.10–2.44; P = 0.02, respectively. Low SVCF and high ACA-RI significantly increased risk of catastrophic IVH P = 0.025 and 0.023, respectively. Combined use of low SVCF < 55 ml/kg/min and ACA-RI > 0.75 is predictor of IVH with sensitivity 40.8% and 82.1% specificity.Conclusions: There are strong relations between both low SVCF and high ACA-RI, and IVH development in premature neonates ≤ 32 weeks and birth weight ≤ 1500 g, with more significance towards catastrophic IVH. Admission RSS and LVO are the strongest factors affecting SVCF. Maternal anemia, patent ductus arteriosus size (mm/kg), and capillary refill time were significantly associated with high ACA-RI. These findings help in more understanding of pathophysiological factors affecting central perfusion that might affect the longer term neurodeveopmental outcome.Trial registration: This work was registered in clinical trial.gv no NCT05050032.What is Known:•Whether SVCF and RI-ACA can predict IVH in preterm neonates is still debatable.What is New:•Low SVC flow and high ACA-RI significantly increased risk of IVH, confirming the role of hypoperfusion-reperfusion cycle in IVH development. The most striking result that combined metrics using the cut-off value of < 41 ml/kg/min for SVCF and > 0.85 for ACA-RI “in the first day of life” can correctly reject the presence of IVH in 98% of patients “during the first week of life.”

Delivery Mode and Neurological Complications in Very Low Birth Weight Infants.

The risk of intraventricular hemorrhage (IVH) and periventricular leukomalacia is associated with low birth weight and gestational age. Caesarean section (CS) may reduce the risk of IVH, although it has been a matter of debate. The aim of this study was to evaluate the influence of the mode of delivery (MOD) on the development of IVH and cystic periventricular leukomalacia (cPVL). We analyzed an initial cohort of 11,023 very low birth weight (VLBW) infants born between January 2010 and December 2019. Infants with major malformations and gestational age <23 weeks and ≥32 weeks were excluded. A final cohort of 8,251 newborns was analyzed. Data was collected from Portuguese National very low birth weight registry. Cases were classified as vaginal delivery (VD) or CS. Outcome was assessed in univariate and logistic regression analyses. The median gestational age was 29 weeks (IQR 3.3) and the median weight was 1,100 g (IQR 555). The prevalence of IVH was significantly higher in the VD group versus the CS group, across all grading levels:1,144 newborns had grade I IVH (16% VD vs. 14% CS, p <0.01), 706 had grade II IVH (12% VD vs. 7.6% CS, p <0.01), and 777 had grade III IVH (14% VD vs. 7.9% CS, p <0.01). Post-hemorrhagic ventricular dilatation occurred in 457 newborns (8.3% VD vs. 4.6% CS, p <0.01) and 456 newborns had periventricular hemorrhagic infarction (8.4% VD vs. 4.5% CS, p <0.01). There was no association between MOD and cPVL. After applying a logistic regression analysis, including known risk factors for IVH and cPVL, VD was independently associated with an increased risk of IVH (odds ratio [OR] 1.600[1.423-1.799], p <0.001) and its complications (OR 1.440[1.195-1.735], p <0.001). MOD was not associated with an increased risk of cPVL. Our study suggests that CS is associated with a reduced risk of IVH and its complications in preterm VLBW infants < 32 weeks of gestational age. A CS should be considered in this group of infants to prevent the development of IVH and its complications. · IVH and cPVL are risk factors for neurological disabilities.. · CS may decrease the risk of IVH in preterms <32 weeks GA.. · There is no association between the MOD and cPVL..

Clinical determinants of cerebrovascular reactivity in very preterm infants during the transitional period

Preterm infants are at enhanced risk of brain injury due to altered cerebral haemodynamics during postnatal transition. This observational study aimed to assess the clinical determinants of transitional cerebrovascular reactivity and its association with intraventricular haemorrhage (IVH). Preterm infants <32 weeks underwent continuous monitoring of cerebral oxygenation and heart rate over the first 72 h after birth. Serial cranial and cardiac ultrasound assessments were performed to evaluate the ductal status and to diagnose IVH onset. The moving correlation coefficient between cerebral oxygenation and heart rate (TOHRx) was calculated. Linear mixed-effect models were used to analyse the impact of relevant clinical variables on TOHRx. The association between TOHRx and IVH development was also assessed. Seventy-seven infants were included. A haemodynamically significant patent ductus arteriosus (hsPDA) (β = 0.044, 95% CI: 0.007-0.081) and ongoing dopamine treatment (β = 0.096, 95% CI: 0.032-0.159) were associated with increasing TOHRx, indicating impaired cerebrovascular reactivity. A significant association between TOHRx, mean arterial blood pressure (β = -0.004, 95% CI: -0.007, -0.001) and CRIB-II score (β = 0.007, 95% CI: 0.001-0.015) was also observed. TOHRx was significantly higher in infants developing high-grade IVH compared to those without IVH. Dopamine treatment, low blood pressure, hsPDA and high CRIB-II are associated with impaired cerebrovascular reactivity during postnatal transition, with potential implications on IVH development. The correlation coefficient between cerebral oxygenation and heart rate (TOHRx) provides a non-invasive estimation of cerebrovascular reactivity, whose failure has a potential pathogenic role in the development of IVH in preterm infants. This study shows that cerebrovascular reactivity during the transitional period improves over time and is affected by specific clinical and therapeutic factors, whose knowledge could support the development of individualized neuroprotective strategies in at-risk preterm infants. The evidence of increased TOHRx in infants developing high-grade compared to low-grade or no IVH during the transitional period further supports the role of impaired cerebrovascular reactivity in IVH pathophysiology.

Does tranexamic acid affect intraventricular hemorrhage growth in acute ICH? An analysis of the STOP-AUST trial.

Trials of tranexamic acid (TXA) in acute intracerebral hemorrhage (ICH) have focused on the imaging outcomes of intraparenchymal hematoma growth. However, intraventricular hemorrhage (IVH) growth is also strongly associated with outcome after ICH. Revised definitions of hematoma expansion incorporating IVH growth have been proposed. We sought to evaluate the effect of TXA on IVH growth. We analyzed data from the STOP-AUST trial, a prospective randomized trial comparing TXA to placebo in ICH patients presenting ≤ 4.5h from symptom onset with a CT-angiography spot sign. New IVH development at follow-up, any interval IVH growth, and IVH growth ≥ 1mL were compared between the treatment groups using logistic regression. The treatment effect of TXA against placebo using conventional (> 6mL or 33%), and revised definitions of hematoma expansion (> 6mL or 33% or IVH expansion ≥ 1mL, > 6mL or 33%, or any IVH expansion, and > 6mL or 33% or new IVH development) were also assessed. Treatment effects were adjusted for baseline ICH volume. The analysis population consisted of 99 patients (50 placebo, 49 TXA). New IVH development at follow-up was observed in 6/49 (12%) who received TXA and 13/50 (26%) who received placebo (aOR: 0.38 [95% CI: 0.13-1.13]). Any interval IVH growth was observed in 12/49 (25%) who received TXA versus 26/50 (32%) receiving placebo (aOR: 0.69 [95% CI: 0.28-1.66]). IVH growth ≥ 1mL did not differ between the two groups. Using revised definitions of hematoma expansion, no significant difference in treatment effect was observed between TXA and placebo. IVH may be attenuated by TXA following ICH; however, studies with larger cohorts are required to investigate this further. http://www.clinicaltrials.gov; Unique identifier: NCT01702636.

Intraventricular hemorrhage clot clearance rate as an outcome predictor in patients with aneurysmal subarachnoid hemorrhage: A retrospective study

BackgroundThe development of intraventricular hemorrhage (IVH) in aneurysmal subarachnoid hemorrhage (aSAH) is linked with higher mortality and poor neurological recovery. Previous studies have investigated the effect of the amount and distribution of the initial IVH on the prognosis of aSAH. However, no studies have assessed the relationship between the changes in IVH over time and the prognosis of aSAH. The aim of this study was to analyze the effect of the clearance rate of IVH, which can be represented by the IVH clot clearance rate (CCR), on the outcomes of aSAH.MethodsThe IVH CCR was calculated based on the difference between the initial and follow-up modified Graeb scores (mGS), which were assessed by initial and 7-day follow-up brain computed tomography, respectively. Poor functional outcome was defined as a modified Rankin Scale score of 3-6. Univariate and multivariable analyses were performed to assess the relationships between IVH CCR and other risk factors and the prognosis of patients. Receiver operating characteristic curve analysis was performed to identify cut-off values of IVH CCR for predicting poor functional outcome.ResultsIn total, 196 consecutive patients were diagnosed with aSAH between January 2014 and March 2018. According to the inclusion and exclusion criteria, 67 patients were finally included in the study. The univariate analysis revealed that a lower IVH CCR (p<0.001), higher initial mGS (p<0.001), older age (p<0.001), higher initial Hunt and Hess grade (p<0.001), presence of delayed infarction (p=0.03), and presence of shunt-dependent hydrocephalus (p=0.004) were significantly related to poor functional outcome. The multivariable analysis revealed that IVH CCR (odds ratio [OR] 0.941; p=0.029), initial mGS (OR 1.632; p=0.043), age (OR 1.561; p=0.007), initial Hunt and Hess grade (OR 227.296; p=0.030), and delayed infarction (OR 5310.632; p=0.023) were independent predictors of poor functional outcome. Optimal cut-off values of IVH CCR and mGS for poor outcome were 36.27%, and 13.5, respectively (all p< 0.001).ConclusionsThe IVH CCR might have an important predictive value on poor functional outcome in patients with aSAH and IVH, along with initial mGS, age, initial Hunt and Hess grade, and delayed infarction.

Placental pathology and intraventricular hemorrhage in preterm and small for gestational age infants.

The aim of this study was to examine the relationship between chorioamnionitis and vascular malperfusion on placental pathology and intraventricular hemorrhage (IVH) in premature and small for gestational age (SGA) infants. A retrospective analysis of 263 infants ≤34 weeks gestation or ≤1800 g and their mothers was conducted by chart review for placental pathology and clinical data from 2014 to 2018. Unadjusted and adjusted odds ratios (OR) for the association of placental pathology with IVH were calculated. Unadjusted OR showed an association between acute chorioamnionitis and IVH, but logistic regression analysis showed a non-significant adjusted OR between acute or chronic chorioamnionitis with IVH. Maternal vascular malperfusion was significantly associated with increased IVH when controlling for confounders. Placental maternal vascular malperfusion is associated with the development of IVH in premature and SGA infants when controlling for other confounders.

Reversal of blood flow in deep cerebral vein in preterm intraventricular hemorrhage: two case reports

BackgroundIntraventricular hemorrhage during the early stage is a major complication in very low birth weight infants. Elevation of venous pressure is one of the contributing factors. The internal cerebral vein receives most of the venous flow from the subependymal germinal matrix, the most common site of origin of intraventricular hemorrhage. Recently, it has been reported that pulsatile or partially interrupted internal cerebral vein waveforms might also be risk factors for intraventricular hemorrhage in extremely low birth weight infants. Here, we report two cases of partially reversed internal cerebral vein flow with intraventricular hemorrhage. There are no published reports documenting this unique flow pattern.Case presentationBetween 2013 and 2020, we had in our neonatal intensive care unit two cases of very low birth weight infants (27 and 25 weeks of gestational age) who showed a partially reversed internal cerebral vein waveform pattern, which was recognized as a new blood flow pattern. Their internal cerebral vein flow patterns were continuously flat early after birth. They showed an intraventricular hemorrhage on the unilateral side with partially interrupted internal cerebral vein flow at 31 and 41 hours after birth (27- and 25-week-old neonates, respectively). Consecutively, their internal cerebral vein flow changed to a partially reversed pattern with intraventricular hemorrhage on the contralateral side at 43 and 87 hours after birth (27- and 25-week-old neonates, respectively). Their flow patterns improved by day 7. These partially reversed patterns were equivalent to triphasic venous flow, and the reverse flow corresponded to A- and V-waves.ConclusionIn the two cases, the internal cerebral vein flow patterns were normal and flat before intraventricular hemorrhage and changed to a severe flow pattern (partially interrupted or reversed flow) at the same time as the detection of intraventricular hemorrhage. After the development of intraventricular hemorrhage, they improved. These cases indicate that a partially reversed or interrupted internal cerebral vein flow pattern may be derived from central venous pressure elevation and related to intraventricular hemorrhage in very low birth weight infants, however, it is difficult to determine when this flow pattern occurs in relation to intraventricular hemorrhage.

Cerebral Oxygenation and Autoregulation in Very Preterm Infants Developing IVH During the Transitional Period: A Pilot Study.

Background: The transitional period, defined as the first 72 h after preterm birth, is often characterized by a significant hemodynamic instability, which represents an important risk factor for such neurological complications of prematurity as intraventricular hemorrhage (IVH). The impairment of cerebral autoregulation plays a key role in the pathogenesis of IVH, whose incidence is highest during the transitional period. This pilot study aimed to evaluate whether patterns of cerebral autoregulation and oxygenation differ in relation to IVH development in very preterm infants during the transitional period.Methods: Infants <32 weeks' gestation were enrolled within 12 h from birth. A simultaneous monitoring of cerebral oxygenation (CrSO2) by near-infrared spectroscopy and of heart rate and peripheral oxygen saturation by pulse oximetry was performed over the first 72 h. Cerebral fractional oxygen extraction (cFTOE) and tissue oxygenation-heart rate reactivity index (TOHRx), which represents a marker of cerebrovascular reactivity, were calculated. Daily cranial and cardiac ultrasound scans were performed, in order to assess the hemodynamic status and to detect a possible IVH onset. CrSO2 and cFTOE, clustered on 6-hour epochs, were compared between infants who developed IVH during the study period and those who did not. A between-group comparison of TOHRx before and after IVH detection was also performed.Results: Twenty preterm infants with a median gestational age of 27 weeks (interquartile range, IQR: 25-30 weeks) and median birth weight of 895 g (IQR: 822-1208 g) were enrolled. Of these, 8 developed IVH. The median age at IVH detection was 40 h (IQR: 30-48 h). Pre-IVH TOHRx was significantly higher compared to matched control periods (p <0.001). CrSO2 was significantly lower from 12 to 30 h and from 42 h onwards in cases compared to controls; however, a temporary CrSO2 rise preceded IVH detection. Similarly, cFTOE was significantly higher in IVH infants from 12 to 30 h and from 48 to 72 h, with a transient decrease between the two periods.Conclusions: In preterm infants during the transitional period, the development of IVH is preceded by transient changes in cerebral oxygenation and oxygen extraction which, in turn, may underlie an early impairment of cerebral autoregulation. Larger studies are needed to confirm these preliminary findings.

FEATURES OF THE NEONATAL PERIOD IN PREMATURE INFANTS WITH THE BIRTH WEIGHT LESS THAN 1500 G, DEPENDING ON THE PLACENTAL CHANGES

Summary. Every year the number of preterm infants in the world and in Ukraine gradually increases - every 10th baby is born prematurely, and premature birth remains the leading cause of 50% neonatal morbidity and mortality. The general condition of this category of infants requires special knowledge and skills, psychological support, patience for both medical staff and parents, and certainly enormous material costs. This is due to the features of the neonatal period of such infants, namely the duration of respiratory support and the need for oxygen therapy, the provision of trophic and complete enteral nutrition, unstable tolerance, and the need for long-term inpatient treatment. However, all these efforts and resources don’t guarantee that the further development of premature babies will be physiological. Placental status provides an important information about explanatory factors that contributed to preterm birth, however, placental features haven’t been properly studied and the correlation between placental changes and neonatal outcomes remains poorly understood. According to the world literature, infection is one of the most important risk factors for premature birth, but the accumulation of evidence based on pathomorphological examination of the placenta and its membranes indicates that the role of specific bacterial and viral infections is not completely convincing and, as a consequence, can be less common cause of premature birth than previously suspected. Different auxiliary activities for preventing premature birth and improving the prognosis for the life and health of premature babies in later childhood’s periods are very important. A better understanding of the underlying mechanisms that regulate uterine-placental blood flow and the impact of other factors on the placenta status can improve diagnostic approaches in early pregnancy and further optimize the principles of preventive activities for both mother and baby.Aim. To establish a connection between pathomorphological changes in the placenta and the effects of premature birth.Materials and methods. A pathomorphological study of the placenta of mothers of 220 premature infants weighing less than 1500 g was performed and based on its results, 5 groups were formed according to the classification of the placental changes. The research was carried out on the basis of the Municipal non-commercial enterprise “Vinnitsa Regional Pathological bureau of Vinnitsa Regional Council” in accordance with the protocol of pathological examination of placenta (form № 013‒1 / o). The investigation was conducted with the support of the director of MNE VRPB Vinnytsia Regional Council Kholod L.P. and the head of the main department of general pathology with histological examinations Hormash P.P. The following research methods were used: macroscopy, slice staining, electronic microscopy and immunohistochemistry, etc. The health of these 220 children in the neonatal period was assessed at the stage of treatment in the Department of Anesthesiology and Neonatal Intensive Care (DANIC), and later - in the Department of Premature Newborns (DPN) of Vinnytsia Regional Children's Clinical Hospital in 2012-2018. Such clinical parameters were analyzed as gestational age, body weight, severity at birth on the Apgar scale for 1 minute, duration of respiratory support and length of hospital stay. Also the frequency of pathological conditions that caused the severity of the neonatal period was taken into account.Results. The study found that pathological changes in the placenta increase the risk of premature birth, the need for respiratory support and oxygen therapy, as well as increase the duration of inpatient treatment. The analysis of clinical indicators of 220 premature infants and pathomorphological studies of the placentas of their mothers showed that the most severe course of the neonatal period was observed in children with inflammatory changes and signs of placental immaturity. Newborns of these groups were diagnosed with a significantly higher frequency of generalized intrauterine infections and neonatal sepsis, severe CNS damage with the development of intraventricular hemorrhage and leukomalacia. The course of the neonatal period in groups of children with signs of premature placental aging and circulatory disorders was characterized by a low incidence of infections, but periventricular leukomalacia, which is an equivalent of adverse effects of preterm birth, was confirmed 5 times more often over the comparison group.Conclusions. All children included in the study had a combination of pathologies that caused the severity of the condition in the neonatal period. The condition of the placenta significantly affected the course of the neonatal period and its inherent pathologies. Thus, newborns with signs of inflammatory changes and immaturity were 10 times more likely to suffer from generalized intrauterine infections and neonatal sepsis. There were more frequent cases of intraventricular hemorrhages, leukomalacia and bronchopulmonary dysplasia in these groups of children.

Cerebral Intraventricular Hemorrhage and Interleukin-6 in Preterm Neonates

Background: Intraventricular hemorrhage (IVH) in preterm neonates is a serious problem in neonatal intensive care units (NICU) worldwide. IVH is reported in approximately 60-70% of very-low-birth-weight (VLBW) neonates. The present study aimed to assess the association of IVH with neonatal characteristics and serum markers, such as serum Interleukin-6 (IL-6) level, in preterm neonates in an academic hospital in the Northeast of Iran.Methods: In this cross-sectional study, a number of 71 VLBW preterm neonates (≤34 weeks of gestational age (GA), birth weight (BW) ≤1500g) were examined regarding the evidence of IVH up to the 40th week of GA in Gorgan, Northeast of Iran. The serum interleukin-6 (IL-6) level was measured within the first 12 hours of lifebirth. The association among the variables was analyzed in SPSS software (version 16) using the chi-square test.Results: Out of 56 preterm neonates who survived until the 40th week, 15 (26.8%) cases demonstrated evidence of IVH at discharge, they had a significantly lower GA (29.04±2 weeks vs. 30.44±1.7 weeks; P=0.003) and BW (1075.43±208 kg vs. 1251.6±199.4 kg; P=0.001), as compared to 41(73.2%) newborns with no IVH. Preterm neonates with IVH had a significantly higher IL-6 serum level, as compared to those without IVH (224±210 pg/ml vs. 91.93±138 pg/ml; P=0.035).Conclusion: As evidenced by the obtained result, low birth weight and premature birth could be serious risk factors for the development of IVH. Furthermore, IL-6 concentration may play a pivotal role in the occurrence of IVH.

Redefining Hematoma Expansion With the Inclusion of Intraventricular Hemorrhage Growth.

Background and Purpose- Definitions of significant hematoma expansion traditionally focus on changes in intraparenchymal volume. The presence of intraventricular hemorrhage (IVH) is a predictor of poor outcome, but current definitions of hematoma expansion do not include IVH expansion. We evaluated whether including IVH expansion to current definitions of hematoma expansion improves the ability to predict 90-day outcome. Methods- Using data from the PREDICT-ICH study (Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT), we compared a standard definition of hematoma expansion (≥6 mL or ≥33%) to revised definitions that includes new IVH development or expansion (≥6 mL or ≥33% or any IVH; ≥6 mL or ≥33% or IVH expansion ≥1 mL). The primary outcome was poor clinical outcome (modified Rankin Scale score, 4-6) at 90 days. Diagnostic accuracy measures were calculated for each definition, and C statistics for each definition were compared using nonparametric methods. Results- Of the 256 patients eligible for primary analysis, 127 (49.6%) had a modified Rankin Scale score of 4 to 6. Sensitivity and specificity for the standard definition (n=80) were 45.7% (95% CI, 36.8-54.7) and 82.9% (95% CI, 75.3-88.9), respectively. The revised definition, ≥6 mL or ≥33% or any IVH (n=113), possessed a sensitivity of 63.8% (95% CI, 54.8-72.1) and specificity of 75.2% (95% CI, 66.8-82.4). Overall accuracy was significantly improved with the revised definition (P=0.013) and after adjusting for relevant covariates, was associated with a 2.55-fold increased odds (95% CI, 1.31-4.94) of poor outcome at 90 days. A second revised definition, ≥6 mL or ≥33% or IVH expansion ≥1 mL, performed similarly (sensitivity, 56.7% [95% CI, 47.6-65.5]; specificity, 78.3% [95% CI, 40.2-85.1]; aOR, 2.40 [95% CI, 1.23-4.69]). Conclusions- In patients with mild-to-moderate ICH, including IVH expansion to the definition of hematoma expansion improves sensitivity with only minimal decreases to specificity and improves overall prediction of 90-day outcome.

Hemostatic profile of infants with spontaneous prematurity: can we predict intraventricular hemorrhage development?

BackgroundDefining hemostatic profile for preterm infants is a challenge when severe bleedings are frequent.MethodsThe aim was to define the hemostatic profile at birth of infants with spontaneous prematurity and to evaluate whether characteristic profiles can predict the development of intraventricular hemorrhage (IVH) in prematures.ResultsWe included 122 newborns with a median age of 315/7 gestational age (GA) [292/7;340/7] and median weight of 1145 g [785;1490]. Levels of fibrinogen, factor II (FII) and factor V (FV) rose with GA (p = 0.017,p = 0.009, p = 0.001). In the group of 230/7 – 286/7 GA, the 5th percentile was defined as 0.6 g/L for fibrinogen, 15 IU/dL for FII and 16 IU/dL for factor V (n = 30). In the group of 290/7–326/7 GA, the 5th percentile was defined as 1.0 g/L for fibrinogen, 24 IU/dL for FII and 41 IU/dL for factor V (n = 46). In the group of 330/7–366/7 GA, the 5th percentile was defined as 1.0 g/L for fibrinogen, 24 IU/dL for FII and 30 IU/dL for factor V (n = 46). Level of fibrinogen was higher in case of vaginal delivery and lower in case of IUGR. Only lower level of FV at birth was significantly associated with IVH (63.5 [46.0; 76.5] vs 74.0 [58.0; 89.0], p = 0.026) with an unadjusted OR per SD increase in FV of 0.57 (95%CI, 0.34 to 0.96). After adjustment for age, the association between FV level and IVH was slightly attenuated (adjusted OR, 0.70; 95%CI, 0.40 to 1.23) but remained not significant (p = 0.22).There was no correlation with FII and fibrinogen.ConclusionsWe can define hemostastic profile of prematures and corroborate references ranges for studied parameters. Further large studies are still called for, to correlate the grade of hemorrhage and the factor V level at birth.

Abstract WP462: New or Expanding Ventricular Hemorrhage Predicts Poor Outcome After Intracerebral Hemorrhage

Introduction: Baseline intraventricular hemorrhage (IVH) is a predictor of poor outcome in acute intracerebral hemorrhage (ICH) patients. However, questions remain as to the exact burden that new IVH development, seen on follow-up imaging, or what degree of interval IVH expansion, impacts long term functioning. Objective: To derive and validate a relationship between IVH change and long term outcome. Methods: Fractional polynomial analysis was used to test linear and non-linear models of 24-hour IVH change and clinical outcome using data from the multicenter PREDICT study. The primary outcome was mRS 4-6 at 90 days. Dichotomous thresholds were derived via assessment of the selected model and diagnostic accuracy measures were calculated. Independent predictors of poor outcome were determined via multivariable logistic regression. The developed model and all derived thresholds were validated in an independent single center cohort. Results: Of the 256 patients from PREDICT, 127 (49.6%) had mRS scores of 4-6 at 90 days. 24-hour IVH change and the primary outcome fit a non-linear relationship, where minimal increases in IVH were associated with a high probability of poor outcome (Figure 1). Mean IVH expansion was 8.6 mL. IVH expansion greater than 1 mL (n=53, Sens 33%, Spec 92%, PPV 79%, NPV 58%, aOR 2.77 [95% CI: 1.12-6.89]) and development of any new IVH (n= 74, Sens 43%, Spec 85%, PPV 74%, NPV 60%, aOR 2.17 [95% CI: 1.02-4.63]) strongly predicted mRS 4-6 at 90 days. The model and developed thresholds reproduced well in a validation cohort of 170 patients. Conclusion: IVH expansion as minimal as 1 mL, or any new IVH is strongly predictive of poor outcome. This can aid in prognostication, be incorporated into definitions of hematoma expansion for future ICH treatment trials, or even imply that IVH treatment is a therapeutic target that may lead to improved outcomes.

Targeted urine metabolomics in preterm neonates with intraventricular hemorrhage

Intraventricular hemorrhage (IVH) is a major cause of morbidity and mortality in preterm neonates. Elucidation of the mechanisms underlying IVH and/or development of disease biomarkers is essential. The aim of the study was to investigate the urine metabolic profile of preterm neonates (gestational age < 32 weeks) IVH and explore the role of metabolomics in understanding pathophysiological mechanisms of the disease from which novel biomarkers could be derived. In this single-center, prospective, case-control study, urine samples were collected from seven preterm infants with early IVH (IVH group) and from 11 preterm ones without IVH (control group) on days 1, 3 and 9 of life. Urine metabolites were evaluated using targeted liquid chromatography-tandem mass spectrometry. Demographic and perinatal-clinical characteristics were recorded. Univariate and multivariate statistical analyses were performed. Orthogonal Partial Least Squares-Discriminant Analysis showed that the study groups differed significantly due to alternation in 20 out of the 40 metabolites detected in the urine. Elevated differentiated metabolites included energy intermediates and other important compounds, whereas reduced ones various amino acids, hypoxanthine and nicotinamide. A set of metabolites showed high performance as indicators of IVH, especially during day 1. As evidenced by metabolomics, preterm neonates with IVH demonstrate significant metabolism perturbations. Potentially, a selected panel of metabolites could be used as urine biomarkers of IVH development and/or progression in high-risk preterm infants.