Severe Peri-intraventricular Haemorrhage Research Articles

Seis meses de aleitamento materno exclusivo no pré-termo de muito baixo peso submetido ao método canguru

OBJECTIVE: To know the rate and factors associated with exclusive breastfeeding in the follow-up of the preterm submitted to the kangaroo method. METHODS: Cross-sectional study performed with pre-terms smaller than 33 weeks and/or birth weight <1,500 grams, born in 2019, submitted to the kangaroo method and followed up to six months. Descriptive analysis and association and comparison tests were carried out for the maternal and neonatal factors for the outcome of exclusive breastfeeding yes (G1) and not (G2) by the IBM-SPSS/Statistics program 22. RESULTS: Of the 111 patients who were discharged, 82 (100%) were followed up to the corrected ages 3.8/4.2 and chronological 5.9/6.3 months, respectively, in the G1/G2. Exclusive breastfeeding was present in G1 at 22 (26.8%) patients and 60 (73.2%) in the G2 had already introduced formula. Maternal age averages 28/29 years, gestational age 30.3/30.4 weeks, birth weight 1295/1434g, mechanical ventilation time 5.0/5.8 and total hospitalization 56/49 days in groups G1 and G2, respectively. Cesarian section frequencies 68/61%, necrotizing enterocolitis 4.5/8.3%, severe peri-intraventricular hemorrhage 4,5/8.3%, late sepsis 19/16.9%, and rehospitalization after discharge 4.5/6,8% in G1 and G2 patients. There was no statistical significance of the variables analyzed for the outcome of exclusive breastfeeding. CONCLUSION: Compared to other cohorts and at the service itself in 2010 analysis, the breastfeeding rate was high and, especially the exclusive breastfeeding, condition associated with the best development of the preterm. The perinatal variables were not determinants of the success of exclusive breastfeeding in these patients treated by the kangaroo method.

Survival and Neurodevelopmental Outcomes of Premature Infants with Severe Peri-Intraventricular Hemorrhage at 24 Months of Age

Severe peri-intraventricular haemorrhage has been associated with higher mortality and neurodevelopmental impairment. The impact of peri-intraventricular haemorrhage alone (without white matter injury) remains controversial. The aim of this study was to evaluate the influence of severe peri-intraventricular haemorrhage, associated or not with cystic peri-ventricular leukomalacia, on mortality and neurodevelopment at 24 months. Retrospective cohort study, that included newborns with severe peri-intraventricular haemorrhage admitted to a maternity hospital with differentiated perinatal support between 2006 and 2015, and two controls with the same gestational age, without peri-intraventricular haemorrhage, who were admitted immediately after the case. Neurodevelopmental assessment, at 24 months, was performed in 99 children, using the Schedule of Growing Skills II scale in 52 and the Ruth Griffiths mental development scale in 47 children. Severe neurodevelopmental deficit was diagnosed in the following conditions: cerebral palsy, delayed psychomotor development, deafness requiring hearing aids and blindness. The study included 41 cases and 82 controls. Out of these, 23 died, 16 (39.0%) in the group of severe peri-intraventricular haemorrhage and seven (8.5%) in the control group (OR 7.6, 95% CI 2.6 - 20.4, p < 0.001). Severe neurodevelopmental deficit was diagnosed in seven (30.4%) in the severe peri-intraventricular haemorrhage group and one (1.3%) in the control group (OR 32; 95% CI 3.7 - 281, p < 0.001). Individualized analysis showed that mortality was higher in peri-intraventricular haemorrhage grade III with associated cystic peri-ventricular leukomalacia (OR 4.4 95% CI 1.3 - 14.2, p = 0.015) and in peri-intraventricular haemorrhage IV (OR 12; 95% CI 3.5 - 41.2, p < 0.001), when compared to controls. Differences were also noticed regarding severe neurodevelopmental deficit when compared with controls (1.3%) in grade III peri-intraventricular haemorrhage with associated cystic peri-ventricular leukomalacia, (75.0%, p < 0.001) and grade IV peri-intraventricular haemorrhage (50.0%, p < 0.001 ). This work showed a higher mortality rate and neurodevelopment impairment in preterm newborns with severe peri-ventricular haemorrhage. Analysis by groups stratified according to gestational age and different grades of peri-ventricular haemorrhage displayed the complications associated with peri-ventricular haemorrhage grade IV or grade III, with or without cystic peri-ventricular leukomalacia. Preterm newborns with peri-intraventricular haemorrhage grade IV or grade III with cystic peri-ventricular leukomalacia, had a higher risk of mortality and severe neurodevelopmental impairment.

Survival Without Major Morbidity Among Very Low Birth Weight Infants in California.

To examine trends in survival without major morbidity and its individual components among very low birth weight infants across California and assess remaining gaps that may be opportune targets for improvement efforts. The study population included infants born between 2008 and 2017 with birth weights of 401 to 1500 g or a gestational age of 22 to 29 weeks. Risk-adjusted trends of survival without major morbidity and its individual components were analyzed. Survival without major morbidity was defined as the absence of death during birth hospitalization, chronic lung disease, severe peri-intraventricular hemorrhage, nosocomial infection, necrotizing enterocolitis, severe retinopathy of prematurity or related surgery, and cystic periventricular leukomalacia. Variations in adjusted rates and/or interquartile ranges were examined. To assess opportunities for additional improvement, all hospitals were reassigned to perform as if in the top quartile, and recalculation of predicted numbers were used to estimate potential benefit. In this cohort of 49 333 infants across 142 hospitals, survival without major morbidity consistently increased from 62.2% to 66.9% from 2008 to 2017. Network variation decreased, with interquartile ranges decreasing from 21.1% to 19.2%. The largest improvements were seen for necrotizing enterocolitis and nosocomial infection. Bronchopulmonary dysplasia rates did not change significantly. Over the final 3 years, if all hospitals performed as well as the top quartile, an additional 621 infants per year would have survived without major morbidity, accounting for an additional 6.6% annual improvement. Although trends are promising, bronchopulmonary dysplasia remains a common and persistent major morbidity, remaining a target for continued quality-improvement efforts.

Impact of peri-intraventricular haemorrhage and periventricular leukomalacia in the neurodevelopment of preterms: Asystematic review and meta-analysis.

ContextWhether all degrees of periventricular leukomalacia (PVL) and peri-intraventricular haemorrhage (PIVH) have a negative impact on neurodevelopment.ObjectiveTo determine the impact of PVL and PIVH in the incidence of cerebral palsy, sensorineural impairment and development scores in preterm neonates. Registered in PROSPERO (CRD42017073113).Data sourcesPubMed, Embase, SciELO, LILACS, and Cochrane databases.Study selectionProspective cohort studies evaluating neurodevelopment in children born preterm which performed brain imaging in the neonatal period.Data extractionTwo independent researchers extracted data using a predesigned data extraction sheet.Statistical methodsA random-effects model was used, with Mantel-Haenszel approach and a Sidik-Jonkman method for the estimation of variances, combined with Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed through the I2 statistic and sensitivity analysis were performed when possible. No funnel plots were generated but publication bias was discussed as a possible limitation.ResultsOur analysis concluded premature children with any degree of PIVH are at increased risk for cerebral palsy (CP) when compared to children with no PIVH (3.4, 95% CI 1.60–7.22; 9 studies), a finding that persisted on subgroup analysis for studies with mean birth weight of less than 1000 grams. Similarly, PVL was associated with CP, both in its cystic (19.12, 95% CI 4.57–79.90; 2 studies) and non-cystic form (9.27, 95% CI 5.93–14.50; 2 studies). We also found children with cystic PVL may be at risk for visual and hearing impairment compared to normal children, but evidence is weak.LimitationsMajor limitations were the lack of data for PVL in general, especially for the outcome of neurodevelopment, the high heterogeneity among methods used to assess neurodevelopment and the small number of studies, which led to meta-analysis with high heterogeneity and wide confidence intervals.ConclusionsThere was no evidence supporting the hypothesis that PIVH causes impairment in neuropsychomotor development in our meta-analysis, but review of newer studies show an increased risk for lower intelligence scores in children with severe lesions, both PIVH and PVL. There is evidence to support the hypothesis that children with any degree of PIVH, especially those born below 1000 grams and those with severe haemorrhage, are at increased risk of developing CP, as well as children with PVL, both cystic and non-cystic.

T-piece versus self-inflating bag ventilation in preterm neonates at birth

ObjectiveTo verify whether the use of the T-piece resuscitator compared with the self-inflating bag in preterm infants ventilated at birth modifies survival to hospital discharge without major morbidities.DesignPragmatic prospective cohort...

Cerebral Oxygenation, Extraction, and Autoregulation in Very Preterm Infants Who Develop Peri-Intraventricular Hemorrhage

To test the hypothesis that near-infrared spectroscopy (NIRS)-determined patterns of regional cerebral oxygen saturation (rScO2), cerebral fractional tissue oxygen extraction (cFTOE), and autoregulatory ability can identify neonates at risk for developing peri-intraventricular hemorrhage (PIVH). This case-control study is a subanalysis of 30 neonates who developed PIVH >12 hours after admission as part of a lager prospective observational cohort study comprising 650 preterm neonates born at ≤32 weeks' gestational age. PIVH was diagnosed by cranial ultrasound, performed at least once daily. Mean arterial blood pressure (MABP), NIRS-determined rScO2, cFTOE, and MABP-rScO2 correlation were monitored from birth to 72 hours of age. Infants with PIVH received more inotropic drugs before being diagnosed with PIVH. Significantly more infants with severe PIVH needed treatment for patent ductus arteriosus. The MABP-rScO2 correlation was >0.5 significantly more often before mild/moderate PIVH and after severe PIVH compared with controls. rScO2 was higher and cFTOE lower in infants before severe PIVH. NIRS-monitored rScO2 and cFTOE suggest cerebral hyperperfusion in infants with severe PIVH. Moreover, MABP-rScO2 correlation indicates more blood pressure-passive brain perfusion in infants with PIVH. Continuous assessment of patterns of cerebral oxygenation and arterial blood pressure may identify those preterm infants at risk for severe PIVH and prompt consideration of preventive measures.

Níveis plasmáticos de cafeína no cordão umbilical e apneia da prematuridade

OBJETIVO: Determinar a influencia da presenca de cafeina no sangue de cordao umbilical na ocorrencia de apneia. METODOS: Estudo de coorte prospectivo de recem-nascidos pre-termo com peso de nascimento menor que 2.000 g. Os criterios de exclusao foram: maes que receberam opioides; ventilacao mecânica durante os primeiros 4 dias de vida; malformacoes cerebrais e cardiacas maiores; asfixia perinatal; hemorragia peri-intraventricular grave; exsanguineotransfusao antes do quarto dia de vida; e uso de metilxantina antes da extubacao. Os recem-nascidos foram divididos em com e sem cafeina detectavel no sangue de cordao umbilical, sendo acompanhados nos primeiros 4 dias para verificar ocorrencia de apneia. RESULTADOS: Oitenta e sete recem-nascidos com e 40 sem cafeina detectavel no sangue de cordao umbilical foram estudados. A mediana da concentracao de cafeina dos 87 pacientes com cafeina detectavel no sangue de cordao umbilical foi 2,3 µg/mL (0,2-9,4 µg/mL). Nao houve associacao entre ocorrencia de apneia e presenca de cafeina no sangue de cordao umbilical. Recem-nascidos com cafeina detectavel no cordao umbilical tiveram tendencia a apresentar apneia mais tardiamente (66,3±4,14 horas) do que aqueles com niveis indetectaveis (54,2±6,26 horas). CONCLUSAO: A deteccao de niveis de cafeina no sangue de cordao umbilical nao diminuiu a ocorrencia de apneia da prematuridade, mas teve um efeito limitrofe atrasando sua ocorrencia, o que sugere que mesmo um nivel baixo de cafeina no sangue de cordao umbilical pode retardar a ocorrencia de apneia.

Serum levels of caffeine in umbilical cord and apnea of prematurity

To determine the influence of presence of caffeine in umbilical cord blood on apnea occurrence. A prospective cohort study with preterm newborns with birth weight lower than 2,000 g was undertaken. Exclusion criteria were: mothers who received opioids; mechanical ventilation during the first 4 days of life; cerebral and major cardiac malformations; perinatal asphyxia; severe periintraventricular hemorrhage; exchange transfusion before the fourth day of life; and those who received methylxanthine prior to extubation. Neonates were divided into detectable and undetectable caffeine in umbilical cord blood. Newborns were followed for the first 4 days for occurrence of apnea spells. Eighty-seven newborns with and 40 without detectable caffeine in umbilical cord blood were studied. Median caffeine concentration of the 87 patients with detectable caffeine in umbilical blood was 2.3 microg/mL (0.2-9.4 microg/mL). There was no association between occurrence of apnea spells and presence of caffeine in umbilical cord blood. Neonates with detectable caffeine in umbilical blood had borderline later apnea (66.3+/-4.14 hours) than those with undetectable levels (54.2+/-6.26 hours). Detected levels of caffeine in umbilical cord blood did not decrease occurrence of apnea of prematurity, but it had a borderline effect delaying its occurrence, suggesting that even a low level of caffeine in umbilical cord blood might delay occurrence of apnea spells.

Background patterns and sleep‐wake cycles on amplitude‐integrated electroencephalography in preterms younger than 30 weeks gestational age with peri‐/intraventricular haemorrhage

The objective of this prospective study was to evaluate the influence of peri-/intraventricular haemorrhage (PIVH) grades I-IV on amplitude-integrated electroencephalographic (aEEG) activity in preterm infants<30 weeks gestational age (GA). The aEEG tracings of the first 2 weeks of life of 56 preterm infants younger than 30 weeks GA (2 groups: group A=23-26 weeks GA, group B=27-29 weeks GA) born during a 4-year period with PIVH grades I-IV were assessed for the relative duration of four background aEEG activity patterns (continuous pattern, discontinuous high-voltage pattern, discontinuous low-voltage pattern and nearly isoelectric pattern), the presence of seizure activity and the appearance of sleep-wake cycles and compared to the tracings of 75 neurologically healthy preterms without PIVH. Analysis of aEEG background activity showed a decrease of continuous activity whereas discontinuous activity increased in both groups with larger haemorrhages (grades III and IV) and when compared to controls. Suspected seizure activity was more common with increasing degree of bleeding in group A (50% with PIVH I or II, 75% with PIVH III or IV) and when compared to controls and was the same with increasing degree of bleeding in group B (47% with PIVH I or II, 45% with PIVH III or IV). Sleep-wake cycles were less common with larger haemorrhages in both groups (group A: 41% with PIVH I or II, 25% with PIVH III or IV; group B: 52% with PIVH I or II, 9% with PIVH III or IV) and when compared to controls. The aEEG characteristics of severe PIVH consist in a combination of a more discontinuous background pattern, a lack of sleep-wake cycles and a higher likelihood of seizure activity when compared to age-matched controls.

Prevent for peri-intraventricular hemorrhage in preterm infant by maternal prenatal administration of vitamin K1

目的 了解早产儿是否存在维生素K(VitK)依赖因子水平低下及其与早产儿脑室周围-脑室内出血的关系,探讨产前应用VitK1对早产儿脑室周围-脑室内出血的预防效果.方法 将有可能早产且至分娩时孕周不足34周的孕妇分为两组:地塞米松(Dex)组118例,在产前给予Dex注射;Dex+VitK1组80例,产前给予Dex及VitK1.两组早产儿各40例留取脐动脉血离心取血清-20 ℃保存,用凝固法检测凝血因子Ⅱ、Ⅶ、Ⅸ、Ⅹ的活性,同时留取同期出生的健康足月新生儿40例脐血标本作对照.早产儿生后1周内常规做头颅超声检查明确有无脑室周围-脑室内出血及其程度.结果 Dex组脐血VitK依赖因子Ⅱ、Ⅶ、Ⅸ、Ⅹ的活性水平分别为(25.1±10.4)%、(58.1±16.9)%、(23.8±9.8)%、(29.6±8.7)%,Dex+VitK1组分别为(36.2±9.4)%、(69.3±17.1)%、(25.4±10.1)%、(39.8±9.1)%,足月儿分别为(37.1±5.9)%、(65.8±13.5)%、(29.7±7.3)%、(37.6±11.3)%.Dex组与足月儿组比较,VitK依赖因子活性水平有显著性差异(P＜0.05).Dex组与Dex+VitK1组比较,Ⅱ、Ⅶ、Ⅹ因子活性水平有显著性差异(P＜0.05).脑室周围-脑室内出血发生率Dex组为52.5%,Dex+VitK1组为32.5%(χ2=7.76,P＜0.05);重度出血发生率Dex组为12.7%,Dex+VitK1组为2.5%(χ2=6.33,P＜0.05).结论 早产儿存在VitK依赖因子水平低下,可能是其易于发生脑室周围-脑室内出血的原因之一.分娩前母亲补充VitK1可显著提高其血浆Ⅱ、Ⅶ和X因子水平,并对脑室周围-脑室内出血有一定预防作用。

Plasma guanosine 3',5'-cyclic monophosphate and severity of peri/intraventricular haemorrhage in the preterm newborn.

A poorly controlled cerebral circulation, caused by excessive production of nitric oxide, has been suggested as predisposing to peri/intraventricular haemorrhage (PIVH) in the immature neonate. It is hypothesized that a relation exists between plasma cyclic GMP (cGMP) as an effector of endogenous vasodilatory nitric oxide production and severity of PIVH. In 83 consecutively admitted preterm neonates, nitric oxide production was assessed by measuring plasma cGMP at 0, 24, 48, 72 and 168 h of age. Simultaneously, cranial ultrasound investigations were performed and haemodynamic parameters registered. The investigations showed that 60 neonates (72%) had no PIVH; 18 neonates (22%) had mild to moderate PIVH; and 5 neonates (6%) had severe PIVH. At 48 and 72 h of age, cGMP levels of infants with severe PIVH were significantly higher than those of infants with no or only mild PIVH, whereas at 72 and at 168 h, infants with moderate PIVHs had significantly higher cyclic cGMP levels than infants without PIVH. Finally, at 168 h of age infants with mild PIVH also had higher cyclic cGMP values than those of infants without PIVH. Maximal cGMP values preceded the final extension of PIVH in moderate and severe PIVHs. Blood pressure support was necessary significantly more often in infants with moderate and severe PIVH. A logistic regression model revealed that cGMP was significantly associated with PIVH, irrespective of gestational age, mean arterial pressure or severity of infant respiratory distress syndrome. Increased cGMP levels are associated with the development of PIVH. It is suggested that vasodilatory nitric oxide-induced impairment of cerebral autoregulation plays a role here.

Plasma guanosine3′,5′‐cyclic monophosphate and severity of peri/intraventricular haemorrhage in the preterm newborn

A poorly controlled cerebral circulation, caused by excessive production of nitric oxide, has been suggested as predisposing to peri/intraventricular haemorrhage (PIVH) in the immature neonate. It is hypothesized that a relation exists between plasma cyclic GMP (cGMP) as an effector of endogenous vasodilatory nitric oxide production and severity of PIVH. In 83 consecutively admitted preterm neonates, nitric oxide production was assessed by measuring plasma cGMP at 0, 24, 48, 72 and 168 h of age. Simultaneously, cranial ultrasound investigations were performed and haemodynamic parameters registered. The investigations showed that 60 neonates (72%) had no PIVH; 18 neonates (22%) had mild to moderate PIVH; and 5 neonates (6%) had severe PIVH. At 48 and 72 h of age, cGMP levels of infants with severe PIVH were significantly higher than those of infants with no or only mild PIVH, whereas at 72 and at 168 h, infants with moderate PIVHs had significantly higher cyclic cGMP levels than infants without PIVH. Finally, at 168 h of age infants with mild PIVH also had higher cyclic cGMP values than those of infants without PIVH. Maximal cGMP values preceded the final extension of PIVH in moderate and severe PIVHs. Blood pressure support was necessary significantly more often in infants with moderate and severe PIVH. A logistic regression model revealed that cGMP was significantly associated with PIVH, irrespective of gestational age, mean arterial pressure or severity of infant respiratory distress syndrome. Conclusion: Increased cGMP levels are associated with the development of PIVH. It is suggested that vasodilatory nitric oxide‐induced impairment of cerebral autoregulation plays a role here.

Prophylactic Administration of Porcine-Derived Lung Surfactant Is a Significant Factor in Reducing the Odds for Peri-Intraventricular Haemorrhage in Premature Infants

We hypothesized that prophylactic treatment with a porcine-modified lung surfactant (PLS) reduces the rate of peri-intraventricular haemorrhage (PIVH) more than rescue treatment. We performed a meta-analysis of three prophylactic versus rescue trials conducted with PLS in four countries using individual data. Overall (grades 1–4) or severe (grades 3 and 4) PIVH of 671 newborns was the outcome. A logistic regression analysis was performed. Prophylactic exposure to PLS was a significant independent factor in reducing the incidence of overall (OR 0.65; 95% CI 0.47–0.90) and severe (OR 0.56; 95% CI 0.35–0.89) PIVH. Moreover, for severe PIVH, the adjusted OR for outborn babies exposed to prophylactic treatment with PLS was highly significant (OR 0.11; 95% CI 0.02–to 0.49). The results we obtained show that prophylactic treatment with PLS reduces the rate of PIVH more than rescue treatment.

Multivariate autoregressive modelling combined with transcephalic electrical impedance: method to relate neonatal systemic circulation and respiration to cerebral circulation.

We studied the pulsatile component of cerebral circulation with transcephalic electrical impedance (delta Z) in six preterm newborns, three of whom had severe cerebral bleeding, peri-intraventricular haemorrhage (PIVH). The transcephalic electrical impedance delta Z signal, ECG, arterial blood pressure, (aBP) and respirogram were recorded on analogue magnetic tape for 30 min. Artefact-free stationary segments (lasting for 2 min) of the four signals were digitised. A digital multivariate autoregressive (MAR) model was used to study frequency-specific variability in the signals and to quantify interrelations between the variabilities of delta Z, HR, aBP and respiratory signals. MAR modelling describes a system where all the signals simultaneously explain each other. The inherent variability of delta Z was lower and the influences of respiration and aBP on delta Z significantly greater in infants with severe PIVH than in controls. These changes were observed at high frequencies corresponding to respiration and heart rate. This may be interpreted as a marker of pressure passivism in the cerebral circulation following PIVH. We conclude that in preterm babies the application of MAR modelling, together with transcephalic impedance, may be a new, helpful and quantitative method for the study of simultaneous interrelations between variables of cerebral and systemic circulations and respiration.

Cerebral circulation assessed by transcephalic electrical impedance during the first day of life--a potential predictor of outcome?

Pulsatile changes in intracranial blood volume (transcephalic electrical impedance, delta Z), arterial blood pressure (aBP) and respiration were studied during the first day after birth in 42 neonates with a birth weight of 1040-3850 g and gestational age of 26-36 weeks. The neurological outcome was assessed at 1 year of age to study the predictive ability of delta Z. delta Z, ECG, respirogram and direct aBP were recorded at 8-h intervals. Outcome was adverse in seven infants of whom two died from severe peri-intraventricular haemorrhage. PCO2 was higher (6.2 kPa) in the infants with adverse outcome than in those infants with favourable outcome (5.0 kPa) (P = 0.004). Blood glucose (4.5 vs. 3.3 mmol/l, P = 0.030) and first day administration of fluid (80 vs. 63 ml/kg/day, P = 0.003) behaved, respectively. Of the infants receiving dopamine therapy, 60% had adverse outcome while only 11% of those not receiving dopamine had adverse outcome (P = 0.016). Of the infants with high diastolic blood pressure levels, 32% had adverse outcome, while none with low diastolic blood pressure levels had adverse outcome (P = 0.031). Spectral analysis was used to examine signal variabilities in the frequency domain. During the first 24 h of life, the variabilities of aBP and respiration were equal in all the infants. The high-frequency delta Z signal variability (1.50-4.00 Hz, heart rate level) was found to be lower in the infants with adverse outcome (330 units) than in the infants with favourable outcome (1280 units, P = 0.017). The low delta Z variability allowed us to assume that there is a decrease of pulsatile cerebral blood flow (CBF) in the infants with adverse outcome. We speculate that this may result from the 'no reflow phenomenon', increased tissue pressure due to ischaemia and/or PIVH, the 'brain sparing effect' or constriction of main cerebral arteries due to increased pressure support or metabolic factors (PCO2, glucose). We believe that transcephalic impedance provides a potential cot-side method for monitoring cerebral circulation in the neonatal period with an ability to predict outcome.