Low prevalence of large intraventricular haemorrhage in very low birthweight infants carrying the factor V Leiden or prothrombin G20210A mutation

The influence of genetic factors that increase coagulation on the extension of intraventricular haemorrhage (IVH) in very low birthweight infants has not been studied previously. This study investigated the frequency and effect of the factor V Leiden and prothrombin G20210A mutations in a population-based cohort of 305 preterm infants with a birthweight below 1500 g. The overall prevalence of IVH was similar in infants with ( n = 43) and without ( n = 262) prothrombotic mutations (18.6% vs 16.4%, respectively). However, infants with prothrombotic mutations had a significantly reduced risk of developing extension to IVH grade II or more [ p = 0.023, odds ratio (OR) 0.11, 95% confidence interval (CI) 0.02-0.5]. The carrier state of a factor V Leiden or prothrombin G20210A mutation was still predictive for a low rate of IVH grade II-IV if possible confounding variables were included in a multivariate regression model (OR 0.12; 95%CI: 0.017- 0.86).     

Risk factors for intraventricular hemorrhage in very low birth weight infants in Tehran, Iran

Intraventricular hemorrhage (IVH) is an important cause of morbidity and mortality in very low birth weight (VLBW) infants; 80-90% of cases occur between birth and the third day of life. In a retrospective case control clinical study, files of all premature infants with birth weights <1500 grams admitted between April 2004 and October 2005 to the Neonatal Intensive Care Unit (NICU) of Akbar Abadi Hospital were reviewed. We determined risk factors that predispose to the development of high-grade IVH (grades 3 and 4) in VLBW infants. Thirty-nine infants with IVH grade 3 and 4 were identified. A control group of 82 VLBW infants were also selected. Prenatal data, delivery characteristics, neonatal course data and reports of cranial ultrasonography were carefully collected for both groups. Those variables that achieved significance (p<0.05) in univariate analysis were entered into multivariate logistic regression analysis. A total of 325 VLBW infants were evaluated. Mortality rate was 21.5%. Multivariate logistic analysis showed that the following factors are associated with greater risk of high-grade IVH occurrence: lower gestational age (OR: 3.72; 95% CI: 1.65-8.38), birth weight (OR: 3.42; 95% CI: 1.65-8.38), mechanical ventilation (OR: 4.14; 95% CI: 1.35-12.2), tocolytic therapy with magnesium sulfate (OR: 4.40; 95% CI: 1.10-24.5), hyaline membrane disease (HMD, OR: 3.16; 95% CI: 1.42-7.45), symptomatic hypotension (OR: 2.32; 95% CI: 1.06-5.42), hypercapnia (OR: 1.9; 95% CI: 1.1-3.4) and Apgar score at 5 minutes (OR: 1.58; 95% CI: 1.59-6.32).     

Grades I-II intraventricular hemorrhage in extremely low birth weight infants: effects on neurodevelopment

OBJECTIVE: To quantify the effect of grades I-II intraventricular hemorrhage (IVH) on the neurosensory and cognitive outcomes of extremely low birth weight infants. STUDY DESIGN: Of 706 extremely low birth weight infants without major malformations admitted to our center from 1992 to 2000, 537 survived to 20 months' corrected age (CA) and had cranial ultrasound studies performed, of whom 490 (91%) had complete neurodevelopmental assessments. Infants with severe cranial ultrasound abnormalities or meningitis were excluded, leaving a population of 362 infants, 258 of whom had a normal cranial ultrasound and 104 had an isolated grade I-II IVH. The groups had similar birth weight (808 vs 801 grams) and gestational age (26.5 vs 26.3 weeks). Outcomes of infants with normal cranial ultrasound were compared with those with grades I-II IVH at 20 months' CA. Outcomes included the Bayley Scales of Infant Development Mental Developmental Index (MDI) and major neurosensory abnormality. Logistic regression was used to assess the effect of grades I-II IVH on outcomes while adjusting for other risk factors. RESULTS: Extremely low birth weight infants with grades I-II IVH had a significantly lower mean MDI score than infants with normal cranial ultrasound (74 +/- 16 vs 79 +/- 14, P = .006). They had higher rates of MDI <70 (45% vs 25%; OR, 2.00; 95% CI, 1.20 to 3.30; P = .008), major neurologic abnormality (13% vs 5%; OR, 2.60; 95% CI, 1.06 to 6.36; P = .036), and neurodevelopmental impairment (47% vs 28%; OR, 1.83; 95% CI, 1.11 to 3.03; P = .018) at 20 months' CA, even when adjusting for confounding factors. CONCLUSIONS: Extremely low birth weight infants with grades I-II IVH have poorer neurodevelopmental outcomes at 20 months' CA than infants with normal cranial ultrasound. Advanced radiologic imaging may indicate additional brain injury associated with grade I-II IVH, which could explain these outcomes.     

Increased risk of intraventricular hemorrhage in preterm infants with thrombophilia

The multifactorial etiology of cerebral intraventricular hemorrhage (IVH) may involve coagulation disturbances and venous infarction. We tested whether coagulation abnormalities associated with adult venous thrombosis would constitute a risk factor for IVH in newborn infants. In 22 infants (gestational age 24.3--39.9 wk, median 28.0 wk) with neonatal IVH grade II to IV, the frequencies of congenital resistance to activated protein C due to a point mutation in the factor V gene (Gln506-FV) and a polymorphism in the prothrombin gene (G20210A-FII) were assessed and compared with those observed in 29 premature newborn infants without IVH and in 302 (Gln506-FV) or 526 (G20210A-FII) healthy adults. In infants with IVH, four (18%) heterozygous carriers of Gln506-FV and one (5%) heterozygous carrier of G20210A-FII were found. One infant without IVH was heterozygous for Gln506-FV (3%). When compared with the frequency of Gln506-FV in the general population, the odds ratio for being a carrier of Gln506-FV for patients with IVH was 5.9 (95% confidence interval 1.7--20.3, p = 0.013) and for patients without IVH 0.9 (95% confidence interval 0.1--7.6, p > 0.99). The absolute risk of IVH in a newborn infant with heterozygous Gln506-FV and born before 30 wk of gestation was estimated at 80%, whereas the corresponding risk for all infants born before 30 wk was 14%. Gln506-FV was more common in newborn infants with IVH than in the general population, whereas there was no difference in the frequencies of Gln506-FV in infants without IVH and in the general population. Thus, Gln506-FV may be a risk factor of IVH. The risk of IVH in a premature infant with Gln506-FV or other established thrombophilic coagulation abnormality may be considerable.     

Thyroid function in very-low-birth-weight infants with intraventricular hemorrhage

The objective of this investigation was to study the natural course of thyroid function in infants with intraventricular hemorrhage (IVH). A cohort of infants < 1,500 grams birth weight, n=247, were included in the analysis. Total T4 and thyrotropin from newborn screening during the 1st week of life (Test 1) and from repeat screening at 2-4 weeks postnatal age (Test 2) were compared in infants with IVH (n=43) and a group of infants without IVH. Fifty-nine percent of infants still had transient hypothyroxinemia at the time of Test 2. After multivariate analysis, infants with IVH had an increased odds of having a T4 < or = 6 microg/dL on Test 1 (OR 2.8, 95% CI 1.2-6.5), but at the time of Test 2 IVH was not associated with an increased odds of having a low T4. Only gestational age (OR 1.6, 95% CI 1.1-2.5) remained associated with an increased odds of having an extremely low T4 (< or = 4 microg/dL) at this time. Transient hypothyroxinemia remains common at 2-4 weeks of age in preterm infants. IVH is not independently associated with having a low T4 at this time.     

Maternal antibiotics and decreased periventricular leukomalacia in very low-birth-weight infants

OBJECTIVE: To investigate the effect of maternal antibiotics, given in the predelivery period, on neonatal outcomes. DESIGN: Retrospective cohort study. SETTING: A single level 3 neonatal intensive care unit. PATIENTS: All infants with birth weights 1500 g or less cared for from July 1994 to July 2000 (n = 834) were included in the study. Mothers were classified as receiving antibiotics if they received any parenteral antibiotics in the predelivery period. Infants whose mothers received antibiotics were compared with infants whose mothers received no antibiotics. MAIN OUTCOME MEASURES: The main outcome variables studied included intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (PVL), sepsis, and mortality. RESULTS: Of 834 mothers, 374 (45%) received antibiotics prior to delivery. On univariate analysis, there were no differences in the relative risk (RR) of mortality (1.26; 95% confidence interval [CI], 0.86-1.79) or grades 3 to 4 IVH (RR, 1.39; 95% CI, 0.82-1.90) between the antibiotics and no-antibiotics groups. Infants born to mothers receiving antibiotics had an increased risk of culture-proven sepsis (RR, 1.4; 95% CI, 1.02-1.64) and a decreased risk of cystic PVL (RR, 0.26; 95% CI, 0.09-0.79) compared with infants whose mothers did not receive antibiotics. After controlling for confounding variables, maternal antibiotics were not associated with a decrease in the risk of mortality (adjusted risk [AR], 1.0; 95% CI, 0.5-2.1), grades 3 to 4 IVH (AR, 1.0; 95% CI, 0.5-1.9), or sepsis (AR, 0.9; 95% CI, 0.7-1.4). However, the use of maternal antibiotics was associated with a decreased risk of developing cystic PVL (AR, 0.09; 95% CI, 0.02-0.5). CONCLUSIONS: In our population of very low-birth-weight infants, maternal antibiotics were associated with a decreased risk of cystic PVL. Maternal antibiotics do not change the risk of mortality, sepsis, or severe IVH.     

Genetic risk factors of thrombophilia in ischaemic childhood stroke of cardiac origin. A prospective ESPED survey

Ischaemic stroke is a rare event in childhood. In approximately one-fourth of cases an underlying cardiac disease can be detected. We investigated the importance of genetic risk factors of venous thromboembolism in childhood or stroke in adulthood as risk factors for ischaemic stroke in children in a multicentre survey focusing on patients with a cardiac disease. 38 of 162 white infants and children (neonate - 18 years) with ischaemic stroke were suffering from a cardiac disorder. An age-matched group of 100 children from the same geographic areas as the patients served as controls. Patients and controls were analysed for increased lipoprotein (a) levels >30 mg/dl, for the presence of the factor V (FV) G1691A mutation, the prothrombin (PT) G20210 A variant, and deficiencies of protein C, protein S, and antithrombin. The following frequencies (patients vs. controls), odds ratios (OR) and confidence intervals (CI) of single risk factors were found: Lp(a) >30 mg/dl (18.4% vs. 5%; OR/CI: 4.3/1.3-14.4; p = 0.03), FV G1691A (13.2% vs. 4%; OR/CI 3.63/0.92-14.3; p = 0.12) protein C type I deficiency (15.8% vs. 1%; OR/CI: 18.5/2.15-16.0; p = 0.0017), anticardiolipin antibodies (10.5% vs. 0%; p = 0.0051). No protein S or antithrombin deficiency was found. Combinations of haemostatic disorders were found in 10.5% of cases but in none of the controls (Fisher 0.005). Conclusion While FV G1691A and prothrombin G20210 A mutations show no significant data in our study, lipoprotein (a) levels >30 mg/dl protein C deficiency, anticardiolipin antibodies and combined prothrombotic disorders seem to be important risk factors for manifestation of ischaemic strokes in children with underlying cardiac disorders.     

Factor V G1691A and prothrombin G20210A in childhood spontaneous venous thrombosis - Evidence of an age-dependent thrombotic onset in carriers of factor V G1691A and prothrombin G20210A mutation

Risk factors for venous thrombosis in adults are the prothrombin (PT) G20210A, the factor (F) V G1691A mutations and hereditary deficiencies of protein C, protein S and antithrombin. However, data are limited on the relevance of these risk factors for thrombosis in children and adolescents. We therefore investigated 119 patients aged 0-18 with spontaneous venous thrombosis and controls (n = 100) for the presence of the factor V G1691A mutation and the prothrombin G20210A variant with respect to thrombotic onset and thrombosis location. The following frequencies (patients vs. controls), odds ratios (OR), 95%-confidence intervals (CI) and p-values were found: FV G1691A, 19.3% vs. 5%, OR/CI 4.55/1.66-12.5, p = 0.0038 and prothrombin G20210A, 8.4% vs. 3%, OR/CI 2.96/0.8-11, p = 0.17. A combination of the FV G1691A mutation with the PT G20210A variant was found in 3 children (2.5% of cases) but only once in the controls. With a median (range) age of 2 years (0-17), carriers of the FV mutation were significantly younger compared with patients carrying the PT variant (16 years: 0-18, p < 0.001). Vascular accidents in carriers of the FV mutation occurred in deep veins of the leg (n = 11), cerebral veins (n = 4), renal veins (n = 3) and portal veins (n = 2). Patients with the PT mutation showed spontaneous thrombosis in the majority of cases in the deep veins of the leg (n = 5) and in the central nervous system (n = 2). Combined defects were found in a neonate with renal venous thrombosis and in two adolescents with deep vein thrombosis. Conclusion Data presented here suggest that the heterozygous FV mutation is the most commonly found prothrombotic risk factor responsible for spontaneous thrombosis during infancy and early childhood. In contrast, the PT G20210A variant is likely to be more important during puberty and adolescence.     

Intrauterine inflammation and the onset of peri-intraventricular hemorrhage in premature infants

BACKGROUND: Peri-intraventricular hemorrhage (P/IVH) is a common neonatal morbidity among premature infants. The aim of the study was to examine the association between placental and/or fetal inflammation and the onset of P/IVH in premature infants. METHODS: A prospective study included 125 infants with gestational age 23-29 weeks. Placentas were examined for the presence of chorioamnionitis and funisitis, cord blood was sampled for the measurement of cytokines (IL-6 and IL-8). Fetal inflammation was defined as levels of IL-6 higher than 7.6 pg/ml. P/IVH was defined as early if diagnosed within the 1st day after birth; thereafter P/IVH was defined as late. RESULTS: Adjusted for the influence of gestational age, early-onset sepsis (OR 3.2, p = 0.045) and no or incomplete antenatal steroid course (OR 6.0, p = 0.001) significantly predicted early P/IVH. Funisitis (OR 1.6, p = 0.06) and fetal inflammation (OR 2.6, p = 0.06) were only partially associated with early hemorrhage. Contrary to that, respiratory distress syndrome (OR 3.4, p = 0.04), mechanical ventilation (OR 5.9, p = 0.008), low blood pressure (OR 3.5, p = 0.02), and vasopressors (OR 5.7, p = 0.002) were associated with late P/IVH. In multivariate analysis no or incomplete steroid course remained independent predictors for early and use of vasopressors for late P/IVH. The interaction of fetal inflammation and vaginal delivery with no or incomplete steroid course increased the risk of early P/IVH. CONCLUSIONS: These results indicate different risk factors for early and late P/IVH. Neither funisitis nor fetal inflammation independently predicts the onset of P/IVH. However, the interaction of fetal inflammation and vaginal delivery with no or incomplete antenatal steroid course increase the risk of early but not also late P/IVH.     

Effect of prenatal antioxidant intake on infants’ respiratory infection is modified by a <Emphasis Type="Italic">CD14</Emphasis> polymorphism

Background:Prenatal maternal diet may influence disease susceptibility in offspring with specific genetic backgrounds.We hypothesized that interactions between prenatal antioxidant intake and polymorphisms in immunity genes influence respiratory tract infection (RTI) susceptibility in infants at 12 months of age.Methods:This study included 550 infants.In the Cohort for Childhood Origin of Asthma and Allergic Diseases (COCOA) birth cohort study,prenatal maternal diet was assessed by administering a food frequency questionnaire.Infants' cord blood was genotyped for CD14 (rs2569190),TLR4 (rs1927911),and GSDMB (rs4794820) polymorphisms by the TaqMan method.Results:Higher prenatal intake of total fruit and vegetables (FV) was associated with the decreased risk of RTI in offspring (P-trend=0.0430).In children with TT genotype at rs2569190,a higher prenatal intake of vitamins A and C,fruits,and total FV decreased RTI risk (P-trend ＜0.05),while in infants with TC+CC genotype,a higher prenatal intake of fruit increased RTI risk (P-trend ＜0.05).When analyzing the 3 genotypes,children with TT genotype at rs2569190 were more protected against RTIs compared with those with CC genotype with respect to vitamin C and fruits [odds ratio (OR)=5.04 and OR=10.30,respectively].In children with CC genotype at rs1927911,RTI risk showed a dose-response association with a higher prenatal intake of vitamin C (P for interaction＜0.05).A higher prenatal intake of fruits and total FV reduced RTI risk in infants with GA+AA genotype of rs4794820 (P for interaction＜0.05).Conclusion:Prenatal antioxidant intake may reduce RTI risk in infants and this relationship may be modified by CD14,TLR4,and GSDMB polymorphisms.     

Early ductal shunting and intraventricular haemorrhage in ventilated preterm infants.

AIM: To establish if there is an association between early cardiovascular adaptation and intraventricular haemorrhage (IVH). METHODS: One hundred and seventeen ventilated preterm infants (mean gestational age 27 weeks, mean birthweight 993 g) were studied echocardiographically within the first 36 hours. Measurements included right (RVO) and left ventricular outputs (LVO), ductus arteriosus (PDA) and atrial shunt diameter using colour Doppler and pulsed Doppler direction and velocity of both shunts. Clinical variables collected over the first 24 hours included use of antenatal steroids, respiratory severity, and mean blood pressure. Cerebral ultrasound scans were reported by a radiologist blinded to clinical and echocardiographic data. RESULTS: Antenatal steroids (two doses) had been given to 73% of the 86 infants with no IVH compared with 48% of the 21 infants with grades 1 and 2 IVH, and just 10% of 10 babies with grades 3 and 4 (P < 0.05). Both groups with IVH had significantly larger PDA diameters than the group with no IVH. Infants with grades 3 and 4 IVH had significantly lower RVO than the other infants. These differences were more pronounced when only infants with definite late IVH were analysed. Logistic regression analysis showed lack of antenatal steroids and larger PDA diameters were significantly associated with any grade of IVH and lack of antenatal steroids; lower RVO was significantly associated with grades 3 and 4 IVH. CONCLUSIONS: Larger early PDA shunts, lower RVO, and lack of antenatal steroids were significantly associated with IVH.     

Neonatal correlates of adverse outcomes in very low‐birthweight infants in the NICU Network

Background: The aim of the present study was to explore the relationships among neonatal morbidity, interventions and death or adverse neurodevelopmental outcomes in very low‐birthweight (VLBW) infants. Methods: Subjects were infants with birthweight ≤1500 g who were cared for in the tertiary neonatal intensive care units in Japan. Multiple logistic regression analysis was performed to examine the odds ratios (OR) and 95% confidence intervals (CI) of neonatal factors for death or cerebral palsy (CP) and death or developmental delay (developmental quotient <70 or delay judged by physicians) at 3 years of age after adjusting for biological and prenatal variables. Results: Of the 3104 subjects, 257 died and 1826 were evaluated at 3 years of age. Cystic periventricular leukomalacia (PVL; OR, 23.9; 95%CI: 11.0–51.7), gastrointestinal perforation (OR, 8.5; 95%CI: 2.8–25.4), intraventricular hemorrhage (IVH) grade 3 or 4 (OR, 3.1; 95%CI: 1.3–7.2) and sepsis (OR, 2.6; 95%CI: 1.4–4.8) were neonatal factors significantly associated with an increased risk of death or CP. Significant correlates with death or developmental delay were cystic PVL (OR, 7.9; 95%CI: 3.7–16.8), gastrointestinal perforation (OR, 6.3; 95%CI: 1.9–20.8), sepsis (OR, 2.8; 95%CI: 1.6–4.8), IVH grade 3 or 4 (OR, 2.6; 95%CI: 1.2–5.7), chronic lung disease at 36 weeks of corrected gestational age (OR, 1.6; 95%CI: 1.1–2.4) and treatment for retinopathy of prematurity (ROP; OR, 1.5; 95%CI: 1.0–2.3). Conclusion: Cystic PVL, gastrointestinal perforation, IVH and sepsis correlated with both death or CP and death or developmental delay in VLBW infants. Chronic lung disease at 36 weeks and treatment for ROP were associated with death or developmental delay, but not with death or CP.     

Incidence of brain injuries in premature infants with gestational age ≤34 weeks in ten urban hospitals in China

Background

There is a large number (1.5 million per year) of premature births in China. It is necessary to obtain the authentic incidences of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL), the common brain injuries, in Chinese premature infants. The present multicenter study aimed to investigate the incidence of brain injuries in premature infants in ten urban hospitals in China.

Methods

The research proposal was designed by the Subspecialty Group of Neonatology of Pediatric Society of the Chinese Medical Association. Ten large-scale urban hospitals voluntarily joined the multicenter investigation. All premature infants with a gestational age ≤34 weeks in the ten hospitals were subjected to routine cranial ultrasound within three days after birth, and then to repeated ultrasound every 3–7 days till their discharge from the hospital from January 2005 to August 2006. A uniform data collection sheet was designed to record cases of brain injuries.

Results

The incidences of overall IVH and severe IVH were 19.7% (305/1551) and 4.6% (72/1551), respectively with 18.4% (56/305) for grade 1, 58.0% (177/305) for grade 2, 17.7% (54/305) for grade 3 and 5.9% (18/305) for grade 4 in nine hospitals. The incidences of overall PVL and cystic PVL were 5.0% (89/1792) and 0.8% (14/1792) respectively, with 84.3% (75/89) for grade 1, 13.5% (12/89) for grade 2, and 2.2% (2/89) for grade 3 in the ten hospitals. The statistically significant risk factors that might aggravate the severity of IVH were vaginal delivery (OR=1.883, 95% CI: 1.099–3.228, P=0.020) and mechanical ventilation (OR=4.150, 95% CI: 2.384–7.223, P=0.000). The risk factors that might result in the development of cystic PVL was vaginal delivery (OR=21.094, 95% CI: 2.650–167.895, P=0.000).

Conclusions

The investigative report can basically reflect the incidence of brain injuries in premature infants in major big cities of China. Since more than 60% of the Chinese population live in the rural areas of China, it is expected to undertake a further multicenter investigation covering the rural areas in the future.     

The Prevalence and Outcomes of Thrombocytopenia in a Neonatal Intensive Care Unit: A Three-Year Report

Neonatal thrombocytopenia is one of the most common hematologic disorders in neonatal intensive care units (NICUs). The purpose of this study was to determine the prevalence of thrombocytopenia and whether thrombocytopenia has an effect on the occurrence of intraventricular hemorrhage (IVH) ≥ grade 2 and on mortality rate. This study was carried out retrospectively in neonates admitted to NICU of Cumhuriyet University in Sivas, Turkey, between 2009 and 2012. Among 2218 neonates evaluated, 208 (9.4%) developed thrombocytopenia. The prevalence of IVH ≥ grade 2 was more in infants with thrombocytopenia (7.2%) than in those without thrombocytopenia (4.4%), although this was not statistically significant (P = .08). In univariate analysis, IVH ≥ grade 2 was higher in cases with very severe thrombocytopenia (35.7%, n = 5) than in those with mild (2.1%, n = 2), moderate (4.7%, n = 3), and severe thrombocytopenia (15.2%, n = 5) (P = .04). Multivariate logistic regression analysis showed that birth weight <1500 g (OR 6.2, 95% CI 3.4–9.8; P = .0001), gram-negative sepsis (OR 2.5, 95% CI 1.8–4.2; P = .01), very severe thrombocytopenia (OR 1.3, 95% CI 1.1–2.1; P = .03), and platelet transfusion ≥2 (OR 7.3, 95% CI 4.1–12.1; P = .001) were significant risk factors for mortality. The results of our study suggest that outcomes of neonates with thrombocytopenia depend not only on platelet count but also on decreased gestational age or birth weight, prenatal factors, and sepsis.     

Prothrombotic factors in neonates with cerebral thrombosis and intraventricular hemorrhage

Aim : To investigate whether the factor V Leiden mutation (FVL), the prothrombin gene G20210A variant or the methylenetetrahydrofolate reductase (MTHFR) C677T genotype are risk factors for central nervous system (CNS) thrombosis or intraventricular hemorrhage (IVH) in neonates. Methods : Thirteen full-term infants with cerebral infarct documented with magnetic resonance imaging were assessed with the whole spectrum of assays for thrombophilia including the three DNA-based prothrombotic factors. The frequency of congenital defects was compared with that observed in 38 healthy full-term infants. The genetic defects were also assessed in 55 premature neonates, gestational age <32wk, 17 of whom developed IVH, grade II-IV. The remaining 38 premature neonates without IVH were used as controls. Results : In the CNS thrombosis group: a prothrombotic factor was detected in 53% of patients and an underlying disease or a triggering event in 61.5%. The frequency of FVL in thrombosed neonates was higher (23%) than in the group of healthy full-term infants (10.5%), although it did not reach statistical significance. IVH developed in 30.9% of premature neonates. Apart from several maternal or neonatal risk factors for IVH, FII G20210A was found in a considerably higher prevalence in the cohort of neonates with IVH (12%) than in those without (2%), although the difference was not statistically significant.
Conclusion : The pathogenesis of cerebral thrombosis or IVH in neonates is multifactorial. Along with underlying diseases or triggering events, congenital prothrombotic factors (FVL or FII G20210A) showed a trend towards a higher frequency in full-term infants with CNS thrombosis or premature neonates with IVH than in controls. However, their contribution to neonatal cerebral thrombosis or IVH remains to be determined.     

Prothrombotic factors in neonates with cerebral thrombosis and intraventricular hemorrhage

AIM: To investigate whether the factor V Leiden mutation (FVL), the prothrombin gene G20210A variant or the methylenetetrahydrofolate reductase (MTHFR) C677T genotype are risk factors for central nervous system (CNS) thrombosis or intraventricular hemorrhage (IVH) in neonates. METHODS: Thirteen full-term infants with cerebral infarct documented with magnetic resonance imaging were assessed with the whole spectrum of assays for thrombophilia including the three DNA-based prothrombotic factors. The frequency of congenital defects was compared with that observed in 38 healthy full-term infants. The genetic defects were also assessed in 55 premature neonates, gestational age <32 wk, 17 of whom developed IVH, grade II-IV. The remaining 38 premature neonates without IVH were used as controls. RESULTS: In the CNS thrombosis group: a prothrombotic factor was detected in 53% of patients and an underlying disease or a triggering event in 61.5%. The frequency of FVL in thrombosed neonates was higher (23%) than in the group of healthy full-term infants (10.5%), although it did not reach statistical significance. IVH developed in 30.9% of premature neonates. Apart from several maternal or neonatal risk factors for IVH, FII G20210A was found in a considerably higher prevalence in the cohort of neonates with IVH (12%) than in those without (2%), although the difference was not statistically significant. CONCLUSION: The pathogenesis of cerebral thrombosis or IVH in neonates is multifactorial. Along with underlying diseases or triggering events, congenital prothrombotic factors (FVL or FII G20210A) showed a trend towards a higher frequency in full-term infants with CNS thrombosis or premature neonates with IVH than in controls. However, their contribution to neonatal cerebral thrombosis or IVH remains to be determined.     

Grade and laterality of intraventricular haemorrhage to predict 18-22 month neurodevelopmental outcomes in extremely low birthweight infants

Aim: To determine whether extremely low‐birthweight (ELBW) infants with bilateral compared to unilateral intraventricular haemorrhage (IVH) have worse neurodevelopmental outcomes at 18–22 months. Methods: A total of 166 ELBW infants (<1000 g) admitted to a Cincinnati NICU from 1998 to 2005 with a head ultrasound showing Grade I–IV IVH and neurodevelopmental assessment at 18–22 months corrected age were included. Multivariable linear and logistic regression models were developed to determine the impact of laterality and grade of IVH and other clinical variables to predict scores on the Bayley Scales of Infant Development, Second Edition, Mental Development Index and Psychomotor Development Index and the combined outcome of neurodevelopmental impairment (NDI). Results: Infants with bilateral grade IV IVH had lower adjusted mean Bayley scores compared with infants with unilateral grade IV IVH. For grades I, II and III IVH, bilaterality of IVH was not associated with lower mean Bayley scores. Infants with grade IV IVH had the highest odds of NDI. The probability of NDI increased with sepsis and postnatal steroid use. Conclusion: ELBW infants with bilateral compared to those with unilateral grade IV IVH had worse neurodevelopmental outcomes. Infants with grades I–III IVH had similar outcomes whether they had unilateral or bilateral IVH.     

Neurodevelopmental sequelae of intraventricular haemorrhage at 8 years of age in a regional cohort of ELBW/very preterm infants

BACKGROUND: Major grades of intraventricular haemorrhage (IVH) are associated with adverse neurodevelopmental sequelae in early childhood but the extent of problems in specific cognitive areas, such as executive function, and the contribution of lesser grades of IVH to neurodevelopmental problems at school age are not well described. AIMS: To determine the neuromotor, cognitive and educational outcome of extremely low birthweight (ELBW, birthweight <1000 g) or very preterm (<28 weeks) infants at 8 years of age related to the severity of IVH diagnosed in the newborn period. DESIGN: Regional cohort study. PATIENTS: Consecutive surviving children of either birthweight <1000 g or gestational age <28 weeks born in the state of Victoria in 1991 or 1992. MAIN OUTCOME MEASURES: Neurological impairments and disabilities, cognitive function and academic progress. RESULTS: Of 298 consecutive ELBW/very preterm survivors 270 (90.6%) with cranial ultrasound data were assessed at 8 years of age. Cerebral palsy, poor motor performance and major neurosensory disability were more prevalent with increasing severity of IVH. Cognitive functioning across domains was worse with increasing severity of IVH. Most of the differences were attributable to the few (n=6) survivors who had grade 4 IVH; there were few substantial differences between survivors with lesser grades of IVH. CONCLUSIONS: Neurodevelopmental dysfunction at school age in ELBW/very preterm survivors varies little with increasing severity of IVH, with the exception of grade 4 IVH.     

Data collection from very low birthweight infants in a geographical region: methods, costs, and trends in mortality, admission rates, and resource utilisation over a five-year period

AIMS: 1. To determine the survival and morbidity of infants at discharge with a birthweight of less than 1500 g in the geographically defined population of East Anglia. 2. To demonstrate a cost-effective method of regional data collection. 3. To determine whether there were any changes in the demand for neonatal care. STUDY DESIGN AND SUBJECTS: A prospective cohort analysis using a single database to collect data on 1244 very low birthweight infants from eight neonatal units in one Region from 1993 to 1997. RESULTS: Estimated ascertainment of VLBW infants to the study was 96%. Over the 5 years survival rates were stable (75-79%). 52% of deaths in infants admitted for neonatal care occurred on day 1, with just 15% of deaths occurring after 28 days of life. Mortality risk significantly decreased with increasing gestational age at birth. Compared to 22-25-week old infants, the mortality risk decreased by 65% for 26-27-week old infants (OR 0.35 95% CI (0.21, 0.59)) and by 92% for 32-39-week old infants (OR 0.08 95% CI (0.03, 0.21)) with intermediate odds ratios of 0.22 (0.12, 0.42) and 0.13 (0.06, 0.28) for the 28-29 and 30-39 weeks gestation, respectively. Higher birthweight, after adjusting for gestation also decreased the mortality risk (OR 0.78 per 100 g difference, 95% CI (0.71, 0.86)). No change was seen in the number of extremely preterm infants admitted for intensive care or resource utilisation, although a significant increase was seen in the number of infants dying in delivery rooms. There was a reduction in the reported incidence of pulmonary interstitial emphysema (10-4%) but no change in the number of ventilation days or the rate of chronic lung disease. The mean maternal age increased from 27.7 years to 28.9 years during the study. Maternal steroid administration increased (30% to 59%) and was associated with a decreased risk of mortality (OR 0.44, 95% CI: 0.31-0.62). CONCLUSIONS: It is possible to collect useful data from the neonatal period at a reasonable cost from a geographically defined population. This information was used for informing clinicians, counselling parents and in the era of managed clinical networks will be useful in guiding the provision of effective health care resources.     

Effect of the Factor V Leiden mutation on the severity of meningococcal disease.

BACKGROUND: One of the most serious complications of meningococcal disease is the syndrome of purpura fulminans, which is characterized by intravascular thrombosis and hemorrhagic infarction of skin, limbs and digits. The reasons why some patients with meningococcal disease develop purpura fulminans while others have minimal thrombotic and skin involvement despite having profound septic shock are not yet understood. The Factor V Leiden mutation (FV(L)) is associated with thrombotic events, and we hypothesized that children carrying FV(L) who develop meningococcal disease may be at increased risk of purpura fulminans. METHODS: We determined the FV(L) genotype by PCR and restriction enzyme digestion (Mnl1) in 259 children with meningococcal disease and 80 healthy controls. In addition 79 parents of children with fatal meningococcal disease were studied. RESULTS: There was no significant increase in the frequency of FV(L) in patients with meningococcal disease (10%) as compared with healthy controls (9%) or with the parents of children who died of meningococcal disease (12%). Although the mortality was not increased in patients heterozygous for FV(L), they had increased complications of purpura fulminans, as assessed by requirement for skin grafting, referral to plastic surgeon and/or amputation. Among survivors 5 of 24 (21%) of those heterozygous for FV(L) had complications, compared with 14 of 233 (7%) who were wild type [P < 0.03; relative risk, 3.1 (95% confidence intervals, 1.2 to 7.9)]. CONCLUSIONS: FV(L) exacerbates purpura fulminans in meningococcal disease but does not have a significant effect on mortality.