Neonatal encephalopathy and the association to asphyxia in labor.

OBJECTIVE: In cases with moderate and severe neonatal encephalopathy, we aimed to determine the proportion that was attributable to asphyxia during labor and to investigate the association between cardiotocographic (CTG) patterns and neonatal outcome. STUDY DESIGN: In a study population of 71,189 births from 2 Swedish university hospitals, 80 cases of neonatal encephalopathy were identified. Cases were categorized by admission CTG patterns (normal or abnormal) and by the presence of asphyxia (cord pH, <7.00; base deficit, ≥12 mmol/L). Cases with normal admission CTG patterns and asphyxia at birth were considered to experience asphyxia related to labor. CTG patterns were assessed for the 2 hours preceding delivery. RESULTS: Admission CTG patterns were normal in 51 cases (64%) and abnormal in 29 cases (36%). The rate of cases attributable to asphyxia (ie, hypoxic ischemic encephalopathy) was 48 of 80 cases (60%), most of which evolved during labor (43/80 cases; 54%). Both severe neonatal encephalopathy and neonatal death were more frequent with an abnormal, rather than with a normal, admission CTG pattern (13 [45%] vs 11 [22%]; P = .03), and 6 [21%] vs 3 [6%]; P = .04), respectively. Comparison of cases with an abnormal and a normal admission CTG pattern also revealed more frequently observed decreased variability (12 [60%] and 8 [22%], respectively) and more late decelerations (8 [40%] and 1 [3%], respectively). CONCLUSION: Moderate and severe encephalopathy is attributable to asphyxia in 60% of cases, most of which evolve during labor. An abnormal admission CTG pattern indicates a poorer neonatal outcome and more often is associated with pathologic CTG patterns preceding delivery.

Suboptimal care and metabolic acidemia is associated with neonatal encephalopathy but not with neonatal seizures alone: a population-based clinical audit.

OBJECTIVE: To determine the incidence of moderate to severe neonatal encephalopathy (NE) and neonatal seizures without encephalopathy, and the association with metabolic acidemia. Secondly, to investigate the occurrence of suboptimal intrapartum care and its impact on neonatal outcome. DESIGN: Clinical audit. SETTING: Two university hospitals in Sweden. POPULATION: Neonates ≥34 weeks with moderate or severe NE and neonatal seizures alone, i.e. without encephalopathy, from a population of 71 189 births, where umbilical blood gases were routinely analyzed. METHODS: Neonates were categorized depending on the presence of metabolic acidemia at birth by umbilical artery pH < 7.00, base deficit ≥12 mmol/L. Records were audited for suboptimal care and a decision was made on whether management was assessed to have impacted neonatal outcome. MAIN OUTCOME MEASURES: Encephalopathy and seizures alone. RESULTS: We identified 80 neonates with NE and 30 with seizures alone, of which 48 (60%) and none, respectively, had metabolic acidemia. Suboptimal care could be assessed in 77 and occurred in 28 (36%) NE cases and in one neonate with seizures alone (p < 0.001). In 47 NE cases with metabolic acidemia, suboptimal care occurred in 22 (47%) vs. 6/30 (20%) without metabolic acidemia (p = 0.02). Suboptimal care had an impact on outcome in 18/77 (23%) NE cases but in no cases with seizures alone. CONCLUSION: Suboptimal care was commonly seen with NE, particularly in neonates with metabolic acidemia, and also affected neonatal outcome. No such associations were found in neonates with seizures alone.

Acidemia at birth, related to obstetric characteristics and to oxytocin use, during the last two hours of labor.

OBJECTIVE: Evaluate obstetric characteristics during the last two hours of labor in neonates born with acidemia. DESIGN: Case-control study. SETTING: Delivery units at two university hospitals in Sweden. STUDY POPULATION: Out of 28,486 deliveries during 1994-2004, 305 neonates had an umbilical artery pH value <7.05 at birth. CASES: neonates with an umbilical artery pH < 7.05. Controls were neonates with pH > or = 7.05 and an Apgar score > or =7 at 5 minutes. Obstetric characteristics, cardiotocographic patterns and oxytocin treatment during the last two hours of labor were recorded. RESULTS: In the univariate analysis, > or =6 contractions/10 minutes (odds ratio (OR) 4.94, 95% confidence interval (CI) 3.25-7.49), oxytocin use (OR 2.20, 95% CI 1.66-2.92), bearing down > or =45 minutes (OR 1.77, 95% CI 1.31-2.38) and occipito-posterior position (OR 2.18, 95% CI 1.19-3.98) were associated with acidemia at birth. In the multivariate analysis, only > or =6 contractions/10 minutes (OR 5.36, 95% CI 3.32-8.65) and oxytocin use (OR 1.89, 95% CI 1.21-2.97) were associated with acidemia at birth. Among cases with > or =6 contractions/10 minutes, 75% had been treated with oxytocin. Pathological cardiotocographic patterns occurred in 68.8% of cases and in 26.1% of controls (p<0.001). CONCLUSION: A hyperactive uterine contraction pattern and oxytocin use are the most important risk factors for acidemia at birth. The increased uterine activity was related to overstimulation in the majority of cases. The duration of bearing down is less important when uterine contraction frequency has been considered.

Placental growth factor and soluble FMS-like tyrosine kinase-1 in early-onset and late-onset preeclampsia.

OBJECTIVE: To estimate whether alterations in plasma levels of the proangiogenic proteins placental growth factor (PlGF) and vascular endothelial growth factor-A (VEGF-A), and the antiangiogenic protein soluble fms-like tyrosine kinase-1 (sFlt1) were more pronounced in early-onset than in late-onset preeclampsia. METHODS: A cross-sectional study was conducted to estimate the levels of sFlt1, PlGF, and VEGF-A in plasma in a control group of nonpregnant women, in an early control group of women at 24-32 weeks of gestation, in a late control group of women at 36-42 weeks of gestation, and in cases of women with early-onset (before 32 weeks of gestation) and late-onset (after 35 weeks of gestation) preeclampsia. RESULTS: Women with early-onset preeclampsia had a 43 times higher median plasma sFlt1 level than early controls (P<.001). Women with late-onset preeclampsia had a three times higher median plasma sFlt1 level than late controls (P<.001). Women with early-onset preeclampsia had a 21 times lower median plasma PlGF level than early controls (P<.001). Women with late-onset preeclampsia had a five times lower median plasma PlGF level than late controls (P=.01). The median level of VEGF-A in plasma was less than 15 pg/mL in all groups of pregnant women. CONCLUSION: Both early- and late-onset preeclampsia are associated with altered plasma levels of sFlt1 and PlGF. The alterations are more pronounced in early-onset rather than in late-onset disease.

Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta.

BACKGROUND: Mesenchymal stem cells (MSC) are progenitors of mesenchymal tissues such as bone, cartilage, and adipose. Adult human leukocyte antigen (HLA)-matched MSC have been used in cellular therapies of bone disorders such as osteogenesis imperfecta, with promising results. METHODS: A female fetus with multiple intrauterine fractures, diagnosed as severe osteogenesis imperfecta, underwent transplantation with allogeneic HLA-mismatched male fetal MSC in the 32nd week of gestation. Engraftment analyses of donor cells, immunologic reaction against donor cells, and the well-being of the patient were assessed. RESULTS: At 9 months of age, on slides stained for osteocalcin or osteopontin, a centromeric XY-specific probe revealed 0.3% of XY-positive cells in a bone biopsy specimen. Whole Y genome fluorescent in situ hybridization staining showed a median of 7.4% Y-positive cells (range, 6.8%-16.6%). Bone histology showed regularly arranged and configurated bone trabeculae. Patient lymphocyte proliferation against donor MSC was not observed in co-culture experiments performed in vitro after MSC injection. Complementary bisphosphonate treatment was begun at 4 months. During the first 2 years of life, three fractures were noted. At 2 years of corrected age, psychomotor development was normal and growth followed the same channel, -5 SD. CONCLUSIONS: The authors' findings show that allogeneic fetal MSC can engraft and differentiate into bone in a human fetus even when the recipient is immunocompetent and HLA-incompatible.

Acidemia at birth in the vigorous infant as a trigger incident to assess intrapartum care with regard to CTG patterns.

OBJECTIVE: To evaluate if acidemia in vigorous infants is a useful variable in the assessment of intrapartum care with regard to cardiotocographic (CTG) patterns during the second stage. METHODS: Cases (n = 241) were infants with an umbilical artery pH < 7.05, controls (n = 482) were infants with pH ≥ 7.05. Apgar score was ≥ 7 at 5 min in both groups. CTGs during the last two hours of labor were assessed and neonatal outcomes compared. A sub-analysis of cases with metabolic acidemia: pH < 7.00 and base deficit ≥ 12 mmol/L and acidemia: 7.00 < pH < 7.05 was performed. RESULTS: 63% of cases had a pathological CTG versus 26% of controls (p < 0.001). Patterns with severe variable decelerations had a significantly longer duration in cases. Metabolic acidemia was significantly associated with severe variable decelerations and decreased variability. Infants to cases were admitted to neonatal care in 19% versus 2% of controls (p < 0.001). With metabolic acidemia, 32% were admitted. CONCLUSION: An umbilical artery pH < 7.05 at birth of vigorous infants may be a useful variable for quality control of intrapartum management with regard to the assessment of second-stage CTGs. Differences in duration of pathological patterns indicate passiveness in academic cases.