Brain-Derived Neurotrophic Factor Levels in Cord Blood from Growth Restricted Fetuses with Doppler Alteration Compared to Adequate for Gestational Age Fetuses.

Background and Objectives: Fetal growth restriction (FGR) is a severe obstetric disease characterized by a low fetal size entailing a set of undesired consequences. For instance, previous studies have noticed a worrisome association between FGR with an abnormal neurodevelopment. However, the precise link between FGR and neurodevelopmental alterations are not yet fully understood yet. Brain-derived neurotrophic factor (BDNF) is a critical neurotrophin strongly implicated in neurodevelopmental and other neurological processes. In addition, serum levels of BDNF appears to be an interesting indicator of pathological pregnancies, being correlated with the neonatal brain levels. Therefore, the aim of this study is to analyze the blood levels of BDNF in the cord blood from fetuses with FGR in comparison to those with weight appropriate for gestational age (AGA). Materials and Methods: In this study, 130 subjects were recruited: 91 in group A (AGA fetuses); 39 in group B (16 FGR fetuses with exclusively middle cerebral artery (MCA) pulsatility index (PI) < 5th percentile and 23 with umbilical artery (UA) PI > 95th percentile). Serum levels of BDNF were determined through ELISA reactions in these groups. Results: Our results show a significant decrease in cord blood levels of BDNF in FGR and more prominently in those with UA PI >95th percentile in comparison to AGA. FGR fetuses with exclusively decreased MCA PI below the 5th percentile also show reduced levels of BDNF than AGA, although this difference was not statistically significant. Conclusions: Overall, our study reports a potential pathophysiological link between reduced levels of BDNF and neurodevelopmental alterations in fetuses with FGR. However, further studies should be conducted in those FGR subjects with MCA PI < 5th percentile in order to understand the possible implications of BDNF in this group.

Diagnostic accuracy of fetal scalp lactate for intrapartum acidosis compared with scalp pH.

OBJECTIVE: To determine the diagnostic accuracy of fetal scalp lactate sampling (FSLS) and to establish an optimal cut-off value for intrapartum acidosis compared with fetal scalp pH. METHODS: A 20-month retrospective cohort study was conducted of all neonates delivered in our institution for whom fetal scalp blood sampling (FSBS) was performed, matching their intrapartum gasometry to their cord gasometry at delivery (n=243). The time taken from the performance of scalp blood sampling to arterial umbilical cord gas acquisition was 45 min at most. Five arterial cord gasometry patterns were set for assessing the predictive ability of both techniques. Subsequent obstetric management for a pathological value was analysed considering the use of both techniques. RESULTS: The optimal cut-off value for FSLS was 4.8 mmol/L: this value has 100% sensitivity and 63% specificity for umbilical arterial cord gas pH≤7.0 and base deficit (BD)≥12 detection, and 100% sensitivity and 64% specificity for umbilical arterial cord gas pH≤7.10 and BD≥12 detection, with a false negative rate of <1.3%, improving fetal scalp pH performance. FSLS showed the best area under the curve (AUC) of 0.86 and 0.84 for both arterial cord gasometry patterns, respectively. Expedite birth following lactate criteria would have been the same as following pH criteria (92 obstetric interventions) with no cases of missed metabolic acidosis. In the cohort, 19.8% of cases were discordant, but no cases of metabolic acidosis were in this group. CONCLUSIONS: FSLS improves the detection of metabolic acidosis via fetal scalp pH with an optimal cut-off value of 4.8 mmol/L. FSLS can be used without increasing obstetrical interventions or missing metabolic acidosis.

Maternal high-dose valacyclovir and its correlation with newborn blood viral load and outcome in congenital cytomegalovirus infection.

BACKGROUND/OBJECTIVE: Currently, there is no validated treatment for fetal cytomegalovirus (CMV). Two studies suggest that high-dose maternal valacyclovir decreases fetal viral load and improves outcomes in moderately-symptomatic fetuses. We offered valacyclovir in cases of fetal infection lacking ultrasound abnormalities or with non-severe infection. Maternal tolerability, fetal outcome and newborn blood viral load were evaluated in pregnancies of mothers receiving valacyclovir. STUDY DESIGN: We performed a case series including 8 pregnancies with fetal CMV classified as unaffected/mildly-moderately affected. Mothers received valacyclovir (8 g/24h) from fetal infection diagnosis to delivery. Standard newborn evaluation was performed, and viremia was determined in the first 48 h of life and compared according to length of maternal treatment and presence/absence of prenatal anomalies. RESULTS: Valacyclovir was administered at a median gestational age of 26.5 weeks (23.8-33.1) in 3 cases without fetal abnormalities, and 5 with mild/moderate abnormalities. Three were 3 first trimester primary infections, one non-primary infection, and in 4 the type of infection was unknown. Valacyclovir was well-tolerated. Fetal features did not progress. Three newborns were asymptomatic, and one was severely affected (bilateral chorioretinitis). The median newborn viral load (IQR) was 502 IU/mL (231-191781) with lower levels when maternal treatment was administered ≥10 weeks, and in cases without fetal abnormalities [median 234 IU/mL (228-711) vs. 4061 (292-510500) p = .18; and 234 IU/mL (228-379500) vs. 711 IU/mL (292-4061) p = .65, respectively], these differences being non-significant. CONCLUSIONS: Fetal CMV lesions remained stable with high-dose maternal valacyclovir. Newborn viral load was unchanged despite treatment duration and fetal/neonatal abnormalities. SUMMARY: Fetal cytomegalovirus lesions remained stable with high-dose maternal valacyclovir. Newborn viral load was unchanged despite treatment duration and fetal/newborn abnormalities.

Influence of Cerebral Vasodilation on Blood Reelin Levels in Growth Restricted Fetuses.

Fetal growth restriction (FGR) is one of the most important obstetric pathologies. It is frequently caused by placental insufficiency. Previous studies have shown a relationship between FGR and impaired new-born neurodevelopment, although the molecular mechanisms involved in this association have not yet been completely clarified. Reelin is an extracellular matrix glycoprotein involved in development of neocortex, hippocampus, cerebellum and spinal cord. Reelin has been demonstrated to play a key role in regulating perinatal neurodevelopment and to contribute to the emergence and development of various psychiatric pathologies, and its levels are highly influenced by pathological conditions of hypoxia. The purpose of this article is to study whether reelin levels in new-borns vary as a function of severity of fetal growth restriction by gestational age and sex. We sub-grouped fetuses in: normal weight group (Group 1, n = 17), FGR group with normal umbilical artery Doppler and cerebral redistribution at middle cerebral artery Doppler (Group 2, n = 9), and FGR with abnormal umbilical artery Doppler (Group 3, n = 8). Our results show a significant association of elevated Reelin levels in FGR fetuses with cerebral blood redistribution compared to the normal weight group and the FGR with abnormal umbilical artery group. Future research should focus on further expanding the knowledge of the relationship of reelin and its regulated products with neurodevelopment impairment in new-borns with FGR and should include larger and more homogeneous samples and the combined use of different in vivo techniques in neonates with impaired growth during their different adaptive phases.

pH, base deficit or lactate. Which is better for predicting neonatal morbidity?

OBJECTIVE: To determine which parameter of the umbilical arterial cord gas analysis, pH, base deficit (BD) or lactate has a bigger predictive ability for neonatal morbidity at term. METHOD: We conducted a four-year retrospective cohort study including all non-anomalous, singleton, vertex, term births with neonatal acidemia (umbilical arterial cord gas pH ≤ 7.1). The primary outcomes were a composite neurological morbidity and a composite systemic morbidity. The predictive ability of lactate, BD and pH was compared using receiver operator characteristic (ROC) curves. Optimal cutoff values of lactate, BD and pH were estimated based on their maximal Youden Index. RESULTS: We identified 466 acidemic neonates who had paired and validated cord blood gas data. The ROC curve analysis revealed that pH, BD and lactate had a similar predictive ability for neurological (AUC: 0.81; 0.78; 0.83, respectively) and systemic neonatal morbidity (AUC: 0.77; 0.82; 0.82, respectively). The combination of pH ≤ 7.0 and lactate ≥ 7.0 mmol/L presented similar validity to that of pH ≤ 7.0 and BD ≥ 12 mmol/L, but both were comparable to pH alone. CONCLUSIONS: pH, BD and lactate have similar predictive ability for adverse neonatal outcomes among acidemic neonates. Umbilical arterial lactate could replace BD as a measure of the metabolic component in acidemic neonates. However, neither BD nor lactate demonstrated in this study to improve the predictive ability of pH alone for short-term neonatal outcomes.

Deceleration area and fetal acidemia.

AIMS: To compare the predictive ability for neonatal acidemia of individual components of intrapartum cardiotocography (CTG) described by National Institute of Child Health and Human Development (NICHD) system and deceleration area. DESIGN: Case-control study. SETTING: Spanish tertiary obstetrical hospital. POPULATION: CTG patterns of 102 acidemic fetus (umbilical arterial cord gas pH ≤7.10, base deficit (BD) > 8) and 102 nonacidemic controls (umbilical arterial cord gas pH > 7.10). METHODS: Two reviewers blind to clinical and outcome data analyzed the last thirty minutes before delivery of 204 fetal heart rate (FHR) tracings, extracting those features defined by NICHD and certain measures of FHR decelerations, including deceleration area, not considered by this system. OUTCOME MEASURES: The primary outcome was the predictive ability of NICHD features and non-NICHD deceleration measures for fetal acidemia. The secondary outcome was the impact of deceleration area in the last 30 min of labor on gasometry components (pH, BD and lactate). RESULTS: Minimal variability (area under the curve (AUC) 0.74), total number of late (AUC: 0.75) and prolonged decelerations (0.77) were the three NICHD features with the greatest predictive ability for fetal acidemia in the last thirty minutes of labor. Total deceleration area demonstrated the highest discrimination power (AUC: 0.83) of all the analyzed elements. For each cm2 the area increases in the last 30 min of labor, pH decreases 0.08 units, BD increases 0.272 mEq/L and lactate 0.183 mEq/L. CONCLUSIONS: Total deceleration area showed the greatest predictive ability for fetal acidemia and its measure could help to estimate intrapartum fetal acid-base status.

Atypical decelerations: do they matter?

OBJECTIVE: To estimate the association between atypical variable decelerations and neonatal acidemia. METHOD: We conducted a one-year case-control study comparing the last thirty minutes before delivery of fetal heart rate tracings of 102 acidemic neonates (umbilical arterial cord gas pH ≤ 7.10) with 100 non-acidemic controls (umbilical arterial cord gas pH > 7.10). Incidence of atypical features and total number of decelerations, number of atypical decelerations, number of slow return decelerations and number of decelerations with loss of moderate variability during deceleration were extracted. We estimated the association between atypical features, neonatal acidemia and neonatal morbidity. RESULTS: Acidemic neonates showed a larger number of atypical decelerations (4 [0-12] vs. 3 [0-10]), "slow return" decelerations (4 [0-11] vs. 1 [0-10]) and decelerations with non-moderate variability (0[0-12] vs. 0 [0-6]) compared to non-acidemic controls. "Slow return" was significantly associated with an increased risk of acidemia at birth (OR 4.46; CI 95%: 2.18 - 9.15) "Slow return" was the most discriminating feature between groups with an AUC: 0.745. CONCLUSION: Certain atypical features, as "slow return" and loss of moderate variability within decelerations are associated with neonatal acidemia. "Slow return" could help in the gradation of acidemia risk levels, as an indicator of gravity.