Roy Z. Mansano

Measures of acidosis with repetitive umbilical cord occlusions leading to fetal asphyxia in the near-term ovine fetus

OBJECTIVE Increasing frequency of severe variable decelerations is associated with acidemia. However, there is little understanding of its development or normalization rate. STUDY DESIGN To quantify the time course of acidemia, 10 near-term fetal sheep underwent a series of mild (1 minute every 5 minutes), moderate (1 minute every 3 minutes), and severe (1 minute every 2 minutes) umbilical cord occlusions (UCO), lasting 1 hour each or until fetal arterial pH decreased to less than 7.00. RESULTS Each minute of UCO resulted in base deficit (BD) and lactate increases at rates of 0.56 and 0.35 mmol/L per minute, respectively. During a 2 h recovery, BD and lactate normalized at rates of 0.09 and 0.04 mmol/L per minute. BD correlated highly with lactate (r = 0.95; P < .001). CONCLUSION Our findings in the near-term ovine fetus suggest that the knowledge of fetal BD deterioration and recovery rates can aid assessing fetal acidemia during labor.

GDNF and MAPK–ERK pathway signaling is reduced during nephrogenesis following maternal under-nutrition

Maternal under-nutrition (MUN) during gestation results in growth-restricted newborns with reduced glomerular number and subsequent hypertension. We investigated dysregulation of glial derived neurotrophic factor (GDNF) and MAPK-ERK (mitogen-activated protein kinase-extracellular signal-regulated protein kinase) signal pathway gene expression following MUN. MUN rats were 50% food restricted from embryonic day 10 till postnatal day 1. Kidneys were harvested at embryonic day (E)20, and postnatal days (P)1 and 21. Kidney protein expression was determined by Western blot. At E20, protein expression of growth factor receptor alpha 1 (GFRα1) and phosphorylated ERK1/2 and mitogen-activated protein kinase kinase (MEK)1/2 were reduced significantly, and immunohistochemistry confirmed reduction of phosphorylated ERK (pERK) with maintenance of pERK localization. Total MEK and ERK were unchanged. At P1, only GFRα1 and pERK1/2 were reduced significantly while at P21, expression of all growth factors except total MEK was unchanged. Total MEK was increased. Glomerular number was decreased by 19% in P21 kidneys and blood pressure was increased in 12-week-old rats. In conclusion, GDNF and MAPK-ERK signaling are dysregulated during active nephrogenesis in fetal and early newborn offspring kidneys in the MUN model. This may be a key mechanism in reduced offspring nephrogenesis and programmed hypertension.

Fetal ST segment heart rate analysis in labor: Improvement of intervention criteria using interpolated base deficit

Objective. The addition of ST waveform analysis (STAN, Neoventa, Sweden) to fetal heart rate (FHR) tracings has been demonstrated to improve fetal outcome and reduce operative delivery rates, though the actual level of fetal acidosis at which STAN indicates intervention has not been assessed. We sought to determine if FHR ST segment analysis recommends intervention at appropriate levels of fetal acidosis. Methods. FHR tracings of 10 acidotic and 10 non-acidotic infants with FHR tracings having a minimum of one STAN flag were retrospectively analyzed. Fetal base deficit (BD) was calculated by interpolation throughout the FHR tracing and STAN ‘action’ and ‘ignore’ flags assigned a fetal BD value. A secondary analysis was performed with a revised interpretation of FHR reassuring status. Results. The mean (±SD) BD of the first STAN action was significantly greater than the first ‘ignore’ (4.0 ± 2.1 vs. 3.0 ± 0.8 mmol/L, p < 0.05). Clarified STAN criteria for reassuring vs. non-reassuring FHR resulted in a first action BD of 6.0 ± 2.0 mmol/L with 90% sensitivity and 100% specificity for prediction of fetal acidosis. Conclusion. The STAN monitor discriminates increasing levels of fetal BD. With clarification of the criteria for reassuring FHR, the calculated BDs of action flags are an appropriate threshold for emergent intervention, successfully predict acidotic fetuses, and avoid unnecessary intervention.