Pathophysiological interpretation of fetal heart rate tracings in clinical practice.

The onset of regular, strong, and progressive uterine contractions may result in both mechanical (compression of the fetal head and/or umbilical cord) and hypoxic (repetitive and sustained compression of the umbilical cord or reduction in uteroplacental oxygenation) stresses to a human fetus. Most fetuses are able to mount effective compensatory responses to avoid hypoxic-ischemic encephalopathy and perinatal death secondary to the onset of anaerobic metabolism within the myocardium, culminating in myocardial lactic acidosis. In addition, the presence of fetal hemoglobin, which has a higher affinity for oxygen even at low partial pressures of oxygen than the adult hemoglobin, especially increased amounts of fetal hemoglobin (ie, 180-220 g/L in fetuses vs 110-140 g/L in adults), helps the fetus to withstand hypoxic stresses during labor. Different national and international guidelines are currently being used for intrapartum fetal heart rate interpretation. These traditional classification systems for fetal heart rate interpretation during labor are based on grouping certain features of fetal heart rate (ie, baseline fetal heart rate, baseline variability, accelerations, and decelerations) into different categories (eg, category I, II, and III tracings, "normal, suspicious, and pathologic" or "normal, intermediary, and abnormal"). These guidelines differ from each other because of the features included within different categories and because of their arbitrary time limits stipulated for each feature to warrant an obstetrical intervention. This approach fails to individualize care because the "ranges of normality" for stipulated parameters apply to the population of human fetuses and not to the individual fetus in question. Moreover, different fetuses have different reserves and compensatory responses and different intrauterine environments (presence of meconium staining of amniotic fluid, intrauterine inflammation, and the nature of uterine activity). Pathophysiological interpretation of fetal heart rate tracing is based on the application of the knowledge of fetal responses to intrapartum mechanical and/or hypoxic stress in clinical practice. Both experimental animal studies and observational human studies suggest that, just like adults undertaking a treadmill exercise, human fetuses show predictable compensatory responses to a progressively evolving intrapartum hypoxic stress. These responses include the onset of decelerations to reduce myocardial workload and preserve aerobic metabolism, loss of accelerations to abolish nonessential somatic body movements, and catecholamine-mediated increases in the baseline fetal heart rate and effective redistribution and centralization to protect the fetal central organs (ie, the heart, brain, and adrenal glands), which are essential for intrauterine survival. Moreover, it is essential to incorporate the clinical context (progress of labor, fetal size and reserves, presence of meconium staining of amniotic fluid and intrauterine inflammation, and fetal anemia) and understand the features suggestive of fetal compromise in nonhypoxic pathways (eg, chorioamnionitis and fetomaternal hemorrhage). It is important to appreciate that the timely recognition of the speed of onset of intrapartum hypoxia (ie, acute, subacute, and gradually evolving) and preexisting uteroplacental insufficiency (ie, chronic hypoxia) on fetal heart rate tracing is crucial to improve perinatal outcomes.

Optimizing the management of acute, prolonged decelerations and fetal bradycardia based on the understanding of fetal pathophysiology.

Any acute and profound reduction in fetal oxygenation increases the risk of anaerobic metabolism in the fetal myocardium and, hence, the risk of lactic acidosis. On the contrary, in a gradually evolving hypoxic stress, there is sufficient time to mount a catecholamine-mediated increase in the fetal heart rate to increase the cardiac output and redistribute oxygenated blood to maintain an aerobic metabolism in the fetal central organs. When the hypoxic stress is sudden, profound, and sustained, it is not possible to continue to maintain central organ perfusion by peripheral vasoconstriction and centralization. In case of acute deprivation of oxygen, the immediate chemoreflex response via the vagus nerve helps reduce fetal myocardial workload by a sudden drop of the baseline fetal heart rate. If this drop in the fetal heart rate continues for >2 minutes (American College of Obstetricians and Gynecologists' guideline) or 3 minutes (National Institute for Health and Care Excellence or physiological guideline), it is termed a prolonged deceleration, which occurs because of myocardial hypoxia, after the initial chemoreflex. The revised International Federation of Gynecology and Obstetrics guideline (2015) considers the prolonged deceleration to be a "pathologic" feature after 5 minutes. Acute intrapartum accidents (placental abruption, umbilical cord prolapse, and uterine rupture) should be excluded immediately, and if they are present, an urgent birth should be accomplished. If a reversible cause is found (maternal hypotension, uterine hypertonus or hyperstimulation, and sustained umbilical cord compression), immediate conservative measures (also called intrauterine fetal resuscitation) should be undertaken to reverse the underlying cause. In reversible causes of acute hypoxia, if the fetal heart rate variability is normal before the onset of deceleration, and normal within the first 3 minutes of the prolonged deceleration, then there is an increased likelihood of recovery of the fetal heart rate to its antecedent baseline within 9 minutes with the reversal of the underlying cause of acute and profound reduction in fetal oxygenation. The continuation of the prolonged deceleration for >10 minutes is termed "terminal bradycardia," and this increases the risk of hypoxic-ischemic injury to the deep gray matter of the brain (the thalami and the basal ganglia), predisposing to dyskinetic cerebral palsy. Therefore, any acute fetal hypoxia, which manifests as a prolonged deceleration on the fetal heart rate tracing, should be considered an intrapartum emergency requiring an immediate intervention to optimize perinatal outcome. In uterine hypertonus or hyperstimulation, if the prolonged deceleration persists despite stopping the uterotonic agent, then acute tocolysis is recommended to rapidly restore fetal oxygenation. Regular clinical audit of the management of acute hypoxia, including the "the onset of bradycardia to delivery interval," may help identify organizational and system issues, which may contribute to poor perinatal outcomes.

Physiological CTG interpretation: the significance of baseline fetal heart rate changes after the onset of decelerations and associated perinatal outcomes.

OBJECTIVE: To determine the perinatal outcomes in fetuses with baseline fetal heart rate changes with preceding decelerations on the cardiotocography (CTG) trace, and to interpret CTG traces from the aspect of fetal physiology. MATERIALS AND METHODS: A retrospective analysis of 500 consecutive CTG traces was carried out. The presence of repetitive variable and late decelerations followed by the changes in the baseline including baseline tachycardia and abnormal baseline variability were determined. Perinatal outcomes including Apgar scores and umbilical arterial pH at birth, NNU admission, and meconium-stained amniotic fluid were analyzed. We interpreted the changes in CTG based on fetal physiology. RESULTS: When repetitive variable and late decelerations were present without tachycardia (n = 81), none of the fetuses had an Apgar score <7 at 5 minutes or an umbilical cord pH <7. After the onset of fetal tachycardia (n = 262), fetuses showed decreased Apgar scores and umbilical arterial pH(p < .01), however, there was no significant difference in the rate of abnormal 5 min Apgar score, abnormal PH and NNU admission, if the baseline variability remained normal. However, if the baseline variability was abnormal (n = 44), (either increased or reduced) after tachycardia, there was a statistically significant increase in poor perinatal outcomes. Fetuses with abnormal versus normal variability had lower Apgar scores ≤7 at 5 min (29.6 versus 0.9%, p = .000); umbilical cord arterial pH <7 at birth (29.5 versus 0%, p = .000); increased admission to the NNU (27.3 versus 3.7%, p = .000) and increased incidence of meconium-stained amniotic fluid (38.6 versus 22.5%, p = .024). These serial changes in CTG could be interpreted and predicted by the application of fetal physiology. CONCLUSIONS: There were significant differences in perinatal outcomes when fetuses were exposed to evolving intrapartum hypoxic stress culminating in an abnormal baseline fetal heart rate variability, which was preceded by repetitive decelerations, followed by an increase in the baseline heart rate. However, despite ongoing decelerations, if the baseline variability remained normal, none of the fetuses had a pH of <7. Therefore, the knowledge of fetal physiological response to evolving hypoxic stress can be reliably used to determine fetal compensation.

Plasma microRNA-16-5p, -17-5p and -20a-5p: Novel diagnostic biomarkers for gestational diabetes mellitus.

AIM: To explore whether plasma microRNA-16-5p, -17-5p and -20a-5p can be used as diagnostic biomarkers in gestational diabetes mellitus (GDM) and to investigate the relationship between those microRNAs and the risk factors of GDM (body mass index [BMI], insulin resistance [IR] and tumor necrosis factor-α (TNF-α)). METHODS: A total of 85 pregnant women with GDM and 72 pregnant women without GDM were enrolled in this study. The plasma concentration of microRNAs (microRNA-16-5p, -17-5p, -19a-3p, -19b-3p, -20a-5p) was measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Spearman's correlation analysis was used to evaluate the correlation between those microRNAs and the risk factors of GDM, and receiver operating characteristic curve analysis was used to evaluate diagnostic sensitivity and specificity. RESULTS: Compared with non-GDM women, the relative and absolute expression of plasma microRNA-16-5p, -17-5p, -20a-5p from GDM women were significantly upregulated, when those women were diagnosed as GDM. During pregnancy, the expression of those microRNAs from GDM women also were significantly upregulated. The expression of those microRNAs was also positively correlated with IR, a risk factor of GDM. Plasma microRNA-16-5p, -17-5p, -20a-5p reflected an obvious separation between GDM women and non-GDM women, with areas under the curve of 0.92 (95%CI: 0.871-0.984), 0.88 (95%CI: 0.798-0.962), and 0.74 (95%CI: 0.618-0.870), respectively, cut-offs >2554, 1820, 3886 copies/µL, respectively; sensitivity 41.6%, 21.4% and 17.8%, respectively; and specificity 95.8%, 95.4% and 95.4%, respectively. CONCLUSION: Plasma microRNA-16-5p, -17-5p and -20a-5p are potential diagnostic biomarkers in GDM.