The study protocol was approved by the Bioethics Committee of the Kharkiv Medical Academy of Postgraduate Education. The eligible participants were informed about the study’s methodology, its aims, objectives, indications and eventual complications before enrollment. Patients from the department of maternal-fetal medicine were selected randomly. All the patients who met the inclusion criteria gave written informed consent to participate [15]. The inclusion criteria: diagnosed PE based on the blood pressure higher than 140/90 mmHg in two separate occasions 6 h apart, a positive proteinuria test in two mild-stream urine samples collected 4 h apart. The exclusion criteria: multiple pregnancy, eclampsia, pre-existing medical disorders like diabetes mellitus, metabolic syndrome, cardiac diseases, renal disease, thyrotoxycosis and chronic hypertension. If blood pressure was 140 to 159 mmHg systolic and 90 to 109 mmHg the patient was included in mild-moderate PE Group. Severe PE was diagnosed in case of blood pressure was higher 160 mmHg systolic and 110 mmHg diastolic or (and) thrombocytopenia, serum creatinine more than 1.1 mg/L, elevated blood concentration of liver transaminases to twice normal concentration, pulmonary oedema, cerebral or visual disturbances. The patients who had no gestational complications and medical disorders including chronic infections and tobacco smoking were enrolled in the control Group. All patients included in the study were inhabitants of Eastern Ukraine. The study was conducted from January 2013 to October 2015.
One hundred six patients at 34–40 weeks of gestation were enrolled. 30 of them had healthy pregnancy and were included into the Group I (control). In Group II, 44 pregnant women with mild-moderate PE were observed. 32 patients with severe PE were monitored in Group III.
All examined pre-eclamptic patients received antihypertensive drugs. The choice of antihypertensive agent was made according to the type of central maternal hemodynamics (CMH) determined by bio-impedance cardiography. It was estimated the values of cardiac index (CI) and total peripheral vascular resistance (TPVR). The hyperkinetic type of CMH was associated with high CI and low TPVR. The pre-eclamptic women with eukinetic type of CMH had high or normal CI and increased TPVR. And the pre-eclamptic patients with low CI and high TPVR had the hypokinetic type of CMH [3]. The pregnant women with hyperkinetic type of CMH took carvedilol 6.25–12.5 mg 2 times daily, in case of the eukinetic type – methyldopa 250–500 mg 4 times a day and in cases of the hypokinetic one – methyldopa 500 mg 4 times daily combined with nifedipine 20 mg 2 times daily.
The fetal and maternal HRV parameters were obtained with the fetal noninvasive computer electrocardiographic system “Cardiolab Baby Card” (Scientific Research Center “KhAI-Medica”, Ukraine). The Ukrainian ECG recordings were included in the Physio Net database [16]. The recording lasted for 10 min in the normal maternal sitting position. The values of total power (TP) and its spectral compounds, i.e. the very low frequency (VLF), the low frequency (LF), the high frequency (HF) and LF/HF ratio or sympatho-vagal balance, were determined. The temporal characteristics of the fetal HRV: the standard deviation of normal to normal intervals (SDNN), RMSSD, the proportion of the number of pairs of NNs differing by more than 50 ms divided by the total number of NNs (pNN50), the amplitude of mode (the most frequent value of NN interval or the highest column in the histogramm) – the number of NN intervals included in the pocket corresponding to the mode measured in percentages (%) (AMo) and the stress index – SI = AMo (%)/(2 × Mo × Var); Var = NNmax – NNmin; (SI) were calculated [17]. The fetal frequency bands of HRV were explored by David M. et al. [18]. The root mean square of successive heartbeat interval differences (RMSSD) was considered as a RSA-related parameter [14]. The level of RMSSD both in mother and fetus was investigated twice within the process of treatment in pre-eclamptic patients. The obtained fetal RR interval time series was transformed into cardiotocographic (CTG) tracing. The following CTG parameters were determined: short term variation (STV), long term variation (LTV) and the number of accelerations and decelerations.
The results thus obtained were analyzed with an ANOVA test to compare data between groups. The significance was set at p-value <0.05. For the statistical analysis of relationship between X and Y, the correlations coefficients were estimated with Spearman’s test. Microsoft Office 2010 Excel software was used for statistical analysis (Washington, USA).