How often should the mothers blood pressure and pulse rate be checked during oxytocin infusion?

Oxytocin intravenous infusion is the most commonly used method. With the improvement of monitoring methods, oxytocin intravenous infusion has become very safe. Oxytocin is a common means to promote uterine contraction and accelerate the progress of labor. Oxytocin is a short-acting drug, which needs continuous intravenous drip to maintain the effect of uterine contraction. Oxytocin itself has no adverse effect on the fetus, but it will produce uterine contraction after use. Excessive uterine contraction may lead to abnormal blood supply of the fetal placenta and fetal hypoxia. Therefore, it is necessary to take care with the injection, and to observe the fetal heart rate and uterine contraction. In case of abnormal fetal heart rate, oxytocin should be stopped immediately.

Oxytocin is an ancient neuropeptide and is a kind of contractile agent that can selectively excite the smooth muscle of the uterus and stimulate its contraction [1], [2], [3]. Studies have shown that normal use of oxytocin seems to be effective in speeding labor and reducing blood loss [4]. However, the use of too much oxytocin and an injection speed that is too fast will cause spasmodic uterine contraction; a narrow birth canal and large fetus can lead to the continuous contraction of the uterus, which affects the decline of the fetus and is likely to cause fetal hypoxia or neonatal asphyxia [5]. Therefore, there are still many uncertain factors in the process of oxytocin injection. In clinics, the main manners of fetal intrauterine monitoring are B-mode ultrasonic examination and fetal heart rate monitoring. However, ultrasound examination can only monitor the contour of the fetus, and an ECG can only monitor whether the fetus has significant abnormalities. Neither measure can directly judge the subtler effects on the nervous system or behavior of the fetus in the process of oxytocin injection. Simpson and James [6] observed the effect of uterine hyperstimulation on fetal oxygen status and FHR patterns when using oxytocin to induce labor. The more uterine contractions in 30 min caused by oxytocin injection, the more obvious the negative effect on fetal status. As few studies examined oxytocin in humans across pregnancy and the postpartum, Levine et al. [7] followed healthy women at first trimester of pregnancy, third trimester, and first postpartum month. The increase in oxytocin from early to late pregnancy correlated with higher maternal-fetal bonding. These data may help set standards for oxytocin levels and underscore links with maternal-infant attachment. McNamara and Johnson [8] found that FSpO2 decreased during uterine contraction and reached the lowest level 92 seconds after contraction reached its peak. It took about 90 seconds for FSpO2 to return to the previous level when they investigated the changes of fetal arterial oxygen saturation during uterine contraction. They monitored 18 women in normal labor with a fetal scalp surface pulse oximetry sensor, intrauterine pressure catheter, and head-to-cervix force transducer, and concluded that uterine contraction during normal delivery affects fetal oxygen saturation.

In addition, there are some studies on oxytocin injection for animals. For instance, Alonso-Spilsbury et al. [9] explored the use of oxytocin in penned sows and its effect on fetal intra-partum asphyxia, the authors found the treatment with oxytocin reduced the duration of the expulsion of the fetus, increased the number of IPS with ruptured umbilical cords and with severe meconium-stain degree and reduced the number of fetuses with inspiration attempts. Tyzio et al. [10] repored a signaling mechanism in rats between mother and fetus aimed at preparing fetal neurons for delivery, and maternal oxytocin inhibits fetal neurons and increases their resistance to insults during delivery.

In the latest behavioral and epigenetic studies on oxytocin therapy, the socially monogamous prairie voles were used to examine the hypothesis that oxytocin exposure at birth can have long-term developmental consequences in Kenkel et al. [11], and cross-fostering showed that long-term effects of perinatal oxytocin may be mediated by an epigenetic mechanism. Besides, when combining spinal-epidural analgesia, Yang et al. [12] found that uterine hypertonus and fetal bradycardia occurred in the oxytocin induction of labor. Szczepanska-Sadowska et al. [13] discussed the regulation of the secretion of oxytocin in and expression of their receptors in the pregnant mother and child, and the direct and indirect effects of oxytocin on the cardiovascular system in the healthy mother and fetus. Their survey idicated that moderate stimulation of the oxytocin played a beneficial role in the healthy pregnant mother and fetus, however, under pathophysiological conditions the inappropriate action of these hormones exerts several negative effects on the cardiovascular system of the mother and progeny, and may potentially contribute to the pathophysiology of heart failure in early life.

However, most of these researches on oxytocin injection are analyzed from the perspective of medical experiments, and there are few researches on mathematical medical models. We intend to study the nonlinear dynamics of fetal ECG sequence from a mathematical perspective, and then analyze the effect of oxytocin injection on fetal cardiovascular system function through multifractal exponents. In this study, multifractal detrended fluctuation analysis (MF-DFA) is utilized. MF-DFA has been a significant and popular tool to analyze chaotic dynamics and nonlinear signals [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26]. It was demonstrated that the circadian rhythm on cardiac dynamics does not affect the endogenous circadian rhythm of human motor activity [27]. Li et al. [28] used MF-DFA to analyze human heart rate variability during exercise, which can provide useful information for athletes to choose the best time to engage in sports and accelerates the development of sports medicine. Recently, Castiglioni et al. [29] proposed a fast algorithm for multifractal analysis of physiological time series. MF-DFA was a useful nonlinear analysis method for the ECG signals of special groups such as maternal and normal sinus women [30]. Multifractality analysis can explain abnormal heart rate behavior under various pathological conditions. However, it is not obvious for the traditional linear and nonlinear heart rate variability techniques. The multifractal method has advantages in differentiating healthy subjects from patients with coronary artery disease or congestive heart failure [31].

In our research, we selected 20 healthy young parturient women aged 20 to 40 years with normal singleton fetuses in full-term pregnancy as research subjects. The multifractal detrended fluctuation analysis of FHR variability was carried out before and during oxytocin injection during labor. The selected data are the FHR signal sequences within 2 h before and during oxytocin injection.

The rest of this paper is organized as follows. We introduce the research method in Section 2. The empirical analysis is presented in Section 3. Section 4 concludes the paper.

Participants

We selected 20 experimental subjects consisting of healthy young parturient women, of age 20 to 40 years, with normal singleton fetuses in full-term pregnancy; they were numbered from 1 to 20. From standard obstetric observation, all of the maternals had no diabetes mellitus, smoking experience, hypertension, administration of cardiovascular effective drugs, or cardiovascular diseases. The exclusion criteria of fetal anomalies included fetal arrhythmia, intrauterine growth restriction, previous

Experiment results

All the calculations in this paper are computed by using Matlab R2018a on an Intel(R) Core(TM) i5-4430 CPU @ 3.00 GHz processor.

Discussions and conclusions

We explored the effect of oxytocin injection on the fetal heart rate from a mathematical perspective. We studied the long-range power-law correlation of the non-stationary time series by analyzing the biological time signals, to examine whether oxytocin injection can affect the autonomic nervous system of the fetus. Multifractal analysis is an effective nonlinear analysis method that is appropriate for the detailed analysis of FHR signals. We applied the MF-DFA technique to present the

CRediT authorship contribution statement

Jian Wang: Methodology, Writing - original draft. Junseok Kim: Data curation, Writing - review & editing. Wei Shao: Writing - review & editing. SeungHyun Nam: Writing - review & editing. Soon-Cheol Hong: Supervision, Writing - review & editing.

Declaration of Competing Interest

Authors declare that they have no conflict of interest.

Acknowledgments

The first author Jian Wang expresses thanks for The Startup Foundation for Introducing Talent of NUIST. The corresponding author(Soon-Cheol Hong) was supported by Institute of Information & Communications Technology Planning & Evaluation (IITP) grant funded by the Korea government (MSIT) (2020-0-00423, Development of Fetal Abnormal Condition Analysis Too Based on FHR/TOCO Data Using Deep Learing ).

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