**5.1 Patient's body position**

Khatib et al. analyzed changes in vascular flow in the fetal circulation when changing the left lateral to supine position in pregnant women in the third trimester. Test time was approximately fifteen minutes. The authors noted a statistically significant decrease in the value of the pulsation index in the middle cerebral and umbilical artery, as well as a decrease in the maximum systolic velocity of the middle cerebral artery and the systolic-diastolic index of the umbilical artery [19]. It is most likely related to the symptom of brain sparring of the fetal circulation. As can be seen from the above studies, the mechanisms of circulatory centralization are not only activated by the pathological condition, but also by a stressful situation for the fetus, such as changing the position from a comfortable left-lateral or vertical position to a supine position, limiting the correct placental-fetal flow. The mechanism of fetal circulation centralization protects the fetus in a situation of persistent limited blood flow. Vascular resistance in the cerebral circulation is reduced, which allows blood flow to the brain to be increased.

Katwijk and Wladimiroff analyzed changes in the value of flows in the umbilical artery when the body position changes. When changing the patient's body position from vertical to lying, they noted an increase in the umbilical artery pulsation and resistance index, regardless of the gestational age, and this is explained by the flow mechanism of a lock [20].

Kinsella et al. in the group of twenty pregnant women in the third trimester did not observe any changes in the flow in the fetal umbilical artery when the patient's body position was changed [21].

Similarly, Armstrong et al. in the group of twenty-five full-term pregnant women qualified for elective cesarean section did not observe changes in vascular flow depending on the different positions of the patient's body. The authors assume that the degree of compression of the inferior vena cava and aorta in different body positions is not significant enough to disturb the vascular flow in the umbilical artery, or that these changes are so subtle that Doppler devices are unable to capture them [22].

Marx et al. monitored the vascular flow in the umbilical cord in various body positions in the early stage of labor. The systolic-diastolic index of the umbilical artery was significantly higher in the supine position compared to the left-lateral position of the patient, which in turn led to an increase in vascular resistance in the umbilical artery [23].

Inferior vena cava syndrome most often occurs in the third trimester of pregnancy, when a large weight of the pregnant uterus presses on the inferior vena cava, especially in the supine position, which disturbs the maternal-fetal flow and may lead to fainting, and consequently the fetus to hypoxia. Ryo et al. undertook studies to determine the risk of inferior vena cava syndrome in the second trimester of pregnancy and its consequences for the fetus. In a group of ninety Japanese pregnant women between the twenty-fourth and twenty-seventh weeks of pregnancy, they assessed umbilical artery flow and its relationship with uteroplacental flow.

There were no changes in the umbilical artery resistance index during the fiveminute supine position of the patient [24].

In a study by Qu et al. on a group of fifty pregnant women between the twentyseventh and forty weeks of gestation, no changes in the umbilical artery flow values were found when the patient's body position was changed [25], similarly to Backe et al. [26], while Sorensen et al. did not report changes in the systolic-diastolic index in patients with normal blood pressure [27].

Kinsella et al. and Witter and Besinger did not find statistically significant changes in uterine artery flows depending on the patient's body position and the duration of the study [21, 28].

In the group between thirty-seven and forty weeks of pregnancy, Qu et al. observed a statistically significant increase in the resistance index in the uterine arteries after changing the position of the pregnant woman [25].

Sohn et al. proved that uterine flow clearly decreases in the sitting and standing position of the pregnant woman, which is associated with an increase in vascular resistance. In the conclusions, the authors emphasize that apart from uterine contractions, there are also other factors influencing uterine flow, which may be important in the monitoring of fetuses with limited growth rate [29]. In another work, the author presents the concept of selecting a safe position of the patient's body based on the results of measurements of vascular flows in the maternalplacental circulation [30]. Similar conclusions were presented by Easterling et al. in each trimester of pregnancy [31], as well as by Ryo et al. [24].

#### **5.2 The influence of tocolytics on vascular flows**

In the study by Bednarek et al. on the safety of tocolytic medications in preterm labor, mean values of vascular flow measurements before the initiation of therapy that inhibits premature uterine contraction and at least one day after their initiation, subjected to statistical analysis, did not show significant changes in most of the parameters studied. The changes mainly concerned the systolic-diastolic index in the umbilical artery, where its decrease was noted, the peak systolic velocity in the middle cerebral artery increased, and the pulsation index decreased. The patients' therapy mainly included nifedipine. The lack of statistically significant changes in the value of vascular flows may indirectly confirm the safety of this medication and the lack of negative impact on the well-being of the mother and the fetus. No patients experienced life-threatening or health-threatening symptoms, and the reported side effects were mainly periodic headache during the first day of therapy and transient reddening of the skin. There was no significant decrease in blood pressure in patients undergoing treatment. This significantly increases the benefits associated with the use of this therapy, especially in relation to therapy with beta-mimetics, especially fenoterol.

Cornette et al. analyzed the effect of nifedipine on the values of vascular flow in the cerebral and placental-fetal circulation. They found no statistically significant changes in the vascular flow of the fetal middle cerebral artery, umbilical cord, uterine arteries and ductus venous. The study was conducted in pregnant women between the thirty-fifth and thirty-seventh week of gestation in a group of fifteen healthy pregnant women, after administering 20 milligrams of nifedipine orally and assessing vascular flow one hour after dosing. The authors emphasize the mechanisms counteracting the disturbance of the uterine circulation despite the significant reduction of maternal afterload under the influence of nifedipine, which means that in healthy pregnant women with normal arterial pressure, trophoblast invasion lowers uterine vascular resistance to such an extent that administration of nifedipine, which has the ability to lower peripheral vascular resistance, is no longer

#### *Haemodynamic Changes during Preterm Birth Treatment DOI: http://dx.doi.org/10.5772/intechopen.96923*

able to lower uterine resistance. Adverse effects of nifedipine have been reported in the situation of significantly lowered blood pressure in pregnant women, therefore it is important that the use of this medication as an inhibitor of uterine contractions ought to be considered only in pregnant women with normal blood pressure [32].

The study by Lima et al. was based on the administration of nifedipine in a dose of 20 milligrams sublingually every twenty minutes to a pregnant woman with uterine contraction, until the activity subsided. Thereafter, 20 milligrams of nifedipine was orally administered every six hours, until a total dose of 120 milligrams per day. Vascular flow in the fetal and maternal circulation was assessed before the initiation of nifedipine, five and twenty-four hours after the initiation of the therapy. Five and twenty-four hours after the initiation of the therapy, there was no change in the resistance index from pre-treatment measurements, while a decrease in the resistance index in the fetal central artery was observed between five and twenty-four hours after the initiation of the therapy.

The value of the peak systolic velocity of the middle cerebral artery was also analyzed. In the Lima study, there was a decrease after five hours, while comparing the measurements before and 24 hours after starting the treatment, no statistically significant changes were noted [33]. In the study by Bednarek et al., the peak systolic velocity of the middle cerebral artery increased statistically significantly after the initiation of the therapy. It is noteworthy, however, that the measurements were made at least twelve hours after the initiation of the therapy. Similarly, Grzesiak et al. reported a decrease in the peak systolic velocity in the middle cerebral artery, with no changes in the remaining parameters during the day after the initiation of oral nifedipine therapy [34].

The special structure of the fetal uteroplacental, umbilical and cerebral circulation ensures constant vascular flow independent of the heart cycle. This system gradually develops in the utero-fetal circulation. A significant effect of this phenomenon consists not only in the gradual increase in the velocity of the enddiastolic flow wave, but also in the accompanying decrease in the pulsation index, which is the difference between the components of the maximum systolic velocity and the end-diastolic velocity [33].

Similarly, Guglu et al. observed a decrease in the pulse index of the central cerebral artery one day after the initiation of nifedipine therapy. The authors note that nifedipine reduces blood pressure while keeping the maternal heart rate unchanged. Moreover, they acknowledged a decrease in resistance in the uterine circulation. The mechanism of increased resistance in the umbilical artery with an accompanying decrease in the pulse index in the central artery of the brain prevents diastolic changes in the fetal heart [35, 36]. It is noteworthy that the maternal-fetal circulation has mechanisms that protect the fetus against changes in flow that may be a real threat to its well-being.

Beta-memetic therapy is now used much less frequently in suppressing preterm labor. Despite the lack of obvious adverse effects on vascular flow in the fetal circulation, side effects in the mother are significant enough to minimize this method of treatment [37–39]. In a study with ritodrine, an increase in the pulse index in the middle artery of the fetal brain was noted, with a decrease in the pulse index in the umbilical artery [40]. Friedman et al. claim that therapy with ritodrine does not increase the resistance to placental circulation, does not lead to fetal hypoxia, changes in the fetal heart rate or preload on the fetal heart, but shortens the systolic fraction of the heart, which may lead to an increase in vascular resistance in the fetal circulation or reduce contractility of the heart muscle [41, 42]. Similarly, terbutaline increases vascular flow through the fetal heart, thus increasing its load [43]. Beta-agonist therapy should be limited as much as possible due to the side effects of these medications on both the mother and the fetus.

Oxytocin receptor blockers are a new class of tocolytic drugs. The oxytocin antagonist atosiban has less side effects than beta-agonists [44]. Atosiban crosses the placenta. Drug concentrations in the fetal circulation do not increase with longer infusion rates, suggesting that the drug does not accumulate in the fetus. Atosiban has the best maternal and fetal safety profile; however, its costs are considerable. Maternal heart rate and blood flow in (R-UtA/L-UtA) were not altered significantly during atosiban administration. No significant changes in FHR as well as Doppler parameters (resistance index, pulsality index, peak systolic velocity) in umbilical artery and middle cerebral artery were recorded after 24/48 hours of tocolytic treatment. The mean values of cerebroplacental ratio (CPR) remained unaltered during treatment. Detailed evaluation of fetal cardiac function parameters (E/A, SF, MPI) calculated independently for both ventricles, revealed no significant changes over the time [45].

Tocolytic treatment with atosiban is associated with elevation of oxidative stress markers after a 48 hours administration. This effect of atosiban may reduce its potency as a tocolytic agent and therefore should be considered with respect to its clinical use, especially because of its connection with the occurrence of premature birth [46].

Indomethacin used as a substance inhibiting premature uterine contractile activity does not negatively affect the cerebral flow in the fetus, however, it should be remembered that long-term therapy with non-steroidal anti-inflammatory medications may lead to blood flow disorders in the arterial duct [47, 48].

Intravenous magnesium sulfate is also allowed in the treatment of preterm labor. Keeley et al. analyzed the effect of this medication on vascular flow and found a decrease in the flow velocity in the fetal middle cerebral artery and an increase in flow velocity in the uterine arteries. There were no disturbances in the flow in the umbilical artery. During the study, the blood circulation was normalized, which the authors associate with the beneficial effects of magnesium sulphate also on the fetus and the tocolytic effect [49]. This is also confirmed by the studies of Pezzati et al., who assessed the fetal and neonatal circulation in the first hours of life of children in the therapy of magnesium sulphate and ritodrine [50].

When analyzing the safety of tocolytic medications, it should be remembered that in most patients, steroid therapy is started parallel to stimulate the fetal respiratory system. In the study by Bednarek et al. no significant haemodynamic changes were found after steroid therapy, however, other authors observed a transient decrease in the pulse index of the fetal middle cerebral artery [51, 52]. It cannot be ruled out that these differences result from the different tocolitics analyzed. Corticosteroids administered to the mother to stimulate the maturation of the fetal lungs in the event of impending preterm labor may temporarily "improve" the flow waves. In such a situation, it is reasonable to repeat the Doppler examination approximately 48 hours after administration [34].

Brar et al. reported lower efficacy of tocolysis in patients with abnormal flows in the maternal-fetal circulation before the therapy, which increases the risk of preterm labor [53].

Summing up, it should be emphasized that drugs inhibiting uterine contractions do not have a significant, long-term and permanent effect on the vascular flow of the maternal-fetal circulation. When considering the efficacy of tocolysis, other factors disrupting normal vascular flow should be taken into account, which may reduce the effectiveness of tocolytic drugs and increase the risk of preterm labor.

#### **5.3 Preterm labor ended with cesarean section**

Nakayi et al. analyzed the vascular flow of the uterine arteries on the third, sixth and ninth day after cesarean section. They found no significant changes in the resistance index in these vessels [54].

The assessment of uterine artery flow seems to be useful in vaginal bleeding in puerperal patients after cesarean section, as one of the complications of this operation may be rupture of the intraoperatively developed pseudoaneurysm of the uterine artery [55].
