The study was conducted to 32 patients who visited Emergency Room of Dr. Hasan Sadikin General Hospital Bandung during the period from December 2017 to February 2018. Two patients experienced a drop-out due to labor occuring less than 48 hours after receiving nifedipine therapy.
Majority of patients in this study were in the optimal reproductive age range of 20–34 years with 18 patients (60%), the remaining 6 patients (20%) aged < 20 years, and 6 patients (20%) belonged to the age > 34 years. Previous study reported that maternal age < 20 years is a risk factor for preterm labor. Likewise, maternal age > 35 years is also a risk factor for preterm labor because at the age > 35 years women are prone to suffer from degenerative diseases such as diabetes mellitus and hypertension during pregnancy.18,19 Yet, our study did not show similar results with these studies. The reason may be Dr. Hasan Sadikin General Hospital Bandung is a referral hospital, and therefore, the patients who refer to this hospital may represent the West Java population in general. Indeed West Java has a high population women with reproductive age, thus these subjects represent the West Java population that consists of pregnant women at optimal reproductive age.20
In this study 6 subjects (53.3%) were primigravida. This result was inline with a study in Egypt that found that primigravida was a risk factor for preterm labor. Primigravida increases the risk of preterm labor associated with young age at first pregnancy and lack of knowledge and awareness from mothers about the importance of good antenatal care.21,22
The highest incidence of preterm labor in this study occurred at gestational age > 32- < 37 weeks 18 subjects (60%) or the most at the age of late preterm. Consistent with previous finding, the majority of preterm deliveries in the United States occur in the late preterm period. In 2015, 71.4% of all preterm births (6.87% of all births) occurred in the late preterm period.23
Most patients were presented with BMI > 26–29 kg/m2 (15 subjects; 50%). Our result was compared to the standard set by Gustaaf Dekker et al. that stated a low BMI < 20 increases the risk of preterm labor (OR 2.1; 95% CI: 0.93–4.54). Previously a low BMI was associated with undernutrition, but now obesity is a low socioeconomic marker with excessive consumption of high-calorie foods but low levels of micronutrients.24
In this study 12 patients (40%) had anemia, this is in accordance with the data from WHO in 2016 that 42% of pregnant women in Indonesia was found with anemia. Anemia is known as an important risk for preterm labor, and poor labor outcomes.25,26
The number of subjects with history of prematurity was as many as 5 patients (16.7%), and only 1 subject (3.3%) had oligohydramnios. Our data is not supported by previous study that described a history of preterm labor or abortion increases the risk of preterm labor. History of prematurity may indicate increase risk, since factors such as abnormalities of uterus, or cervical incompetence can cause repeated preterm labor.27 Unlike in our study, other researchers found that oligohydramnios increased the risk for impending preterm delivery and intra-amniotic inflammation. Patients with oligohydramnios had a higher frequency of amniotic fluid infection and/or inflammation than those without oligohydramnios. The reason may be patients with oligohydramnios had a higher median amniotic fluid MMP-8 concentration than those without oligohydramnios. Moreover women with preterm labor associated with oligohydramnios had a shorter interval to delivery than those without oligohydramnios.28
Decreased PI of uterine arterial blood flow 48 hours after nifedipine therapy
Doppler examination of uterine arterial blood flow is one indicator of maternal blood flow that can be used as a reference for assessing uteroplacental flow. Interference to the uterine artery blood flow carries detrimental impact on the development of intrauterine fetus.29
Doppler blood flow resistance assessment can use various parameters such as PI, resistance index, systolic/diastolic ratio (S/D). However, in this study we used the PI parameter with the consideration that the PI has a minimum range of variation values, has the smallest error rate. Unlike SD ratio parameter, PI has defined value. Lastly the PI value is directly proportional to blood flow resistance.
Based on Table 4.3 the mean value PI of uterine artery before therapy was 0.79 ± 0.21 with a median of 0.70, whereas 48 hours after therapy the mean value of PI uterine artery was 0.70 ± 0.22 with a median of 0.68 that is statistically significant.
Nifedipine is a calcium channel blocker that works on the L- calcium channel that is found in all smooth muscle including the uterus and systemic vascular vessels. Nifedipine shows effect by blocking the entry of calcium ions into the cell so that calcium cannot pass through the voltage gate calcium channel (VGCC) / L-type calcium channel, so that calcium cannot bind to calmodulin. By not forming the calcium calmodulin complex, myosin light chain kinase (MLCK) cannot phosphorylate serine 19 in the regulatory light chain of myosin (MLC20) causing no crossbridge cycling, thus preventing cell contraction. In blood vessels this causes a vasodilation effect resulting in a decrease in vascular resistance. This is in line with what we found in this study that there was a significant decrease in uterine artery PI after 48 hours of nifedipine therapy. A decrease in uterine artery PI represents the vasodilation of uterine arteries, assuming that there is an increase in uterine artery blood flow so that it has a positive effect on uteroplacental blood flow.14,30
The same finding was obtained by previous study that administration of nifedipine in maintenance doses caused a decrease in uterine artery PI at earlier observation, 24 hours and als long as 48 hours of therapy.17,31
Decreased of UA PI 48 hours after nifedipine therapy
Based on Table 4.3, UA PI before nifedipine, the mean was 0.97 ± 0.31, whereas after 48 hours of nifedipine therapy the mean was 0.88 ± 0.15 with a significant decrease in UA blood flow after nifedipine therapy.
This proves that nifedipine can cross the placental barrier with a high ratio, and maternal administration of nifedipine will be followed by increased levels of nifedipine in fetal serum. In addition, this preparation has a direct effect on vascular structure and acts on receptors throughout the body, so that nifedipine can decrease UA PI.32
An umbilical arterial blood flow Doppler examination is one indicator of fetal blood flow that can provide an overview of intrauterine fetal conditions. Disrupted UA blood flow can cause fetal hypoxia and a unfavorable outcome on intrauterine fetal development. Changes in hemodynamics and intrauterine oxygenation will show initial efecet on UA blood flow.16,17 This finding contradicts with that by Guclu et al, that administration of nifedipine maintenance dose did not cause differences in UA PI after 24 hours and 48 hours of therapy.33
Changes in MCA PI blood flow before and after 48 hours after nifedipine therapy
From table 4.3 the mean MCA PI before therapy was 1.67 ± 0.48, while the average MCA PI after 48 hours of nifedipine therapy was 1.64 ± 0.50 without any statistical significant difference. So it can be explained that Doppler changes in fetal blood flow only affect the early fetal hemodynamic stage, which is UA blood flow. Applying nifedipine does not cause redistribution of blood flow to the cerebral.34
Changes in CPR PI blood flow before and after 48 hours after nifedipine therapy
The mean of CPR PI before therapy was 1.79 ± 0.54, while the mean of CPR PI after 48 hours of nifedipine therapy was 1.89 ± 0.58 without statistically significant. CPR is an important indicator that describes fetal well-being and as a predictor of fetal output. CPR can also describe the presence or absence of placental insufficiency. Based on these results it can be concluded that administration of nifedipine does not affect the welfare of the fetus, and does not cause any signs of placental insufficiency.34
DV PI changes in blood flow before and after 48 hours after nifedipine therapy
Table 4.3 showed the mean DV PI before therapy was 0.50 ± 0.17, while the mean of DV PI after nifedipine therapy for 48 hours was 0.50 ± 0.18 without any significancy. The DV is a blood vessel that has a thin muscle. Nifedipine works in vascular smooth muscle by blocking the entry of calcium into vascular smooth muscle. This indicates the administration of nifedipine does not greatly affect the blood flow of the fetal venous system.
Hemodynamic changes in venous fetal blood flow occur in an advanced stage, i.e. if the changes in arterial system blood flow in uncompensated stage. This means that changes in venous fetal blood flow will only occur if there has been a change in the blood flow parameters UA, MCA, and CPR.35