39
The principal investigator was involved in the area of conceptualization of the project, organizing training session for the residents that were involved in the study. Also involved in patient’s selection and drug administration to some of the patients, he was involved in data entry, data analysis, writing out the outcome results from analysis and finally the project summary.
4.5 Statistical analysis
The effect of the drug and patient’s sociodemographic characteristics were imputed into a proforma and this was processed into data form. The fetal heart rate was processed into normal value 120b/m – 160b/m, tachycardial >160b/m and bradycardia<120b/m during data entry and statistical package for the social sciences (SPSS) version 17 was used for analysis and result tested for significance using t-test for continuous variable and chi-square for categorical variable.
Level of confidence was set at 95% and level of significance was set at 0.05.
4.6 Ethical Consideration
The ethical clearance for this study was obtained from the Research and Ethics Committee of the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife. Taking part in the study was by voluntary participation. The participants were fully informed about the study both verbally and with use of patient information sheet. Informed consent was taken by a consent form (sample attached) that was signed by each participant. Participant had the right to withdraw for whatever reasons at any stage of the study without any penalty. Confidentiality was maintained by identifying patient using a sequential numbers which was only available to the investigator and supervising consultants. Also the data obtained was secured using a pass worded computer programming to keep information. Beneficence, the patient and others tend to derive
40
benefit in the study in that it help to ascertain the minimum dose of nifedipine to achieve the optimum result in the management of the condition. Also the drug is an essential component in the management of the patient and was provided free of charge to the patient. Non maleficence , the drug is been used originally in the management of the condition and had been found not to be harmful so far to human. The principle of justice and equality was maintained by treating equally all the participants during the recruitment and during the course of the study, there was no favoritism.
41
CHAPTER FIVE RESULTS
A total of 86 consecutive pregnant women with preterm labour who met the inclusion criteria for this study were recruited out of a total of 1261 admissions over the recruitment period hence preterm labour accounted for 6.8% of admissions over the study period. Of the 86 participant only 81 women (40 women in LD group and 41 women in HD group) completed the study while 5 women(3women in LDgroup and 2women in HD group) progressed in labour to delivery.
Table 1 shows the comparison of baseline characteristics between the two groups. The mean age of the subjects in the low dose group and the high dose group were 29.23±3.9 years vs 28.86±3.6years p>0.05, there was no significant difference in the mean age in both groups. The mean estimated gestational age at recruitment in the low dose group and high dose were
31.72±1.9 weeks vs 31.05±2.4 weeks p>0.05 respectively, there was no significant statistical difference in the mean gestational age at recruitment. The cervical dilatation, the cervical length and the frequency of contraction at admission had same median value when compared.
Table 2 shows the comparison of the low and high dose nifedipine regimen with respect to uterine quiescence and need for rescue treatment. The mean uterine quiescence time were 13.60±11.69hrs vs 12.16±8.90 hours p>0.05 in the low and high dose regimen respectively, there was no significant difference when the two groups were compared.
The women who remained undelivered at 48 hours were the patients that achieved uterine quiescence within 48 hours were 41 patients (95%) versus 40 patients ( 93%) p>0.05 in high vs
42
low dose regimen respectively, there was no statistical significance difference on comparing the two groups. However, 5 patients progressed to delivery during the study out of which 3patients (7%) vs 2 patients(5%) p>0.05 among low vs high dose groups respectively, this shows that there was no significant difference in the number of women that progressed to delivery between the two groups. None of the patient needed rescue treatment.
Table 3 shows comparison of fetomaternal side effects between the low and high nifedipine dose regimen. All (100%) the patients in both groups had a normal fetal heart rate changes at the end of the study. However the only maternal side effect recorded in this study was headache in which 2patients (5%) vs 8patients (19%), p>0.05 on correction using fisher exact, in low and high dose respectively, this shows that there was no significant statistical difference in the maternal side effect experienced by the women.
Tables 4 showed the odd ratio and 95% confidence interval for outcome predictors of uterine quiescence at 48hrs (OR 1.66, 95%CI 0.24 to 11.68) and at 12hrs(OR 1.52, 95%CI 0.51 to 4.52) which showed that there was no advantage of the high dose regimen over the low dose regimen. Also the maternal side effect (OR 2.14, 95%CI 0.95 to 4.81) showed that there was no difference in both arms of the treatment.
43
Table 1: Comparison of baseline characteristics between the low and high Nifedipine dose regime.
Low Dose N = 43
High Dose t df N = 43
X2 p-value Mean age (years) 29.23 3.9 28.86 3.6 71.16 0.966 Occupation [freq(%)]
Civil servant Artisan Unemployed student
13(30.2%) 11(25.6%) 10(23.3%) 9(20.9%)
15(34.9%) 10(23.3%) 8(18.5%)
10(23.3%) 3 0.74 Education [freq(%)]
Tertiary Secondary Primary
No formal education
28(65.1%) 10(23.3%) 5(11.6%) 0(0%)
24(55.8%) 16(37.2%) 3(7%)
0(0%) 3 0.33*
Religion [freq(%)]
Christianity Islam Others
41(95.3%) 2(4.7%) 0(0%)
40(93.0) 3(7%)
0(0%) 2 0.50*
Mean parity (median) 1.0 1.0 Gestational age
(mean±SD in weeks) Cervical dilatation (median in cm)
Cervical length (median in cm)
Frequency of contraction (median in 10min)
31.72 1.9
1.0
2.0
2.0
31.05 7.13
1.0
2.0
2.0
0.159
SD – standard deviation, N- Number, t - student t-test, df- degree of freedom, x2-chisquare, p- level of significance
- fishers exact test.
44
Table 2: Comparison of the low and high dose Nifedipine regime with respect to uterine quiescence and need for rescue tocolysis.
Low Dose (N-43)
High Dose (N-43)
t df x2 P value
Time to achieve uterine quiescence
(mean±SD hours) 13.60±11.69 12.16±8.90 11.54 0.747
Number Undelivered at 48hrs freq (%)
Failed to treatment Freq(%)
40(93%)
3(7%)
41(95%)
2(5%)
1 0.64
1 0.24
Need for rescue treatment
freq(%) 0(0%) 0(0%)
SD – standard deviation, N- Number, t - student t-test, df- degree of freedom, x2-chisquare, p-level of significance
45
Table 3: Comparison of fetomaternal side effect between the low and high dose regime of Nifedipine Low Dose
(N-43) Frq(%)
High Dose (N -43) Frq(%)
df x2 Fetal heart rate
<120 120-160
>160
0 43 0
0 43 0
1 0.25
Maternal side effect
Hypotension Tachycardia Headache Flushing Dizziness Nausea Palpation Vomiting Others
0(0%) 0(0%) 2(5%) 0(0%) 0(0%) 0(0%) 0(0%) 0(0%) 0(0%)
0(0%) 0(0%) 8(19%) 0(0%) 0(0%) 0(0%) 0(0%) 0(0%) 0(0%)
1 0.08*
N- Number, t - student t-test, df- degree of freedom, x2-chisquare, p- level of significance, * - fisher exact test
46
Table 4: Odds ratio and confidence interval of both low and high dosage regime outcomes
OUTCOME df OR
95%CI lower upper Uter.quicent at
48hrs Side effect.
Uter.quicent. at 12hrs
1 1.66
1 2.14 1 1.52
0.24 11.68
0.95 4.81 0.51 4.52
df- degree of freedom, OR-odd ratio, CI- confidence interval
47
DISCUSSION
The dosage regimen of oral nifedipine had been varied from one researcher to another , there was no particular regimen used and there appears to be no consensus on the ideal regimen.
The present study compared two of the previously tested regimens of nifedipine in the treatment of preterm labour, therefore the two regimes were compared with respect to there efficacy and side effect. The high dose was recommended by Bracerol et al53 and the low dose was recommended by Papatsonis et al.40
The present study found no statistically significant difference between the two regimen with respect to efficacy and side effect.
Nifedipine has been used and strongly recommended to inhibit uterine contraction for over 30 years and used as effective tocolytic to delay delivery for at least 48hours to allow corticosteroid administration to take effect or to allow for transfer of patient to tertiary care center with neonatal intensive care facility.10
The mean ages of women in this study in the low dose was 29.23±3.9 years and high dose was 28.86±3.6 years which is comparable to the study of Ghazi A et al.55 Also in this study most of the patients were of low parity which is contradictory to the results found in the study of copper L et al,56 where the incidence of preterm labour was high in high parity women. This may be due to the fact that all the patients in this study were low parity or may be due to the fact that more of the high parity women deliver at home and did not come to the hospital. In the study the mean gestational age of 31weeks at admission were similar in both groups, this means there
48
was no bias with respect to the application of the drug regimen in both groups with respect to the gestational age.This is also comparable to the study by Weerakul W et al57 where the mean gestation age was 31.7weeks.
This study showed that the high dose regimen had a shorter mean time to achieve uterine quescience than the low dose group, interestingly the difference was found not to be statistically significant when compared with each other. Also there was no statistical difference in the number of women achieving uterine quiescence at 48hours when both groups were compared. This is comparable to what was obtained by Anwar et al9 in a study comparing two dose regimes of nifedipine for the management of preterm labour where the result showed that there was no significant difference in the number of women attaining uterine quiescence at 48hours between the high and the low dose of nifedipine used in that study, with the high dose group having shorter mean time to achieving uterine quiescent.
Also in this study none of the patient had a rescue treatment, the 3 patients(7%) noted in the low dose regimen with the 2 patients (5%) noted in the high dose group who did not complete the treatment with nifedipine actually progressed to active phase of labour and subsequently delivered within 6-8 hours of admission. However comparing the two groups with regards to failure of treatment, there was no advantage conferred on the high dose regimen as against the low dose . This result is comparable to the study by chawanpaiboon et al59 in which there was failure of tocolysis in 2% of the study group.
Concerns about the fetal heart rate abnormality due to the effect of nifedipine on both fetal and placental circulation is yet to be confirmed in human study,54 this was further
49
confirmed in this study as none of the women in both groups had fetal tachycardia or bradycardia during the course of the treatment. All had a normal fetal heart rate pattern. Also this result is comparable with the study done by Tsatsaris et al,58 which observed that there was no fetal heart rate abnormality noticed in all the patients studied.
Also there were concerns about the maternal side effect, nifedipine been an antihypertensive with vasodilation effect which may predispose to hypotension and other effects, interestingly none of the patients had hypotension in the two groups, this is not comparable with the study by Tsatsaris et al58 in which hypotension was second to headache in terms of maternal sideeffect, however a total of 679 patients were studied , the result of the side effect obtained in this study could be possibly due to small sample size. However in the study by chawanpaiboon et al59 complications of nifedipine were not detected at all in the nifedipine study group.
The only maternal side effect recorded in this study was headache. Headache was found to be more among women that were in the high dose group which was not significant, however the headache was not that severe to require discontinuation of treatment in view of the fact that all the patients with headache tolerated the treatment well. This is comparable to the side effects noted by Anwar et al9 in which headache was the commonest side effect noted among the two groups of women that took two different regimen of nifedipine.
The result of this study showed that high dose of oral nifedipine does not seem to have an advantage over the low dose of oral nifedipine in terms of the mean time to achieve uterine quiescence and the number of women undelivered at 48hours. However, more women in the high dose regime had headache though this was not significant. None of the patient had abnormal fetal heart rate changes.
50
The limitation of the study.
1) The non availability of constant power supply to power the CTG machine made monitoring of patient frustrating.
2) The limited CTG machine made monitoring of more patient than two impossible at a time.
51
CONCLUSION AND RECOMMENDATION
This prospective study demonstrates that there was no difference in the efficacy of the high dose of oral nifedipine regimen compared to low dose oral nifedipine regimen with respect to the mean time to achieve uterine quiescence and the number of women undelivered after 48 hours period. Also there was no fetal heart rate abnormality in both groups but the high dose had a higher maternal side effect of headache though this was not significant in this study. This means that the low dose was equally effective in the management of preterm labour with lower maternal side effect. Though the cost effectiveness was not reported in the study however the purchase price of low dose is far lower than the high dose regimen.
Recommendation:
In view of the effectiveness and reduced side effect associated with low dose nifedipine regimen as seen in this study and the fact that the lower dose nifedipine attracts a lower purchase price, the low dose is therefore recommended for treatment of preterm labour.
Further research work with larger sample size and a much lower dose than the low dose used in this study could be explored.
52
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