Effects of Date fruit (Phoenix Dactylifera) on Bishop Score and Frequency of Caesarean Section: A Systematic Review and Meta-Analysis


 Background : The rate of cesarean section is increasing in the world with different drafts in various countries. This growth increases unpleasant outcomes of delivery. Recent studies explained benefits of date palm fruit on labor process improvement. Date fruit can be a factor to increase vaginal delivery and to reduce frequency of cesarean section to prevent its great complications. This systematic review has been designed to review clinical studies that investigate the effects of date palm fruit on labor outcomes (duration of labor stages, bishop score and frequency of cesarean section) compared with routine cares. Methods : This study was performed in 2019. Required data has been gathered from electronic databases and manual searches. All randomized clinical trials evaluating the effects of date palm fruit on labor and delivery that have been published from January 2000 to August 2019 in English and Persian languages were included in this systematic review. The methodological quality of the included studies were evaluated according to the risk of bias assessment of Cochrane handbook of systematic reviews and were reported using, Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Results : Six studies were included in the qualitative and quantitative synthesis. Meta-Analysis showed that date fruit consumption significantly reduces active phase of labor (MD= -60.26, 95%CI (-107.18, -13.34), P=0.01) and significantly reduces duration of the first stage of labor (MD= -50.90, 95%CI (-100.63, -1.16), P=0.04) and significantly improves the bishop score (MD = 2.45, 95%CI (1.87, 3.04), P<0.00001) and it reduces the frequency of cesarean section but not significantly (Odds Ratio= 0.67, 95%CI (0.44, 1.02), P=0.06). Conclusion : Date can reduce the duration of active phase and the first stage of labor and the rate of cesarean section and improves the bishop score, but due to from the low to mediate quality of the studies, it seems that the other studies are needed to prove these results better than this. Key words : Date palm, date fruit, Phoenix dactiylifera, delivery, labor, systematic review, meta-analysis.

fruit on labor outcomes (duration of labor stages, bishop score and frequency of cesarean section) compared with routine cares.

Methods
This systematic review and meta-analysis is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement.

Eligibility criteria Inclusion and Exclusion criteria of studies
All randomized clinical trials evaluating the effects of date palm fruit on labor and delivery that have been published from 2000 until August 2019 in English and Persian languages were included in this systematic review. Editorials, reviews, books, case reports, case series, letter to editors, qualitative studies, and short communications were excluded. There was no limitation for the length of follow-up or treatment.

Inclusion criteria (PICOS format)
1) Participants: all pregnant women in 36-42 weeks of pregnancy with no restrictions on patient's age, nationality and the number of parity without any serious complication.
2) Interventions: consumption of date (fruit or extract) without restriction in the number of the fruit and the duration of intervention.
3) Controls: The routine cares of pregnant women. 4) Outcomes: The primary outcomes were duration of labor stages and the secondary outcomes were frequency of caesarian section and bishop score. Nasiri et al [30], in their systematic review investigated and explained the duration of labor stages but they included three duplicated published studies in their metaanalysis. They are publication bias and reporting bias.

Study Selection
The selected studies which were extracted from the databases by Endnote software were evaluated by two authors independently. Disagreements between them were referred to the third inspector. First, the titles of all papers were reviewed and inconsistent studies with the objectives of the study were excluded from the study. In the next step, abstract of chosen studies were reviewed and incompatible studies were excluded. Then full texts of chosen studies were extracted. In the last stage, full-text articles were surveyed to exclude those that did not match the inclusion criteria and the study aims. The authors elicited data from all eligible studies and registered the elicited data in the appropriate forms. Data for the primary objective of the review was gathered from the full text of each paper consisted the trial name, year of publication, study design, sample size, participants, intervention protocol, used parts of plant, comparisons, results, and other characteristics.

Assessment of risk of Bias
The methodological quality of the included studies and their risk of bias were evaluated by two reviewers independently using RevMan 5.3.0 software, according to the risk of Bias assessment of the Cochrane handbook. The assessment criteria consist of ve items: Selection bias (allocation concealment and random sequence generation); Performance bias (blinding of participants and personnel); Detection bias (blinding of outcome assessors); Attrition bias (dropouts and exclusion addressing and intention to treat analysis); Reporting bias (selective or nonselective reporting). Each study was evaluated as High, Low, or Unclear risk of bias for each item. Any disagreements between the two reviewers were resolved by discussion with the corresponding author. Because the number of included studies in meta-analysis was lower than 10 studies, therefore the graphical or statistical methods were not used to evaluate publication bias.

Statistical analysis
The results of the studies were analyzed by "Review Manager" software (RevMan 5.3.0 provided by Cochrane Collaboration). The types of intervention in included studies were the same. We integrated the studies according to the types of outcomes (labor phases duration, frequency of caesarian section and bishop score). Dichotomous data were summarized as risk ratio (RR) and continuous data as mean difference (MD). Heterogeneity between the studies was evaluated by using X 2 (chi-squared) test with p-value of p<.05 and I 2 statistic. I 2 was used to assess heterogeneity between studies, with≥50% was considered to indicate a substantial heterogeneity. The xed-effects model would be used if there was no signi cant heterogeneity between the studies, otherwise the random-effects model would be employed. 95%CI was calculated, and p<.05 was regarded as statistical signi cant.

General characteristics
We gathered 1531 studies from databases and other hand search sorces.9 of 1531 studies had eligibility criteria [31][32][33][34][35][36][37][38][39] but three of them had the same ethic code (910732) (approval code of research ethics committee) . One of them with higher numbers of participants was included to study and others were excluded. Two another studies were the same and were duplicated published [34][35]. One of them was included to this study. Finally six studies were included in qualitative and quantitative analysis after excluding duplicate published and inappropriate studies [31,34,[36][37][38][39]. The owchart of searching and inclusion process of studies is shown in Figure 1(According to PRISMA statement). Five of included studies had used the date palm fruit and one study had used date fruit honey. Descriptions and characteristics of the reviewed studies are shown in Table 1. No side effects were observed for date palm in any of the studies. The minimum and maximum intervention durations of founded studies are two days and four weeks respectively. Date palm and that's extracts were utilized orally in all of the studies. Sample sizes of these studies were 89 to 210 people. 767 participants were included in the analysis, 394 participants in intervention group and 373 in control group. Ages of participants were 20 to 40. All of these studies had control groups that consists placebo and routine cares in one study and routine cares in other studies. But placebo control group was not included in meta-analysis and qualitative analysis.   The details of risk of bias within included studies and authors judgment listed in table 2.
Random sequence generation 4 studies of 6 studies had used random number table, random generator or computer programmed random sequencing, and thus were evaluated as low risk of bias. Other 2 studies didn't use any reliable randomization method and were evaluated as high risk of bias.

Allocation concealment
One study of included studies had used sealed-envelopes method to the allocation concealment and was evaluated as low risk of bias. Three studies of six included studies did not determine the method of allocation concealment and were evaluated as unclear risk of bias. Two studies had not concealment and were evaluated as high risk of bias.

Blinding of participants and personnel
Due to the consumption of date fruit as intervention and routine care as control, all of the included studies had not performed blinding and were evaluated as high risk of bias.

Blinding of outcome assessment
All of these studies were evaluated as high risk of bias because they had no evidence of blinding of outcome assessors.

Incomplete outcome data
Of 6 studies, 3 studies have mentioned the dropped out and have analyzed the intention to treat and 2 studies had not any dropped out or lost to follow up, thus they were rated as low risk of bias. One study had attrition for missing participants but the statistical analysis had not followed by the intention to treat.

Selective reporting
One study had registered protocol but reported outcomes did not match with registered outcomes and were given high risk of bias. Expected outcomes of two studies had not determined and were evaluated as unclear risk of bias. Other included studies had reported their expected outcomes and were rated as low risk of bias.

Discussion
Based on the performed searches, this is the rst systematic review about effects of date on bishop score and frequency of caesarean section and second about effects of date on the duration of labor stages. Meta-analysis of this study that based on the random-effect model for high heterogeneity and xed effect model for low heterogeneity and mean differences of outcomes showed that the consumption of date fruit signi cantly reduces the duration of active phase and rst stage of labor and increases the bishop score in intervention group compared with control group. Also, the consumption of date fruit reduced the frequency of cesarean section in intervention group compared with control group, but this reduction was not signi cant. Based on meta-analysis, date palm fruit consumption resulted in a signi cant decrease in the duration of active phase and rst stage of labor compared with control group but not in the second and the third stage of labor.
Nasiri et al, in their systematic review, have achieved different results about the duration of labor stages. Those results are not reliable, because they had included three duplicated published studies in their meta-analysis. In that study, bishop score and frequency of caesarean section had not been investigated [30].
Different mechanisms have been expressed on the effects of date palm on the labor process. Date palm fruit has high calorie and proposed as an energizer.
The sugar in date fruit is glucose with simple digestion and absorption. Date fruit provide and maintain required energy for pregnant woman to prevent of tiredness. It leads to normal progress of labor because provides continual glucose and preserves body electrolytes [21,23]. Oxytocin and prostaglandins have been utilized widely for ripening of cervix, stimulation of uterine contractions and induction and stimulation of labor especially when the duration of latent phase of labor has been expanded [40,41]. Misuse of oxytocin and prostaglandins and insu cient maternal care in labor, lead to delivery complications [42,43]. Myometer oxytocin receptors increase in the last weeks of pregnancy. Estrogen and progesterone levels change in the 34-35 weeks of pregnancy that these changes led to the improvement of irritability of uterine and improvement of responsiveness of uterine to contractor factors and the improvement of cervical preparation to labor [44]. Therefore date fruit consumption in last weeks of pregnancy causes labor induction and stimulation, because date fruit acts on prostaglandin receptors and causes early stimulation of uterine contractions and improves response to syntocinon if it is necessary [40]. Fatty acids in date palm in addition to production and reservation of energy have important role in the prostaglandins production and following that reinforcement of uterine muscles [24, 25, and 45]. On the other hand, drinking water after consuming date fruit during labor is effective on labor progress and shortens the second and the third stages of labor [46]. As well as date palm can increase antioxidant capacity for 4 hours and following that increases pain tolerance, and this lead to reduce of the rst and the third stages of labor [20,24]. Also date fruit has anti-in ammatory and antioxidant properties and it is rich in calcium, serotonin and tannin and can play role in contraction of smooth muscles of uterine [20,47]. As mentioned, consumption of date fruit had increased signi cantly the bishop score and cervical dilatation. Bishop score (that contains cervical dilatation and …) has known as evaluation criteria of labor progress and the increasing factor of normal vaginal labor [48,49]. Lack of preparation of cervix and induction of labor can lead to increasing of caesarean section rate and postpartum hemorrhage [50][51][52]. Whereas increasing of the bishop score and preparation of cervix increase normal vaginal labor rate and reduce the caesarean section rate [53]. Forasmuch as low dose of oxytocin causes the improvement of the bishop score and the preparation of cervix [54], thus the consumption of date fruit affects on the improvement of the bishop score by increasing the activity of myometer contraction. This is a con rmation of possible hypothesis of oxytocin in date fruit and that's effect on uterine muscle contraction [21, 22, and 55]. Also date fruit contains saturated and unsaturated fatty acids linoleic, oleic and stearic. Linoleic acid breaks down to the arachidonate then to the eicosanoid. The eicosanoids nally convert to the prostaglandins and they improve the preparation of cervix by increasing subserosal uid and making changes in collagen bands and they cause the increasing of sensitivity of uterine to oxytocin [34, 47, and 56].
Generally the mechanism of cervical preparation is unknown, but changes in levels of estrogen and progesterone, increasing of the prostaglandins production, increasing of myometer sensitivity to oxytocin and prostaglandins, and their interactions can be effective [44,53].
Based on results of our systematic review, date fruit had reduced the rate of cesarean section, although not statistically signi cant. As we know the most common causes of cesarean section are abnormal progress of labor and non effective contractions of uterine [9,10,14]. Lack of eating energizer foods during labor lead to the increasing of non effective contractions of uterine and following that increasing of the augmented delivery and increasing the cesarean section rate [18]. Limited reserves of glycogen and body uids in pregnant women that have limited consumption of food and liquids during labor, cause low perfusion and low nutrition of uterine, it follows by abnormal labor progress and prolonged labor and the increasing rate of cesarean section [34]. While date fruit can reduce the need to oxytocin for labor and increase spontaneous labor because date fruit has Psudo-oxytocin effect that leads to the increasing of sensitivity and inducing the contractions of uterine and that leads to reducing of cesarean section rate [39].

Limitations
One of the limitations of this study was the lack of speci ed standard for the kind and the amount of date fruit that must be consumed that leads to positive effects on labor progression and cervix preparation. Also, it is not determined that, how long at what intervals of consumption of date fruit need to energy supply during labor and reducing of cesarean section rate and promotion of labor outcomes.
Another limitation of this study was the high risk of bias in done studies. Especially, due to the methods of studies and using the date palm fruit in the studies, blinding of participants and researchers was not possible. Therefore, that causes the rising of performance bias in included studies. Furthermore, none of these studies had not outcome assessor blinding.
The other one of this study was unknown time of intervention and duration of intervention in the most studies.

Conclusions
Despite widespread utilizing of date palm, there is not enough clinical evidence to support the clinical effects which mentioned in review articles and traditional medical systems. Based on this study results, date fruit can reduce the duration of active phase and the rst stage of labor and the frequency of cesarean section and improves the bishop score. The growing trend of recent studies about date palm provides scienti c rationale for date palm clinical abilities, but due to from the low to mediate quality of the studies, it seems that the other studies are needed to prove these results better than this. Availability of data and materials

List Of Abbreviations
All data generated during this study are included in this article, tables, gures and its supplementary information les.

Competing interests
The authors declare that they have no competing interests.         Supplementary Files This is a list of supplementary les associated with this preprint. Click to download. PRISMAchecklistPRCHD1901240.docx