Neonatal jaundice is a common complication in newborns seen in 60% of term and 80% of preterm, during the first week of life  . It is mostly benign, however, in some cases may turn into catastrophe and needs to be taken seriously. High level of bilirubin for prolonged periods of time could result in permanent brain damage  .
Although phototherapy is suggested as the first-line treatment of hyperbilirubinemia in neonates, it may put the infant at the risk of important complications such as retinal injury, loose stools, erythematous macular rash, purpuric rash, overheating, dehydration, hypothermia, and a benign condition called bronze baby syndrome   .
Nowadays, effective prevention of unfavorable and dangerous jaundice requires ongoing vigilance and a practical system-based approach in order to distinguish infants with benign neonatal jaundice from those whose course may be less predictable and potentially harmful  . Majority of relevant studies have directed their attention on prevention of jaundice in infants, especially those with risk factors   .
Although some topics such as women’s life style and nutrition and using some special medicines during pregnancy have been discussed and demonstrated as effective factors on infant’ healthy  , to the best of our knowledge, there is no specific, proved or practical recommendation for women during pregnancy to prevent occurrence of jaundice in their newborns.
Various medicinal herbs and traditional medicine remedies have been used for neonatal jaundice for ages globally    . Recently, herbal medicines have received a particular attention to discover and develop bilirubin-lowering agents in newborns   .
In the light of the above mentioned points and since health hazards have not been reported in proper administration of taken routine dosages of pomegranate paste and while it is considered as safe in pregnancy   we designed a single-blinded clinical trial to investigate the rate of occurrence of jaundice in newborns whose mothers had consumed pomegranate paste from 34th week of their pregnancy compared to control group.
2. Materials and Methods
This single-blind randomized clinical trial was carried out in Lolagar Hospital, Teheran, Iran, from February to August 2015. The performed protocol of the study was approved by the ethical committee on human research of Shahid Sadoughi University of medical sciences, Yazd, Iran. The clinical trial has been registered in Iranian registry of clinical trials (IRCT) database under code: IRCT2015010314760N2.
Eighty nulliparous pregnant women aged between 18 - 35 years were invited to participate in the clinical trial. Pregnant women with any underlying diseases such as diabetes, hypertension, hypothyroidism, and etcetera were excluded from the study. Written informed consent was obtained from all of the participants.
Ripe and sweet pomegranates were purchased from a local store in Kan, Tehran, Iran. The washed fruits were manually peeled and the yielded arils were compressed to extract the juice. The seeds were separated and the filtered juice was conventionally heated and stirred at 90˚C for 3 hours to achieve proper viscosity and formation the paste     .
The participants were assigned into two 40-member groups: 1. the pomegranate paste group (PG) in which the cases were advised to take 1 table spoon of the prepared pomegranate paste, twice a day, before meal from 34th week of the pregnancy until delivery, and 2. the control group (CG) whose members were advised to keep on their routine diet.
The participants were requested to attend our hospital on the 5th day of their childbirth to measure the total serum bilirubin concentration using a Bilitest transcutaneous bilirubin measurement device. The mothers were requested to inform us immediately in the case of witnessing visible icterus before the appointed time. The neonates whose apgar was below 8, and the neonates whose gestational age was less than 38 weeks, have been excluded.
One-way analysis of variance (ANOVA) and chi-square test were performed to analyze the collected data. P values < 0.05 were considered statically significant.
A flow chart for the study is shown in the Figure 1. 40 women were allocated to the control group and 40 to the pomegranate paste group. 6 women from CG and 10 from PG were excluded prior to attention scheduled follow-up visit.
There were no statistically significant differences between the two groups with respect to baseline data such as body mass index (BMI), age of subjects, the type of delivery and the neonates’ gender and weight (Table 1). The number of neonates whom were undergone phototherapy in the PG was significantly lesser than that in the CG (Figure 2. P value = 0.029). By measuring the total bilirubin, statically significant difference between the PG and the CG was seen (Figure 3, P value = 0.043 and Figure 4, P value = 0.021).
In spite of the fact that many researchers have evaluated the effect of herbal remedies on occurred neonatal jaundice, to the best of our knowledge there is not any reported study in which the incidence of jaundice is evaluated in newborns
Figure 1. Flow chart of the study.
Figure 2. Comparison of the number of the newborns who needed phototherapy (P and NP stand for “performed” and “not performed”, respectively. P value = 0.029).
Table 1. Distribution of women according to baseline variables (・Chi-square, *ANOVA).
Figure 3. Comparison of the levels of bilirubin in blood samples (P value = 0.043).
Figure 4. Comparison of the bilirubin level between groups (mean ± SD, P value = 0.021).
whose mothers took natural products as “prophylactic” during pregnancy. In addition, as far as we know, this is the first randomized comparative trial of the pomegranate paste in the field of jaundice, globally.
Different varieties of pomegranate―the fruit of Punica granatum L. belonging to the family Lythraceae-known as a nutritious fruit in Quran, have been administered in the Iranian traditional medicine to treat hepatic and biliary tract disorders such as jaundice    . It has been known and prescribed as tonic to reinforce liver and gastrointestinal tract, to treat jaundice, as hematopoietic in anemia, to treat urinary tract infection, for fatigue feeling, in depression and melancholia and many other complications         .
Recently, clinical trials have been in progress exploring the beneficial effects of pomegranate’s various extracts. Several fields of potential clinical applications of pomegranate have been reported in recent years, showing the importance of such natural product in skin care, dental and periodontal conditions, different types of cancer, atherosclerosis, hypertension, diabetes, depression, erectile dysfunction, male infertility, ischemic brain injury, Alzheimer’s disease, obesity, inflammation, hyperlipidemia, carotid artery stenosis etcetera      .
In Iranian traditional medicine, jaundice has its roots in liver’s excessive warmness    . According to Iranian traditional medicine written literature, pomegranate could decrease the blood and liver warmness in pregnant women leading to decline the warmness of their fetus’s liver. The decline of fetus liver warmness improves its function, and as a result, incidence of jaundice is reduced    .
Our findings demonstrated the effectiveness of pomegranate paste for the first time in the incidence of jaundice in newborns whose mothers used it during pregnancy as administered.
Regarding the consumption of pomegranate paste according to the direction by the mother’s perfectly, we have no choice but to trust on their own reports.
Further investigations are needed to shed more light on the involved mechanisms of action and to confirm or refute pomegranate paste clinical prophylactic effects on neonatal jaundice.
The authors would like to express their sincere gratitude to the research center of Ardakan’s faculty of traditional medicine, Shahid Sadoughi University of Medical Sciences and Lolagar hospital for their support. We must acknowledge Dr. Masih Hashemi Khorasgani, Mr. Majid Ghobadi and Dr. Amir Mohammadkhan for their unfailing help.
Conflict of Interests
The authors declare that they have not any financial interests.