A systematic review and Meta-Analysis on the effect of Cotoneaster manna on Neonatal Jaundice

Document Type: Review article


1 Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;

2 Essence of Parsiyan Wisdom Institute, Traditional Medicine and Medicinal Plant Incubator, Shiraz University of Medical Sciences, Shiraz, Iran;

3 Clinical Research Development Center, "the Persian Gulf Martyrs" Hospital, Bushehr University of Medical Sciences, Bushehr, Iran


Background & Aim: The manna of Cotoneaster nummularia (purgative manna) has been traditionally used in the Persian medicine for the treatment of neonatal jaundice. The effect of Cotoneaster manna on neonatal jaundice was investigated with systematic review and meta-analysis.
Experimental: This study intended to explore the clinical trials of the efficacy of Cotoneaster manna on neonatal jaundice. The aspects considered in this study included searching for relevant English and Persian data bases up to March 2016. The methodological quality was assessed using the Consort checklist for herbal interventions. Seven studies with low or moderate risk of bias involved 804 participants of which 410 cases versus 394 controls were selected for systematic review and meta-analysis with CMA software version 2.2.
Results: Total plasma bilirubin in 0, 12, 24, 36, 48 hours and the duration of hospital stay were checked and no adverse effect was reported. The Meta-analysis exhibited marked heterogeneity of the results (Q-value = 132.446, P< 0.0001, I2 = 87.165, τ = 0.998). However, it showed favorable effect of Cotoneaster manna on reducing neonatal jaundice (n= 804, OR = 0.242, 95% CI: 0.147 to 0.399, P< 0.0001). Also it was effective on reducing duration of hospital stay (n= 804, SMD= -1.154, 95% CI: -1.854 to -0.455, P< 0.001). However, the results obtained were heterogeneous (Q-value= 119.642, P< 0.0001, I2= 94.985, τ= 0.913).
Recommended applications/ industries: Although the meta-analysis of Cotoneaster manna showed positive effect on treatment of neonatal jaundice in these studies, it is warranted to carry out further multi-centre randomized clinical trials with larger samples and controlled risk factors, alongside comparison with phototherapy. 


Article Title [Persian]

اثر شیر خشت بر زردی نوزادان یک مرور نظامند همراه با متا آنالیز

Authors [Persian]

  • علیرضا صالحی 1
  • محدثه استوار 2
  • مریم مرزبان 3
1 مرکز تحقیقات طب سنتی، دانشگاه علوم پزشکی شیراز، شیراز، ایران
2 گروه طب سنتی، دانشگاه علوم پزشکی شیراز، شیراز، ایران
3 مرکز توسعه پژوهش های بالینی، بیمارستان شهدای خلیج فارس، دانشگاه علوم پزشکی بوشهر، بوشهر، ایران
Abstract [Persian]

زمینه و هدف: در طب سنتی از شیر خشت به عنوان یک روش درمانی به صورت سنتی در طب ایرانی برای درمان زردی نوزادان استفاده میشود. با استفاده از متا آنالیز و مرور متون، اثر شیر خشت بر زردی نوزادان بررسی شد.
روش تحقیق: هدف از این مطالعه بررسی اثر کارآزمایی های  بالینی  انجام شده در مورد  شیرخشت بر زردی نوزادان است. شیوه اصلی که در این مطالعه استفاده شده شامل جستجو  مقالات انگلیسی و فارسی تا مارچ 2016 بوده است. کیفبت کارآزمایی های بالینی با استفاده از چک لیست کانسورت برای مداخلات دارویی بررسی شد. هفت مطالعه که دارای تورش پایین یا متوسط بوده اند با  804 شرکت کننده برابر با  410 مورد در برابر 394 شاهد برای ورود به مطالعه مروری و یا متا آنالیز با نرم افزار CMA نسخه 2.2 انتخاب شدند.
نتایج: مقدار کلی بیلی روبین پلاسما در 0، 12، 24 ، 36، 48 ساعت و طول دوره اقامت در بیمارستان کنترل شده و هیچگونه عارضه جانبی گزارش نشده است. متاآنالیز نشان دهنده هتروژنیتی برجسته ای از نتایج بوده است(Q-value = 132.446, P< 0.0001,   I2 = 87.165, τ = 0.998).  با این حال، اثرات موثر شیرخشت بر زردی نوزادان نشان داده شده است(n= 804, OR = 0.242, 95% CI:  0.147 to 0.399, P < 0.0001).  همچنین میتوان اذعان نمود که شیر خشت میتواند مدت اقامت در بیمارستان را نیز کاهش دهد(n= 804, SMD= -1.154, 95% CI:  -1.854 to -0.455, P< 0.001). با این حال نتایج به دست آمده هتروژن و ناهمگن بوده است(Q-value= 119.642, P< 0.0001,   I2= 94.985, τ= 0.913).
توصیه های کاربردی/ صنعتی: گرچه که متاآنالیز شیر خشت بر زردی نوزدان نشان دهنده اثر مثبت شیرخشت بر زردی نوزادان در این مطالعات بوده، با این حال انجام مطالعات چند مرکزی کارآزمایی بالینی با حجم نمونه بالاتر که برای عوامل خطر کنترل شده و مقایسه آن با روش درمان رایج که فتوتراپی می باشد توصیه می­شود. 

Keywords [Persian]

  • شیر خشت
  • زردی نوزادان
  • پرژک
  • بیلیناستر
  • طب سنتی ایرانی
Adam, T., Lim, S.S., Mehta, S., Bhutta, Z.A., Fogstad, H., Mathai, M. and Darmstadt, G.L. 2005. Cost effectiveness analysis of strategies for maternal and neonatal health in developing countries. British Medical Journal,331(7525): 1107.

Aghili, M.H. 2009. Makhzan al- Adviyeh (Vol. 1). Tehran: IUMS.

Ahmadipour, S., Mohsenzadeh, A. and Hassanzadazar, H. 2015. Neonatal jaundice treatment with Iranian native medicinal plants: Cotoneaster persicus, most important medicinal plant affecting on neonatal jaundice, Der Pharmacia Lettre 7(12): 313-315.

Ahmadipour, S., Mohsenzadeh,A., Eftekhari, Z. and Ahmadipour, S. 2016. An overview of the most important medicinal plants affecting on child's jaundice in ethnobotanical resource of Iran, Der Pharmacia Lettre, 8(1): 135-139.

Amin, G. 1383. The Most Common Medicinal Plants in Iran. Tehran: Tehran University of Medical Sciences and Health Services, Research Center for Medical Ethics and History.

Amiri,M.S., Joharchi, M.R. and TaghavizadehYazdi, M.E. 2014. Ethno-medicinal plants used to cure jaundice by traditional healers of Mashhad, Iran, Iranian journal of pharmaceutical research, 13(1): 157.

Amoli, E. 2010. Comparison of the effect of Cotoneaster and placebo on neonaatal jaundice of infants who were admitted at Avicenna Hospital from March 2009 till August 2009. (Medical Doctor), Islamic Azad University, Tehran, Tehran. (4300)

Atarzadeh, F., Jaladat, A., Dastgheib, L., Amin, G., Nimrouzi, M. and Kamalinejad, M. 2016. Cassiafistula: A remedy from Traditional Persian Medicine for treatment of cutaneous lesions of pemphigus vulgaris. Avicenna Journal of Phytomedicine, 1-8.

Aynehchi, Y. 1986. Pharmacognosy and medicinal plants of Iran. Tehran university.

Azadbakht, M., Pishva, N., Mohammadi Samani, S., andAlinejad, F. 2005. The effect of Purgative Manna on the infant jaundice. Iranian Journal of Pharmaceutical Sciences, 1(2): 95-100.

Beheshtipoor, N., Rambod, M., Jamali Moghadam, N. and Salehi,A. 2013. The Use of Herbal Medicines in the Infants Admitted to the Emergency Department of One of the Hospitals Affiliated to Shiraz University of Medical Sciences, Sadra Medical Sciences Journal, 1(3 Jul).

Bertini, G., Dani, C., Tronchin, M. and Rubaltelli, F.F. 2001. Is breastfeeding really favoring early neonatal jaundice? Pediatrics, 107(3): 41-41.

Cuvellier, J., Gottrand, F., Largillière, C., and Farriaux, J. 1990. [The bronze baby syndrome Apropos of 3 cases]. Paper presented at the Annales de pediatrie.

Drew, J., Marriage, K., Bayle, V., Bajraszewski, E., and McNammara, J. 1976. Phototherapy. Short and long-term complications. Archives of disease in childhood, 51(6): 454-458.

Ennever,J. 1990. Blue light, green light, white light, more light: treatment of neonatal jaundice. Clinics in perinatology, 17(2): 467-481.

Etebari, M., Ghannadi, A., Jafarian-Dehkordi, A. and Ahmadi, F. 2012. Genotoxicity evaluation of aqueous extracts of co-toneaster discolor and Alhagi pseudalhagi by com-et assay. Journal of Research in Medical Sciences, 17.

Fakhri, M., Hamze, M.A.Z. and Farhadi,R. 2016. Cotoneaster in traditional Persian medicine and new resources unit. Iranian Traditional Medicine Journal, 6(4): 347-353.

Fallah, R., Ali Fallahzadeh, M.and Noori-Shadkam, M. 2014. Evaluation of Safety and Efficacy of Purgative Manna (Billinaster Drop) and Glycerin Suppository in Icterus of Healthy Term Newborns. Current drug safety, 9(1): 29-33.

Fallah, R., Islami, Z., and Lotfi, S. R. 2012. Single dose of 50 mg/kg clofibrate in jaundice of healthy term neonates: randomised clinical trial of efficacy and safety. The Indian Journal of Pediatrics, 79(2): 194-197.

Farhat, A.S., Mohammadzadeh, A., and Amir, M. 2006. Effect of cotoneaster tricolor pojark manna on serum bilirubin levels in neonates. International Journal of Pharmacology, 2(4):455-458.

Fayaz, F. 2006. Assessment of the actions taken by parents in dealing with neonatal jaundice in newborns admitted to Hazrat Ali Asghar (AS) in June, July and August 2004, Pediatrics, Zahedan University of Medical Sciences, Zahedan.

Friedman, L., Lewis, P., Clifton, P. and Bulpitt, C. 1978. Factors influencing the incidence of neonatal jaundice. British Medical Journal, 1(6122): 1235-1237.

Ghotbi, F., Nahidi, S., and Zangi, M. 2006. Surveying the effect ofcotoneaster spp.(shir khesht) on neonatal jaundice.

Gürhan, N., Akyüz, A., Oflaz, F., Atici, D., and Vural, G. 2007. Effectiveness of nursing counseling on coping and depression in women undergoing in vitro fertilization. Psychological reports, 100(2): 374-365.

Hansen, T. 2000. Kernicterus in term and near‐term infants–the specter walks again. Acta Paediatrica, 89(10): 1155-1157.

Heydari, M., Homayouni, K., Hashempur, M.H.and Shams, M. 2015. Topical Citrullus colocynthis (bitter apple) extract oil in painful diabetic neuropathy: A double‐blind randomized placebo‐controlled clinical trial. Journal of diabetes.

Jafarpour, M., Yousefi, G., Hamedi, A., Shariat, A., Salehi, A.and Heydari, M.2016. Effect of a traditional syrup from Citrus medica L.fruit juice on migraine headache: A randomized double blind placebo controlled clinical trial. Journal of ethnopharmacology, 179: 170-176.

Joharchi, M.R. 2014. Ethno-Medicinal Plants Used to Cure Jaundice byTraditional Healers of Mashhad, Iran, Iranian Journal of Pharmaceutical Research, 13.

Khalid, S., Qadir, M., and Salat, M.S. 2015. Spontaneous improvement in sensorineural hearing loss developed as acomplication of neonatal hyperbilirubinemia. Journal of the Pakistan Medical Association, 65(9): 1018-1021.

KhodaShenas, A.K.A., Momeni, E., Sinayii, M. and Mir, M. 2015. Systemic review of herbal medicine efficacy on neonatal Icterus. Journal of North Khorasan University of Medical Sciences, 3(7): 683-689.

khodashenas, E. khakshour, A., momeni,E.sinaii, M. and Mir, M. 2015. Systemic review of herbal medicine efficacy on neonatal Icterus, Journal of North Khorasan University of Medical Sciences, 3(7): 683-689.

Kliegman, R., and Stanton, B. 2016. Nelson textbook of pediatrics (Vol. 1, pp. 871-880). Philadelphia, PA: Elsevier/Saunders.

Kliegman, R., Behrman, R.E.and Nelson, W.E. 2016. Nelson textbook of pediatrics.

Liberati, A., Altman, D.G., Tetzlaff, J., Mulrow, C., Gotzsche, P.C., Ioannidis, J.P. and Moher, D. 2009. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Annals of internal medicine, 151(4), W-65-W-94.

Maisels, M.J. 2006. Neonatal jaundice. Pediatrics in Review, 27(12): 443.

Maisels, M.J.and Gifford, K. 1986. Normal serum bilirubin levels in the newborn and the effect of breast-feeding. Pediatrics, 78(5): 837-843.

Mosavat, S.H., Ghahramani, L., Sobhani, Z., Haghighi, E.R., Chaijan, M.R., and Heydari, M. 2015. The effect of leek (Allium iranicum (Wendelbo) leaves extract cream on hemorrhoid patients: A double blind randomized controlled clinical trial. European Journal of Integrative Medicine, 7(6): 669-673.

Muchowski, K.E. 2014. Evaluation and treatment of neonatal hyperbilirubinemia. American Family Physician Journal, 89(11): 873-878.

Najib, K.S., Saki, F., Hemmati, F. and Inaloo, S. 2013. Incidence, risk factors and causes of severe neonatal hyperbilirubinemia in the South of iran (fars province). Iranian Red Crescent Medical Journal, 15(3): 260-263.

Newman, T.B.and Maisels, M.J. 1992. Evaluation and treatment of jaundice in the term newborn: a kinder, gentler approach. Pediatrics, 89(5): 809-818.

Newman, T.B., Escobar, G.J., Gonzales, V.M., Armstrong, M.A., Gardner, M.N.and Folck, B.F. 1999. Frequency of neonatal bilirubin testing and hyperbilirubinemia in a large health maintenance organization. Pediatrics, 104(Supplement 6):1198-1203.

Olusanya, B., Akande, A., Emokpae, A., and Olowe, S. 2009. Infants with severe neonatal jaundice in Lagos, Nigeria: incidence, correlates and hearing screening outcomes. Tropical Medicine and International Health, 14(3): 301-310.

Rafieian-Kopaei, M., Khoshdel, A., Kheiri, S. and Shemian, R. 2016. Cotoneaster: A Safe and Easy Way to Reduce Neonatal Jaundice. Journal of clinical anddiagnostic research: 10(4), SC01.

Ramezany, F., Kiyani, N. and Khademizadeh, M. 2013. Persian manna in the past and the present: an overview, American Journal of Pharmacological Sciences, 1(3): 35-37.

Reshadmanesh, N., Fayazmoghadam, K. and Kamali,S.H. 2001. Study of the effect of Manna Ash on the management of neonatal Jaundice. Scientific Journal of Kurdistan University of Medical Sciences, 4(13): 20-23.

Shakiba, M. and Pishva, N. 1992. Comparing Shirkhesht and Taranjebin with phototherapy in icteric neonates. Thesis]. Shiraz: Shiraz University of Medical Sciences.

Siegfried, E.C., Stone, M.S., and Madison, K.C. 1992. Ultraviolet light burn: a cutaneous complication of visible light phototherapy of neonatal jaundice. Pediatric dermatology, 9(3): 278-282.

Tan, K. 1991. Phototherapy for neonatal jaundice. Clinics in perinatology, 18(3): 423-439.

Tan, K. 1996. Phototherapy for neonatal jaundice. Acta Paediatrica, 85(3): 277-279.

The Plant List. 2013.Version 1.1. Published on the Internet; http://www.theplantlist.org/ (accessed 1st January).

Warren, S.E.andBlantz, R.C. 1981. Mannitol. Archives of internal medicine, 141(4): 493-497.

Watchko, J.andMaisels, M. 2003. Jaundice in low birthweight infants: pathobiology and outcome. Archives of Disease in Childhood-Fetal and Neonatal Edition, 88(6): F455-F458.

Yamauchi, Y.and Yamanouchi, I. 1989. Differencein TcB readings between full term newborn infants born vaginally and by cesarean section. Acta Paediatrica, 78(6): 824-828.