Zinc, Beta-Carotene, and Vitamin D₃ Supplementation and Placental IL-1β in Spontaneous Preterm Labor

Rima Irwinda^1, , Saptawati Bardosono², Ali Sungkar¹ and Noroyono Wibowo¹

¹Maternal Fetal Medicine Division, Department of Obstetrics and Gynaecology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

²Department of Nutrition, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

Cite this paper:
Rima Irwinda, Saptawati Bardosono, Ali Sungkar and Noroyono Wibowo. Zinc, Beta-Carotene, and Vitamin D₃ Supplementation and Placental IL-1β in Spontaneous Preterm Labor. Journal of Food and Nutrition Research. 2021; 9(10):531-538. doi: 10.12691/jfnr-9-10-5

Abstract

Preterm birth (PTB) is one of the leading causes of neonatal death. Studies have shown that Interleukin-1 (IL-1β) critically contributes to inflammation-induced PTB, and micronutrients deficiencies might influence the inflammatory pathways. Since zinc, vitamin A, and vitamin D deficiencies are common in Indonesia, this study aims to evaluate those nutrients supplementation on placental IL-1β in PTB. A quasi-experimental study was conducted in pregnant women who underwent spontaneous delivery. They were divided into 3 groups; control-term group (n=25), control-preterm group (n=27), and experimental-preterm group (n=26). No intervention was given to the control-term and the control-preterm groups, while the experimental-preterm group was given zinc 50 mg/day, a single dose beta-carotene 25,000 IU, and vitamin D3 50,000 IU/week until delivery. Zinc, all-trans retinoic acid (AtRA) and 25-hydroxyvitamin D (25(OH)D) concentrations in maternal serum were measured before and after intervention, followed by assessment of placental concentration of those nutrients and IL-1β expression after delivery. One-way ANOVA and Kruskal Wallis tests were performed for comparison analysis and using Pearson or Spearman test for correlation analysis correlation test using Statistical Package for Social Sciences (SPSS). No significant difference in zinc, AtRA, and 25(OH)D concentrations was found in maternal serum, before and after the intervention. However, the experimental-preterm group had the lowest IL-1β concentration (7.17 pg/g (0.45–283.29), p=0.009). This study suggests that the administration of zinc, beta-carotene, and vitamin D3 in PTB was associated with lower placental IL-1β expressions, although it did not directly increase those nutrient concentrations in serum and placenta.

Keywords:
preterm birth micronutrients Indonesian women

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References:

[1]	World Health Organization, “Preterm birth 2104.”
[2]	H. Blencowe et al., “National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications.,” Lancet (London, England), vol. 379, no. 9832, pp. 2162–2172, Jun. 2012.
[3]	E. S. Green and P. C. Arck, “Pathogenesis of preterm birth: bidirectional inflammation in mother and fetus.,” Semin. Immunopathol., vol. 42, no. 4, pp. 413-429, Aug. 2020.
[4]	M. W. Kemp, “Preterm birth, intrauterine infection, and fetal inflammation,” Front. Immunol., vol. 5, p. 574, 2014.
[5]	J. M. Melville and T. J. M. Moss, “The immune consequences of preterm birth,” Front. Neurosci., vol. 7, p. 79, May 2013.
[6]	M. Nadeau-Vallée et al., “A critical role of interleukin-1 in preterm labor.,” Cytokine Growth Factor Rev., vol. 28, pp. 37-51, Apr. 2016.
[7]	U. Ramakrishnan, F. Grant, T. Goldenberg, A. Zongrone, and R. Martorell, “Effect of women’s nutrition before and during early pregnancy on maternal and infant outcomes: a systematic review.,” Paediatr. Perinat. Epidemiol., vol. 26 Suppl 1, pp. 285-301, Jul. 2012.
[8]	C. J. Ashworth and C. Antipatis, “Micronutrient programming of development throughout gestation.,” Reproduction, vol. 122, no. 4, pp. 527-535, Oct. 2001.
[9]	J. Wu, N. Ma, L. J. Johnston, and X. Ma, “Dietary Nutrients Mediate Intestinal Host Defense Peptide Expression.,” Adv. Nutr., vol. 11, no. 1, pp. 92-102, Jan. 2020.
[10]	N. Wibowo and R. Irwinda, “The effect of multi-micronutrient and protein supplementation on iron and micronutrients status in pregnant women,” Med. J. Indones., vol. 24, no. 3, pp. 168-175, 2015.
[11]	S. Riva’i, E. Darwin, E. Nasrul, and J. Effendi, “Role of nuclear factor kappa beta, tumor necrosis factor α, and cyclooxygenase-2 in preterm labor.,” Med J Indones, vol. 23, no. 4, pp. 213-7, 2014.
[12]	Depatemen Kesehatan Indonesia, “Peraturan Menteri Kesehatan Republik Indonesia No 75Tahun 2013 tentang Angka Kecukupan Gizi yang Dianjurkan bagi Bangsa Indonesia,” 2013.
[13]	N. Wibowo, S. Bardosono, R. Irwinda, I. Syafitri, A. S. Putri, and N. Prameswari, “Assessment of the nutrient intake and micronutrient status in the first trimester of pregnant women in Jakarta,” Med. J. Indones., vol. 26, no. 2, pp. 109-115, 2017.
[14]	J. A. Grieger, L. E. Grzeskowiak, and V. L. Clifton, “Preconception dietary patterns in human pregnancies are associated with preterm delivery.,” J. Nutr., vol. 144, no. 7, pp. 1075-1080, Jul. 2014.
[15]	C. M. Reynolds, M. H. Vickers, C. J. Harrison, S. A. Segovia, and C. Gray, “High fat and/or high salt intake during pregnancy alters maternal meta-inflammation and offspring growth and metabolic profiles.,” Physiol. Rep., vol. 2, no. 8, Aug. 2014.
[16]	L. He et al., “Autophagy: The Last Defense against Cellular Nutritional Stress.,” Adv. Nutr., vol. 9, no. 4, pp. 493-504, Jul. 2018.
[17]	V. Agrawal et al., “Altered autophagic flux enhances inflammatory responses during inflammation-induced preterm labor.,” Sci. Rep., vol. 5, p. 9410, Mar. 2015.
[18]	G. Chiudzu, A. T. Choko, A. Maluwa, S. Huber, and J. Odland, “Maternal Serum Concentrations of Selenium, Copper, and Zinc during Pregnancy Are Associated with Risk of Spontaneous Preterm Birth: A Case-Control Study from Malawi,” J. Pregnancy, vol. 2020, p. 9435972, Apr. 2020.
[19]	P. Christian and K. P. J. West, “Interactions between zinc and vitamin A: an update.,” Am. J. Clin. Nutr., vol. 68, no. 2 Suppl, pp. 435S-441S, Aug. 1998.
[20]	G. K. Schwalfenberg and S. J. Genuis, “Vitamin D, Essential Minerals, and Toxic Elements: Exploring Interactions between Nutrients and Toxicants in Clinical Medicine.,” Scientific World Journal., vol. 2015, p. 318595, 2015.
[21]	D. L. Watts, “The nutritional relationships of zinc,” J. Orthomol. Med., vol. 3, no. 2, pp. 63-7, 1998.
[22]	T. Claro da Silva, C. Hiller, Z. Gai, and G. A. Kullak-Ublick, “Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor.,” J. Steroid Biochem. Mol. Biol., vol. 163, pp. 77-87, Oct. 2016.
[23]	A. Bogale, S. L. Clarke, J. Fiddler, K. M. Hambidge, and B. J. Stoecker, “Zinc Supplementation in a Randomized Controlled Trial Decreased ZIP4 and ZIP8 mRNA Abundance in Peripheral Blood Mononuclear Cells of Adult Women.,” Nutr. Metab. Insights, vol. 8, pp. 7-14, 2015.
[24]	T. B. Aydemir, R. K. Blanchard, and R. J. Cousins, “Zinc supplementation of young men alters metallothionein, zinc transporter, and cytokine gene expression in leukocyte populations.,” Proc. Natl. Acad. Sci. U. S. A., vol. 103, no. 6, pp. 1699-1704, Feb. 2006.
[25]	R. Irwinda, N. Wibowo, and A. S. Putri, “The Concentration of Micronutrients and Heavy Metals in Maternal Serum, Placenta, and Cord Blood: A Cross-Sectional Study in Preterm Birth,” J. Pregnancy, vol. 2019, 2019.
[26]	D. Sari, Z. Tala, S. Lestari, S. Hutagalung, and R. Ganie, “Vitamin D receptor gene polymorphism among Indonesian women in North Sumatera,” Asian J Clin Nutr, vol. 9, no. 1, pp. 44-50, 2016.
[27]	A. Balduit et al., “Zinc oxide exerts anti-inflammatory properties on human placental cells,” Nutrients, vol. 12, no. 6, pp. 1-11, 2020.
[28]	S.-K. Bai et al., “beta-Carotene inhibits inflammatory gene expression in lipopolysaccharide-stimulated macrophages by suppressing redox-based NF-kappaB activation.,” Exp. Mol. Med., vol. 37, no. 4, pp. 323-334, Aug. 2005.
[29]	T. K. Wöbke, B. L. Sorg, and D. Steinhilber, “Vitamin D in inflammatory diseases,” Front. Physiol., vol. 5, p. 244, Jul. 2014.