Disertasi

Pengaruh Seng, Beta-Carotene dan Vitamin D3 terhadap Regulator Inflamasi Kelahiran Preterm: Kajian Ekspresi Protein Adaptor MyD88 dan TRIF, Aktivitas Faktor Transkripsi NFκB, dan Sitokin Proinflamasi IL-1β. = Role of Zinc, Beta-Carotene and Vitamin D3 towards Inflammatory Regulator of Preterm Birth: The Study of Expression of Adaptor Protein MyD88 and TRIF, Activity of Transcription Factor NFκB and Pro-Inflammatory Cytokine IL1β.

Kelahiran preterm masih merupakan masalah global, dan menimbulkan berbagai komplikasi jangka pendek dan panjang pada bayi dan maternal. Penyebab kelahiran preterm bersifat multifaktor, di antaranya adalah proses inflamasi dan status nutrisi. Beberapa mikronutrien seperti seng, vitamin A dan D memengaruhi patomekanisme kelahiran preterm melalui regulasi respons inflamasi. Penelitian ini bertujuan mengetahui pengaruh seng, AtRA dan 25(OH)D pada regulasi respons inflamasi pada kelahiran preterm melalui pemeriksaan MyD88, TRIF, NFκB dan IL-1β. Desain kuasi eksperimental dilakukan selama periode Januari–Juni 2017 di IGD RSUPN-CM dan RS Budi Kemuliaan, Jakarta. Terdapat tiga kelompok subjek yang diteliti: kelompok aterm (n = 25), kelompok preterm kontrol (n = 27), dan kelompok preterm perlakuan (n = 26). Kelompok preterm perlakuan diberikan seng 50 mg oral/hari, beta-carotene 25.000 IU oral dosis tunggal dan vitamin D3 50.000 IU oral/minggu. Seluruh subjek dilakukan wawancara asupan nutrisi, pengukuran konsentrasi seng, AtRA dan 25(OH)D serum dan plasenta, serta kadar MyD88, TRIF, NFκB dan IL-1β plasenta. Data dianalisis menggunakan program IBM SPSS versi 20 dengan uji statistik Anova atau Kruskal Wallis dan uji korelasi Pearson atau Spearman. Pada kelompok aterm didapatkan konsentrasi AtRA serum lebih tinggi dibandingkan kelompok preterm kontrol dan perlakuan (p < 0,001), konsentrasi serum lebih tinggi dibandingkan plasenta. Pada kelompok preterm perlakuan, tidak didapatkan adanya perbedaan bermakna konsentrasi seng, AtRA dan 25(OH)D serum sebelum dan sesudah perlakuan. Konsentrasi seng, AtRA dan 25(OH)D plasenta pada kelompok aterm lebih tinggi dibandingkan kelompok preterm kontrol dan perlakuan (p < 0,001). Ditemukan NFκB dan TRIF lebih rendah pada kelompok aterm, dibandingkan kelompok preterm kontrol. Pada kelompok perlakuan, TRIF dan IL-1β lebih rendah dibandingkan kelompok kontrol. Pada kelompok kontrol, MyD88, TRIF dan NFκB lebih tinggi dibandingkan kelompok aterm dan preterm perlakuan. Simpulan Konsentrasi seng, AtRA dan 25(OH)D plasenta yang rendah berhubungan dengan lebih tingginya ekspresi MyD88, TRIF, NFκB dan IL-1β pada kelahiran preterm. Pemberian seng, beta-carotene dan vitamin D3 tidak meningkatkan konsentrasi seng, AtRA dan 25(OH)D serum pada subjek yang datang dengan persalinan preterm, namun berhubungan dengan ekspresi TRIF dan IL-1β yang lebih rendah.
Kata kunci : AtRA, kelahiran preterm, respons inflamasi, seng, 25(OH)D.


Preterm birth is still a global burden leading to various infant and maternal complications in short-term and long-term. Inflammation process and nutritional status are among the multifactorial etiology of preterm birth. Micronutrients such as vitamin A, D and zinc regulate inflammatory respons and affect mechanism of preterm birth. The objective of this studi is to attain knowledge about the role of zinc, beta-carotene and vitamin D3 towards inflammatory regulator of preterm birth. Quasi-experimental design was conducted during January–June 2017 in ER of Cipto Mangunkusumo Hospital and Budi Kemuliaan Hospital, Jakarta. There were 3 subject groups: term group (n = 25), control preterm group (n = 27), and experimental preterm group (n = 26). Subjects in experimental preterm group were given oral zinc 50 mg/day, single dose oral beta-carotene 25,000 IU and oral vitamin D3 50,000 IU/week. Nutrient intake interview was performed in all subjects following the birth, as well as the measurement of concentration of zinc, AtRA and 25(OH)D in serum and placenta, also the placental expression of MyD88, TRIF, NFκB and IL-1β. Data was then analyzed using IBM SPSS version 20 program with statistical test of One Way ANOVA or Kruskal Wallis, and correlation test of Pearson of Spearman The term group had higher AtRA concentration in serum compared to preterm control and treated group (p < 0,001). The AtRA serum concentration is higher than placenta. No significant difference of serum zinc, AtRA and 25(OH)D concentration was found in treated group before and after intervention. Term group had higher placental concentration of zinc, AtRA and 25(OH)D (p < 0,001). NFκB and TRIF were lower in term group compared to control group. Treated group had lower expression of TRIF and IL-1β compared to control group. Expression of MyD88, TRIF and NFκB was higher in control group compared to term and treated group. Conclusion Low placenta concentration of zinc, AtRA and 25(OH)D were related to high expression of MyD88, TRIF, NFκB and IL-1β in preterm birth. The supplementation of zinc, beta-carotene and vitamin D3 did not elevate serum concentration of zinc, AtRA and 25(OH)D in women undergoing preterm labor, but were related to lower expression of TRIF and IL-1β.
Key words : AtRA, inflammatory respons, preterm birth, zinc, 25(OH)D.