Tesis

Pengaruh Suplementasi Mikronutrisi Maternal Terhadap Faktor Angiogenesis dan Vaskulogenesis Serta Biometri Janin = The Effect of Maternal Micronutrient Supplementation on Angiogenic and Vasculogenic Factors and Fetal Biometry.

Latar Belakang : Makro dan mikronutrisi berperan penting dalam angiogenesis dan vaskulogenesis plasenta serta pada pertumbuhan janin. Penelitian ini bertujuan untuk mengetahui pengaruh suplementasi mikronutrisi maternal terhadap faktor angiogenesis, vaskulogenesis dan biometri janin. Metode penelitian : Penelitian intervensi dengan desain uji klinis acak terkendali tersamar tunggal berbasis kelompok (single blind clustered randomized controlled trial), terbagi atas kelompok kontrol dan perlakuan. Suplementasi mikronutrisi maternal yang diberikan pada kelompok perlakuan, meliputi : mikronutrisi multipel, kalsium, vitamin D3 dan DHA selama 12 minggu; sedangkan kelompok kontrol, meliputi : Asam folat dan zat besi. Luaran utama pada penelitian meliputi : perbandingan kadar PlGF, kadar sFlt-1, rasio sFlt-1/PlGF, rerata Pulsatility Index Arteri Uterina dan biometri janin (persentil lingkar kepala, persentil panjang femur dan persentil taksiran berat janin) antara kelompok. Luaran tambahan penelitian mengetahui perbedaan asupan makro dan mikronutrisi tiap trimester pada tiap kelompok. Analisis menggunakan ANOVA repeated measurement analysis, uji T tidak berpasangan dan Mann-Whitney. Hasil Penelitian: Partisipan awal penelitian berjumlah 228, dilakukan eksklusi 43, sehingga didapatkan 89 partisipan kontrol dan 96 partisipan perlakuan. Luaran utama penelitian didapatkan perbedaan bermakna kadar PlGF tiap trimester (p = 0,000), peningkatan kadar PlGF kelompok perlakuan lebih tinggi bermakna (p = 0,001); kadar sFlt-1 kelompok kontrol lebih tinggi namun tidak bermakna (p = 0.212); rasio sFlt-1/PlGF kelompok perlakuan lebih rendah bermakna (p = 0,001); serta persentil rerata PI arteri uterine kelompok perlakuan lebih rendah namun tidak bermakna (p = 0,381). Pada biometri janin, didapatkan persentil lingkar kepala janin kelompok perlakuan lebih besar bermakna (p = 0,001), persentil panjang femur dan taksiran berat janin tidak didapatkan perbedaan bermakna (p = 0,727; dan p = 0,486). Luaran tambahan pada penelitian didapatkan perbaikan asupan kalori (58,4% vs 71 ,9%; p = 0,055) dan protein (57,3% vs 63,5%; p = 0,386) pada kedua kelompok partisipan ditrimester kedua tanpa perbedaan bermakna, sedangkan asupan karbohidrat (75,3% vs 81 ,2%; p = 0,290) tinggi dan asupan lemak kelompok kontrol lebih tinggi bermakna (100% vs 94,8%; p = 0,014). Asupan mikronutrisi zat besi trimester kedua kedua kelompok meningkat (80,9% vs 79,1%; p = 0,849); asupan vitamin D kedua kelompok masih rendah, namun terdapat peningkatan asupan bermakna pada kelompok perlakuan (12,4% vs 45,8%; p = 0,000); asupan seng kelompok perlakuan meningkat bermakna (28,1% vs 64,6%; p = 0.000); asupan asam folat kedua kelompok meningkat tidak bermakna (75,3% vs 78,1%; p = 0,874); asupan vitamin B12 kelompok perlakuan meningkat tidak bermakna (47,2% vs 51%; p = 0,601); perbedaan bermakna tampak pada asupan omega-3 kelompok perlakuan meningkat (60,7% vs 92,7%; p = 0,000) dan kalsium (55,1% vs 90,6%; p = 0,000) Kesimpulan : Suplementasi mikronutrisi maternal bermanfaat pada proses angiogenesis, menjaga keseimbangan faktor angionesis dan anti-angiogenesis serta pertumbuhan lingkar kepala janin.
Kata kunci : Angiogenesis, Biometri janin, Suplementasi mikronutrisi, Vaskulogenesis


Introduction : Macro and micronutrients have an important role in angiogenic and vasculogenic factors and fetal growth. This study aims to assess the effect of maternal micronutrient supplementations on angiogenic and vasculogenic factors and fetal biometry. Methods : This is an interventional study with a single blind clustered randomized controlled trial design, divided into control and treatment groups. The control group was received folic acid and sulfas ferosus supplementation; while the intervention group was received multiple micronutrients, calcium, vitamin D3 and DHA. The intervention was given for 12 weeks. The main outcomes of this study was comparison of PlGF levels, sFlt-1 levels, sFlt-1/PlGF ratio, mean Uterine Arteries Pulsatility Index and fetal biometry (head circumference percentile, femur length percentile and estimated fetal weight percentile) between groups. Secondary outcomes were to assess differences in macro and micronutrient intake in each trimester in each group. The analysis was using ANOVA repeated measurement analysis, unpaired T test and Mann-Whitney. Results : The initial participants of the study were 228. We excluded 43 participants, resulting in 89 control group and 96 treatment participants. The main outcome of the study were including : a significant difference in PlGF levels in each trimester (p = 0,000) with a significant increasing ofPlGF levels in the treatment group (p = 0,001); not significant increasing ofsFlt-1 levels in the control group (p = 0,212); the ratio of sFlt-1/PlGF in the treatment group was significantly lower (p = 0,001); and insignificant lower centile of the mean uterine artery PI in the treatment group (p = 0,381). In fetal biometry, the centile of fetal head circumference in the treatment group was significantly larger (p = 0,001); while the percentile of femur length and estimated fetal weight were not differ significantly (p = 0,727; and p = 0,486). Secondary outcomes in the study was to assess the improvement in nutrition consumption, including : Improving in calorie intake (58,4% vs 71,9%; p = 0,055) and protein (57,3% vs 63,5%; p = 0,386) in both groups in the second trimester but not different significantly. Carbohydrate intake remains high in both groups (75,3% vs 81 ,2%; p = 0,290); while fat consumption in the control group was significantly higher (100% vs 94,8%; p = 0,014).. Iron supplementation intake in the second trimester increased in both groups (80,9% vs 79,1%; p = 0,849); vitamin D intake in both groups was still low, but there was a significant increasing in the treatment group (12,4% vs 45,8%; p = 0,000); zinc intake in the treatment group increased significantly (28,1% vs 64,6%; p = 0.000); Folic acid intake in both groups increased insignificantly (75,3% vs 78,1%; p = 0,874); vitamin B12 intake in the treatment group increased insignificantly (47,2% vs 51%;p = 0,601); and significant differences were seen in omega-3 intake (60,7% vs 92,7%; p = 0,000) and calcium intake (55,1% vs 90,6%; p = 0,000) were increasing in participant group. Conclusions : Maternal micronutrition supplementation have the effect on increasing angiogenic levels, maintaining the balance of angiogenic and anti-angiogenic factors and fetal head circumference growth.
Keywords : Angiogenic, Fetal biometry, Micronutrient supplementation, Vasculogenic