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Abstrak :
Latar Belakang: Kelahiran preterm adalah kelahiran sebelum usia kehamilan 37 minggu lengkap. Secara global, kelahiran preterm menyebabkan morbiditas dan mortalitas bayi yang tinggi. Laporan World Health Organization (WHO) tahun 2010, Indonesia saat ini termasuk dalam 10 besar negara dengan jumlah kelahiran preterm terbanyak yaitu 15,5 per 100 kelahiran hidup. Berbagai faktor dihubungkan dengan penyebab terjadinya kelahiran preterm, termasuk salah satunya adanya defisiensi asam lemak tidak jenuh rantai panjang selama kehamilan. Tujuan: Mengetahui kadar asam lemak tidak jenuh rantai panjang (ALA, EPA, DHA, LA dan AA) pada ibu hamil dengan kelahiran preterm dan aterm. Metode: Penelitian dilakukan dengan uji potong-lintang dengan subjek penelitian ibu hamil preterm dan aterm yang melakukan persalinan di RSUPN Dr. Cipto Mangunkusumo dan RS Budi Kemuliaan Jakarta pada Juli hingga Desember 2019. Hasil: Diperoleh 60 subjek penelitian dengan 30 subjek pada masing-masing kelompok. Hasil dengan kategori rendah didapatkan pada kelompok preterm dengan median kadar ALA 47 μmol/L, AA 491 μmol/L dengan perbedaan yang bermakna dengan kelompok aterm (p=0,03 dan p=0,01). Indeks omega-3 pada masing-masing kelompok juga rendah yaitu 2,5% pada preterm dan 3% pada aterm. Kesimpulan: Terdapat perbedaan yang bermakna antara kadar ALA dan AA pada ibu yang mengalami kelahiran preterm dan aterm. Tidak terdapat perbedaan yang bermakna kadar EPA, DHA, LA, indeks omega-3, rasio omega-6/ omega-3, dan rasio AA/EPA pada ibu yang mengalami kelahiran preterm dan aterm.

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Background: Approximately 15 million babies were born prematurely every year with one million of them dying from preterm birth complications. Indonesia was among the top 10 countries worldwide with the highest number of preterm births, which was 15.5 preterm births per 100 live births. In recent years, several studies have been investigating the role of nutrition in reducing the risk of preterm birth, one that seems promising is long-chain unsaturated fatty acids (LCPUFA). This study was conducted to determine LCPUFA status in pregnant women who undergo preterm and term births in Jakarta, Indonesia. Objective: To determine the levels of long-chain unsaturated fatty acids (ALA, EPA, DHA, LA dan AA) in pregnant women undergoing preterm and term birth. Method: A descriptive study was conducted on 30 pregnant women in each group who experienced preterm and term births at Cipto Mangunkusumo and Budi Kemuliaan Hospital Jakarta between July and December 2019. Maternal blood plasma was examined by measuring the concentration of alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LA), arachidonic acid (AA), omega-3 index, omega-6/ omega-3, and AA/ EPA ratio. Result: The median levels of ALA and AA were low in the preterm birth group with significant differences between the two groups (p= 0,03 and p= 0,01). The median total concentrations of ALA, EPA, DHA, LA, AA, omega-3 index, omega-6/ omega-3, and AA/EPA ratio in preterm birth group were as follows: 47 μmol/L, 18,5 μmol/L, 262 μmol/L, LA 3382 μmol/L, 491 μmol/L, 2,5%, 13 and 26,5. While in the term birth group were as follows 58,5 μmol/L, 19 μmol/L, 262 μmol/L, LA 3382 μmol/L, 491 μmol/L, 2,5%, 13 and 26,5. The median concentration of EPA and DHA on both groups were in a normal range. Most of the subjects had a low omega-3 index, 86,7% from total subjects in preterm and 66,7% in term group. Conclusion: There are significant differences between ALA and AA concentration in women who experienced preterm and term birth. There were no significant differences in levels of EPA, DHA, LA, omega-3 index, omega-6/ omega-3 ratio, and AA/EPA ratio between the two groups.

Abstrak :
ABSTRAK
Patomekanisme dermatitis atopik melibatkan interaksi yang kompleks antara genetik dan lingkungan. Satu gen yang secara konsisten berhubungan dengan DA adalah mutasi gen Filaggrin yang dapat mengganggu agregasi sitoskeleton epidermis. Beberapa usaha pencegahan telah dilakukan antara lain dengan pemberian ASI eksklusif dan suplementasi LCPUFA, tetapi studi klinis dan meta-analisis tidak menunjukkan hasil yang konsisten. Inkonsistensi ini dapat disebabkan adanya variasi aktivitas enzim desaturase yang dapat memodulasi metabolisme PUFA, yang diatur oleh gen FADS1 dan FADS2, serta usia saat intervensi dilakukan. Diperkirakan periode in-utero memegang peran penting untuk keberhasilan intervensi. Penelitian ini bertujuan mengetahui peran mutasi gen FLG dan polimorfisme gen FADS1 dan FADS2 terhadap timbulnya DA pada usia satu tahun. Tujuan Khusus yaitu mengetahui frekuensi mutasi gen FLG dan polimorfisme gen FADS1 dan FADS2, mengetahui peran polimorfisme gen FADS1 dan FADS2 terhadap substrat dan produk LCPUFA dan efeknya terhadap timbulnya DA, mengetahui pengaruh peningkatan rasio AA terhadap DHA di awal kehidupan terhadap timbulnya DA, mengetahui peran protektif ASI eksklusif untuk pencegahan DA. Digunakan dua desain penelitian 1) potong lintang untuk mengetahui peran polimorfisme gen FADS1 dan FADS2 terhadap perubahan komposisi LCPUFA saat lahir, 2) analisis kesintasan untuk melihat pengaruh mutasi gen Filaggrin dan polimorfisme gen FADS1 dan FADS2 terhadap timbulnya DA, mengetahui peran peningkatan rasio AA/DHA serta mengetahui efek protektif ASI eksklusif terhadap timbulnya DA pada usia satu tahun. Insidens DA dalam penelitian ini sebesar 15,4%. Tidak ditemukan 5 mutasi gen Filaggrin sesuai dengan data NCBI. Frekuensi alel minor pada polimorfisme gen FADS1 22−27%, sedangkan untuk FADS2 berkisar 15−48%. Dalam penelitian ini terlihat pengaruh polimorfisme gen FADS1 dan FADS2 terhadap perubahan komposisi LCPUFA, khususnya peningkatan asam arakidonat pada kelompok alel minor. Dalam penelitian ini tidak ditemukan hubungan antara komposisi LCPUFA dan polimorfisme gen FADS terhadap timbulnya DA. Pemberian ASI eksklusif selama 3−6 bulan tampaknya memberi efek proteksi terhadap DA PeneIitian ini diharapkan dapat menjadi landasan untuk tindakan pencegahan DA. Penelitian ini tidak berhasil menemukan common mutation yang dilaporkan NCBI. Mutasi gen Filaggrin tergantung perbedaan ras, maka untuk menemukan mutasi yang baru lebih baik digunakan sekuensing gen secara penuh. Adanya perbedaan frekuensi alel minor antara anak Indonesia dan Eropa dan aktivitas enzim yang bekerja dengan arah yang berlawanan dengan alel minor populasi Eropa, mengakibatkan peningkatan kadar AA dan DGLA pada populasi alel minor dalam penelitian ini.

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ABSTRACT
Pathomechanism of atopic dermatiis is linked to the gene-environment interactions. One genetic locus consistently linked with AD is mutations of filaggrin gene that can induce disruption in epidermal cytoskeleton aggregation. Some protective measures for the prevention of AD are breastfeeding and the provision of LCPUFA, but clinical studies and meta-analysis have shown inconsistent results, which maybe due variation in the activity of desaturating enzymes modulating PUFA metabolism, which are encoded by the FADS1 and FADS2 gene cluster and the age at which LCPUFA interventions are provided. The general objective is to characterize the impact of genetic variation in the FLG and FADS1, FADS2 genes cluster on LC-PUFA concentration in Indonesian infants. Specific objectives including the characterization of the frequency of FLG and FADS1, FADS2 gene single nucleotide polymorphisms (SNPs), the influence of FADS gene polymorphisms on fatty acid composition and on the occurence of AD, the impact of increasing ratio of arachidonic acid to docosahexaenoic acid on the progression of AD, and to see the protective effect of exclusive breastfeeding for the prevention of AD in the first year of life in Indonesian infants. Designs were 1) cross-sectional study to see the role of FADS1 and FADS2 gene polymorphism on the composition of LCPUFA at birth, 2) survival analysis to see the role of FLG mutation and FADS1 and FADS2 gene polymorphism on the progression of AD, the role of increasing ratio of AA/DHA and the protective effect of exclusively breastfeeding on the occurence of AD in the first year of life. The incidence of AD in this study is 15.4%, No Filaggrin gene mutations based on 5 reported pathogenic SNP was found. The minor allele frequency of FADS1 gene polymorphism were 22−27%, whereas for FADS2 were 15−48%. We found a strong correlation between FADS gene polymorphisms with the changes of LCPUFA composition, especially for the increment of arachidonic acid. No association was found between the composition of LCPUFA and between FADS genes polymorphisms with AD. Exclusive breastfeeding until 3 months was found to be protective against AD. In this study we did not find Filaggrin mutation that reported as pathogenic from NCBI. The frequency of FADS1 polymorphism were 22−27%, whereas FADS2 polymorphism were 15−48%. Strong correlation was seen between genetic variations of FADS genes with the alteration of LCPUFA. Arachidonic acid as the product of LCPUFA was higher in the minor allele compared with the major allele. No association were found between genetic variation of FADS genes and the increased ratio of AA/DHA with the occurence of AD. Exclusive breastfeeding for 3−6 months seems to give protective effect