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- Original Article Influence of Fish Oil-Containing Lipid Emulsions on Parenteral Nutrition-Associated Liver Disease in Neonates
- Jeong-A Park1, Ji-Eun Park1,2, Min-Jae Jeong1,2, Jae-Song Kim1, Eun-Sun Son1, Ho-Seon Eun2,3
- 신생아 환자에서 지방 유제 사용 시 어유 함유 여부에 따른 Parenteral Nutrition-Associated Liver Disease 발생 정도 분석
- 박정아1, 박지은1,2, 정민재1,2, 김재송1, 손은선1, 은호선2,3
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Journal of the Korean Society for Parenteral and Enteral Nutrition 2017;9(1):21-29.
DOI: https://doi.org/10.15747/jcn.2017.9.1.21
Published online: June 30, 2017
Department of Pharmacy, Severance Hospital, Seoul, Korea
Pediatric Nutrition Support Team, Severance Hospital, Seoul, Korea
Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
- Correspondence to Jeong-A Park Department of Pharmacy, Severance Hospital, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea Tel: +82-2-2228-6896, Fax: +82-2-312-5732, E-mail: japark1216@yuhs.ac
• Received: February 8, 2017 • Revised: February 26, 2017 • Accepted: February 27, 2017
Copyright: © Korean Society for Parenteral and Enteral Nutrition
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Abstract
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Purpose: This study is a comparative evaluation of the incidence of parenteral nutrition-associated liver disease (PNALD) when administering intravenous fat emulsions containing fish oil.
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Methods: The medical records of patients who were in the neonatal intensive care unit at Severance Hospital from January, 2012 to December 2015, were reviewed retrospectively. Patients who were administered either soybean oil (SO) or SMOF (containing soybean oil, medium chain triglycerides, olive oil, and fish oil) more than 14 days were included. The patients were excluded if they were administered both agents or had underlying hepatic disease. An increase in bilirubin to 2 mg/dL was defined as PNALD.
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Results: PNALD occurred in only 8 out of a total of 77 patients: 6 out of 31 (19.4%) in the SO group and 2 out of 46 (4.3%) in the SMOF group (P=0.055). The number of patients, whose lab values, such as direct bilirubin, total bilirubin, asparate aminotransferase (AST), alanine amino-transferase, gamma-glutamyl transpeptidase, C-reactive protein, serum triglyceride, and alkaline phosphate, exceeded the normal range, were similar in both groups. The gestational age, birth body weight, and APGAR score at 1 min and 5 min were significantly higher in the SO group and the PN duration was significantly long in the SMOF group. Considering only term infants, there were no significant differences in baseline characteristics and incidence of PNALD. The number of patients whose AST exceeded the normal range was significantly higher in the SO group (P=0.034).
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Conclusion: The incidence of PNALD was similar in both groups. On the other hand, considering the tendency, there was a high correlation between the type of lipid emulsion and an increased direct bilirubin level in the SO group.
서론
위장관 기능이 원활하지 않은 소아 환자에서의 정맥영양(parenteral nutrition, PN) 공급은 질병 치료와 원활한 성장에 도움을 주지만, 장기간 공급할 경우 담즙 정체와 같은 간 질환이 발생한다고 알려져 있다.1 이와 같은 PN에 의한 간담도계 합병증을 parenteral nutrition-associated liver disease (PNALD)라고 한다. PNALD는 담즙 울체에서부터 간부전에 이르기까지 그 증상이 다양하며, 심할 경우 간이식이나 사망에 이르는 경우도 있으므로 예방 및 치료가 중요하다.2
PNALD 발생은 미숙아이거나 저체중 출생아일수록 위험성이 증가하고, 괴사성 장염(necrotic enterocolitis, NEC), 경장 영양 공급의 부족, 동맥관 개존증(patent ductus arteriosus, PDA) 등에 따른 장기간의 정맥 영양 공급, 패혈증(sepsis) 등의 요인도 영향을 미친다.2,3 또한 PN 성분 중 지방 유제의 종류도 PNALD의 발생 정도에 영향을 미치는 것으로 알려져 있으며, 지방 유제 중 대두유(soybean oil)가 주 원인이 되는 것으로 알려져 있다.2
대두유는 필수 지방산을 공급하기 때문에 소아의 원활한 성장에 필요하지만, 간 손상을 유발하는 것으로 알려진 오메가-6와 phytosterol 등이 높은 비율로 함유되어 있다.1,4,5 오메가-6는 염증 반응이나 간효소의 산화 유발 등 여러 가지 기전으로 간 손상을 일으키고,6,7 식물성 steroid인 phytosterol은 담즙 분비와 관련된 신호물질에 길항제로 작용하여 담즙 배설을 감소시킨다.6,8 특히 phytosterol은 위장관으로 흡수가 거의 되지 않아 경구 섭취 시에는 큰 문제가 되지 않지만 정맥 투여 시 공급량에 비례하여 혈중 농도가 증가하고 이것이 간에 축적되기 때문에 정맥 투여될 경우 주로 문제가 된다.6,9,10
반면 어유(fish oil)의 경우 docosahexaenoic acid, eicosapentanoic acid 등을 포함하는 오메가-3가 주 구성성분으로, 염증 유발 정도가 적어 PNALD의 예방과 치료 모두에 효과가 있다는 이론이 최근 제시되고 있다.11,12 이에 따라 지방 유제의 조성에 따른 PNALD에 대한 영향에 대해 많은 연구가 진행 중이지만,13-16 국내 비교 연구는 미흡한 실정이다.
신생아 중환자실에서는 PNALD 발생의 위험요인을 가지고 있으면서 장기간의 PN 공급이 필요한 환자가 많기 때문에 PNALD 예방을 위해 적절한 지방 유제의 선택이 중요하다. 이에 본 연구에서는 신생아 환자에서 대두유 단일 제제 투여군과 어유 함유 제제 투여군 간의 임상적 변화를 비교하여 지방유제의 어유 함유 여부에 따른 PNALD의 발생 정도를 분석함으로써 안전한 지방유제 선택에 기여하고자 하였다.
대상 및 방법
1) 대상자 선정기준
2012년 1월 1일부터 2015년 12월 31일까지 세브란스병원 신생아 중환자실에 입원하여 지방 유제를 투여한 환자 중 대두유 단일 제제(soybean oil, 100%) 혹은 어유 함유 제제(soybean oil 30%, middle chain triglyceride 30%, olive oil 25%, fish oil 15%)를 14일 이상 투여한 환자를 연구대상으로 선정하였다.
2) 대상자 제외기준
두 제제 모두 투여한 이력이 있는 환자, 간 관련 기저질환을 가진 환자와 총 정맥영양(total parenteral nutrition, TPN) 투여기간에 사망한 환자는 제외하였다.
3) 데이터 수집 항목
환자의 출생 시 특성과 관련된 항목으로 재태기간(gestational age), 출생 시 체중, 성별, APGAR score 1 min, APGAR score 5 min값을 수집하였다. PNALD 발생의 위험요인을 파악하기 위해 패혈증, NEC, PDA 등의 기저질환 여부를 확인하였고, PN 투여기간은 연속해서 투여한 총 투여기간을 수집한 후 PN을 금식(nothing per oral, NPO) 상태로 투여한 기간과 경장영양(enteral nutrition, EN)을 병용하여 투여한 기간으로 분류하였다.
Direct bilirubin이 2 mg/dL 이상으로 측정된 것을 PNALD가 발생했다고 정의하여6 이를 primary endpoint로 보았고, 간기능 관련 수치인 direct bilirubin, total bilirubin, asparate aminotransferase (AST), alanine amino-transferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ- GT), C-reactive protein (CRP), serum triglyceride가 원내 기준에 따라 정상수치를 초과한 환자수와 진단명을 기준으로 대사성 산증이 발생한 환자수를 secondary endpoint로 보았다.
TPN 공급량이 미치는 영향을 보기 위해 glucose infusion rate (GIR, mg/kg/min), total protein intake (g/kg/d), total lipid intake (g/kg/d)를 수집하였다.
연속형 변수는 Student’s t-test로 비교하여 결과값을 평균±표준편차로 표시하고, 범주형 변수는 chi-square test를 시행하여 결과값을 빈도(%)로 표시하였다, 통계 분석은 IBM SPSS Statistics ver. 23.0 (IBM Co., Armonk, NY, USA)을 사용하여 수행하였다. P가 0.05 미만인 경우 통계적으로 유의한 차이가 있는 것으로 평가하였다.
본 연구는 연구대상자의 안전 및 보호에 관한 사항 등을 포함한 연구 계획을 세브란스병원 연구심의위원회로부터 승인(IRB no. 4-2016-1039)을 받았으며, 전자의무기록에 기록된 내용만을 수집하여 분석하는 후향적 연구이기 때문에 연구대상자의 동의는 생략하였다.
결과
2012년 1월 1일부터 2015년 12월 31까지 두 지방 유제 중 한 종류만을 14일 이상 투여한 환자는 총 82명이었고, 이 중 TPN 투여기간에 사망한 환자 5명을 제외하여 최종 77명을 대상으로 후향적 전자의무기록 검토를 시행하였다(Fig. 1). 대두유 단일 제제군 31명, 어유 함유 제제군 46명을 대상으로 하였으며, 생화학적 검사 결과는 TPN 종료 후 일주일 이내 가장 최근 결과까지, TPN 공급량은 투여 시작 후 14일 동안만을 수집하여 분석하였다.
Fig. 1 
Fig. 1 Flow chart of study population. IVFE = intravenous fat emulsion; NICU = neonatal intensive care unit; SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; TPN = total parenteral nutrition.
Download Figure 지방 유제 종류 이외에 PNALD 발생에 영향을 줄 수 있는 요인인 출생 시 특성, TPN 투여기간 및 PNALD와 관련된 질병 등을 비교하였다.
1) 출생 시 특성
신생아의 출생 시 건강상태가 PNALD 발생에 미치는 영향을 파악하기 위해 두 환자군의 출생시 특성을 비교하였다. 성비는 대두유 단일 제제군(남, 51.6% vs. 여, 48.4%)과 어유 함유 제제군(남, 50.0% vs. 여, 50.0%) 둘 다 비슷한 비율이었고, 재태기간(대두유 단일 제제군 vs. 어유 함유 제제군, 35.69주 vs. 32.37주, P=0.001)과 출생 시 체중(2.35 kg vs. 1.80 kg, P= 0.003), 그리고 APGAR score 1 min (5.13 vs. 3.84, P=0.016) 및 5 min (6.77 vs. 5.63, P=0.010) 모두 어유 함유 제제군에서 유의하게 낮은 것을 확인할 수 있었다(Table 1). 그러나 재태기간이 37주 미만인 미숙아가 대두유 단일 제제군(58.1%)에 비해 어유 함유 제제군(78.3%)에서 높은 비율로 나타났고(Fig. 2), 출생 시 체중을 저체중 출생아 분류 기준(Appendix 1)에 따라 분류했을 때 초극소 저체중 출생아가 대두유 단일 제제군 0%, 어유 함유 제제군 28.3% (P=0.001)으로 어유 함유 제제군에서 유의하게 많았다(Fig. 3).
Fig. 2
Fig. 3
Fig. 2 Distribution of gestational age. SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil.
Download Figure
Fig. 3 Distribution of birth weight. SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; ELBW = extremely low body; VLBW = very low body weight; LBW = low body weight.
Download Figure
Table 1
Download Table
Birth characteristics (n=77)
| Characteristic | SO group (n=31) | SMOF group (n=46) | P-value |
|---|---|---|---|
| Sex | |||
| Male | 16 (51.6) | 23 (50.0) | |
| Female | 15 (48.4) | 23 (50.0) | |
| GA (wk) | 35.69±3.13 | 32.37±5.02 | 0.001 |
| GA<28 | 1 (3.2) | 10 (21.7) | 0.023 |
| 28≤GA<37 | 17 (54.8) | 26 (56.5) | 0.884 |
| GA≥37 | 13 (41.9) | 10 (21.7) | 0.058 |
| Birth weight (kg) | 2.35±0.65 | 1.80±0.93 | 0.003 |
| APGAR scorea | |||
| 1 min | 5.13±1.94 | 3.84±2.40 | 0.016 |
| 5 min | 6.77±1.54 | 5.63±2.20 | 0.010 |
Values are presented as number (%) or mean±standard deviation. SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; GA = gestational age.
aAPGAR score: Method to quickly summarize the health of neonate by scoring of breathing effort, heart rate, muscle tone, reflexes, skin color
2) TPN 투여기간
TPN을 연속해서 투여한 총 투여 기간을 비교하고, PN을 NPO 상태로 투여한 기간과 EN을 병용하여 투여한 기간으로 분류하여 분석하였다(Table 2). 총 투여 기간(대두유 단일 제제군 vs. 어유 함유 제제군, 19.42일 vs. 25.85일, P=0.006) 및 총 투여 기간에 대한 EN 병용 기간의 비율(59.24% vs. 80.10%, P=0.014)이 어유 함유 제제군에서 유의하게 길었다.
Table 2
Download Table
TPN duration (n=77)
| Duration | SO group (n=31) | SMOF group (n=46) | P-value |
|---|---|---|---|
| TPN duration (d) | 19.42±8.31 | 25.85±11.49 | 0.006 |
| TPN duration depending on combination with ENa (n=49) | |||
| NPO+PN (d) | 6.96±5.30 | 4.58±4.76 | 0.107 |
| EN+PN (d) | 12.57±11.47 | 23.46±14.18 | 0.005 |
| EN+PN/total TPN duration ratio (%) | 59.24±29.33 | 80.10±27.87 | 0.014 |
Values are presented as mean±standard deviation.
TPN = total parenteral nutrition; SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; NPO = nothing per oral; EN = enteral nutrition; PN = parenteral nutrition.
aEvaluation of patients who only can be checked about feeding.
3) PNALD 관련 질병
PNALD 발생과 연관성 있는 질병을 진단명 기준으로 분석하였을 때, PDA (대두유 단일 제제군 vs. 어유 함유 제제군, 41.9% vs. 39.1%, P=0.894)와 NEC (0% vs. 2.2%, P=0.401) 및 패혈증(12.9% vs. 21.7%, P=0.296) 모두 두 군 간 유의한 차이가 없었다(Table 3).
Table 3
Download Table
Underlying diseases related to parenteral nutrition-associated liver disease (n=77)
| Underlying diseases | SO group (n=31) | SMOF group (n=46) | P-value |
|---|---|---|---|
| PDA | 13 (41.9) | 18 (39.1) | 0.894 |
| NEC | 0 (0) | 1 (2.2) | 0.401 |
| Sepsis | 4 (12.9) | 10 (21.7) | 0.296 |
Values are presented as number (%).
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; PDA = patent ductus arteriosus; NEC = necrotic enterocolitis.
Primary endpoint인 direct bilirubin이 2 mg/dL 이상으로 측정된 환자수는 대두유 단일 제제군에서 6명(19.4%), 어유 함유 제제군에서 2명(4.3%)이었다(P=0.055).
한편 간 관련 수치들이 정상범위를 초과한 환자수는 direct bilirubin (대두유 단일 제제군 vs. 어유 함유 제제군, 77.4% vs. 84.8%, P=0.207), total bilirubin (90.3% vs. 89.1%, P= 1.000), AST (64.5% vs. 45.7%, P=0.104), ALT (12.9% vs. 4.3%, P=0.213), triglyceride (12.9% vs. 15.2%, P=1.000), ALP (74.2% vs. 84.8%, P=0.250), CRP (12.9% vs. 10.9%, P=1.000), γ-GT (12.9% vs. 10.9%, P=1.000)에서 모두 통계적으로 유의한 차이가 없었다. 대사성 산증 발생 빈도 역시(0% vs. 2.2%, P=0.409) 통계적으로 유의한 차이가 없었다(Table 4).
Table 4
Download Table
Laboratory test (n=77)
Values are presented as number (%).
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; AST = asparate aminotransferase; ALT = alanine amino-transferase; ALP = alkaline phosphatase; CRP = C-reactive protein; γ-GT = gamma-glutamyl transpeptidase.
TPN 공급량은 두 군 간 유의한 차이는 있었지만 두 군 모두 lipid (대두유 단일 제제군 vs. 어유 함유 제제군, 2.83 g/kg/d vs. 3.06 g/kg/d, P<0.05), amino acid (2.48 g/kg/d vs. 2.61 g/kg/d, P<0.05) 공급량 및 GIR (10.17 mg/kg/min vs. 9.32 mg/kg/min, P<0.05)의 평균값이 미국경장정맥영양학회(American Society for Parenteral and Enteral Nutrition, ASPEN) 권장 공급량(Appendix 2) 범위 내에 포함되는 것을 확인할 수 있었다(Table 5).
Table 5
Download Table
TPN supply
| TPN supply | SO group (n=31) | SMOF group (n=46) | P-value |
|---|---|---|---|
| Lipid (g/kg/d) | 2.83±0.83 | 3.06±1.09 | <0.05 |
| GIR (mg/kg/min) | 10.17±9.74 | 9.32±8.43 | <0.05 |
| Amino acid (g/kg/d) | 2.48±0.72 | 2.61±0.90 | <0.05 |
Values are presented as mean±standard deviation.
TPN = total parenteral nutrition; SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; GIR = glucose infusion rate.
PNALD 영향 요인을 보정하기 위해 재태기간이 37주 미만인 미숙아를 제외하여 만삭아 환자 23명(Fig. 2의 37주 이상에 해당하는 환자)을 대상으로 추가 분석을 시행하였다.
출생 시 체중과 APGAR score, PN 투여기간 및 PNALD 관련 진단명에서 모두 두 군 간 유의한 차이가 없었다(Table 6).
Table 6
Download Table
Data of term infants (n=23)
| Term infants | SO group (n=13) | SMOF group (n=10) | P-value |
|---|---|---|---|
| Sex | |||
| Male | 6 (46.2) | 4 (40.0) | |
| Female | 7 (53.8) | 6 (60.0) | |
| Birth weight (kg) | 2.92±0.42 | 3.01±0.33 | 0.574 |
| APGAR scorea | |||
| 1 min | 6.23±1.54 | 6.50±2.07 | 0.736 |
| 5 min | 7.46±1.20 | 7.75±1.58 | 0.640 |
| TPN duration (d) | 24.64±13.18 | 22.30±8.95 | 0.631 |
| TPN duration depending on combination with ENb (n=13) | |||
| NPO+PN (d) | 9.00±6.57 | 8.60±6.91 | 0.918 |
| EN+PN (d) | 16.13±18.22 | 14.80±15.42 | 0.895 |
| PDA | 8 (61.5) | 4 (40.0) | 0.305 |
| NEC | 0 (0) | 0 (0) | - |
| Sepsis | 2 (15.4) | 0 (0) | 0.194 |
Values are presented as number (%) or mean±standard deviation.
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; TPN = total parenteral nutrition; NPO = nothing per oral; PN = parenteral nutrition; EN = enteral nutrition; PDA = patent ductus arteriosus; NEC = necrotic enterocolitis.
aAPGAR score: Method to quickly summarize the health of neonate by scoring of breathing effort, heart rate, muscle tone, reflexes, skin color.
bEvaluation of patients who only can be checked about feeding.
AST가 대두유 단일 제제군 13명 모두에게서 정상 범위를 초과한 것으로 관찰되어 7명(70%)인 어유 함유 제제군과 유의한 차이를 보였다(P=0.034). Direct bilirubin이 2 mg/dL 이상으로 관찰된 환자수는 대두유 단일 제제군 4명(30.8%), 어유 함유 제제군 1명(10.0%)으로 유의한 차이가 없었고, AST를 제외한 간 관련 수치가 정상 범위를 초과한 환자수 역시 통계적으로 유의한 차이가 없었다(Table 7).
Table 7
Download Table
Laboratory test_term infants (n=23)
Values are presented as number (%).
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; AST = asparate aminotransferase; ALT = alanine amino-transferase; ALP = alkaline phosphatase; CRP = C-reactive protein; γ-GT = gamma-glutamyl transpeptidase.
고찰
본 연구 결과 지방 유제 투여 후 PNALD 발생에 있어서 통계적으로 두 군 간 유의한 차이가 없었다. 하지만 PNALD 위험요인과 발생 빈도 사이의 연관성을 분석했을 때 두 군 간 차이가 있었다.
어유 함유 제제군은 재태기간, 출생 시 체중 및 APGAR score가 유의하게 낮고 미숙아와 저체중 출생아의 비율이 높은 것을 고려할 때, 대두유 단일 제제군에 비해 유의한 차이로 더 미숙한 상태임을 알 수 있으며 이는 PNALD의 위험성이 더 높은 것을 의미한다.2,3 그럼에도 불구하고 PNALD 발생 환자수와 비율이 대두유 단일 제제군에 비해 적은 것으로 보아 어유 함유 제제 사용 시 PANLD 예방에 효과가 있다는 이론을 뒷받침할 수 있을 것이다.11,12
반면에 대두유 단일 제제군에서 PNALD가 발생한 환자들의 기본 특성과 지방 유제 투여 추이를 분석해 보았을 때, 재태기간이 평균 37.2주, 출생 시 체중이 평균 2.63 kg으로 정상이었고 6명 중 5명의 환자에서 지방 유제 투여가 지속됨에 따라 direct bilirubin이 점차 상승하였다(Table 8, Fig. 4). 이를 통해 direct bilirubin 상승의 영향 요인 중 지방 유제 투여가 그 원인으로서 가능성이 높은 것으로 판단할 수 있다.
Fig. 4
Fig. 4 Correlation between the type of lipid emulsions and changes of direct bilirubin (D) in patients get parenteral nutrition associated-liver disease. Patients labeld as follows: SO group, S1∼S6; SMOF group, F1∼F2. SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; PN = parenteral nutrition.
Download Figure
Table 8
Download Table
Birth characteristics of patients diagnosed parenteral nutrition-associated liver disease (n=8)
| Characteristic | SO group (n=6) | SMOF group (n=2) | P-value |
|---|---|---|---|
| Gestational age (wk) | 37.1±2.65 | 32.85±8.84 | 0.622 |
| Birth weight (kg) | 2.63±0.52 | 1.92±1.35 | 0.589 |
| APGAR scorea | |||
| 1 min | 5.50±2.35 | 2.00±2.83 | 0.128 |
| 5 min | 6.50±2.81 | 4.00±2.83 | 0.318 |
Values are presented as mean±standard deviation.
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil.
aAPGAR score: Method to quickly summarize the health of neonate by scoring of breathing effort, heart rate, muscle tone, reflexes, skin color.
Vlaardingerbroek 등의 전향적 연구17에서도 대두유 단일 제제군과 어유 함유 제제군의 담즙 정체 발생 빈도와 total bilirubin 및 direct bilirubin의 최대값은 두 군 간 유의한 차이가 없었다. 하지만 담즙 정체를 일으키는 성분인 phytosterol의 혈중 농도가 대두유 단일 제제군에서 유의하게 높았고, 지방 유제 투여 일수가 증가함에 따라 혈중 농도가 유의한 차이로 높아지는 것을 확인하였다. 본 연구는 후향적으로 진행되어 혈중 phytosterol 농도를 확인하지 않았지만, 지방 유제 투여에 따른 direct bilirubin의 상승 추이 분석을 통해 해당 연구 결과와 동일하게 대두유 단일 제제의 PNALD 발생 위험성을 확인한 것에 의의가 있다(Table 8, Fig. 4).
대사성 산증으로 진단된 환자수도 두 군 간 유의한 차이가 없었다. 대사성 산증은 정맥 영양 공급 시 발생할 수 있는 합병증이나,18 재태기간 및 패혈증 등의 기저질환에 의해서도 발생할 수 있다. 어유 함유 제제군에서 대사성 산증이 발생한 환자 1명의 경우 재태기간이 28.4주, 출생 시 체중이 1.66 kg인 저체중 미숙아였으며 패혈증 진단된 것을 고려할 때 이로 인한 영향을 배제할 수 없었다.
본 연구는 두 환자군을 동일한 기저상태에서 비교할 수 없었던 한계점이 있었다. 세브란스병원에서 어유 함유 제제 도입 시 PNALD 발생 위험도가 높은 미숙아들을 위주로 투여하였기 때문에, 출생 시 특성에서 두 군 간 유의한 차이가 있었고 TPN 총 투여 기간이 어유 함유 제제군에서 유의하게 길었다. 또한 EN 병용 기간의 비율이 어유 함유 제제군에서 유의하게 길었던 것으로 보아 EN 투여가 PNALD 발생 빈도를 낮추는 데에 영향을 미쳤을 가능성도 배제할 수 없고(Table 2), EN 병용 여부에 대한 정보를 얻기 어려운 환자는 제외하고 EN 병용 기간의 비율을 비교한 점이 한계였다.
환자의 특성 차이를 줄이기 위하여 재태기간 보정 후 만삭아만을 비교했을 때 대상 환자수의 부족으로 인해 PNALD 발생 빈도는 통계적으로 유의한 차이를 확인하기 어려웠다. 하지만 지방 유제 종류 이외의 요인에서 유의한 차이가 없었으며 AST가 정상범위를 초과한 환자수가 유의한 차이로 대두유 단일 제제군에서 많았던 결과를 통해 대두유 단일 제제와 간기능 변화와의 연관성을 확인할 수 있었다. 따라서 본 연구는 신생아 중환자를 대상으로 한 대두유와 어유의 비교연구로서 지방 유제 종류에 따른 간기능 변화의 차이를 확인한 연구라는 점에서 의의가 있다.
결론
본 연구는 지방 유제가 투여된 신생아를 대상으로 지방 유제 종류에 따른 PNALD 발생 정도 및 간기능 관련 수치의 변화를 분석하였다. 지방 유제에 따른 PNALD 발생 빈도는 유의한 차이가 없었지만 대두유 단일 제제군에서 발생 경향이 높았고, 만삭아만을 대상으로 추가 분석하였을 때 AST가 정상범위를 초과한 환자수가 대두유 단일 제제군에서 유의하게 더 많았다. 이번 연구는 신생아 지방 유제 선택 시 기초 자료로 활용할 수 있겠으나, 앞으로 지방 유제에 따른 PNALD 발생 빈도의 유의한 차이를 확인하기 위해서 이번 연구의 한계점을 보완한 추가적 연구가 필요하겠다.
Appendix
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- 2. Wales PW, Allen N, Worthington P, George D, Compher C. American Society for Parenteral, and Enteral Nutrition, Teitelbaum D. A.S.P.E.N. clinical guidelines:support of pediatric patients with intestinal failure at risk of parenteral nutrition-associated liver disease. JPEN J Parenter Enteral Nutr 2014;38(5):538-57. PubMed
- 3. Rangel SJ, Calkins CM, Cowles RA, Barnhart DC, Huang EY, Abdullah F, et al. Parenteral nutrition-associated cholestasis:an American Pediatric Surgical Association Outcomes and Clinical Trials Committee systematic review. J Pediatr Surg 2012;47(1):225-40. ArticlePubMed
- 4. Park HW, Lee NM, Kim JH, Kim KS, Kim SN. Parenteral fish oil-containing lipid emulsions may reverse parenteral nutrition- associated cholestasis in neonates:a systematic review and meta-analysis. J Nutr 2015;145(2):277-83. ArticlePubMed
- 5. Deshpande G, Simmer K. Lipids for parenteral nutrition in neonates. Curr Opin Clin Nutr Metab Care 2011;14(2):145-50. ArticlePubMed
- 6. Hojsak I, Colomb V, Braegger C, Bronsky J, Campoy C, Domellöf M, et al. ESPGHAN Committee on Nutrition Position Paper. Intravenous lipid emulsions and risk of hepatotoxicity in infants and children:a systematic review and meta-analysis. J Pediatr Gastroenterol Nutr 2016;62(5):776-92. ArticlePubMed
- 7. Krohn K, Koletzko B. Parenteral lipid emulsions in paediatrics. Curr Opin Clin Nutr Metab Care 2006;9(3):319-23. ArticlePubMed
- 8. Iyer KR, Spitz L, Clayton P. BAPS prize lecture:new insight into mechanisms of parenteral nutrition-associated cholestasis:role of plant sterols. British Association of Paediatric Surgeons. J Pediatr Surg 1998;33(1):1-6. PubMed
- 9. Clayton PT, Bowron A, Mills KA, Massoud A, Casteels M, Milla PJ. Phytosterolemia in children with parenteral nutrition- associated cholestatic liver disease. Gastroenterology 1993;105(6):1806-13. ArticlePubMed
- 10. Nikkilä K, Nissinen MJ, Gylling H, Isoniemi H, Miettinen TA. Serum sterols in patients with primary biliary cirrhosis and acute liver failure before and after liver transplantation. J Hepatol 2008;49(6):936-45. ArticlePubMed
- 11. Puder M, Valim C, Meisel JA, Le HD, de Meijer VE, Robinson EM, et al. Parenteral fish oil improves outcomes in patients with parenteral nutrition-associated liver injury. Ann Surg 2009;250(3):395-402. ArticlePubMed
- 12. Yoon JH. Parenteral nutrition support in preterm infants. J Clin Nutr 2014;6(2):51-5. Article
- 13. Skouroliakou M, Konstantinou D, Agakidis C, Delikou N, Koutri K, Antoniadi M, et al. Cholestasis, bronchopulmonary dysplasia, and lipid profile in preterm infants receiving MCT/ω-3- PUFA-containing or soybean-based lipid emulsions. Nutr Clin Pract 2012;27(6):817-24. ArticlePubMedPDF
- 14. Savini S, D’Ascenzo R, Biagetti C, Serpentini G, Pompilio A, Bartoli A, et al. The effect of 5 intravenous lipid emulsions on plasma phytosterols in preterm infants receiving parenteral nutrition:a randomized clinical trial. Am J Clin Nutr 2013;98(2):312-8. ArticlePubMed
- 15. Tomsits E, Pataki M, Tölgyesi A, Fekete G, Rischak K, Szollár L. Safety and efficacy of a lipid emulsion containing a mixture of soybean oil, medium-chain triglycerides, olive oil, and fish oil:a randomised, double-blind clinical trial in premature infants requiring parenteral nutrition. J Pediatr Gastroenterol Nutr 2010;51(4):514-21. ArticlePubMed
- 16. Beken S, Dilli D, Fettah ND, Kabataş EU, Zenciroğlu A, Okumuş N. The influence of fish-oil lipid emulsions on retinopathy of prematurity in very low birth weight infants:a randomized controlled trial. Early Hum Dev 2014;90(1):27-31. ArticlePubMed
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References
Figure & Data
Fig. 1 Flow chart of study population. IVFE = intravenous fat emulsion; NICU = neonatal intensive care unit; SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; TPN = total parenteral nutrition.
Download Figure
Fig. 2 Distribution of gestational age. SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil.
Download Figure
Fig. 3 Distribution of birth weight. SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; ELBW = extremely low body; VLBW = very low body weight; LBW = low body weight.
Download Figure
Table 1
Download Table
Birth characteristics (n=77)
| Characteristic | SO group (n=31) | SMOF group (n=46) | P-value |
|---|---|---|---|
| Sex | |||
| Male | 16 (51.6) | 23 (50.0) | |
| Female | 15 (48.4) | 23 (50.0) | |
| GA (wk) | 35.69±3.13 | 32.37±5.02 | 0.001 |
| GA<28 | 1 (3.2) | 10 (21.7) | 0.023 |
| 28≤GA<37 | 17 (54.8) | 26 (56.5) | 0.884 |
| GA≥37 | 13 (41.9) | 10 (21.7) | 0.058 |
| Birth weight (kg) | 2.35±0.65 | 1.80±0.93 | 0.003 |
| APGAR scorea | |||
| 1 min | 5.13±1.94 | 3.84±2.40 | 0.016 |
| 5 min | 6.77±1.54 | 5.63±2.20 | 0.010 |
Values are presented as number (%) or mean±standard deviation. SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; GA = gestational age.
aAPGAR score: Method to quickly summarize the health of neonate by scoring of breathing effort, heart rate, muscle tone, reflexes, skin color
Table 2
Download Table
TPN duration (n=77)
| Duration | SO group (n=31) | SMOF group (n=46) | P-value |
|---|---|---|---|
| TPN duration (d) | 19.42±8.31 | 25.85±11.49 | 0.006 |
| TPN duration depending on combination with ENa (n=49) | |||
| NPO+PN (d) | 6.96±5.30 | 4.58±4.76 | 0.107 |
| EN+PN (d) | 12.57±11.47 | 23.46±14.18 | 0.005 |
| EN+PN/total TPN duration ratio (%) | 59.24±29.33 | 80.10±27.87 | 0.014 |
Values are presented as mean±standard deviation.
TPN = total parenteral nutrition; SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; NPO = nothing per oral; EN = enteral nutrition; PN = parenteral nutrition.
aEvaluation of patients who only can be checked about feeding.
Table 3
Download Table
Underlying diseases related to parenteral nutrition-associated liver disease (n=77)
| Underlying diseases | SO group (n=31) | SMOF group (n=46) | P-value |
|---|---|---|---|
| PDA | 13 (41.9) | 18 (39.1) | 0.894 |
| NEC | 0 (0) | 1 (2.2) | 0.401 |
| Sepsis | 4 (12.9) | 10 (21.7) | 0.296 |
Values are presented as number (%).
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; PDA = patent ductus arteriosus; NEC = necrotic enterocolitis.
Table 4
Download Table
Laboratory test (n=77)
Values are presented as number (%).
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; AST = asparate aminotransferase; ALT = alanine amino-transferase; ALP = alkaline phosphatase; CRP = C-reactive protein; γ-GT = gamma-glutamyl transpeptidase.
Table 5
Download Table
TPN supply
| TPN supply | SO group (n=31) | SMOF group (n=46) | P-value |
|---|---|---|---|
| Lipid (g/kg/d) | 2.83±0.83 | 3.06±1.09 | <0.05 |
| GIR (mg/kg/min) | 10.17±9.74 | 9.32±8.43 | <0.05 |
| Amino acid (g/kg/d) | 2.48±0.72 | 2.61±0.90 | <0.05 |
Values are presented as mean±standard deviation.
TPN = total parenteral nutrition; SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; GIR = glucose infusion rate.
Table 6
Download Table
Data of term infants (n=23)
| Term infants | SO group (n=13) | SMOF group (n=10) | P-value |
|---|---|---|---|
| Sex | |||
| Male | 6 (46.2) | 4 (40.0) | |
| Female | 7 (53.8) | 6 (60.0) | |
| Birth weight (kg) | 2.92±0.42 | 3.01±0.33 | 0.574 |
| APGAR scorea | |||
| 1 min | 6.23±1.54 | 6.50±2.07 | 0.736 |
| 5 min | 7.46±1.20 | 7.75±1.58 | 0.640 |
| TPN duration (d) | 24.64±13.18 | 22.30±8.95 | 0.631 |
| TPN duration depending on combination with ENb (n=13) | |||
| NPO+PN (d) | 9.00±6.57 | 8.60±6.91 | 0.918 |
| EN+PN (d) | 16.13±18.22 | 14.80±15.42 | 0.895 |
| PDA | 8 (61.5) | 4 (40.0) | 0.305 |
| NEC | 0 (0) | 0 (0) | - |
| Sepsis | 2 (15.4) | 0 (0) | 0.194 |
Values are presented as number (%) or mean±standard deviation.
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; TPN = total parenteral nutrition; NPO = nothing per oral; PN = parenteral nutrition; EN = enteral nutrition; PDA = patent ductus arteriosus; NEC = necrotic enterocolitis.
aAPGAR score: Method to quickly summarize the health of neonate by scoring of breathing effort, heart rate, muscle tone, reflexes, skin color.
bEvaluation of patients who only can be checked about feeding.
Table 7
Download Table
Laboratory test_term infants (n=23)
Values are presented as number (%).
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; AST = asparate aminotransferase; ALT = alanine amino-transferase; ALP = alkaline phosphatase; CRP = C-reactive protein; γ-GT = gamma-glutamyl transpeptidase.
Fig. 4 Correlation between the type of lipid emulsions and changes of direct bilirubin (D) in patients get parenteral nutrition associated-liver disease. Patients labeld as follows: SO group, S1∼S6; SMOF group, F1∼F2. SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; PN = parenteral nutrition.
Download Figure
Table 8
Download Table
Birth characteristics of patients diagnosed parenteral nutrition-associated liver disease (n=8)
| Characteristic | SO group (n=6) | SMOF group (n=2) | P-value |
|---|---|---|---|
| Gestational age (wk) | 37.1±2.65 | 32.85±8.84 | 0.622 |
| Birth weight (kg) | 2.63±0.52 | 1.92±1.35 | 0.589 |
| APGAR scorea | |||
| 1 min | 5.50±2.35 | 2.00±2.83 | 0.128 |
| 5 min | 6.50±2.81 | 4.00±2.83 | 0.318 |
Values are presented as mean±standard deviation.
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil.
aAPGAR score: Method to quickly summarize the health of neonate by scoring of breathing effort, heart rate, muscle tone, reflexes, skin color.
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XML DownloadInfluence of Fish Oil-Containing Lipid Emulsions on Parenteral Nutrition-Associated Liver Disease in Neonates
Fig. 1
Flow chart of study population. IVFE = intravenous fat emulsion; NICU = neonatal intensive care unit; SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; TPN = total parenteral nutrition.
Fig. 2
Distribution of gestational age. SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil.
Fig. 3
Distribution of birth weight. SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; ELBW = extremely low body; VLBW = very low body weight; LBW = low body weight.
Fig. 4
Correlation between the type of lipid emulsions and changes of direct bilirubin (D) in patients get parenteral nutrition associated-liver disease. Patients labeld as follows: SO group, S1∼S6; SMOF group, F1∼F2. SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; PN = parenteral nutrition.
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Influence of Fish Oil-Containing Lipid Emulsions on Parenteral Nutrition-Associated Liver Disease in Neonates
Birth characteristics (n=77)
| Characteristic | SO group (n=31) | SMOF group (n=46) | P-value |
|---|---|---|---|
| Sex | |||
| Male | 16 (51.6) | 23 (50.0) | |
| Female | 15 (48.4) | 23 (50.0) | |
| GA (wk) | 35.69±3.13 | 32.37±5.02 | 0.001 |
| GA<28 | 1 (3.2) | 10 (21.7) | 0.023 |
| 28≤GA<37 | 17 (54.8) | 26 (56.5) | 0.884 |
| GA≥37 | 13 (41.9) | 10 (21.7) | 0.058 |
| Birth weight (kg) | 2.35±0.65 | 1.80±0.93 | 0.003 |
| APGAR score |
|||
| 1 min | 5.13±1.94 | 3.84±2.40 | 0.016 |
| 5 min | 6.77±1.54 | 5.63±2.20 | 0.010 |
Values are presented as number (%) or mean±standard deviation. SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; GA = gestational age.
aAPGAR score: Method to quickly summarize the health of neonate by scoring of breathing effort, heart rate, muscle tone, reflexes, skin color
TPN duration (n=77)
| Duration | SO group (n=31) | SMOF group (n=46) | P-value |
|---|---|---|---|
| TPN duration (d) | 19.42±8.31 | 25.85±11.49 | 0.006 |
| TPN duration depending on combination with EN |
|||
| NPO+PN (d) | 6.96±5.30 | 4.58±4.76 | 0.107 |
| EN+PN (d) | 12.57±11.47 | 23.46±14.18 | 0.005 |
| EN+PN/total TPN duration ratio (%) | 59.24±29.33 | 80.10±27.87 | 0.014 |
Values are presented as mean±standard deviation.
TPN = total parenteral nutrition; SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; NPO = nothing per oral; EN = enteral nutrition; PN = parenteral nutrition.
aEvaluation of patients who only can be checked about feeding.
Underlying diseases related to parenteral nutrition-associated liver disease (n=77)
| Underlying diseases | SO group (n=31) | SMOF group (n=46) | P-value |
|---|---|---|---|
| PDA | 13 (41.9) | 18 (39.1) | 0.894 |
| NEC | 0 (0) | 1 (2.2) | 0.401 |
| Sepsis | 4 (12.9) | 10 (21.7) | 0.296 |
Values are presented as number (%).
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; PDA = patent ductus arteriosus; NEC = necrotic enterocolitis.
Laboratory test (n=77)
| Laboratory test | SO group (n=31) | SMOF group (n=46) | P-value |
|---|---|---|---|
| The number of patients who observed on direct bilirubin ≥2 mg/dL | 6 (19.4) | 2 (4.3) | 0.055 |
| Lab value exceeded normal range | |||
| Direct bilirubin | 24 (77.4) | 39 (84.8) | 0.207 |
| Total bilirubin | 28 (90.3) | 41 (89.1) | 1.000 |
| AST | 20 (64.5) | 21 (45.7) | 0.104 |
| ALT | 4 (12.9) | 2 (4.3) | 0.213 |
| Triglyceride | 4 (12.9) | 7 (15.2) | 1.000 |
| ALP | 23 (74.2) | 39 (84.8) | 0.250 |
| CRP | 4 (12.9) | 5 (10.9) | 1.000 |
| γ-GT | 4 (12.9) | 5 (10.9) | 1.000 |
| Diagnosed with metabolic acidosis | 0 (0) | 1 (2.2) | 0.409 |
Values are presented as number (%).
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; AST = asparate aminotransferase; ALT = alanine amino-transferase; ALP = alkaline phosphatase; CRP = C-reactive protein; γ-GT = gamma-glutamyl transpeptidase.
TPN supply
| TPN supply | SO group (n=31) | SMOF group (n=46) | P-value |
|---|---|---|---|
| Lipid (g/kg/d) | 2.83±0.83 | 3.06±1.09 | <0.05 |
| GIR (mg/kg/min) | 10.17±9.74 | 9.32±8.43 | <0.05 |
| Amino acid (g/kg/d) | 2.48±0.72 | 2.61±0.90 | <0.05 |
Values are presented as mean±standard deviation.
TPN = total parenteral nutrition; SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; GIR = glucose infusion rate.
Data of term infants (n=23)
| Term infants | SO group (n=13) | SMOF group (n=10) | P-value |
|---|---|---|---|
| Sex | |||
| Male | 6 (46.2) | 4 (40.0) | |
| Female | 7 (53.8) | 6 (60.0) | |
| Birth weight (kg) | 2.92±0.42 | 3.01±0.33 | 0.574 |
| APGAR score |
|||
| 1 min | 6.23±1.54 | 6.50±2.07 | 0.736 |
| 5 min | 7.46±1.20 | 7.75±1.58 | 0.640 |
| TPN duration (d) | 24.64±13.18 | 22.30±8.95 | 0.631 |
| TPN duration depending on combination with EN |
|||
| NPO+PN (d) | 9.00±6.57 | 8.60±6.91 | 0.918 |
| EN+PN (d) | 16.13±18.22 | 14.80±15.42 | 0.895 |
| PDA | 8 (61.5) | 4 (40.0) | 0.305 |
| NEC | 0 (0) | 0 (0) | - |
| Sepsis | 2 (15.4) | 0 (0) | 0.194 |
Values are presented as number (%) or mean±standard deviation.
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; TPN = total parenteral nutrition; NPO = nothing per oral; PN = parenteral nutrition; EN = enteral nutrition; PDA = patent ductus arteriosus; NEC = necrotic enterocolitis.
aAPGAR score: Method to quickly summarize the health of neonate by scoring of breathing effort, heart rate, muscle tone, reflexes, skin color.
bEvaluation of patients who only can be checked about feeding.
Laboratory test_term infants (n=23)
| Laboratory test | SO group (n=13) | SMOF group (n=10) | P-value |
|---|---|---|---|
| Observed on direct bilirubin≥2 mg/dL | 4 (30.8) | 1 (10.0) | 0.231 |
| Lab value exceeded normal range | |||
| Direct bilirubin | 9 (69.2) | 5 (50.0) | 0.349 |
| Total bilirubin | 11 (84.6) | 7 (70.0) | 0.400 |
| AST | 13 (100.0) | 7 (70.0) | 0.034 |
| ALT | 3 (23.1) | 1 (10.0) | 0.412 |
| Triglyceride | 2 (15.4) | 1 (10.0) | 0.704 |
| ALP | 9 (69.2) | 7 (70.0) | 0.968 |
| CRP | 4 (30.8) | 4 (40.0) | 0.645 |
| γ-GT | 4 (30.8) | 3 (30.0) | 0.968 |
| Diagnosed with metabolic acidosis | 0 (0) | 1 (10.0) | 0.244 |
Values are presented as number (%).
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; AST = asparate aminotransferase; ALT = alanine amino-transferase; ALP = alkaline phosphatase; CRP = C-reactive protein; γ-GT = gamma-glutamyl transpeptidase.
Birth characteristics of patients diagnosed parenteral nutrition-associated liver disease (n=8)
| Characteristic | SO group (n=6) | SMOF group (n=2) | P-value |
|---|---|---|---|
| Gestational age (wk) | 37.1±2.65 | 32.85±8.84 | 0.622 |
| Birth weight (kg) | 2.63±0.52 | 1.92±1.35 | 0.589 |
| APGAR score |
|||
| 1 min | 5.50±2.35 | 2.00±2.83 | 0.128 |
| 5 min | 6.50±2.81 | 4.00±2.83 | 0.318 |
Values are presented as mean±standard deviation.
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil.
aAPGAR score: Method to quickly summarize the health of neonate by scoring of breathing effort, heart rate, muscle tone, reflexes, skin color.
Table 1 Birth characteristics (n=77)
Values are presented as number (%) or mean±standard deviation. SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; GA = gestational age.
APGAR score: Method to quickly summarize the health of neonate by scoring of breathing effort, heart rate, muscle tone, reflexes, skin color
Table 2 TPN duration (n=77)
Values are presented as mean±standard deviation.
TPN = total parenteral nutrition; SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; NPO = nothing per oral; EN = enteral nutrition; PN = parenteral nutrition.
Evaluation of patients who only can be checked about feeding.
Table 3 Underlying diseases related to parenteral nutrition-associated liver disease (n=77)
Values are presented as number (%).
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; PDA = patent ductus arteriosus; NEC = necrotic enterocolitis.
Table 4 Laboratory test (n=77)
Values are presented as number (%).
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; AST = asparate aminotransferase; ALT = alanine amino-transferase; ALP = alkaline phosphatase; CRP = C-reactive protein; γ-GT = gamma-glutamyl transpeptidase.
Table 5 TPN supply
Values are presented as mean±standard deviation.
TPN = total parenteral nutrition; SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; GIR = glucose infusion rate.
Table 6 Data of term infants (n=23)
Values are presented as number (%) or mean±standard deviation.
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; TPN = total parenteral nutrition; NPO = nothing per oral; PN = parenteral nutrition; EN = enteral nutrition; PDA = patent ductus arteriosus; NEC = necrotic enterocolitis.
APGAR score: Method to quickly summarize the health of neonate by scoring of breathing effort, heart rate, muscle tone, reflexes, skin color.
Evaluation of patients who only can be checked about feeding.
Table 7 Laboratory test_term infants (n=23)
Values are presented as number (%).
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil; AST = asparate aminotransferase; ALT = alanine amino-transferase; ALP = alkaline phosphatase; CRP = C-reactive protein; γ-GT = gamma-glutamyl transpeptidase.
Table 8 Birth characteristics of patients diagnosed parenteral nutrition-associated liver disease (n=8)
Values are presented as mean±standard deviation.
SO = soybean oil; SMOF = soybean oil, medium-chain triglycerides, olive oil, fish oil.
APGAR score: Method to quickly summarize the health of neonate by scoring of breathing effort, heart rate, muscle tone, reflexes, skin color.
