Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Ophthalmology, Institute of Clinical Sciences Lund, Lund University and Skane University Hospital, Lund, Sweden.
JAMA Netw Open. 2021 Oct 1;4(10):e2128771. doi: 10.1001/jamanetworkopen.2021.28771.
Supplementing preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA) has been inconsistent in reducing the severity and incidence of retinopathy of prematurity (ROP). Furthermore, few studies have measured the long-term serum lipid levels after supplementation.
To assess whether ROP severity is associated with serum levels of LC-PUFA, especially docosahexaenoic acid (DHA) and arachidonic acid (AA), during the first 28 postnatal days.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed the Mega Donna Mega study, a randomized clinical trial that provided enteral fatty acid supplementation at 3 neonatal intensive care units in Sweden. Infants included in this cohort study were born at a gestational age of less than 28 weeks between December 20, 2016, and August 6, 2019.
Severity of ROP was classified as no ROP, mild or moderate ROP (stage 1-2), or severe ROP (stage 3 and type 1). Serum phospholipid fatty acids were measured through gas chromatography-mass spectrometry. Ordinal logistic regression, with a description of unadjusted odds ratio (OR) as well as gestational age- and birth weight-adjusted ORs and 95% CIs, was used. Areas under the curve were used to calculate mean daily levels of fatty acids during postnatal days 1 to 28. Blood samples were obtained at the postnatal ages of 1, 3, 7, 14, and 28 days.
A total of 175 infants were included in analysis. Of these infants, 99 were boys (56.6%); the median (IQR) gestational age was 25 weeks 5 days (24 weeks 3 days to 26 weeks 6 days), and the median (IQR) birth weight was 785 (650-945) grams. A higher DHA proportion was seen in infants with no ROP compared with those with mild or moderate ROP or severe ROP (OR per 0.5-molar percentage increase, 0.49 [95% CI, 0.36-0.68]; gestational age- and birth weight-adjusted OR, 0.66 [95% CI, 0.46-0.93]). The corresponding adjusted OR for AA levels per 1-molar percentage increase was 0.83 (95% CI, 0.66-1.05). The association between DHA levels and ROP severity appeared only in infants with sufficient AA levels, suggesting that a mean daily minimum level of 7.8 to 8.3 molar percentage of AA was necessary for a detectable association between DHA level and less severe ROP.
This cohort study found that higher mean daily serum levels of DHA during the first 28 postnatal days were associated with less severe ROP even after adjustment for known risk factors, but only in infants with sufficiently high AA levels. Further studies are needed to identify LC-PUFA supplementation strategies that may prevent ROP and other morbidities.
给早产儿补充长链多不饱和脂肪酸（LC-PUFA）在降低早产儿视网膜病变（ROP）的严重程度和发生率方面一直不一致。此外，很少有研究测量补充后的长期血清脂质水平。
评估 ROP 严重程度是否与第 1 至 28 天内的 LC-PUFA 血清水平相关，特别是二十二碳六烯酸（DHA）和花生四烯酸（AA）。
设计、地点和参与者：本队列研究分析了 Mega Donna Mega 研究，这是一项在瑞典的 3 个新生儿重症监护病房进行的随机临床试验，提供肠内脂肪酸补充。本队列研究纳入的婴儿出生时胎龄不足 28 周，于 2016 年 12 月 20 日至 2019 年 8 月 6 日期间。
ROP 严重程度分为无 ROP、轻度或中度 ROP（1-2 期）和重度 ROP（3 期和 1 型）。通过气相色谱-质谱法测量血清磷脂脂肪酸。使用无序逻辑回归，描述未经调整的比值比（OR）以及调整胎龄和出生体重后的 OR 和 95%置信区间，计算了 1 至 28 天的平均每日脂肪水平。在出生后 1、3、7、14 和 28 天采集血液样本。
共纳入 175 名婴儿进行分析。其中，99 名男婴（56.6%）；中位（IQR）胎龄为 25 周 5 天（24 周 3 天至 26 周 6 天），中位（IQR）出生体重为 785（650-945）克。与轻度或中度 ROP 或重度 ROP 相比，无 ROP 的婴儿 DHA 比例较高（每增加 0.5 摩尔百分比的 OR，0.49 [95%CI，0.36-0.68]；调整胎龄和出生体重后的 OR，0.66 [95%CI，0.46-0.93]）。AA 水平每增加 1 摩尔百分比，相应的调整后 OR 为 0.83（95%CI，0.66-1.05）。DHA 水平与 ROP 严重程度之间的关联仅出现在 AA 水平足够高的婴儿中，表明在出生后第 1 至 28 天内，AA 的平均每日最低水平为 7.8 至 8.3 摩尔百分比，才能检测到 DHA 水平与较轻的 ROP 之间的关联。
本队列研究发现，在出生后第 1 至 28 天内，血清 DHA 水平较高与 ROP 严重程度较低相关，即使在调整了已知风险因素后也是如此，但仅在 AA 水平足够高的婴儿中如此。需要进一步研究确定 LC-PUFA 补充策略，以预防 ROP 和其他并发症。
