University of Kansas Medical Center, Department of Dietetics and Nutrition, Kansas City, KS, USA.
University of Kansas Medical Center, Department of Biostatistics & Data Science, Kansas City, KS, USA.
Clin Nutr. 2023 Feb;42(2):235-243. doi: 10.1016/j.clnu.2023.01.009. Epub 2023 Jan 11.
Intention-to-treat analyses do not address adherence. Per protocol analyses treat nonadherence as a protocol deviation and assess if the intervention is effective if followed.
To determine the rate of early preterm birth (EPTB, <34 weeks gestation) and preterm birth (PTB, <37 weeks gestation) in participants who adhered to a randomly assigned docosahexaenoic acid (DHA) dose of 1000 mg/day.
Eleven hundred women with a singleton pregnancy were enrolled before 20-weeks' gestation, provided a capsule with 200 mg/day DHA and randomly assigned to two additional capsules containing a placebo or 800 mg of DHA. In the Bayesian Adaptive Design, new randomization schedules were determined at prespecified intervals. In each randomization, the group with the most EPTB was assigned fewer participants than the other group. Adherence was defined a priori as a postpartum red blood cell phospholipid DHA (RBC-PL-DHA) ≥5.5%.and post hoc as ≥8.0% RBC-PL-DHA, the latter after examination of postpartum RBC-PL-DHA. Bayesian mixture models were fitted for gestational age and dichotomized for EPTB and PTB as a function of baseline RBC-PL-DHA and dose-adherence. Bayesian hierarchical models were also fitted for EPTB by dose adherence and quartiles of baseline RBC-PL-DHA.
Adherence to the high dose using both RBC-PL-DHA cut points resulted in less EPTB compared to 200 mg [Bayesian posterior probability (pp) = 0.93 and 0.92, respectively]. For participants in the two lowest quartiles of baseline DHA status, adherence to the higher dose resulted in lower EPTB (≥5.5% RBC-PL-DHA, quartiles 1 and 2, pp = 0.95 and 0.96; ≥8% RBC-PL-DHA, quartiles 1 and 2, pp = 0.94 and 0.95). Using the Bayesian model, EPTB was reduced by 65%, from 3.45% to 1.2%, using both cut points. Adherence also reduced PTB before 35, 36 and 37 weeks using both cut points (pp ≥ 0.95). In general, performance of the nonadherent subgroup mirrored that of participants assigned to 200 mg.
Adherence to high dose DHA reduced EPTB and PTB. The largest effect of adherence on reducing EPTB was observed in women with low baseline DHA levels.
gov (NCT02626299).
意向治疗分析不考虑依从性。方案依从性分析将不依从视为方案偏差，并评估如果遵循干预措施是否有效。
确定遵守随机分配的二十二碳六烯酸（DHA）剂量为 1000mg/天的参与者中早期早产（EPTB，<34 周妊娠）和早产（PTB，<37 周妊娠）的发生率。
1100 名单胎妊娠妇女在 20 周妊娠前入组，给予 200mg/天 DHA 胶囊，并随机分配至另外两个含有安慰剂或 800mg DHA 的胶囊。在贝叶斯自适应设计中，在预设间隔确定新的随机分组方案。在每次随机分组中，EPTB 最多的组分配的参与者少于另一组。依从性预先定义为产后红细胞磷酯 DHA（RBC-PL-DHA）≥5.5%，随后在检查产后 RBC-PL-DHA 后定义为≥8.0% RBC-PL-DHA。贝叶斯混合模型适用于胎龄，并根据基线 RBC-PL-DHA 和剂量依从性进行 EPTB 和 PTB 的二分类。还根据剂量依从性和基线 RBC-PL-DHA 的四分位数，为 EPTB 拟合了贝叶斯层次模型。
使用两个 RBC-PL-DHA 切点的高剂量依从性导致 EPTB 减少，与 200mg 相比[贝叶斯后验概率（pp）分别为 0.93 和 0.92]。对于基线 DHA 状态最低两个四分位数的参与者，高剂量依从性导致 EPTB 降低（≥5.5% RBC-PL-DHA，四分位数 1 和 2，pp 分别为 0.95 和 0.96；≥8% RBC-PL-DHA，四分位数 1 和 2，pp 分别为 0.94 和 0.95）。使用贝叶斯模型，两个切点均使用时，EPTB 降低 65%，从 3.45%降至 1.2%。使用两个切点，依从性还降低了 35 周、36 周和 37 周前的 PTB（pp≥0.95）。一般来说，非依从亚组的表现与被分配到 200mg 的参与者相似。
高剂量 DHA 的依从性降低了 EPTB 和 PTB。依从性对降低 EPTB 的最大影响见于基线 DHA 水平较低的女性。
gov（NCT02626299）。
