Dataset Information

Predicting the effect of maternal docosahexaenoic acid (DHA) supplementation to reduce early preterm birth in Australia and the United States using results of within country randomized controlled trials.

ABSTRACT: The DHA to Optimize Mother Infant Outcome (DOMInO) and Kansas DHA Outcomes Study (KUDOS) were randomized controlled trials that supplemented mothers with 800 and 600mg DHA/day, respectively, or a placebo during pregnancy. DOMInO was conducted in Australia and KUDOS in the United States. Both trials found an unanticipated and statistically significant reduction in early preterm birth (ePTB; i.e., birth before 34 weeks gestation). However, in each trial, the number of ePTBs were small. We used a novel Bayesian approach to estimate statistically derived low, moderate or high risk for ePTB, and to test for differences between the DHA and placebo groups. In both trials, the model predicted DHA would significantly reduce the expected proportion of deliveries in the high risk group under the trial conditions of the parent studies. Among the next 300,000 births in Australia we estimated that 1112 ePTB (95% credible interval 51-2189) could be avoided by providing DHA. And in the USA we estimated that 106,030 ePTB (95% credible interval 6400 to 175,700) could be avoided with DHA.

SUBMITTER: Yelland LN

PROVIDER: S-EPMC5028118 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Predicting the effect of maternal docosahexaenoic acid (DHA) supplementation to reduce early preterm birth in Australia and the United States using results of within country randomized controlled trials.

Yelland L N LN Gajewski B J BJ Colombo J J Gibson R A RA Makrides M M Carlson S E SE

Prostaglandins, leukotrienes, and essential fatty acids 20160817

The DHA to Optimize Mother Infant Outcome (DOMInO) and Kansas DHA Outcomes Study (KUDOS) were randomized controlled trials that supplemented mothers with 800 and 600mg DHA/day, respectively, or a placebo during pregnancy. DOMInO was conducted in Australia and KUDOS in the United States. Both trials found an unanticipated and statistically significant reduction in early preterm birth (ePTB; i.e., birth before 34 weeks gestation). However, in each trial, the number of ePTBs were small. We used a n ...[more]

PMID: 27637340

Similar Datasets

Project description:BackgroundIntention-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.ObjectiveTo 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.Study designEleven 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.ResultsAdherence 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.ConclusionAdherence 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.Clinicaltrialsgov (NCT02626299).

Project description:BackgroundPreterm birth is serious public health worldwide, and early prediction of preterm birth in pregnant women may provide assistance for timely intervention and reduction of preterm birth. This study aimed to develop a preterm birth prediction model that is readily available and convenient for clinical application.MethodsData used in this case-control study were extracted from the National Vital Statistics System (NVSS) database between 2018 and 2019. Univariate and multivariate logistic regression analyses were utilized to find factors associated with preterm birth. Odds ratio (OR) and 95% confidence interval (CI) were used as effect measures. The area under the curve (AUC), accuracy, sensitivity, and specificity were utilized as model performance evaluation metrics.ResultsData from 3,006,989 pregnant women in 2019 and 3,039,922 pregnant women in 2018 were used for the model establishment and external validation, respectively. Of these 3,006,989 pregnant women, 324,700 (10.8%) had a preterm birth. Higher education level of pregnant women [bachelor (OR = 0.82; 95%CI, 0.81-0.84); master or above (OR = 0.82; 95%CI, 0.81-0.83)], pre-pregnancy overweight (OR = 0.96; 95%CI, 0.95-0.98) and obesity (OR = 0.94; 95%CI, 0.93-0.96), and prenatal care (OR = 0.48; 95%CI, 0.47-0.50) were associated with a reduced risk of preterm birth, while age ≥ 35 years (OR = 1.27; 95%CI, 1.26-1.29), black race (OR = 1.26; 95%CI, 1.23-1.29), pre-pregnancy underweight (OR = 1.26; 95%CI, 1.22-1.30), pregnancy smoking (OR = 1.27; 95%CI, 1.24-1.30), pre-pregnancy diabetes (OR = 2.08; 95%CI, 1.99-2.16), pre-pregnancy hypertension (OR = 2.22; 95%CI, 2.16-2.29), previous preterm birth (OR = 2.95; 95%CI, 2.88-3.01), and plurality (OR = 12.99; 95%CI, 12.73-13.24) were related to an increased risk of preterm birth. The AUC and accuracy of the prediction model in the testing set were 0.688 (95%CI, 0.686-0.689) and 0.762 (95%CI, 0.762-0.763), respectively. In addition, a nomogram based on information on pregnant women and their spouses was established to predict the risk of preterm birth in pregnant women.ConclusionsThe nomogram for predicting the risk of preterm birth in pregnant women had a good performance and the relevant predictors are readily available clinically, which may provide a simple tool for the prediction of preterm birth.

Project description:BackgroundSeveral meta analyses have concluded n-3 fatty acids, including docosahexaenoic acid (DHA), reduce early preterm birth (EPB, < 34 weeks), however, the amount of DHA required is unclear. We hypothesized that 1000 mg DHA per day would be superior to 200 mg, the amount in most prenatal supplements.MethodsThis randomised, multicentre, double-blind, adaptive-design, superiority trial was conducted in three USA medical centres. Women with singleton pregnancies and 12 to 20 weeks gestation were eligible. randomization was generated in SAS® by site in blocks of 4. The planned adaptive design periodically generated allocation ratios favoring the better performing dose. Managing study personnel were blind to treatment until 30 days after the last birth. The primary outcome was EPB by dose and by enrolment DHA status (low/high). Bayesian posterior probabilities (pp) were determined for planned efficacy and safety outcomes using intention-to-treat. The study is registered with ClinicalTrials.gov (NCT02626299) and closed to enrolment.FindingsEleven hundred participants (1000 mg, n = 576; 200 mg, n = 524) were enrolled between June 8, 2016 and March 13, 2020 with the last birth September 5, 2020. 1032 (n = 540 and n = 492) were included in the primary analyses. The higher dose had a lower EPB rate [1.7% (9/540) vs 2.4% (12/492), pp=0.81] especially if participants had low DHA status at enrolment [2.0% (5/249) vs 4.1%, (9/219), pp=0.93]. Participants with high enrolment DHA status did not realize a dose effect [1000 mg: 1.4% (4/289); 200 mg: 1.1% (3/271), pp = 0.57]. The higher dose was associated with fewer serious adverse events (maternal: chorioamnionitis, premature rupture of membranes and pyelonephritis; neonatal: feeding, genitourinary and neurologic problems, all pp>0.90).InterpretationClinicians could consider prescribing 1000 mg DHA daily during pregnancy to reduce EPB in women with low DHA status if they are able to screen for DHA.FundingThe National Institutes of Health Child Health and Human Development (NICHD) funded the study. Life's DHA™-S oil, DSM Nutritional Products LLC, Switzerland provided all capsules.

Project description:ImportanceMaternal docosahexaenoic acid (DHA) supplementation may prevent bronchopulmonary dysplasia, but evidence remains inconclusive.ObjectiveTo determine whether maternal DHA supplementation during the neonatal period improves bronchopulmonary dysplasia-free survival in breastfed infants born before 29 weeks of gestation.Design, setting, and participantsSuperiority, placebo-controlled randomized clinical trial at 16 Canadian neonatal intensive care units (June 2015-April 2018 with last infant follow-up in July 2018). Lactating women who delivered before 29 weeks of gestation were enrolled within 72 hours of delivery. The trial intended to enroll 800 mothers, but was stopped earlier.InterventionsThere were 232 mothers (273 infants) assigned to oral capsules providing 1.2 g/d of DHA from randomization to 36 weeks' postmenstrual age and 229 mothers (255 infants) assigned to placebo capsules.Main outcomes and measuresThe primary outcome was bronchopulmonary dysplasia-free survival in infants at 36 weeks' postmenstrual age. There were 22 secondary outcomes, including mortality and bronchopulmonary dysplasia.ResultsEnrollment was stopped early due to concern for harm based on interim data from this trial and from another trial that was published during the course of this study. Among 461 mothers and their 528 infants (mean gestational age, 26.6 weeks [SD, 1.6 weeks]; 253 [47.9%] females), 375 mothers (81.3%) and 523 infants (99.1%) completed the trial. Overall, 147 of 268 infants (54.9%) in the DHA group vs 157 of 255 infants (61.6%) in the placebo group survived without bronchopulmonary dysplasia (absolute difference, -5.0% [95% CI, -11.6% to 2.6%]; relative risk, 0.91 [95% CI, 0.80 to 1.04], P = .18). Mortality occurred in 6.0% of infants in the DHA group vs 10.2% of infants in the placebo group (absolute difference, -3.9% [95% CI, -6.8% to 1.4%]; relative risk, 0.61 [95% CI, 0.33 to 1.13], P = .12). Bronchopulmonary dysplasia occurred in 41.7% of surviving infants in the DHA group vs 31.4% in the placebo group (absolute difference, 11.5% [95% CI, 2.3% to 23.2%]; relative risk, 1.36 [95% CI, 1.07 to 1.73], P = .01). Of 22 prespecified secondary outcomes, 19 were not significantly different.Conclusions and relevanceAmong breastfed preterm infants born before 29 weeks of gestation, maternal docosahexaenoic acid supplementation during the neonatal period did not significantly improve bronchopulmonary dysplasia-free survival at 36 weeks' postmenstrual age compared with placebo. Study interpretation is limited by early trial termination.Trial registrationClinicalTrials.gov Identifier: NCT02371460.

Dataset Information

Predicting the effect of maternal docosahexaenoic acid (DHA) supplementation to reduce early preterm birth in Australia and the United States using results of within country randomized controlled trials.

Publications

Predicting the effect of maternal docosahexaenoic acid (DHA) supplementation to reduce early preterm birth in Australia and the United States using results of within country randomized controlled trials.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets