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Study protocol for a randomised controlled trial evaluating the effect of prenatal omega-3 LCPUFA supplementation to reduce the incidence of preterm birth: the ORIP trial.

ABSTRACT: INTRODUCTION:Preterm birth accounts for more than 85% of all perinatal complications and deaths. Seventy-five per cent of early preterm births (EPTBs) occur spontaneously and without identifiable risk factors. The need for a broadly applicable, effective strategy for primary prevention is paramount. Secondary outcomes from the docosahexaenoic acid (DHA) to Optimise Mother Infant Outcome trial showed that maternal supplementation until delivery with omega-3 (?-3) long chain polyunsaturated fatty acid (LCPUFA), predominantly as DHA, resulted in a 50% reduction in the incidence of EPTB and an increase in the incidence of post-term induction or post-term prelabour caesarean section due to extended gestation. We aim to determine the effectiveness of supplementing the maternal diet with ?-3 LCPUFA until 34 weeks' gestation on the incidence of EPTB. METHODS AND ANALYSIS:This is a multicentre, parallel group, randomised, blinded and controlled trial. Women less than 20 weeks' gestation with a singleton or multiple pregnancy and able to give informed consent are eligible to participate. Women will be randomised to receive high DHA fish oil capsules or control capsules without DHA. Capsules will be taken from enrolment until 34 weeks' gestation. The primary outcome is the incidence of EPTB, defined as delivery before 34 completed weeks' gestation. Key secondary outcomes include length of gestation, incidence of post-term induction or prelabour caesarean section and spontaneous EPTB. The target sample size is 5540 women (2770 per group), which will provide 85% power to detect an absolute reduction in the incidence of preterm birth of 1.16% (from 2.45% to 1.29%) between the DHA and control group (two sided ?=0.05). The primary analysis will be based on the intention-to-treat principle. TRIAL REGISTRATION NUMBER:Australia and New Zealand Clinical Trial Registry Number: 2613001142729; Pre-results.

SUBMITTER: Zhou SJ

PROVIDER: S-EPMC5623491 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

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Study protocol for a randomised controlled trial evaluating the effect of prenatal omega-3 LCPUFA supplementation to reduce the incidence of preterm birth: the ORIP trial.

Zhou Shao J SJ Best Karen K Gibson Robert R McPhee Andrew A Yelland Lisa L Quinlivan Julie J Makrides Maria M

BMJ open 20170924 9

<h4>Introduction</h4>Preterm birth accounts for more than 85% of all perinatal complications and deaths. Seventy-five per cent of early preterm births (EPTBs) occur spontaneously and without identifiable risk factors. The need for a broadly applicable, effective strategy for primary prevention is paramount. Secondary outcomes from the docosahexaenoic acid (DHA) to Optimise Mother Infant Outcome trial showed that maternal supplementation until delivery with omega-3 (ω-3) long chain polyunsaturate ...[more]

PMID: 28947468

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Project description:BackgroundChildren born preterm are at increased risk of autism spectrum disorder (ASD). n-3 (ω-3) Combined with n-6 (ω-6) fatty acids including γ-linolenic acid (GLA) may benefit children born preterm showing early signs of ASD. Previous trials have reported that docosahexaenoic acid (DHA) promotes cognitive development in preterm neonates and n-3 fatty acids combined with GLA improve attention-deficit-hyperactivity disorder.ObjectivesThe objectives of the pilot Preemie Tots Trial were 1) to confirm the feasibility of a full-scale trial in toddlers born very preterm and exhibiting ASD symptoms and 2) to explore the effects of supplementation on parent-reported ASD symptoms and related behaviors.MethodsThis was a 90-d randomized, fully blinded, placebo-controlled trial in 31 children 18-38 mo of age who were born at ≤29 wk of gestation. One group was assigned to daily Omega-3-6-9 Junior (Nordic Naturals, Inc.) treatment (including 338 mg eicosapentaenoic acid, 225 mg DHA, and 83 mg GLA), and the other group received canola oil (124 mg palmitic acid, 39 mg stearic acid, 513 mg linoleic acid, 225 mg α-linolenic acid, and 1346 mg oleic acid). Mixed-effects regression analyses followed intent-to-treat analysis and explored effects on parent-reported ASD symptoms and related behaviors.ResultsOf 31 children randomly assigned, 28 had complete outcome data. After accounting for baseline scores, those assigned to treatment exhibited a greater reduction in ASD symptoms per the Brief Infant Toddler Social Emotional Assessment ASD scale than did those assigned to placebo (difference in change = - 2.1 points; 95% CI: - 4.1, - 0.2 points; standardized effect size = - 0.71). No other outcome measure reflected a similar magnitude or a significant effect.ConclusionsThis pilot trial confirmed adequate numbers of children enrolled and participated fully in the trial. No safety concerns were noted. It also found clinically-significant improvements in ASD symptoms for children randomly assigned to receive Omega-3-6-9 Junior, but effects were confined to one subscale. A future full-scale trial is warranted given the lack of effective treatments for this population. This trial was registered at www.clinicaltrials.gov as NCT01683565.

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:BACKGROUND:Preterm birth is the leading cause of death in children under five. A recent Cochrane review found a 42% reduction in early preterm birth (< 34 weeks' gestation) and 11% reduction in preterm birth (< 37 weeks' gestation) with omega-3 fatty acid supplementation. To assist in the development of implementation strategies to increase pregnant women's omega-3 fatty acid intake, we assessed the awareness of Australian pregnant women about preterm birth, their nutrition and supplementation behaviours during pregnancy, and intentions to increase omega-3 fatty acid intake. METHODS:A ten-minute survey was conducted online to assess the knowledge, attitudes, behaviours, and intentions of Australian pregnant women across three domains: (1) preterm birth; (2) nutrition and supplementation during pregnancy; and (3) omega-3 fatty acid consumption to prevent preterm birth. Participants were recruited from Survey Sampling International's research panels. RESULTS:Of the 763 women who completed the survey, less than two-thirds had heard of preterm birth. Over 55% of respondents had changed their diet during pregnancy and a prenatal dietary supplement was consumed by 82% of the women surveyed. Respondents' main source of information about preterm birth and nutrition during pregnancy was from a health professional. When asked about their intentions to increase their omega-3 fatty acid intake following a health professional's recommendation, the vast majority of participants indicated they would increase their omega-3 fatty acid intake (90%). When a hypothetical scenario was presented of an omega-3 fatty acid supplement being offered from a health service at no cost, the number of respondents who selected they would increase their intake through supplementation increased from 54 to 79%. CONCLUSIONS:The main information source for women about preterm birth and dietary supplementation recommendations during pregnancy is their health professional. Therefore, informing women about ways to prevent preterm birth, including the role of omega-3 fatty acids, should occur during antenatal visits. The results from our study are useful for clinicians caring for pregnant women and for the next stage of translation of the Cochrane review findings - the design of implementation strategies to increase the intake of omega-3 fatty acids during pregnancy where needed.

Project description:BackgroundInfections acquired in hospital are an important cause of morbidity and mortality in very preterm infants. Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein processed from cow's milk, prevents infections and associated complications. The aim of this large randomised controlled trial was to collect data to enhance the validity and applicability of the evidence from previous trials to inform practice.MethodsIn this randomised placebo-controlled trial, we recruited very preterm infants born before 32 weeks' gestation in 37 UK hospitals and younger than 72 h at randomisation. Exclusion criteria were presence of a severe congenital anomaly, anticipated enteral fasting for longer than 14 days, or no realistic prospect of survival. Eligible infants were randomly assigned (1:1) to receive either enteral bovine lactoferrin (150 mg/kg per day; maximum 300 mg/day; lactoferrin group) or sucrose (same dose; control group) once daily until 34 weeks' postmenstrual age. Web-based randomisation minimised for recruitment site, gestation (completed weeks), sex, and single versus multifetal pregnancy. Parents, caregivers, and outcome assessors were unaware of group assignment. The primary outcome was microbiologically confirmed or clinically suspected late-onset infection (occurring >72 h after birth), which was assessed in all participants for whom primary outcome data was available by calculating the relative risk ratio with 95% CI between the two groups. The trial is registered with the International Standard Randomised Controlled Trial Number 88261002.FindingsWe recruited 2203 participants between May 7, 2014, and Sept 28, 2017, of whom 1099 were assigned to the lactoferrin group and 1104 to the control group. Four infants had consent withdrawn or unconfirmed, leaving 1098 infants in the lactoferrin group and 1101 in the sucrose group. Primary outcome data for 2182 infants (1093 [99·5%] of 1098 in the lactoferrin group and 1089 [99·0] of 1101 in the control group) were available for inclusion in the modified intention-to-treat analyses. 316 (29%) of 1093 infants in the intervention group acquired a late-onset infection versus 334 (31%) of 1089 in the control group. The risk ratio adjusted for minimisation factors was 0·95 (95% CI 0·86-1·04; p=0·233). During the trial there were 16 serious adverse events for infants in the lactoferrin group and 10 for infants in the control group. Two events in the lactoferrin group (one case of blood in stool and one death after intestinal perforation) were assessed as being possibly related to the trial intervention.InterpretationEnteral supplementation with bovine lactoferrin does not reduce the risk of late-onset infection in very preterm infants. These data do not support its routine use to prevent late-onset infection and associated morbidity or mortality in very preterm infants.FundingUK National Institute for Health Research Health Technology Assessment programme (10/57/49).

Project description:ObjectiveAllostatic load refers to cumulative neuroendocrine burden and has been postulated to mediate and moderate physiological and psychological stress-related responses. This may have important implications for the risk of preterm birth. This systematic review examines the evidence on the association between prenatal allostatic load and preterm birth.Data sourcesA comprehensive search of seven electronic databases was conducted from inception to August 23, 2022 to identify all English-language observational and mixed methods studies examining allostatic load and preterm birth with no year or geographic restrictions.Study eligibility criteriaStudies were included if they measured allostatic load, evaluated as the cumulative effect of any combination of more than one allostatic load biomarker, during pregnancy. Studies must have observed preterm birth, defined as < 37 weeks' gestational age, as a primary or secondary outcome of interest.Study appraisal and synthesis methodsThe Quality In Prognosis Studies tool was used to evaluate risk of bias within included studies. A narrative synthesis was conducted to explore potential associations between allostatic load and preterm birth, and sources of heterogeneity.ResultsThree prospective cohort studies were identified and revealed mixed evidence for an association between allostatic load and preterm birth. One study reported a statistically significant association while the other two studies reported little to no evidence for an association. Heterogeneity in when and how allostatic load was measured, limitations in study design and cohort socio-demographics may have contributed to the mixed evidence.ConclusionsThis review provides insight into key individual-, community-, and study-level characteristics that may influence the association between allostatic load and preterm birth. Knowledge gaps are identified as foci for future research, including heterogeneity in allostatic load biomarkers and allostatic load index algorithms as well as pregnancy-specific considerations for allostatic load measurement. Further investigation of the allostatic load framework in the context of perinatal mental health is needed to advance understandings of maternal, infant, and child health.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020208990, PROSPERO, identifier: CRD42020208990.

Dataset Information

Study protocol for a randomised controlled trial evaluating the effect of prenatal omega-3 LCPUFA supplementation to reduce the incidence of preterm birth: the ORIP trial.

Publications

Study protocol for a randomised controlled trial evaluating the effect of prenatal omega-3 LCPUFA supplementation to reduce the incidence of preterm birth: the ORIP trial.

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