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Omega-3 fatty acid deficiency in infants before birth identified using a randomized trial of maternal DHA supplementation in pregnancy.

ABSTRACT: BACKGROUND:DHA is accumulated in the central nervous system (CNS) before birth and is involved in early developmental processes, such as neurite outgrowth and gene expression. OBJECTIVE:To determine whether fetal DHA insufficiency occurs and constrains CNS development in term gestation infants. DESIGN:A risk reduction model using a randomized prospective study of term gestation single birth healthy infants born to women (n = 270) given a placebo or 400 mg/day DHA from 16 wk gestation to delivery. Fetal DHA deficiency sufficient to constrain CNS development was assessed based on increased risk that infants in the placebo group would not achieve neurodevelopment scores in the top quartile of all infants in the study. RESULTS:Infants in the placebo group were at increased risk of lower language development assessed as words understood (OR 3.22, CL 1.49-6.94, P = 0.002) and produced (OR 2.61, CL 1.22-5.58, P = 0.01) at 14 mo, and words understood (OR 2.77, CL 1.23-6.28, P = 0.03) and sentences produced (OR 2.60, CL 1.15-5.89, P = 0.02) at 18 mo using the McArthur Communicative Developmental Inventory; receptive (OR 2.23, CL 1.08-4.60, P = 0.02) and expressive language (OR 1.89, CL 0.94-3.83, P = 0.05) at 18 mo using the Bayley Scales of Infant Development III; and visual acuity (OR 2.69, CL 1.10-6.54, P = 0.03) at 2 mo. TRIAL REGISTRATION:ClinicalTrials.gov NCT00620672.

SUBMITTER: Mulder KA

PROVIDER: S-EPMC3888379 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Omega-3 fatty acid deficiency in infants before birth identified using a randomized trial of maternal DHA supplementation in pregnancy.

Mulder Kelly A KA King D Janette DJ Innis Sheila M SM

PloS one 20140110 1

<h4>Background</h4>DHA is accumulated in the central nervous system (CNS) before birth and is involved in early developmental processes, such as neurite outgrowth and gene expression.<h4>Objective</h4>To determine whether fetal DHA insufficiency occurs and constrains CNS development in term gestation infants.<h4>Design</h4>A risk reduction model using a randomized prospective study of term gestation single birth healthy infants born to women (n = 270) given a placebo or 400 mg/day DHA from 16 wk ...[more]

PMID: 24427279

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Project description:OBJECTIVES/BACKGROUND: Given the widespread prevalence of micronutrient deficiencies in developing countries, supplementation with multiple micronutrients rather than iron-folate alone, could be of potential benefit to the mother and the fetus. These benefits could relate to prevention of maternal complications and reduction in other adverse pregnancy outcomes such as small-for-gestational age (SGA) births, low birth weight, stillbirths, perinatal and neonatal mortality. This review evaluates the evidence of the impact of multiple micronutrient supplements during pregnancy, in comparison with standard iron-folate supplements, on specific maternal and pregnancy outcomes of relevance to the Lives Saved Tool (LiST). DATA SOURCES/REVIEW METHODS: A systematic review of randomized controlled trials was conducted. Search engines used were PubMed, the Cochrane Library, the WHO regional databases and hand search of bibliographies. A standardized data abstraction and Child Health Epidemiology Reference (CHERG) adaptation of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) technique were used for data abstraction and overall quality of evidence. Meta-analyses were performed to calculate summary estimates of utility to the LiST model for the specified outcome of incidence of SGA births. We also evaluated the potential impact of multiple micronutrients on neonatal mortality according to the proportion of deliveries occurring in facilities (using a threshold of 60% to indicate functionality of health systems for skilled births). RESULTS: We included 17 studies for detailed data abstraction. There was no significant benefit of multiple micronutrients as compared to iron folate on maternal anemia in third trimester [Relative risk (RR) = 1.03; 95% confidence interval (CI): 0.87 - 1.22 (random model)]. Our analysis, however, showed a significant reduction in SGA by 9% [RR = 0.91; 95% CI: 0.86 - 0.96 (fixed model)]. In the fixed model, the SGA outcome remained significant only in women with mean body mass index (BMI) ? 22 kg/m2. There was an increased risk of neonatal mortality in studies with majority of births at home [RR = 1.47, 95% CI: 1.13-1.92]; such an effect was not evident where ? 60% of births occurred in facility settings [RR = 0.94, 95% CI: 0.81-1.09]. Overall there was no increase in the risk of neonatal mortality [RR = 1.05, 95% CI: 0.92 - 1.19 (fixed model)]. CONCLUSION: This review provides evidence of a significant benefit of MMN supplementation during pregnancy on reducing SGA births as compared to iron-folate, with no significant increase in the risk of neonatal mortality in populations where skilled birth care is available and majority of births take place in facilities. Given comparability of impacts on maternal anemia, the decision to replace iron-folate with multiple micronutrients during pregnancy may be taken in the context of available services in health systems and birth outcomes monitored.

Project description:ImportanceMaternal emergency department (ED) use before or during pregnancy is associated with worse obstetrical outcomes, for reasons including preexisting medical conditions and challenges in accessing health care. It is not known whether maternal prepregnancy ED use is associated with higher use of the ED by their infant.ObjectiveTo study the association between maternal prepregnancy ED use and risk of infant ED use in the first year of life.Design, setting, and participantsThis population-based cohort study included all singleton livebirths in all of Ontario, Canada, from June 2003 to January 2020.ExposuresAny maternal ED encounter within 90 days preceding the start of the index pregnancy.Main outcomes and measuresAny infant ED visit up to 365 days after the index birth hospitalization discharge date. Relative risks (RR) and absolute risk differences (ARD) were adjusted for maternal age, income, rural residence, immigrant status, parity, having a primary care clinician, and number of prepregnancy comorbidities.ResultsThere were 2 088 111 singleton livebirths; the mean (SD) maternal age was 29.5 (5.4) years, 208 356 (10.0%) were rural dwelling, and 487 773 (23.4%) had 3 or more comorbidities. Among singleton livebirths, 206 539 mothers (9.9%) had an ED visit within 90 days before the index pregnancy. ED use in the first year of life was higher among infants whose mother had visited the ED before pregnancy (570 per 1000) vs those whose mother had not (388 per 1000) (RR, 1.19 [95% CI, 1.18-1.20]; ARD, 91.1 per 1000 [95% CI, 88.6-93.6 per 1000]). Compared with mothers without a prepregnancy ED visit, the RR of infant ED use in the first year was 1.19 (95% CI, 1.18-1.20) if its mother had 1 prepregnancy ED visit, 1.18 (95% CI, 1.17-1.20) following 2 visits, and 1.22 (95% CI, 1.20-1.23) after at least 3 maternal visits. A low-acuity maternal prepregnancy ED visit was associated with an adjusted odds ratio (aOR) of 5.52 (95% CI, 5.16-5.90) for a low-acuity infant ED visit, which was numerically higher than the pairing of a high-acuity ED use between mother and infant (aOR, 1.43, 95% CI, 1.38-1.49).Conclusions and relevanceIn this cohort study of singleton livebirths, prepregnancy maternal ED use was associated with a higher rate of ED use by the infant in the first year of life, especially for low-acuity ED use. This study's results may suggest a useful trigger for health system interventions aimed at reducing some ED use in infancy.

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).

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Omega-3 fatty acid deficiency in infants before birth identified using a randomized trial of maternal DHA supplementation in pregnancy.

Publications

Omega-3 fatty acid deficiency in infants before birth identified using a randomized trial of maternal DHA supplementation in pregnancy.

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