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Feasibility and Acceptability of Maternal Choline Supplementation in Heavy Drinking Pregnant Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

ABSTRACT: BACKGROUND:Choline, an essential nutrient, serves as a methyl-group donor for DNA methylation and is a constituent of the neurotransmitter acetylcholine and a precursor to major components of cell membranes. Findings from animal studies suggest that choline supplementation during pregnancy can mitigate adverse effects of prenatal alcohol exposure on growth and neurocognitive function. We conducted a randomized, double-blind exploratory trial to examine feasibility and acceptability of a choline supplementation intervention during pregnancy. METHODS:Seventy heavy drinkers, recruited in mid-pregnancy, were randomly assigned to receive a daily oral dose of 2 g of choline or a placebo from time of enrollment until delivery. Each dose consisted of an individually wrapped packet of powder that, when mixed with water, produced a sweet tasting grape-flavored drink. Adherence was assessed by collecting used and unused drink packets on a monthly basis and tabulating the number used. Side effects were assessed in monthly interviews. Blood samples obtained at enrollment and at 4 and 12 weeks after randomization were assayed for plasma choline concentration. RESULTS:Adherence was good-to-excellent (median doses taken = 74.0%; interquartile range = 53.9 to 88.7%) and was not related to a range of sociodemographic characteristics or to alcohol consumption ascertained using a timeline follow-back interview. By 4 weeks, plasma choline concentrations were significantly higher in the choline supplementation than the placebo arm, and this group difference continued to be evident at 12 weeks. The only side effect was a small increase in nausea/dyspepsia. No effects were seen for diarrhea, vomiting, muscle stiffness, blood pressure, or body odor changes. CONCLUSIONS:This study demonstrated that a choline supplementation program with very heavy drinkers during pregnancy is feasible even among highly disadvantaged, poorly educated women. The broad acceptability of this intervention is indicated by our finding that adherence was not related to maternal education, intellectual function, depression, nutritional status, or alcohol use.

SUBMITTER: Jacobson SW

PROVIDER: S-EPMC6028314 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Feasibility and Acceptability of Maternal Choline Supplementation in Heavy Drinking Pregnant Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Jacobson Sandra W SW Carter R Colin RC Molteno Christopher D CD Meintjes Ernesta M EM Senekal Marjanne S MS Lindinger Nadine M NM Dodge Neil C NC Zeisel Steven H SH Duggan Christopher P CP Jacobson Joseph L JL

Alcoholism, clinical and experimental research 20180613 7

<h4>Background</h4>Choline, an essential nutrient, serves as a methyl-group donor for DNA methylation and is a constituent of the neurotransmitter acetylcholine and a precursor to major components of cell membranes. Findings from animal studies suggest that choline supplementation during pregnancy can mitigate adverse effects of prenatal alcohol exposure on growth and neurocognitive function. We conducted a randomized, double-blind exploratory trial to examine feasibility and acceptability of a ...[more]

PMID: 29750366

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Project description:BackgroundFetal alcohol spectrum disorders (FASDs) are conditions characterized by physical anomalies, neurodevelopmental abnormalities, and neurocognitive deficits, including intellectual, executive, and memory deficits. There are no specific biological treatments for FASDs, but rodent models have shown that prenatal or postnatal choline supplementation reduces cognitive and behavioral deficits. Potential mechanisms include phospholipid production for axonal growth and myelination, acetylcholine enhancement, and epigenetic effects.ObjectiveOur primary goal was to determine whether postnatal choline supplementation has the potential to improve neurocognitive functioning, particularly hippocampal-dependent memory, in children with FASDs.DesignThe study was a double-blind, randomized, placebo-controlled pilot trial in children (aged 2.5-5 y at enrollment) with FASDs (n = 60) who received 500 mg choline or a placebo daily for 9 mo. Outcome measures were Mullen Scales of Early Learning (primary) and the elicited imitation (EI) memory paradigm (secondary).ResultsThe administration proved feasible, and choline was well tolerated. Participants received a dose on 88% of enrolled days. The only adverse event linked to choline was a fishy body odor. Choline supplementation improved the secondary outcome (EI) only after immediate recall performance was controlled for, and the outcome was moderated by age. The treatment effect on EI items recalled was significant in the younger participants (2.5- to ≤4.0-y-olds); the young choline group showed an increase of 12-14 percentage points greater than that of the young placebo group on delayed recall measures during treatment. However, there was a marginal baseline difference in delayed item recall between the young choline and placebo groups as well as a potential ceiling effect for item recall, both of which likely contributed to the observed treatment effect. We also observed a trend toward a negative effect of choline supplementation on the immediate EI recall of ordered pairs; the young placebo group showed an increase of 8-17 percentage points greater than that of the choline group during treatment. There was an inverse relation between choline dose (in mg/kg) and memory improvement (P = 0.041); the data suggest that weight-adjusted doses may be a better alternative to a fixed dose in future studies. Limitations included trend-level baseline differences in performance, the post-hoc determination of age moderation, and potential ceiling effects for the memory measure.ConclusionsThis pilot study suggests that an additional evaluation of choline supplementation as an intervention for memory functioning in children with FASDs is warranted. The observed interaction between age and choline's effect on EI suggests that potential sensitive periods should be considered in future work. This trial was registered at clinicaltrials.gov as NCT01149538.

Project description:Post hoc analyses of 2 randomized controlled trials suggest naltrexone may reduce alcohol use and improve smoking cessation outcomes among heavy drinkers receiving smoking cessation treatment. However, no studies have been conducted specifically to examine naltrexone for this purpose or to test whether naltrexone has benefit when added to smoking cessation counseling that explicitly addresses heavy drinking.We recruited heavy-drinking smokers from the community and randomized them to receive 10 weeks of either (i) 50 mg naltrexone (n = 75) or (ii) placebo (n = 75) daily. Participants received 6 weeks of transdermal nicotine patch and 6 sessions of counseling that addressed both heavy drinking and smoking. Participants were followed for 26 weeks after their target quit smoking date.Across medication conditions, there were substantial reductions at follow-up in percent heavy drinking days (primary outcome) and average drinks per week (secondary outcome). However, participants receiving naltrexone did not differ significantly from those receiving placebo on percent heavy drinking days (effect size d = -0.04, 95% CI [-0.30, 0.22], p = 0.76) or average drinks per week (d = -0.09, 95% CI [-0.35, 0.18], p = 0.54) during follow-up. Naltrexone compared to placebo was not associated with a significant increase in smoking abstinence rates during follow-up, odds ratio = 0.93, 95% CI [0.46, 1.86], p = 0.83. The effect of naltrexone on these outcomes was not significantly moderated by current alcohol dependence or gender.Results indicate that heavy-drinking smokers, including those with current alcohol dependence, can make substantial reductions in drinking in the context of smoking cessation treatment. However, this study provided no evidence that naltrexone is efficacious for enhancing reductions in drinking or improving smoking cessation in this population. Limitations of this study included lower-than-desired sample size and modest adherence to study medication.

Project description:BACKGROUND:Prenatal alcohol exposure results in a broad range of cognitive and behavioral impairments. Because of the long-lasting problems that are associated with fetal alcohol spectrum disorders (FASDs), the development of effective treatment programs is critical. Preclinical animal studies have shown that choline, which is an essential nutrient, can attenuate the severity of alcohol-related cognitive impairments. OBJECTIVE:We aimed to translate preclinical findings to a clinical population to investigate whether choline supplementation can ameliorate the severity of memory, executive function, and attention deficits in children with FASDs. DESIGN:In the current study, which was a randomized, double-blind, placebo-controlled clinical trial, we explored the effectiveness of a choline intervention for children with FASDs who were aged 5-10 y. Fifty-five children with confirmed histories of heavy prenatal alcohol exposure were randomly assigned to either the choline (n = 29) or placebo (n = 26) treatment arms. Participants in the choline group received 625 mg choline/d for 6 wk, whereas subjects in the placebo group received an equivalent dose of an inactive placebo treatment. Primary outcomes, including the performance on neuropsychological measures of memory, executive function, and attention and hyperactivity, were assessed at baseline and postintervention. RESULTS:Compared with the placebo group, participants in the choline group did not differentially improve in cognitive performance in any domain. Treatment compliance and mean dietary choline intake were not predictive of treatment outcomes. CONCLUSIONS:Findings of the current study do not support that choline, administered at a dose of 625 mg/d for 6 wk, is an effective intervention for school-aged (5-10 y old) children with FASDs. This research provides important information about choline's therapeutic window. Combined with other studies of choline and nutritional interventions in this population, this study emphasizes a further need for the continued study of the role of nutritional status and supplementation in children with FASDs and the contributions of nutrition to neurocognition. This trial was registered at clinicaltrials.gov as NCT01911299.

Project description:BACKGROUND:Maternal vitamin D status has been associated with bone mass of offspring in many, but not all, observational studies. However, maternal vitamin D repletion during pregnancy has not yet been proven to improve offspring bone mass in a randomised controlled trial. We aimed to assess whether neonates born to mothers supplemented with vitamin D during pregnancy have greater whole-body bone mineral content (BMC) at birth than those of mothers who had not received supplementation. METHODS:The Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a multicentre, double-blind, randomised, placebo-controlled trial that recruited pregnant women from three study sites in the UK (Southampton, Oxford, and Sheffield). Eligible participants were older than 18 years, with a singleton pregnancy, gestation of less than 17 weeks, and a serum 25-hydroxyvitamin D (25[OH]D) concentration of 25-100 nmol/L at 10-17 weeks' gestation. P'articipants were randomly assigned (1:1), in randomly permuted blocks of ten, to either cholecalciferol 1000 IU/day or matched placebo, taken orally, from 14 weeks' gestation (or as soon as possible before 17 weeks' gestation if recruited later) until delivery. Participants and the research team were masked to treatment allocation. The primary outcome was neonatal whole-body BMC, assessed within 2 weeks of birth by dual-energy x-ray absorptiometry (DXA), analysed in all randomly assigned neonates who had a usable DXA scan. Safety outcomes were assessed in all randomly assigned participants. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN 82927713, and the European Clinical Trials Database, EudraCT 2007-001716-23. FINDINGS:Between Oct 10, 2008, and Feb 11, 2014, we randomly assigned 569 pregnant women to placebo and 565 to cholecalciferol 1000 IU/day. 370 (65%) neonates in the placebo group and 367 (65%) neonates in the cholecalciferol group had a usable DXA scan and were analysed for the primary endpoint. Neonatal whole-body BMC of infants born to mothers assigned to cholecalciferol 1000 IU/day did not significantly differ from that of infants born to mothers assigned to placebo (61·6 g [95% CI 60·3-62·8] vs 60·5 g [59·3-61·7], respectively; p=0·21). We noted no significant differences in safety outcomes, apart from a greater proportion of women in the placebo group with severe post-partum haemorrhage than those in the cholecalciferol group (96 [17%] of 569 mothers in the placebo group vs 65 [12%] of 565 mothers in the cholecalciferol group; p=0·01). No adverse events were deemed to be treatment related. INTERPRETATION:Supplementation of women with cholecalciferol 1000 IU/day during pregnancy did not lead to increased offspring whole-body BMC compared with placebo, but did show that 1000 IU of cholecalciferol daily is sufficient to ensure that most pregnant women are vitamin D replete, and it is safe. These findings support current approaches to vitamin D supplementation in pregnancy. Results of the ongoing MAVIDOS childhood follow-up study are awaited. FUNDING:Arthritis Research UK, Medical Research Council, Bupa Foundation, and National Institute for Health Research.

Project description:BackgroundMaternal obesity is associated with increased birthweight, and obesity and premature mortality in adult offspring. The mechanism by which maternal obesity leads to these outcomes is not well understood, but maternal hyperglycaemia and insulin resistance are both implicated. We aimed to establish whether the insulin sensitising drug metformin improves maternal and fetal outcomes in obese pregnant women without diabetes.MethodsWe did this randomised, double-blind, placebo-controlled trial in antenatal clinics at 15 National Health Service hospitals in the UK. Pregnant women (aged ≥16 years) between 12 and 16 weeks' gestation who had a BMI of 30 kg/m(2) or more and normal glucose tolerance were randomly assigned (1:1), via a web-based computer-generated block randomisation procedure (block size of two to four), to receive oral metformin 500 mg (increasing to a maximum of 2500 mg) or matched placebo daily from between 12 and 16 weeks' gestation until delivery of the baby. Randomisation was stratified by study site and BMI band (30-39 vs ≥40 kg/m(2)). Participants, caregivers, and study personnel were masked to treatment assignment. The primary outcome was Z score corresponding to the gestational age, parity, and sex-standardised birthweight percentile of liveborn babies delivered at 24 weeks or more of gestation. We did analysis by modified intention to treat. This trial is registered, ISRCTN number 51279843.FindingsBetween Feb 3, 2011, and Jan 16, 2014, inclusive, we randomly assigned 449 women to either placebo (n=223) or metformin (n=226), of whom 434 (97%) were included in the final modified intention-to-treat analysis. Mean birthweight at delivery was 3463 g (SD 660) in the placebo group and 3462 g (548) in the metformin group. The estimated effect size of metformin on the primary outcome was non-significant (adjusted mean difference -0·029, 95% CI -0·217 to 0·158; p=0·7597). The difference in the number of women reporting the combined adverse outcome of miscarriage, termination of pregnancy, stillbirth, or neonatal death in the metformin group (n=7) versus the placebo group (n=2) was not significant (odds ratio 3·60, 95% CI 0·74-17·50; p=0·11).InterpretationMetformin has no significant effect on birthweight percentile in obese pregnant women. Further follow-up of babies born to mothers in the EMPOWaR study will identify longer-term outcomes of metformin in this population; in the meantime, metformin should not be used to improve pregnancy outcomes in obese women without diabetes.FundingThe Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council and National Institute for Health Research partnership.

Dataset Information

Feasibility and Acceptability of Maternal Choline Supplementation in Heavy Drinking Pregnant Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Publications

Feasibility and Acceptability of Maternal Choline Supplementation in Heavy Drinking Pregnant Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Similar Datasets

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