The High Prevalence of Vitamin D Insufficiency in Cord Blood in Calgary, Alberta (APrON-D Study).

OBJECTIVE: Vitamin D is important in promoting healthy pregnancy and fetal development. We undertook this study to measure 25-hydroxyvitamin D in maternal and cord blood and to identify maternal factors related to vitamin D status in Calgary. METHODS: Blood samples collected at the time of delivery from the Alberta Pregnancy Outcomes and Nutrition study cohort (ApronStudy.ca) participants were processed for plasma and assayed using liquid chromatography mass spectrometry methodology for 25(OH)D3. RESULTS: Ninety-two pairs of maternal and cord blood samples were obtained. The prevalence of 25(OH)D3 insufficiency-25(OH)D3 <75 nmol/L-was 38% and 80% in women and neonates, respectively. Vitamin D supplementation was the only clinical factor associated with 25(OH)D3 sufficiency, and the odds of sufficiency were 3.75 (95% CI 1.00 to 14.07) higher for women and 5.27 (95% CI 1.37 to 20.27) when over 2000 IU/day were used. CONCLUSION: Using liquid chromatography mass spectrometry, we demonstrated a very high prevalence of vitamin D insufficiency in cord blood and that the use of high dose vitamin D was associated with greater odds of sufficiency in pregnant women and cord blood in Alberta.

Plasma 3-Epi-25-Hydroxycholecalciferol Can Alter the Assessment of Vitamin D Status Using the Current Reference Ranges for Pregnant Women and Their Newborns.

BACKGROUND: Vitamin D is critical for healthy pregnancies and normal fetal development. It is important to accurately ascertain vitamin D status in mothers and their newborns to establish the optimal vitamin D concentration during pregnancy. There are many different metabolites and epimers of vitamin D in peripheral blood and controversy as to the importance of epimers in estimating vitamin D status in maternal and infant health. OBJECTIVES: We undertook this study to measure 25-hydroxyvitamin D metabolites and epimers and their relations in maternal and cord blood and to evaluate the impact of the inclusion of epimers on assessing vitamin D status. METHODS: We performed a substudy in a longitudinal cohort of pregnant women and their infants in Alberta, Canada [APrON (Alberta Pregnancy Outcomes and Nutrition) Study]. Maternal and cord blood plasma collected at the time of newborn delivery was stored at -70°C until testing and assayed for 25-hydroxyergocalciferol [25(OH)D2], 25-hydroxycholecalciferol [25(OH)D3], and 3-epi-25-hydroxycholecalciferol [3-epi-25(OH)D3] by using LC-tandem mass spectrometry. The effect of 3-epi-25(OH)D3 on estimates of vitamin D adequacy was explored by using McNemar's chi-square test at both recommended thresholds of 50 and 75 nmol/L. RESULTS: Ninety-two pairs of maternal and cord blood samples were obtained. 3-Epi-25(OH)D3 was detected in all samples, comprising 6.0% and 7.8% of 25(OH)D3 in maternal and cord blood, respectively. Positive correlations were found between 25(OH)D3 and 3-epi-25(OH)D3 for both maternal and cord blood (maternal blood: r = 0.34, P = 0.01; cord blood: r = 0.44, P = 0.01). In addition, regression analysis showed a significant association between vitamin D supplementation and 3-epi-25(OH)D3 in maternal and cord blood (ß: 0.423; 95% CI: 0.173, 0.672). When 3-epi-25(OH)D3 was not included in plasma vitamin D estimations, 38% of women and 80% of neonates were classified as having an insufficient concentration (<75 nmol/L); however, with 3-epi-25(OH)D3 included, the estimates of insufficiency were significantly lower: 33% and 73% for women and neonates, respectively. CONCLUSIONS: Using LC-MS/MS we showed the presence of 3-epi-25(OH)D3 in all samples of pregnant women and their cord blood, and when the 3-epimer was included in the estimation of status the prevalence of vitamin D insufficiency (<75 nmol/L) was significantly lower. Our data suggest that the high use of dietary supplements in this group of women contributes to 3-epi-25(OH)D3 concentrations in both maternal and cord blood. Further research on the role of the epimers in characterizing vitamin D status in pregnancy and infancy is imperative.

Food insecurity in adults with mood disorders: prevalence estimates and associations with nutritional and psychological health.

BACKGROUND: Because little is known about food insecurity in people with mental health conditions, we investigated relationships among food insecurity, nutrient intakes, and psychological functioning in adults with mood disorders. METHODS: Data from a study of adults randomly selected from the membership list of the Mood Disorder Association of British Columbia (n = 97), Canada, were analyzed. Food insecurity status was based on validated screening questions asking if in the past 12 months did the participant, due to a lack of money, worry about or not have enough food to eat. Nutrient intakes were derived from 3-day food records and compared to the Dietary Reference Intakes (DRIs). Psychological functioning measures included Global Assessment of Functioning, Hamilton Depression scale, and Young Mania Rating Scale. Using binomial tests of two proportions, Mann-Whitney U tests, and Poisson regression we examined: (1) food insecurity prevalence between the study respondents and a general population sample from the British Columbia Nutrition Survey (BCNS; n = 1,823); (2) differences in nutrient intakes based on food insecurity status; and (3) associations of food insecurity and psychological functioning using bivariate and Poisson regression statistics. RESULTS: In comparison to the general population (BCNS), food insecurity was significantly more prevalent in the adults with mood disorders (7.3% in BCNS vs 36.1%; p < 0.001). Respondents who were food-insecure had lower median intakes of carbohydrates and vitamin C (p < 0.05). In addition, a higher proportion of those reporting food insecurity had protein, folate, and zinc intakes below the DRI benchmark of potential inadequacy (p < 0.05). There was significant association between food insecurity and mania symptoms (adjusted prevalence ratio = 2.37, 95% CI 1.49-3.75, p < 0.05). CONCLUSIONS: Food insecurity is associated with both nutritional and psychological health in adults with mood disorders. Investigation of interventions aimed at food security and income can help establish its role in enhancing mental health.

Maternal perspectives on the use of probiotics in infants: a cross-sectional survey.

BACKGROUND: Probiotic products that may modify the intestinal microbiota are becoming increasingly available and known to consumers due to their potential to prevent or treat many pediatric health conditions. As scientific knowledge of the health benefits of probiotics increases, it is important to identify factors that may prevent their successful integration into patient care as well as to ensure effective translation of research findings. The aim of this study was to describe maternal perspectives on probiotics and their use in infants. METHODS: Mothers with a child aged two years or younger enrolled in the Alberta Pregnancy Outcomes and Nutrition (APrON) study were invited by email to complete a 29 item self-administered web-based questionnaire. RESULTS: A total of 413 mothers of the 1327 contacted completed the questionnaire. The majority (99.3%) of respondents had heard of probiotics and were aware that they contained live bacteria (87.0%); 89.3% had used a product containing probiotics themselves but only 50.8% had given one to their infant. Most mothers indicated they believed that probiotics were beneficial (73.1%) and none thought they were harmful. Over a third of mothers did not feel informed enough to make a decision on whether probiotics were safe to use in infants (36.6%). CONCLUSIONS: The study demonstrates that awareness and understanding of probiotics is high among mothers in Alberta, Canada. However, there is still uncertainty regarding the benefit of probiotics as well as safety in infants which could be important factors determining therapeutic use in the future. Further studies that demonstrate beneficial effects and safety of probiotics in healthy infants as well as targeted knowledge translation should help to address these potential concerns.

The Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study: rationale and methods.

The Alberta Pregnancy Outcomes and Nutrition (APrON) study is an ongoing prospective cohort study that recruits pregnant women early in pregnancy and, as of 2012, is following up their infants to 3 years of age. It has currently enrolled approximately 5000 Canadians (2000 pregnant women, their offspring and many of their partners). The primary aims of the APrON study were to determine the relationships between maternal nutrient intake and status, before, during and after gestation, and (1) maternal mood; (2) birth and obstetric outcomes; and (3) infant neurodevelopment. We have collected comprehensive maternal nutrition, anthropometric, biological and mental health data at multiple points in the pregnancy and the post-partum period, as well as obstetrical, birth, health and neurodevelopmental outcomes of these pregnancies. The study continues to follow the infants through to 36 months of age. The current report describes the study design and methods, and findings of some pilot work. The APrON study is a significant resource with opportunities for collaboration.

The buffering effect of social support on hypothalamic-pituitary-adrenal axis function during pregnancy.

OBJECTIVE: Recent studies suggest that effective social support during pregnancy may buffer adverse effects of maternal psychological distress on fetal development. The mechanisms whereby social support confers this protective advantage, however, remain to be clarified. The aim of this study was to assess whether individual differences in social support alter the covariation of psychological distress and cortisol during pregnancy. METHODS: Eighty-two pregnant women's psychological distress and cortisol were prospectively assessed in all three trimesters using an ecological momentary assessment strategy. Appraisal of partner social support was assessed in each trimester via the Social Support Effectiveness questionnaire. RESULTS: In multilevel analysis, ambulatory assessments of psychological distress during pregnancy were associated with elevated cortisol levels (unstandardized ß = .023, p < .001). Consistent with the stress-buffering hypothesis, social support moderated the association between psychological distress and cortisol (unstandardized ß = -.001, p = .039), such that the covariation of psychological distress and cortisol increased with decreases in effective social support. The effect of social support for women with the most effective social support was a 50.4% reduction in the mean effect of distress on cortisol and a 2.3-fold increase in this effect for women with the least effective social support scores. CONCLUSIONS: Pregnant women receiving inadequate social support secrete higher levels of cortisol in response to psychological distress as compared with women receiving effective social support. Social support during pregnancy may be beneficial because it decreases biological sensitivity to psychological distress, potentially shielding the fetus from the harmful effects of stress-related increases in cortisol.

Comparison of sample characteristics in two pregnancy cohorts: community-based versus population-based recruitment methods.

BACKGROUND: One of the biggest challenges for population health studies is the recruitment of participants. Questions that investigators have asked are "who volunteers for studies?" and "does recruitment method influence characteristics of the samples?" The purpose of this paper was to compare sample characteristics of two unrelated pregnancy cohort studies taking place in the same city, in the same time period, that employed different recruitment strategies, as well as to compare the characteristics of both cohorts to provincial and national statistics derived from the Maternity Experiences Survey (MES). METHODS: One pregnancy cohort used community-based recruitment (e.g. posters, pamphlets, interviews with community media and face-to-face recruitment in maternity clinics); the second pregnancy cohort used both community-based and population-based (a centralized system identifying pregnant women undergoing routine laboratory testing) strategies. RESULTS: The pregnancy cohorts differed in education, income, ethnicity, and foreign-born status (p < 0.01), but were similar for maternal age, BMI, and marital status. Compared to the MES, the lowest age, education, and income groups were under-represented, and the cohorts were more likely to be primiparous. CONCLUSIONS: The findings suggest that non-stratified strategies for recruitment of participants will not necessarily result in samples that reflect the general population, but can reflect the target population of interest. Attracting and retaining young, low resource women into urban studies about pregnancy may require alternate and innovative approaches.

Prenatal micronutrient supplementation and postpartum depressive symptoms in a pregnancy cohort.

BACKGROUND: Postpartum depression is a serious problem for women and their offspring. Micronutrient supplements are recommended for pregnant women because of their documented protective effects for the offspring, but their potential beneficial effects on maternal mental health are unknown. This study investigated the association between prenatal micronutrient supplementation and the risk for symptoms of postpartum depression in a longitudinal pregnancy cohort from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. METHODS: Participants came from a cohort of the first 600 APrON women. Supplemental nutrient intake and symptoms of depression (measured with the Edinburgh Postnatal Depression Scale (EPDS)) were collected at each trimester and 12 weeks postpartum. RESULTS: Of the 475 participants who completed the EPDS at least twice in pregnancy and at 12 weeks postpartum, 416 (88%) scored <10 and 59 (12%) scored ≥10, where an EPDS ≥10 is considered to be "at least probable minor depression". Mean nutrient intakes from supplements were higher in women with lower EPDS scores, particularly selenium (p = 0.0015) and omega-3s (p = 0.01). Bivariate analyses showed that several demographic and social/lifestyle variables were associated with EPDS ≥10: not having been born in Canada (p = 0.01), greater number of chronic conditions (p = 0.05), greater number of stressful life events during this pregnancy (p = 0.02), and lower prenatal and postnatal support (p = 0.0043 and p = 0.0001, respectively). Adjusting for covariates and nutrients known to be associated with postpartum depression, logistic regression showed that having a prenatal EPDS ≥ 10 increased the odds of postpartum depressive symptoms (second and third trimester OR = 3.29, 95% CI = 1.55 - 7.01, p = 0.004 and OR = 4.26, 95% CI = 2.05 - 8.85, p < 0.0001, respectively), while prenatal supplemental selenium (per 10 mcg, OR = 0.76, 95% CI = 0.74 - 0.78, p = 0.0019) and postnatal social support (OR = 0.87, 95% CI = 0.78 - 0.97, p = 0.0015) were protective. CONCLUSIONS: Multiple factors, including supplementary selenium intake, are associated with the risk of postpartum depressive symptoms. Future research on dietary supplementation in pregnancy with special attention to selenium intake is warranted.

The most effective strategy for recruiting a pregnancy cohort: a tale of two cities.

BACKGROUND: Pregnant women were recruited into the Alberta Pregnancy Outcomes and Nutrition (APrON) study in two cities in Alberta, Calgary and Edmonton. In Calgary, a larger proportion of women obtain obstetrical care from family physicians than from obstetricians; otherwise the cities have similar characteristics. Despite similarities of the cities, the recruitment success was very different. The purpose of this paper is to describe recruitment strategies, determine which were most successful and discuss reasons for the different success rates between the two cities. METHODS: Recruitment methods in both cities involved approaching pregnant women (< 27 weeks gestation) through the waiting rooms of physician offices, distributing posters and pamphlets, word of mouth, media, and the Internet. RESULTS: Between May 2009 and November 2010, 1,200 participants were recruited, 86% (1,028/1,200) from Calgary and 14% (172/1,200) from Edmonton, two cities with similar demographics. The most effective strategy overall involved face-to-face recruitment through clinics in physician and ultrasound offices with access to a large volume of women in early pregnancy. This method was most economical when clinic staff received an honorarium to discuss the study with patients and forward contact information to the research team. CONCLUSION: Recruiting a pregnancy cohort face-to-face through physician offices was the most effective method in both cities and a new critically important finding is that employing this method is only feasible in large volume maternity clinics. The proportion of family physicians providing antenatal and post-natal care may impact recruitment success and should be studied further.

Nutrient- and non-nutrient-based natural health product (NHP) use in adults with mood disorders: prevalence, characteristics and potential for exposure to adverse events.

BACKGROUND: To address knowledge gaps regarding natural health product (NHP) usage in mental health populations, we examined their use in adults with mood disorders, and explored the potential for adverse events. METHODS: Food and NHP intake was obtained from 97 adults with mood disorders. NHP data was used to compare prevalence with population norms (British Columbia Nutrition Survey; BCNS). Bivariate and regression analyses examined factors associated with NHP use. Assessment of potential adverse effects of NHP use was based on comparing nutrient intakes from food plus supplements with the Dietary Reference Intakes and by reviewing databases for reported adverse health effects. RESULTS: Two-thirds (66%; 95% CI 56 to 75) were taking at least one NHP; 58% (95% CI 47 to 68) were taking NHPs in combination with psychiatric medications. The proportion of each type of NHP used was generally higher than the BCNS (range of p's < 0.05 to 0.0001). When intakes from food and NHP sources were combined, a small proportion exceeded any Lowest-Observed-Adverse-Effect-Levels: only for niacin (n = 17) and magnesium (n = 6), two nutrients for which the potential for adverse effects is minimal. Conversely, about 38% (95% CI 28 to 49) of the sample were taking a non-nutrient based NHP for which previous adverse events had been documented. CONCLUSIONS: The prevalent use of NHPs in this population suggests that health care providers need to be knowledgeable about their characteristics. The efficacy and safety of NHPs in relation to mental health warrants further investigation.

Food intake and blood cholesterol levels of community-based adults with mood disorders.

BACKGROUND: A growing body of literature links nutrition to mood, especially in epidemiological surveys, but there is little information characterizing food intake in people with diagnosed mood disorders. METHODS: Food intake obtained from 3-day food records was evaluated in 97 adults with mood disorders, whose diagnoses were confirmed in structured interviews. Information from a population nutrition survey, national guidelines for nutritional intakes (Eating Well with Canada's Food Guide) and North American dietary guidelines (Dietary Reference Intakes) was utilized to evaluate the quality of their food intake. RESULTS: Compared to the regional nutrition survey data and national guidelines, a greater proportion of study participants consumed fewer of the recommended servings of grains (p < 0.001) and vegetables and fruits (p < 0.05), and less than the lower boundary of the Adequate Macronutrient Distribution Range (AMDR) for α-linolenic acid (p < 0.001). The study sample also had greater intakes of high-fat whole grain products (p < 0.01), processed meats (p < 0.00001), and higher sugar, fat or salty foods (p < 0.00001). Of the 1746 total meals and snacks consumed, 39% were from sources outside the home, suggesting a lack of time devoted to meal preparation. Finally, a subsample of 48 participants agreed to have blood tests: 44% had mild hypercholesterolemia (> 5.2 and ≤ 6.2 mmol/L) and 21% had hypercholesterolemia (> 6.2 mmol/L). CONCLUSIONS: Much research has proposed multiple ways in which healthier diets may exert protective effects on mental health. The results of this study suggest that adults with mood disorders could benefit from nutritional interventions to improve diet quality.

Nutrient intakes are correlated with overall psychiatric functioning in adults with mood disorders.

OBJECTIVE: To evaluate the relation between nutrient intake and psychiatric functioning in adults with confirmed mood disorders. METHOD: A cross-sectional study was conducted of the intake of major (that is, carbohydrates, fat, and protein) and minor (that is, vitamins and minerals) nutrients (from 3-day food records and a Food Frequency Questionnaire), Global Assessment of Functioning (GAF) scores, and symptoms of depression and mania (the Hamilton Depression Rating Scale and the Young Mania Rating Scale) in 97 community-based adults with mood disorders whose diagnoses were confirmed with structured interviews. RESULTS: Significant correlations were found between GAF scores and energy (kilocalories), carbohydrates, fibre, total fat, linoleic acid, riboflavin, niacin, folate, vitamin B6, vitamin B12, pantothenic acid, calcium, phosphorus, potassium, and iron (all P values < 0.05), as well as magnesium (r = 0.41, P < 0.001) and zinc (r = 0.35, P < 0.001). Though modest in magnitude, the pattern of correlations was consistent, indicating higher levels of mental function associated with a higher intake of nutrients. Depression and mania scores, which were generally mild or moderate, did not individually show consistent patterns. When dietary supplement use was added to nutrient intakes from food, GAF scores remained positively correlated (P < 0.05) with all dietary minerals. CONCLUSION: This detailed analysis in a clinically diagnosed sample was consistent with prior epidemiologic surveys, revealing an association between higher levels of nutrient intakes and better mental health. Nutrient intakes warrant further consideration in the treatment of people with mood disorders.

Affective experience in ecologically relevant contexts is dynamic and not progressively attenuated during pregnancy.

Pregnancy is thought to diminish a woman's appraisal of and affective response to stressors. To examine this assumption, we used an electronic diary and an ecological momentary assessment strategy to record women's (n = 85) experiences of positive and negative affect five times each day over 2 days within each trimester of pregnancy. The women also completed the Edinburgh Postnatal Depression Scale in each trimester. Multilevel modeling indicated nonlinear patterns for both positive and negative affect that differed by the level of depressive symptoms. The findings suggest that changes in the psychological experience over the course of pregnancy are dynamic and not progressively attenuated.

Vitamin and mineral intakes in adults with mood disorders: comparisons to nutrition standards and associations with sociodemographic and clinical variables.

OBJECTIVE: The purpose of this study was to investigate the nutrient intakes of people with mood disorders. METHOD: A cross-sectional survey using 3-day food records was carried out in 97 adults with bipolar or major depressive disorder to compare nutrient intakes with Dietary Reference Intakes and British Columbia Nutrition Survey (BCNS) data. Blood levels of selected nutrients were compared to reference ranges. Bivariate and multivariate analyses examined the effects of sociodemographic and clinical variables on nutrient intakes. RESULTS: The average age of respondents was 46 (±13) years; most were women (n = 69) who had less than a university degree (n = 60) and whose incomes were in the government-defined lower range (n = 39). Compared with the BCNS, a larger proportion of the sample was below the estimated average requirement for thiamin (26% vs 8%), riboflavin (21% vs 4%), folate (64% vs 27%), phosphorous (12% vs 1%), and zinc (39% vs 15%; all P < 0.0001), as well as vitamin B(6) (25% vs 16%) and vitamin B(12) (27% vs 8%; both P < 0.05). Combined intakes of food and supplements helped reduce the prevalence of inadequacy; however, with supplementation, the proportion of participants exceeding the tolerable upper intake levels for niacin, vitamin B(6), folate, vitamin C, calcium, magnesium, iron, and zinc ranged from 1%-8%. Income, relationship status, age, gender, and caloric intake were associated with intakes of many nutrients. Types of medications were associated with nutrient intakes, as lower intakes of thiamin and phosphorous (P < 0.05) were found with antidepressant use, higher calcium and iron intakes (P < 0.05) were associated with antianxiety medication use, and magnesium intakes were increased with mood stabilizers (regression coefficient = 52.61, P < 0.05, 95% confidence interval = 0.74 to 104.48). CONCLUSIONS: Adults with mood disorders are at risk for many nutrient inadequacies, as well as occasional excesses; social, demographic, and clinical factors may affect their nutrient intakes.

Evaluating treatments in health care: the instability of a one-legged stool.

BACKGROUND: Both scientists and the public routinely refer to randomized controlled trials (RCTs) as being the 'gold standard' of scientific evidence. Although there is no question that placebo-controlled RCTs play a significant role in the evaluation of new pharmaceutical treatments, especially when it is important to rule out placebo effects, they have many inherent limitations which constrain their ability to inform medical decision making. The purpose of this paper is to raise questions about over-reliance on RCTs and to point out an additional perspective for evaluating healthcare evidence, as embodied in the Hill criteria. The arguments presented here are generally relevant to all areas of health care, though mental health applications provide the primary context for this essay. DISCUSSION: This article first traces the history of RCTs, and then evaluates five of their major limitations: they often lack external validity, they have the potential for increasing health risk in the general population, they are no less likely to overestimate treatment effects than many other methods, they make a relatively weak contribution to clinical practice, and they are excessively expensive (leading to several additional vulnerabilities in the quality of evidence produced). Next, the nine Hill criteria are presented and discussed as a richer approach to the evaluation of health care treatments. Reliance on these multi-faceted criteria requires more analytical thinking than simply examining RCT data, but will also enhance confidence in the evaluation of novel treatments. SUMMARY: Excessive reliance on RCTs tends to stifle funding of other types of research, and publication of other forms of evidence. We call upon our research and clinical colleagues to consider additional methods of evaluating data, such as the Hill criteria. Over-reliance on RCTs is similar to resting all of health care evidence on a one-legged stool.

Systematic review of safety and tolerability of a complex micronutrient formula used in mental health.

BACKGROUND: Theoretically, consumption of complex, multinutrient formulations of vitamins and minerals should be safe, as most preparations contain primarily the nutrients that have been in the human diet for millennia, and at safe levels as defined by the Dietary Reference Intakes. However, the safety profile of commercial formulae may differ from foods because of the amounts and combinations of nutrients they contain. As these complex formulae are being studied and used clinically with increasing frequency, there is a need for direct evaluation of safety and tolerability. METHODS: All known safety and tolerability data collected on one complex nutrient formula was compiled and evaluated. RESULTS: Data were assembled from all the known published and unpublished studies for the complex formula with the largest amount of published research in mental health. Biological safety data from 144 children and adults were available from six sources: there were no occurrences of clinically meaningful negative outcomes/effects or abnormal blood tests that could be attributed to toxicity. Adverse event (AE) information from 157 children and adults was available from six studies employing the current version of this formula, and only minor, transitory reports of headache and nausea emerged. Only one of the studies permitted a direct comparison between micronutrient treatment and medication: none of the 88 pediatric and adult participants had any clinically meaningful abnormal laboratory values, but tolerability data in the group treated with micronutrients revealed significantly fewer AEs and less weight gain. CONCLUSIONS: This compilation of safety and tolerability data is reassuring with respect to the broad spectrum approach that employs complex nutrient formulae as a primary treatment.

Does prenatal micronutrient supplementation improve children's mental development? A systematic review.

BACKGROUND: Although maternal nutrient status influences all aspects of fetal development including the brain, the impact of micronutrient supplementation on the baby's mental function is a topic of debate. This systematic review assesses the effect of single and multiple micronutrient supplementation during pregnancy on offspring mental development. METHODS: Eleven electronic literature databases were searched using key terms of various combinations and filter string terms. Reference lists of articles selected for review were scanned for citations fitting the same inclusion criteria. Each stage of the literature retrieval and review process was conducted independently by two reviewers. The CONSORT checklist was used to assess study quality. RESULTS: A total of 1316 articles were retrieved from the electronic database search, of which 18 met the inclusion criteria and were evaluated. The selected studies were randomized controlled trials published from 1983 to 2010, with high variance in sample size, intervention type, and outcome measures. The median CONSORT score was 15 (range 12 - 19). Due to inconsistent interventions and outcome measures among the studies, no conclusive evidence was found that enhancing the intrauterine environment through micronutrient supplementation was associated with child mental development in a number of dimensions. There was some evidence to support n-3 fatty acids or multi-micronutrients having some positive effect on mental development, but the evidence for single nutrients was much weaker. CONCLUSIONS: The study of children's mental outcomes as a function of prenatal supplementation is still relatively new, but the results of this systematic review suggest that further work with multiple micronutrients and/or n-3 fatty acids should be conducted.

Preliminary fMRI findings on the effects of event rate in adults with ADHD.

Inhibition problems in attention deficit hyperactivity disorder (ADHD) are sensitive to stimulus event rate. This pilot study explores the neural basis of this increased susceptibility to event rate in ADHD. Event-related functional magnetic resonance imaging was used in conjunction with the administration of a fast (1.5 s) and a slow (7 s) Go/No-Go task. Brain activity patterns and reaction times of ten young male adults with ADHD (two of whom were in partial remission) and ten healthy male controls were compared. The ADHD group responded slower than controls with greater variability but with similar number of errors. Accurate response inhibition in the ADHD group in the slow condition was associated with widespread fronto-striatal activation, including the thalamus. For correct Go trials only, the ADHD group compared with controls showed substantial under-activation in the slow condition. The observed abnormal brain activation in the slow condition in adults with ADHD supports a fronto-striatal etiology, and underlines a presumed activation regulation deficit. Larger sample sizes to further validate these preliminary findings are needed.

Differentiating attention deficits in children with fetal alcohol spectrum disorder or attention-deficit-hyperactivity disorder.

AIM: The attention and inhibition problems found in children with attention-deficit-hyperactivity disorder (ADHD) are also common in children with fetal alcohol spectrum disorders (FASDs). Attempts to distinguish ADHD from FASDs in terms of these deficits are rare and were pursued in this study. METHOD: A total of 116 children (47 with ADHD, 31 males, 16 females; 30 with FASDs, 17 males, 13 females; and 39 comparison children, 20 males, 19 females) participated. The mean age was 9 years 4 months (SD 1y 8mo) in the ADHD groups, 8 years 10 months (SD 1y 2mo) in the FASD group, and 9 years 1 month (SD 1y 1mo) in the comparison group. Sustained attention was tested with a slow event rate continuous performance task (CPT). Inhibitory control was tested with both a slow and fast event rate Go/No-Go task. RESULTS: On the CPT task, children with ADHD, combined type (ADHD-C), ADHD, primarily inattentive type (ADHD-PI), and FASDs showed greater declines in task performance as a function of time than comparison children, suggesting sustained attention problems in all clinical groups. Children's Go/No-Go performance was event-rate dependent, with the ADHD-C group being affected in the slow condition and the ADHD-PI and FASD groups having problems with the fast condition. INTERPRETATION: Children with ADHD-C are typically impaired in handling understimulation, while children with FASDs may have problems with overstimulation. The dissociation in responsivity to event rate between groups may have significant differential diagnostic value.

Database analysis of children and adolescents with bipolar disorder consuming a micronutrient formula.

BACKGROUND: Eleven previous reports have shown potential benefit of a 36-ingredient micronutrient formula (known as EMPowerplus) for the treatment of psychiatric symptoms. The current study asked whether children (7-18 years) with pediatric bipolar disorder (PBD) benefited from this same micronutrient formula; the impact of Attention-Deficit/Hyperactivity Disorder (ADHD) on their response was also evaluated. METHODS: Data were available from an existing database for 120 children whose parents reported a diagnosis of PBD; 79% were taking psychiatric medications that are used to treat mood disorders; 24% were also reported as ADHD. Using Last Observation Carried Forward (LOCF), data were analyzed from 3 to 6 months of micronutrient use. RESULTS: At LOCF, mean symptom severity of bipolar symptoms was 46% lower than baseline (effect size (ES) = 0.78) (p < 0.001). In terms of responder status, 46% experienced >50% improvement at LOCF, with 38% still taking psychiatric medication (52% drop from baseline) but at much lower levels (74% reduction in number of medications being used from baseline). The results were similar for those with both ADHD and PBD: a 43% decline in PBD symptoms (ES = 0.72) and 40% in ADHD symptoms (ES = 0.62). An alternative sample of children with just ADHD symptoms (n = 41) showed a 47% reduction in symptoms from baseline to LOCF (ES = 1.04). The duration of reductions in symptom severity suggests that benefits were not attributable to placebo/expectancy effects. Similar findings were found for younger and older children and for both sexes. CONCLUSIONS: The data are limited by the open label nature of the study, the lack of a control group, and the inherent self-selection bias. While these data cannot establish efficacy, the results are consistent with a growing body of research suggesting that micronutrients appear to have therapeutic benefit for children with PBD with or without ADHD in the absence of significant side effects and may allow for a reduction in psychiatric medications while improving symptoms. The consistent reporting of positive changes across multiple sites and countries are substantial enough to warrant a call for randomized clinical trials using micronutrients.