The Role of Fresh Beef Intake and Mediterranean Diet Adherence during Pregnancy in Maternal and Infant Health Outcomes.

Beef is an excellent source of nutrients important for maternal health and fetal development. It is also true that the Mediterranean diet is beneficial for the health of both the mother and offspring; however, the relative value of fresh beef intake within Mediterranean diet patterns during pregnancy is unknown. The objective of this project was two-fold: (1) assess the relationship between beef intake and nutrient intake in a pregnant population; (2) assess the relationship between maternal beef consumption among varying degrees of Mediterranean diet adherence with maternal risk of anemia and infant health outcomes. This is a secondary analysis of an existing cohort of pregnant women (n = 1076) who participated in one of two completed clinical trials examining the effect of a docosahexaenoic acid supplementation on birth and offspring outcomes. Women were enrolled between 12 and 20 weeks of gestation and were followed throughout their pregnancies to collect maternal and infant characteristics, food frequency questionnaires [providing beef intake and Mediterranean diet (MedD) adherence], and supplement intake. Women with the highest fresh beef intake had the highest intake of many micronutrients that are commonly deficient among pregnant women. Fresh beef intake alone was not related to any maternal or infant outcomes. There was a reduced risk of anemia among women with medium to high MedD quality and higher fresh beef intake. Women in the medium MedD group had 31% lower odds of anemia, and women in the high MedD group had 38% lower odds of anemia with every one-ounce increase in fresh beef intake, suggesting that diet quality indices may be misrepresenting the role of fresh beef within a healthy diet. These findings show that beef intake increases micronutrient intake and may be protective against maternal anemia when consumed within a healthy Mediterranean diet pattern.

Hypertriglyceridemia in equines with refractory hyperinsulinemia treated with SGLT2 inhibitors.

Background: Sodium-Glucose CoTransporter-2 (SGLT2) inhibitors, the -flozin group of drugs, which block glucose reuptake in the renal proximal tubule, are being increasingly used off-label to treat horses with refractory hyperinsulinemia. After 2 years of use by animals in our group, a horse on canagliflozin was incidentally noted to be hyperlipemic. Case Description: We have been following a cohort of equines (n = 20) treated with SGLT2 inhibitors due to refractory hyperinsulinemia. The animals are owned by members of the Equine Cushing's and Insulin Resistance Group and treated by their attending veterinarians. The index case was a 23 years old gelding with a 2 years history of recurring laminitis that began canagliflozin therapy to control hyperinsulinemia which was no longer responsive to metformin. Between 6 and 10 weeks post start of therapy, significant weight loss was noticed. Two days later he was hospitalized with colic symptoms and hyperlipemia but was bright, alert, and eating well throughout. Canagliflozin was discontinued and triglycerides returned to normal reference values within 10 days. A subsequent study of 19 other horses on SGLT2 inhibitors revealed varying degrees of hypertriglyceridemia, all asymptomatic. Conclusion: While this class of drugs holds great promise for cases of refractory hyperinsulinemia and laminitis that do not respond to diet or metformin therapy, hypertriglyceridemia is a potential side effect. In our experience, animals remained asymptomatic and eating well. Further study of hypertriglyceridemia in horses on SGLT2 inhibitors and the possible mitigating effect of diet is indicated. To our knowledge, this is the first report of hypertriglyceridemia with canagliflozin treatment in equines.

Effect of Cognitive Reserve on Physiological Measures of Cognitive Workload in Older Adults with Cognitive Impairments.

BACKGROUND: Cognitive reserve may protect against cognitive decline. OBJECTIVE: This cross-sectional study investigated the association between cognitive reserve and physiological measures of cognitive workload in older adults with cognitive impairment. METHODS: 29 older adults with cognitive impairment (age: 75±6, 11 (38%) women, MoCA: 20±7) and 19 with normal cognition (age: 74±6; 11 (58%) women; MoCA: 28±2) completed a working memory test of increasing task demand (0-, 1-, 2-back). Cognitive workload was indexed using amplitude and latency of the P3 event-related potential (ERP) at electrode sites Fz, Cz, and Pz, and changes in pupillary size, converted to an index of cognitive activity (ICA). The Cognitive Reserve Index questionnaire (CRIq) evaluated Education, Work Activity, and Leisure Time as a proxy of cognitive reserve. Linear mixed models evaluated the main effects of cognitive status, CRIq, and the interaction effect of CRIq by cognitive status on ERP and ICA. RESULTS: The interaction effect of CRIq total score by cognitive status on P3 ERP and ICA was not significant. However, higher CRIq total scores were associated with lower ICA (p = 0.03). The interaction effects of CRIq subscores showed that Work Activity affected P3 amplitude (p = 0.03) and ICA (p = 0.03) differently between older adults with and without cognitive impairments. Similarly, Education affected ICA (p = 0.02) differently between the two groups. No associations were observed between CRIq and P3 latency. CONCLUSION: Specific components of cognitive reserve affect cognitive workload and neural efficiency differently in older adults with and without cognitive impairments.

Intake of eggs, choline, lutein, zeaxanthin, and DHA during pregnancy and their relationship to fetal neurodevelopment.

BACKGROUND: Maternal intake of eggs and nutrients contained within eggs during pregnancy have the potential to impact fetal neurodevelopment; however, this area is understudied. The purpose of this study was to determine whether maternal egg and choline intake and nutrient interactions between choline, lutein and zeaxanthin (L/Z), and DHA predict fetal neurodevelopment in a large cohort of pregnant women (n = 202). NCT02709239. METHODS: Food frequency questionnaires were used to assess egg and nutrient intake during pregnancy. Fetal neurodevelopment was measured using fetal biomagnetometry at 32 and 36wks gestation, and fetal autonomic indices (SDNN, RMSSD) and brain maturation indices (fABAS) were calculated. Generalized linear models tested the relationships between choline intake, egg intake, and nutrient interactions with fetal neurodevelopment. RESULTS: Maternal egg intake predicted RMSSD at 32wks and fABAS at 36wks. The interaction between choline and L/Z intake predicted fABAS at 32wks and 36wks and the interaction between choline intake, L/Z intake, and DHA predicted fABAS at 36wks. At 36wks, SDNN was predicted by L/Z intake and interactions between choline and L/Z, L/Z and DHA, and choline, L/Z, and DHA. CONCLUSION: Eggs and the nutrients contained within eggs showed synergistic associations with fetal neurodevelopment, and consumption should be encouraged among pregnant women.

DHA Supplementation During Pregnancy Enhances Maternal Vagally Mediated Cardiac Autonomic Control in Humans.

BACKGROUND: DHA is an essential omega-3 (ω-3; n-3) fatty acid that has well-established benefits for the fetus. DHA also has the potential to influence the health of the mother, but this area is understudied. OBJECTIVES: The objective of this secondary analysis was to determine if DHA was related to maternal heart rate (HR) and heart rate variability (HRV) metrics in a large cohort of pregnant women. METHODS: In the parent trial (1R01HD086001) eligible participants (≥18 y old, English speaking, carrying a singleton pregnancy, 12-20 wk of gestation) were randomly assigned to consume 200 mg/d or 800 mg/d DHA for the duration of their pregnancy (n = 300). Weight, blood pressure, and magnetocardiograms (MCGs) were collected at 32 wk and 36 wk of gestation (n = 221). Measures of HR and HRV in time-, frequency-, and nonlinear-domains were determined from the isolated maternal MCG. Treatment group and timepoint were examined as predictors in association with HR and HRV metrics using random-intercept mixed-effects ANOVA unadjusted and adjusted models accounting for weight and dietary DHA intake. RESULTS: Women receiving the higher dose of DHA (800 mg/d) during pregnancy had lower HR, lower sympathetic index, higher vagally mediated HRV indices, and greater HRV complexity when compared with the women who received the lower dose (200 mg/d; all P < 0.05). All the dose relations remained significant even after controlling for the effect of time, maternal weight, and dietary DHA intake. CONCLUSIONS: DHA supplementation increases vagal tone in pregnant women. Longitudinal studies examining the potential link between DHA, enhanced vagal tone, and reported reduction in early preterm birth are warranted.

Autonomic nervous system markers of music-elicited analgesia in people with fibromyalgia: A double-blind randomized pilot study.

Purpose: To investigate the feasibility of using music listening by adults with fibromyalgia (FM) as a potential tool for reducing pain sensitivity. Patients and methods: We report results from a double-blind two-arm parallel randomized pilot study (NCT04059042) in nine participants with FM. Pain tolerance and threshold were measured objectively using quantitative sensory tests; autonomic nervous system (ANS) reactivity was measured with an electrocardiogram. Participants were randomized to listen to instrumental Western Classical music or a nature sound control to test whether music listening elicits greater analgesic effects over simple auditory distraction. Participants also completed separate control testing with no sound that was counterbalanced between participants. Results: Participants were randomized 1:1 to music or nature sounds (four Music and five Nature). Although the groups were not different on FM scores, the Music group had marginally worse temporal pain summation (p = 0.06), and the Nature group had higher anxiety scores (p < 0.05). Outcome measures showed a significant difference between groups in the magnitude of change in temporal summation between sessions (p < 0.05), revealing that the Nature group had greater pain reduction during audio compared to silence mode, while the Music group had no difference between the sessions. No significant effects were observed for either mechanical pain tolerance or ANS testing. Within the Music group, there was a trend of vagal response increase from baseline to music listening, but it did not reach statistical significance; this pattern was not observed in the Nature group. Conclusion: Auditory listening significantly altered pain responses. There may be a greater vagal response to music vs. nature sounds; however, results could be due to group differences in pain and anxiety. This line of study will help in determining whether music could be prophylactic for people with FM when acute pain is expected.

Use of the SGLT2 inhibitor canagliflozin for control of refractory equine hyperinsulinemia and laminitis.

Background: Hyperinsulinemia associated with pituitary pars intermedia dysfunction (PPID) and/or equine metabolic syndrome is well documented to put horses at high risk of laminitis. While dietary control of simple sugars and starch is the most effective therapy to control hyperinsulinemia, some horses fail to respond. Case Descriptions: Ten horses with hyperinsulinemia refractory to diet control, metformin, levothyroxine, and pergolide (if diagnosed with PPID) were treated with sodium-glucose cotransporter-2 inhibitor canagliflozin (Invokana®). Nine horses were hyperglycemic (>5.5 mmol/l) or had a history of hyperglycemia. Before instituting therapy, renal function was assessed by determining serum creatinine and blood urea nitrogen concentrations. Canagliflozin was administered orally once a day, with food. Dipstick urinalysis was performed every 2 weeks to confirm glucosuria and screen for proteinuria. Owners were also instructed regarding clinical signs consistent with urinary tract infection. All horses responded with a substantial decrease in serum insulin concentrations to normal or near normal values. Laminitis pain resolved in all cases, with regression of fat deposits. Owner satisfaction with outcomes was 100%. Conclusion: Once daily administration of the SGLT2 inhibitor canagliflozin corrected hyperglycemia, reduced insulin to normal or near normal levels, and was 100% effective in reversing or reducing abnormal fat pads and eliminating laminitis pain in horses with refractory hyperinsulinemia and laminitis. The core aspects of therapy-diet control, exercise when possible, and adequate treatment of PPID-must also be maintained if using canagliflozin. Canagliflozin should be reserved for refractory cases. Further controlled trials to investigate canagliflozin pharmacokinetics, pharmacodynamics, efficacy, and safety are needed.

Maternal Docosahexaenoic Acid Exposure Needed to Achieve Maternal-Newborn EQ.

Achieving maternal docosahexaenoic acid (DHA) status equal to or greater than the infant's DHA status at delivery is known as maternal-newborn DHA equilibrium (EQ) and is thought to be important for optimizing newborn DHA status throughout infancy. The objective of this study was to determine the daily DHA intake during pregnancy most likely to result in EQ. The participants (n = 1145) were from two randomized control trials of DHA supplementation in pregnancy. DHA intake was estimated using an abbreviated food frequency questionnaire. Total DHA exposure during pregnancy was calculated as a weighted average of the estimated DHA intake throughout pregnancy and the randomized DHA dose (200, 800, 1000 mg). Red blood cell DHA was measured from maternal and cord blood plasma at delivery and EQ status was calculated. The DHA intake required to achieve EQ was estimated by regression. In terms of DHA exposure, the point estimate and 95% confidence interval to achieve EQ was 643 (583, 735) mg of DHA/day. The results of our trial suggest an intake of 650 mg of DHA/day is necessary to increase the potential for EQ at delivery. The clinical benefits of achieving EQ deserves continued study.

Cortical Correlates of Increased Postural Task Difficulty in Young Adults: A Combined Pupillometry and EEG Study.

The pupillary response reflects mental effort (or cognitive workload) during cognitive and/or motor tasks including standing postural control. EEG has been shown to be a non-invasive measure to assess the cortical involvement of postural control. The purpose of this study was to understand the effect of increasing postural task difficulty on the pupillary response and EEG outcomes and their relationship in young adults. Fifteen adults completed multiple trials of standing: eyes open, eyes open while performing a dual-task (auditory two-back), eyes occluded, and eyes occluded with a dual-task. Participants stood on a force plate and wore an eye tracker and 256-channel EEG cap during the conditions. The power spectrum was analyzed for absolute theta (4−7 Hz), alpha (8−13 Hz), and beta (13−30 Hz) frequency bands. Increased postural task difficulty was associated with greater pupillary response (p < 0.001) and increased posterior region alpha power (p = 0.001) and fronto-central region theta/beta power ratio (p = 0.01). Greater pupillary response correlated with lower posterior EEG alpha power during eyes-occluded standing with (r = −0.67, p = 0.01) and without (r = −0.69, p = 0.01) dual-task. A greater pupillary response was associated with lower CoP displacement in the anterior−posterior direction during dual-task eyes-occluded standing (r = −0.60, p = 0.04). The pupillary response and EEG alpha power appear to capture similar cortical processes that are increasingly utilized during progressively more challenging postural task conditions. As the pupillary response also correlated with task performance, this measurement may serve as a valuable stand-alone or adjunct tool to understand the underlying neurophysiological mechanisms of postural control.

Prenatal docosahexaenoic acid supplementation has long-term effects on childhood behavioral and brain responses during performance on an inhibitory task.

Introduction: Offsprings from a prenatal docosahexaenoic acid (DHA) supplementation trial, in which pregnant women were assigned to placebo or 600mg DHA/day, were followed to determine the effect of prenatal DHA supplementation on the behavior and brain function at 5.5 years (n=81 placebo, n=86 supplemented).Methods: Event-related potentials (ERP) were recorded during a visual task requiring a button press (Go) to frequent target stimuli and response inhibition to the rare stimuli (No-Go). Univariate ANOVAs were used to test differences between group and sex for behavioral measures. ERP differences were tested using a three-way mixed-design multivariate analysis of variance (MANOVA).Results: There was a significant sex × group interaction for hit rate and errors of omission; there was no difference between males and females in the placebo group, but DHA males outperformed DHA females. Males overall and the placebo group made more errors requiring response inhibition; DHA females were significantly better than placebo females and DHA males. ERP P2 amplitude was larger in the DHA group. A significant N2 amplitude condition effect was observed in females and DHA group males, but not in placebo group males.Discussion: Prenatal DHA supplementation improved inhibitory performance overall, especially for females in the DHA group, possibly accounting for their conservative behavior during Go trials. Development of brain regions responsible for visual processing may be sensitive to maternal DHA status, evidenced by greater P2 amplitude. Males may benefit more from maternal DHA supplementation, indicated by the N2 condition effect seen only in males in the DHA group.

Prenatal docosahexaenoic acid effect on maternal-infant DHA-equilibrium and fetal neurodevelopment: a randomized clinical trial.

INTRODUCTION: Maternal-infant equilibrium occurs when cord blood docosahexaenoic acid (DHA) is less than or equal to maternal DHA at delivery. Equilibrium may be an indicator of sufficient DHA for optimal fetal and infant neurodevelopment. The purpose of this study was to test the effect of maternal DHA supplementation on equilibrium status and fetal neurodevelopment. METHODS: Women enrolled between 12 and 20 weeks gestation and were randomized to 200 or 800 mg DHA/day until delivery. Maternal red blood cell (RBC) phospholipids were measured at enrollment, 32 weeks, delivery, and in cord blood at delivery. Fetal neurodevelopment was measured at 32 and 36 weeks gestation. Intent-to-treat analyses were conducted to test differences in equilibrium status by group. Fetal outcomes were assessed by equilibrium status and group. RESULTS: Three hundred women enrolled and 262 maternal-infant dyads provided blood samples at delivery. No maternal-infant dyads with maternal RBC-DHA ≤ 6.96% at delivery achieved equilibrium. The incidence of equilibrium was significantly higher in the 800 mg group. There was no effect of maternal group or equilibrium status on fetal neurodevelopment. CONCLUSION: The significance of maternal-infant DHA equilibrium remains unknown. Ongoing research will test the effect of treatment group, equilibrium, and nutrient status on infant behavior and brain function. IMPACT: Pregnant women who received a higher dose of docosahexaenoic acid (DHA) were more likely to achieve maternal-infant DHA equilibrium at delivery. Equilibrium status had no effect on fetal neurodevelopment in this sample. While DHA is crucial for early life neurodevelopment, the significance of achieving maternal-infant equilibrium above the lower threshold is uncertain. There is a lower threshold of maternal DHA status where maternal-infant DHA equilibrium never occurs. The lack of equilibrium associated with low maternal DHA status may indicate insufficient maternal status for optimal placental transfer.

Effects of Transcranial Direct Current Stimulation (tDCS) on Go/NoGo Performance Using Food and Non-Food Stimuli in Patients with Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a neurodevelopmental genetic disorder characterized by multiple system involvement with hypotonia, poor suck with feeding difficulties, growth and other hormone deficiencies, intellectual disability, and behavioral problems with childhood onset of hyperphagia resulting in obesity, if not externally controlled. Transcranial direct current stimulation (tDCS) has been increasingly shown to modulate cognitive and behavioral processes in children and adults, including food-intake behaviors in patients with PWS. This study further reports the positive effects of brief tDCS sessions on Go/NoGo task performance involving food and non-food stimuli images, alterations in N2 brain amplitude, and genetic subgroup differences (maternal disomy 15, UPD; 15q11-q13 deletion, DEL) before and after tDCS as assessed by event-related potentials (ERPs) in 10 adults with PWS. The results indicate a group effect on baseline NoGo N2 amplitude in PWS patients with DEL vs UPD (p =0.046) and a decrease in NoGo N2 amplitude following tDCS (p = 0.031). Our tDCS approach also demonstrated a trend towards decreased response time. Collectively, these results replicate and expand prior work highlighting neurophysiological differences in patients with PWS according to genetic subtype and demonstrate the feasibility in examining neuromodulatory effects of tDCS on information processing in this patient population to stimulate additional research and treatment.

Possible dysmetabolic hyperferritinemia in hyperinsulinemic horses.

Background: Hyperinsulinemia associated with equine metabolic syndrome and pituitary pars intermedia dysfunction is a risk factor for laminitis. Research in other species has shown elevated body iron levels as both a predictor and consequence of insulin resistance. In humans, this is known as dysmetabolic hyperferritinemia. Aim: To explore the relationship between equine hyperinsulinemia and body iron levels. Methods: We reviewed case histories and laboratory results from an open access database maintained by the Equine Cushing's and Insulin Resistance Group Inc. (ECIR). We identified 33 horses with confirmed hyperinsulinemia and laboratory results for serum iron, total iron binding capacity, and ferritin. Pearson correlation was used to test the relationship between insulin and iron indices. Additionally, we performed a secondary analysis of a previously reported controlled trial that was originally designed to test the correlation between iron status and the insulin response in horses. Here, we used a t-test to compare the mean values of insulin and ferritin between horses we categorized as normal or hyperinsulinemic based on their response to an oral challenge. Results: Serum ferritin exceeded published reference range in 100% of the horses identified from the ECIR database. There were no statistically significant associations between insulin indices (RISQI, log insulin) and iron indices (log serum iron, log TSI%, log ferritin). There were trends for a negative association between RISQI and log iron [r(31) = -0.33, p = 0.058] and a positive association between age and ferritin [r(30) = 0.34, p = 0.054]. From the secondary data analysis of published data, we found significantly elevated ferritin (p = 0.05) in horses considered hyperinsulinemic by dynamic insulin testing compared to horses with a normal response. Conclusion: These results suggest the potential for iron overload in hyperinsulinemic horses, a feature documented in other species and should stimulate further study into the relationship between insulin and iron dysregulation in the horse.

Preferential activation for emotional Western classical music versus emotional environmental sounds in motor, interoceptive, and language brain areas.

Recent meta analyses suggest there is a common brain network involved in processing emotion in music and sounds. However, no studies have directly compared the neural substrates of equivalent emotional Western classical music and emotional environmental sounds. Using functional magnetic resonance imaging we investigated whether brain activation in motor cortex, interoceptive cortex, and Broca's language area during an auditory emotional appraisal task differed as a function of stimulus type. Activation was relatively greater to music in motor and interoceptive cortex - areas associated with movement and internal physical feelings - and relatively greater to emotional environmental sounds in Broca's area. We conclude that emotional environmental sounds are appraised through verbal identification of the source, and that emotional Western classical music is appraised through evaluation of bodily feelings. While there is clearly a common core emotion-processing network underlying all emotional appraisal, modality-specific contextual information may be important for understanding the contribution of voluntary versus automatic appraisal mechanisms.

Heart rate variability categories of fluctuation amplitude and complexity: diagnostic markers of fetal development and its disturbances.

OBJECTIVE: In fetal diagnosis the myriad and diversity of heart rate variability (HRV) indices prevents a comparable routine evaluation of disturbances in fetal development and well-being. The work aims at the extraction of a small set of HRV key indices that could help to establish a universal, overarching tool to screen for any disturbance. APPROACH: HRV indices were organized in categories of short-term (prefix s) and long-term (prefix l) amplitude fluctuations (AMP), complexity (COMP), and patterns (PATTERN) and common representatives for each category were extracted. This procedure was done with respect to the diagnostic value in the evaluation of the maturation age throughout the second and complete third trimester of pregnancy as well as to potential differences associated with maternal life-style factors (physical exercise, smoking), nutrient intervention (docosahexaenoic acid (DHA) supplementation), and complications of pregnancy (gestational diabetes mellitus (GDM), intra-uterine growth restriction (IUGR)). MAIN RESULTS: We found a comprehensive minimal set that includes [lAMP: short term variation (STV), initially introduced in cardiotocography, sAMP: heart rate increase across one interbeat interval of phase rectified averaged signal - acceleration capacity (ACst1), lCOMP: scale 4 multi-scale entropy (MSE4), PATTERN: skewness] for the maturation age prediction, and partly overlapping [lAMP: STV, sAMP: ACst1, sCOMP: Lempel Ziv complexity (LZC)] for the discrimination of the deviations. SIGNIFICANCE: The minimal set of category-based HRV representatives allows for a screening of fetal development and well-being. These results are an important step towards a universal and comparable diagnostic tool for the early identification of developmental disturbances. Novelty & Significance Fetal development and its disturbances have been reported to be associated with a multiplicity of HRV indices. Furthermore, these HRV indices change with maturation. We propose the abstraction of HRV categories defined by short- and long-term fluctuation amplitude, complexity, and pattern indices that cover all relevant aspects of maturational age, behavioral influences and a series of pathological disturbances. The study data are provided by multiple centers. Our approach is an important step towards the goal of a standardized diagnostic tool for early identification of fetal developmental disturbances with respect to the reduction of serious complications in the later life.

Critical and Sensitive Periods in Development and Nutrition.

Critical or sensitive periods in the life of an organism during which certain experiences or conditions may exert disproportionate influence (either for harm or benefit) on long-term developmental outcomes have been the subject of investigation for over a century. This chapter reviews research in the context of the development of social preferences and sensory systems, with a summary of the criteria for defining such a period and the evidence necessary to establish its existence. The notion of nutritional programming, central to the Barker/Developmental Origins hypotheses of health and disease, represents a variant of the critical/sensitive period concept. It is implicit in these hypotheses that the fetal period is a time during which metabolic and physiological systems are malleable and thus susceptible to either insult or enhancement by nutrient intake. Evidence for critical/sensitive periods or nutritional programming requires a systematic manipulation of the age at which nutritional conditions or supplements are implemented. While common in research using animal models, the approach is difficult to establish in epidemiological studies and virtually nonexistent in human clinical trials. Future work seeking to establish definitive evidence for critical/sensitive periods or programming may be advanced by harmonized outcome measures in experimental trials across which the timing, duration, and dose of nutrients is varied.

Long-chain polyunsaturated fatty acid supplementation in the first year of life affects brain function, structure, and metabolism at age nine years.

The present study sought to determine whether supplementation of long-chain polyunsaturated fatty acids (LCPUFA) during the first year of life influenced brain function, structure, and metabolism at 9 years of age. Newborns were randomly assigned to consume formula containing either no LCPUFA (control) or formula with 0.64% of total fatty acids as arachidonic acid (ARA; 20:4n6) and variable amounts of docosahexaenoic acid (DHA; 22:6n3) (0.32%, 0.64%, or 0.96% of total fatty acids) from birth to 12 months. At age 9 years (±0.6), 42 children enrolled in a follow-up multimodal magnetic resonance imaging (MRI) study including functional (fMRI, Flanker task), resting state (rsMRI), anatomic, and proton magnetic resonance spectroscopy (1 H MRS). fMRI analysis using the Flanker task found that trials requiring greater inhibition elicited greater brain activation in LCPUFA-supplemented children in anterior cingulate cortex (ACC) and parietal regions. rsMRI analysis showed that children in the 0.64% group exhibited greater connectivity between prefrontal and parietal regions compared to all other groups. In addition, voxel-based analysis (VBM) revealed that the 0.32% and 0.64% groups had greater white matter volume in ACC and parietal regions compared to controls and the 0.96% group. Finally, 1 H MRS data analysis identified that N-acetylaspartate (NAA) and myo-inositol (mI) were higher in LCPUFA groups compared to the control group. LCPUFA supplementation during infancy has lasting effects on brain structure, function, and neurochemical concentrations in regions associated with attention (parietal) and inhibition (ACC), as well as neurochemicals associated with neuronal integrity (NAA) and brain cell signaling (mI).

Dose-response relationship between docosahexaenoic acid (DHA) intake and lower rates of early preterm birth, low birth weight and very low birth weight.

As previously reported, intention-to-treat findings from our phase III randomized clinical trial found that a supplement of 600 mg docosahexaenoic acid (DHA)/day during the last half of pregnancy reduced the incidence of early preterm birth (ePTB, <34 weeks gestation) and very low birth weight (VLBW < 1500 g) offspring. Given the potentially immense clinical significance of these findings, the goal of this secondary analysis was to (1) identify maternal characteristics related with capsule intake (i.e. DHA dose exposure) and (2) determine if DHA dose was associated with low (<2500 g) and very low birth weight after controlling for any relevant maternal characteristics. Three hundred forty-five pregnant mothers were recruited from hospitals in the Kansas City metropolitan area between 2006 and 2011. Most participants (n = 299) were from the phase III trial mentioned above, but we also included 46 participants from a second smaller, randomized trial that utilized an identical intervention design and was conducted concurrent to the larger trial. Both trials assigned participants to either 3 daily capsules of vegetable oil without DHA (n = 169) or 3 daily capsules of 200 mg DHA each (n = 176). Total capsules consumed was recorded by pharmacy supervised capsule count or participant self-report when needed. Maternal age, education, race and gestational age at delivery as well as infant birth weight were available for both trials. A Bayesian linear model indicated capsule intake increased with maternal age (p = 0.0100) and years of education (p = 0.0002). A Bayesian bivariate mixture-model associated capsule intake with simultaneous lower probability of ePTB, low birth weight (LBW, <2500 g) and VLBW (p = 0.0327). This, in conjunction with the positive findings in the clinical trial, support the need for future research to examine intervention methods to improve capsule compliance strategies in younger and less educated mothers.

Programming of infant neurodevelopment by maternal obesity: potential role of maternal inflammation and insulin resistance.

BACKGROUND AND OBJECTIVES: Recent studies show that maternal obesity is associated with impaired offspring neurodevelopmental outcomes. The mechanism underlying the association is unclear. However, there is evidence to suggest a role for intra-uterine exposure to inflammation and insulin resistance (IR). We aimed to determine if maternal IR and inflammation were associated to fetal neurodevelopment as indicated by fetal heart rate variability (HRV), an index of fetal cardiac autonomic nervous system development. METHODS AND STUDY DESIGN: A total of 44 healthy maternal-fetal pairs (maternal pre-pregnancy BMI distribution: n=20 normal weight, 8 overweight, 16 obese) were analyzed. We assessed maternal inflammation (plasma IL-6 and TNF-α) and IR (HOMA index). Fetal HRV, a proxy for fetal neurodevelopment, was assessed using fetal magnetocardiogram at the 36th week of pregnancy. The relationships between maternal inflammation and IR with fetal HRV (SD1 and SD2) were estimated individually by Pearson bivariate correlations. RESULTS: No correlations were observed between the fetal HRV components with maternal HOMA-IR and maternal plasma levels of IL-6 and TNF-α (all p<0.05). However, the negative association between maternal TNF-α level and fetal SD2 approached significance (correlation coefficient=-0.29, 95% confidence interval=-0.62,-0.03, p=0.07). CONCLUSION: Maternal IR and inflammation during pregnancy were not associated with fetal cardiac autonomic nervous system development. Further studies with a larger sample size and more maternal inflammatory indicators are needed to explore these relationships.

A magnetoencephalography investigation of coherence source imaging in panic disorder.

Limbic and frontal structures are largely implicated in panic disorder (PD). Decreased coherence imaging values, as determined by magnetoencephalography (MEG), are suggestive of decreased or inefficient communication among these structures. We have previously demonstrated that coherence source imaging (CSI) values could be similar or higher in some PD patients. The purpose of the current investigation was to replicate these finding in a larger sample. Nine strictly diagnosed PD patients and nine age-matched and sex-matched healthy controls were examined. The CSI-MEG values of 26 frontotemporal regions (FTRs) and 28 extra-frontotemporal regions (ex-FTR; Brodmann areas) were determined for each participant. MEG scans were acquired using a 151-channel whole-head biomagnetometer system. Despite the relatively small sample size, CSI values were significantly lower in a number of FTRs in PD patients. In none of the ex-FTRs (i.e. posterior regions) were there differences between panic and control groups. The above data add to the complexity of understanding the nature of the pathophysiology of PD. Our finding of decreased focal coherence imaging values may reflect decreased excitability in these areas. The preliminary finding could be interpreted as an inhibitory process guarding against the spread of activity in closer hyperexcitable areas as seen in epilepsy. The current data provide evidence for dysfunctional communication within the frontotemporal structures. The findings have implications for the understanding of the neural circuitry underlying PD.