Therapy with JAK inhibitors or bDMARDs and the risk of cardiovascular events in the Dutch rheumatoid arthritis population.

OBJECTIVE: Caution has been advocated recently when using Janus kinase inhibitors (JAKi) in rheumatoid arthritis (RA) patients with an unfavorable cardiovascular risk profile. We aimed to compare the incidences in cardiovascular events between JAKi or bDMARDs in a large population of RA patients. METHODS: RA patients starting a new bDMARD or JAKi between August 1st 2018 and January 31st 2022 have been selected from IQVIA's Dutch Real-World Data Longitudinal Prescription database, covering about 63% of outpatient prescriptions in the Netherlands. Study outcome was a cardiovascular event, defined as the start of platelet aggregation inhibitors during study period. The incidence densities of cardiovascular events were compared between JAKi and bDMARDs using multilevel Poisson regression, adjusted for exposition time and confounders. RESULTS: 15 191 unique patients were included, with 28 481 patient-years on treatment with either JAKi (2,373) or bDMARDs (26 108). Most patients were female (72%) and median age was 62 years. We found 36 cardiovascular events (1.52 events/100 patient years) during therapy with JAKi and 383 events (1.47 events/100 patient years) during therapy with bDMARDs, respectively, resulting in an adjusted incidence rate ratio (IRR) of 0.99 for JAKi compared with bDMARDs (95% confidence interval (CI), 0.70-1.41). Sub-analyses in patients >65 years, by sex, or separately for tofacitinib and baricitinib, yielded similar results. CONCLUSION: In a large Dutch general RA population, the risk of cardiovascular events seems not different between JAKi users and those using bDMARDs, although a small increase in higher risk patients cannot be excluded.

Fetal DHA inadequacy and the impact on child neurodevelopment: a follow-up of a randomised trial of maternal DHA supplementation in pregnancy.

DHA is an important component of neural lipids accumulating in neural tissue during development. Inadequate DHA in gestation may compromise infant development, but it is unknown whether there are lasting effects. We sought to determine whether the observed effects of fetal DHA inadequacy on infant development persist into early childhood. This follow-up study assessed children (5-6 years) whose mothers received 400 mg/d DHA or a placebo during pregnancy. Child neurodevelopment was assessed with several age-appropriate tests including the Kaufman Assessment Battery for Children. A risk-reduction model was used whereby the odds that a child from the maternal placebo group would fail to achieve a test score in the top quartile was calculated. The association of maternal DHA intake and status in gestation with child test scores, as well as with child DHA intake and status, was also determined. No differences were detected in children (n 98) from the maternal placebo and DHA groups achieving a high neurodevelopment test score (P>0·05). However, maternal DHA status was positively related to child performance on some tests including language and short-term memory. Furthermore, child DHA intake and status were related to the mother's intake and status in gestation. The neurodevelopment effects of fetal DHA inadequacy may have been lost or masked by other variables in the children. Although we provide evidence that maternal DHA status is related to child cognitive performance, the association of maternal and child DHA intake and status limits the interpretation of whether DHA before or after birth is important.

Novel homologous lactate transporter improves L-lactic acid production from glycerol in recombinant strains of Pichia pastoris.

BACKGROUND: Crude glycerol is the main byproduct of the biodiesel industry. Although it can have different applications, its purification is costly. Therefore, in this study a biotechnological route has been proposed for further utilization of crude glycerol in the fermentative production of lactic acid. This acid is largely utilized in food, pharmaceutical, textile, and chemical industries, making it the hydroxycarboxylic acid with the highest market potential worldwide. Currently, industrial production of lactic acid is done mainly using sugar as the substrate. Thus here, for the first time, Pichia pastoris has been engineered for heterologous L-lactic acid production using glycerol as a single carbon source. For that, the Bos taurus lactate dehydrogenase gene was introduced into P. pastoris. Moreover, a heterologous and a novel homologous lactate transporter have been evaluated for L-lactic acid production. RESULTS: Batch fermentation of the P. pastoris X-33 strain producing LDHb allowed for lactic acid production in this yeast. Although P. pastoris is known for its respiratory metabolism, batch fermentations were performed with different oxygenation levels, indicating that lower oxygen availability increased lactic acid production by 20 %, pushing the yeast towards a fermentative metabolism. Furthermore, a newly putative lactate transporter from P. pastoris named PAS has been identified by search similarity with the lactate transporter from Saccharomyces cerevisiae Jen1p. Both heterologous and homologous transporters, Jen1p and PAS, were evaluated in one strain already containing LDH activity. Fed-batch experiments of P. pastoris strains carrying the lactate transporter were performed with the batch phase at aerobic conditions followed by an aerobic oxygen-limited phase where production of lactic acid was favored. The results showed that the strain containing PAS presented the highest lactic acid titer, reaching a yield of approximately 0.7 g/g. CONCLUSIONS: We showed that P. pastoris has a great potential as a fermentative organism for producing L-lactic acid using glycerol as the carbon source at limited oxygenation conditions (below 0.05 % DO in the bioreactor). The best strain had both the LDHb and the homologous lactate transporter encoding genes expressed, and reached a titer 1.5 times higher than the strain with the S. cerevisiae transporter. Finally, it was also shown that increased lactic acid production was concomitant to reduction of acetic acid formation by half.

Construction and analysis of a modified transposable element carrying an outward directed inducible promoter for Bacillus subtilis.

Transposons are important tools to inactivate chromosomal genes followed by a correlation with a particular phenotype or genotype. Here we demonstrated the development of a special type of genetically engineered transposon carrying an outward-directed inducible promoter in order to allow transcription of nearby genes. We have modified the mariner transposon TnYLB able to transpose in B. subtilis. This modified TnYLB carries an expression unit consisting of the xylose repressor xylR and an outward-directed promoter negatively controlled by this repressor. This TnYLB-XylOut transposon is able to turn on gene expression if insertion occurs close to a promoter-less gene. It will be an important tool to identify the function of genes either by turning on their expression or by enhanced expression depending on the xylose concentration.

Real world insights for psoriasis: the association of severity of skin lesions with work productivity, medical consumption costs and quality of life.

BACKGROUND: Psoriasis is a prevalent, chronic skin disease with a potential impact on work productivity, medical consumption costs, and quality of life. The influence of the extent of skin lesions on these outcomes is not well known. OBJECTIVE: We determined associations of self-reported skin lesions with self-reported work productivity, medical consumption costs, and health-related quality of life in respondents with psoriasis. METHODS: In this cross-sectional study, we included respondents with self-reported psoriasis in the Netherlands in an online questionnaire. We assessed the self-reported percentage body surface area (BSA) of psoriasis lesions. We used validated instruments to assess work productivity (WPAI-PsO), medical consumption costs (iMCQ), and health-related quality of life (EQ-5D-5L and the DLQI). We used ordinal logistic regression to associate BSA categories >1% versus 0-1% with outcomes adjusted for multiple confounders. RESULTS: We included 501 respondents with a mean age of 43 ± 12 years; 64% were men. Median BSA was 2% (interquartile range 1-5%). A higher BSA was associated with higher overall work impairment due to psoriasis (common odds ratio [cOR] 2.44, 95% confidence interval [CI] 1.40-4.29; n = 205), higher medical consumption costs (cOR 2.06, 95% CI 1.45-2.94) and lower health-related quality of life. Associations were strongest with a BSA cutoff of 0% or 1% compared to 2% or higher categories. DISCUSSION: In our study, having few to no lesions in psoriasis was associated with lower overall work impairment due to psoriasis, lower medical consumption costs, and higher health-related quality of life.

Construction of an artificial secYEG operon allowing high level secretion of α-amylase.

The key components of the major secretion pathway in bacteria, the Sec pathway, are the proteins SecA, an ATPase that generates the energy required for protein translocation, and the heterotrimeric protein complex SecYEG, which functions as the preprotein-conducting channel through the cytoplasmic membrane, named translocon. Overexpression of exoproteins can cause jamming of the membrane, e.g., due to a shortage of translocons. Therefore, we decided to increase the number of translocons by first creating an artificial secYEG operon and then fusing it to an inducible promoter. By Western- and Northern-blot analysis, we could first show that the amount of the SecY protein and the secYEG transcript can be increased after addition of the inducer. Next, we proved by immunoblot experiments that the amount of α-amylase secreted in the presence of increased amounts of SecYEG proteins is enhanced. Therefore, increasing the number of translocons is accompanied by a concomitant increase in the amount exoenzymes. This finding will be of importance for high-level secretion of recombinant proteins.

Sources of trans and saturated fatty acids in the diets of Vancouver children.

PURPOSE: Amounts and sources of trans fatty acids (TFA) and saturated fatty acids (SFA) were examined in the diets of children aged five to six years after changes in TFA in Canadian foods. METHODS: Dietary intake was assessed for 100 Vancouver children, using three 24-hour recalls during parental interviews. Trans fatty acid and SFA intakes and food sources were determined for each child. RESULTS: The TFA intake was 0.71 ± 0.31% of energy, and 12% of children consumed over 1% of energy from TFA. Saturated fatty acids intakes were 12.5 ± 3.39% of energy, and 81% of the children consumed more than 10% of energy from SFA. Monounsaturated and polyunsaturated fatty acid intakes were 12.0 ± 3.0% and 5.79 ± 2.16% of energy, respectively. Major sources of TFA were dairy products, fast foods, and bakery products. Major sources of SFA were dairy products, processed foods, fast food, and bakery products. CONCLUSIONS: The TFA intakes of children aged five to six years have decreased since 2004 to a 95th percentile intake of 1.28% of energy, but more than 80% of children consume over 10% of energy from SFA. Removing TFA from snacks and bakery products would decrease the highest TFA intakes to 1% of energy. This study suggests that increased efforts by industry or educational guidance for parents is required to enable selection of foods lower in TFA, and that greater emphasis is needed on SFA.

Prevalence and Predictors of Nonadherence to Direct Oral Anticoagulant Treatment in Patients with Atrial Fibrillation.

Background For most patients with newly diagnosed atrial fibrillation (AF), direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists. However, there is concern that the lack of monitoring may impair therapy adherence and therefore the anticoagulant effect. Objective To assess 1-year DOAC nonadherence in patients with AF and a treatment indication of at least 1 year in the Dutch health care setting, and to identify predictors of nonadherence. Methods We performed a near-nationwide historical cohort study in patients with a novel DOAC indication for AF. Data were obtained from a pharmacy database, covering 65% of all outpatient prescriptions dispensed in the Netherlands. The 1-year nonadherence was assessed by the proportion of days covered; the threshold was set at <80%. Robust Poisson regression analyses were performed to identify predictors of nonadherence. Results A total of 46,211 patients were included and the 1-year nonadherence was 6.5%. We identified male sex (risk ratio [RR] 1.23, 95% confidence interval [CI]: 1.15-1.33), younger age (age ≥60 to <70 years: RR: 1.15, 95% CI: 1.00-1.33, age <60 years: RR: 2.22, 95% CI: 1.92-2.57; reference age ≥85 years), a reduced DOAC dose (RR: 1.10, 95% CI: 1.00-1.22), a twice-daily dosing regimen (RR: 1.21, 95% CI: 1.12-1.30), and treatment with apixaban (RR: 1.16, 95% CI: 1.06-1.26, reference rivaroxaban) or dabigatran (RR: 1.25, 95% CI: 1.14-1.37) as independent predictors of 1-year nonadherence. Conclusion One-year nonadherence to DOACs was low yet relevant in patients with AF newly prescribed a DOAC. Understanding the predictors for nonadherence may help identify patients at risk.

Complexity of understanding the role of dietary and erythrocyte docosahexaenoic acid (DHA) on the cognitive performance of school-age children.

Background: Early childhood is a period of rapid brain development, with increases in synapses rich in the omega-3 (ω-3) fatty acid, DHA (22:6ω-3) continuing well beyond infancy. Despite the importance of DHA to neural phospholipids, the requirement of dietary DHA for neurodevelopment remains unclear. Objectives: The aim was to assess the dietary DHA and DHA status of young children, and determine the association with cognitive performance. Methods: This was a cross-sectional study of healthy children (5-6 y), some of whom were enrolled in a follow-up of a clinical trial (NCT00620672). Dietary intake data (n = 285) were assessed with a food-frequency questionnaire (FFQ) and three 24-h recalls. Family characteristics were collected by questionnaire, and anthropometric data measured. Venous blood was collected, cognitive performance assessed using several age-appropriate tools including the Kaufman Assessment Battery for Children. The relation between dietary DHA, RBC DHA, and child neurodevelopment test scores was determined using Pearson's correlation or Spearman's rho, and quintiles of test scores compared by Mann-Whitney U test. Results: Child DHA intakes were highly variable, with a stronger association between RBC DHA and DHA intake assessed by FFQ (rho = 0.383, P < 0.001) compared with one or three 24-h recalls. Observed ethnic differences in DHA intake status as well as neurodevelopmental test scores led to analysis of the association between DHA intake and status with neurodevelopment test scores for White children only (n = 190). Child RBC DHA status was associated with neurodevelopment test scores, including language (rho = 0.211, P = 0.009) and short-term memory (rho = 0.187, P = 0.019), but only short-term memory was associated with dietary DHA (rho = 0.221, P = 0.003). Conclusions: Child RBC DHA but not dietary DHA was associated with multiple tests of cognitive performance. In addition, DHA intake was only moderately associated with RBC DHA, raising complex questions on the relation between diet, DHA transfer to membrane lipids, and neural function.

High dietary sodium intake among young children in Vancouver, British Columbia.

OBJECTIVE: To determine the intake distribution and food sources of sodium among young children. METHODS: Dietary intake was determined for 190 children, 16 months to 6 years of age, using a food frequency questionnaire completed by interviewing a parent. Dietary intake of all nutrients, including dietary sodium, was analyzed. The major food sources of sodium were assessed by grouping foods into categories based on Canada's Food Guide, with subsequent subdivision into food type categories. RESULTS: Dietary sodium intakes were skewed, with a median intake of 2021 mg/d and 5th-95th percentile range of 888-3975 mg/d. The sodium intake of 91.6% of children was above the recommended 1000 or 1200 mg/d for children 1-3 or 3-6 years, respectively, and 85% and 54% had intakes above the tolerable upper limits of 1500 and 1900 mg/d, respectively. The 5 food sources providing the highest amount of sodium were soups, processed/fast foods, dairy products, breads, and processed meats. CONCLUSION: Children are vulnerable to high sodium intake as a result of their food patterns and the high sodium content of these foods. This report demonstrates that Canadian children have high sodium intakes. Knowledge of feeding practices involving high-sodium foods can assist parents and caregivers in reducing the high sodium intake of young children.

A partially hydrolyzed formula with synbiotics supports adequate growth and is well tolerated in healthy, Chinese term infants: A double-blind, randomized controlled trial.

OBJECTIVES: The aim of this study was to evaluate growth and gastrointestinal tolerance in infants fed a partially hydrolyzed protein formula (pHF) with a synbiotic mixture of short-chain galacto-oligosaccharides and long-chain fructooligosaccharides (scGOS/lcFOS; 9:1) and Bifidobacterium breve M-16V (test formula) compared with an intact protein infant formula (IF) with scGOS/lcFOS (control formula). METHODS: This randomized, double-blind, controlled, multicenter trial enrolled healthy, fully formula-fed Chinese infants (≤44 d) who received either the test (n = 112) or control formula (n = 112) until 17 wk of age. Fully breastfed infants served as a reference (n = 60). Anthropometrics, gastrointestinal symptoms, and adverse events were assessed monthly. Primary outcome was weight gain in grams per day from baseline to 17 wk of age. RESULTS: Equivalence in daily weight gain (primary outcome) was demonstrated between the test and control groups (estimated mean difference [SE]: -0.36 [0.93] g/d, 90% confidence interval [CI], -1.90 to 1.18) as well as between each IF group and the breastfed reference group (test: 0.02 [1.05] g/d, 90% CI, -1.71 to 1.75; control: 0.36 [1.04] g/d, 90% CI, -1.35 to 2.08). There were no clinically relevant differences in gastrointestinal tolerance or adverse events between the formula groups. CONCLUSION: A pHF with synbiotics supports adequate growth and is well tolerated in healthy, term-born Chinese infants. Additionally, infant growth and gastrointestinal tolerance measures of both IF groups were comparable to the breastfed group and can be considered suitable and well tolerated for use.

A Partly Fermented Infant Formula with Postbiotics Including 3'-GL, Specific Oligosaccharides, 2'-FL, and Milk Fat Supports Adequate Growth, Is Safe and Well-Tolerated in Healthy Term Infants: A Double-Blind, Randomised, Controlled, Multi-Country Trial.

This study investigated growth, safety, and tolerance in healthy infants consuming a partly fermented infant formula (IF) with postbiotics, 2'-linked fucosyllactose (2'-FL), a specific prebiotic mixture of short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharides (lcFOS), and milk fat. This double-blind, controlled trial randomised 215 fully IF-fed infants ≤ 14 days of age to either: Test Group (IF) containing 26% fermented formula with postbiotics derived from Lactofidus fermentation process (including 3'-Galactosyllactose; 3'-GL), 0.8 g/100 mL scGOS/lcFOS (9:1), 0.1 g/100 mL 2'-FL, and milk fat), or Control group (IF with 0.8 g/100 mL scGOS/lcFOS (9:1)) until 17 weeks of age. Fully breastfed infants were included as a reference. Anthropometric measures, gastrointestinal symptoms, and safety were assessed monthly. Equivalence in weight gain (primary outcome) between the Test and Control groups was confirmed (difference in means -0.08 g/day; 90% CI (-1.47;1.31)) with estimated mean weight gain (SE) of 31.00 (0.59) g/day and 31.08 (0.60) g/day, respectively, (PP population, n = 196). Equivalence in length and head circumference gain between the randomised groups was also confirmed. No statistically significant differences were observed in adverse events or gastrointestinal tolerance between randomised IF groups. A partly fermented IF with postbiotics, specific oligosaccharides, 2'-FL, and milk fat supports adequate infant growth and is safe and well-tolerated in healthy term infants.

Gastrointestinal Tolerance, Growth and Safety of a Partly Fermented Formula with Specific Prebiotics in Healthy Infants: A Double-Blind, Randomized, Controlled Trial.

This study evaluated the effect of a partly fermented infant formula (using the bacterial strains Bifidobacterium breve C50 and Streptococcus thermophilus 065) with a specific prebiotic mixture (short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharides (lcFOS; 9:1)) on the incidence of gastrointestinal symptoms, stool characteristics, sleeping and crying behaviour, growth adequacy and safety. Two-hundred infants ≤28 days of age were assigned either to experimental infant formula containing 30% fermented formula and 0.8 g/100 mL scGOS/lcFOS or to non-fermented control infant formula without scGOS/lcFOS. A group of breastfed infants served as a reference. No relevant differences in parent-reported gastrointestinal symptoms were observed. Stool consistency was softer in the experimental versus control group with values closer to the breastfed reference group. Daily weight gain was equivalent for both formula groups (0.5 SD margins) with growth outcomes close to breastfed infants. No clinically relevant differences in adverse events were observed, apart from a lower investigator-reported prevalence of infantile colic in the experimental versus control group (1.1% vs. 8.7%; p < 0.02). Both study formulae are well-tolerated, support an adequate infant growth and are safe for use in healthy term infants. Compared to the control formula, the partly fermented formula with prebiotics induces stool consistencies closer to breastfed infants.

Effect of Pyruvate Decarboxylase Knockout on Product Distribution Using Pichia pastoris (Komagataella phaffii) Engineered for Lactic Acid Production.

Lactic acid is the monomer unit of the bioplastic poly-lactic acid (PLA). One candidate organism for lactic acid production is Pichia pastoris, a yeast widely used for heterologous protein production. Nevertheless, this yeast has a poor fermentative capability that can be modulated by controlling oxygen levels. In a previous study, lactate dehydrogenase (LDH) activity was introduced into P. pastoris, enabling this yeast to produce lactic acid. The present study aimed to increase the flow of pyruvate towards the production of lactic acid in P. pastoris. To this end, a strain designated GLp was constructed by inserting the bovine lactic acid dehydrogenase gene (LDHb) concomitantly with the interruption of the gene encoding pyruvate decarboxylase (PDC). Aerobic fermentation, followed by micro-aerophilic culture two-phase fermentations, showed that the GLp strain achieved a lactic acid yield of 0.65 g/g. The distribution of fermentation products demonstrated that the acetate titer was reduced by 20% in the GLp strain with a concomitant increase in arabitol production: arabitol increased from 0.025 g/g to 0.174 g/g when compared to the GS115 strain. Taken together, the results show a significant potential for P. pastoris in producing lactic acid. Moreover, for the first time, physiological data regarding co-product formation have indicated the redox balance limitations of this yeast.

Production of a polar fish antimicrobial peptide in Escherichia coli using an ELP-intein tag.

An important aspect related to infectious pathogens is their exceptional adaptability in developing resistance, which leads to a perpetual challenge in the discovery of antimicrobial drugs with novel mechanisms of action. Among them, antimicrobial peptides (AMPs) stand out as promising anti-infective molecules. In order to overcome the high costs associated with isolation from natural sources or chemical synthesis of AMPs we propose the expression of Pa-MAP 2, a polyalanine AMP. Pa-MAP 2 was fused to an ELP-intein tag where the ELP (Elastin-like polypeptide) was used to promote aggregation and fast and cost-effective isolation after expression, and the intein was used to stimulate a controlled AMP release. For these, the vector pET21a was used to produce Pa-MAP 2 fused to the N-termini region of a modified Mxe GyrA intein followed by 60 repetitions of ELP. Purified Pa-MAP 2 showed a MIC of 25µM against E. coli ATCC 8739. Batch fermentation demonstrated that Pa-MAP-2 can be produced in both rich and defined media at yields 50-fold higher than reported for other AMPs produced by the ELP-intein system, and in comparable yields to expression systems with protease or chemical cleavage.

Production of a modified peptide clavanin in Pichia pastoris: cloning, expression, purification and in vitro activities.

Antimicrobial peptides are one of the most promising peptide-based drugs due to their enormous potential as novel biopharmaceuticals in both human and animal industries. In order to develop strategies to over produce such molecules, heterologous production of a modified version of clavanin A, here named clavanin MO (clavMO), was successfully achieved in the methylothopic yeast Pichia pastoris. ClavMO was fused to thioredoxin as a carrier protein and the construction was tested using two promoters, PAOX1 and PGAP, based on either induced or constitutive expression systems, respectively. After growth in 5 L Bioreactor, clavMO-thio was recovered and purified through size exclusion chromatography. Our findings show that both constitutive and inducible expression systems produce active clavMO fused to thioredoxin against both Gram-negative Klebsiella pneumoniae and Gram-positive Staphylococcus aureus microorganisms.

Lovastatin production: From molecular basis to industrial process optimization.

Lovastatin, composed of secondary metabolites produced by filamentous fungi, is the most frequently used drug for hypercholesterolemia treatment due to the fact that lovastatin is a competitive inhibitor of HMG-CoA reductase. Moreover, recent studies have shown several important applications for lovastatin including antimicrobial agents and treatments for cancers and bone diseases. Studies regarding the lovastatin biosynthetic pathway have also demonstrated that lovastatin is synthesized from two-chain reactions using acetate and malonyl-CoA as a substrate. It is also known that there are two key enzymes involved in the biosynthetic pathway called polyketide synthases (PKS). Those are characterized as multifunctional enzymes and are encoded by specific genes organized in clusters on the fungal genome. Since it is a secondary metabolite, cultivation process optimization for lovastatin biosynthesis has included nitrogen limitation and non-fermentable carbon sources such as lactose and glycerol. Additionally, the influences of temperature, pH, agitation/aeration, and particle and inoculum size on lovastatin production have been also described. Although many reviews have been published covering different aspects of lovastatin production, this review brings, for the first time, complete information about the genetic basis for lovastatin production, detection and quantification, strain screening and cultivation process optimization. Moreover, this review covers all the information available from patent databases covering each protected aspect during lovastatin bio-production.

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

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.

Plasma lutein concentrations are related to dietary intake, but unrelated to dietary saturated fat or cognition in young children.

Lutein and zeaxanthin are xanthophyll carotenoids present in highly pigmented vegetables and fruits. Lutein is selectively accumulated in the brain relative to other carotenoids. Recent evidence has linked lutein to cognition in older adults, but little is known about lutein in young children, despite structural brain development. We determined lutein intake using FFQ, one 24 h recall and three 24 h recalls, plasma lutein concentrations and their association with cognition in 160 children 5·6-5·9 years of age, at low risk for neurodevelopmental delay. Plasma lutein was skewed, with a median of 0·23 (2·5th to 95th percentile range 0·11-0·53) µmol/l. Plasma lutein showed a higher correlation with lutein intake estimated as the average of three 24 h recalls (r 0·479; P = 0·001), rather than one 24 h recall (r 0·242; P = 0·003) or FFQ (r 0·316; P = 0·001). The median lutein intake was 697 (2·5th to 95th percentile range 178-5287) µg/d based on three 24 h recalls. Lutein intake was inversely associated with SFA intake, but dietary fat or SFA intakes were not associated with plasma lutein. No associations were found between plasma lutein or lutein intake and any measure of cognition. While subtle independent effects of lutein on child cognition are possible, separating these effects from covariates making an impact on both child diet and cognition may be difficult.

Low plasma vitamin B-12 is associated with a lower pregnancy-associated rise in plasma free choline in Canadian pregnant women and lower postnatal growth rates in their male infants.

BACKGROUND: Choline needs are increased in pregnancy. Choline can be used as a source of methyl for homocysteine remethylation to methionine, but choline synthesis requires methyls from methionine. Vitamin B-12 deficiency increases choline use for homocysteine methylation. OBJECTIVES: We investigated whether poor vitamin B-12 status occurs and contributes to low plasma choline and altered biomarkers of choline synthesis in pregnant women. With the use of a post hoc analysis, we addressed the association of maternal plasma vitamin B-12 status with postnatal growth rates in term infants. DESIGN: Blood was analyzed for a prospective study of 264 and 220 pregnant women at 16 and 36 wk of gestation, respectively, and 88 nonpregnant women as a reference. RESULTS: The proportion of women with a plasma total vitamin B-12 concentration <148 pmol/L (deficient) or 148-220 pmol/L (marginal) increased with pregnancy and pregnancy duration, which affected 3% and 9% of nonpregnant women, 10% and 21% of women at 16 wk of gestation, and 23% and 35% of women at 36 wk of gestation, respectively. Plasma free choline, betaine, and dimethylglycine were lower in women at 36 wk of gestation with a deficient or marginal compared with sufficient plasma total vitamin B-12 concentration (>220 pmol/L). Plasma total vitamin B-12 was positively associated with the increase in plasma free choline from midgestation to late gestation (P < 0.001). The postnatal growth rate to 9 mo was lower in infant boys of women classified as total vitamin B-12 deficient compared with sufficient. CONCLUSION: This study shows that maternal vitamin B-12 status is related to choline status in late gestation in a folate-replete population and may be a determinant of infant growth even in the absence of undernutrition.