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Some health agencies have issued precautionary principle fish advisories to pregnant women based on the presence of methylmercury (MeHg) in fish that could possibly be harmful to the developing fetus. Fish, however, is a rich source of selenium (Se) and other nutrients essential for normal brain development. Selenium is also thought to have a key role in alleviating MeHg toxicity. We estimated the dietary Se and MeHg intakes and dietary Se:Hg molar ratios from the fish consumed in a high fish-eating pregnant cohort where no adverse associations of fish consumption and outcomes has been reported. We used dietary data collected as part of the Seychelles Child Development Study Nutrition Cohort 2 (n = 1419). In this cohort 98% of participants consumed fish, with an average intake of 106.2 g per day. Daily Se intakes from fish consumption were 61.6 µg/ d, within the range recommended during pregnancy. The mean dietary Se:Hg molar ratios was 6. These findings demonstrate that fish consumption exposes pregnant Seychellois women to Se in excess of MeHg. Based on these findings, fish consumption, especially fish with Se:Hg ratios above 1, may help pregnant women achieve optimum dietary Se intakes, which may protect against MeHg toxicity.
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Mercúrio , Compostos de Metilmercúrio , Selênio , Criança , Animais , Feminino , Humanos , Gravidez , Mercúrio/análise , Selênio/análise , Seicheles , Desenvolvimento Infantil , PeixesRESUMO
BACKGROUND: Humans differ in the metabolism of the neurotoxicant methyl mercury (MeHg). This variation may be partially due to variation in genes encoding the transcription factor Nuclear factor E2-related factor 2 (NRF2) and its negative regulator Kelch-like ECH-Associated Protein 1 (KEAP1), which regulate glutathione and related transporter and antioxidant proteins that play a role in the metabolism and neurotoxicity of MeHg. AIM: To elucidate a potential risk from genetic variation in NFE2L2 (encoding NRF2) and KEAP1 toward prenatal mercury exposure and child neurodevelopmental outcomes at 20 months and 7 years of age in a population with variable prenatal exposure to MeHg from maternal fish consumption. MATERIAL AND METHODS: Nutrition Cohort 2 is a mother-child cohort in the Republic of Seychelles. Children were genotyped for NFE2L2 (rs2364723, rs13001694) and KEAP1 (rs8113472, rs9676881) polymorphisms (N = 1285 after removing siblings). Total mercury (Hg) was measured in cord blood as a biomarker for prenatal MeHg exposure. Child neurodevelopmental outcomes included the Bayley Scales of Infant Development II administered at 20 months of age, and outcomes across multiple neurodevelopmental domains from 14 tests administered in children and 3 instruments completed by parents when children were 7 years of age. RESULTS: The mean cord blood MeHg concentration was 34 (95% CI 11, 75) µg/L. None of the four polymorphisms had a significant association (p < 0.05) with either cord MeHg or neurodevelopmental test results at 20 months. There were no significant associations between either NFE2L2 polymorphism and any developmental test scores. At 7 years, children carrying KEAP1 rs8113472 CA showed significantly worse performance on psychomotor function than children with the CC variant (finger tapping, dominant hand: ß - 1.19, SE 0.34; finger tapping, non-dominant hand: ß - 0.92, SE 0.31) and worse social communication (SCQ Total: ß 0.65, SE 0.27). Children carrying rs8113472 AA, versus children with CC, showed significantly better performance on social communication (SRS Total: ß - 8.88, SE 3.60). Children carrying KEAP1 rs9676881 AG, versus children with GG, showed significantly worse performance on psychomotor function (trailmaking A time: ß 8.66, SE 3.37) and cognition (KBIT Matrices: ß - 0.96, SE 0.36). CONCLUSION: No associations between NFE2L2 and KEAP1 polymorphisms and MeHg concentration were identified. However, at 7 years, KEAP1 polymorphisms were associated with differences in neurodevelopmental outcomes in children from a population with high fish intake.
Assuntos
Proteína 1 Associada a ECH Semelhante a Kelch , Mercúrio , Compostos de Metilmercúrio , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Humanos , Lactente , Gravidez , Desenvolvimento Infantil , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Mercúrio/efeitos adversos , Mercúrio/toxicidade , Compostos de Metilmercúrio/efeitos adversos , Compostos de Metilmercúrio/toxicidade , Fator 2 Relacionado a NF-E2/genética , Efeitos Tardios da Exposição Pré-Natal/genética , SeichelesRESUMO
In 2001 the U.S. Food and Drug Administration (FDA) issued precautionary advice to pregnant women to limit fish consumption over concern that the methylmercury content might harm their children's neurodevelopment. This concern was based largely on results from an epidemiological study of mothers primarily exposed to methylmercury from consuming pilot whale. Subsequently, FDA and the World Health Organization/Food and Agriculture Organization (WHO/FAO) undertook independent assessments of fish consumption that considered net effects from both fish nutrients, primarily omega-3 fatty acids, as beneficial and methylmercury as harmful. Both assessments estimated that when mothers regularly consume fish during pregnancy, their children are likely to have improved neurodevelopment compared to children of non-fish eaters despite their exposure to methylmercury. These estimated improvements included gains of two to over five full scale IQ points from levels of maternal consumption that are achievable in most of the world. Consistent with those estimates, human research on fish consumption and child neurodevelopment from more than 200,000 mother-child pairs now collectively reports 51 beneficial associations with neurodevelopmental outcomes and three adverse associations, the latter with no discernable pattern. These associations include full scale IQ gains similar to, or somewhat higher than, those estimated by FDA and FAO/WHO. Also consistent with the FDA and FAO/WHO estimates, research has reported beneficial associations with fish consumption when pregnant women are exposed to methylmercury from fish in excess of the U.S. Environmental Protection Agency's (EPA) Reference Dose (RfD). Our analysis evaluates how the net effects approach as utilized by FDA and FAO/WHO provides a holistic explanation for these results with implications for public health policy. This concordance of net effects modeling and empirical scientific evidence supports a clarification of current public health recommendations to focus on greater fish consumption by pregnant women for their children's neurodevelopment.
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Ácidos Graxos Ômega-3 , Compostos de Metilmercúrio , Animais , Humanos , Feminino , Gravidez , Compostos de Metilmercúrio/toxicidade , Compostos de Metilmercúrio/análise , Alimentos Marinhos/efeitos adversos , Alimentos Marinhos/análise , Peixes , Mães , Contaminação de Alimentos/análiseRESUMO
Fish is an important source of nutrients, particularly the long chain n-3 polyunsaturated fatty acids (n-3 PUFAs). The incorporation of fish into the diet has been shown to have several health benefits, including lowering the risk of cardiovascular disease (CVD). Elevated plasma lipids are one of the main modifiable risk factors contributing to CVD and may be partly mediated by n-3 PUFAs. Although n-3 PUFAs in the form of supplementation have been shown to exert lipid modifying effects, the effects of fish consumption on the lipid profile have not been well summarised to date. Therefore, the aim of the present review is to discuss the current evidence from intervention studies investigating the effect of fish consumption on the lipid profile in both apparently healthy and non-healthy populations. Existing evidence appears to support the role of fish in promoting a shift towards a less inflammatory lipid profile through raising n-3 PUFAs and potentially lowering n-6 PUFA and triglyceride concentrations in both healthy and non-healthy populations. Fish consumption has a negligible effect on cholesterol concentrations; however, fish consumption may promote a small increase in high density lipoprotein (HDL) cholesterol amongst people with lower HDL at baseline. Limited studies have shown fish consumption to result in shifts in phospholipid and sphingolipid species and structure, albeit it is not yet clear whether these alterations have any meaningful impact on CVD risk. Future well-designed studies that utilise NMR and/or lipidomics analysis are warranted to explore the effects of these shifts in lipid content and structure in the context of disease development. Public health guidance should emphasise the cardioprotective benefits of fish and encourage consumption particularly in the Global North where fish consumption remains low.
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Doenças Cardiovasculares , Ácidos Graxos Ômega-3 , Humanos , Animais , Ácidos Graxos Insaturados , Fosfolipídeos , Colesterol , HDL-Colesterol , Doenças Cardiovasculares/prevenção & controleRESUMO
BACKGROUND: Consumption of fish yields many nutritional benefits, but also results in exposure to methylmercury (MeHg). The developing brain is known to be particularly susceptible to MeHg toxicity in high doses. However, the potential impact of low-level environmental exposure from fish consumption on children's neurodevelopment remains unclear. METHODS: We investigated postnatal MeHg exposure at 7 years and its association with a battery of 17 neurodevelopmental outcomes in a subset of children (n = 376) from 1535 enrolled mother-child pairs in Nutrition Cohort 2 of the Seychelles Child Development Study (SCDS NC2). Each outcome was modeled in relation to postnatal MeHg exposure using linear regression, adjusting for prenatal MeHg exposure, levels of maternal polyunsaturated fatty acids (PUFA), and several other covariates known to be associated with neurodevelopmental outcomes. RESULTS: Median postnatal MeHg exposure at 7 years was 2.5 ppm, while the median prenatal MeHg exposure was 3.5 ppm. We found no statistically significant associations between postnatal MeHg exposure and any of the 17 neurodevelopmental outcomes after adjusting for prenatal MeHg exposure and other covariates. CONCLUSIONS: These findings are consistent with previous cross-sectional analyses of the SCDS Main Cohort. Continued follow-up of the entire NC2 cohort at later ages with repeated exposure measures is needed to further confirm these findings.
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Compostos de Metilmercúrio , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Feminino , Animais , Humanos , Compostos de Metilmercúrio/toxicidade , Compostos de Metilmercúrio/análise , Desenvolvimento Infantil , Seicheles/epidemiologia , Estudos Transversais , Estudos de Coortes , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Contaminação de Alimentos/análise , Exposição Materna/efeitos adversosRESUMO
Selenium (Se) is an essential trace element for normal neurodevelopment. It is incorporated into multiple selenoenzymes which have roles in the brain and neurological function, the synthesis of thyroid hormones, the antioxidant defense system, DNA synthesis, and reproduction. Fish is a source of both Se and neurotoxic methylmercury (MeHg). Selenium is known to ameliorate the effects of MeHg in experimental animals, but studies in children exposed to both Se and MeHg through prenatal fish consumption have been inconclusive. Research on Se's implications for pregnancy and child neurodevelopment is limited. The aims of this review are to summarize the literature on the biological roles of Se during pregnancy and the potential role in mitigating the effects of MeHg exposure from fish consumption on human health. This review has shown that Se concentrations among pregnant women globally appear insufficient, with the majority of pregnant women reporting Se concentrations below 70 µg/L during pregnancy. The role of Se in child development and its interactions with MeHg in children are inconclusive. Further investigation of the interaction between Se and MeHg in relation to child neurodevelopment in high fish-eating populations is required to fully elucidate effects.
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Compostos de Metilmercúrio , Selênio , Oligoelementos , Animais , Criança , Humanos , Feminino , Gravidez , Compostos de Metilmercúrio/toxicidade , Antioxidantes , Exposição Materna , PeixesRESUMO
BACKGROUND: High concentrations of taurine are present in the developing human brain and maternal breast milk. Taurine is thought to influence fetal growth and brain development based on experimental rodent studies. As fish is an important dietary source of taurine, we investigated associations between taurine concentrations and child outcomes in a high fish consuming population. OBJECTIVE: To examine associations between maternal and cord serum taurine concentrations and birth anthropometric measures and cognitive development in children at 20 months of age. METHODS: Pregnant women were recruited between 2008 and 2011 as part of Nutrition Cohort 2 (NC2) of the Seychelles Child Development Study (SCDS). Maternal taurine serum concentrations were measured at 28 week's gestation and in cord serum. Child weight, length and head circumference were measured at birth and neurodevelopment was assessed using Bayley Scales of Infant Development II (BSID-II) at 20 months of age. Associations between taurine status, birth measures and neurodevelopmental outcomes were examined (n = 300) using regression models and adjusted for relevant covariates. RESULTS: Mean (SD) maternal and cord taurine concentrations were 124.9 (39.2) µmol/L (range 28.2-253.9 µmol/L) and 187.6 (60.0) µmol/L (range 55.0-417.4 µmol/L) respectively. We found no associations between maternal taurine concentrations and child anthropometric and neurodevelopmental measures (weight ß = -0.001, SE=0.001; length ß = -0.006, SE=0.006; head circumference ß = -0.002, SE=0.002; MDI ß = -0.005, SE=0.015; PDI ß = -0.004, SE=0.016; all P > 0.05), or between cord taurine concentrations and outcomes (weight ß = -0.001, SE<0.000; length ß = -0.001, SE=0.004; head circumference ß < 0.000, SE=0.002; MDI ß = 0.004, SE=0.010; PDI ß = -0.015, SE=0.012; all P > 0.05). CONCLUSION: The Seychellois population have high maternal and cord taurine concentrations owing to their high fish intake and may be considered taurine replete compared to individuals who consume a Westernised diet. This high taurine status may explain why there were no significant associations between maternal and cord taurine concentrations and outcomes after adjusting for covariates.
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Desenvolvimento Infantil , Mães , Lactente , Recém-Nascido , Criança , Animais , Humanos , Feminino , Gravidez , Seicheles , Estado Nutricional , Desenvolvimento FetalRESUMO
Maternal fish consumption exposes the fetus to beneficial nutrients and potentially adverse neurotoxicants. The current study investigated associations between maternal fish consumption and child neurodevelopmental outcomes. Maternal fish consumption was assessed in the Seychelles Child Development Study Nutrition Cohort 1 (n 229) using 4-day food diaries. Neurodevelopment was evaluated at 9 and 30 months, and 5 and 9 years with test batteries assessing twenty-six endpoints and covering multiple neurodevelopmental domains. Analyses used multiple linear regression with adjustment for covariates known to influence child neurodevelopment. This cohort consumed an average of 8 fish meals/week and the total fish intake during pregnancy was 106·8 (sd 61·9) g/d. Among the twenty-six endpoints evaluated in the primary analysis there was one beneficial association. Children whose mothers consumed larger quantities of fish performed marginally better on the Kaufman Brief Intelligence Test (a test of nonverbal intelligence) at age 5 years (ß 0·003, 95 % CI (0, 0·005)). A secondary analysis dividing fish consumption into tertiles found no significant associations when comparing the highest and lowest consumption groups. In this cohort, where fish consumption is substantially higher than current global recommendations, maternal fish consumption during pregnancy was not beneficially or adversely associated with children's neurodevelopmental outcomes.
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Compostos de Metilmercúrio , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Animais , Desenvolvimento Infantil , Seicheles , Estado NutricionalRESUMO
A cross-sectional survey questionnaire was developed in-house to investigate pet cat owners' beliefs and attitudes related to the fundamental care of their pet cats. The questionnaire consisted of questions which were grouped into the following sections: (i) owners' socio-demographics; (ii) cat(s) body weight and body condition monitoring; (iii) owners' attitudes to cats' dietary preferences, needs and satisfaction, (iv) owners' perceptions of their cats' physical exercise needs and satisfaction. The sample size of 376 was estimated to be required to represent the population of the given geographical location (Belfast, NI, UK). Hard copies of the questionnaires were distributed in January and February 2019 and in total 402 completed questionnaires were collected; questionnaires which included >20% of missing or incomprehensible responses were excluded from the database, resulting in 398 questionnaires being included in the final database. The study identified a number of socio-demographic factors associated with owners' beliefs and attitudes that directly affect care provided to pet cats, e.g., the owner's occupation has been identified as a factor associated with owner perception of certain cats' behaviours, e.g., a cat brushing against the owner as food requests by their animal (Chi-Square 7.711 (df1), exact p = 0.006). Furthermore, most female respondents, aged 26−67 years and in an occupation not related to animals, reported selecting cat food based on their animal preferences (Chi-Square 10.332 (df1), exact p = 0.003). In contrast, female owners in animal and veterinary occupations were significantly more likely as compared to other respondents (Chi-Square 15.228 (df1), exact p < 0.001), to select cat food based on its perceived health benefit to the cat. Analysis of the respondents' opinions of cats' abilities to self-regulate physical activity showed that owners age was the main differentiating determinant, i.e., cat owners over 25 years old were significantly more likely than younger adults to believe that pet cats can regulate their own physical activity to keep healthy (Chi-Square 6.313 (df1), exact p = 0.025). Furthermore, respondents' opinions of their cat's ability to self-regulate feed intake were mainly associated with owner's education level (Chi-Square 6.367 (df1), exact p = 0.036). The study results indicated that the attitude and beliefs behind the fundamental care practices provided to pet cats depends on particular demographic factors, especially owners' education and occupation.
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BACKGROUND: Maternal fish consumption increases infant methylmercury (MeHg) exposure and polyunsaturated fatty acid (PUFA) concentrations. The n-3 PUFA are regulators of inflammation while MeHg may impact the cord cytokine profile and, subsequently, contribute to immune mediated outcomes. This study aimed to investigate associations between infant MeHg exposure and cord cytokine concentrations while adjusting for cord PUFA. METHODS: We studied participants in the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2), a large birth cohort in a high fish-eating population. Whole blood MeHg, serum PUFA and serum cytokine concentrations (IFN-γ, IL-1ß, IL-2, IL-12p70, TNF-α, IL-4, IL-10, IL-13, IL-6 and IL-8) were measured in cord blood collected at delivery (n = 878). Linear regression examined associations between infant MeHg exposure and cord cytokines concentrations, with and without adjustment for cord PUFA. An interaction model examined cord MeHg, cytokines and tertiles of the n-6:n-3 ratio (low/medium/high). RESULTS: There was no overall association between cord MeHg (34.08 ± 19.98 µg/L) and cytokine concentrations, with or without adjustment for PUFA. Increased total n-3 PUFA (DHA, EPA and ALA) was significantly associated with lower IL-10 (ß = -0.667; p = 0.007) and lower total Th2 (IL-4, IL-10 and IL-13) (ß = -0.715; p = 0.036). In the interaction model, MeHg and IL-1ß was positive and significantly different from zero in the lowest n-6:n-3 ratio tertile (ß = 0.002, p = 0.03). CONCLUSION: Methylmercury exposure from fish consumption does not appear to impact markers of inflammation in cord blood. The association of cord n-3 PUFA with lower IL-10 and total Th2 cytokines suggests that they may have a beneficial influence on the regulation of the inflammatory milieu. These findings are important for public health advice and deserve to be investigated in follow up studies.
Assuntos
Ácidos Graxos Ômega-3 , Compostos de Metilmercúrio , Animais , Coorte de Nascimento , Criança , Desenvolvimento Infantil , Citocinas , Ácidos Graxos Insaturados , Sangue Fetal , Humanos , Lactente , SeichelesRESUMO
Maternal thyroid hormones facilitate optimal foetal neurodevelopment; however, the exact role of the thyroid hormones on specific cognitive outcomes is unknown. The present study aimed to investigate associations between maternal thyroid function and neurodevelopmental outcomes in the Seychelles Child Development Study (SCDS) Nutrition 2 cohort (n 1328). Maternal free thyroid hormones (fT3, fT4 and fTSH) were assessed at 28 weeks' gestation with a range of child cognitive outcomes analysed at 20 months. Dietary iodine intake was analysed for a subset of women through a Food Frequency Questionnaire. Linear regression analysis was used to test associations between serum concentrations of maternal thyroid hormones and child neurodevelopment outcomes. Thyroid hormones were analysed as continuous data and categorised as quintiles. 95% of mothers had optimal thyroid function based on fTSH concentrations. Overall, the present study shows that maternal thyroid function is not associated with neurodevelopmental outcomes in this high fish-eating population. However, a positive association, using quintiles for fT3, was reported for the Mental Developmental Index, between Q3 v. Q4 (ß 0â 073; P 0â 043) and for Q3 v. Q5 (ß value 0â 086; P 0â 018). To conclude, mothers in our cohort, who largely have optimal thyroid function and iodine intakes, appear able to regulate thyroid function throughout pregnancy to meet neurodevelopmental needs. However, it is possible that minor imbalances of fT3, as indicated from our secondary analysis, may impact offspring neurodevelopment. Further investigation of the relationship between maternal thyroid function and infant neurodevelopment is warranted, particularly in populations with different dietary patterns and thereby iodine intakes.
Assuntos
Desenvolvimento Infantil , Sistema Nervoso/crescimento & desenvolvimento , Glândula Tireoide , Feminino , Humanos , Lactente , Iodo/administração & dosagem , Mães , Gravidez , Seicheles , Glândula Tireoide/fisiologia , Hormônios Tireóideos/sangueRESUMO
OBJECTIVE: Mild to moderate iodine deficiency during pregnancy has been associated with adverse neurodevelopmental outcomes in offspring. Few research studies to date combine assessment of urinary iodine (UIC and/or ICr), biomarkers that best reflect dietary intake, with reported dietary intake of iodine rich foods in their assessment of iodine deficiency. Thus, a systematic review was conducted to incorporate both these important measures. DESIGN: Using PRISMA guidelines, a comprehensive search was conducted in three electronic databases (EMBASE®, MedLine® and Web of Science®) from January 1970-March 2021. Quality assessment was undertaken using the Newcastle Ottawa Scale. Eligible studies included reported assessment of iodine status through urinary iodine (UIC and/or ICr) and/or dietary intake measures in pregnancy alongside neurodevelopmental outcomes measured in the children. Data extracted included study author, design, sample size, country, gestational age, child age at testing, cognitive tests, urinary iodine assessment (UIC in µg/L and/or ICr in µg/g), dietary iodine intake assessment and results of associations for the assessed cognitive outcomes. RESULTS: Twelve studies were included with nine reporting women as mild-moderately iodine deficient based on World Health Organization (WHO) cut-offs for urinary iodine measurements < 150 µg/l, as the median UIC value in pregnant women. Only four of the nine studies reported a negative association with child cognitive outcomes based on deficient urinary iodine measurements. Five studies reported urinary iodine measurements and dietary intakes with four of these studies reporting a negative association of lower urinary iodine measurements and dietary iodine intakes with adverse offspring neurodevelopment. Milk was identified as the main dietary source of iodine in these studies. CONCLUSION: The majority of studies classified pregnant women to be mild-moderately iodine deficient based on urinary iodine assessment (UIC and/or ICr) and/or dietary intakes, with subsequent offspring neurodevelopment implications identified. Although a considerable number of studies did not report an adverse association with neurodevelopmental outcomes, these findings are still supportive of ensuring adequate dietary iodine intakes and urinary iodine monitoring throughout pregnancy due to the important role iodine plays within foetal neurodevelopment. This review suggests that dietary intake data may indicate a stronger association with cognitive outcomes than urinary iodine measurements alone. The strength of this review distinguishes results based on cognitive outcome per urinary iodine assessment strategy (UIC and/or ICr) with dietary data. Future work is needed respecting the usefulness of urinary iodine assessment (UIC and/or ICr) as an indicator of deficiency whilst also taking account of dietary intakes.
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BACKGROUND: The achievement of target 25-hydroxyvitamin D [25(OH)D] concentrations in pregnancy may be altered by maternal obesity. OBJECTIVE: The authors examined the effects of maternal supplementation of 10 µg compared with 20 µg vitamin D3/d on maternal and umbilical cord 25(OH)D. The secondary aim was to investigate the influence of maternal BMI (in kg/m2) on the response of the primary outcomes. METHODS: The authors performed a 2-arm parallel double-blind randomized trial with 240 pregnant women recruited throughout the year in Northern Ireland. Women were stratified by BMI to receive 10 or 20 µg vitamin D3/d from 12 gestational wk (GW) until delivery. Maternal blood samples collected at 12, 28, and 36 GW and from the umbilical cord were analyzed for total serum 25(OH)D. A total of 166 women completed the study. RESULTS: Mean ± SD 25(OH)D at 36 GW was 80.8 ± 28.2 compared with 94.4 ± 33.2 nmol/L (P < 0.001) (10 compared with 20 µg vitamin D3/d, respectively). In those classified with 25(OH)D <50 nmol/L at baseline and assigned 10 µg vitamin D3/d, mean 25(OH)D concentrations remained <50 nmol/L at 36 GW, whereas those <50 nmol/L at baseline and assigned 20 µg vitamin D3/d, had mean 25(OH)D concentrations ≥50 nmol/L at 28 and 36 GW. In women with obesity and 25(OH)D <50 nmol/L at baseline, the related mean umbilical cord 25(OH)D was deficient (<25 nmol/L) in both treatment groups, whereas those with obesity and 25(OH)D ≥50 nmol/L at baseline had an average umbilical cord 25(OH)D between 25 and 50 nmol/L in both treatment groups. CONCLUSIONS: Supplementation of 20 µg vitamin D3/d is needed to attain maternal and umbilical cord 25(OH)D concentrations ≥50 nmol/L on average, in those who start pregnancy with low 25(OH)D concentrations (<50 nmol/L). Under current recommendations, women with obesity and low 25(OH)D in early pregnancy are particularly vulnerable to maintaining a low 25(OH)D concentration throughout pregnancy and having an infant born with deficient 25(OH)D concentrations. This trial was registered at ClinicalTrials.gov as NCT02713009.
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Suplementos Nutricionais , Obesidade Materna , Deficiência de Vitamina D/tratamento farmacológico , Vitamina D/administração & dosagem , Vitamina D/sangue , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Sangue Fetal , Humanos , Recém-Nascido , GravidezRESUMO
The maternal immune response is essential for successful pregnancy, promoting immune tolerance to the fetus while maintaining innate and adaptive immunity. Uncontrolled, increased proinflammatory responses are a contributing factor to the pathogenesis of preeclampsia. The Th1/Th2 cytokine shift theory, characterised by bias production of Th2 anti-inflammatory cytokine midgestation, was frequently used to reflect the maternal immune response in pregnancy. This theory is simplistic as it is based on limited information and does not consider the role of other T cell subsets, Th17 and Tregs. A range of maternal peripheral cytokines have been measured in pregnancy cohorts, albeit the changes in individual cytokine concentrations across gestation is not well summarised. Using available data, this review was aimed at summarising changes in individual maternal serum cytokine concentrations throughout healthy pregnancy and evaluating their association with preeclampsia. We report that TNF-α increases as pregnancy progresses, IL-8 decreases in the second trimester, and IL-4 concentrations remain consistent throughout gestation. Lower second trimester IL-10 concentrations may be an early predictor for developing preeclampsia. Proinflammatory cytokines (TNF-α, IFN-γ, IL-2, IL-8, and IL-6) are significantly elevated in preeclampsia. More research is required to determine the usefulness of using cytokines, particularly IL-10, as early biomarkers of pregnancy health.
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Citocinas , Pré-Eclâmpsia , Biomarcadores , Feminino , Feto , Humanos , Tolerância Imunológica , GravidezRESUMO
Optimal maternal long-chain PUFA (LCPUFA) status is essential for the developing fetus. The fatty acid desaturase (FADS) genes are involved in the endogenous synthesis of LCPUFA. The minor allele of various FADS SNP have been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of arachidonic acid (AA) and DHA. There is limited research on the influence of FADS genotype on cord PUFA status. The current study investigated the influence of maternal and child genetic variation in FADS genotype on cord blood PUFA status in a high fish-eating cohort. Cord blood samples (n 1088) collected from the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Of those with cord PUFA data available, maternal (n 1062) and child (n 916), FADS1 (rs174537 and rs174561), FADS2 (rs174575), and FADS1-FADS2 (rs3834458) were determined. Regression analysis determined that maternal minor allele homozygosity was associated with lower cord blood concentrations of DHA and the sum of EPA + DHA. Lower cord blood AA concentrations were observed in children who were minor allele homozygous for rs3834458 (ß = 0·075; P = 0·037). Children who were minor allele carriers for rs174537, rs174561, rs174575 and rs3834458 had a lower cord blood AA:LA ratio (P < 0·05 for all). Both maternal and child FADS genotype were associated with cord LCPUFA concentrations, and therefore, the influence of FADS genotype was observed despite the high intake of preformed dietary LCPUFA from fish in this population.
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Ácidos Graxos Dessaturases , Sangue Fetal , Animais , Desenvolvimento Infantil , Dessaturase de Ácido Graxo Delta-5 , Ácidos Graxos Dessaturases/genética , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , SeichelesRESUMO
PURPOSE: Long-chain polyunsaturated fatty acids (LCPUFA) can be synthesised endogenously from linoleic acid (LA) and α-linolenic acid (ALA) in a pathway involving the fatty acid desaturase (FADS) genes. Endogenous synthesis is inefficient; therefore, dietary intake of preformed LCPUFA from their richest source of fish is preferred. This study investigated the effect of fish consumption on PUFA concentrations in women of childbearing age while stratifying by FADS genotype. The influence of fish consumption on lipid profile, and markers of inflammation and oxidative stress was also examined. METHODS: Healthy women (n = 49) provided a buccal swab which was analysed for FADS2 genotype (rs3834458; T/deletion). Participants were stratified according to genotype and randomised to an intervention group to receive either no fish (n = 18), 1 portion (n = 14) or 2 portions (n = 17) (140 g per portion) of fish per week for a period of 8 weeks. Serum PUFA was analysed at baseline and post-intervention. Lipid profile, and markers of inflammation and oxidative stress were also analysed. RESULTS: Participants consuming 2 portions of fish per week had significantly higher concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and total n-3 PUFA, and a lower n-6:n-3 ratio compared to those in the no fish or 1 portion per week group (all p < 0.05). Fish consumption did not have a significant effect on biomarkers of oxidative stress, inflammation and lipid profile in the current study. CONCLUSION: Consumption of 2 portions of fish per week has beneficial effects on biological n-3 PUFA concentrations in women of childbearing age; however, no effects on oxidative stress, inflammation or lipid profile were observed. This trial was registered at www.clinicaltrials.gov (NCT03765580), registered December 2018.
Assuntos
Ácidos Graxos Dessaturases , Ácidos Graxos Ômega-3 , Animais , Ácidos Docosa-Hexaenoicos , Ácido Eicosapentaenoico , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Insaturados , Feminino , Peixes , Humanos , Ácido LinoleicoRESUMO
BACKGROUND: Fish is a primary source of protein and n-3 PUFA but also contains methylmercury (MeHg), a naturally occurring neurotoxicant to which, at sufficient exposure levels, the developing fetal brain is particularly sensitive. OBJECTIVES: To examine the association between prenatal MeHg and maternal status of n-3 and n-6 PUFA with neurodevelopment, and to determine whether PUFA might modify prenatal MeHg associations with neurodevelopment. METHODS: We examined the Seychelles Child Development Study Nutrition Cohort 2 (NC2) at age 7 y. We used a sophisticated and extensive neurodevelopmental test battery that addressed 17 specific outcomes in multiple neurodevelopmental domains: cognition, executive and psychomotor function, language development, behavior, scholastic achievement, and social communication. Analyses were undertaken on 1237 mother-child pairs with complete covariate data (after exclusions) and a measure of at least 1 outcome. We examined the main and interactive associations of prenatal MeHg exposure (measured as maternal hair mercury) and prenatal PUFA status (measured in maternal serum at 28 weeks' gestation) on child neurodevelopmental outcomes using linear regression models. We applied the Bonferroni correction to account for multiple comparisons and considered P values <0.0029 to be statistically significant. RESULTS: Prenatal MeHg exposure and maternal DHA and arachidonic acid (20:4n-6) (AA) status were not significantly associated with any neurodevelopmental outcomes. Findings for 4 outcomes encompassing executive function, cognition, and linguistic skills suggested better performance with an increasing maternal n-6:n-3 PUFA ratio (P values ranging from 0.004 to 0.05), but none of these associations were significant after adjusting for multiple comparisons. No significant interaction between MeHg exposure and PUFA status was present. CONCLUSIONS: Our findings do not support an association between prenatal MeHg exposure or maternal DHA and AA status with neurodevelopmental outcomes at age 7 y. The roles of n-6 and n-3 PUFA in child neurodevelopment need further research.
Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Ácidos Graxos Insaturados/metabolismo , Compostos de Metilmercúrio/toxicidade , Transtornos do Neurodesenvolvimento/etiologia , Efeitos Tardios da Exposição Pré-Natal , Biomarcadores/sangue , Biomarcadores/química , Criança , Feminino , Cabelo/química , Humanos , Compostos de Metilmercúrio/química , Gravidez , SeichelesRESUMO
BACKGROUND: Maternal status of long-chain PUFAs (LC-PUFAs) may be related to fetal growth. Maternal fish consumption exposes the mother to the neurotoxicant methylmercury (MeHg), which, in contrast, may restrict fetal growth. OBJECTIVE: Our aim was to examine relations between maternal LC-PUFA status at 28 wk and birth outcomes (birth weight, length, and head circumference), controlling for MeHg exposure throughout pregnancy, in the Seychelles Child Development Study Nutrition Cohort 2. Our secondary aim was to examine the influence of maternal variation in genes regulating the desaturation of LC-PUFAs [fatty acid desaturase (FADS)] on birth outcomes. METHODS: From nonfasting blood samples collected at 28 wk of gestation, we measured serum total LC-PUFA concentrations and FADS1 (rs174537, rs174561), FADS1-FADS2rs3834458, and FADS2rs174575 genotypes, with hair total mercury concentrations assessed at delivery. Data were available for n = 1236 mother-child pairs. Associations of maternal LC-PUFAs, MeHg, and FADS genotype with birth outcomes were assessed by multiple linear regression models, adjusting for child sex, gestational age, maternal age, BMI, alcohol use, socioeconomic status, and parity. RESULTS: In our cohort of healthy mothers, neither maternal LC-PUFA status nor MeHg exposure were significant determinants of birth outcomes. However, when compared with major allele homozygotes, mothers who were heterozygous for the minor allele of FADS1 (rs174537 and rs174561, GT compared with TT, ß = 0.205, P = 0.03; TC compared with CC, ß = 0.203, P = 0.04) and FADS1-FADS2 (rs3834458, Tdel compared with DelDel, ß = 0.197, P = 0.04) had infants with a greater head circumference (all P < 0.05). Homozygosity for the minor allele of FADS2 (rs174575) was associated with a greater birth weight (GG compared with CC, ß = 0.109, P = 0.04). CONCLUSIONS: In our mother-child cohort, neither maternal LC-PUFA status nor MeHg exposure was associated with birth outcomes. The observed associations of variation in maternal FADS genotype with birth outcomes should be confirmed in other populations.
Assuntos
Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos Insaturados/sangue , Peixes , Compostos de Metilmercúrio/sangue , Animais , Desenvolvimento Infantil , Dessaturase de Ácido Graxo Delta-5 , Ácidos Graxos Dessaturases/genética , Feminino , Contaminação de Alimentos , Regulação Enzimológica da Expressão Gênica , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Compostos de Metilmercúrio/toxicidade , Mães , Seicheles , Poluentes Químicos da Água/sangue , Poluentes Químicos da Água/toxicidadeRESUMO
BACKGROUND: Exposure to the environmental toxicant mercury (Hg) has been associated with immune dysregulation, including autoimmune disease, but few human studies have examined methylmercury (MeHg) exposure from fish consumption. OBJECTIVES: We examined associations between MeHg exposure and biological markers of autoimmunity and inflammation while adjusting for long chain polyunsaturated fatty acids (LCPUFA). METHOD: At age 19 years, hair total Hg (Y19Hg), LCPUFA status, a panel of 13 antinuclear antibodies (ANA), total serum immunoglobulins (Ig) IgG, IgA, and IgM and serum markers of inflammation (IL-1, IL-2, IL-6, IL-10, C-reactive protein (CRP), IFN-γ, TNF-α) were measured in the Seychelles Child Development Study (SCDS) Main Cohort (n = 497). Multivariable regression models investigated the association between Y19Hg and biomarkers, adjusting for prenatal total hair Hg (MatHg) and other relevant covariates, and with and without adjustment for LCPUFA. RESULTS: With each 1 ppm increase in Y19Hg (mean 10.23 (SD 6.02) ppm) we observed a 4% increased odds in a positive Combined ANA following adjustment for the n6:n3 LCPUFA ratio (ß = 0.036, 95%; CI: 0.001, 0.073). IgM was negatively associated with Y19Hg (ß = -0.016, 95%CI: 0.016, -0.002) in models adjusted for n-3, n-6 LCPUFA and when separately adjusted for the n-6:n-3 LCPUFA ratio. No associations were observed with MatHg. Total n-3 LCPUFA status was associated with reduced odds of a positive anti-ribonuclear protein (RNP) A. The n-3 LCPUFA were negatively associated with IL-6, IL-10, CRP, IFN-γ, TNF-α and positively with TNF-α:IL-10. There were positive associations between the n-6:n-3 ratio and IL-6, IL-10, CRP, IFN-γ, TNF-α and a negative association with TNF-α:IL-10. DISCUSSION: The Y19Hg exposure was associated with higher ANA and lower IgM albeit only following adjustment for the n-3 LCPUFA or the n-6:n-3 LCPUFA ratio. The clinical significance of these findings is unclear, but warrant follow up at an older age to determine any relationship to the onset of autoimmune disease.
Assuntos
Doenças Autoimunes , Ácidos Graxos Ômega-3 , Compostos de Metilmercúrio , Animais , Doenças Autoimunes/etiologia , Criança , Dieta , Ácidos Graxos Insaturados , Feminino , Humanos , Masculino , Compostos de Metilmercúrio/toxicidade , Gravidez , Seicheles , Adulto JovemRESUMO
CONTEXT: Polyunsaturated fatty acids (PUFA) are important during pregnancy for fetal development and child health outcomes. The fatty acid desaturase (FADS) genes also influence PUFA status, with the FADS genes controlling how much product (eg, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid) is metabolized from the precursor molecules linoleic acid and α-linolenic acid. OBJECTIVE: The current review discusses the influence of FADS genotype on PUFA status of pregnant women, breast milk, and children, and also how FADS may influence child health outcomes. DATA SOURCES: The Ovid Medline, Scopus, Embase, Cochrane Library, CINAHL Plus, PubMed and Web of Science databases were searched from their inception to September 2018. DATA EXTRACTION: Eligible studies reported FADS genotype and blood concentrations of PUFA during pregnancy, in childhood, breast milk concentrations of PUFA or child health outcomes. DATA ANALYSIS: In pregnant and lactating women, minor allele carriers have higher concentrations of linoleic acid and α-linolenic acid, and lower concentrations of arachidonic acid, in blood and breast milk, respectively. In children, FADS genotype influences PUFA status in the same manner and may impact child outcomes such as cognition and allergies; however, the direction of effects for the evidence to date is not consistent. CONCLUSION: Further studies are needed to further investigate associations between FADS and outcomes, as well as the diet-gene interaction.