Leptin gene polymorphism (rs7799039; G2548A) is associated with changes in serum lipid concentrations during pregnancy: a prospective cohort study.

PURPOSE: Little is known about the effects of leptin and leptin receptor polymorphisms on lipid changes during pregnancy. The aims of this study were to evaluate the associations between the single nucleotide polymorphisms (SNPs) of leptin and leptin receptor genes and the lipid concentrations during pregnancy; and to test whether dietary intake is a mediator in these associations. METHODS: A prospective cohort of 154 pregnant women was followed up in Rio de Janeiro, Brazil during the following gestational periods: 5-13th, 20-26th and 30-36th weeks. HDL-C, total cholesterol (TC) and triglyceride (TG) were measured by the enzymatic colorimetric method, and LDL-C was calculated. DNA was extracted by the phenol-chloroform method, and leptin (G2548A, rs7799039) and leptin receptor SNPs (Q223R; rs1137101 and K109R; rs1137100) were genotyped using real-time PCR. Statistical analyses included linear mixed-effect models. RESULTS: Women with the AA genotype of G2548A polymorphism reported a higher fat and total energy intake and had a higher increase in TG concentration during pregnancy than women with AG or GG genotype. The association between G2548A SNP and TG concentrations was not attenuated by adjusting for total lipid (g) and energy (kcal) intake. We did not observe significant associations between the Q223R and K109R SNPs and the lipid concentrations. CONCLUSIONS: Women homozygous for the A allele of the leptin SNP (G2548A) had a higher increase in TG concentrations per gestational week compared with women with the AG or GG genotype. This is an exploratory and hypothesis-generating study, and the results need confirmation in studies with larger sample sizes.'

Longitudinal association of 25-hydroxyvitamin D with adipokines and markers of glucose metabolism among Brazilian pregnant women.

This study aimed to evaluate the longitudinal association of vitamin D status with glycaemia, insulin, homoeostatic model assessment of insulin resistance, adiponectin and leptin. A prospective cohort with 181 healthy, pregnant Brazilian women was followed at the 5th-13th, 20th-26th and 30th-36th gestational weeks. In this cohort, 25-hydroxyvitamin D (25(OH)D) plasma concentrations were analysed using liquid chromatography-tandem MS. Vitamin D status was categorised as sufficient or insufficient using the Endocrine Society Practice Guidelines (≥75/<75 nmol/l) and the Institute of Medicine (≥50/<50 nmol/l) thresholds. Linear mixed-effect regression models were employed to evaluate the association between vitamin D status and each outcome, considering interaction terms between vitamin D status and gestational age (P<0·1). At baseline, 70·7 % of pregnant women had 25(OH)D levels <75 nmol/l and 16 % had levels <50 nmol/l. Women with sufficient vitamin D status at baseline, using both thresholds, presented lower glycaemia than those with insufficient 25(OH)D. Pregnant women with 25(OH)D concentrations <75 nmol/l showed lower insulin (ß=-0·12; 95 % CI -0·251, 0·009; P=0·069) and adiponectin (ß=-0·070; 95 % CI -0·150, 0·010; P=0·085) concentrations throughout pregnancy than those with 25(OH)D levels ≥75 nmol/l. Pregnant women with 25(OH)D <50 nmol/l at baseline presented significantly higher leptin concentrations than those with 25(OH)D levels ≥50 nmol/l (ß=-0·253; 95 % CI -0·044, 0·550; P=0·095). The baseline status of vitamin D influences the biomarkers involved in glucose metabolism. Vitamin D-sufficient women at baseline had higher increases in insulin and adiponectin changes throughout gestation than those who were insufficient.

Serum fatty acids are positively associated with changes in systemic blood pressure throughout pregnancy.

OBJECTIVES: To assess whether serum concentrations of saturated (SFAs), polyunsaturated (PUFAs), and monounsaturated (MUFAs) fatty acids are associated with changes in blood pressure (BP) throughout pregnancy. STUDY DESIGN: Prospective cohort. MAIN OUTCOME MEASURES: Longitudinal measurements of systolic (SBP) and diastolic (DBP) BP. METHODS: Two hundred twenty-three healthy pregnant women were recruited in a public health center in Rio de Janeiro, Brazil between 2009 and 2011. Fasting blood samples and BP measurements were obtained at the 1st (5th-13th weeks), 2nd (20th-26th) and 3rd trimester (30th-36th). Crude and adjusted (maternal age, education, energy intake, gestational body weight change, leptin concentrations, early pre-pregnancy BMI, leisure time physical activity prior to pregnancy and linear and quadratic gestational weeks) longitudinal linear mixed-effects models were employed. RESULTS: SBP and DBP decreased from the 1st to the 2nd trimester and slightly increased from the 2nd to the 3rd trimester (P < 0.001). In the adjusted model (ß and 95% CI), total SFAs [0.005 (0.001-0.008); P = 0.008], total MUFAs [0.005 (0.001-0.009); P = 0.019] and total n-6 PUFAs [0.005 (0.001-0.009); P = 0.025] were positively associated with SBP throughout pregnancy. CONCLUSIONS: Maternal serum concentrations of total SFAs, MUFAs and n-6 PUFAs were positively associated with BP levels in normotensive pregnant women.

A systematic review of the associations between maternal nutritional biomarkers and depression and/or anxiety during pregnancy and postpartum.

BACKGROUND: Nutritional requirements need to be met in order to adapt to pre- and postnatal changes. Our aim was to systematically review the evidence of associations between nutritional biomarkers and psychological distress during pregnancy and in the first postnatal year. METHODS: MEDLINE, EMBASE, PsycINFO, Scielo, LILACS, clinicaltrials.gov, International Clinical Trials Registry, Cochrane Library, Scopus and Web of Science databases were searched for articles from inception to 4/15/2016. Studies of maternal nutritional biomarkers in blood (fatty acids/micronutrients/amino acids) and associations with psychological distress (depression/anxiety/stress) were included. Two independent reviewers extracted data based on study designs, participants, outcomes, exposures, and association measures. RESULTS: Thirty-eight studies were included. A total of 13 studies showed divergent or no associations between serum/plasma/erythrocyte fatty acid concentrations and depression/anxiety during pregnancy and postpartum. Changes in serum cholesterol levels from pregnancy to postpartum showed a significant inverse correlation with depression in one out of three studies. Five out of seven studies found an inverse association between serum vitamin D levels and pre- and postnatal depression. Plasma tryptophan levels were inversely correlated with postnatal depression scores in three out of four studies. We identified that one out of two studies presented no significant association between vitamin B12/folate/ferritin concentrations and depression in postpartum. LIMITATIONS: There was higher variability between association measures, time and scales of depression and anxiety assessments. CONCLUSIONS: The majority of high-quality studies suggest that lower vitamin D levels may be associated with postpartum depression. However, further evidence is needed for guiding clinical practice on nutritional biomarkers.

Early pregnancy body mass index modifies the association of pre-pregnancy dietary patterns with serum polyunsaturated fatty acid concentrations throughout pregnancy in Brazilian women.

Dietary patterns (DPs) have been described as an important factor that may influence polyunsaturated fatty acid (PUFA) concentrations and body mass index (BMI) during pregnancy. We aim to evaluate the association between pre-pregnancy DPs and serum PUFA percentages throughout pregnancy considering early pregnancy BMI as a possible effect modifier. A prospective cohort of 154 pregnant women was followed (5th-13th, 20th-26th, and 30th-36th gestational weeks). Serum PUFA concentrations (total n-3 and total n-6, eicosapentaenoic + docosahexaenoic acids) were measured in each trimester and expressed as percentages. The n-6/n-3 ratio was calculated. Longitudinal linear mixed-effects models including interaction terms between DPs and early pregnancy BMI were employed. Serum PUFA percentages declined, whereas the n-6/n-3 ratio, monounsaturated, and saturated percentages increased throughout pregnancy for all BMI categories. Three pre-pregnancy DPs were identified by principal component analysis (common Brazilian, healthy, and processed). Overweight women with higher adherence to the common-Brazilian and to the healthy DPs presented reduced n-3 PUFA percentage and increased n-6 percentages and n-6/n-3 ratio compared to under or normal weight women. Obese women with higher adherence to the processed DP presented a more pronounced decrease of total n-3 percentage compared to under or normal weight women. Early pregnancy BMI modified the effect of pre-pregnancy DPs on PUFA profile throughout gestation. Higher adherence to the healthy pattern was associated with increased n-3 percentage, except for overweight women. Only for processed DP was the behaviour of PUFA the same for all BMI categories, showing a worse evolution profile, that is, increased n-6 and reduced n-3 fractions.

Association between early pregnancy vitamin D status and changes in serum lipid profiles throughout pregnancy.

OBJECTIVE: To evaluate the associations between first trimester 25-hydroxyvitamin D [25(OH)D] status and changes in high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), total cholesterol (TC), triglyceride (TG) concentrations, TG/HDL-c, and TC/HDL-c ratios throughout pregnancy. We hypothesized that first trimester 25(OH)D inadequacy is associated with lower concentrations of HDL-c and higher LDL-c, TC, TG, TG/HDL-c, and TC/HDL-c ratios throughout pregnancy. METHODS: A prospective cohort study with 3 visits at 5-13 (baseline), 20-26, and 30-36 gestational weeks, recruited 194 pregnant women attending a public health care center in Rio de Janeiro, Brazil. Plasma 25(OH)D concentrations were measured in the first trimester using liquid chromatography-tandem mass spectrometry. 25(OH)D concentrations were classified as adequate (≥75nmol/L) or inadequate (<75nmol/L). Serum TC, HDL-c, and TG concentrations were measured enzymatically. Crude and adjusted longitudinal linear mixed-effects models were employed to evaluate the association between the first trimester 25(OH)D status and changes in serum lipid concentrations throughout pregnancy. Confounders adjusted for in the multiple analysis were age, homeostatic model assessment (HOMA), early pregnancy BMI, leisure time physical activity before pregnancy, energy intake, and gestational age. RESULTS: At baseline, 69% of the women had inadequate concentrations of 25(OH)D. Women with 25(OH)D inadequacy had higher mean LDL-c than those with adequate concentrations (91.3 vs. 97.5mg/dL; P=0.064) at baseline. TC, HDL-c, LDL-c TG, TG/HDL-c ratios, and TC/HDL-c ratios, increased throughout pregnancy independently of 25(OH)D concentrations (ANOVA for repeated measures P<0.001). The adjusted models showed direct associations between the first trimester 25(OH)D status and changes in TC (ß=9.53; 95%CI=1.12-17.94), LDL-c (ß=9.99; 95% CI=3.62-16.36) concentrations, and TC/HDL-c ratios (ß=0.16; 95% CI=0.01-0.31) throughout pregnancy. CONCLUSIONS: Inadequate plasma 25(OH)D concentrations during early pregnancy were associated with more pronounced changes of TC, LDL-c concentrations, and TC/HDL-c ratios throughout pregnancy. Changes in these cardiovascular markers suggest the importance of ensuring adequate vitamin D status at the beginning of pregnancy.

High cholesterol dietary intake during pregnancy is associated with large for gestational age in a sample of low-income women of Rio de Janeiro, Brazil.

The association between the quality of maternal dietary fat intake during pregnancy and the infant's birthweight (BW) remains controversial. Our goal was to investigate the association between maternal dietary fat intake during pregnancy and the rate of large for gestational age (LGA) newborns. This study employed a cross-sectional analysis of 297 pairs of mothers/children attending a public maternity at Rio de Janeiro, Brazil. BW for gestational age according to the Intergrowth 21st was defined as follows: adequate for gestational age (AGA ≤ 90th percentile) and LGA (>90th percentile). The statistical analysis was a Poisson regression with robust estimations of the standard errors. Maternal dietary fat intake variables comprised lipids (% total energy); saturated (mg/1000 kcal), monounsaturated (mg/1000 kcal) and polyunsaturated (mg/1000 kcal) fats; and cholesterol (mg/1000 kcal), all of which were obtained with a Food Frequency Questionnaire. The mean BW was 3338 g (SD = 446.9), and the rate of LGA newborns was 13.1%. The mean maternal total energy intake was 2880 kcal (SD = 1074), cholesterol was 154.3 mg/1000 kcal (SD = 68.1) and monounsaturated fat was 6.9 mg/1000 kcal (SD = 2). Mothers of LGA newborns reported higher cholesterol dietary intake (195.8 vs. 148 mg/1000 kcal; P < 0.001), pre-pregnancy body mass index (25.1 vs. 23.5 kg/m2 ; P = 0.026) when compared with mothers of AGA newborns. Women with cholesterol intake within the fourth quartile were 2.48 (95% confidence interval: 1.31-4.66) times more likely to have an LGA infant compared with those in the 1-3 quartiles. Dietary intake of cholesterol during pregnancy influences LGA even after adjusting for other confounders.

Serum saturated fatty acid decreases plasma adiponectin and increases leptin throughout pregnancy independently of BMI.

OBJECTIVE: The aim of this study was to investigate whether serum concentrations of total saturated fatty acids (SFAs), polyunsaturated fatty acids (PUFAs), and their fractions are associated with plasma adiponectin and leptin concentrations throughout pregnancy. METHODS: A prospective cohort of 201 pregnant women was followed from gestational weeks 5 to 13, 20 to 26, and 30 to 36. Blood samples were collected at the three visits after 12 h of fasting. Fatty acid concentrations were determined using fast gas-liquid chromatography. Plasma adiponectin (µg/mL) and leptin (ng/dL) concentrations were evaluated using enzyme-linked immunosorbent assay kits. Statistical analyses included median adipokine concentrations according to the tertiles of fatty acid distribution and multiple linear mixed-effect models adjusted for body mass index, gestational age, total energy intake, alcohol consumption, and smoking. RESULTS: Women classified in the third SFA concentration tertile had lower median values of adiponectin compared with those in the first tertile ([first trimester: first tertile = 5.36; third tertile = 5.00]; [second trimester: first tertile = 6.39; third tertile = 4.47]; [third trimester: first tertile = 6.46; third tertile = 4.60]). Similar trends were observed for the 14:0, 16:0 and 18:0 fractions. In the multiple longitudinal models, total SFA (ß = -41.039; P = 0.008) and 16:0 were negatively associated with plasma adiponectin (16:0, ß = -0.511; P = 0.001). Total PUFA ω-6 (ß = 28.961; P = 0.002) and 18:2 ω-6 (ß = 0.259, P = 0.006) were positively associated with the adiponectin. Total SFA (ß = 0.110, P = 0.007), 14:0 (ß = 0.072, P = 0.011), and 20:3 ω-6 (ß = 0.039; P = 0.035) were positively associated with plasma leptin. CONCLUSIONS: Total serum SFA and the 16:0 fraction were negatively associated with plasma adiponectin and positively associated with leptin concentrations. Total ω-6 PUFA was positively associated only with plasma adiponectin concentrations throughout pregnancy.

Factors associated with maternal serum C-reactive protein throughout pregnancy: A longitudinal study in women of Rio de Janeiro, Brazil.

OBJECTIVES: The aim of this study was to evaluate the longitudinal changes of C-reactive protein (CRP) concentrations during pregnancy and to assess whether socioeconomic, anthropometric, dietary, behavioral, and biochemical factors are associated with these changes. METHODS: This was a prospective cohort study of 115 adult pregnant women, followed at gestational weeks 5 to 13, 20 to 26, and 30 to 36. Serum concentrations of CRP (mg/L) were measured by the immunoturbidimetric method with ultrasensitive kits (sensitivity 0.05 mg/dL). The statistics included descriptive analysis (mean + SD) and longitudinal linear mixed-effects models, reporting the ß coefficient and 95% confidence intervals (CI). RESULTS: Serum CRP concentrations progressively increased throughout pregnancy (ß = 0.121; 95% CI, 0.071-0.171). Parity (ß = 1.579; 95% CI, 0.731-2.427) and prepregnancy body mass index (BMI) (ß = 0.316; 95% CI, 0.053-0.587) were positively associated and dietary glycemic load was negatively associated (ß = -0.203; 95% CI, -0.380 to -0.026) with CRP concentrations in the multiple model. Prepregnancy obese women presented a more pronounced increase of CRP concentrations compared with normal weight women (ß = 0.210; 95% CI, 0.059-0.360 versus 0.115, respectively; 95% CI, 0.049-0.181). A statistically significant interaction was observed between parity and gestational age (ß = -0.045; 95% CI, -0.084 to -0.005), indicating that the variation of CRP throughout pregnancy differed according to parity categories. CONCLUSION: CRP concentrations increased throughout pregnancy. Parity and prepregnancy BMI were positively associated and dietary glycemic load was negatively associated with concentrations of CRP.

Association of Prepregnancy Dietary Patterns and Anxiety Symptoms from Midpregnancy to Early Postpartum in a Prospective Cohort of Brazilian Women.

BACKGROUND: Adherence to unhealthy dietary patterns may alter the risk of mental disorders during pregnancy and the postpartum period. OBJECTIVE: To analyze the association between prepregnancy dietary patterns and prospective variations on anxiety symptoms from midpregnancy to early postpartum. METHODS: A prospective cohort of 207 healthy pregnant women was followed at 5 to 13, 20 to 26, and 30 to 36 gestational weeks, and once at 30 to 45 days postpartum. The State-Trait Anxiety Inventory was used to evaluate anxiety symptoms at the second and third gestational trimesters and during the postpartum period. Dietary intake was assessed using a food frequency questionnaire administered during the first trimester of pregnancy that referred to the 6 months before pregnancy. Principal components analysis was used to identify dietary patterns and three prepregnancy dietary patterns were identified: common-Brazilian, healthy, and processed. Three longitudinal mixed-effect models were estimated to verify the association between dietary patterns and anxiety symptoms, adjusted for confounding variables. RESULTS: The mean anxiety symptom scores were 40.4, 40.5, and 37.2 for the second trimester, third trimester, and postpartum, respectively. The rate of variation of the State-Trait Anxiety Inventory score was 0.535 (95% CI -0.035 to 1.107; P=0.066) and -0.010 (95% CI -0.018 to -0.002; P=0.019) when accounting for gestational age and quadratic gestational age, respectively. The common-Brazilian pattern, comprised mainly of rice and beans (ß=-1.200, 95% CI -2.220 to -0.181; P=0.021), and the healthy pattern comprised mostly of vegetables, fruits, fish, and tea (ß=-1.290, 95% CI -2.438 to -0.134; P=0.029), were negatively associated with prospective changes in anxiety symptoms. CONCLUSIONS: High adherence to the common-Brazilian or healthy patterns was negatively associated with higher anxiety symptom scores from mid-pregnancy to early postpartum in this group of Brazilian women.

Lower inter-partum interval and unhealthy life-style factors are inversely associated with n-3 essential fatty acids changes during pregnancy: a prospective cohort with Brazilian women.

OBJECTIVE: To analyze serum fatty acids concentrations during healthy pregnancy and evaluate whether socioeconomic, demographic, obstetric, nutritional, anthropometric and lifestyle factors are associated with their longitudinal changes. STUDY DESIGN: A prospective cohort of 225 pregnant women was followed in the 5th-13th, 20th-26th and 30th-36th weeks of gestation. Serum samples were collected in each trimester of pregnancy and analyzed to determine the fatty acids composition using a high-throughput robotic direct methylation method coupled with fast gas-liquid chromatography. The independent variables comprised the subjects' socioeconomic and demographic status, obstetric history, early pregnancy body mass index (BMI), dietary and lifestyle parameters. Analyses were performed using linear mixed-effects models. RESULTS: The overall absolute concentrations of fatty acids increased from the 1st to the 2nd trimester and slightly increased from the 2nd to the 3rd trimester. Early pregnancy BMI, inter-partum interval and weekly fish intake were the factors associated with changes in eicosapentaenoic + docosahexaenoic acids (EPA+DHA) and total n-3 polyunsaturated fatty acids (PUFAs). Early pregnancy BMI, age and monthly per-capita income were inversely associated with the changes in the n-6/n-3 ratio. Alcohol consumption was positively associated with the n-6/n-3 ratio. CONCLUSION: Early pregnancy BMI was positively associated with EPA+DHA and total n-3 PUFAs, while presenting a reduced weekly fish intake and a lower inter-partum interval were associated with lower levels of n-3 PUFAs. A lower per-capita family income and a drinking habit were factors that were positively associated with a higher n-6/n-3 ratio.

Serum docosahexaenoic acid (DHA) is inversely associated with anxiety disorders in early pregnancy.

Little is known about the association between polyunsaturated fatty acids (PUFAs) and anxiety disorders during pregnancy. We evaluated this association at the first pregnancy trimester in 228 women. The study endpoint was the diagnosis of any anxiety disorder assessed by the Mini International Neuropsychiatric Interview. The independent variables were the serum concentrations of total n-3 and fractions (18:2, 20:5, 22:5, 22:6), total n-6 and fractions (18:2, 18:3, 20:2, 20:3, 20:4, 22:4, 22:5) and the n-6/n-3 ratio PUFAs. The prevalence of any anxiety disorders was 25%. The first tertile of the docosahexaenoic acid (DHA, 22:6 n-3) distribution represented 1.95 (95% CI: 1.00-3.77) higher chance of having an anxiety disorder diagnosis, compared to those in the second and third tertiles after adjusting the analyses for parity, family income, early pregnancy BMI and gestational age at the blood sampling. Serum concentrations of DHA were inversely associated with the occurrence of early pregnancy anxiety disorders.

Plasma adiponectin is inversely associated with antenatal anxiety: Results from a Brazilian cohort.

Antenatal anxiety may increase the risk of undesirable birth outcomes. Studies have demonstrated an association between adiponectin and anxiety, but this issue has not been investigated during pregnancy. This study aimed to evaluate the association between plasma adiponectin, measured throughout gestation, and the occurrence of anxiety at late pregnancy (30-36th weeks). A prospective cohort was investigated in Rio de Janeiro, Brazil. Healthy pregnant women, aged 20-40 years, were evaluated between gestational weeks 5-13, 22-26 and 30-36. State anxiety was measured using a validated version of the State-Trait Anxiety Inventory, and women were categorized as high (score≥50, n=30) or low anxiety (score<50, n=129). Plasma samples for all trimesters were analyzed using commercial ELISA kits to determine adiponectin concentrations (U/mL). Statistical analysis involved student's t-tests, chi-square, Pearson correlation, multiple logistic regression and linear mixed effects (LME) regression to model longitudinal trends of adiponectin, stratified for anxiety categories. Women with higher anxiety scores had lower mean concentrations of 3rd trimester adiponectin compared with those with lower scores (7.9; 95% CI: 7.0-8.9 vs. 9.9; 95% CI: 9.1-10.7). Women with 3rd trimester adiponectin values within the third tertile (10.47-26.57U/mL) were less likely to have high antenatal anxiety (adjusted OR=0.30; 95% CI: 0.09-0.98) compared with those within the first tertile (2.25-7.08U/mL). Unlike women with low levels of anxiety, those with high levels had a significant decrease of plasma adiponectin throughout pregnancy (ß=-0.07; 95% CI: -0.13-[-0.01] vs. ß=-0.01; 95% CI: -0.05 to 0.03). Multiple LME model indicated higher adiponectin throughout pregnancy for women with low anxiety (ß=-1.57; 95% CI: -2.78-[-0.37]). In conclusion, plasma adiponectin throughout pregnancy was inversely associated with antenatal anxiety.