Maternal diet during pregnancy and micronuclei frequency in peripheral blood T lymphocytes in mothers and newborns (Rhea cohort, Crete).

PURPOSE: The study assessed whether diet and adherence to cancer prevention guidelines during pregnancy were associated with micronucleus (MN) frequency in mothers and newborns. MN is biomarkers of early genetic effects that have been associated with cancer risk in adults. METHODS: A total of 188 mothers and 200 newborns from the Rhea cohort (Greece) were included in the study. At early-mid pregnancy, we conducted personal interviews and a validated food frequency questionnaire was completed. With this information, we constructed a score reflecting adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention guidelines on diet, physical activity and body fatness. At delivery, maternal and/or cord blood was collected to measure DNA and hemoglobin adducts of dietary origin and frequencies of MN in binucleated and mononucleated T lymphocytes (MNBN and MNMONO). RESULTS: In mothers, higher levels of red meat consumption were associated with increased MNBN frequency [2nd tertile IRR = 1.34 (1.00, 1.80), 3rd tertile IRR = 1.33 (0.96, 1.85)] and MNMONO frequency [2nd tertile IRR = 1.53 (0.84, 2.77), 3rd tertile IRR = 2.69 (1.44, 5.05)]. The opposite trend was observed for MNBN in newborns [2nd tertile IRR = 0.64 (0.44, 0.94), 3rd tertile IRR = 0.68 (0.46, 1.01)], and no association was observed with MNMONO. Increased MN frequency in pregnant women with high red meat consumption is consistent with previous knowledge. CONCLUSIONS: Our results also suggest exposure to genotoxics during pregnancy might affect differently mothers and newborns. The predictive value of MN as biomarker for childhood cancer, rather than adulthood, remains unclear. With few exceptions, the association between maternal carcinogenic exposures during pregnancy and childhood cancer or early biologic effect biomarkers remains poorly understood.

Suicide Attempts and Their Interrelation With the Economic Crisis in Chania, Greece: A Time-Series Analysis of the Period 2008-2015.

BACKGROUND: Greece has been in the grip of a severe economic crisis since 2008. It is well known that suicide attempts and actual suicides increase during periods of recession and austerity. The main aim of this study was to examine the economic crisis in relation to recorded suicide attempts in Chania, Greece, from 2008 to 2015, also taking unemployment rates into consideration. METHODS: During the research period from January 1, 2008, to December 31, 2015, 436 suicide attempts (females: n = 305 and males: n = 131) were recorded in the archives of the General Hospital of Chania. The data collected, analyzed, and used in the present study were from the archives of the emergency outpatient unit of the hospital. The unemployment data are from the Hellenic Statistical Authority. RESULTS: The rate of suicide attempts peaked in 2012 and remained relatively high until 2015. The most common suicide attempt method was poisoning by medication, with a percentage of 74.4%. In addition, the most prominent stressors related to the suicide attempts were family problems and relationship problems between couples: 40.2%. There was a statistically significant relationship between suicide attempts and unemployment rates (adjusted RR: 1.08; 95% CI, 1.07-1.09). CONCLUSIONS: Severe economic crisis seems to increase the rates of suicide attempts. The need for more detailed investigation is essential to provide insight into this global problem.

Effect of parental obesity and gestational diabetes on child neuropsychological and behavioral development at 4 years of age: the Rhea mother-child cohort, Crete, Greece.

Studies have suggested an association between maternal obesity pre-pregnancy and gestational diabetes (GDM) with impaired offspring neurodevelopment, but it is not clear if these associations are explained by shared familiar characteristics. We aimed to assess the associations of maternal and paternal obesity, maternal glucose intolerance in early pregnancy and GDM, with offspring neurodevelopment at 4 years of age. We included 772 mother-child pairs from the "Rhea" Mother-Child cohort in Crete, Greece. Data on maternal/paternal body mass index (BMI) and maternal fasting serum samples for glucose and insulin measurements were collected at 12 weeks of gestation. GDM screening was performed at 24-28 weeks. Neurodevelopment at 4 years was assessed using the McCarthy Scales of Children's Abilities. Behavioral difficulties were assessed by Strengths and Difficulties Questionnaire and Attention Deficit Hyperactivity Disorder Test. Multivariate linear regression analyses showed that maternal obesity was associated with a significant score reduction in general cognitive ability (ß-coeff -4.03, 95% CI: -7.08, -0.97), perceptual performance (ß-coeff -4.60, 95% CI: -7.74, -1.47), quantitative ability (ß-coeff -4.43, 95% CI: -7.68, -1.18), and executive functions (ß-coeff -4.92, 95% CI: -8.06, -1.78) at 4 years of age, after adjustment for several confounders and paternal BMI. Maternal obesity was also associated with increased behavioral difficulties (ß-coeff 1.22, 95% CI: 0.09, 2.34) and ADHD symptoms (ß-coeff 4.28, 95% CI: 1.20, 7.36) at preschool age. Paternal obesity maternal glucose intolerance in early pregnancy and GDM was not associated with child neurodevelopment. These findings suggest that maternal obesity may impair optimal child neurodevelopment at preschool age independently of family shared characteristics.

Vitamin D insufficient levels during pregnancy and micronuclei frequency in peripheral blood T lymphocytes mothers and newborns (Rhea cohort, Crete).

BACKGROUND & AIMS: Vitamin D deficiency is common among pregnant women and may be associated with several adverse health outcomes including cancer. Micronuclei frequency is a biomarker of early genetic effects and has been used to examine the association between genotoxic exposures and cancer. We examined maternal vitamin D levels during pregnancy in associations with micronuclei frequency in maternal blood and in cord blood. METHODS: 173 mothers and 171 newborns born between 2007 and 2008 in Heraklion (Crete, Greece) were included in the study. Between 14th and 18th weeks of gestation we collected information on maternal diet using food frequency questionnaires (FFQs). We measured maternal serum concentrations of 25-hydroxyvitamin D [25(OH)D] between the first and second trimester of pregnancy. We estimated dietary vitamin D intake using information from FFQ. After delivery we collected cord blood and maternal peripheral blood. We used the cytokinesis-block micronucleus (CBMN) assay to assess the frequencies of micronucleated cells in binucleated T lymphocytes (MNBN). RESULTS: Maternal insufficient serum levels of 25(OH)D (<50 nmol/L) during pregnancy were associated with increased MNBN frequency in cord blood [IRR = 1.32 (95%CI: 1.00, 1.72)]. This increase was higher for newborns with birth weight above the third quartile [≥3.500 kg; IRR = 2.21 (1.26, 3.89)]. Similarly, low levels of dietary vitamin D were associated with increased MNBN frequency in cord blood [middle tertile IRR = 1.08 (0.78, 1.47), lower tertile IRR = 1.51 (1.06, 2.14)]. Insufficient levels of vitamin D were not associated with MNBN in mothers. CONCLUSION: Our results suggest that vitamin D deficiency during pregnancy increases genotoxic risks in newborns. The prevalence of vitamin D deficiency globally is high and it is important to further investigate whether vitamin D supplementation or similar interventions during pregnancy could prevent DNA damage at early stages of life.

Impact of prenatal exposure to cadmium on cognitive development at preschool age and the importance of selenium and iodine.

The evidence regarding a potential link of low-to-moderate iodine deficiency, selenium status, and cadmium exposure during pregnancy with neurodevelopment is either contradicting or limited. We aimed to assess the prenatal impact of cadmium, selenium, and iodine on children's neurodevelopment at 4 years of age. The study included 575 mother-child pairs from the prospective "Rhea" cohort on Crete, Greece. Exposure to cadmium, selenium and iodine was assessed by concentrations in the mother's urine during pregnancy (median 13 weeks), measured by ICPMS. The McCarthy Scales of Children's Abilities was used to assess children's general cognitive score and seven different sub-scales. In multivariable-adjusted regression analysis, elevated urinary cadmium concentrations (≥0.8 µg/L) were inversely associated with children's general cognitive score [mean change: -6.1 points (95 % CI -12; -0.33) per doubling of urinary cadmium; corresponding to ~0.4 SD]. Stratifying by smoking status (p for interaction 0.014), the association was restricted to smokers. Urinary selenium was positively associated with children's general cognitive score [mean change: 2.2 points (95 % CI -0.38; 4.8) per doubling of urinary selenium; ~0.1 SD], although the association was not statistically significant. Urinary iodine (median 172 µg/L) was not associated with children's general cognitive score. In conclusion, elevated cadmium exposure in pregnancy of smoking women was inversely associated with the children's cognitive function at pre-school age. The results indicate that cadmium may adversely affect neurodevelopment at doses commonly found in smokers, or that there is an interaction with other toxicants in tobacco smoke. Additionally, possible residual confounding cannot be ruled out.

Is there an association between eating behaviour and attention-deficit/hyperactivity disorder symptoms in preschool children?

BACKGROUND: There is some evidence that aberrant eating behaviours and obesity co-occur with attention-deficit/hyperactivity disorder (ADHD) symptoms. The present study is the first that aims to investigate the association between eating behaviours and ADHD symptoms in early childhood in a population-based cohort. METHODS: We included 471 preschool children from the Rhea mother-child cohort in Crete, Greece. Parents completed the Children's Eating Behaviour Questionnaire to assess children's eating behaviour and the 36-item ADHD test (ADHDT) to evaluate ADHD symptoms at 4 years of age. Multivariable linear regression models were used to examine the association of eating behaviours with ADHD symptoms. RESULTS: Regarding children's food approach eating behaviours, we observed a positive association between food responsiveness and total ADHD index, as well as impulsivity, inattention and hyperactivity subscale, separately. Similarly, there was a significant positive association between emotional overeating and ADHD symptoms. With regard to children's food avoidant behaviours, food fussiness was found to be significantly associated with the impulsivity subscale. A dose-response association between the food approach behaviours and ADHD symptoms was also observed. Children on the medium and highest tertile of the food responsiveness subscale had increased scores on the ADHD total scale, as compared to those on the lowest tertile. As regards emotional overeating, children in the highest tertile of the scale had higher scores on ADHD total and hyperactivity. CONCLUSIONS: Our findings provide evidence that food approach eating behaviours such as food responsiveness and emotional overeating are associated with the increased ADHD symptoms in preschool children. Future studies to better understand this overlap will enhance potential interventions.

Ocular rigidity and outflow facility in nonproliferative diabetic retinopathy.

PURPOSE: To compare ocular rigidity (OR) and outflow facility (C) in patients with nonproliferative diabetic retinopathy (NPDR) and control subjects. METHODS: Twenty-four patients with NPDR (NPDR group) and 24 controls (control group) undergoing cataract surgery were enrolled. NPDR group was further divided into patients with mild NPDR (NPDR1-group) and patients with moderate and/or severe NPDR (NPDR2-group). After cannulation of the anterior chamber, a computer-controlled device was used to infuse saline and increase the intraocular pressure (IOP) in a stepping procedure from 15 to 40 mmHg. Ocular rigidity and outflow facility coefficients were estimated from IOP and volume recordings. RESULTS: Ocular rigidity was 0.0205 µL(-1) in NPDR group and 0.0202 µL(-1) in control group (P = 0.942). In NPDR1-group, OR was 0.017 µL(-1) and in NPDR2-group it was 0.025 µL(-1) (P = 0.192). Outflow facility was 0.120 µL/min/mmHg in NPDR-group compared to 0.153 µL/min/mmHg in the control group at an IOP of 35 mmHg (P = 0.151). There was no difference in C between NPDR1-group and NPDR2-group (P = 0.709). CONCLUSIONS: No statistically significant differences in ocular rigidity and outflow facility could be documented between diabetic patients and controls. No difference in OR and C was detected between mild NPDR and severe NPDR.

Metabolic profile in early pregnancy is associated with offspring adiposity at 4 years of age: the Rhea pregnancy cohort Crete, Greece.

CONTEXT: Maternal pre-pregnancy obesity may increase the risk of childhood obesity but it is unknown whether other metabolic factors in early pregnancy such as lipid profile and hypertension are associated with offspring cardiometabolic traits. OBJECTIVE: Our objective was to investigate whether fasting lipid, glucose, and insulin levels during early pregnancy and maternal pre-pregnancy weight status, are associated with offspring adiposity measures, lipid levels and blood pressure at preschool age. DESIGN AND METHODS: The study included 618 mother-child pairs of the pregnancy cohort "Rhea" study in Crete, Greece. Pregnant women were recruited at the first prenatal visit (mean: 12 weeks, SD: 0.7). A subset of 348 women provided fasting serum samples for glucose and lipid measurements. Outcomes measures were body mass index, abdominal circumference, sum of skinfold thickness, and blood pressure measurements at 4 years of age. A subsample of 525 children provided non-fasting blood samples for lipid measurements. RESULTS: Pre-pregnancy overweight/obesity was associated with greater risk of offspring overweight/obesity (RR: 1.83, 95%CI: 1.19, 2.81), central adiposity (RR: 1.97, 95%CI: 1.11, 3.49), and greater fat mass by 5.10 mm (95%CI: 2.49, 7.71) at 4 years of age. These associations were more pronounced in girls. An increase of 40 mg/dl in fasting serum cholesterol levels in early pregnancy was associated with greater skinfold thickness by 3.30 mm (95%CI: 1.41, 5.20) at 4 years of age after adjusting for pre-pregnancy BMI and several other confounders. An increase of 10 mmHg in diastolic blood pressure in early pregnancy was associated with increased risk of offspring overweight/obesity (RR: 1.22, 95%CI: 1.03, 1.45), and greater skinfold thickness by 1.71 mm (95% CI: 0.57, 2.86) at 4 years of age. CONCLUSIONS: Metabolic dysregulation in early pregnancy may increase the risk of obesity at preschool age.

Association of Prenatal Exposure to Persistent Organic Pollutants with Obesity and Cardiometabolic Traits in Early Childhood: The Rhea Mother-Child Cohort (Crete, Greece).

BACKGROUND: Prenatal exposure to endocrine-disrupting chemicals such as persistent organic pollutants (POPs) may increase risk of obesity later in life. OBJECTIVE: We examined the relation of in utero POPs exposure to offspring obesity and cardiometabolic risk factors at 4 years of age in the Rhea mother-child cohort in Crete, Greece (n = 689). METHODS: We determined concentrations of polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), and hexachlorobenzene (HCB) in first-trimester maternal serum. We measured child weight, height, waist circumference, skinfold thicknesses, blood pressure (BP), blood levels of lipids, C-reactive protein, and adipokines at 4 years of age. Childhood obesity was defined using age- and sex-specific cut points for body mass index (BMI) as recommended by the International Obesity Task Force. RESULTS: On multivariable regression analyses, a 10-fold increase in HCB was associated with a higher BMI z-score (adjusted ß = 0.49; 95% CI: 0.12, 0.86), obesity [relative risk (RR) = 8.14; 95% CI: 1.85, 35.81], abdominal obesity (RR = 3.49; 95% CI: 1.08, 11.28), greater sum of skinfold thickness (ß = 7.71 mm; 95% CI: 2.04, 13.39), and higher systolic BP (ß = 4.34 mmHg; 95% CI: 0.63, 8.05) at 4 years of age. Prenatal DDE exposure was associated with higher BMI z-score (ß = 0.27; 95% CI: 0.04, 0.5), abdominal obesity (RR = 3.76; 95% CI: 1.70, 8.30), and higher diastolic BP (ß = 1.79 mmHg; 95% CI: 0.13, 3.46). PCBs were not significantly associated with offspring obesity or cardiometabolic risk factors. CONCLUSIONS: Prenatal exposure to DDE and HCB was associated with excess adiposity and higher blood pressure levels in early childhood.

Pregestational excess weight, maternal obstetric complications and mode of delivery in the Rhea cohort in Crete.

BACKGROUND: There has been a significant increase in overweight and obesity worldwide reaching global epidemic, with dramatic increase also among women of reproductive age or entering pregnancy. Aims of the study were to estimate the prevalence of maternal pregestational overweight and obesity and their association with and contribution to maternal obstetric complications and mode of delivery. METHODS: One thousand two hundred eighty-six women with singleton pregnancies were followed-up prospectively from early pregnancy to delivery in Crete. RESULTS: The prevalence of pre-pregnancy overweight and obesity were 20 and 11.5%, respectively. After adjusting for potential confounders, overweight and/or obesity were associated with an increased risk for caesarean deliveries [RR(overweight_vs._normal) BMI = 1.21, 95% CI (1.06, 1.38), RR(obese_vs._normal) BMI = 1.21, 95% CI (1.02, 1.42)], gestational diabetes mellitus [RR(obese_vs._normal) BMI = 2.11, 95% CI (1.28, 3.47)] and high blood pressure [RR(severy.obese_vs._normal) BMI = 3.32, 95% CI (1.36, 8.06)] any time in pregnancy. Pre-pregnancy excess weight has potentially contributed to 21% of planned caesarean deliveries in primiparae (almost 45% of such cases among overweight/obese primiparea were potentially attributed to pregestational excess weight). One-third of gestational hypertension and gestational diabetes cases among overweight/obese mothers could be attributed to pregestational excess weight, although results did not reach statistical significance. CONCLUSIONS: Pregestational overweight and obesity continued to increase even more in recent years. Findings further support that maternal excess weight has a significant effect on and contribution to multiple maternal obstetric complications and the mode of delivery, underlining the necessity of obesity prevention, health policy strategies and health care that can result in significant individual and societal benefits.

Association of trimester-specific gestational weight gain with fetal growth, offspring obesity, and cardiometabolic traits in early childhood.

OBJECTIVE: The purpose of this study was to investigate the association of trimester-specific gestational weight gain with offspring fetal growth, obesity risk, and cardiometabolic health outcomes from birth to 4 years of age. STUDY DESIGN: We conducted the present study with 977 mother-child pairs of the pregnancy cohort "Rhea" study in Crete, Greece. We measured birthweight, body mass index from 6 months to 4 years of age, waist circumference, skinfold thickness, blood pressure, and blood levels of lipids, C-reactive protein, and adipose tissue hormones at 4 years of age. We used multiple linear and log Poisson regression models to examine the association of exposure with continuous or binary outcomes, respectively. RESULTS: Greater rate of gestational weight gain in the first trimester of pregnancy (per 200 g/wk) was associated with increased risk of overweight/obesity from 2 years (relative risk [RR], 1.25; 95% confidence interval [CI], 1.09-1.42) to 4 years of age (RR, 1.15; 95% CI, 1.05-1.25), but not with birth size. Each 200 g/wk of weight gain in the first trimester of pregnancy was also associated with greater risk of high waist circumference (RR, 1.13; 95% CI, 1.04-1.23), high sum of skinfold thickness (RR, 1.15; 95% CI, 1.02-1.29), and higher diastolic blood pressure at 4 years of age (ß, 0.43 mm Hg; 95% CI, 0.00-0.86). Greater rate of gestational weight gain during the second and third trimesters of pregnancy (per 200 g/wk) was associated with greater risk of large-for-gestational-age neonates (RR, 1.22; 95% CI, 1.02, 1.45) and higher levels of cord blood leptin (ratio of geometric means, 1.08; 95% CI, 1.00-1.17), but not with child anthropometry at later ages. CONCLUSION: Timing of gestational weight gain may influence childhood cardiometabolic outcomes differentially.

Social capital, tolerance of diversity and adherence to Mediterranean diet: the Rhea Mother-Child Cohort in Crete, Greece.

OBJECTIVE: To estimate the associations of individual maternal social capital and social capital dimensions (Participation in the Community, Feelings of Safety, Value of Life and Social Agency, Tolerance of Diversity) with adherence to the Mediterranean diet during pregnancy. DESIGN: This is a cross-sectional analysis of data from a prospective mother-child cohort (Rhea Study). Participants completed a social capital questionnaire and an FFQ in mid-pregnancy. Mediterranean diet adherence was evaluated through an a priori score ranging from 0 to 8 (minimal-maximal adherence). Maternal social capital scores were categorized into three groups: the upper 10 % was the high social capital group, the middle 80 % was the medium and the lowest 10 % was the low social capital group. Multivariable log-binomial and linear regression models adjusted for confounders were performed. SETTING: Heraklion, Crete, Greece. SUBJECTS: A total of 377 women with singleton pregnancies. RESULTS: High maternal Total Social Capital was associated with an increase of almost 1 point in Mediterranean diet score (highest v. lowest group: ß coefficient=0·95, 95 % CI 0·23, 1·68), after adjustment for confounders. Similar dose-response effects were noted for the scale Tolerance of Diversity (highest v. lowest group: adjusted ß coefficient=1·08, 95 % CI 0·39, 1·77). CONCLUSIONS: Individual social capital and tolerance of diversity are associated with adherence to the Mediterranean diet in pregnancy. Women with higher social capital may exhibit a higher sense of obligation to themselves and to others that may lead to proactive nutrition-related activities. Less tolerant women may not provide the opportunity to new healthier, but unfamiliar, nutritional recommendations to become part of their regular diet.

Relative validity of an FFQ for pre-school children in the mother-child 'Rhea' birth cohort in Crete, Greece.

OBJECTIVE: To examine the relative validity of an FFQ based on parental report for pre-school children in the mother-child 'Rhea' birth cohort. DESIGN: The children's mothers completed an FFQ that referred to the children's dietary intake for the previous year by telephone interview. Mothers completed also three food records, two on weekdays and one on a weekend day. Spearman correlation coefficients were calculated for the energy-adjusted values. Weighted kappa statistics (κ(w)) and the Bland-Altman technique were used to test the degree of agreement between the two dietary methods. SETTING: Heraklion, Crete, Greece, 2011-2012. SUBJECTS: A total of ninety-nine mothers (corresponding to fifty-one boys and forty-eight girls) participated in the validation study. RESULTS: The mean and median values of all food group and nutrient intakes did not differ significantly between the two dietary methods. Overall, fair agreement was observed between the FFQ and the food records for ranking participants based on their intake, with κ(w) ranging from 0·21 to 0·40 for most foods and nutrients. On average, 88 % of participants were classified into the same or adjacent tertiles for nutrient and food group intakes by both dietary methods. The degree of agreement was also confirmed by the visual examination of the Bland-Altman plots. CONCLUSIONS: The study indicates that the Rhea 4 years FFQ is a relatively accurate tool for assessing habitual food group and nutrient intakes among pre-school children in Crete, Greece.

Antenatal maternal mental health as determinant of postpartum depression in a population based mother-child cohort (Rhea Study) in Crete, Greece.

PURPOSE: Antenatal maternal mental health has been identified as an important determinant of postpartum depression (PPD). We investigated the occurrence of depression both antenatally and postnatally and examined whether maternal trait anxiety and depression during pregnancy were associated with PPD at 8 weeks postpartum in a prospective mother-child cohort (Rhea Study) in Crete, Greece. METHODS: 438 women completed the Edinburgh Postnatal Depression Scale (EPDS) and the Trait subscale of the State-Trait Anxiety Inventory (STAI-Trait) questionnaires assessing antenatal depression and anxiety, respectively, during the third trimester of pregnancy as well as the EPDS at 8 weeks postpartum. RESULTS: The prevalence of women with probable depression (EPDS score ≥13) was 16.7 % at 28-32 weeks of pregnancy and 13.0 % at 8 weeks postpartum. A per 5 unit increase in the STAI-Trait subscale increased the odds for PPD by 70 % (OR = 1.70, 95 % CI 1.41, 2.05), whereas a per unit increase in EPDS during pregnancy increased the odds for PPD by 27 % (OR = 1.27, 95 % CI 1.19, 1.36). CONCLUSIONS: Our findings suggest that antenatal maternal psychological well-being has a significant effect on PPD, which might have important implications for early detection during pregnancy of women at risk for postpartum depression.

Maternal weight status, cord blood leptin and fetal growth: a prospective mother-child cohort study (Rhea study).

BACKGROUND: Leptin is an adipocyte-secreted hormone that regulates energy homeostasis, while its role in fetal programming remains poorly understood. We aimed to evaluate the effect of maternal weight status on cord blood leptin levels and their combined effect on fetal growth. METHODS: We included 638 mother-child pairs from the prospective mother-child cohort 'Rhea' study in Crete, Greece with singleton pregnancies, providing cord blood serum samples for leptin analysis and complete data on birth outcomes. Multivariable logistic and linear regression models were used adjusting for confounders. Generalised additive models were used to explore the form of the relationship between cord leptin and continuous birth outcomes. RESULTS: Log cord leptin was positively associated with birthweight {ß-coef: 176.5 [95% confidence interval (CI): 133.0, 220.0] }, ponderal index (ß-coef: 1.0 [95% CI: 0.6, 1.4] ) and gestational age (ß-coef: 0.7 [95% CI: 0.5, 0.8] ). Excessive weight gain during pregnancy was associated with a threefold increased risk for cord hyperleptinaemia {relative risk (RR): 3.0, [95% CI: 1.5, 6.3] }. Maternal pre-pregnancy overweight/obesity [body mass index (BMI) ≥25 kg/m(2) ] increased the risk of giving birth to a hyperleptinaemic neonate (RR: 2.1 [95% CI: 1.4, 3.2] and the effect of log leptin on birthweight (ß-coef: 219.1 [95% CI: 152.3, 285.9] compared with women with a BMI <25 kg/m(2) (ß-coef: 150.5 [95% CI: 93.1, 207.9]. CONCLUSIONS: Higher cord blood leptin levels are associated with increased size at birth and gestational age, while maternal pre-pregnancy BMI and weight gain during pregnancy represent significant indicators of cord blood leptin.

Social capital in pregnancy and postpartum depressive symptoms: a prospective mother-child cohort study (the Rhea study).

BACKGROUND: Depression, and to a lesser extent postpartum depressive symptoms, have been associated with characteristics of the social environment and social capital. Up to the present, mostly cross-sectional studies have explored such an association without providing a clear temporal relationship between social capital and depression. OBJECTIVES: To estimate prospectively the effect of individual-level self-reported maternal social capital during pregnancy on postpartum depressive symptoms. DESIGN: Prospective mother-child cohort (Rhea study). SETTINGS: 4 prenatal clinics in Heraklion, Crete, Greece. PARTICIPANTS: All women for one year beginning in February 2007. From the 1388 participants, complete data were available for 356 women. METHODS: Women self-completed two questionnaires: The Social Capital Questionnaire at about the 24th week of gestation and the Edinburgh Postnatal Depression Scale (range 0-30) at about the 8-10th week postpartum. Maternal social capital scores were categorized into three groups: the upper 10% was the high social capital group, the middle 80% was the medium and the lowest 10% was the low social capital group that served as the reference category. Multivariable log-binomial and linear regression models were performed for: the whole available sample; for participants with a history of depression and/or prenatal EPDS≥13; for participants without any previous or current depression and prenatal EPDS score<13. Potential confounders included demographic, socio-economic, lifestyle and pregnancy characteristics that have an established or potential association with maternal social capital in pregnancy or postpartum depressive symptoms or both. RESULTS: Higher maternal social capital was associated with lower EPDS scores (highest vs lowest group: ß-coefficient=-3.95, 95% CI -7.75, -0.14). Similar effects were noted for the subscale value of life/social agency (highest vs lowest group: ß-coefficient=-5.96, 95% CI -9.52, -2.37). This association remained significant for women with and without past and/or present depression only for the subscale value of life/social agency although with a more imprecise estimate. No effect was found for participation, a structural dimension of social capital. CONCLUSIONS: Women with higher individual-level social capital in mid-pregnancy reported less depressive symptoms 6-8 weeks postpartum. Given the proposed association of perceptions of the social environment with postpartum depressive symptoms, health professionals should consider evidence-based interventions to address depression in a social framework.

Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes.

CONTEXT: Maternal thyroid dysfunction, especially in early pregnancy, may lead to pregnancy complications and adverse birth outcomes. Few population-based prospective studies have evaluated these effects and results are discrepant. OBJECTIVE: We examined the association of thyroid function and autoimmunity in early pregnancy with adverse pregnancy and birth outcomes. SETTING AND PARTICIPANTS: The study used data from the prospective mother-child cohort "Rhea" study in Crete, Greece. A total of 1170 women with singleton pregnancies participated in this analysis. Maternal serum samples in the first trimester of pregnancy were tested for thyroid hormones (TSH, free T(4), and free T(3)) and thyroid antibodies (thyroid peroxidase antibody and thyroglobulin antibody). Multivariable log-Poisson regression models were used adjusting for confounders. MAIN OUTCOME MEASURES: Outcomes included gestational diabetes, gestational hypertension/preeclampsia, cesarean section, preterm delivery, low birth weight, and small-for-gestational-age neonates. RESULTS: The combination of high TSH and thyroid autoimmunity in early pregnancy was associated with a 4-fold increased risk for gestational diabetes [relative risk (RR) 4.3, 95% confidence interval (CI) 2.1-8.9)] and a 3-fold increased risk for low birth weight neonates (RR 3.1, 95% CI 1.2-8.0) after adjustment for several confounders. Women positive for thyroid antibodies without elevated TSH levels in early pregnancy were at high risk for spontaneous preterm delivery (RR 1.7, 95% CI 1.1-2.8), whereas the combined effect of high TSH and positive thyroid antibodies did not show an association with preterm birth. CONCLUSIONS: High TSH levels and thyroid autoimmunity in early pregnancy may detrimentally affect pregnancy and birth outcomes.

Gender-specific reference intervals for cord blood leptin in Crete, Greece.

Cord leptin is a biomarker of fetal growth and adiposity with a role in predicting weight gain during the first months of life and childhood obesity. Our objective was to calculate gender-specific reference intervals for cord blood leptin in healthy neonates in Crete, Greece. We used data from the prospective mother-child cohort ("Rhea" study) in Crete, Greece. The analysis included 398 neonates chosen with strict inclusion criteria based on maternal and fetal characteristics. Cord leptin reference intervals for male neonates were 1.4-18.2 ng/mL and for females 2.0-25.8 ng/mL. Females had higher leptin levels (median 7.4; IQR 4.7-10.9) compared to males (median 4.9; IQR 3.2-7.6) (p < 0.001). Conclusion Gender-specific reference ranges are essential in clinical practice for correct interpretation of leptin values in cord blood and early detection of childhood obesity.

Effect of high doses of folic acid supplementation in early pregnancy on child neurodevelopment at 18 months of age: the mother-child cohort 'Rhea' study in Crete, Greece.

OBJECTIVE: To investigate whether high doses of folic acid supplementation in early pregnancy are associated with child neurodevelopment at 18 months of age. DESIGN: The study uses data from the prospective mother-child cohort 'Rhea' study. Pregnant women completed an interviewer-administered questionnaire on folic acid supplementation at 14-18 weeks of gestation. Neurodevelopment at 18 months was assessed with the use of the Bayley Scales of Infant and Toddler Development (3rd edition). Red-blood-cell folate concentrations in cord blood were measured in a sub-sample of the study population (n 58). SETTING: Heraklion, Crete, Greece, 2007-2010. SUBJECTS: Five hundred and fifty-three mother-child pairs participating in the 'Rhea' cohort. RESULTS: Sixty-eight per cent of the study participants reported high doses of supplemental folic acid use (5 mg/d), while 24 % reported excessive doses of folic acid (>5 mg/d) in early pregnancy. Compared with non-users, daily intake of 5 mg supplemental folic acid was associated with a 5-unit increase on the scale of receptive communication and a 3·5-unit increase on the scale of expressive communication. Doses of folic acid supplementation higher than 5 mg/d were not associated with additional increase in the neurodevelopmental scales. CONCLUSIONS: This is the first prospective study showing that high doses of supplementary folic acid in early pregnancy may be associated with enhanced vocabulary development, communicational skills and verbal comprehension at 18 months of age. Additional longitudinal studies and trials are needed to confirm these results.

Maternal social capital and birth outcomes in the mother-child cohort in Crete, Greece (Rhea study).

This cohort study aimed to estimate the effect of individual maternal social capital during pregnancy on birth outcomes in the context of the Mother-child cohort (Rhea study), in Crete-Greece. Women were recruited from four prenatal clinics in Heraklion-Crete for one year beginning in February 2007. 610 women completed the self-administered Social Capital Questionnaire at about the 24th week of gestation. The scale assessed total maternal social capital and four social capital subscales: Participation in the Community, Feelings of Safety, Value of Life and Social Agency, and Tolerance of Diversity. Potential confounders included characteristics that have an established or potential association with the maternal social capital, and the birth outcomes (preterm birth, small weight for the gestational age, fetal weight growth restriction, weight, length and head circumference). The results of logistic and linear regression models indicated that there was an increase in the risk of preterm birth for every unit increase in maternal participation (range 12-48), and especially in the risk of medically indicated preterm birth. Although the findings suggest that participation is associated with an increased probability for preterm birth, we cannot know whether this is a protective or damaging social capital effect. Women who participate more in their communities may have enhanced access to information and/or resources, easier access to health care and support when they face maternal and fetal conditions that trigger the need for medical intervention. On the other hand, women may be more exposed to social and/or environmental stressors. Future research needs to distinguish between different types of participation and different components of social capital to better understand their associations with birth outcomes.