Lila Papadopoulou - Academia.edu (original) (raw)

Papers by Lila Papadopoulou

Background: Anogenital distance has been associated with prenatal exposure to chemicals with anti... more Background: Anogenital distance has been associated with prenatal exposure to chemicals with anti-androgenic effects. There are limited data in humans concerning descriptive patterns, predictors, and the reliability of measurement of anogenital distances. We examined anogenital distance measurements and their predictors in males and females and further estimated the reliability of these measurements. Methods: Anogenital distances were measured in repeated time periods among 352 newborns and 732 young children in two cohorts, one in Crete, Greece and one in Barcelona, Spain. Mixed effect models were used to estimate the between-children, between-and within-examiners variance, as well as the reliability coefficients. Results: Genitalia distances were longer in males than in females. Anogenital distances in both sexes increased rapidly from birth to 12 months, while the additional increase during the second year was small. Birthweight was associated with an increase of 1.9 mm/kg [95% CI 0.1, 3.8] (CI, confidence interval) in the anogenital distance measured from the anus to anterior base of the penis in newborn males, 2.9 mm/kg [95% CI 1.8, 3.9] in anoclitoral distance and 1.0 mm/kg [95% CI 0.0, 2.0] in anofourchettal distance in newborn females, after adjustment for gestational age. In children, body weight was the main predictor of all genitalia measurements. Moreover, anogenital distances at birth were associated with the corresponding distances at early childhood. High reliability coefficients (>90%) were found for all anogenital distances measurements in males and females. Conclusions: Anogenital distances are strongly related to gestational age and birthweight and later, to growth. They track through early life and are highly reliable measures in both sexes.

JAMA Network Open, 2020

IMPORTANCE The balance of mercury risk and nutritional benefit from fish intake during pregnancy ... more IMPORTANCE The balance of mercury risk and nutritional benefit from fish intake during pregnancy for the metabolic health of offspring to date is unknown. OBJECTIVE To assess the associations of fish intake and mercury exposure during pregnancy with metabolic syndrome in children and alterations in biomarkers of inflammation in children. DESIGN, SETTING, AND PARTICIPANTS This population-based prospective birth cohort study used data from studies performed in 5 European countries (France, Greece, Norway, Spain, and the UK) between April 1, 2003, and February 26, 2016, as part of the Human Early Life Exposome (HELIX) project. Mothers and their singleton offspring were followed up until the children were aged 6 to 12 years. Data were analyzed between March 1 and August 2, 2019. EXPOSURES Maternal fish intake during pregnancy (measured in times per week) was assessed using validated food frequency questionnaires, and maternal mercury concentration (measured in micrograms per liter) was assessed using maternal whole blood and cord blood samples. MAIN OUTCOMES AND MEASURES An aggregate metabolic syndrome score for children was calculated using the z scores of waist circumference, systolic and diastolic blood pressures, and levels of triglyceride, high-density lipoprotein cholesterol, and insulin. A higher metabolic syndrome score (score range, −4.9 to 7.5) indicated a poorer metabolic profile. Three protein panels were used to measure several cytokines and adipokines in the plasma of children. RESULTS The study included 805 mothers and their singleton children. Among mothers, the mean (SD) age at cohort inclusion or delivery of their infant was 31.3 (4.6) years. A total of 400 women (49.7%) had a high educational level, and 432 women (53.7%) were multiparous. Among children, the mean (SD) age was 8.4 (1.5) years (age range, 6-12 years). A total of 453 children (56.3%) were boys, and 734 children (91.2%) were of white race/ethnicity. Fish intake consistent with health recommendations (1 to 3 times per week) during pregnancy was associated with a 1-U decrease in metabolic syndrome score in children (β = −0.96; 95% CI, −1.49 to −0.42) compared with low fish consumption (<1 time per week) after adjusting for maternal mercury levels and other covariates. No further benefit was observed with fish intake of more than 3 times per week. A higher maternal mercury concentration was independently associated with an increase in the metabolic syndrome score of their offspring (β per 2-fold increase in mercury concentration = 0.18; 95% CI, 0.01-0.34). Compared with low fish intake, moderate and high fish intake during pregnancy were associated with reduced levels of proinflammatory cytokines and adipokines in children. An integrated analysis identified a cluster of children with increased susceptibility to metabolic disease, which was (continued) Key Points Question Is fish consumption during pregnancy associated with benefits for the metabolic health of children? Findings In this cohort study of 805 mothers and their singleton offspring, moderate fish consumption during pregnancy was associated with the downregulation of inflammation and improvements in the metabolic profile of children; high mercury exposure during pregnancy had the opposite associations. Meaning The results of this study suggest that fish consumption consistent with current recommendations during pregnancy was associated with improvements in the metabolic health of children.

Environmental Research, 2019

BMC Medicine, 2018

Background: Gestational weight gain differs according to pre-pregnancy body mass index and is rel... more Background: Gestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different prepregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies.

Environmental science & technology, 2017

Currently, there is limited knowledge on the distribution of poly- and perfluoroalkyl substances ... more Currently, there is limited knowledge on the distribution of poly- and perfluoroalkyl substances (PFASs) in different blood matrices, particularly for novel PFASs such as polyfluoroalkyl phosphate esters (PAPs) and perfluoroalkyl phosphonates (PFPAs). To explore this, serum, plasma, and whole blood from 61 adults in Oslo, Norway were collected. The largest number of PFASs were detected in whole blood. For PAPs and PFPAs, the highest frequencies of detection and concentrations were observed in plasma. PAPs contributed to 8% of total PFASs in plasma (median, 0.81 ng mL(-1)). Perfluorohexylphosphonate (PFHxPA) was the dominant PFPA, regardless of blood matrix. The relative composition profiles of PFASs in blood matrices differed. For some specific PFASs such as perfluorooctanesulfonamide (PFOSA) and perfluorohexanoate (PFHxA), the highest concentrations were observed in whole blood. The PFAS concentration ratios varied between blood matrices, depending on the compounds. However, simila...

Norsk Epidemiologi, 2014

Awareness that maternal diet may influence the outcome of pregnancy as well as the long-term heal... more Awareness that maternal diet may influence the outcome of pregnancy as well as the long-term health of mother and child has increased in recent years. A new food frequency questionnaire (FFQ) was developed and validated specifically for the Norwegian Mother and Child Cohort Study (MoBa). The MoBa FFQ is a semi-quantitative tool which covers the average intake of food, beverages and dietary supplements during the first 4 to 5 months of pregnancy. It includes questions about intakes of 255 foods and dishes and was used from 2002 onwards. Data assessed by the MoBa FFQ is available for 87,700 pregnancies. Numerous sub-studies have examined associations between dietary factors and health outcomes in MoBa. The aim of this paper is to summarize the results from 19 studies of maternal diet and pregnancy outcomes, which is the complete collection of studies based on the MoBa FFQ and published before September 2014. The overall research question is whether maternal diet – from single substanc...

Environmental Health Perspectives, 2015

Background: The etiologies of the male urogenital anomalies hypospadias and cryptorchidism remain... more Background: The etiologies of the male urogenital anomalies hypospadias and cryptorchidism remain unclear. It has been suggested that maternal diet and environmental contaminants may affect the risk of these anomalies via placental or hormonal disturbances. Objectives: To examine associations between organic food consumption during pregnancy and prevalence of hypospadias and cryptorchidism at birth. Methods: Our study includes 35,107 women participating in the Norwegian Mother and Child Cohort Study (MoBa) who delivered a singleton male infant. Information about use of six groups of organically produced food (vegetables, fruit, bread/cereal, milk/dairy products, eggs and meat) during pregnancy was collected by a food frequency questionnaire. Women who indicated that they sometimes, often, or mostly consumed organic foods in at least one of the six food groups were classified as organic food consumers in analyses. Hypospadias and cryptorchidism diagnoses were retrieved from the Medical Birth Registry of Norway. We estimated odds ratios (ORs) and 95 percent confidence intervals (95% CIs) using multiple logistic regression. Results: Seventy-four male newborns were diagnosed with hypospadias (0.2%) and 151 with cryptorchidism (0.4%). Women who consumed any organic food during pregnancy were less likely to give birth to a boy with hypospadias (OR=0.42; 95% CI: 0.25, 0.70 based on 21 exposed cases) than women who reported they never or seldom consumed organic food. Associations with specific organic foods were strongest for vegetable (OR=0.36; 95% CI: 0.15, 0.85; 10 exposed cases) and milk/dairy (OR=0.43; 95% CI: 0.17, 1.07; 7 exposed cases) consumption. No substantial association was observed for consumption of organic food and cryptorchidism.

Environmental research, Jan 6, 2015

The potential toxicity of background exposure to perfluoroalkyl substances (PFASs) is currently u... more The potential toxicity of background exposure to perfluoroalkyl substances (PFASs) is currently under active investigation. Such investigations typically rely on a single measure of PFAS concentration, yet the longer-term reliability of a single measure has not been well characterized, especially among reproductive-aged women. Our aim was to investigate the association between PFAS plasma concentrations of 100 women in two consecutive pregnancies and explore changes in plasma concentration related to reproductive factors. The women in our study were enrolled in the Norwegian Mother and Child Cohort Study (MoBa) from 2003 to 2009. About half of them breastfed exclusively for 6 months and the rest of the participants did not breastfeed between the two consecutive pregnancies (median time between pregnancies: 18 months). Maternal blood was collected at mid-pregnancy and plasma was analyzed for 10 PFASs. Statistical analyses were restricted to 6 PFASs that were quantifiable in more than...

Public Health Nutrition, 2012

ObjectiveTo investigate whether high doses of folic acid supplementation in early pregnancy are a... more ObjectiveTo investigate whether high doses of folic acid supplementation in early pregnancy are associated with child neurodevelopment at 18 months of age.DesignThe 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).SettingHeraklion, Crete, Greece, 2007–2010.SubjectsFive hundred and fifty-three mother–child pairs participating in the ‘Rhea’ cohort.ResultsSixty-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 ...

Science of The Total Environment, 2014

• Dioxin-diet score was defined using RRR in a five country population. • Dioxin-diet score was p... more • Dioxin-diet score was defined using RRR in a five country population. • Dioxin-diet score was positively correlated to dioxin-like activity in maternal blood. • Women following a diet high in meat and fish had a higher dioxin-diet score. • High dioxin-diet score was associated with a 121 g reduction in birth weight. • Maternal diet can contribute to foetal exposure to dioxins and dioxin-like compounds.

Science of The Total Environment, 2013

Personality and Individual Differences, 2013

ABSTRACT The second to fourth digit ratio (2D:4D) indicates androgen exposure during early develo... more ABSTRACT The second to fourth digit ratio (2D:4D) indicates androgen exposure during early development. Numerous methods are used in the assessment of 2D:4D, however, some are not reliable enough and others are difficult to perform in large epidemiological studies. We assessed the reliability of 2D:4D using a direct method with a caliper, and compared it with a computer-assisted analysis on scanned images. Both methods were moderately correlated, but the scan method produced slightly lower 2D:4D. The main source of variation was differences between subjects (real variation). Reliability was higher among men and among younger participants. All reliability coefficients were higher than 0.8 when three repeated measurements were averaged. Our results suggest that reliability is influenced by participants’ characteristics. Digit ratios determined directly with calipers are reliable when repeated measurements are averaged.

Paediatric and Perinatal Epidemiology, 2013

Background: Leptin is an adipocyte-secreted hormone that regulates energy homeostasis, while its ... more 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 {β-coef: 176.5 [95% confidence interval (CI): 133.0, 220.0] }, ponderal index (β-coef: 1.0 [95% CI: 0.6, 1.4]) and gestational age (β-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 (β-coef: 219.1 [95% CI: 152.3, 285.9] compared with women with a BMI <25 kg/m 2 (β-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.

European Journal of Nutrition, 2012

Environmental Health Perspectives, 2012

Environment International, 2013

Maternal diet not only provides essential nutrients to the developing fetus but is also a source ... more Maternal diet not only provides essential nutrients to the developing fetus but is also a source of prenatal exposure to environmental contaminants. We investigated the association between dietary intake of dioxins and PCBs during pregnancy and birth size. The study included 50,651 women from the Norwegian Mother and Child Cohort Study (MoBa). Dietary information was collected by FFQs and intake estimates were calculated by combining food consumption and food concentration of dioxins, dioxin-like PCBs and non-dioxin-like PCBs. We used multivariable regression models to estimate the association between dietary intake of dioxins and PCBs and fetal growth. The contribution of fish and seafood intake during pregnancy was 41% for dietary dioxins and dioxin-like PCBs and 49% for dietary non-dioxin-like PCBs. Further stratified analysis by quartiles of seafood intake during pregnancy was conducted. We found an inverse dose-response association between dietary intake of dioxins and PCBs and fetal growth after adjustment for confounders. Newborns of mothers in the upper quartile of dioxin and dioxin-like PCBs intake had 62 g lower birth weight (95% CI: −73, −50), 0.26 cm shorter birth length (95% CI: −0.31, −0.20) and 0.10 cm shorter head circumference (95% CI: −0.14, −0.06) than newborns of mothers in the lowest quartile of intake. Similar negative associations for intake of dioxins and dioxin-like PCBs were found after excluding women with intakes above the tolerable weekly intake (TWI = 14 pg TEQ/kg bw/week). The negative association of dietary dioxins and PCBs with fetal growth was weaker as seafood intake was increasing. No association was found between dietary dioxin and PCB intake and the risk for small-forgestational age neonate. In conclusion, dietary intakes of dioxins and PCBs during pregnancy were negatively associated with fetal growth, even at intakes below the TWI.

Maternal & Child Nutrition, 2012

Although benefits of breastfeeding have been widely promoted and accepted, exclusive breastfeedin... more Although benefits of breastfeeding have been widely promoted and accepted, exclusive breastfeeding for the first 6 months of life is far from the norm in many countries. In a prospective mother-child cohort study in Crete, Greece ('Rhea' study), we assessed the frequency of breastfeeding and its socio-demographic predictors. Information on breastfeeding was available for a period of 18 months post-partum for a cohort of 1181 mothers and their 1208 infants. The frequency of exclusive and predominant breastfeeding in the first month post-partum was 17.8% and 3.4%, respectively, with almost three-quarters of women (73.6%) ceasing any breastfeeding after 4 months post-partum. Women were less likely to initiate breastfeeding if they had a caesarean delivery (CD), whereas they were more likely to initiate breastfeeding if they had a higher education or gave birth to a private clinic. Among women breastfeeding, those who had a CD, were ex-smokers or smokers during pregnancy had a statistically significant shorter duration of breastfeeding, whereas higher education and being on leave from work were associated with a longer duration of breastfeeding. Study findings suggest suboptimal levels of exclusive and any breastfeeding and difficulty maintaining longer breastfeeding duration. CD and smoking are common in Greece and are strong negative predictors for breastfeeding initiation and/or duration, necessitating targeting women at risk early in the prenatal period so as to have a meaningful increase of breastfeeding practices in future cohorts of mothers.