Mediation analysis aims at estimating to what extent the effect of an exposure on an outcome is explained by a set of mediators on the causal pathway between the exposure and the outcome. The total ...effect of the exposure on the outcome can be decomposed into an indirect effect, i.e. the effect explained by the mediators jointly, and a direct effect, i.e. the effect unexplained by the mediators. However finer decompositions are possible in presence of independent or sequential mediators.
We review four statistical methods to analyse multiple sequential mediators, the inverse odds ratio weighting approach, the inverse probability weighting approach, the imputation approach and the extended imputation approach. These approaches are compared and implemented using a case-study with the aim to investigate the mediating role of adverse reproductive outcomes and infant respiratory infections in the effect of maternal pregnancy mental health on infant wheezing in the Ninfea birth cohort.
Using the inverse odds ratio weighting approach, the direct effect of maternal depression or anxiety in pregnancy is equal to a 59% (95% CI: 27%,94%) increased prevalence of infant wheezing and the mediated effect through adverse reproductive outcomes is equal to a 3% (95% CI: -6%,12%) increased prevalence of infant wheezing. When including infant lower respiratory infections in the mediation pathway, the direct effect decreases to 57% (95% CI: 25%,92%) and the indirect effect increases to 5% (95% CI: -5%,15%). The estimates of the effects obtained using the weighting and the imputation approaches are similar. The extended imputation approach suggests that the small joint indirect effect through adverse reproductive outcomes and lower respiratory infections is due entirely to the contribution of infant lower respiratory infections, and not to an increased prevalence of adverse reproductive outcomes.
The four methods revealed similar results of small mediating role of adverse reproductive outcomes and early respiratory tract infections in the effect of maternal pregnancy mental health on infant wheezing. The choice of the method depends on what is the effect of main interest, the type of the variables involved in the analysis (binary, categorical, count or continuous) and the confidence in specifying the models for the exposure, the mediators and the outcome.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
Perinatal maternal depression and anxiety are associated with adverse maternal outcomes, and nutrition may play an important role in their emergence. Previous research shows that certain ...micro and macronutrients found in different dietary patterns may influence perinatal mood disorders.
Objectives
This study aims to explore relationships between nutrition during pregnancy and perinatal maternal depression and anxiety symptoms using network analyses.
Methods
Using data from the French EDEN mother-child cohort, the sample consisted of 1438 women with available perinatal mental health outcomes (CES-D, STAI and EPDS) and nutritional markers collected from food frequency questionnaires. Four networks were constructed to explore the relationships between prenatal nutrient status, dietary patterns, and perinatal mental health, while accounting for important confounders.
Results
The Healthy dietary pattern was associated with the presence of vital micronutrients, while the Western dietary pattern was consistently associated with poorer intake of vital micronutrients and contained an excess of certain macronutrients. Western dietary pattern and symptoms of postnatal depression were connected by a positive edge in both the macronutrient and micronutrient networks. Lower education levels were associated with higher Western dietary pattern scores, from which a positive edge linked to postnatal depression symptoms in both models.
Conclusions
A Western dietary pattern was associated with increased symptoms of postnatal depression in our adjusted network models; The Healthy dietary pattern was associated with essential micronutrients but not with symptoms of depression or anxiety. Perinatal mental health might be impacted by specific dietary patterns in the context of psychosocial and physical stress associated with pregnancy.
Disclosure of Interest
None Declared
Studies in high-income countries show that despite the positive association of weight with socioeconomic position at birth, an inverse socioeconomic gradient in overweight (OW) appears later in ...childhood. The objectives were to understand the natural history of socioeconomic inequalities in weight, height and body mass index (BMI), by investigating their associations with maternal educational level between birth and 5 years, separately in boys and girls.
A published work of growth modelling between birth and 5 years allowed us to calculate predicted weight, height and BMI at 1 month, 6 months, 1, 3 and 5 years for 1735 children from the French EDEN mother-child cohort. Associations between maternal education and predicted measures of body size were analysed with marginal linear and logistic models, stratified by sex.
In girls, despite a positive association between maternal education and birthweight, an inverse socioeconomic gradient was observed as early as 1 month for BMI. Girls whose mothers had low education levels were shorter on the whole than their counterparts with better-educated mothers, despite their similar weights. In boys, no socioeconomic gradient in BMI was observed at any age, including birth, but positive associations were found as early as 1 month for both weight and height.
The emergence of an inverse socioeconomic gradient in BMI and OW apparently results from a complex pattern of socioeconomic inequalities in weight and height from 1 month onwards. The very start of life thus appears to be an important window of opportunity for addressing socioeconomic inequalities in growth.
Although exposure to cigarette smoking during pregnancy has been associated with alterations of DNA methylation in the cord blood or placental cells, whether such exposure before pregnancy could ...induce epigenetic alterations in the placenta of former smokers has never been investigated.
Our approach combined the analysis of placenta epigenomic (ENCODE) data with newly generated DNA methylation data obtained from 568 pregnant women, the largest cohort to date, either actively smoking during their pregnancy or formerly exposed to tobacco smoking.
This strategy resulted in several major findings. First, among the 203 differentially methylated regions (DMRs) identified by the epigenome-wide association study, 152 showed "reversible" alterations of DNA methylation, only present in the placenta of current smokers, whereas 26 were also found altered in former smokers, whose placenta had not been exposed directly to cigarette smoking. Although the absolute methylation changes were smaller than those observed in other contexts, such as in some congenital diseases, the observed alterations were consistent within each DMR. This observation was further supported by a demethylation of LINE-1 sequences in the placentas of both current (beta-coefficient (β) (95% confidence interval (CI)), - 0.004 (- 0.008; 0.001)) and former smokers (β (95% CI), - 0.006 (- 0.011; - 0.001)) compared to nonsmokers. Second, the 203 DMRs were enriched in epigenetic marks corresponding to enhancer regions, including monomethylation of lysine 4 and acetylation of lysine 27 of histone H3 (respectively H3K4me1 and H3K27ac). Third, smoking-associated DMRs were also found near and/or overlapping 10 imprinted genes containing regions (corresponding to 16 genes), notably including the NNAT, SGCE/PEG10, and H19/MIR675 loci.
Our results pointing towards genomic regions containing the imprinted genes as well as enhancers as preferential targets suggest mechanisms by which tobacco could directly impact the fetus and future child. The persistence of significant DNA methylation changes in the placenta of former smokers supports the hypothesis of an "epigenetic memory" of exposure to cigarette smoking before pregnancy. This observation not only is conceptually revolutionary, but these results also bring crucial information in terms of public health concerning potential long-term detrimental effects of smoking in women.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
Behavioral (externalizing) and emotional (internalizing) problems were showed to be associated with the prenatal environment. Changes in placental DNA methylation was identified as a ...relevant potential mechanism of such association.
Objectives
We aimed to explore the associations between placental DNA methylation and child behavior in order to explore pathways that could link prenatal exposures to child behavior.
Methods
Data including 441 children of 3 years of age from the EDEN mother-child cohort. Child behavior assessed using the Strengths and Difficulties Questionnaire (SDQ). Both hypotheses-driven and exploratory analyses (including epigenome-wide association studies (EWAS) and differentially methylated regions (DMR) analyses) were conducted. The analyses were adjusted for confounding and technical factors and estimated placental cell composition. All the p-values were corrected using a false discovery rate (FDR) procedure for multiple tests.
Results
In the hypothesis-driven analysis,
cg26703534
(
AHRR
), was significantly associated with emotional problems (p
FDR
= 0.03). In the exploratory analyses,
cg09126090
(p
FDR
= 0.04) and
cg10305789
(
PPP1R16B;
p
FDR
< 0.01) were significantly associated with peer-relationship problems and 33 DMRs were significantly associated with at least one of the SDQ subscales. Placental DNA methylation showed more associations with internalizing than externalizing symptoms, especially among girls. DMRs tented to include highly methylated CpGs.
Conclusions
This study investigated for the first time the associations between placental DNA methylation and internalizing and externalizing symptoms in preschoolers. Further analyses, such as consortium meta-analyses would be necessary to confirm and extend our results.
Disclosure of Interest
None Declared
Pregnant women and their unborn child are exposed to a large number of substances during pregnancy. Some of these substances may cross the placenta, resulting in exposure of the foetus. There is ...growing evidence that certain substances could interact to produce a mixture effect. It is therefore essential to identify the main mixtures mothers are exposed to.
This study aimed to identify the major mixtures French pregnant women included in EDEN and ELFE cohorts were exposed to, on the basis of the 441 substances analysed in the second French total diet study. Exposure systems and the composition of substances were identified from co-exposures using sparse non-negative matrix under-approximation to generate the main mixtures. Individuals were clustered to define clusters with similar co-exposure profiles.
Six clusters associated with eight mixtures were identified. For example in ELFE, cluster 2 comprising 10% of the population was characterised by mixtures “Pest-1” mainly contains pesticides and ”TE-F-PAH″ contains trace elements, furans and polycyclic aromatic hydrocarbons. Five other clusters were also described with their associated mixtures. Similar results were observed for EDEN.
This study helps to prioritise mixtures for which it is crucial to investigate possible toxicological effects and to recommend epidemiological studies concerning health effects.
•Exposures to 200 substances were assessed for French women before and during their pregnancy.•Co-exposure data was reduced into two matrices using SNMU method: exposure systems and individuals' coefficients.•Eight main mixtures were defined from exposure systems and six of them were common.•Six clusters of mothers with similar pattern of contaminant intake were identified.
Children with developmental coordination disorder also manifest difficulties in non-motor domains (attentional, emotional, behavioral and socialization skills). Longitudinal studies can help ...disentangle the complex relationships between the development of motor skills and other cognitive domains. This study aims to examine the contribution of early cognitive factors to changes in motor skills during the preschool period. Children (
N
= 1144) from the EDEN mother–child cohort were assessed for motor skills with the Copy Design task (NEPSY battery) and the parent-rated Ages and Stages Questionnaire (fine and gross motor skills scores) at ages 3 and 5–6 years. At 3 years, language skills were evaluated using tests from the NEPSY and ELOLA batteries. Emotional problems, conduct problems, inattention and hyperactivity symptoms, peer relationships and pro-social behavior were assessed with the Strengths and Difficulties Questionnaire (SDQ) also at 3 years. Linear and logistic regression models were performed to examine whether positive and negative changes in motor skills between 3 and 5–6 years are associated with specific cognitive skills at 3 years, while adjusting for a broad range of pre- and postnatal environmental factors. In the linear regression model, the SDQ Inattention symptoms score at 3 years was associated with negative changes in motor skills (standardized
β
= − 0.09, SD = 0.03,
p
value = 0.007) and language skills at 3 years were associated with positive changes in motor skills (standardized
β
= 0.05, SD = 0.02,
p
value = 0.041) during the preschool period. In logistic regression models, the SDQ Inattention symptoms score at 3 years was associated with a higher likelihood of a declining trajectory of motor skills (OR 95% CI = 1.37 1.02–1.84). A higher language skills score at 3 years was associated with an increased likelihood of a resilient trajectory (1.67 1.17–2.39). This study provides a better understanding of the natural history of developmental coordination delays by identifying cognitive factors that predict changes in motor skills between the ages of 3 and 5–6 years.
To study the relationship between pre-pregnancy body mass index (BMI) and weight gain during pregnancy with pregnancy and birth outcomes, with a focus on gestational diabetes and hypertension and ...their role in the association with fetal growth. We studied 1,884 mothers and offspring from the Eden mother–child cohort. Weight before pregnancy (W1) and weight after delivery (W2) were collected and we calculated BMI and net gestational weight gain (netGWG = (W2 − W1)/(weeks of gestation)). Gestational diabetes, hypertension gestational age and birth weight were collected. We used multivariate linear or logistic models to study the association between BMI, netGWG and pregnancy and birth outcomes, adjusting for center, maternal age and height, parity and average number of cigarettes smoked per day during pregnancy. High BMI was more strongly related to the risk of giving birth to a large-for-gestational-age (LGA) baby than high netGWG (odds ratio OR 95% CI of 3.23 1.86–5.60 and 1.61 0.91–2.85, respectively). However, after excluding mothers with gestational diabetes or hypertension the ORs for LGA, respectively weakened (OR 2.57 1.29–5.13) for obese women and strengthened for high netGWG (OR 2.08 1.14–3.80). Low in comparison to normal netGWG had an OR of 2.18 1.20–3.99 for pre-term birth, which became stronger after accounting for blood pressure and glucose disorders (OR 2.70 1.37–5.34). Higher net gestational weight gain was significantly associated with an increased risk of LGA only after accounting for blood pressure and glucose disorders. High gestational weight gain should not be neglected in regard to risk of LGA in women without apparent risk factors.
Sedentary behavior, physical activity and dietary behavior are formed early during childhood and tend to remain relatively stable into later life. No longitudinal studies have assessed the ...independent influence of these three energy balance-related behaviors during toddlerhood on later adiposity. We aimed to analyze the associations between TV/DVD watching time, outdoor play time and dietary patterns at the age of 2 years and child adiposity at the age of 5 years, in boys and girls separately.
This study included 883 children from the French EDEN mother-child cohort. TV/DVD watching time, outdoor play time and dietary intakes were reported by parents in questionnaires when the child was aged 2 years. Two dietary patterns, labeled 'Guidelines' and 'Processed, fast foods', were identified in a previous study. The percentage of body fat (%BF) based on bioelectrical impedance analysis and body mass index were measured at the age of 5 years.
In boys, TV/DVD watching time at the age of 2 years was positively associated with %BF at the age of 5 years (β=0.50 (95% confidence interval: 0.001, 1.00) for those boys with ⩾60 min per day of TV/DVD watching time vs those with ⩽15 min per day, P-value for trend 0.05). In girls, outdoor play was inversely associated with %BF (β=-0.96 (95% confidence interval: -1.60, -0.32) for those in the highest tertile of outdoor play time vs those in the lowest tertile, P=0.001). Overall, at the age of 2 years, dietary patterns were associated with both TV/DVD watching time and outdoor play time, but no significant and independent association was observed between dietary patterns and later adiposity.
This study shows longitudinal and gender-differentiated relations between both TV/DVD watching time and outdoor play time in toddlerhood and later adiposity, whereas evidence for a relation between dietary patterns and subsequent fat development was less conclusive. Early childhood-by the age of 2 years-should be targeted as a critical time for promoting healthy energy balance-related behaviors.
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