Associations of Cannabis and Cigarette Use with Depression and Anxiety at Age 18: Findings from the Avon Longitudinal Study of Parents and Children

Introduction

Substance use is associated with common mental health disorders, but the causal effect of specific substances is uncertain. We investigate whether adolescent cannabis and cigarette use is associated with incident depression and anxiety, while attempting to account for confounding and reverse causation.

Methods

We used data from ALSPAC, a UK birth cohort study, to investigate associations between cannabis or cigarettes (measured at age 16) and depression or anxiety (measured at age 18), before and after adjustment for pre-birth, childhood and adolescent confounders. Our imputed sample size was 4561 participants.

Results

Both cannabis (unadjusted OR 1.50, 95% CI 1.26, 1.80) and cigarette use (OR 1.37, 95% CI 1.16, 1.61) increased the odds of developing depression. Adjustment for pre-birth and childhood confounders partly attenuated these relationships though strong evidence of association persisted for cannabis use. There was weak evidence of association for cannabis (fully adjusted OR 1.30, 95% CI 0.98, 1.72) and insufficient evidence for association for cigarette use (fully adjusted OR = 0.97, 95% CI 0.75, 1.24) after mutually adjusting for each other, or for alcohol or other substance use. Neither cannabis nor cigarette use were associated with anxiety after adjustment for pre-birth and childhood confounders.

Conclusions

Whilst evidence of association between cannabis use and depression persisted after adjusting for pre-term and childhood confounders, our results highlight the difficulties in trying to estimate and interpret independent effects of cannabis and tobacco on psychopathology. Complementary methods are required to robustly examine effects of cannabis and tobacco on psychopathology.     

Dietary Patterns,n-3 Fatty Acids Intake from Seafood and High Levels of Anxiety Symptoms during Pregnancy: Findings from the Avon Longitudinal Study of Parents and Children

Background

Little is known about relationships between dietary patterns, n-3 polyunsaturated fatty acids (PUFA) intake and excessive anxiety during pregnancy.

Objective

To examine whether dietary patterns and n-3 PUFA intake from seafood are associated with high levels of anxiety during pregnancy.

Design

Pregnant women enrolled from 1991–1992 in ALSPAC (n 9,530). Dietary patterns were established from a food frequency questionnaire using principal component analysis. Total intake of n-3 PUFA (grams/week) from seafood was also examined. Symptoms of anxiety were measured at 32 weeks of gestation with the Crown-Crisp Experiential Index; scores ≥9 corresponding to the 85^th percentile was defined as high anxiety symptoms. Multivariate logistic regression models were used to estimate the OR and 95% CI, adjusted by socioeconomic and lifestyle variables.

Results

Multivariate results showed that women in the highest tertile of the health-conscious (OR 0.77; 0.65–0.93) and the traditional (OR 0.84; 0.73–0.97) pattern scores were less likely to report high levels of anxiety symptoms. Women in the highest tertile of the vegetarian pattern score (OR 1.25; 1.08–1.44) were more likely to have high levels of anxiety, as well as those with no n-3 PUFA intake from seafood (OR 1.53; 1.25–1.87) when compared with those with intake of >1.5 grams/week.

Conclusions

The present study provides evidence of a relationship between dietary patterns, fish intake or n-3 PUFA intake from seafood and symptoms of anxiety in pregnancy, and suggests that dietary interventions could be used to reduce high anxiety symptoms during pregnancy.     

Vitamin B-12 Status during Pregnancy and Child’s IQ at Age 8: A Mendelian Randomization Study in the Avon Longitudinal Study of Parents and Children

Vitamin B-12 is essential for the development and maintenance of a healthy nervous system. Brain development occurs primarily in utero and early infancy, but the role of maternal vitamin B-12 status during pregnancy on offspring cognitive function is unclear. In this study we assessed the effect of vitamin B-12 status in well-nourished pregnant women on the cognitive ability of their offspring in a UK birth cohort (ALSPAC). We then examined the association of SNPs in maternal genes FUT2 (rs492602) and TCN2 (rs1801198, rs9606756) that are related to plasma vitamin B-12, with offspring IQ. Observationally, there was a positive association between maternal vitamin B-12 intake and child’s IQ that was markedly attenuated after adjustment for potential confounders (mean difference in offspring IQ score per doubling of maternal B-12 intake, before adjustment: 2.0 (95% CI 1.3, 2.8); after adjustment: 0.7 (95% CI −0.04, 1.4)). Maternal FUT2 was weakly associated with offspring IQ: mean difference in IQ per allele was 0.9 (95% CI 0.1, 1.6). The expected effect of maternal vitamin B-12 on offspring IQ, given the relationships between SNPs and vitamin B-12, and SNPs and IQ was consistent with the observational result. Our findings suggest that maternal vitamin B-12 may not have an important effect on offspring cognitive ability. However, further examination of this issue is warranted.     

Associations of Maternal Diabetes During Pregnancy with Overweight in Offspring: Results from the Prospective TEDDY Study

Objective: This study aimed to determine the relationship between different forms of, and potential pathways between, maternal diabetes and childhood obesity at different ages. Methods: Prospective cohort data from The Environmental Determinants of Diabetes in the Young (TEDDY) study, which was composed of 5,324 children examined from 0.25 to 6 years of age, were analyzed. Cross‐sectional and longitudinal analyses taking into account potential confounders and effect modifiers such as maternal prepregnancy BMI and birth weight z scores were performed. Results: Offspring of mothers with gestational diabetes mellitus (GDM) or type 1 diabetes mellitus (T1DM) showed a higher BMI standard deviation score and increased risk for overweight and obesity at 5.5 years of age than offspring of mothers without diabetes. While these associations could be substantially explained by maternal prepregnancy BMI in offspring of mothers with GDM, significant associations disappeared after adjustment for birth weight z scores in offspring of T1DM mothers. Furthermore, overweight risk became stronger with increasing age in offspring of mothers with diabetes compared with offspring of mothers without diabetes. Conclusions: Maternal diabetes is associated with increased risk of offspring overweight, and the association appears to get stronger as children grow older. Indeed, intrauterine exposure to maternal T1DM may predispose children to later obesity through increased birth weight, while maternal BMI is more important in children exposed to GDM.     

Metabolic Profile in Early Pregnancy Is Associated with Offspring Adiposity at 4 Years of Age: The Rhea Pregnancy Cohort Crete,Greece

ContextMaternal 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.ObjectiveOur 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.ResultsPre-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 5.10mm (95%CI: 2.49, 7.71) at 4 years of age. These associations were more pronounced in girls. An increase of 40mg/dl in fasting serum cholesterol levels in early pregnancy was associated with greater skinfold thickness by 3.30mm (95%CI: 1.41, 5.20) at 4 years of age after adjusting for pre-pregnancy BMI and several other confounders. An increase of 10mmHg 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 1.71mm (95% CI: 0.57, 2.86) at 4 years of age.ConclusionsMetabolic dysregulation in early pregnancy may increase the risk of obesity at preschool age.     

A Preference Based Measure of Complementary Feeding Quality: Application to the Avon Longitudinal Study of Parents and Children

This paper presents the development of the Complementary Feeding Utility Index (CFUI), a composite index aimed to measure adherence to infant feeding guidelines. Through an axiomatic characterization this paper shows the advantages in using the CFUI are the following: it avoids the use of arbitrary cut-offs, and by converting observed diet preferences into utilities, summing the score is meaningful. In addition, as the CFUI is designed to be scored continuously, it allows the transition from intake of beneficial foods (in low quantities) and intake of detrimental foods (in high quantities) to be more subtle. The paper first describes the rationale being the development of the CFUI and then elaborates on the methodology used to develop the CFUI, including the process of selecting the components. The methodology is applied to data collected from the Avon Longitudinal Study of Parents and Children to show the advantages of the CFUI over traditional diet index approaches. Unlike traditional approaches, the distribution of the CFUI does not peak towards mean value but distributes evenly towards the tails of the distribution.     

Maternal Insulin Sensitivity During Pregnancy Predicts Infant Weight Gain and Adiposity at 1 Year of Age

Emerging evidence suggests that fetal environmental exposures impact on future development of obesity. The objectives of this study were to assess the relationships between (i) maternal insulin sensitivity and glucose tolerance status in pregnancy and (ii) early infant weight gain and adiposity in the first year of life. In this prospective cohort study, 301 women underwent oral glucose tolerance testing for assessment of glucose tolerance status and insulin sensitivity (IS_OGTT) in pregnancy. Their infants underwent anthropometric assessment at 12 months of age, including determination of weight gain in the first year of life and sum of skinfold thickness (SFT), a measure of infant adiposity. Infant weight gain and sum of SFT at 12 months did not differ according to maternal glucose tolerance status. On univariate analyses, weight gain from 0 to 12 months and sum of SFT were negatively associated with maternal IS_OGTT during pregnancy. On multiple linear regression analysis, negative independent predictors of weight gain from 0 to 12 months were maternal IS_OGTT during pregnancy (t = ?2.73; P = 0.007), infant female gender (t = ?3.16; P = 0.002), and parental education (t = ?1.98; P = 0.05), whereas white ethnicity was a positive independent predictor (t = 2.68; P = 0.008). Maternal IS_OGTT (t = ?2.7; P = 0.008) and parental education (t = ?2.58; P = 0.01) were independent negative predictors of sum of SFT at 12 months. Independent of maternal glucose tolerance status, maternal insulin resistance during pregnancy is associated with increased infant weight gain and adiposity over the first year of life. Further longitudinal study to evaluate obesity in this group of children will increase our understanding of the contribution of the intrauterine environment to their long‐term health.     

Prospective Investigation of Video Game Use in Children and Subsequent Conduct Disorder and Depression Using Data from the Avon Longitudinal Study of Parents and Children

There is increasing public and scientific concern regarding the long-term behavioural effects of video game use in children, but currently little consensus as to the nature of any such relationships. We investigated the relationship between video game use in children, degree of violence in games, and measures of depression and a 6-level banded measure of conduct disorder. Data from the Avon Longitudinal Study of Parents and Children were used. A 3-level measure of game use at age 8/9 years was developed, taking into account degree of violence based on game genre. Associations with conduct disorder and depression, measured at age 15, were investigated using ordinal logistic regression, adjusted for a number of potential confounders. Shoot-em-up games were associated with conduct disorder bands, and with a binary measure of conduct disorder, although the strength of evidence for these associations was weak. A sensitivity analysis comparing those who play competitive games to those who play shoot-em-ups found weak evidence supporting the hypothesis that it is violence rather than competitiveness that is associated with conduct disorder. However this analysis was underpowered, and we cannot rule out the possibility that increasing levels of competition in games may be just as likely to account for the observed associations as violent content. Overall game exposure as indicated by number of games in a household was not related to conduct disorder, nor was any association found between shoot-em-up video game use and depression.     

Maternal Functional Hemodynamics in the Second Half of Pregnancy: A Longitudinal Study

Objective

Cardiovascular response to passive leg raising (PLR) is useful in assessing preload reserve, but it has not been studied longitudinally during pregnancy. We aimed to investigate gestational age associated serial changes in maternal functional hemodynamics and establish longitudinal reference ranges for the second half of pregnancy.

Materials and Methods

This was a prospective longitudinal study on 98 healthy pregnant women who were examined 3–5 times during 20–40 weeks of gestation (a total of 441 observations). Maternal cardiac function and systemic hemodynamics were assessed at baseline and 90 seconds after PLR using impedance cardiography (ICG). The main outcome measures were gestational age specific changes in ICG-derived variables of maternal cardiovascular function and functional hemodynamic response to PLR.

Results

Hemodynamic response to PLR varied during pregnancy. PLR led to an insignificant increase in stroke volume during 20⁺⁰ to 31⁺⁶ weeks, but later in gestation the stroke volume was slightly lower at PLR compared to baseline. PLR caused no significant change in cardiac output between 20⁺⁰ and 23⁺⁶ weeks and a significant decrease after 24⁺⁰ weeks. A decrease in heart rate, mean arterial pressure, and cardiac contractility was observed during PLR throughout the second half of pregnancy. Systemic vascular resistance was reduced by PLR up to 32⁺⁰ weeks, but increased slightly thereafter.

Conclusion

Healthy pregnant women appear to have limited preload reserve and reduced cardiac contractility, especially in the third trimester, which makes them vulnerable to fluid overload and cardiac failure.     

Association of Adiposity and Mental Health Functioning across the Lifespan: Findings from Understanding Society (The UK Household Longitudinal Study)

Background

Evidence on the adiposity-mental health associations is mixed, with studies finding positive, negative or no associations, and less is known about how these associations may vary by age.

Objective

To examine the association of adiposity -body mass index (BMI), waist circumference (WC) and percentage body fat (BF%)- with mental health functioning across the adult lifespan.

Methods

Data from 11,257 participants (aged 18+) of Understanding Society: the UK Household Longitudinal Study (waves 2 and 3, 5/2010-7/2013) were employed. Regressions of mental health functioning, assessed by the Mental Component Summary (MCS-12) and the General Health Questionnaire (GHQ-12), on adiposity measures (continuous or dichotomous indicators) were estimated adjusted for covariates. Polynomial age-adiposity interactions were estimated.

Results

Higher adiposity was associated with poorer mental health functioning. This emerged in the 30s, increased up to mid-40s (all central adiposity and obesity-BF% measures) or early 50s (all BMI measures) and then decreased with age. Underlying physical health generally accounted for these associations except for central adiposity, where associations remained statistically significant from the mid-30s to50s. Cardiovascular, followed by arthritis and endocrine, conditions played the greatest role in attenuating the associations under investigation.

Conclusions

We found strong age-specific patterns in the adiposity-mental health functioning association that varied across adiposity measures. Underlying physical health had the dominant role in attenuating these associations. Policy makers and health professionals should target increased adiposity, mainly central adiposity, as it is a risk factor for poor mental health functioning in those aged between mid-30s to 50 years.     

Maternal Serum and Breast Milk Vitamin D Levels: Findings from the Universiti Sains Malaysia Pregnancy Cohort Study

Background

Vitamin D deficiency has become a global health issue in pregnant women. This study aimed to assess the adequacy of maternal vitamin D status by measuring maternal serum and breast milk 25-hydroxyvitamin D [25(OH)D] levels and to determine the association between maternal serum and milk 25(OH)D levels.

Methods

Data was obtained from the Universiti Sains Malaysia Pregnancy Cohort Study. This study was conducted from April 2010 to December 2012 in the state of Kelantan, Malaysia. Blood samples from pregnant women aged 19 to 40 years were drawn in the second and third trimesters of pregnancy, while breast milk samples at delivery, 2, 6 and 12 months postpartum were collected to analyze for 25(OH)D levels. A total of 102 pregnant women were included in the analysis.

Results

Vitamin D deficiency [25(OH)D <50 nmol/L] was detected in 60% and 37% of women in the second and third trimesters of pregnancy, respectively. There were 6% and 23% of women who reached normal level of vitamin D status in the second trimester and the third trimester, respectively. Multivitamin intakes during pregnancy were significantly associated with higher serum 25(OH)D levels in the second trimester (β = 9.16, p = 0.005) and the third trimester (β = 13.65, p = 0.003). 25(OH)D levels in breast milk during the first year of lactation ranged from 1.01 to 1.26 nmol/L. Higher maternal serum 25(OH)D level in the second trimester of pregnancy was associated with an elevated level of 25(OH)D in breast milk at delivery (β = 0.002, p = 0.026).

Conclusions

This study shows that high proportions of Malay pregnant women are at risk of vitamin D deficiency. Maternal vitamin D status in the second trimester of pregnancy was found to influence vitamin D level in breast milk at delivery.     

Effect of Maternal Schistosoma mansoni Infection and Praziquantel Treatment During Pregnancy on Schistosoma mansoni Infection and Immune Responsiveness among Offspring at Age Five Years

Introduction

Offspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S. mansoni during pregnancy on prevalence of S. mansoni and immune responsiveness among offspring at age five years.

Methods

In a trial in Uganda (ISRCTN32849447, http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women treated with praziquantel or placebo during pregnancy were examined for S. mansoni infection and for cytokine and antibody responses to SWA and SEA, as well as for T cell expression of FoxP3, at age five years.

Results

Of the 1343 children examined, 32 (2.4%) had S. mansoni infection at age five years based on a single stool sample. Infection prevalence did not differ between children of treated or untreated mothers. Cytokine (IFNγ, IL-5, IL-10 and IL-13) and antibody (IgG1, Ig4 and IgE) responses to SWA and SEA, and FoxP3 expression, were higher among infected than uninfected children. Praziquantel treatment of S. mansoni during pregnancy had no effect on immune responses, with the exception of IL-10 responses to SWA, which was higher in offspring of women that received praziquantel during pregnancy than those who did not.

Conclusion

We found no evidence that maternal S. mansoni infection and its treatment during pregnancy influence prevalence and intensity of S. mansoni infection or effector immune response to S. mansoni infection among offspring at age five years, but the observed effects on IL-10 responses to SWA suggest that maternal S. mansoni and its treatment during pregnancy may affect immunoregulatory responsiveness in childhood schistosomiasis. This might have implications for pathogenesis of the disease.     

Adiposity and Diabetes Risk in Adults with Prediabetes: Heterogeneity of Findings Depending on Age and Anthropometric Measure

Objective

The study aimed to evaluate the effect of age on diabetes incidence by general and central adiposity after 3‐year follow‐up in adults with prediabetes.

Methods

Data were taken from a cohort of 1,184 subjects with prediabetes included in The Cohort Study in Primary Health Care on the Evolution of Patients with Prediabetes (PREDAPS). General adiposity was defined using body mass index (BMI), and central adiposity was defined with waist circumference and waist to height ratio. Data were analyzed by age groups 30 to 59 and 60 to 74 years. The association between adiposity and diabetes incidence was assessed using hazard ratios (HR).

Results

Adjusting for sociodemographic characteristics, lifestyles, and metabolic parameters, diabetes HR for central adiposity based on the waist circumference clinical cutoff were 2.14 (1.12‐4.09) and 1.48 (0.80‐2.74) for people aged 30 to 59 and 60 to 74 years, respectively. In the model additionally adjusted for BMI, diabetes HR were 2.65 (1.24‐5.65) and 1.33 (0.68‐2.59), respectively. The use of a 1‐SD increase rather than cutoff points did not alter this pattern. Similar findings were observed with central adiposity based on waist to height ratio.

Conclusions

The association of central adiposity with type 2 diabetes incidence was lower for people in the older age group than for those in the younger age group.

     

Effects of Gestational Cadmium Exposure on Pregnancy Outcome and Development in the Offspring at Age 4.5 Years

The objective of the present study was to evaluate the potential effect of maternal cadmium exposure on pregnancy outcome and development in the offspring at age 4.5 years. Between November 2002 and December 2003, 109 normal pregnant women were enrolled in our cohort from Da-Ye Country, Hubei Province in Central China. The placental, whole blood, and cord blood levels of cadmium were determined by inductively coupled plasma mass spectrometer (ICP-MS). The 106 children at 4.5 years of age given birth by the aforementioned women were followed up and the following rate was 97.25%. Detailed questionnaire surveys, anthropometric measurements were performed, and IQ development was evaluated by Wechsler Preschool and Primary Scale of Intelligence Revised Edition (WPPSI-R). Multiple linear regression analysis indicated that cord blood cadmium level was significantly negatively correlated with fetus development. Low birth weight (less than 2,500 g) occurred significantly more frequently in infants with higher cord blood cadmium than in those exposed to lower levels of cord blood cadmium. Significantly negative correlation was found between cord blood cadmium exposure and WPPSI-R IQ full score after controlling for confounding variables. It was concluded that cord blood cadmium concentration was a factor that influenced fetus growth and later IQ development.     

Sex-Differences in the Metabolic Health of Offspring of Parents with Diabetes: A Record-Linkage Study

Maternal diabetes in pregnancy affects offspring health. The impact of parental diabetes on offspring health is unclear. We investigated the impact of parental diabetes on the metabolic-health of adult-offspring who did not themselves have diabetes. Data from the Generation Scotland: Scottish Family Health Study, a population-based family cohort, were record-linked to subjects’ own diabetes medical records. From F₀-parents, we identified F₁-offspring of: mothers with diabetes (OMD, n = 409), fathers with diabetes (OFD, n = 468), no parent with diabetes (ONoPD, n = 2489). Metabolic syndrome, body, biochemical measurements and blood-pressures were compared between F₁-offspring groups by sex. A higher proportion of female OMD had metabolic syndrome than female OFD or ONoPD (P<0.0001). In female offspring, predictors of metabolic syndrome were: having a mother with diabetes (OR = 1.78, CI 1.03–3.07, [reference ONoPD]), body mass index (BMI, OR = 1.21, CI 1.13–1.30) and age (OR = 1.03, CI 1.01–1.06). In male offspring, predictors of metabolic syndrome were: BMI (OR = 1.18, CI 1.09–1.29) and percent body-fat (OR = 1.12, CI 1.05–1.19). In both sexes, OMD had higher blood-pressures than OFD (P<0.0001). In females, OMD had higher glucose (P<0.0001) and percent body-fat (P<0.0001) compared with OFD or ONoPD. OMD and OFD both had increased waist-measurements (P<0.0001), BMI (P<0.0001) and percent body-fat (P<0.0001) compared with ONoPD. Female OMD and OFD had lower HDL-cholesterol levels (P<0.0001) than female ONoPD. Parental diabetes is associated with higher offspring-BMI and body-fat. In female offspring, maternal diabetes increased the odds of metabolic syndrome, even after adjusting for BMI. Further investigations are required to determine the mechanisms involved.     

Associations between Passive Maternal Smoking during Pregnancy and Preterm Birth: Evidence from a Meta-Analysis of Observational Studies

Previous studies investigating the relationship between passive maternal smoking and preterm birth reveal inconsistent results. We conducted the current meta-analysis of observational studies to evaluate the relationship between passive maternal smoking and preterm birth. We identified relevant studies by searching PubMed, EMBASE, and ISI Web of Science databases. We used random-effects models to estimate summary odds ratios (SORs) and 95% confidence intervals (CIs) for aforementioned association. For the analysis, we included 24 studies that involved a total of 5607 women who experienced preterm birth. Overall, the SORs of preterm birth for women who were ever exposed to passive smoking versus women who had never been exposed to passive smoking at any place and at home were 1.20 (95%CI = 1.07–1.34,I² = 36.1%) and 1.16 (95%CI = 1.04–1.30,I² = 4.4%), respectively. When we conducted a stratified analysis according to study design, the risk estimate was slightly weaker in cohort studies (SOR = 1.10, 95%CI = 1.00–1.21,n = 16) than in cross-sectional studies (SOR = 1.47, 95%CI = 1.23–1.74,n = 5). Additionally, the associations between passive maternal smoking and preterm birth were statistically significant for studies conducted in Asia (SOR = 1.26, 95%CI = 1.05–1.52), for studies including more than 100 cases of preterm birth (SOR = 1.22, 95%CI = 1.05–1.41), and for studies adjusted for maternal age (SOR = 1.27,95%CI = 1.09–1.47), socioeconomic status and/or education (SOR = 1.28, 95%CI = 1.10–1.49), body mass index (SOR = 1.33, 95%CI = 1.04–1.71), and parity (SOR = 1.27, 95%CI = 1.13–1.43). Our findings demonstrate that passive maternal smoking is associated with an increased risk of preterm birth. Future prospective cohort studies are warranted to provide more detailed results stratified by passive maternal smoking during different trimesters of pregnancy and by different types and causes of preterm birth.