Luciana Anselmi

What are the causal effects of breastfeeding on IQ, obesity and blood pressure? Evidence from comparing high-income with middle-income cohorts

Background A novel approach is explored for improving causal inference in observational studies by comparing cohorts from high-income with low- or middle-income countries (LMIC), where confounding structures differ. This is applied to assessing causal effects of breastfeeding on child blood pressure (BP), body mass index (BMI) and intelligence quotient (IQ). Methods Standardized approaches for assessing the confounding structure of breastfeeding by socio-economic position were applied to the British Avon Longitudinal Study of Parents and Children (ALSPAC) (N ≃ 5000) and Brazilian Pelotas 1993 cohorts (N ≃ 1000). This was used to improve causal inference regarding associations of breastfeeding with child BP, BMI and IQ. Analyses were extended to include results from a meta-analysis of five LMICs (N ≃ 10 000) and compared with a randomized trial of breastfeeding promotion. Findings Although higher socio-economic position was strongly associated with breastfeeding in ALSPAC, there was little such patterning in Pelotas. In ALSPAC, breastfeeding was associated with lower BP, lower BMI and higher IQ, adjusted for confounders, but in the directions expected if due to socioeconomic patterning. In contrast, in Pelotas, breastfeeding was not strongly associated with BP or BMI but was associated with higher IQ. Differences in associations observed between ALSPAC and the LMIC meta-analysis were in line with those observed between ALSPAC and Pelotas, but with robust evidence of heterogeneity detected between ALSPAC and the LMIC meta-analysis associations. Trial data supported the conclusions inferred by the cross-cohort comparisons, which provided evidence for causal effects on IQ but not for BP or BMI. Conclusion While reported associations of breastfeeding with child BP and BMI are likely to reflect residual confounding, breastfeeding may have causal effects on IQ. Comparing associations between populations with differing confounding structures can be used to improve causal inference in observational studies.

Early determinants of physical activity in adolescence: prospective birth cohort study

Abstract Objective To examine the effects of early social, anthropometric, and behavioural variables on physical activity in adolescence. Design Prospective birth cohort study. Setting Pelotas, southern Brazil. Participants 4453 adolescents aged 10-12 years participating in the Pelotas 1993 birth cohort study (follow-up rate 87.5%). Main outcome measures Sedentary lifestyle (< 300 minutes of physical activity per week) and median physical activity score (minutes per week). Results The prevalence of a sedentary lifestyle at age 10-12 years was 58.2% (95% confidence interval 56.7% to 59.7%). Risk factors for a sedentary lifestyle in adolescence were female sex, high family income at birth, high maternal education at birth, and low birth order. Weight gain variables at ages 0-1, 1-4, and 4-11 years and overweight at age 1 or 4 years were not significant predictors of physical activity. Levels of physical activity at age 4 years, based on maternal report, were inversely related to a sedentary lifestyle at age 10-12 years. Conclusions Physical activity in adolescence does not seem to be programmed by physiological factors in infancy. A positive association between birth order and activity may be due to greater intensity of play in childhood and adolescence. Tracking of physical activity from age 4 to 10-12 years, however, suggests that genetic factors or early habit formation may be important.

Methodological aspects of the 1993 Pelotas (Brazil) birth cohort study

This paper describes the main methodological aspects of a cohort study, with emphasis on its recent phases, which may be relevant to investigators planning to carry out similar studies. In 1993, a population based study was launched in Pelotas, Southern Brazil. All 5,249 newborns delivered in the citys hospitals were enrolled, and sub-samples were visited at the ages of one, three and six months and of one and four years. In 2004-5 it was possible to trace 87.5% of the cohort at the age of 10-12 years. Sub-studies are addressing issues related to oral health, psychological development and mental health, body composition, and ethnography. Birth cohort studies are essential for investigating the early determinants of adult disease and nutritional status, yet few such studies are available from low and middle-income countries where these determinants may differ from those documented in more developed settings.

Maternal Smoking and Child Psychological Problems: Disentangling Causal and Noncausal Effects

OBJECTIVE: To explore associations of maternal prenatal smoking and child psychological problems and determine the role of causal intrauterine mechanisms. PATIENTS AND METHODS: Maternal smoking and child psychological problems were explored in 2 birth cohorts in Pelotas, Brazil (n = 509, random subsample), and the Avon Longitudinal Study of Parents and Children (ALSPAC) in Britain (n = 6735). Four approaches for exploring causal mechanisms were applied: (1) cross-population comparisons between a high-income and a middle-income country; (2) multiple adjustment for socioeconomic and parental psychological factors; (3) maternal-paternal comparisons as a test of putative intrauterine effects; and (4) searching for specific effects on different behavioral subscales. RESULTS: Socioeconomic patterning of maternal prenatal smoking was stronger in the ALSPAC compared with the Pelotas cohort. Despite this difference in a key confounder, consistency in observed associations was found between these cohorts. In both cohorts, unadjusted maternal smoking was associated with greater offspring hyperactivity, conduct/externalizing problems, and peer problems but not with emotional/internalizing problems. After adjusting for confounders and paternal prenatal smoking, only the association with conduct/externalizing problems persisted in both cohorts (conduct problems in the ALSPAC cohort, odds ratio [OR]: 1.24 [95% confidence interval (CI): 1.07–1.46], P = .005; externalizing problems in the Pelotas cohort, OR: 1.82 [95% CI: 1.19–2.78], P = .005; ORs reflect ordinal odds ratios of maternal smokers having offspring with higher scores). Maternal smoking associations were stronger than paternal smoking associations, although statistical evidence that these associations differed was weak in 1 cohort. CONCLUSION: Evidence from 4 approaches suggests a possible intrauterine effect of maternal smoking on offspring conduct/externalizing problems.

Attention-Deficit/Hyperactivity Disorder Trajectories From Childhood to Young Adulthood: Evidence From a Birth Cohort Supporting a Late-Onset Syndrome.

IMPORTANCE The requirement of a childhood onset has always been a key criterion for the diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults, but recently this requirement has become surrounded by controversy. OBJECTIVE To investigate whether impaired young adults with ADHD symptoms always have a childhood-onset disorder in a population-based longitudinal study. DESIGN, SETTING, AND PARTICIPANTS Participants belonged to the 1993 Pelotas Birth Cohort Study, including 5249 individuals born in Pelotas, Brazil, in 1993. They were followed up to 18 to 19 years of age, with 81.3% retention. The data analysis was performed between August 8, 2015, and February 5, 2016. MAIN OUTCOMES AND MEASURES The ADHD status was first ascertained at 11 years of age using a screening instrument (hyperactivity subscale of the Strength and Difficulties Questionnaire) calibrated for a DSM-IV ADHD diagnosis based on clinical interviews with parents using the Development and Well-Being Assessment. At 18 to 19 years of age, ADHD diagnosis was derived using DSM-5 criteria, except age at onset. We estimated the overlap between these groups assessed at 11 and 18 to 19 years of age and the rates of markers of impairment in these 2 groups compared with those without ADHD. RESULTS At 11 years of age, childhood ADHD (C-ADHD) was present in 393 individuals (8.9%). At 18 to 19 years of age, 492 individuals (12.2%) fulfilled all DSM-5 criteria for young adult ADHD (YA-ADHD), except age at onset. After comorbidities were excluded, the prevalence of YA-ADHD without comorbidities decreased to 256 individuals (6.3%). Children with C-ADHD had a male preponderance not observed among children without ADHD (251 [63.9%] vs 1930 [47.9%] male, P < .001), whereas the YA-ADHD group had a female preponderance (192 [39.0%] vs 1786 [50.4%] male, P < .001). Both groups had increased levels of impairment in adulthood, as measured by traffic incidents, criminal behavior, incarceration, suicide attempts, and comorbidities. However, only 60 children (17.2%) with ADHD continued to have ADHD as young adults, and only 60 young adults (12.6%) with ADHD had the disorder in childhood. CONCLUSIONS AND RELEVANCE The findings of this study do not support the assumption that adulthood ADHD is necessarily a continuation of childhood ADHD. Rather, they suggest the existence of 2 syndromes that have distinct developmental trajectories.

The 11-year follow-up of the 1993 Pelotas (Brazil) birth cohort study: methods

The aim of this study is to describe the methodology of the 2004-2005 follow-up visit of the 1993 Pelotas (Brazil) birth cohort. All children born in Pelotas in 1993 and whose mothers lived in the city at that time were eligible to be enrolled in a longitudinal study. Between July 2004 and March 2005, all cohort participants were sought for a follow-up visit. Several strategies were used to help trace cohort members, including a census of the citys schools and a census of all households in the municipality. The Mortality Information System was monitored in order to identify deaths among cohort members. Of the 5,249 cohort members, 4,452 were interviewed in 2004-5. When added to the 141 deaths, these represent 87.5% of the original cohort. In spite of the logistic and financial difficulties, it is possible to carry out prospective studies with long-term follow-up in the Brazilian context.

Trajectories of maternal depression and offspring psychopathology at 6 years: 2004 Pelotas cohort study.

Background Few studies have addressed the course and severity of maternal depression and its effects on child psychiatric disorders from a longitudinal perspective. This study aimed to identify longitudinal patterns of maternal depression and to evaluate whether distinct depression trajectories predict particular psychiatric disorders in offspring. Methods Cohort of 4231 births followed-up in the city of Pelotas, Brazil. Maternal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale (EPDS) at 3, 12, 24 and 48 months and 6 years after delivery. Psychiatric disorders in 6-year-old children were evaluated through the development and well-being assessment (DAWBA) instrument. Trajectories of maternal depression were calculated using a group-based modelling approach. Results We identified five trajectories of maternal depressive symptoms: a “low” trajectory (34.8%), a “moderate low” (40.9%), a “increasing” (9.0%), a “decreasing” (9.9%), and a “high-chronic” trajectory (5.4%). The probability of children having any psychiatric disorder, as well as both internalizing and externalizing problems, increased as we moved from the “low” to the “high-chronic” trajectory. These differences were not explained by maternal and child characteristics examined in multivariate analyses. Limitations Data on maternal depression at 3-months was available on only a sub-sample. In addition, we had to rely on maternal report of child’s behavior alone. Conclusions The study revealed an additive effect on child outcome of maternal depression over time. We identified a group of mothers with chronic and severe symptoms of depression throughout the first six years of the child life and for this group child psychiatric outcome was particularly compromised.

ADHD in DSM-5: a field trial in a large, representative sample of 18- to 19-year-old adults

Background The DSM criteria for adult attention-deficit/hyperactivity disorder (ADHD) have not been tested in American Psychiatric Association (APA) field trials for either DSM-IV or DSM-5. This study aimed to assess: (a) the prevalence of ADHD according to DSM-5 criteria; (b) the factor solution that provides the best fit for ADHD symptoms; (c) the symptoms with the highest predictive value for clinical impairment; and (d) the best symptomatic threshold for each ADHD dimension (inattention and hyperactivity/impulsivity). Method Trained psychologists evaluated 4000 young adults from the 1993 Pelotas Birth Cohort Study with an instrument covering all DSM-5 ADHD criteria. A series of confirmatory factor analyses (CFAs) tested the best factor structure. Complex logistic regressions assessed differential contributions of each symptom to clinical impairment. Receiver-operating characteristic (ROC) analyses tested which would be the best symptomatic cut-off in the number of symptoms for predicting impairment. Results The prevalence of DSM-5 ADHD was 3.55% [95% confidence interval (CI) 2.98–4.12]. The estimated prevalence of DSM-IV ADHD was 2.8%. CFA revealed that a bifactor model with a single general factor and two specific factors provided the best fit for DSM-5 symptoms. Inattentive symptoms continued to be the most important predictors of impairment in adults. The best cut-offs were five symptoms of inattention and four symptoms of hyperactivity/impulsivity. Conclusions Our results, combined with previous findings, suggest a 27% increase in the expected prevalence of ADHD among young adults, comparing DSM-IV to DSM-5 criteria. The DSM-5 symptomatic organization derived a similar factor structure for adults as DSM-IV symptoms. Data using DSM-5 criteria support lowering the symptomatic threshold for diagnosing ADHD in adults.

Continuity of behavioral and emotional problems from pre-school years to pre-adolescence in a developing country.

BACKGROUND All previous longitudinal community studies assessing the continuity of child behavioral/emotional problems were conducted in developed countries. METHOD Six hundred and one children randomly selected from a Brazilian birth cohort were evaluated for behavioral/emotional problems through mother interview at 4 and 12 years with the same standard procedure - Child Behavior Checklist (CBCL). RESULTS CBCL Total Problem score presented a medium stability (r = .42) with externalizing problems showing higher stability and more homotypic continuity than internalizing problems. Of the children presenting deviant scores at the age of 4, only 31% remained deviant at the age of 12 (p < .001). A deviant CBCL Total Problem score at 12 years old was predicted by Rule-Breaking Behavior [OR = 7.46, 95% CI 2.76-20.19] and Social Problems [OR = 3.56, 95% CI 1.36-9.30] scores at 4 years of age. Either Rule-Breaking or Aggressive Behavior - externalizing syndromes - were part of the predictors for the three broad-band CBCL scores and six out of the eight CBCL syndromes. CONCLUSIONS Behavioral/emotional problems in preschool children persist moderately up to pre-adolescence in a community sample. Externalizing problems at the age of 4 comprise the developmental history of most behavioral/emotional problems at pre-adolescence. Our findings concur with findings from developed countries and are quite similar for continuity, stability and predictability.

Gene-environment interaction in externalizing problems among adolescents: evidence from the Pelotas 1993 Birth Cohort Study

Background The study of gene–environment interactions (G × E) is one of the most promising strategies to uncover the origins of mental disorders. Replication of initial findings, however, is essential because there is a strong possibility of publication bias in the literature. In addition, there is a scarcity of research on the topic originated from low- and middle-income countries (LMIC). The aim of this study was to replicate G × E hypotheses for externalizing problems among adolescents in a middle-income country. Methods As part of the Pelotas 1993 Birth Cohort Study, 5,249 children were enrolled at birth and followed up to the age of 15 years, with an 85.7% retention rate. We sought an interaction between the homozygosity of the 10-repeat allele at the dopamine transporter (DAT1) gene and prenatal maternal smoking in the development of hyperactivity problems during adolescence assessed by the Strengths and Difficulties Questionnaire. We also tested for an interaction between the uVNTR polymorphism at the monoamine oxidase A (MAOA) and the experience of childhood maltreatment in the occurrence of conduct problems among adolescent boys. Results Although there was a clear association between prenatal maternal smoking and hyperactivity scores in adolescence (p < 0.001), no main genetic or interaction effects for the DAT1 gene were detected. Similarly, childhood maltreatment showed to be associated with conduct problems among boys (p < 0.001), with no observable main genetic or interaction effects for the MAOA gene. Conclusions In the largest mental health G × E study performed in a LMIC to date, we did not replicate previous positive findings from the literature. Despite the presence of main environmental effects, there was no evidence of effect modification by genotype status. Additional replication efforts to measure G × E are needed to better understand the origins of mental health and illness, especially in LMIC.