[Association between birth conditions and bone mineral density in adults from the 1982 and 1993 birth cohorts in Pelotas, Rio Grande do Sul State, Brazil]. / Associação entre as condições de nascimento e a densidade mineral óssea de adultos das coortes de nascimentos de 1982 e 1993 de Pelotas, Rio Grande do Sul, Brasil.

This study assessed the association of birth weight, gestational age, and intrauterine growth with bone mineral density (BMD) at 22 and 30 years of age in the 1982 and 1993 birth cohorts in Pelotas, Rio Grande do Sul State, Brazil. BMD was measured by dual-energy X-ray absorptiometry (DXA) and the association was assessed using analysis of variance. Multiple linear regression was used to control for confounding factors: sex; household income at birth; maternal smoking during pregnancy; maternal schooling; maternal ethnicity/skin color; and pre-pregnancy body mass index. The study tested whether body fat in adulthood was a mediator of the association analyzed, using the G-computation Formula. A total of 6,803 participants from the 1982 and 1993 cohorts were evaluated at 30 and 22 years of age, respectively. Birth weight was associated with BMD at all sites, with a greater difference at the femoral neck. Individuals born weighing less than 2,000g had on average -0.036g/cm2 (95%CI: -0.064; -0.008) of BMD in the femoral neck than individuals weighing more than 3,500g. Individuals with an intrauterine growth z-score at least 1.28 standard deviation below the mean had an average of -0.013g/cm2 (95%CI: -0.024; -0.002) of BMD in the lumbar spine compared with individuals with an above-average z-score. The mediation analysis showed that body fat in adulthood did not mediate the association. Birth conditions have been associated with BMD in adulthood and the identification of early factors related to bone loss is essential due to the demographic inversion that has been taking place in low- and middle-income countries.

Este estudo avaliou a associação do peso ao nascer, idade gestacional e crescimento intrauterino com a densidade mineral óssea (DMO) aos 22 e 30 anos, nas coortes de nascimentos de 1982 e 1993 de Pelotas, Rio Grande do Sul, Brasil. A DMO foi medida por absorciometria por raios X com dupla energia (DXA), a associação foi avaliada usando análise de variância e a regressão linear múltipla para o controle de confundimento por: sexo, renda familiar ao nascer, tabagismo materno na gestação, escolaridade materna, cor da pele materna e índice de massa corporal pré-gestacional. Foi testado se a gordura corporal na vida adulta era mediadora da associação analisada, por meio da G-computation Formula. Foram avaliados 6.803 participantes das coortes de 1982 e 1993, aos 30 e 22 anos, respectivamente. O peso ao nascer teve associação com a DMO em todos os sítios, com maior diferença no colo femoral. Os nascidos com menos de 2.000g apresentaram, em média, -0,036g/cm2 (IC95%: -0,064; -0,008) de DMO no colo femoral em comparação àqueles com mais de 3.500g. Aqueles com escore-z de crescimento intrauterino com pelo menos 1,28 desvio padrão abaixo da média apresentaram, em média, -0,013g/cm2 (IC95%: -0,024; -0,002) de DMO na coluna lombar, em relação aos com escore-z acima da média. A análise de mediação mostrou que gordura corporal na idade adulta não mediou a associação. As condições de nascimento foram associadas com a densidade mineral óssea na vida adulta, e a identificação dos fatores precoces relacionados à perda de DMO é essencial devido à inversão demográfica em progresso em países de média e baixa renda.

Este estudio evaluó la asociación del peso al nacer, la edad gestacional y el crecimiento intrauterino con la densidad mineral ósea (DMO) a los 22 y 30 años de edad, en las Cohortes de Nacimiento de 1982 y 1993 de Pelotas, Rio Grande do Sul, Brasil. La DMO se midió mediante absorciometría de rayos X de doble emisión (DXA), y la asociación se evaluó mediante ANOVA y regresión lineal múltiple para controlar la confusión por sexo, ingresos familiares al nacer, tabaquismo materno durante el embarazo, escolaridad materna, color de piel materno e índice de masa corporal antes del embarazo. Se comprobó si la grasa corporal en la edad adulta era un mediador de la asociación analizada, utilizando G-computation Formula. Se evaluaron 6.803 participantes de las cohortes 82 y 93, de 30 y 22 años, respectivamente. El peso al nacer se asoció con la DMO en todos los sitios, con la mayor diferencia en el cuello femoral. Los nacidos con un peso inferior a 2.000g tuvieron una media de -0,036g/cm2 (IC95%: -0,064; -0,008) de DMO en el cuello femoral, que aquellos con más de 3.500g. Aquellos con una puntuación z de crecimiento intrauterino de al menos 1,28 desviaciones estándar por debajo de la media presentaron un promedio de -0,013g/cm2 (IC95%: -0,024; -0,002) de DMO en la columna lumbar, con relación a aquellos con un puntaje z superior a la media. El análisis de mediación mostró que la grasa corporal en la edad adulta no medió la asociación. Las condiciones de nacimiento se asociaron con la DMO en la edad adulta, y la identificación temprana de factores relacionados con la pérdida de DMO es esencial debido a la inversión demográfica que ha estado ocurriendo en los países de ingresos medios y bajos.

Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study.

BACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality. OBJECTIVE: This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern. STUDY DESIGN: INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile. RESULTS: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women ≤100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns. CONCLUSION: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

Structural Relationships between Asthma and Dental Caries in Children: A Birth Cohort Study in Southern Brazil.

INTRODUCTION: There is an inconclusive causal association between asthma symptoms and dental caries in the primary dentition. This study aimed to investigate, using SEM (structural equation modeling), a possible causal relation between asthma and dental caries in the primary dentition. METHODS: Using data from the 2004 Pelotas Birth Cohort Study, a sub-sample of 1,303 individuals was selected. Dental caries was clinically evaluated at 5 years old based on decayed, missing, and filled tooth (dmft) index criteria. Asthma-related symptoms (wheezing and shortness of breath) at 1- and 4-year-olds composed a latent variable and were the main exposures to caries occurrence. SEM was used to identify possible direct, indirect, and mediated effects of asthma in primary dentition dental caries. RESULTS: The general prevalence of caries at age 5 was 1.95 (SD: 3.56). When comparing the dmft values for children with asthma symptoms and those without, they presented similar values in both periods where asthma symptoms were evaluated (1- and 4-year-old). SEM analysis showed that asthma was neither directly nor indirectly related to dental caries. CONCLUSION: Asthma, using a latent variable constructed based on asthma symptoms, showed no causal effect on dental caries occurrence in the primary dentition.

Evaluation of genomic factors and early childhood stimulation on intelligence in children from a Brazilian birth cohort: The primary role of independent factors.

BACKGROUND: Childhood cognitive abilities are a predictor of health outcomes and adult income potential. Identifying factors associated with childhood intelligence and their interactions is essential in behavioral research. We assessed the impact of genetic variants and early child stimulation (ECS) on child intelligence and examined their possible interaction as potential modifiers of IQ in a population-based longitudinal study. METHODS: Participants of the 2004 Pelotas Birth Cohort study (N = 4231) underwent intelligent quotient (IQ) by WISC-III assessment at 6 years of age. At 24 and 48-months, mothers answered five ECS marker questions, whose sum was used to create a score. The polygenic score for intelligence (IQ-PGS) was constructed from the GWAS-weighted estimate of cognition. Association was assessed using multiple linear regression models adjusted for maternal, family, and child confounding variables. To explore the possible influence of skin color and ethnoracial classification, the regression models were stratified according to the skin color variable, as a sensitivity analysis. RESULTS: In the adjusted analysis, IQ-PGS (ß = 0.79, 95% confidence interval [95% CI] 0.26;1.31) as well as ECS (ß = 2.34; 95% CI: 1.76;2.92) were associated with IQ in this sample. The association between IQ-PGS and IQ was significant only in the white Brazilian group in the sensitivity analysis. However, there was no interaction between IQ-PGS and ECS on IQ (p(IQ-PGS x ECS) = 0.46). CONCLUSIONS: ECS did not modify the impact of genetic potential on intellectual development during childhood, suggesting that genetic factors and ECS exert independent effects on the IQ levels of children.

Premorbid intelligence quotient and school failure as risk markers for bipolar disorder and major depressive disorder.

Mood disorders significantly impact global health, with MDD ranking as the second leading cause of disability in the United States and BD ranking 18th. Despite their prevalence and impact, the relationship between premorbid intelligence and the subsequent development of BD and MDD remains inconclusive. This study investigates the potential of premorbid Intelligence Quotient (IQ) and school failure frequency as risk factors for Bipolar Disorder (BD) and Major Depressive Disorder (MDD) in a birth cohort setting. We analyze data from the Pelotas population-based birth cohort study, comprising 3580 participants aged 22, who had no prior mood disorder diagnoses. Utilizing regression models and accounting for potential confounders, we assess the impact of IQ and school failure, measured at age 18, on the emergence of BD and MDD diagnoses at age 22, using individuals without mood disorders as comparators. Results reveal that lower IQ (below 70) at 18 is associated with an increased risk of BD (Adjusted Odds Ratio [AOR] 1.75, 95%CI: 1.00-3.09, p < 0.05), while higher IQ (above 120) is linked to MDD (AOR 2.16, 95%CI: 1.24-3.75, p < 0.001). Moreover, an elevated number of school failures is associated with increased BD risk (AOR 1.23, 95%CI: 1.11-1.41, p < 0.001), particularly for BD type 1 (AOR 1.36, 95% CI: 1.17-1.58, p < 0.001). These findings offer insights into the distinct premorbid intellectual characteristics of BD and MDD and contribute to a deeper understanding of their developmental trajectories, potentially informing the development of risk assessment tools for mood disorders.

Associação entre as condições de nascimento e a densidade mineral óssea de adultos das coortes de nascimentos de 1982 e 1993 de Pelotas, Rio Grande do Sul, Brasil / Association between birth conditions and bone mineral density in adults from the 1982 and 1993 birth cohorts in Pelotas, Rio Grande do Sul State, Brazil / Asociación entre las condiciones de nacimiento y la densidad mineral ósea de adultos de las cohortes de nacimiento de 1982 y 1993 en Pelotas, Rio Grande do Sul, Brasil

Resumo: Este estudo avaliou a associação do peso ao nascer, idade gestacional e crescimento intrauterino com a densidade mineral óssea (DMO) aos 22 e 30 anos, nas coortes de nascimentos de 1982 e 1993 de Pelotas, Rio Grande do Sul, Brasil. A DMO foi medida por absorciometria por raios X com dupla energia (DXA), a associação foi avaliada usando análise de variância e a regressão linear múltipla para o controle de confundimento por: sexo, renda familiar ao nascer, tabagismo materno na gestação, escolaridade materna, cor da pele materna e índice de massa corporal pré-gestacional. Foi testado se a gordura corporal na vida adulta era mediadora da associação analisada, por meio da G-computation Formula. Foram avaliados 6.803 participantes das coortes de 1982 e 1993, aos 30 e 22 anos, respectivamente. O peso ao nascer teve associação com a DMO em todos os sítios, com maior diferença no colo femoral. Os nascidos com menos de 2.000g apresentaram, em média, -0,036g/cm2 (IC95%: -0,064; -0,008) de DMO no colo femoral em comparação àqueles com mais de 3.500g. Aqueles com escore-z de crescimento intrauterino com pelo menos 1,28 desvio padrão abaixo da média apresentaram, em média, -0,013g/cm2 (IC95%: -0,024; -0,002) de DMO na coluna lombar, em relação aos com escore-z acima da média. A análise de mediação mostrou que gordura corporal na idade adulta não mediou a associação. As condições de nascimento foram associadas com a densidade mineral óssea na vida adulta, e a identificação dos fatores precoces relacionados à perda de DMO é essencial devido à inversão demográfica em progresso em países de média e baixa renda.

Abstract: This study assessed the association of birth weight, gestational age, and intrauterine growth with bone mineral density (BMD) at 22 and 30 years of age in the 1982 and 1993 birth cohorts in Pelotas, Rio Grande do Sul State, Brazil. BMD was measured by dual-energy X-ray absorptiometry (DXA) and the association was assessed using analysis of variance. Multiple linear regression was used to control for confounding factors: sex; household income at birth; maternal smoking during pregnancy; maternal schooling; maternal ethnicity/skin color; and pre-pregnancy body mass index. The study tested whether body fat in adulthood was a mediator of the association analyzed, using the G-computation Formula. A total of 6,803 participants from the 1982 and 1993 cohorts were evaluated at 30 and 22 years of age, respectively. Birth weight was associated with BMD at all sites, with a greater difference at the femoral neck. Individuals born weighing less than 2,000g had on average -0.036g/cm2 (95%CI: -0.064; -0.008) of BMD in the femoral neck than individuals weighing more than 3,500g. Individuals with an intrauterine growth z-score at least 1.28 standard deviation below the mean had an average of -0.013g/cm2 (95%CI: -0.024; -0.002) of BMD in the lumbar spine compared with individuals with an above-average z-score. The mediation analysis showed that body fat in adulthood did not mediate the association. Birth conditions have been associated with BMD in adulthood and the identification of early factors related to bone loss is essential due to the demographic inversion that has been taking place in low- and middle-income countries.

Resumen: Este estudio evaluó la asociación del peso al nacer, la edad gestacional y el crecimiento intrauterino con la densidad mineral ósea (DMO) a los 22 y 30 años de edad, en las Cohortes de Nacimiento de 1982 y 1993 de Pelotas, Rio Grande do Sul, Brasil. La DMO se midió mediante absorciometría de rayos X de doble emisión (DXA), y la asociación se evaluó mediante ANOVA y regresión lineal múltiple para controlar la confusión por sexo, ingresos familiares al nacer, tabaquismo materno durante el embarazo, escolaridad materna, color de piel materno e índice de masa corporal antes del embarazo. Se comprobó si la grasa corporal en la edad adulta era un mediador de la asociación analizada, utilizando G-computation Formula. Se evaluaron 6.803 participantes de las cohortes 82 y 93, de 30 y 22 años, respectivamente. El peso al nacer se asoció con la DMO en todos los sitios, con la mayor diferencia en el cuello femoral. Los nacidos con un peso inferior a 2.000g tuvieron una media de -0,036g/cm2 (IC95%: -0,064; -0,008) de DMO en el cuello femoral, que aquellos con más de 3.500g. Aquellos con una puntuación z de crecimiento intrauterino de al menos 1,28 desviaciones estándar por debajo de la media presentaron un promedio de -0,013g/cm2 (IC95%: -0,024; -0,002) de DMO en la columna lumbar, con relación a aquellos con un puntaje z superior a la media. El análisis de mediación mostró que la grasa corporal en la edad adulta no medió la asociación. Las condiciones de nacimiento se asociaron con la DMO en la edad adulta, y la identificación temprana de factores relacionados con la pérdida de DMO es esencial debido a la inversión demográfica que ha estado ocurriendo en los países de ingresos medios y bajos.

Pathways from maternal depression to child resilience: Socioeconomic, family, and individual factors in the 2004 Pelotas (Brazil) birth cohort.

Background: The negative impacts of maternal depression on child mental health outcomes are well-documented. However, some children show adaptive functioning following exposure to maternal depression, demonstrating resilience. In a large birth cohort from Brazil, a middle-income country, we examined direct and indirect pathways, considering socioeconomic, family, and individual factors, contributing to the development of resilience. Methods: Using data from the 2004 Pelotas Birth Cohort (N = 4231), we restricted the sample to those exposed to maternal depression up to age 6 years (depression present at ≥2 out of 5 assessment waves; n = 1132; 50% boys). Resilience was defined as scoring below or equal to the mean of the unexposed group on all four problem subscales of the parent-report Strengths and Difficulties Questionnaire at age 11 years. We examined pathways from socioeconomic status (SES; measured at birth) to resilience via cognitive stimulation (CS) (at 24 and 48 months) and Intelligence quotient (IQ) (at 6 years), and from CS to resilience via IQ, using counterfactual mediation. Results: A minority of children exposed to maternal depression showed resilience (12.4%). There was evidence of indirect pathways from SES to resilience via CS (odds ratio (OR) = 1.76, 95% confidence interval (CI) 1.02-3.38) and IQ (OR = 1.19, 95% CI 1.01-1.42), such that higher SES was associated with resilience via both higher levels of CS and higher IQ, which, in turn, were each positively associated with resilience. Furthermore, there was evidence of a direct (OR = 1.86, 95% CI 1.01-3.76) and total effect (OR = 1.94, 95% CI 1.05-3.89) of CS on resilience, even after controlling for SES. However, these effects varied depending on how persistent and severe depression was defined. Conclusions: These findings suggest that CS in early childhood may represent a modifiable protective factor for children exposed to maternal depression and a promising intervention target to promote child resilience in the context of maternal depression exposure.

Normative spatiotemporal fetal brain maturation with satisfactory development at 2 years.

Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1. We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2, selected using World Health Organization recommendations for growth standards3. Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age4,5. The atlas was produced using 1,059 optimal quality, three-dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6-8. The atlas corresponds structurally to published magnetic resonance images9, but with finer anatomical details in deep grey matter. The between-study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31 weeks' gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14 weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26 weeks' gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment.

[Birth conditions and attention deficit/hyperactivity disorders (ADHD) in adults in the Pelotas (Brazil) birth cohorts of 1982 and 1993]. / Condições de nascimento e transtorno do déficit de atenção com hiperatividade (TDAH) em adultos nas coortes de nascimento de Pelotas, Rio Grande do Sul, Brasil, de 1982 e 1993.

This study evaluates the association of birth conditions with attention deficit/hyperactivity disorders (ADHD) in adults using data from two birth cohorts in the city of Pelotas Rio Grande do Sul State, Brazil. In 1982 and 1993 all births in the city were identified and have been prospectively monitored. In the follow-ups at 30 and 22 years of the 1982 (n = 3,574) and 1993 (n = 3,780) cohorts, respectively, participants were examined, and trained psychologists applied the Mini-International Neuropsychiatric Interview (M.I.N.I.). Those individuals who met the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria were defined as positive for ADHD. Poisson regression with robust variance adjustment was used to estimate the prevalence ratio (PR) adjusted for sex, maternal skin color, family income, maternal age, maternal schooling during pregnancy, maternal marital status, parity, and maternal smoking during pregnancy. The prevalence of adult ADHD was 4.4% and 4.5% in the 1982 and 1993 cohorts, respectively. The prevalence of ADHD was higher in those born with lower weight, but no linear trend was observed, and those born with weight between 3,000 and 3,499 grams (PR = 1.40; 95%CI: 1.05-1.86) had the highest risk. For gestational age, we observed an inversely proportional relationship for the presence of ADHD: preterm infants had a 33% higher risk (95%CI: 0.90-1.96) of being considered as having ADHD than those born at 39 or more weeks, but as the confidence interval included nullity, this association may have occurred at random. These results indicate that birth weight and gestational age may be associated with adult ADHD.

Este artigo avaliou a associação das condições de nascimento com o transtorno do déficit de atenção com hiperatividade (TDAH) em adultos utilizando dados de duas coorte de nascimento da cidade de Pelotas, Rio Grande do Sul, Brasil. Em 1982 e 1993, todos os nascimentos ocorridos na cidade foram identificados e prospectivamente acompanhados. Nos acompanhamentos aos 30 e 22 anos das coortes 1982 (n = 3.574) e 1993 (n = 3.780), respectivamente, os participantes foram examinados e psicólogos treinados aplicaram a Mini-International Neuropsychiatric Interview (M.I.N.I.). Aqueles indivíduos que preencheram os critérios diagnósticos do Manual Diagnóstico e Estatístico de Transtornos Mentais (DSM-5) foram definidos como positivos para TDAH. A regressão de Poisson com ajuste robusto da variância foi usada para estimar a razão de prevalência (RP) ajustadas para sexo, cor da pele materna, renda familiar, idade materna, escolaridade materna durante a gestação, estado civil materno, paridade e tabagismo materno durante a gestação. A prevalência do TDAH adulto foi de 4,4% e 4,5% nas coortes de 1982 e 1993, respectivamente. A prevalência de TDAH foi maior naqueles que nasceram com menor peso, mas não foi observada tendencia linear. Além disso, aqueles que nasceram com peso entre 3.000 e 3.499 gramas (g) (RP = 1,40, IC95%: 1,05-1,86) apresentaram maior risco para o transtorno. Para a idade gestacional, observamos uma relação inversamente proporcional acerca da presença de TDAH, os pré-termos apresentaram risco 33% maior (IC95%: 0,90-1,96) de ser considerado com TDAH do que os nascidos com 39 ou mais semanas, mas como o intervalo de confiança incluiu a nulidade, essa associação pode ter ocorrido ao acaso. Tais resultados indicam que o peso ao nascer e a idade gestacional podem estar associados ao TDAH adulto.

El presente estudio evaluó la asociación de las condiciones de nacimiento con el trastorno por déficit de atención con hiperactividad (TDAH) en adultos utilizando datos de dos cohortes de nacimiento de la ciudad de Pelotas. En 1982 y 1993 se identificaron todos los nacimientos de la ciudad y se les ha hecho un seguimiento prospectivo. En los seguimientos a los 30 y 22 años de las cohortes de 1982 (n = 3.574) y 1993 (n = 3.780), respectivamente, los participantes fueron examinados y psicólogos capacitados aplicaron la Mini-International Neuropsychiatric Interview (M.I.N.I.). Aquellas personas que cumplieron con los criterios de diagnóstico del Manual Diagnóstico y Estadístico de los Trastornos Mentales (DSM-5) se definieron como positivos para TDAH. Se utilizó la regresión de Poisson con ajuste robusto de la varianza para estimar la razón de prevalencia (RP) ajustada por sexo, color de piel materna, ingreso familiar, edad materna, educación materna en la gestación, estado civil materno, paridad y tabaquismo materno en la gestación. La prevalencia del TDAH en adultos fue de 4,4% y 4,5 %, en las cohortes de 1982 y 1993, respectivamente. La prevalencia de TDAH fue mayor en aquellos que nacieron con menor peso, pero no se observó una tendencia lineal, y aquellos que nacieron con peso entre 3.000 y 3.499 gramos (RP = 1,40; IC95%: 1,05-1,86) presentaron el mayor riesgo. Para la edad gestacional, se observó una relación inversamente proporcional para la presencia de TDAH, los niños prematuros presentaron un 33 % más de riesgo (IC95 %: 0,90-1,96), de ser considerado como teniendo TDAH que los nacidos con 39 o más semanas, pero como el intervalo de confianza incluyó la nulidad, esa asociación puede haber ocurrido al azar. Tales resultados indican que el peso al nacer y la edad gestacional pueden estar asociados con el TDAH en adultos.

Relationship between sleep problems and headaches among adolescents: Pelotas 2004 Birth cohort.

Objective: To investigate the cross-sectional association between sleep problems (the exposure) and headaches (the outcome) among 15-year-olds from the Pelotas 2004 Birth Cohort, a population-based study in the south of Brazil. Method: The occurrence of headaches was obtained through the question: "Do you usually suffer headaches?" and the ICHD-3 criteria were used to classify as: tension-type headache, headache with characteristics of migraine with or without aura, or other. Regarding sleep, the weekly frequency in the last month of insomnia and bad dreams/nightmares, and self-reported sleep quality were investigated. Unadjusted and adjusted prevalence ratios (PR) with 95% confidence intervals were calculated using Poisson regression with robust variance. Results: A total of 1916 adolescents were analyzed. The prevalence of headaches was 51.6% (69.0% in females and 34.8% in males): 31.8% (39.7% vs. 24.1%) reported tension-type headache; 14.7% (21.9% vs. 7.8%), headaches with characteristics of migraines without aura; 3.6%, headaches with characteristics of migraines with aura; and 1.5% (5.1% vs. 2.3%), other types. Adolescents with insomnia ≥3 times/week presented higher probability of headaches (PR = 1.54; 95%CI 1.23-1.93), compared with those with no problems falling asleep or maintaining sleep. Among those who classified their sleep as poor/very poor, the probability of headaches was 33% higher (PR = 1.33; 95%CI 1.13-1.57) than among those who classified their sleep as very good. Conclusions: Headaches were highly prevalent among the adolescents and were related to sleep problems even after allowing for several confounders.

Machine learning for accurate estimation of fetal gestational age based on ultrasound images.

Accurate estimation of gestational age is an essential component of good obstetric care and informs clinical decision-making throughout pregnancy. As the date of the last menstrual period is often unknown or uncertain, ultrasound measurement of fetal size is currently the best method for estimating gestational age. The calculation assumes an average fetal size at each gestational age. The method is accurate in the first trimester, but less so in the second and third trimesters as growth deviates from the average and variation in fetal size increases. Consequently, fetal ultrasound late in pregnancy has a wide margin of error of at least ±2 weeks' gestation. Here, we utilise state-of-the-art machine learning methods to estimate gestational age using only image analysis of standard ultrasound planes, without any measurement information. The machine learning model is based on ultrasound images from two independent datasets: one for training and internal validation, and another for external validation. During validation, the model was blinded to the ground truth of gestational age (based on a reliable last menstrual period date and confirmatory first-trimester fetal crown rump length). We show that this approach compensates for increases in size variation and is even accurate in cases of intrauterine growth restriction. Our best machine-learning based model estimates gestational age with a mean absolute error of 3.0 (95% CI, 2.9-3.2) and 4.3 (95% CI, 4.1-4.5) days in the second and third trimesters, respectively, which outperforms current ultrasound-based clinical biometry at these gestational ages. Our method for dating the pregnancy in the second and third trimesters is, therefore, more accurate than published methods.

Association between preterm infant size at 1 year and ADHD later in life: data from 1993 and 2004 Pelotas Birth Cohorts.

The objective of this study is to examine the association between preterm infants' size at 1 year and attention-deficit/hyperactivity disorder (ADHD) assessed categorically and dimensionally in childhood and adolescence. We studied infants born < 37 weeks' gestation from two Brazilian birth cohorts (n = 653). ADHD was evaluated using the Development and Well-Being Assessment (DAWBA) interview at the age of 6 years in one cohort and by a structured interview according to DSM-5 criteria at 18 years in the other one. The presence of child attention difficulties was measured by the Strengths and Difficulties Questionnaire (SDQ) at 6 and 11 years in the 2004 and 1993 cohorts, respectively. We estimated associations of weight, length, head circumference, and BMI z-scores at 1-year chronological age with ADHD using Poisson Regression Model; and with attention difficulties using Linear Regression, adjusting for covariates. Mean birth weight was 2500 g and gestational age was 34.5 weeks. The aggregated ADHD prevalence in the two cohorts was 2.7%, and the median score for attention difficulties was 3.0. We found that increased head circumference at 1 year was associated with a lower risk of ADHD diagnosis (RR = 0.7, 95% CI 0.4, 0.9; p = 0.04 per standard deviation difference) and with fewer dimensional attention symptoms. In sensitivity analysis with other mental disorders, head circumference was associated with depression, but not with anxiety. Our findings emphasize poor head growth in the first year of life as a potential determinant of attentional difficulties in the preterm infant population.

Two decades of socioeconomic inequalities in the prevalence of untreated dental caries in early childhood: Results from three birth cohorts in southern Brazil.

OBJECTIVES: To estimate the socioeconomic disparities in untreated dental caries in early childhood according to socioeconomic characteristics in three birth cohorts in Southern Brazil. METHODS: The socioeconomic data to this study were collected at the 48-month follow-up and oral health studies of 1993, 2004 and 2015 Pelotas birth cohort studies. The outcome was untreated dental caries in children aged 6 (1993 cohort), 5 (2004 cohort) and 4 years (2015 cohort), dichotomized into absence/presence. Analyses were stratified by maternal skin colour/race, maternal education and family income. For statistical purposes, the prevalence difference, relative risk and absolute and relative indices of health inequality (Slope Index of Inequality-SII and Concentration Index-CIX) were used. RESULTS: The prevalence of untreated dental caries in primary dentition was 63.4%, 45.5% and 15.6%, in 1993, 2004 and 2015 cohorts, respectively. The prevalence of untreated dental caries was concentrated in the poorest quintile and lower maternal education group in both absolute (SII) and relative (CIX) measures of inequality, being characterized as a pro-poor event. A higher risk of untreated caries was found in the poorest quintile of family income compared with the richest quintile in the 1993 cohort (RR 1.44 [95% CI 1.05; 1.98]). That risk was higher considering the 2004 Cohort (RR 1.78 [95% CI 1.42; 2.23]) and 2015 cohort (RR 4.20 [95% CI 2.97; 5.94]) data. CONCLUSIONS: Over the course of two decades, a higher prevalence of untreated dental caries is concentrated among the most socioeconomically deprived children.

Socioeconomic inequalities related to maternal perception of children's oral health at age 4: Results of a birth cohort.

OBJECTIVES: To estimate socioeconomic inequalities in the maternal perception of children's oral health from a birth cohort study in Brazil. METHODS: The data from this study were collected through perinatal interviews and at the 48-month follow-up from the 2015 Pelotas Birth Cohort Study. The main outcome was the maternal perception of children's oral health, dichotomized into positive (good/very good) and negative (fair/bad/very bad). The secondary outcome was untreated dental caries (absence and presence, according to the ICDAS index - International Caries Detection and Assessment System). For the statistical analysis, the absolute inequality index (Slope Index of Inequality - SII) and the relative concentration index (Concentration Index - CIX) were used. Analyses were stratified by maternal educational level, family income and wealth index. RESULTS: The prevalence of outcomes was 19.4% (95% CI 18.2; 20.7) for the negative maternal perception of children's oral health and 15.6% (95% CI 14.4; 16.8) for untreated dental caries. Socioeconomics inequalities were observed in negative maternal perception of children's oral health in both absolute and relative terms. A SII of -16.6 (95% CI -20.8; -12.5) was observed for family income, with higher prevalence in poor families. A higher prevalence of the negative maternal perception of children's oral health was observed in mothers without any educational level or a few years of study (CIX -21.1 [95% CI -24.5; -17.7]). CONCLUSIONS: This study demonstrates socioeconomics disparities in the maternal perception of children's oral health and in the prevalence of untreated caries in children. A higher concentration of negative maternal perception of children's oral health was identified among the most socioeconomically vulnerable individuals. The findings reinforce the presence of socioeconomic inequalities in subjective measures about children's oral health.

Maternal depression trajectories in childhood, subsequent maltreatment, and adolescent emotion regulation and self-esteem: the 2004 Pelotas birth cohort.

This study aimed to examine the impact of maternal depressive symptoms trajectories on 15-year-old adolescents' self-esteem and emotion regulation and test the mediating role of child maltreatment in this association. The 2004 Pelotas Birth Cohort is an ongoing cohort study originally comprised of 4231 live births in a southern Brazilian city. We examined a subsample of 1949 adolescents at age 15 years. Maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale. Trajectories of maternal depression from 3 months until the 11-year follow-up were calculated using a group-based modeling approach. Child maltreatment at age 11 years was measured using the parent-report version of the Parent-Child Conflict Tactics Scale. Adolescent outcomes at age 15 years were assessed by the self-report version of the Rosenberg Self-esteem Scale and the Emotion Regulation Index for Children and Adolescents. Path model analysis was conducted using a structural equation modeling framework in Mplus software. All maternal depression trajectories were negatively associated with offspring self-esteem and emotion regulation compared to the reference group (low depression trajectory). There was a significant indirect effect of maternal depression trajectories on emotion regulation mediated via child maltreatment. No evidence of moderation by sex was found for any pathway. The effects of maternal depression on adolescents' emotion regulation are partly mediated by child maltreatment at age 11.

Child and Maternal Mental Health Before and During the COVID-19 Pandemic: Longitudinal Social Inequalities in a Brazilian Birth Cohort.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has caused major stress for families and children, particularly in the context of prolonged school closures. Few longitudinal studies are available on young children's mental health, including data both before and during the pandemic. This study examined experiences that might increase risk for mental health problems among caregivers and young children during the COVID-19 pandemic and inequalities driven by pre-pandemic disadvantage. METHOD: This prospective, population-based birth cohort study in Pelotas, Brazil, analyzed 2,083 children and caregivers with data from before the pandemic in 2019, when children were 4 years old, and again in 2020, when schools were closed for a long period during the pandemic. Child conduct problems, emotional problems, and hyperactivity-inattention problems were assessed using the Strengths and Difficulties Questionnaire. Family financial hardship, relationship difficulties, caregiver mental health, parenting practices, and child fears and isolation were considered as potential risk factors. RESULTS: Across the whole population, the only significant increase in mental health problems from before to during the pandemic was found for maternal depression. However, poorer families were at far greater risk of experiencing serious financial problems, food shortages, increased conflict in adult relationships, parenting problems, and child worries about food availability during the pandemic. In turn, these difficulties were associated with increases in multiple mental health problems for both caregivers and children. Increased child mental health problems were most strongly associated with concurrent maternal anxiety (ß > 0.20, p < .001, for each of child conduct, emotional, and hyperactivity problems), maternal depression (ß = 0.26, p < .001, for child emotional problems), partner criticism (ß = 0.21, p < .001, for child conduct problems), and harsh parenting (ß > 0.20, p < .001, for both child conduct and hyperactivity problems). Child worry about COVID-19 was associated with increased emotional problems (ß = 0.14, p < .001), but children's isolation was not associated with their mental health. CONCLUSION: Overall, the impact of the COVID-19 pandemic on mental health is a mixed picture, but for families in poverty, marked material and interpersonal difficulties were associated with increases in mental health problems among children and caregivers.

Condições de nascimento e transtorno do déficit de atenção com hiperatividade (TDAH) em adultos nas coortes de nascimento de Pelotas, Rio Grande do Sul, Brasil, de 1982 e 1993 / Birth conditions and attention deficit/hyperactivity disorders (ADHD) in adults in the Pelotas (Brazil) birth cohorts of 1982 and 1993 / Condiciones de nacimiento y trastorno por déficit de atención con hiperactividad (TDAH) en adultos en las cohortes de nacimiento de Pelotas, Rio Grande do Sul, Brasil, de 1982 y 1993

Este artigo avaliou a associação das condições de nascimento com o transtorno do déficit de atenção com hiperatividade (TDAH) em adultos utilizando dados de duas coorte de nascimento da cidade de Pelotas, Rio Grande do Sul, Brasil. Em 1982 e 1993, todos os nascimentos ocorridos na cidade foram identificados e prospectivamente acompanhados. Nos acompanhamentos aos 30 e 22 anos das coortes 1982 (n = 3.574) e 1993 (n = 3.780), respectivamente, os participantes foram examinados e psicólogos treinados aplicaram a Mini-International Neuropsychiatric Interview (M.I.N.I.). Aqueles indivíduos que preencheram os critérios diagnósticos do Manual Diagnóstico e Estatístico de Transtornos Mentais (DSM-5) foram definidos como positivos para TDAH. A regressão de Poisson com ajuste robusto da variância foi usada para estimar a razão de prevalência (RP) ajustadas para sexo, cor da pele materna, renda familiar, idade materna, escolaridade materna durante a gestação, estado civil materno, paridade e tabagismo materno durante a gestação. A prevalência do TDAH adulto foi de 4,4% e 4,5% nas coortes de 1982 e 1993, respectivamente. A prevalência de TDAH foi maior naqueles que nasceram com menor peso, mas não foi observada tendencia linear. Além disso, aqueles que nasceram com peso entre 3.000 e 3.499 gramas (g) (RP = 1,40, IC95%: 1,05-1,86) apresentaram maior risco para o transtorno. Para a idade gestacional, observamos uma relação inversamente proporcional acerca da presença de TDAH, os pré-termos apresentaram risco 33% maior (IC95%: 0,90-1,96) de ser considerado com TDAH do que os nascidos com 39 ou mais semanas, mas como o intervalo de confiança incluiu a nulidade, essa associação pode ter ocorrido ao acaso. Tais resultados indicam que o peso ao nascer e a idade gestacional podem estar associados ao TDAH adulto.

This study evaluates the association of birth conditions with attention deficit/hyperactivity disorders (ADHD) in adults using data from two birth cohorts in the city of Pelotas Rio Grande do Sul State, Brazil. In 1982 and 1993 all births in the city were identified and have been prospectively monitored. In the follow-ups at 30 and 22 years of the 1982 (n = 3,574) and 1993 (n = 3,780) cohorts, respectively, participants were examined, and trained psychologists applied the Mini-International Neuropsychiatric Interview (M.I.N.I.). Those individuals who met the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria were defined as positive for ADHD. Poisson regression with robust variance adjustment was used to estimate the prevalence ratio (PR) adjusted for sex, maternal skin color, family income, maternal age, maternal schooling during pregnancy, maternal marital status, parity, and maternal smoking during pregnancy. The prevalence of adult ADHD was 4.4% and 4.5% in the 1982 and 1993 cohorts, respectively. The prevalence of ADHD was higher in those born with lower weight, but no linear trend was observed, and those born with weight between 3,000 and 3,499 grams (PR = 1.40; 95%CI: 1.05-1.86) had the highest risk. For gestational age, we observed an inversely proportional relationship for the presence of ADHD: preterm infants had a 33% higher risk (95%CI: 0.90-1.96) of being considered as having ADHD than those born at 39 or more weeks, but as the confidence interval included nullity, this association may have occurred at random. These results indicate that birth weight and gestational age may be associated with adult ADHD.

El presente estudio evaluó la asociación de las condiciones de nacimiento con el trastorno por déficit de atención con hiperactividad (TDAH) en adultos utilizando datos de dos cohortes de nacimiento de la ciudad de Pelotas. En 1982 y 1993 se identificaron todos los nacimientos de la ciudad y se les ha hecho un seguimiento prospectivo. En los seguimientos a los 30 y 22 años de las cohortes de 1982 (n = 3.574) y 1993 (n = 3.780), respectivamente, los participantes fueron examinados y psicólogos capacitados aplicaron la Mini-International Neuropsychiatric Interview (M.I.N.I.). Aquellas personas que cumplieron con los criterios de diagnóstico del Manual Diagnóstico y Estadístico de los Trastornos Mentales (DSM-5) se definieron como positivos para TDAH. Se utilizó la regresión de Poisson con ajuste robusto de la varianza para estimar la razón de prevalencia (RP) ajustada por sexo, color de piel materna, ingreso familiar, edad materna, educación materna en la gestación, estado civil materno, paridad y tabaquismo materno en la gestación. La prevalencia del TDAH en adultos fue de 4,4% y 4,5 %, en las cohortes de 1982 y 1993, respectivamente. La prevalencia de TDAH fue mayor en aquellos que nacieron con menor peso, pero no se observó una tendencia lineal, y aquellos que nacieron con peso entre 3.000 y 3.499 gramos (RP = 1,40; IC95%: 1,05-1,86) presentaron el mayor riesgo. Para la edad gestacional, se observó una relación inversamente proporcional para la presencia de TDAH, los niños prematuros presentaron un 33 % más de riesgo (IC95 %: 0,90-1,96), de ser considerado como teniendo TDAH que los nacidos con 39 o más semanas, pero como el intervalo de confianza incluyó la nulidad, esa asociación puede haber ocurrido al azar. Tales resultados indican que el peso al nacer y la edad gestacional pueden estar asociados con el TDAH en adultos.

Linear growth and relative weight gain in childhood and bone mass in adolescence: findings from the Pelotas (Brazil) 2004 birth cohort.

With the objective to investigate the relationship of weight and height growth with bone mass at 11 years, we found that boys who grew in weight and height, especially at 48 months, and girls, who grew in weight at 24 months and height at 11 years, gained more bone mass. PURPOSE: To investigate independent relationships of linear growth and relative weight gain during defined periods of infancy, childhood, and early adolescence with areal bone mineral density (aBMD) of three sites at 11 years. METHODS: Data on weight and length/height were obtained at birth, 3, 12, and 24 months, and the ages of 4, 6, and 11. The outcome was whole body, femoral neck, and lumbar spine aBMD (g/cm2) measured at 11 years using dual-energy X-ray absorptiometry. The effects of weight gain and linear growth were analyzed using conditional relative weight and conditional length/height. Associations between conditional growth and outcomes were analyzed using linear regression, adjusted for multiple confounders. RESULTS: Individuals with data available for exposures and bone outcomes were 2875 and comprised the sample. For boys, the greatest magnitude of increase for whole body and height gain was at 48 months (ß 0.014, 95% CI 0.010; 0.018). For girls, higher aBMD was observed for those with greater height gain at 11 years, representing for lumbar spine an increase of 0.056 g/cm2 (95% CI 0.050; 0.062). For body weight, among boys, the greatest magnitude in the whole body was also associated with weight gain at 48 months (ß 0.014, 95% CI 0.010; 0.018). For girls, the highest coefficient was at 24 months, representing for lumbar spine an increase of 0.028 g/cm2, (95% CI 0.021; 0.035). CONCLUSION: Positive associations were demonstrated between length/height and weight gain and aBMD in both sexes, with emphasis on girls' aBMD in response to the linear growth achieved mainly at 11 years.

Preeclampsia prediction with blood pressure measurements: A global external validation of the ALSPAC models.

OBJECTIVE: The prediction of preeclampsia in pregnancy has resulted in a plethora of prognostic models. Yet, very few make it past the development stage and most fail to influence clinical practice. The timely identification of high-risk pregnant women could deliver a tailored antenatal care regimen, particularly in low-resource settings. This study externally validated and calibrated previously published models that predicted the risk of preeclampsia, based on blood pressure (BP) at multiple time points in pregnancy, in a geographically diverse population. METHODS: The prospective INTERBIO-21st Fetal Study included 3,391 singleton pregnancies from Brazil, Kenya, Pakistan, South Africa, Thailand and the UK, 2012-2018. Preeclampsia prediction was based on baseline characteristics, BP and deviation from the expected BP trajectory at multiple time points in pregnancy. The prediction rules from the Avon Longitudinal Study of Parents and Children (ALSPAC) were implemented in the INTERBIO-21st cohort. RESULTS: Model discrimination was similar to the development cohort. Performance was best with baseline characteristics and a BP measurement at 34 weeks' gestation (AUC 0.85, 95 % CI 0.80-0.90). The ALSPAC models largely overestimated the true risk of preeclampsia incidence in the INTERBIO-21st cohort. CONCLUSIONS: After recalibration, these prediction models could potentially serve as a risk stratifying tool to help identify women who might benefit from increased surveillance during pregnancy.