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1.  Effect of tobacco smoke exposure during pregnancy and preschool age on growth from birth to adolescence: a cohort study 
BMC Pediatrics  2014;14:99.
Background
There is strong evidence of an association between maternal smoking during pregnancy and restriction of intrauterine growth, but the effects of this exposure on postnatal linear growth are not well defined. Furthermore, few studies have investigated the role of tobacco smoke exposure also after pregnancy on linear growth until adolescence. In this study we investigated the effect of maternal smoking exposure during pregnancy and preschool age on linear growth from birth to adolescence.
Methods
We evaluated a cohort of children born between 1994 and 1999 in Cuiabá, Brazil, who attended primary health clinics for vaccination between the years 1999 and 2000 (at preschool age) and followed-up after approximately ten years. Individuals were located in public and private schools throughout the country using the national school census. Height/length was measured, and length at birth was collected at maternity departments. Stature in childhood and adolescence was assessed using the height-for-age index sex-specific expressed as z-score from curves published by the World Health Organization. Linear mixed effects models were used to estimate the association between exposure to maternal smoking, during pregnancy and preschool age, and height of children assessed at birth, preschool and school age, adjusted for age of the children.
Results
We evaluated 2405 children in 1999–2000, length at birth was obtained from 2394 (99.5%), and 1716 at follow-up (71.4% of baseline), 50.7% of the adolescents were male. The z-score of height-for-age was lower among adolescents exposed to maternal smoking both during pregnancy and childhood (p < 0.01). Adjusting for age, sex, maternal height, maternal schooling, socioeconomic position at preschool age, and breastfeeding, children exposed to maternal smoking both during pregnancy and preschool age showed persistent lower height-for-age since birth to adolescence (coefficient: −0.32, p < 0.001) compared to non-exposed. Paternal smoking at preschool age was not associated with growth after adjustment for confounders.
Conclusion
Exposure to maternal smoking not only during pregnancy, but also at early childhood, showed long-term negative effect on height of children until adolescence.
doi:10.1186/1471-2431-14-99
PMCID: PMC3989847  PMID: 24721026
Smoking; Growth; Body height; Adolescent; Longitudinal studies
2.  Maternal smoking and child psychological problems: Disentangling causal and non-causal effects 
Pediatrics  2010;126(1):e57-e65.
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 sub-sample) and Avon Longitudinal Study of Parents and Children (ALSPAC), Britain (n=6,735). 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) search for specific effects on different behavioural 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 ORs of maternal smokers having offspring with higher scores). Maternal smoking associations were stronger than paternal smoking associations, although statistical evidence for differences was weak in 1 cohort.
Conclusions
Evidence from 4 approaches suggests a possible intrauterine effect of maternal smoking on offspring conduct/externalizing problems.
doi:10.1542/peds.2009-2754
PMCID: PMC3605780  PMID: 20587678
ALSPAC; Pelotas; prenatal smoking; child; behavioral problems; developmental origins
3.  Maternal smoking during pregnancy and offspring trajectories of height and adiposity: comparing maternal and paternal associations 
Background Maternal smoking during pregnancy is associated with reduced offspring birth length and has been postulated as a risk factor for obesity. Causality for obesity is not established. Causality is well-supported for birth length, but evidence on persistence of height deficits is inconsistent.
Methods We examined the association between maternal smoking during pregnancy and trajectories of offspring height (0–10 years, N = 9424), ponderal index (PI) (0–2 years, N = 9321) and body mass index (BMI) (2–10 years, N = 8887) in the Avon Longitudinal Study of Parents and Children. To strengthen inference, measured confounders were controlled for, maternal and partner smoking associations were compared, dose–response and associations with post-natal smoking were examined.
Results Maternal smoking during pregnancy was associated with shorter birth length, faster height growth in infancy and slower growth in later childhood. By 10 years, daughters of women who smoke during pregnancy are on average 1.11 cm (SE = 0.27) shorter after adjustment for confounders and partner smoking; the difference is 0.22 cm (SE = 0.22) for partner's smoking. Maternal smoking was associated with lower PI at birth, faster PI increase in infancy, but not with BMI changes 2–10 years. Associations were stronger for maternal than partner smoking for PI at birth and PI changes in infancy, but not for BMI changes after 2 years. A similar dose–response in both maternal and partner smoking was seen for BMI change 2–10 years.
Conclusion Maternal smoking during pregnancy has an intrauterine effect on birth length, and possibly on adiposity at birth and changes in height and adiposity in infancy. We do not find evidence of a specific intrauterine effect on height or adiposity changes after the age of 2 years.
doi:10.1093/ije/dys025
PMCID: PMC3396309  PMID: 22407859
Smoking; growth; obesity; pregnancy; child; ALSPAC
4.  Life Course Association of Maternal Smoking During Pregnancy and Offspring's Height: Data From the 1993 Pelotas (Brazil) Birth Cohort 
The Journal of Adolescent Health  2012;51(6):S53-S57.
Purpose
To evaluate the effect of (1) maternal smoking during pregnancy; and (2) partner smoking on offspring's height in infancy, childhood, and adolescence.
Methods
All hospital live births from 1993 (5,249) were identified, and these infants were followed up at several ages. Height for age, expressed as z-scores using the World Health Organization growth curves, was measured at all follow-up visits. Maternal smoking during pregnancy was collected retrospectively at birth and analyzed as number of cigarettes/day smoked categorized in four categories (never smoked, <10, 10–19, and ≥20 cigarettes/day). Partner smoking was analyzed as a dichotomous variable (No/Yes). Unadjusted and adjusted analyses were performed by use of linear regression.
Results
The prevalence of self-reported maternal smoking during pregnancy was 33.5%. In the crude analysis, the number of cigarettes/day smoked by the mother during pregnancy negatively affected offspring's height in infancy, childhood, and adolescence. After adjustment for confounders and mediators, this association remained statistically significant, although the magnitude of the regression coefficients was reduced. Paternal smoking was not associated with offspring's height in the adjusted analyses.
Conclusions
In addition to the well-known harmful effects of smoking, maternal smoking during pregnancy negatively affects offspring's height. Public health policies aimed at continuing to reduce the prevalence of maternal smoking during pregnancy must be encouraged.
doi:10.1016/j.jadohealth.2012.08.014
PMCID: PMC3508408  PMID: 23283162
Smoking; Height by age; Body height; Growth; Child; Adolescent; Cohort studies
5.  Exploring the Developmental Overnutrition Hypothesis Using Parental–Offspring Associations and FTO as an Instrumental Variable 
PLoS Medicine  2008;5(3):e33.
Background
The developmental overnutrition hypothesis suggests that greater maternal obesity during pregnancy results in increased offspring adiposity in later life. If true, this would result in the obesity epidemic progressing across generations irrespective of environmental or genetic changes. It is therefore important to robustly test this hypothesis.
Methods and Findings
We explored this hypothesis by comparing the associations of maternal and paternal pre-pregnancy body mass index (BMI) with offspring dual energy X-ray absorptiometry (DXA)–determined fat mass measured at 9 to 11 y (4,091 parent–offspring trios) and by using maternal FTO genotype, controlling for offspring FTO genotype, as an instrument for maternal adiposity. Both maternal and paternal BMI were positively associated with offspring fat mass, but the maternal association effect size was larger than that in the paternal association in all models: mean difference in offspring sex- and age-standardised fat mass z-score per 1 standard deviation BMI 0.24 (95% confidence interval [CI]: 0.22 to 0.26) for maternal BMI versus 0.13 (95% CI: 0.11, 0.15) for paternal BMI; p-value for difference in effect < 0.001. The stronger maternal association was robust to sensitivity analyses assuming levels of non-paternity up to 20%. When maternal FTO, controlling for offspring FTO, was used as an instrument for the effect of maternal adiposity, the mean difference in offspring fat mass z-score per 1 standard deviation maternal BMI was −0.08 (95% CI: −0.56 to 0.41), with no strong statistical evidence that this differed from the observational ordinary least squares analyses (p = 0.17).
Conclusions
Neither our parental comparisons nor the use of FTO genotype as an instrumental variable, suggest that greater maternal BMI during offspring development has a marked effect on offspring fat mass at age 9–11 y. Developmental overnutrition related to greater maternal BMI is unlikely to have driven the recent obesity epidemic.
Using parental-offspring associations and theFTO gene as an instrumental variable for maternal adiposity, Debbie Lawlor and colleagues found that greater maternal BMI during offspring development does not appear to have a marked effect on offspring fat mass at age 9-11.
Editors' Summary
Background.
Since the 1970s, the proportion of children and adults who are overweight or obese (people who have an unhealthy amount of body fat) has increased sharply in many countries. In the US, 1 in 3 adults is now obese; in the mid-1970s it was only 1 in 7. Similarly, the proportion of overweight children has risen from 1 in 20 to 1 in 5. An adult is considered to be overweight if their body mass index (BMI)—their weight in kilograms divided by their height in meters squared—is between 25 and 30, and obese if it is more than 30. For children, the healthy BMI depends on their age and gender. Compared to people with a healthy weight (a BMI between 18.5 and 25), overweight or obese individuals have an increased lifetime risk of developing diabetes and other adverse health conditions, sometimes becoming ill while they are still young. People become unhealthily fat when they consume food and drink that contains more energy than they need for their daily activities. It should, therefore, be possible to avoid becoming obese by having a healthy diet and exercising regularly.
Why Was This Study Done?
Some researchers think that “developmental overnutrition” may have caused the recent increase in waistline measurements. In other words, if a mother is overweight during pregnancy, high sugar and fat levels in her body might permanently affect her growing baby's appetite control and metabolism, and so her offspring might be at risk of becoming obese in later life. If this hypothesis is true, each generation will tend to be fatter than the previous one and it will be very hard to halt the obesity epidemic simply by encouraging people to eat less and exercise more. In this study, the researchers have used two approaches to test the developmental overnutrition hypothesis. First, they have asked whether offspring fat mass is more strongly related to maternal BMI than to paternal BMI; it should be if the hypothesis is true. Second, they have asked whether a genetic indicator of maternal fatness—the “A” variant of the FTO gene—is related to offspring fat mass. A statistical association between maternal FTO genotype (genetic make-up) and offspring fat mass would support the developmental nutrition hypothesis.
What Did the Researchers Do and Find?
In 1991–1992, the Avon Longitudinal Study of Parents and Children (ALSPAC) enrolled about 14,000 pregnant women and now examines their offspring at regular intervals. The researchers first used statistical methods to look for associations between the self-reported prepregnancy BMI of the parents of about 4,000 children and the children's fat mass at ages 9–11 years measured using a technique called dual energy X-ray absorptiometry. Both maternal and paternal BMI were positively associated with offspring fat mass (that is, fatter parents had fatter children) but the effect of maternal BMI was greater than the effect of paternal BMI. When the researchers examined maternal FTO genotypes and offspring fat mass (after allowing for the offspring's FTO genotype, which would directly affect their fat mass), there was no statistical evidence to suggest that differences in offspring fat mass were related to the maternal FTO genotype.
What Do These Findings Mean?
Although the findings from first approach provide some support for the development overnutrition hypothesis, the effect of maternal BMI on offspring fat mass is too weak to explain the recent obesity epidemic. Developmental overnutrition could, however, be responsible for the much slower increase in obesity that began a century ago. The findings from the second approach provide no support for the developmental overnutrition hypothesis, although these results have wide error margins and need confirming in a larger study. The researchers also note that the effects of developmental overnutrition on offspring fat mass, although weak at age 9–11, might become more important at later ages. Nevertheless, for now, it seems unlikely that developmental overnutrition has been a major driver of the recent obesity epidemic. Interventions that aim to improve people's diet and to increase their physical activity levels could therefore slow or even halt the epidemic.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050033.
See a related PLoS Medicine Perspective article
The MedlinePlus encyclopedia has a page on obesity (in English and Spanish)
The US Centers for Disease Control and Prevention provides information on all aspects of obesity (in English and Spanish)
The UK National Health Service's health Web site (NHS Direct) provides information about obesity
The International Obesity Taskforce provides information about preventing obesity and on childhood obesity
The UK Foods Standards Agency, the United States Department of Agriculture, and Shaping America's Health all provide useful advice about healthy eating for adults and children
The ALSPAC Web site provides information about the Avon Longitudinal Study of Parents and Children and its results so far
doi:10.1371/journal.pmed.0050033
PMCID: PMC2265763  PMID: 18336062
6.  Parental smoking during pregnancy and offspring bone mass at age 10 years: findings from a prospective birth cohort 
Osteoporosis International  2010;22(6):1809-1819.
Summary
We investigated an intrauterine influence of maternal smoking during pregnancy on childhood bone mass. Daughters, but not sons, of mothers who smoked had higher bone mass at age 10 years. This appears to be due to familial factors related to parental smoking influencing increased offspring adiposity rather than a direct intrauterine effect.
Introduction
Neonatal studies have demonstrated an adverse relationship between maternal smoking in pregnancy and foetal bone mineral accrual. We aimed to investigate an intrauterine influence of maternal smoking during pregnancy on offspring bone mass at mean age 9.9 years.
Methods
We compared associations of maternal and paternal smoking in pregnancy with offspring total body less head (TBLH) and spine bone mineral content (BMC), bone area (BA), bone mineral density (BMD) and area-adjusted BMC (ABMC) in 7,121 children in the Avon Longitudinal Study of Parents and Children.
Results
Maternal smoking in any trimester was associated with increased TBLH BMC, BA and BMD in girls (mean difference [95% CI] (sex-specific SD scores), 0.13 [0.05–0.22], 0.13 [0.04–0.21], 0.13 [0.04–0.22], respectively) but not boys (0.01 [−0.07–0.09], 0.00 [−0.08–0.08], 0.04 [−0.05–0.12]), and also with spine BMC, BA and BMD in girls (0.13 [0.03–0.23], 0.12 [0.03–0.22], 0.10 [0.00–0.21]) but not boys (0.03 [−0.06–0.12], 0.00 [−0.09–0.09], 0.05 [−0.04–0.14]), but not with ABMC. Paternal smoking associations were similar, with no statistical evidence for a difference between maternal and paternal effects. Maternal associations increased on adjustment for offspring birth weight and gestational age, but attenuated to the null after adjustment for current height and weight.
Conclusions
We found little evidence that maternal smoking was related to bone mass in boys. In girls, maternal smoking associations were similar to those of paternal smoking, suggesting that these were attributable to shared familial characteristics, not intrauterine mechanisms.
Electronic supplementary material
The online version of this article (doi:10.1007/s00198-010-1415-y) contains supplementary material, which is available to authorized users.
doi:10.1007/s00198-010-1415-y
PMCID: PMC3092913  PMID: 20967424
ALSPAC; Bone mineral content (BMC); Bone mineral density (BMD); Childhood; Pregnancy; Smoking
7.  Maternal education inequalities in height growth rates in early childhood: 2004 Pelotas birth cohort study 
Summary
Matijasevich A, Howe LD, Tilling K, Santos IS, Barros AJD, Lawlor DA. Maternal education inequalities in height growth rates in early childhood: 2004 Pelotas birth cohort study. Paediatric and Perinatal Epidemiology 2012; 26: 236–249.
Socio-economic inequalities in attained height have been reported in many countries. The aim of this study was to explore the age at which maternal education inequalities in child height emerge among children from a middle-income country. Using data from the 2004 Pelotas cohort study from Brazil we modelled individual height growth trajectories in 2106 boys and 1947 girls from birth to 4 years using a linear spline mixed-effects model. We examined the associations of maternal education with birth length and trajectories of growth in length/height, and explored the effect of adjusting for a number of potential confounder or mediator factors.
We showed linear and positive associations of maternal education with birth length and length/height growth rates at 0–3 months and 12–29/32 months with very little association at 3–12 months, particularly in boys. By age 4 years the mean height of boys was 101.06 cm (SE = 0.28) in the lowest and 104.20 cm (SE = 0.15) in the highest education category (mean difference 3.14 cm, SE = 0.32, P < 0.001). Among girls the mean height was 100.02 cm (SE = 0.27) and 103.03 cm (SE = 0.15) in the lowest and highest education categories, respectively (mean difference 3.01 cm, SE = 0.31, P < 0.001). For both boys and girls there was on average a 3-cm difference between the extreme education categories. Adjusting for maternal height reduced the observed birth length differences across maternal education categories, but differences in postnatal growth rates persisted.
Our data demonstrate an increase in the absolute and relative inequality in height after birth; inequality increases from approximately 0.2 standard deviations of birth length to approximately 0.7 standard deviations of height at age 4, indicating that height inequality, which was already present at birth, widened through differential growth rates to age 2 years.
doi:10.1111/j.1365-3016.2011.01251.x
PMCID: PMC3491696  PMID: 22471683
childhood height; Pelotas birth cohort; maternal education; child growth
8.  Early life determinants of low IQ at age 6 in children from the 2004 Pelotas Birth Cohort: a predictive approach 
BMC Pediatrics  2014;14(1):308.
Background
Childhood intelligence is an important determinant of health outcomes in adulthood. The first years of life are critical to child development. This study aimed to identify early life (perinatal and during the first year of life) predictors of low cognitive performance at age 6.
Methods
A birth cohort study started in the city of Pelotas, southern Brazil, in 2004 and children were followed from birth to age six. Information on a broad set of biological and social predictors was collected. Cognitive ability—the study outcome—was assessed using the Wechsler Intelligence Scale for Children (WISC). IQ scores were standardized into z-scores and low IQ defined as z < −1. We applied bootstrapping methods for internal validation with a multivariate logistic regression model and carried out external validation using a second study from the 1993 Pelotas Birth Cohort.
Results
The proportion of children with IQ z-score < −1 was 16.9% (95% CI 15.6–18.1). The final model included the following early life variables: child’s gender; parents’ skin color; number of siblings; father’s and mother’s employment status; household income; maternal education; number of persons per room; duration of breastfeeding; height-for-age deficit; head circumference-for-age deficit; parental smoking during pregnancy; and maternal perception of the child’s health status. The area under the ROC curve for our final model was 0.8, with sensitivity of 72% and specificity of 74%. Similar results were found when testing external validation by using data from the 1993 Pelotas Birth Cohort.
Conclusions
The study results suggest that a child’s and her/his family’s social conditions are strong predictors of cognitive ability in childhood. Interventions for promoting a healthy early childhood development are needed targeting children at risk of low IQ so that they can reach their full cognitive potential.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-014-0308-1) contains supplementary material, which is available to authorized users.
doi:10.1186/s12887-014-0308-1
PMCID: PMC4272809  PMID: 25510879
Child development; Birth cohort; Intelligence; Cognition; Social determinants of health; Brazil
9.  Association between postnatal catch-up growth and obesity in childhood: prospective cohort study 
BMJ : British Medical Journal  2000;320(7240):967-971.
Objective
To identify predictors of postnatal catch-up growth from birth to two years and its relation to size and obesity at five years.
Design
Regional prospective cohort study.
Setting
Avon longitudinal study of pregnancy and childhood, United Kingdom.
Subjects
848 full term singletons from a 10% random sample of the Avon longitudinal study of pregnancy and childhood.
Main outcome measures
Maternal birth weight, prepregnancy weight, pregnancy weight gain, height, smoking, and parity, and paternal height. Weight and length of infants at birth, two years, and five years expressed as standard deviation (SD) scores from the UK reference scores for 1990. Percentage fat mass and total fat mass (estimated from skinfolds) and waist circumference at five years.
Results
Size at birth was representative of the national reference. Overall, 30.7% (260 of 848) of infants showed a gain in SD score for weight greater than 0.67 SD scores between zero and two years, indicating clinically significant catch-up growth. These children had lower weight, length, and ponderal index at birth than other children, and were more often from primiparous pregnancies. They also had taller fathers than other children, and their mothers had lower birth weights and were more likely to smoke during pregnancy. Children who showed catch-up growth between zero and two years were heavier, taller, and fatter (body mass index, percentage body fat, and waist circumference) at five years than other children.
Conclusions
In this contemporary well nourished cohort, catch-up growth was predicted by factors relating to intrauterine restraint of fetal growth. Children who showed catch-up growth between zero and two years were fatter and had more central fat distribution at five years than other children. Mechanisms that signal and regulate early catch-up growth in the postnatal period may influence associations between small size at birth and risks for disease in adulthood.
PMCID: PMC27335  PMID: 10753147
10.  Intergenerational effect of weight gain in childhood on offspring birthweight 
Background Some studies suggest that weight gain in childhood may increase the risk of chronic diseases in adulthood, and recent studies have noticed that the timing of weight gain may be related to its long-term consequence. However, weight gain in childhood has clear short-term benefits, and the literature on the pro and cons of weight gain in childhood is limited.
Methods In 1982, all 5914 hospital births (over 99% of all deliveries) occurring in Pelotas, Southern Brazil, were identified and studied prospectively on several occasions. In 2004–05, we attempted to trace the whole cohort and information on offspring birthweight was collected. Conditional growth modelling was used to assess the association between offspring birthweight and weight gain from birth to 20 months, and from 20 to 42 months.
Results In 2004–05, we interviewed 4297 subjects, with a follow-up rate of 77.4%. This manuscript includes data from 848 women who had already delivered a child and 525 men who were fathers at the mean age of 23 years. Maternal birthweight, weight and length for age Z-score at 20 months of age were positively associated with next-generation birthweight, whereas paternal variables were not related to the outcome. Conditional growth modelling analyses showed that women whose weight gain in the first 20 months of life was faster than predicted had heavier babies, whereas paternal weight gain was not associated. The association was strongest for mothers whose birthweight for gestational age was in the lowest tertile.
Conclusion Maternal, but not paternal birthweight and weight gain in early childhood are positively associated with next-generation birthweight.
doi:10.1093/ije/dyp168
PMCID: PMC2689398  PMID: 19376883
Weight gain; intergenerational effect; birthweight
11.  The impact of a minimal smoking cessation intervention for pregnant women and their partners on perinatal smoking behaviour in primary health care: A real-life controlled study 
BMC Public Health  2008;8:325.
Background
There is a demand for strategies to promote smoking cessation in high-risk populations like smoking pregnant women and their partners. The objectives of this study were to investigate parental smoking behaviour during pregnancy after introduction of a prenatal, structured, multi-disciplinary smoking cessation programme in primary care, and to compare smoking behaviour among pregnant women in the city of Trondheim with Bergen and Norway.
Methods
Sequential birth cohorts were established to evaluate the intervention programme from September 2000 to December 2004 in primary care as a part of the Prevention of Allergy among Children in Trondheim study (PACT). The primary outcome variables were self reported smoking behaviour at inclusion and six weeks postnatal. Data from the Medical Birth Registry of Norway (MBR) were used to describe smoking cessation during pregnancy in Trondheim, Bergen and Norway 1999–2004.
Results
Maternal smoking prevalence at inclusion during pregnancy were 5% (CI 95% 4–6) in the intervention cohort compared to 7% (CI 95% 6–9), p = 0.03, in the control cohort. Of the pre-pregnancy maternal smokers 25% (CI 95% 20–31) and 32% (CI 95% 26–38), p = 0.17, were still smoking at inclusion in the intervention and control cohorts, respectively. Six weeks postnatal 72% (CI 95% 59–83) and 68% (CI 95% 57–77), p = 0.34 of the maternal smokers at inclusion still smoked. No significant difference in paternal smoking between the cohorts was found after the intervention period. Data from the MBR showed a significantly higher proportion of women who stopped smoking during pregnancy in Trondheim than in Bergen in 2003 and 2004, p = 0.03 and < 0.001, respectively.
Conclusion
No impact on parental smoking behaviour between the cohorts was observed after the smoking intervention programme. Of the women who stopped smoking during pregnancy most of them stopped smoking before the intervention. However, we observed a significantly higher quitting rate in Trondheim than in Bergen in 2003 and 2004 which may have been facilitated by the supplemental attention on smoking behaviour the PACT study initiated.
doi:10.1186/1471-2458-8-325
PMCID: PMC2559841  PMID: 18808705
12.  Maternal anthropometric characteristics in pregnancy and blood pressure among adolescents: 1993 live birth cohort, Pelotas, southern Brazil 
BMC Public Health  2010;10:434.
Background
We investigated the association between maternal anthropometric measurements in prepregnancy and at the end of pregnancy and their children's systolic (SBP) and diastolic (DBP) blood pressure at 11 years of age, in a prospective cohort study.
Methods
All hospital births which took place in 1993 in the city of Pelotas - Brazil, were identified (5,249 live births). In 2004, the overall proportion of follow-up was 85% and we obtained arterial blood pressure measurements of 4,452 adolescents.
Results
Independent variables analyzed included maternal prepregnancy weight and body mass index (BMI) and maternal weight, and height at the end of pregnancy. Multiple linear regression analysis controlling for the following confounders were carried out: adolescent's skin color, family income at birth, smoking, alcohol intake during pregnancy, and gestational arterial hypertension. Mean SBP and DBP were 101.9 mmHg (SD 12.3) and 63.4 mmHg (SD 9.9), respectively. Maternal prepregnancy weight and BMI, and weight at the end of pregnancy were positively associated with both SBP and DBP in adolescent subjects of both sexes; maternal height was positively associated with SBP only among males.
Conclusions
Adequate evaluation of maternal anthropometric characteristics during pregnancy may prevent high levels of blood pressure among adolescent children.
doi:10.1186/1471-2458-10-434
PMCID: PMC2918557  PMID: 20653949
13.  Effect of Maternal Smoking Cessation Before and During Early Pregnancy on Fetal and Childhood Growth 
Journal of Epidemiology  2014;24(1):60-66.
Background
Maternal smoking during pregnancy is a major cause of intrauterine growth restriction and childhood obesity, but only a few studies have examined the association of smoking cessation before and during pregnancy with fetal and childhood growth. We examined this association in a prospective cohort study in Japan.
Methods
Our study included children born between 1991 and 2006 and their mothers. Using a questionnaire, maternal smoking status was recorded at pregnancy. The anthropometric data of the children were collected during a medical check-up at age 3 years. Multiple linear and logistic regression models were used for data analysis stratified by sex.
Results
In total, 2663 mothers reported their smoking status during early pregnancy, and data were collected from 2230 (83.7%) children at age 3 years. Maternal smoking during pregnancy was associated with a significant reduction in birth weight (approximately 120–150 g). Body mass index at age 3 years was significantly higher among boys born to smoking mothers than among boys born to nonsmoking mothers. Maternal smoking during pregnancy was associated with overweight at age 3 years among boys (adjusted odds ratio, 2.4; 95% CI, 1.03–5.4). However, among women who stopped smoking in early pregnancy, there was no increase in the risks of a small for gestational age birth or childhood overweight at age 3 years.
Conclusions
Children born to mothers who stopped smoking before or during early pregnancy had appropriate fetal and childhood growth.
doi:10.2188/jea.JE20130083
PMCID: PMC3872526  PMID: 24335086
smoking cessation; pregnancy; fetal growth; childhood growth
14.  Association of socioeconomic position with maternal pregnancy and infant health outcomes in birth cohort studies from Brazil and the UK 
Background
Socioeconomic inequalities in health outcomes are dynamic and vary over time. Differences between countries can provide useful insights into the causes of health inequalities. The study aims to compare the associations between two measures of socioeconomic position (SEP)—maternal education and family income—and maternal and infant health outcomes between ALSPAC and Pelotas cohorts.
Methods
Birth cohort studies were started in Avon, UK, in 1991 (ALSPAC) and in the city of Pelotas, Brazil, in 1982, 1993 and 2004. Maternal outcomes included smoking during pregnancy, caesarean section and delivery not attended by a doctor. Infant outcomes were preterm birth, intra-uterine growth restriction (IUGR) and breast feeding for <3 months. The relative index of inequality was used for each measure of SEP so that results were comparable between cohorts.
Results
An inverse association (higher prevalence among the poorest and less educated) was observed for almost all outcomes, with the exception of caesarean sections where a positive association was found. Stronger income-related inequalities for smoking and education-related inequalities for breast feeding were found in the ALSPAC study. However, greater inequalities in caesarean section and education-related inequalities in preterm birth were observed in the Pelotas cohorts.
Conclusions
Mothers and infants have more adverse health outcomes if they are from poorer and less well-educated socioeconomic backgrounds in both Brazil and the UK. However, our findings demonstrate the dynamic nature of the association between SEP and health outcomes. Examining differential socioeconomic patterning of maternal and infant health outcomes might help understanding of mechanisms underlying such inequalities.
doi:10.1136/jech.2010.108605
PMCID: PMC3245894  PMID: 20628081
Socioeconomic factors; health status disparities; cohort studies; pregnancy; infant; longitudinal studies; social inequalities
15.  Lifecourse relationship between maternal smoking during pregnancy, birth weight, contemporaneous anthropometric measurements and bone mass at 18 years old. The 1993 Pelotas Birth Cohort 
Early Human Development  2014;90(12):901-906.
Background
Maternal smoking during pregnancy is associated with short-term and also long-term harmful effects on offspring.
Objective
The aim of this study is to evaluate the associations of maternal smoking during pregnancy with offspring bone health at 18 years old, and the role of birth weight and contemporaneous height, weight and body mass index (BMI) in this association.
Data from the 1993 Pelotas Birth Cohort were analyzed using path analysis stratified by sex.
Adolescents at 18 years old (N = 1512 males, 1563 females).
DXA-determined total body bone mineral density (BMD) and bone mineral content (BMC) were assessed at 18 years old.
Results
Each additional cigarette smoked during pregnancy was associated with a lower BMC by − 4.20 g in males (95% CI − 8.37; − 0.05), but not in females [− 2.22 g (95% CI − 5.49; 1.04)]; weaker inverse associations were observed for BMD. This inverse association was explained by the influence of maternal smoking on birth weight and contemporaneous anthropometry, particularly height. A 1 kg higher birth weight was associated with a higher BMC by around 144 g in males and by around 186 g in females, and also with a higher BMD by around 0.019 g/cm2 in males and by around 0.018 g/cm2 in females, respectively.
Conclusions
Lifecourse analysis using path models has enabled to evaluate the role of mediators in the associations of maternal smoking during pregnancy and birth weight with bone mass in the offspring, thus generating improved understanding of the etiology of bone health and the importance of early life experiences.
Highlights
•Each additional cigarette smoked during pregnancy was associated with a lower BMC by − 4.20 g in males at 18 years old.•This inverse association was mediated by birth weight and contemporaneous anthropometry, particularly height.•Birth weight was associated with a higher BMD/BMC in both sexes.
doi:10.1016/j.earlhumdev.2014.08.024
PMCID: PMC4252063  PMID: 25463840
Smoking; Birth weight; Height; Body mass index; Bone mass; Bone density; Bone content; Absorptiometry; Photon; Longitudinal studies; Path analysis; Structural equation model
16.  Advancing maternal age is associated with lower bone mineral density in young adult male offspring 
Osteoporosis International  2011;23(2):475-482.
Summary
Advancing maternal age has been related to increased risk of fetal death and morbidity, as well as higher fracture risk during childhood, in the offspring. In the present study, we demonstrate that advancing maternal age is independently associated with reduced bone mass in the young adult male offspring.
Introduction
In Sweden the maternal age in both primi- and multipara mothers has steadily increased during the last three decades. It has been previously reported that advancing maternal age increases the risk of fetal death, but also of morbidity in the offspring, such as chromosome abnormalities, leukemia, diabetes mellitus type 1, and schizophrenia. Whether or not maternal age influences peak bone mass has not been reported. The aim of the present study was to investigate whether a high maternal age was associated with lower peak bone mass, as measured using DXA in a large cohort of male offspring [the Gothenburg Osteoporosis and Obesity Determinants study (GOOD)].
Methods
Through the Swedish multi-generation register, we identified the mothers of 1,009 GOOD study subjects. From the Swedish medical birth register detailed information about the medical circumstances at the time of child birth were obtained, including maternal and offspring anthropometrics (birth height and weight), maternal age, and smoking habits, parity and length of pregnancy.
Results
Maternal age was inversely correlated to areal BMD (aBMD) at the total body (r =−0.07, p = 0.03) and the lumbar spine (r =−0.09, p < 0.01). Using a linear regression model (with covariates including current physical activity, smoking, calcium intake, weight, present height and birth height, total body lean and fat mass in the offspring, and length of pregnancy), we found that maternal age negatively independently predicted lumbar spine aBMD (β =−0.08, p < 0.01) in the male offspring.
Conclusions
In conclusion, our results suggest that advancing maternal age could negatively affect bone mass in young adult men.
doi:10.1007/s00198-011-1558-5
PMCID: PMC3261413  PMID: 21350896
Bone mineral density; Dual X-ray absorptiometry; Maternal age; Men
17.  The role of early life variables on the risk of fractures from birth to early adolescence: a prospective birth cohort study 
Osteoporosis International  2009;20(11):1873-1879.
Summary
In a prospective cohort from Brazil, we evaluated the incidence of fractures from birth to early adolescence and examined risk factors for fractures. The incidence was 14.2% (95%CI 13.2, 15.2). Male sex, birth length, and maternal age at delivery were positively associated with the risk of fractures.
Introduction
This study aims to evaluate the incidence of fractures from birth to 11 years of age and to explore the effect of early life variables on the risk of fractures.
Methods
All children (N = 5,249) born in 1993 in the city of Pelotas, Brazil were enrolled in a prospective birth cohort study. In 2004–2005, 87.5% of the cohort members were sought for a follow-up visit. History of fractures, including anatomic site and age of the fracture were asked to mothers.
Results
The incidence of fractures from birth to 11 years of age was 14.2% (95%CI 13.2, 15.2). Out of the 628 subjects who experienced a fracture, 91 reported two and only 20 reported three or more fractures. Male sex, birth length, and maternal age at delivery were positively associated with the risk of fractures. No consistent associations were found for family income, maternal body mass index, smoking during pregnancy, and birth weight.
Conclusions
Birth length seems to have long-term effect on musculoskeletal health. The higher risk of fractures among children of older mothers needs to be confirmed by other studies. In accordance to the developmental origins of diseases, fractures seem to be, at least in part, programmed in early life.
doi:10.1007/s00198-009-0889-y
PMCID: PMC2765653  PMID: 19271096
Epidemiology; Fractures; Musculoskeletal disorders; Prospective studies
18.  Maternal Depressive Symptoms Not Associated with Reduced Height in Young Children in a US Prospective Cohort Study 
PLoS ONE  2010;5(10):e13656.
Background
Shorter stature is associated with greater all cause and heart disease mortality, but taller stature with increased risk of cancer mortality. Though childhood environment is important in determining height, limited data address how maternal depression affects linear growth in children. We examined the relationships between antenatal and postpartum depressive symptoms and child height and linear growth from birth to age 3 years in a U.S. sample.
Methods
Subjects were 872 mother-child pairs in Project Viva, a prospective pre-birth cohort study. The study population is relatively advantaged with high levels of income and education and low risk of food insecurity. We assessed maternal depression at mid-pregnancy (mean 28 weeks' gestation) and 6 months postpartum with the Edinburgh Postnatal Depression Scale (score > = 13 on 0–30 scale indicating probable depression). Child outcomes at age 3 were height-for-age z-score (HAZ) and leg length. HAZ was also available at birth and ages 6 months, 1, 2, and 3 years.
Findings
Seventy (8.0%) women experienced antenatal depression and 64 (7.3%) experienced postpartum depression. The mean (SD) height for children age 3 was 97.2 cm (4.2), with leg length of 41.6 cm (2.6). In multivariable linear regression models, exposure to postpartum depression was associated with greater HAZ (0.37 [95% confidence interval: 0.16, 0.58]) and longer leg length (0.88 cm [0.35, 1.41]). The relationship between postpartum depression and greater HAZ was evident starting at 6 months and continued to age 3. We found minimal relationships between antenatal depression and child height outcomes.
Conclusion
Our findings do not support the hypothesis that maternal depression is associated with reduced height in children in this relatively advantaged sample in a high-income country.
doi:10.1371/journal.pone.0013656
PMCID: PMC2965089  PMID: 21048958
19.  Cardio-metabolic risk in 5-year-old children prenatally exposed to maternal psychosocial stress: the ABCD study 
BMC Public Health  2010;10:251.
Background
Recent evidence, both animal and human, suggests that modifiable factors during fetal and infant development predispose for cardiovascular disease in adult life and that they may become possible future targets for prevention. One of these factors is maternal psychosocial stress, but so far, few prospective studies have been able to investigate the longer-term effects of stress in detail, i.e. effects in childhood. Therefore, our general aim is to study whether prenatal maternal psychosocial stress is associated with an adverse cardio-metabolic risk profile in the child at age five.
Methods/design
Data are available from the Amsterdam Born Children and their Development (ABCD) study, a prospective birth cohort in the Netherlands. Between 2003-2004, 8,266 pregnant women filled out a questionnaire including instruments to determine anxiety (STAI), pregnancy related anxiety (PRAQ), depressive symptoms (CES-D), parenting stress (PDH scale) and work stress (Job Content Questionnaire).
Outcome measures in the offspring (age 5-7) are currently collected. These include lipid profile, blood glucose, insulin sensitivity, body composition (body mass index, waist circumference and bioelectrical impedance analysis), autonomic nervous system activity (parasympathetic and sympathetic measures) and blood pressure.
Potential mediators are maternal serum cortisol, gestational age and birth weight for gestational age (intrauterine growth restriction). Possible gender differences in programming are also studied.
Discussion
Main strengths of the proposed study are the longitudinal measurements during three important periods (pregnancy, infancy and childhood), the extensive measurement of maternal psychosocial stress with validated questionnaires and the thorough measurement of the children's cardio-metabolic profile. The availability of several confounding factors will give us the opportunity to quantify the independent contribution of maternal stress during pregnancy to the cardio-metabolic risk profile of her offspring. Moreover, the mediating role of maternal cortisol, intrauterine growth, gestational age and potential gender differences can be explored extensively. If prenatal psychosocial stress is indeed found to be associated with the offspring's cardio-metabolic risk, these results support the statement that primary prevention of cardiovascular disease may start even before birth by reducing maternal stress during pregnancy.
doi:10.1186/1471-2458-10-251
PMCID: PMC2882911  PMID: 20470407
20.  Maternal Overweight and Obesity and Risks of Severe Birth-Asphyxia-Related Complications in Term Infants: A Population-Based Cohort Study in Sweden 
PLoS Medicine  2014;11(5):e1001648.
Martina Persson and colleagues use a Swedish national database to investigate the association between maternal body mass index in early pregnancy and severe asphyxia-related outcomes in infants delivered at term.
Please see later in the article for the Editors' Summary
Background
Maternal overweight and obesity increase risks of pregnancy and delivery complications and neonatal mortality, but the mechanisms are unclear. The objective of the study was to investigate associations between maternal body mass index (BMI) in early pregnancy and severe asphyxia-related outcomes in infants delivered at term (≥37 weeks).
Methods and Findings
A nation-wide Swedish cohort study based on data from the Medical Birth Register included all live singleton term births in Sweden between 1992 and 2010. Logistic regression analyses were used to obtain odds ratios (ORs) with 95% CIs for Apgar scores between 0 and 3 at 5 and 10 minutes, meconium aspiration syndrome, and neonatal seizures, adjusted for maternal height, maternal age, parity, mother's smoking habits, education, country of birth, and year of infant birth. Among 1,764,403 term births, 86% had data on early pregnancy BMI and Apgar scores. There were 1,380 infants who had Apgar score 0–3 at 5 minutes (absolute risk  = 0.8 per 1,000) and 894 had Apgar score 0–3 at 10 minutes (absolute risk  = 0.5 per 1,000). Compared with infants of mothers with normal BMI (18.5–24.9), the adjusted ORs (95% CI) for Apgar scores 0–3 at 10 minutes were as follows: BMI 25–29.9: 1.32 (1.10–1.58); BMI 30–34.9: 1.57 (1.20–2.07); BMI 35–39.9: 1.80 (1.15–2.82); and BMI ≥40: 3.41 (1.91–6.09). The ORs for Apgar scores 0–3 at 5 minutes, meconium aspiration, and neonatal seizures increased similarly with maternal BMI. A study limitation was lack of data on effects of obstetric interventions and neonatal resuscitation efforts.
Conclusion
Risks of severe asphyxia-related outcomes in term infants increase with maternal overweight and obesity. Given the high prevalence of the exposure and the severity of the outcomes studied, the results are of potential public health relevance and should be confirmed in other populations. Prevention of overweight and obesity in women of reproductive age is important to improve perinatal health.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Economic, technologic, and lifestyle changes over the past 30 years have created an abundance of cheap, accessible, high-calorie food. Combined with fewer demands for physical activity, this situation has lead to increasing body mass throughout most of the world. Consequently, being overweight or obese is much more common in many high-income and low-and middle-income countries compared to 1980. Worldwide estimates put the percentage of overweight or obese adults as increasing by over 10%, between 1980 and 2008.
As being overweight becomes a global epidemic, its prevalence in women of reproductive age has also increased. Pregnant women who are overweight or obese are a cause for concern because of the possible associated health risks to both the infant and mother. Research is necessary to more clearly define these risks.
Why Was This Study Done?
In this study, the researchers investigated the complications associated with excess maternal weight that could hinder an infant from obtaining enough oxygen during delivery (neonatal asphyxia). All fetuses experience a loss of oxygen during contractions, however, a prolonged loss of oxygen can impact an infant's long-term development. To explore this risk, the researchers relied on a universal scoring system known as the Apgar score. An Apgar score is routinely recorded at one, five, and ten minutes after birth and is calculated from an assessment of heart rate, respiratory effort, and color, along with reflexes and muscle tone. An oxygen deficit during delivery will have an impact on the score. A normal score is in the range of 7–10. Body mass index (BMI) a calculation that uses height and weight, was used to assess the weight status (i.e., normal, overweight, obese) of the mother during pregnancy.
What Did the Researchers Do and Find?
Using the Swedish medical birth registry (a database including nearly all the births occurring in Sweden since 1973) the researchers selected records for single births that took place between 1992 to 2010. The registry also incorporates prenatal care data and researchers further selected for records that included weight and height measurement taken during the first prenatal visit. BMI was calculated using the weight and height measurement. Based on BMI ranges that define weight groups as normal, overweight, and obesity grades I, II, and III, the researchers analyzed and compared the number of low Apgar scoring infants (Apgar 0–3) in each group. Mothers with normal weight gave birth to the majority of infants with Apgar 0–3. In comparison the proportion of low Apgar scores were greater in babies of overweight and obese mothers. The researchers found that the rates of low Apgar scores increased with maternal BMI: the authors found that rates of low Apgar score at 5 minutes increased from 0.4 per 1,000 among infants of underweight women (BMI <18.5) to 2.4 per 1,000 among infants of women with obesity class III (BMI ≥40). Furthermore, overweight (BMI 25.0–29.9) was associated with a 55% increased risk of low Apgar scores at 5 minutes; obesity grade I (BMI 30–34.9) and grade II (BMI 35.0–39.9) with an almost 2-fold and a more than 2-fold increased risk, respectively; and obesity grade ΙΙΙ (BMI ≥40.0) with a more than 3-fold increase in risk. Finally, maternal overweight and obesity also increase the risks for seizures and meconium aspiration in the neonate.
What Do These Findings Mean?
These findings suggest that the risk of experiencing an oxygen deficit increases for the babies of women who are overweight or obese. Given the high prevalence of overweight and obesity in many countries worldwide, these findings are important and suggest that preventing women of reproductive age from becoming overweight or obese is therefore important to the health of their children.
A limitation of this study is the lack of data on the effects of clinical interventions and neonatal resuscitation efforts that may have been performed at the time of birth. Also Apgar scoring is based on five variables and a low score is not the most direct way to determine if the infant has experienced an oxygen deficit. However, these findings suggest that early detection of perinatal asphyxia is particularly relevant among infants of overweight and obese women although more studies are necessary to confirm the results in other populations.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001648.
The US National Institutes of Health explains and calculates body mass index
The NIH also defines the Apgar scoring system
The United Kingdom's National Health Service has information for pregnant woman who are overweight
The UK-based Overseas Development Institute discusses how changes in diet have led to a worldwide health crisis in its “Future Diets” publication
Information about the Swedish health care system is available
Information in English is available from the National Board of Health and Welfare in Sweden
doi:10.1371/journal.pmed.1001648
PMCID: PMC4028185  PMID: 24845218
21.  Maternal smoking during pregnancy and offspring smoking initiation: assessing the role of intrauterine exposure 
Addiction (Abingdon, England)  2014;109(6):1013-1021.
Aims
To assess whether associations between maternal smoking during pregnancy and offspring smoking initiation are due to intrauterine mechanisms.
Design
Comparison of associations of maternal and partner smoking behaviour during pregnancy with offspring smoking initiation using partner smoking as a negative control (n = 6484) and a Mendelian randomization analysis (n = 1020), using a genetic variant in the mothers as a proxy for smoking cessation during pregnancy.
Setting
A longitudinal birth cohort in South West England.
Participants
Participants of the Avon Longitudinal Study of Parents and Children (ALSPAC).
Measurements
Smoking status during pregnancy was self-reported by mother and partner in questionnaires administered at pregnancy. Latent classes of offspring smoking initiation (non-smokers, experimenters, late-onset regular smokers and early-onset regular smokers) were previously developed from questionnaires administered at 14–16 years. A genetic variant, rs1051730, was genotyped in the mothers.
Findings
Both mother and partner smoking were similarly positively associated with offspring smoking initiation classes, even after adjustment for confounders. Odds ratios (OR) [95% confidence interval (CI)] for class membership compared with non-smokers were: experimenters: mother OR = 1.33 (95% CI = 1.06, 1.67), partner OR = 1.28 (95% CI = 1.06, 1.55), late-onset regular smokers: mother OR = 1.80 (95% CI = 1.43, 2.26), partner OR = 1.86 (95% CI = 1.52, 2.28) and early-onset regular smokers: mother OR = 2.89 (95% CI = 2.12, 3.94), partner OR = 2.50 (95% CI = 1.85, 3.37). There was no clear evidence for a dose–response effect of either mother or partner smoking heaviness on class membership. Maternal rs1051730 genotype was not clearly associated with offspring smoking initiation class in pre-pregnancy smokers (P = 0.35).
Conclusion
The association between smoking during pregnancy and offspring smoking initiation does not appear to operate through intrauterine mechanisms.
doi:10.1111/add.12514
PMCID: PMC4114534  PMID: 24521169
ALSPAC; intrauterine; maternal smoking; Mendelian randomization; negative control; offspring smoking; pregnancy; tobacco
22.  Maternal and Paternal Smoking During Pregnancy and Risk of ADHD Symptoms in Offspring: Testing for Intrauterine Effects 
American Journal of Epidemiology  2012;176(3):261-268.
Maternal smoking during pregnancy is associated with attention deficit hyperactivity disorder (ADHD) in offspring. It is assumed by many that this association is causal. Others suggest that observed associations are due to unmeasured genetic factors or other confounding factors. The authors compared risks of maternal smoking during pregnancy with those of paternal smoking during pregnancy. With a causal intrauterine effect, no independent association should be observed between paternal smoking and offspring ADHD. If the association is due to confounding factors, risks of offspring ADHD should be of similar magnitudes regardless of which parent smokes. This hypothesis was tested in 8,324 children from a well-characterized United Kingdom prospective cohort study, the Avon Longitudinal Study of Parents and Children (data from 1991–2000). Associations between offspring ADHD and maternal and paternal smoking during pregnancy were compared using regression analyses. Offspring ADHD symptoms were associated with exposure to both maternal and paternal smoking during pregnancy (mothers: β = 0.25, 95% confidence interval: 0.18, 0.32; fathers: β = 0.21, 95% confidence interval: 0.15, 0.27). When paternal smoking was examined in the absence of maternal smoking, associations remained and did not appear to be due to passive smoking exposure in utero. These findings suggest that associations between maternal smoking during pregnancy and child ADHD may be due to genetic or household-level confounding rather than to causal intrauterine effects.
doi:10.1093/aje/kwr510
PMCID: PMC3406617  PMID: 22791738
attention deficit disorder with hyperactivity; causality; confounding factors (epidemiology); maternal exposure; paternal exposure; pregnancy; prenatal exposure delayed effects; smoking
23.  Pregnancy, Maternal Tobacco Smoking, and Early Age Leukemia in Brazil 
Frontiers in Oncology  2012;2:151.
Background: Cigarette smoking has been associated with acute myeloid leukemia (AML) but hypothesis on the association between maternal smoking during pregnancy and childhood leukemia remains unclear. Objectives: To investigate the association between maternal exposure to tobacco smoking during pregnancy and early age (<2 year) leukemia (EAL). Methods: A hospital-based multicenter case-control study aiming to explore EAL risk factors was carried out in Brazil during 1999–2007. Data were collected by direct interview with the biological mothers using a standardized questionnaire. The present study included 675 children (193 acute lymphoid leukemia – ALL, 59 AML and 423 controls), being the latter age frequency matched and paired by area of residence with the cases. Unconditional logistic regression was performed, and odds ratios (OR) on the association between tobacco smoking (3 months before pregnancy, during pregnancy, and 3 months after delivery) and EAL were ascertained after adjustment for selected variables (maternal age at birth and education, birth weight, infant skin color, and oral contraceptives use during pregnancy). Results: Smoking was reported by 17.5% of case mothers and 20.6% of controls. Among women who reported to have smoked 20 or more cigarettes during the index pregnancy, an adjusted OR = 5.28 (95% CI 1.40–19.95) for ALL was observed. Heavy smoking during breastfeeding yielded an adjusted risk estimate for ALL, OR = 7.78 (95% CI 1.33–45.5). No dose-response effect was observed according to smoking exposure during pregnancy and EAL. An association between secondhand smoking during pregnancy or breastfeeding was not observed. Conclusion: An association between maternal smoking and EAL in the offspring was restricted to women who have reported an intense exposure to tobacco smoke during pregnancy and breastfeeding.
doi:10.3389/fonc.2012.00151
PMCID: PMC3494108  PMID: 23162789
smoking; pregnancy; childhood cancer; infant leukemia; lactation
24.  Maternal smoking during pregnancy and risk factors for cardiovascular disease in adulthood 
Atherosclerosis  2011;219(2):815-820.
Objective
This study was aimed at assessing the effect of maternal smoking during pregnancy on metabolic cardiovascular risk factors in early adulthood in a Brazilian birth cohort, after controlling for possible confounding variables and health behaviors in early adulthood.
Methods
In 1982, the maternity hospitals in Pelotas, southern Brazil, were visited and all births were identified. Those livebirths whose family lived in the urban area of the city were studied prospectively. In 2004–2005, we attempted to follow the whole cohort, the subjects were interviewed, examined and blood sample was collected. The following outcomes were studied: blood pressure; HDL cholesterol; triglycerides; random blood glucose and C-reactive protein. To explore the effect of maternal smoking, we adjusted the coefficients for the following possible mediators: perinatal factors (low birthweight and preterm births); adult behavioral factors (physical activity, dietary pattern, intake of fat and fiber, and tobacco smoking) and adult anthropometry (body mass index and waist circumference).
Results
In 2004–2005, we interviewed 4297 subjects, with a follow-up rate of 77.4%. The only significant finding in the unadjusted analyses was lower HDL cholesterol among females. After adjustment for lifestyle variables in early adulthood, birthweight and waist circumference, the difference in HDL levels between offspring of smokers and non-smokers reduced from −2.10 mg/dL (95% confidence interval: −3.39; −0.80) to −1.03 mg/dL (−2.35; 0.30).
Conclusion
Evidence that maternal smoking during pregnancy programs offspring metabolic cardiovascular risk factors are scarce, and reported associations are likely due to postnatal exposure to lifestyle patterns.
doi:10.1016/j.atherosclerosis.2011.08.018
PMCID: PMC3234339  PMID: 21885051
Maternal smoking; Pregnancy; Cardiovascular; Risk factor
25.  Parental depressive and anxiety symptoms during pregnancy and attention problems in children: a cross-cohort consistency study 
Background
Maternal depression and anxiety during pregnancy have been associated with offspring-attention deficit problems.
Aim
We explored possible intrauterine effects by comparing maternal and paternal symptoms during pregnancy, by investigating cross-cohort consistency, and by investigating whether parental symptoms in early childhood may explain any observed intrauterine effect.
Methods
This study was conducted in two cohorts (Generation R, n = 2,280 and ALSPAC, n = 3,442). Pregnant women and their partners completed questionnaires to assess symptoms of depression and anxiety. Child attention problems were measured in Generation R at age 3 with the Child Behavior Checklist, and in ALSPAC at age 4 with the Strengths and Difficulties Questionnaire.
Results
In both cohorts, antenatal maternal symptoms of depression (Generation R: OR 1.23, 95% CI 1.05–1.43; ALSPAC: OR 1.33, 95% CI 1.19–1.48) and anxiety (Generation R: OR 1.24, 95% CI 1.06–1.46; ALSPAC: OR 1.32, 95% CI 1.19–1.47) were associated with a higher risk of child attention problems. In ALSPAC, paternal depression was also associated with a higher risk of child attention problems (OR 1.11, 95% CI 1.00–1.24). After adjusting for maternal symptoms after giving birth, antenatal maternal depression and anxiety were no longer associated with child attention problems in Generation R. Moreover, there was little statistical evidence that antenatal maternal and paternal depression and anxiety had a substantially different effect on attention problems of the child.
Conclusions
The apparent intrauterine effect of maternal depression and anxiety on offspring-behavioural problems may be partly explained by residual confounding. There was little evidence of a difference between the strength of associations of maternal and paternal symptoms during pregnancy with offspring-attention problems. That maternal symptoms after childbirth were also associated with offspring-behavioural problems may indicate a contribution of genetic influences to the association.
doi:10.1111/jcpp.12023
PMCID: PMC3796855  PMID: 23215861
Parental depression or anxiety; child attention problems; cohort studies; intrauterine effect

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