Recent Featured Publications
This is a small selection of recent publications on Project Viva research. For a more comprehensive list please click here.
Due to copyright issues, we are not able to post copies of the published articles. If Viva participants would like a copy of the article, please email us, Project_Viva@hphc.org.
Exposure to per- and poly-fluoroalkyl substances (PFAS), a group of human-made chemicals, has been associated with several health issues in adults and children including high cholesterol, thyroid disease and immune dysfunction. PFAS can be found in many things of our daily life such as non-stick cookware, water resistant clothing and cleaning products. Food is also a major source of PFAS exposure in adults as PFAS are commonly used to make food utensils and packaging and may migrate into foods from packaging or during preparation. However, studies of dietary patterns and PFAS in children are limited.
To examine this association, Project Viva researchers analyzed data taken from dietary questionnaires during the early childhood visit and PFAS plasma concentration from blood samples during the mid-childhood visit. They found that children who consumed more fish and packaged foods, especially ice cream and soda, had higher concentrations of certain PFAS chemicals. Identifying these childhood exposures to PFAS helps us understand the connection between dietary patterns or certain food choices and PFAS levels in children which may help minimize potential adverse health effects.
Seshasayee, S.M., Rifas-Shiman, S.L., Chavarro, J.E., Carwile, J.L., Lin, P.I.D., Calafat, A.M., Sagiv, S.K., Oken, E. and Fleisch, A.F., 2021. Dietary patterns and PFAS plasma concentrations in childhood: Project Viva, USA. Environment International, 151, p.106415.
Characterization of longitudinal wheeze phenotypes from infancy to adolescence in Project Viva, a prebirth cohort study
Wheezing, a condition characterized by a high-pitched sound made when breathing, is common among infant and children in early childhood. Wheezing in early life is an important indicator for the risk of developing asthma later in life. A study by Project Viva, published in the Journal of Allergy and Clinical Immunology, characterized wheeze patterns from infancy to adolescence and determined associations between early-life factors and specific genetic variants.
The investigators relied on responses from annual questionnaires to create four trajectories demonstrating the probability of wheezing at certain ages. They found four wheeze patterns: never/infrequent wheeze (62%), mid-childhood onset wheeze (10%), early transient infancy wheeze (22%), and persistent wheeze across childhood (6%). Several factors in early life predicted which pattern the child had. For example, children of mothers who had asthma, or who themselves had eczema during infancy, were more likely to have the mid-childhood onset wheezing. Interestingly, mothers who consumed acetaminophen (Tylenol) during pregnancy were more likely to have children wheezing at any timepoint. Also, genetic determinants shown to be related to asthma risk in prior genetic studies predicted the persistent wheeze pattern in Project Viva children.
Sordillo, J.E., Coull, B.A., Rifas-Shiman, S.L., Wu, A.C., Lutz, S.M., Hivert, M.F., Oken, E. and Gold, D.R., 2020. Characterization of longitudinal wheeze phenotypes from infancy to adolescence in Project Viva, a prebirth cohort study. Journal of Allergy and Clinical Immunology, 145(2), pp.716-719.
Americans, on average, consume 300 calories of added sugar daily that is substantially higher than the recommended limit. Overconsuming sugar may have adverse health implications, and excess intake may influence brain development in kids. Project Viva investigators examined the associations of prenatal and child sugar intake and child cognition. Investigators used food frequency questionnaires completed by Viva moms in the first and second trimesters of pregnancy and early childhood to assess sugar consumption from foods, fruit juices, and sugary beverages, as well as consumption of diet soda. They assessed brain development in Viva children at both early and mid-childhood using several tests that assessed memory, verbal skills, and motor skills.
This study found that greater sugar and sugary beverage consumption during both pregnancy and childhood adversely impacted a child's memory and learning. However, child consumption of fructose and fruit in early childhood was associated with higher brain development test scores in later childhood.
Cohen, J.F., Rifas-Shiman, S.L., Young, J. and Oken, E., 2018. Associations of prenatal and child sugar intake with child cognition. American journal of preventive medicine, 54(6), pp.727-735.
Asthma is a condition that affects the lungs, causing wheezing and difficulty breathing. It has been shown that high levels of air pollution in outdoor environments, also known as ambient pollution, can trigger symptoms of asthma, and exposure to pollution generally increases asthma risk. A study with Project Viva participants looked into whether long-term ‘low-grade’ pollution exposure over a person’s lifetime is associated with asthma in childhood. This study included 1522 children whose mothers enrolled in Project Viva during their pregnancy and calculated pollution exposure for each participant based on the geographic location of their home.
It was found that being exposed to higher levels of ambient pollution by living within 100 meters of a major road was associated with having asthma at some point during childhood. This association was strongest in girls during early-childhood (ages 3-5 years) and mid-childhood (ages 7-10 years). Investigators concluded that, even in the greater Boston area where pollution levels are generally lower and within standards set by the US Environmental Protection Agency (EPA), long-term pollution exposure from living close to a major road was associated with childhood asthma.
Rice, M.B., Rifas-Shiman, S.L., Litonjua, A.A., Gillman, M.W., Liebman, N., Kloog, I., Luttmann-Gibson, H., Coull, B.A., Schwartz, J., Koutrakis, P. and Oken, E., 2018. Lifetime air pollution exposure and asthma in a pediatric birth cohort. Journal of Allergy and Clinical Immunology, 141(5), pp.1932-1934.
Maternal diet during pregnancy is thought to influence the health outcomes of her child later in life, including adiposity (body fat) levels. Drinking sugar-sweetened beverages (SSBs), such as soda or fruit drinks, has been shown to predict excess weight gain and obesity in adults and children, and may be a key target for obesity prevention. In this study, Project Viva researchers examined the effects of maternal consumption of SSBs during pregnancy on mid-childhood adiposity levels.
Investigators observed that at mid-childhood (mean age = 7.7 years), children showed higher levels of adiposity when their mothers consumed more SSBs during their second trimester of pregnancy, compared to children of mothers who reported lower SSB consumption. Further, investigators observed that maternal consumption of SSBs, particularly soda, showed a stronger association with child adiposity than did child’s own consumption of SSBs. These findings suggest that limiting maternal intake of sugar-sweetened beverages during pregnancy could help in targeting childhood obesity.
Gillman MW, Rifas-Shiman SL, Fernandez-Barres S, Kleinman K, Taveras EM, Oken E. Beverage Intake during Pregnancy and Childhood Adiposity. Pediatrics. 2017 Aug; 140(2). pii: e20170031. Doi: 10.1542/peds.2017-0031.
Perfluoroalkyl substances, or PFASs, are synthetic compounds that are used in the production of items such as food packaging, insecticides, firefighting foam, and stain-resistant coatings. Humans are exposed to PFASs through these items, and previous research suggests that once in the body, PFASs may interrupt a person’s metabolism. Project Viva investigators were interested in studying the association of prenatal PFAS exposure on a child’s body composition in early and mid-childhood.
The investigators first analyzed PFAS levels in blood collected from 1,645 Project Viva mothers during early pregnancy. Then, using measurements recorded during Project Viva’s early and mid-childhood visits, the investigators assessed the child’s total and abdominal body fat measurements in relation to the mother’s PFAS level. Investigators found that there was no association between prenatal PFAS exposure and early childhood body fat or risk of being overweight in either boys or girls. They did, however, find a modest relationship between prenatal PFAS exposure and increased body fat measurements in girls only. These results were consistent with other studies such as a Danish study that observed positive associations between prenatal PFOA (a type of PFAS) and BMI in 20 year old women. What set this study apart from others though, was its large population size and unique methods like directly measuring adiposity by using a DXA machine.
Because PFASs are so common in the environment, it is important to better understand the effect PFASs have on public health. This study suggests that there may be some associations between PFASs and child adiposity, though these may be small and sex-specific.
Mora AM, Oken E, Rifas-Shiman SL, Webster TF, Gillman MW, Calafat AM, Ye X, Sagiv SK. Prenatal Exposure to Perfluoroalkyl Substances and Adiposity in Early and Mid-Childhood. Environ Health Perspect. 2017 Mar; 125(3):467-473. doi: 10.1289/EHP246. PMID: 27352404.
There are many risk factors for wheezing, such as parental history of asthma and early respiratory tract infections; however, a recent Project Viva study found that some of these risk factors for wheezing are specific to whether a child is male or female.
The investigators analyzed data from 1,623 Project Viva children who had at least one wheezing incident between the ages of 1 and 9, as reported by their mothers or guardians through yearly questionnaires. Wheezing was categorized into three different patterns: never or infrequent wheezing, periodic wheezing, and persistent wheezing. Persistent wheezing, which is focused on in the results, was defined as having a high or increasing probability of wheezing from ages 1 to 9.
The results of the analysis confirmed already known risk factors that affect both boys and girls, such as maternal asthma and infant bronchiolitis before age 1 year. In addition, the investigators identified sex-specific risk factors for persistent childhood wheeze; specifically, paternal asthma was a risk factor for boys, while being black or Hispanic was a risk factor for girls.
This is one of few studies that has defined different patterns of wheezing and focused on sex-specific risk factors for wheezing in children. These results could be used to improve clinical diagnosis for wheezing and asthma. In the future, researchers would like to further investigate why these sex-specific associations occur.
Tse SM, Rifas-Shiman SL, Coull BA, Litonjua AA, Oken E, Gold DR. Sex-Specific Risk Factors for Childhood Wheeze and Longitudinal Phenotypes of Wheeze. J Allergy Clin Immunol 2016 Dec; 138(6): 1561-1568.e6. doi: 10.1016/j.jaci.2016.04.005
Dietary Inflammatory Potential during Pregnancy Is Associated with Lower Fetal Growth and Breastfeeding Failure: Results from Project Viva
Levels of inflammation in the body are influenced by lifestyle factors, including an individual’s diet. Excess inflammation, particularly during pregnancy, has been linked to negative health outcomes, including prematurity, restricted fetal growth, and preeclampsia. Project Viva investigators were interested in examining the influence of maternal diet on inflammation during pregnancy and on pregnancy outcomes for both mother and child.
Project Viva investigators analyzed biological markers for inflammation – C-reactive protein (CRP) levels and white blood cell (WBC) count – and maternal diet during pregnancy. Investigators then examined whether dietary inflammation influenced pre- and postnatal outcomes, such as: gestational diabetes, preeclampsia, fetal growth, mode of delivery, length of gestation, gestational weight gain, and breastfeeding duration.
Investigators found that mothers who consumed a diet that was high in pro-inflammatory foods – such as breads, rice, or pastries – were more likely to have higher CRP levels in the second-trimester of pregnancy, as well as low infant birth weight and lower breastfeeding success. Investigators did not find a relationship between dietary inflammation and gestational diabetes, preeclampsia, gestational weight gain, length of gestation, or mode of delivery. These results suggest that proinflammatory diets during pregnancy are associated with increased levels of systemic inflammation in the mother, and may contribute to lower birth weight and breastfeeding failure.
Sen S, Rifas-¬Shiman SL, Shivappa N, Wirth MD, Hébert JR, Gold DR, Gillman MW, Oken E. Dietary Inflammatory Potential during Pregnancy Is Associated with Lower Fetal Growth and Breastfeeding Failure: Results from Project Viva.. J Nutr. 2016 Apr;146(4):728¬36. doi: 10.3945/jn.115.225581. Epub 2016 Mar 2. PMID: 26936137
Prenatal, perinatal, and childhood vitamin D exposure and their association with childhood allergic rhinitis and allergic sensitization
Project Viva investigators recently studied the association between prenatal vitamin D exposure and a child’s risk of having allergies at school age (median 7.7y). Vitamin D regulates certain parts of the immune system. Vitamin D deficiency can weaken a body’s tolerance for allergens, therefore increasing the likelihood of having an allergic reaction, such as to seasonal allergies. Additionally, vitamin D can begin regulating an infant’s immune system before birth, which makes this a very interesting and appropriate topic for Project Viva investigators to study.
Using food frequency questionnaires from 1,248 Project Viva mothers, the study investigators assessed maternal vitamin D intake from food during the first and second trimesters of pregnancy. Separate questionnaires were used to assess vitamin D intake from dietary supplements and a blood test was administered at 3 time points to measure serum 25-Hydroxyvitamin D 25(OH)D, which is another form of vitamin D in the body. At the mid-childhood visit, the mother reported whether her Project Viva child had ever been diagnosed with seasonal allergies. Children’s sensitization to common environmental allergens was also assessed.
In this analysis, the investigators determined that when the mother had higher food-based vitamin D intake during the first or second trimesters of her pregnancy, the chances of her school-age child ever having allergic rhinitis, commonly triggered by seasonal allergies, were reduced. The investigators did not find an association between vitamin D supplement intake and allergic rhinitis. They also did not find an association between serum 25(OH)D and IgE levels in the children. IgE is the antibody that is produced by the immune system and causes allergic reactions. Finally there was no association found between vitamin D and sensitization to environmental allergens.
Investigators think that the difference in associations between food and supplement intake may have to do with the other nutrients that accompany vitamin D in foods, as well as the fact that different forms of vitamin D are available in foods but not in supplements.
The results of this Project Viva analysis were consistent with those from another study, which found a relationship between maternal food-based vitamin D intake and a reduction of allergic rhinitis in 5-year old children. There is also a study that found no association between these variables; however, the amount of vitamin D intake for those mothers was lower than the intake of Project Viva mothers. The relationship between prenatal vitamin D exposure and childhood allergies is part of an ongoing debate, but this Project Viva study has provided solid evidence to support continued research on this topic.
Bunyavanich S, Rifas-Shiman SL, Platts-Mills TA, Workman L, Sordillo JE, Camargo CA, Jr., Gillman MW, Gold DR, Litonjua AA. Prenatal, Perinatal, and Childhood Vitamin D Exposure and Their Association with Childhood Allergic Rhinitis and Allergic Sensitization. J Allergy Clin Immunol 2016 Apr;137(4):1063-70.e1-2. doi: 10.1016/j.jaci.2015.11.031. Epub 2016 Feb 10. PMID: 26874366
Peanut, milk, and wheat intake during pregnancy is associated with reduced allergy and asthma in children
The prevalence of asthma and allergies has increased in the United States; an estimated 8.4% of the population has asthma and 5% has a food allergy. During the fetal period, the human immune system begins to develop by training its cells to differentiate harmful intruders from helpful or benign substances. A recent Project Viva study showed that early exposure to potential allergens via maternal diet during this critical period can be protective against childhood allergy and asthma. Using prenatal food frequency questionnaires, mother-reported data on child asthma and allergy, and child blood antibody levels for common allergens at mid-childhood, Dr. Bunyavanich and her team of investigators assessed the association between prenatal diet and offspring risk of allergy and asthma in mid-childhood. The study focused on five foods commonly associated with childhood allergies: egg, soy, peanut, milk, and wheat. Children of mothers with diets higher in peanuts during the first trimester of pregnancy were at a lower risk of experiencing peanut allergic reaction in mid-childhood. Additionally, higher maternal milk intake during the first trimester was associated with reduced childhood risk of asthma and allergic rhinitis, and higher maternal wheat intake in the second trimester was associated with reduced childhood risk of atopic dermatitis. Egg and soy consumption did not show a correlation to mid-childhood allergy and asthma. This study supports the idea that a mother’s diet during pregnancy helps to shape her child’s immune system, and prenatal exposure to milk, wheat and peanuts through the mother’s diet can protect children against allergy and asthma.
Bunyavanich S, Rifas-Shiman SL, Platts-Mills TA, Workman L, Sordillo JE, Camargo CA Jr, Gillman MW, Gold DR, Litonjua AA. Peanut, milk and wheat intake during pregnancy is associated with reduced allergy and asthma in children. J. Allergy Clin Immunol. 2014 May;133(5):1373-82.
While previous research has determined a strong association between air pollution exposure and respiratory infection, few studies have specifically examined the association between traffic related emissions and early childhood respiratory infection. Project Viva investigators were particularly interested in this because early-life respiratory infection is the leading cause of infant morbidity in the United States.
Project Viva investigators specifically looked at how far our participants lived from major roadways and traffic dense areas during their pregnancy and whether the air quality in these areas was associated with a doctor-diagnosed case of early-life respiratory infection in their children. In order to do this, analytic methods were used to determine the distance from participants’ homes to major roadways and traffic-dense areas during the first trimester of pregnancy.
Over half of the 1,263 Project Viva children included in this analysis had one or more doctor-diagnosed respiratory infections by the Age 3 (early-childhood) visit. The results indicate that living near a major roadway during pregnancy or at the time of birth is associated with a higher risk of having a child who develops early-life respiratory infections. Furthermore, the results suggest that living in areas with higher traffic density leads to a higher risk of early-life respiratory infection. Since most Project Viva mothers did not move during pregnancy, we cannot conclude whether the increased risk of respiratory infection was due to pre- or early post-natal exposures. These findings are important because they can potentially motivate policy change on controlling traffic emissions or help doctors identify children at risk of respiratory infection, such as those living in certain traffic dense communities.
Rice MB, Rifas-Shiman SL, Oken E, Gillman MW, Ljungman PL, Litonjua AA, Schwartz J, Coull BA, Zanobetti A, Koutrakis P, Melly SJ, Mittleman MA, Gold DR. Exposure to traffic and early life respiratory infection: A cohort study. Pediatr Pulmonol. 2014 Mar 27. doi: 10.1002/ppul.23029.
Investigators from Project Viva and similar studies were interested in determining if the bronchodilator response (BDR), a test used for diagnosing asthma in adults, could be applied to children as well. Typically, people with asthma experience what we call “reversible airflow obstruction.” Airflow obstruction refers to the blockage or inflammation in a person’s respiratory system that makes it difficult to breathe. Since this obstruction can be alleviated with the help of a bronchodilator—a medication that opens airways—it is considered to be reversible.
BDR is a tool used to demonstrate the reversibility of airflow obstruction and is determined by measuring the difference in lung function, as determined by spirometry, before and after inhaling a bronchodilator. In adult populations, a BDR change of 12% or greater may indicate that a person has asthma. Currently, there is no established BDR percentage that indicates asthma in pediatric populations. Investigators analyzed BDRs from 3 different studies (Childhood Asthma Management Program [n = 1041], Project Viva [n = 197] and Home Allergens [n = 53]) to see if 12% would be a sensitive cut off for children.
Sensitivity analyses were used to verify the effectiveness of the BDR as a diagnostic test. A higher sensitivity meant that less individuals suffering from asthma would go undiagnosed and untreated. Investigators reported that the widely used 12% or greater change in BDR offered worse sensitivity than a lower BDR cutoff of 8% or greater. However, even though investigators found that a lower BDR provided higher sensitivity, they did not recommend using a specific BDR cutoff at all when diagnosing asthma in pediatric populations due to measurement variability. Instead, the BDR test should be used as a general guideline in the treatment and diagnosis of asthma.
Tse, Sze Man, Diane R. Gold, Joanne E. Sordillo, Elaine B. Hoffman, Matthew W. Gillman, Sheryl L. Rifas-Shiman, Anne L. Fuhlbrigge, Kelan G. Tantisira, Scott T. Weiss, and Augusto A. Litonjua. Diagnostic Accuracy of the Bronchodilator Response in Children. Journal of Allergy and Clinical Immunology. 2013 Sep; 132(3): 554-559.e5.
Sleep curtailment is defined as a shortened sleep compared to average sleep duration, and is the most common cause of sleepiness in children. Evidence has linked sleep problems with negative effects on cognitive function, psychiatric disorders, and behavior. 1288 participants were studied for associations between race/ethnic and sleep curtailment from infancy to mid-childhood, to determine the extent to which socioeconomic and contextual factors both explain racial/ethnic differences and are independently associated with sleep curtailment.
In adjusted models, Black, Hispanic and Asian children had lower sleep curtailment scores than White children. These scores were partially explained by socio-contextual variables. Children from lower socioeconomic status and those with greater exposures to TV also had more sleep curtailment.
Taveras EM, Gillman MW, Peña MM, Redline S, Rifas-Shiman SL. Chronic sleep curtailment and adiposity. Pediatrics. 2014 Jun;133(6):1013-22.
Sleep curtailment is defined as a shortened sleep compared to average sleep duration, and may contribute to metabolic dysfunction. 652 children in the Project Viva cohort were studied for associations of chronic insufficient sleep with mid-childhood cardio-metabolic health.
Chronic insufficient sleep from infancy to school age was associated with higher mid-childhood metabolic risk. This association was explained by sleep duration’s influence on mid-childhood adiposity.
Cespedes EM, Gillman MW, Kleinman K, Rifas-Shiman SL, Redline S, Taveras EM. Television Viewing, Bedroom Television, and Sleep Duration From Infancy to Mid-Childhood. Pediatrics. 2014 Apr 14. [Epub ahead of print] PubMed PMID: 24733878.
Infant Feeding and Childhood Cognition at Ages 3 and 7 Years: Effects of Breatfeeding Duration and Exclusivity
A total of 1321 Project Viva mothers and children helped researchers in investigating the associations between breastfeeding and child cognition. While breastfeeding is important for many aspects of infant health, the link between breastfeeding and childhood cognitive development is unclear. Additionally, some nutrients in fish that are important for brain development are transferred to breast milk and may affect the relationship between breastfeeding and child cognition. Project Viva has collected data on many factors that might influence this relationship, including how long Viva babies were breastfed, when they started to eat solid foods, drink other liquids, and how much fish their mothers ate while breastfeeding. This rich set of information allowed Dr. Mandy Belfort to lead a team in investigating two important research questions: 1) Is duration and exclusivity of breastfeeding related to childhood cognitive development and 2) How does maternal fish consumption during lactation impact this relationship?
We found that the longer children were breastfed and the more exclusive the breastfeeding, the higher their scores on measures of cognitive development at ages 3 and 7. Children at age 3 had a better understanding of language, and children at age 7 had higher verbal and nonverbal IQ scores. These associations remained after accounting for other factors that can affect child cognition, such as maternal intelligence and home environment. These findings support national recommendations for exclusive breastfeeding to 4-6 months of age and continued breastfeeding through the first year of life. Also, there were greater beneficial effects of breasfeeding on child cognition for women who consumed two or more servings of fish per week during the 6 months after delivery, compared to women who had fewer servings of fish at that time. These findings show not only that breastfeeding is important for childhood cognitive development, but also that better maternal diet may increase these beneficial effects.
Belfort MB, Rifas-Shiman SL, Kleinman KP, Guthrie LB, Bellinger DC, Taveras EM, Gillman MW, Oken E. Infant Feeding and Childhood Cognition at Ages 3 and 7 Years: Effects of Breastfeeding Duration and Exclusivity. JAMA Pediatr. 2013 Jul 29.
If a mother develops diabetes during pregnancy (gestational diabetes mellitus aka GDM), her baby is more likely to be heavier and have more fat at birth than a baby whose mother had normal blood sugar levels. Project Viva investigators, led by Nolwenn Regnault, a visiting post-doctoral research fellow from France, were interested in looking at the relationship between mothers' blood sugar levels during pregnancy and the body composition of their children during mid-childhood. To assess body composition we used the information from dual X--ray absorptiometry (DXA) scans at the Mid-Childhood visit.
Viva investigators found that moms with high blood sugar during pregnancy had children with greater fat mass in mid-childhood, but the results differed depending on whether the child was a boy or a girl. Sons of mothers with gestational diabetes had higher fat mass in mid-childhood, but girls had a higher fat mass when their mothers had intermediate glucose intolerance (elevated blood sugar that is not as high as in gestational diabetes. Differences in the sensitivity to sugar levels between male and female babies while in the womb may explain this.
Regnault N, Gillman MW, Rifas-Shiman SL, Eggleston E, Oken E. Sex-Specific Associations of Gestational Glucose Tolerance with Childhood Body Composition. Diabetes Care. 2013 Jul 22.
Research and national statistics have shown that black and Hispanic children are more likely to be overweight or obese than their white peers. A 2010 article by Project Viva Investigator Elsie Taveras revealed a greater prevalence of early childhood obesity risk factors in black and Hispanic children than in white children. This suggested that the disparities in risk factors may lead to greater rates of obesity amongst minority children. Dr. Taveras's 2013 article aimed to test that hypothesis and examine the extent to which the racial/ethnic disparities in childhood overweight and obesity are explained by the differences in early life obesity risk factors.
Taveras looked at early life risk factors during pregnancy, infancy, and early childhood in Project Viva mother-child pairs, examining things such as (but not limited to) excessive weight gain during pregnancy, length of breastfeeding, infant daily sleep duration, and fast food consumption at 3 years of age. She found that the racial/ethnic disparities in childhood obesity were largely explained by the prevalence of risk exposures in each group in early life (especially during infancy and early childhood). The investigators concluded that reducing these risk factors could reduce the racial disparities in childhood obesity rates.
Taveras EM, Gillman MW, Kleinman KP, Rich-Edwards JW, Rifas-Shiman SL. Reducing Racial/Ethnic Disparities in Childhood Obesity: The Role of Early Life Risk Factors. JAMA Pediatr. 2013 Jun 3:1-7.