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1.  Functional status at 18 months of age as a predictor of childhood disability after neonatal hypoxic-ischemic encephalopathy 
AIM
In children with neonatal hypoxic-ischemic encephalopathy (HIE), we examined the association between 18-month functional status by parental report and disability at 6-7 years.
METHOD
Prospective observational study involving participants in the NICHD randomized controlled trial of hypothermia for HIE. Parent questionnaires-Functional Status-II (FS-II), Impact on Family (IOF) and Family Resource Scale (FRS) at 18 months were correlated with 6- to 7-year developmental assessments. Disability at 6-7 years was defined as IQ < 70, gross motor functional classification scale level III-V, bilateral blindness, deafness, or epilepsy.
RESULTS
Rates of severe HIE (32 vs. 15%), public insurance (73% vs. 47%) and IOF scales were higher and mean (SD) FS-II independence (I) {54 (SD 35) vs. 98 (SD 8)} and general health (GH) {87 (SD 14) vs. 98 (SD 6)} scores were significantly lower in children with disability (n=37) at 6-7 years, compared to those (n=74) without disability. FS-II I scores were significantly associated with disability (OR 0.92; 95% CI 0.87-0.97; p=0.003). On path analysis, severe HIE, greater IOF and public insurance were associated with poorer 18-month FS-II I scores, which, in turn, were associated with disability at 6 to 7 years.
INTERPRETATION
Poor independent functioning by parental report at 18 months in children with HIE was associated with childhood disability.
doi:10.1111/dmcn.12512
PMCID: PMC4324462  PMID: 24957482
2.  Early working memory as a racially and ethnically neutral measure of outcome in extremely preterm children at 18-22 months 
Early human development  2013;89(12):10.1016/j.earlhumdev.2013.08.009.
Background
Difficulties with executive function has been found in preterm children, resulting in difficulties with learning and school performance.
Aim
This study evaluated the relationship of early working memory as measured by object permanence items to the cognitive and language scores on the Bayley Scales-III in a cohort of children born extremely preterm.
Study Design
Logistic regression models were conducted to compare object permanence scores derived from the Bayley Scales-III by race/ethnicity and maternal education, controlling for medical covariates.
Subjects
Extremely preterm toddlers (526), who were part of a Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network's multi-center study, were evaluated at 18-22 months corrected age.
Outcome Measures
Object permanence scores derived from the Bayley Developmental Scales were compared by race/ethnicity and maternal education, controlling for medical covariates.
Results
There were no significant differences in object permanence mastery and scores among the treatment groups after controlling for medical and social variables, including maternal education and race/ethnicity. Males and children with intraventricular hemorrhage, retinopathy of prematurity, and bronchopulmonary dysplasia were less likely to demonstrate object permanence mastery and had lower object permanence scores. Children who attained object permanence mastery had significantly higher Bayley Scales-III cognitive and language scores after controlling for medical and socio-economic factors.
Conclusions
Our measure of object permanence is free of influence from race, ethnic and socio-economic factors. Adding this simple task to current clinical practice could help detect early executive function difficulties in young children.
doi:10.1016/j.earlhumdev.2013.08.009
PMCID: PMC3830714  PMID: 23993309
Working memory; prematurity; development
3.  Neurodevelopmental Outcome of Extremely Low Birth Weight Infants with Candida Infection 
The Journal of pediatrics  2013;163(4):961-967.e3.
Objective
Candida remains an important cause of late-onset infection in preterm infants. Mortality and neurodevelopmental outcome of extremely low birthweight (ELBW) infants enrolled in the Candida study was evaluated based on infection status.
Study design
ELBW infants born at NICHD Neonatal Research Network (NRN) centers between March 2004 and July 2007 screened for suspected sepsis were eligible for inclusion in the Candida study. Primary outcome data for neurodevelopmental impairment (NDI) or death were available for 1317/1515 (90%) of the infants enrolled in the Candida study. The Bayley Scales of Infant Development (BSID)-II or the BSID-III was administered at 18 months adjusted age. A secondary comparison with 864 infants registered with NRN enrolled during the same cohort never screened for sepsis and therefore not eligible for the Candida study was performed.
Results
Among ELBW infants enrolled in the Candida study, 31% with Candida and 31% with late-onset non-Candida sepsis had NDI at 18 months. Infants with Candida sepsis and/or meningitis had an increased risk of death and were more likely to have the composite outcome of death and/or NDI compared with uninfected infants in adjusted analysis. Compared with infants in the NRN registry never screened for sepsis, overall risk for death were similar but those with Candida infection were more likely to have NDI (OR 1.83 (1.01,3.33, p=0.047).
Conclusion
In this cohort of ELBW infants, those with infection and/or meningitis were at increased risk for death and/or NDI. This risk was highest among those with Candida sepsis and/or meningitis.
doi:10.1016/j.jpeds.2013.04.034
PMCID: PMC3786056  PMID: 23726546
Candida; Neonatal sepsis; Neurodevelopmental and Prematurity
4.  Apgar scores at 10 min and outcomes at 6–7 years following hypoxic-ischaemic encephalopathy 
Aim
To determine the association between 10 min Apgar scores and 6–7-year outcomes in children with perinatal hypoxic-ischaemic encephalopathy (HIE) enrolled in the National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) whole body cooling randomised controlled trial (RCT).
Methods
Evaluations at 6–7 years included the Wechsler Preschool and Primary Scale of Intelligence III or Wechsler Intelligence Scale for Children IV and Gross Motor Functional Classification Scale. Primary outcome was death/moderate or severe disability. Logistic regression was used to examine the association between 10 min Apgar scores and outcomes after adjusting for birth weight, gestational age, gender, outborn status, hypothermia treatment and centre.
Results
In the study cohort (n=174), 64/85 (75%) of those with 10 min Apgar score of 0–3 had death/disability compared with 40/89 (45%) of those with scores >3. Each point increase in 10 min Apgar scores was associated with a significantly lower adjusted risk of death/disability, death, death/IQ <70, death/cerebral palsy (CP) and disability, IQ<70 and CP among survivors (all p<0.05). Among the 24 children with a 10 min Apgar score of 0, five (20.8%) survived without disability. The risk-adjusted probabilities of death/disability were significantly lower in cooled infants with Apgar scores of 0–3; there was no significant interaction between cooling and Apgar scores (p=0.26).
Conclusions
Among children with perinatal HIE enrolled in the NICHD cooling RCT, 10 min Apgar scores were significantly associated with school-age outcomes. A fifth of infants with 10 min Apgar score of 0 survived without disability to school age, suggesting the need for caution in limiting resuscitation to a specified duration.
doi:10.1136/archdischild-2013-303692
PMCID: PMC4166405  PMID: 23896791
5.  Health and reproductive experiences of women with an FMR1 premutation with and without fragile X premature ovarian insufficiency 
Frontiers in Genetics  2014;5:300.
Recently, research has indicated an increased risk for greater medical and emotional comorbidity and physical health symptoms among women with an FMR1 expansion. However, these studies have generally been limited in their ability to model multiple risk factors associated with these symptoms by small numbers (n = 112–146) of participants. This study used survey methodology to examine the health experiences of 458 adult women with the premutation with and without a history of a fragile X primary ovarian insufficiency (FXPOI) diagnosis. Results suggest similar findings to those reported in the literature with regard to the frequency of medical, emotional, and reproductive experiences of women with the premutation. In addition to expected reproductive differences, women with a diagnosis of FXPOI were also more likely to experience dizziness, nausea, and muscle weakness than women without a diagnosis of FXPOI. Women with and without FXPOI were more likely to have used reproductive assistance and were more likely to have experienced preeclampsia during at least one pregnancy than is reported in the general population. Having comorbid depression and anxiety was predictive of increased medical conditions and increased daily physical health symptoms.
doi:10.3389/fgene.2014.00300
PMCID: PMC4157548  PMID: 25250044
FMR1 premutation; fragile X primary ovarian insufficiency; women’s health
6.  Association Between Feeding Difficulties and Language Delay in Preterm Infants Using Bayley III 
The Journal of pediatrics  2013;163(3):680-685.e3.
Objective
To evaluate the relationship between abnormal feeding patterns and language performance on the Bayley Scales of Infant Development-III (BSID-III) at 18–22 months adjusted age among a cohort of extremely premature infants.
Study design
This is a descriptive analysis of 1477 preterm infants born ≤ 26 weeks gestation or enrolled in a clinical trial between January 1, 2006 and March 18, 2008 at a NICHD Neonatal Research Network center who completed the 18 month Neurodevelopmental Follow-Up assessment. At 18–22 months adjusted age, a comprehensive neurodevelopmental evaluation was performed by certified examiners including the Receptive and Expressive Language Subscales of the BSID-III and a standardized adjusted age feeding behaviors and nutritional intake. Data were analyzed using bivariate and multilevel linear and logistic regression modeling.
Results
Abnormal feeding behaviors were reported in 193 (13%) of these infants at 18–22 months adjusted age. Abnormal feeding patterns, days of mechanical ventilation, hearing impairment and Gross Motor Functional Classification Score ≥ 2 each independently predicted lower composite language scores.
Conclusions
At 18 months adjusted age, premature infants with a history of feeding difficulties are more likely to have language delay. Neuromotor impairment and days of mechanical ventilation are both important risk factors associated with these outcomes.
doi:10.1016/j.jpeds.2013.03.006
PMCID: PMC3755022  PMID: 23582139
7.  Outcomes of extremely preterm infants following severe intracranial hemorrhage 
Objective
Severe intracranial hemorrhage (ICH) is an important prognostic variable in extremely preterm (EPT) infants. We examined imaging and clinical variables that predict outcomes in EPT infants with severe ICH.
Study design
Retrospective analysis of 353 EPT infants with severe ICH. Outcomes were compared by examining: i) unilateral vs. bilateral ICH; and ii) presence vs. absence of hemorrhagic parenchymal infarction (HPI). Regression analyses identified variables associated with death or neurodevelopmental impairment (NDI).
Results
Bilateral ICH and HPI had higher rates of adverse outcomes and were independently associated with death/NDI. HPI was the most important variable for infants of lower birth weight, and bilateral ICH for larger infants. For infants surviving to 36 weeks, shunt placement was most associated with death/NDI.
Conclusions
Bilateral ICH and the presence of HPI in EPT infants with severe ICH are associated with death/NDI, though the importance depends on birth weight and survival to 36 weeks.
doi:10.1038/jp.2013.162
PMCID: PMC4143234  PMID: 24370654
intraventricular hemorrhage; neurodevelopmental impairment; extremely low birth weight; cranial ultrasound
8.  Risk-Taking Behavior among Adolescents with Prenatal Drug Exposure and Extrauterine Environmental Adversity 
Objective
High-risk environments characterized by familial substance use, poverty, inadequate parental monitoring, and violence exposure are associated with an increased propensity for adolescents to engage in risk-taking behaviors (e.g., substance use, sexual behavior, and delinquency). However, additional factors such as drug exposure in utero and deficits in inhibitory control among drug-exposed youth may further influence the likelihood that adolescents in high-risk environments will engage in risk-taking behavior. This study examined the influence of prenatal substance exposure, inhibitory control, and sociodemographic/environmental risk factors on risk-taking behaviors in a large cohort of adolescents with and without prenatal cocaine exposure (PCE).
Method
Risk-taking behavior (delinquency, substance use, and sexual activity) was assessed in 963 adolescents (433 cocaine-exposed, 530 nonexposed) at 15 years of age.
Results
PCE predicted later arrests and early onset of sexual behavior in controlled analyses. Associations were partially mediated, however, by adolescent inhibitory control problems. PCE was not associated with substance use at this age. In addition, male gender, low parental involvement, and violence exposure were associated with greater odds of engaging in risk-taking behavior across the observed domains.
Conclusions
Study findings substantiate concern regarding the association between prenatal substance exposure and related risk factors and the long-term outcomes of exposed youth. Access to the appropriate social, educational, and medical services are essential in preventing and intervening with risk-taking behaviors and the potential consequences (e.g., adverse health outcomes, incarceration), especially among high-risk adolescent youth and their families.
doi:10.1097/01.DBP.0000437726.16588.e2
PMCID: PMC4139145  PMID: 24220515
prenatal drug exposure; cocaine; adolescence; risk-taking behavior
9.  Neurodevelopmental Outcomes of Extremely Low Gestational Age Neonates with Low Grade Periventricular-Intraventricular Hemorrhage 
JAMA pediatrics  2013;167(5):451-459.
Objective
To compare neurodevelopmental outcomes at 18–22 months corrected age for extremely low gestational age infants with low grade (Grade 1 or 2) periventricular-intraventricular hemorrhage to infants with either no hemorrhage or severe (Grade 3 or 4) hemorrhage on cranial ultrasound.
Design
Longitudinal observational study
Setting
Sixteen centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
Participants
1472 infants born at <27 weeks gestational age between 2006–2008 with ultrasound results within the first 28 days of life and surviving to 18–22 months with complete follow-up assessments were eligible.
Main Exposure
Low grade periventricular-intraventricular hemorrhage
Outcome Measures
Outcomes included cerebral palsy, gross motor functional limitation, Bayley III cognitive and language scores, and composite measures of neurodevelopmental impairment. Regression modeling evaluated the association of hemorrhage severity with adverse outcomes while controlling for potentially confounding variables and center differences.
Results
Low grade hemorrhage was not associated with significant differences in unadjusted or adjusted risk of any adverse neurodevelopmental outcome compared to infants without hemorrhage. Compared with low grade hemorrhage, severe hemorrhage was associated with decrease in adjusted continuous cognitive (−3.91, [95% Confidence Interval [CI]: −6.41, −1.42]) and language (−3.19 [−6.19, −0.19]) scores as well as increased odds of each adjusted categorical outcome except severe cognitive impairment (OR: 1.46 [0.74, 2.88]) and mild language impairment (OR: 1.35 [0.88, 2.06]).
Conclusion
At 18–22 months, the neurodevelopmental outcomes of extremely low gestational age infants with low grade periventricular-intraventricular hemorrhage are not significantly different from those without hemorrhage.
doi:10.1001/jamapediatrics.2013.866
PMCID: PMC3953349  PMID: 23460139
10.  A Population-based Case-Control Study of Stillbirth: The Relationship of Significant Life Events to the Racial Disparity for African Americans 
American Journal of Epidemiology  2013;177(8):755-767.
Stillbirths (fetal deaths occurring at ≥20 weeks' gestation) are approximately equal in number to infant deaths in the United States and are twice as likely among non-Hispanic black births as among non-Hispanic white births. The causes of racial disparity in stillbirth remain poorly understood. A population-based case-control study conducted by the Stillbirth Collaborative Research Network in 5 US catchment areas from March 2006 to September 2008 identified characteristics associated with racial/ethnic disparity and interpersonal and environmental stressors, including a list of 13 significant life events (SLEs). The adjusted odds ratio for stillbirth among women reporting all 4 SLE factors (financial, emotional, traumatic, and partner-related) was 2.22 (95% confidence interval: 1.43, 3.46). This association was robust after additional control for the correlated variables of family income, marital status, and health insurance type. There was no interaction between race/ethnicity and other variables. Effective ameliorative interventions could have a substantial public health impact, since there is at least a 50% increased risk of stillbirth for the approximately 21% of all women and 32% of non-Hispanic black women who experience 3 or more SLE factors during the year prior to delivery.
doi:10.1093/aje/kws381
PMCID: PMC3625065  PMID: 23531847
African Americans; case-control studies; continental population groups; life change events; psychosocial stress; socioeconomic factors; stillbirth; stress
11.  Prevalence of Suicidal Thoughts and Attempts Among Pregnant Pakistani Women 
Objective
To determine the prevalence of suicidal thoughts and attempts and to identify demographic variables and mental health correlates such as anxiety/depression and domestic violence among pregnant women in an urban community in Pakistan.
Design
Cross sectional data from a prospective cohort study are presented.
Setting
Women enrolled in an antenatal care clinic and followed to delivery in an urban area of Pakistan
Population
Cohort of pregnant women in Pakistan.
Methods
1,369 pregnant women were enrolled and interviewed regarding various maternal characteristics and pregnancy outcomes, and were asked specific questions about suicidal thoughts and attempts and administered the Aga Khan University Anxiety Depression Scale at 20–26 weeks of gestation.
Main outcome measures
Suicidal thoughts and attempts, verbal, sexual or physical abuse.
Results
Overall, 148 of the 1369 (11%) women studied had considered suicide. Of these, 148 women, 67 (45%) had attempted suicide. Eighteen percent of the women were classified as having depression/anxiety, almost half (48%) reported experiencing verbal abuse and 20% reported physical/sexual abuse. Women who had anxiety/depression or had experienced verbal or physical/sexual abuse were significantly more likely to have had suicidal thoughts and attempts.
Conclusions
Women at greatest risk for having suicidal thoughts or a suicide attempt were those who were depressed/anxious and had experienced some form of domestic abuse. With the high prevalence of these conditions, attention should be given to the establishment of effective mental health treatment programs for pregnant women.
doi:10.3109/00016349.2010.526185
PMCID: PMC3918941  PMID: 21050149
Suicidal thoughts; suicide attempts; pregnancy; abuse; anxiety/depression
12.  Prevalence of Anxiety, Depression and Associated Factors among Pregnant Women of Hyderabad, Pakistan 
The International journal of social psychiatry  2009;55(5):10.1177/0020764008094645.
Background
Few studies have examined the relationship between antenatal depression, anxiety and domestic violence in pregnant women in developing countries, despite the World Health Organization's estimates that depressive disorders will be the second leading cause of the global disease burden by 2020. There is a paucity of research on mood disorders, their predictors and sequelae among pregnant women in Pakistan.
Aims
To determine the prevalence of anxiety and depression and evaluate associated factors, including domestic violence, among pregnant women in an urban community in Pakistan.
Methods
All pregnant women living in identified areas of Hyderabad, Pakistan were screened by government health workers for an observational study on maternal characteristics and pregnancy outcomes. Of these, 1368 (76%) of eligible women were administered the validated Aga Khan University Anxiety Depression Scale at 20–26 weeks of gestation.
Results
18 percent of the women were anxious and/or depressed. Psychological distress was associated with husband unemployment (p=0.032), lower household wealth (p=0.027), having 10 or more years of formal education (p=0.002), a first (p=0.002) and an unwanted pregnancy (p<0.001). The strongest factors associated with depression/anxiety were physical/sexual and verbal abuse; 42% of women who were physically and/or sexually abused and 23% of those with verbal abuse had depression/anxiety compared to 8% of those who were not abused.
Conclusions
Anxiety and depression commonly occur during pregnancy in Pakistani women; rates are highest in women experiencing sexual/physical as well as verbal abuse, but they also are increased among women with unemployed spouses and those with lower household wealth. These results suggest that developing a screening and treatment program for domestic violence and depression/anxiety during pregnancy may improve the mental health status of pregnant Pakistani women.
doi:10.1177/0020764008094645
PMCID: PMC3875176  PMID: 19592433
Pregnancy; depression; anxiety; Pakistan; measurement
13.  Improving the Neonatal Research Network Annual Certification for Neurologic Examination of the 18–22 month Child 
The Journal of pediatrics  2012;161(6):1041-1046.e2.
Objective
To describe the Neonatal Research Network’s (NRN) efforts to improve the certification process for the Follow-up Study neurologic exam and to evaluate inter-rater agreement before and after two annual training workshops.
Study design
The NRN Follow-up Study is a multi-center observational study that has examined more than 11,500 infants from 1998–2010 and born ≤ 26 weeks gestational age at 18 – 22 months corrected age for neurodevelopmental outcome. The percentages of examiners who agreed with the Gold Standard examiner on four neurodevelopmental outcomes on the initial training video and a test video were calculated. Consistency among examiners was assessed with the first-order agreement coefficient (AC1) statistic.
Results
Improvements in agreement among examiners occurred between 2009 and 2010 and between initial training and test. Examiner agreement with the Gold Standard during the initial training was 83% – 91% in 2009 and 89% – 99% in 2010. Examiner agreement on the workshop test video increased from 2009 to 2010 with agreement reaching 100% for all four neurodevelopmental outcomes examined in 2010. AC1 values for the four neurodevelopmental outcomes on the training videos ranged from 0.64 – 0.82 in 2009 and 0.77 – 0.97 in 2010.
Conclusions
We demonstrate the importance of annual certification and the benefits of evaluation and revision of certification protocols to achieve high levels of confidence in neurodevelopmental study outcomes for multi-center networks.
doi:10.1016/j.jpeds.2012.05.048
PMCID: PMC3465479  PMID: 22748517
examiner training; neurodevelopmental outcome; inter-rater agreement
14.  Protective Factors Can Mitigate Behavior Problems After Prenatal Cocaine and Other Drug Exposures 
Pediatrics  2012;130(6):e1479-e1488.
BACKGROUND:
We determined the role of risk and protective factors on the trajectories of behavior problems associated with high prenatal cocaine exposure (PCE)/polydrug exposure.
METHODS:
The Maternal Lifestyle Study enrolled 1388 children with or without PCE, assessed through age 15 years. Because most women using cocaine during pregnancy also used other substances, we analyzed for the effects of 4 categories of prenatal drug exposure: high PCE/other drugs (OD), some PCE/OD, OD/no PCE, and no PCE/no OD. Risks and protective factors at individual, family, and community levels that may be associated with behavior outcomes were entered stepwise into latent growth curve models, then replaced by cumulative risk and protective indexes, and finally by a combination of levels of risk and protective indexes. Main outcome measures were the trajectories of externalizing, internalizing, total behavior, and attention problems scores from the Child Behavior Checklist (parent).
RESULTS:
A total of 1022 (73.6%) children had known outcomes. High PCE/OD significantly predicted externalizing, total, and attention problems when considering the balance between risk and protective indexes. Some PCE/OD predicted externalizing and attention problems. OD/no PCE also predicted behavior outcomes except for internalizing behavior. High level of protective factors was associated with declining trajectories of problem behavior scores over time, independent of drug exposure and risk index scores.
CONCLUSIONS:
High PCE/OD is a significant risk for behavior problems in adolescence; protective factors may attenuate its detrimental effects. Clinical practice and public health policies should consider enhancing protective factors while minimizing risks to improve outcomes of drug-exposed children.
doi:10.1542/peds.2011-3306
PMCID: PMC3507246  PMID: 23184114
behavior problems; cumulative risks; prenatal cocaine exposure; protective factors
15.  Are Outcomes of Extremely Preterm Infants Improving? Impact of Bayley Assessment on Outcomes 
The Journal of pediatrics  2012;161(2):222-8.e3.
Objectives
To compare 18- to 22-month cognitive scores and neurodevelopmental impairment (NDI) in 2 time periods using the National Institute of Child Health and Human Development’s Neonatal Research Network assessment of extremely low birth weight infants with the Bayley Scales of Infant Development, Second Edition (Bayley II) in 2006–2007 (period 1) and using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III), with separate cognitive and language scores, in 2008–2011 (period 2).
Study design
Scores were compared with bivariate analysis, and regression analyses were run to identify differences in NDI rates.
Results
Mean Bayley III cognitive scores were 11 points higher than mean Bayley II cognitive scores. The NDI rate was reduced by 70% (from 43% in period 1 to 13% in period 2; P < .0001). Multivariate analyses revealed that Bayley III contributed to a decreased risk of NDI by 5 definitions: cognitive score <70 and <85, cognitive or language score <70; cognitive or motor score <70, and cognitive, language, or motor score <70 (P < .001).
Conclusion
Whether the Bayley III is overestimating cognitive performance or whether it is a more valid assessment of emerging cognitive skills than the Bayley II is uncertain. Because the Bayley III identifies significantly fewer children with disability, it is recommended that all extremely low birth weight infants be offered early intervention services at the time of discharge from the neonatal intensive care unit, and that Bayley scores be interpreted with caution.
doi:10.1016/j.jpeds.2012.01.057
PMCID: PMC3796892  PMID: 22421261
16.  Mental, social, and physical well-being in New Hampshire, Oregon, and Washington, 2010 Behavioral Risk Factor Surveillance System: implications for public health research and practice related to Healthy People 2020 foundation health measures on well-being 
Background
Well-being is now accepted as one of four cross-cutting measures in gauging progress for Healthy People 2020. This shift to population indicators of well-being redresses notions of health that have focused on absence of illness (negative health) as a primary or sufficient indicator of positive functioning. The purpose of this study was to estimate mental, social, and physical well-being in three US states using new measures piloted on the 2010 Behavioral Risk Factor Surveillance Survey System (BRFSS). Baseline estimates were provided for states overall, and within states for demographic subgroups, those with chronic health conditions or disabilities, and those with behavioral risk factors.
Methods
Ten validated questions designed to assess mental (e.g., satisfaction with life, satisfaction with life domains, happiness), physical (e.g., satisfaction with energy level), and social dimensions (e.g., frequency of social support) of well-being were selected with state input for inclusion on BRFSS. 18,622 individuals responded to the BRFSS surveys administered by New Hampshire (N = 3,139), Oregon (N = 2,289), and Washington (N = 13,194). Multivariate adjusted proportions of positive responses to well-being items were examined.
Results
After adjustment for confounders, about 67% of adults in these states had high levels of well-being, including >80% reporting experiencing happiness. Most adults were satisfied with their work, neighborhood, and education, but significant differences were seen in subgroups. Well-being differed by demographic characteristics such as marital status, health behaviors, chronic conditions, and disability status, with those who reported a disability and smokers consistently experiencing the worst well-being.
Conclusions
Well-being is accepted as one of four cross-cutting measures in gauging progress for Healthy People 2020. Well-being differs by important sociodemographic factors and health conditions (e.g., age, employment, smoking, disability status). These findings provide baseline estimates for the three states to use in gauging improvements in well-being and can serve as a model for other state-level or national surveillance systems. These findings also assist states in identifying vulnerable subgroups who may benefit from potential interventions such as those in the National Prevention Strategy that focus on enhancing well-being where such disparities exist.
doi:10.1186/1478-7954-11-19
PMCID: PMC3852954  PMID: 24063647
17.  Screening for Autism Spectrum Disorders in Extremely Preterm Infants 
Background
Extremely preterm (EP) infants screen positive for Autism Spectrum Disorders (ASD) at high rates. However it is not clear whether this is due to high rates of ASD in EPs or to high rates of false positive screens for ASD in children with a high rate of underlying neurodevelopmental impairments. Combining a parent questionnaire designed to distinguish developmental delay from ASD with direct observation of infant behavior may more accurately screen for ASD in EPs.
Objectives
To determine rates of positive screen for ASD at 18–22months(m) in EPs using three screens; to determine factors associated with a positive screen.
Methods
554 infants born <27 weeks were screened at 18–22m using the Pervasive Developmental Disorders Screening Test, 2nd edition, Stage 2 (PDDST-II) and the response to name and response to joint attention items from the Autism Diagnostic Observation Schedule. Infants with severe cerebral palsy, deafness and blindness were excluded. Associations between positive screen and neonatal/infant characteristics were determined.
Results
113/554 (20 %) had ≥1 positive screen. 10% had a positive PDDST-II, 6% response to name, 9% response to joint attention; in only 1% were all 3 screens positive. Positive screen was associated with male gender, more hospital days, white race, lower maternal education, abnormal behavioral scores, and cognitive/language delay.
Conclusions
The use of three screens for ASD in EPs results in higher screen positive rates than use of one screen alone. Diagnostic confirmation is needed before true rates of ASD in EPs are known.
doi:10.1097/DBP.0b013e31825fd0af
PMCID: PMC3434239  PMID: 22926660
Autism; Prematurity; Screening
18.  Translating Medical Evidence to Promote Informed Health Care Decisions 
Health Services Research  2011;46(4):1200-1223.
Objective
To examine the effects of a community-based intervention on decisions about prostate-specific antigen (PSA) screening using multiple measures of informed decision making (IDM).
Data Sources/Study Setting
Nonequivalent control group time series design collecting primary data in late 2004 and 2005.
Study Design
We developed a multimodal intervention designed to convey the medical uncertainty about the benefits of PSA screening and early treatment and the limited predictive ability of both the PSA test and pathological specimens collected from prostate biopsy. We examined (1) patients' recognition that there is a decision to be made about PSA screening, (2) prostate cancer knowledge levels, (3) their preferred and actual levels of participation in decision making about screening at three points in time, and (4) screening decision.
Data Collection
Baseline data collection occurred in community-based organizations. These organizations served as recruiting sources and as sites for the intervention. We collected follow-up data by mail with telephone reminders.
Principal Findings
Our intervention was associated with greater recognition of the PSA test as a decision to be made, levels of knowledge, both preferred and actual levels of involvement in decision making, but did not have an impact on the screening decision.
Conclusions
Community-based interventions can influence key measures of IDM about PSA screening.
doi:10.1111/j.1475-6773.2011.01248.x
PMCID: PMC3165184  PMID: 21352225
Decision making; prostate cancer screening; level of involvement; patient–provider communication
19.  Long-Term Impact of Maternal Substance Use during Pregnancy and Extrauterine Environmental Adversity: Stress Hormone Levels of Preadolescent Children 
Pediatric research  2011;70(2):213-219.
Prenatal cocaine exposure (PCE) is associated with blunted stress responsivity within the extrauterine environment. This study investigated the association between PCE and diurnal salivary cortisol levels in preadolescent children characterized by high biological and/or social risk (N = 725). Saliva samples were collected at their home. Analyses revealed no group differences in basal evening or morning cortisol levels; however, children with higher degrees of PCE exhibited blunted overnight increases in cortisol, controlling for additional risk factors. Race and caregiver depression were also associated with diurnal cortisol patterns. While repeated PCE may contribute to alterations in the normal or expected stress response later in life, sociodemographic and environmental factors are likewise important in understanding hormone physiology, especially as more time elapses from the PCE. Anticipating the potential long-term medical, developmental, or behavioral effects of an altered ability to mount a normal protective cortisol stress response is essential in optimizing the outcomes of children with PCE.
doi:10.1203/PDR.0b013e3182291b13
PMCID: PMC3686483  PMID: 21546861
20.  Maintaining Participation and Momentum in Longitudinal Research Involving High-Risk Families 
Journal of Nursing Scholarship  2012;44(2):120-126.
Purpose
The purpose of the current study was to identify and describe strategies available to optimize retention of a high-risk research cohort and assist in the recovery of study participants following participant dropout.
Design and Methods
The Maternal Lifestyle Study (MLS), which investigated the effects of prenatal substance exposure (cocaine or opiates) on child outcome, is a prospective longitudinal follow-up study that extended from birth through 15 years of age. Retention strategies to maximize participation and factors that might negatively impact compliance were examined over the course of five follow-up phases.
Findings
At the conclusion of the 15-year visits, MLS had successfully maintained compliance at 76%. Retention rates did not differ by exposure group.
Conclusions
Maintaining ongoing participation of enrolled study subjects is a critical element of any successful longitudinal study. Strategies that can be used to reengage and maintain participants in longitudinal research include persistence, flexibility with scheduling, home visits, long-distance trips, increased incentives, and development of a computerized tracking system. Establishing rapport with families and ensuring confidentiality contributed to overall participant retention. The use of multiple tracking techniques is essential.
Clinical Relevance
Researchers are challenged to maintain participants in longitudinal studies to ensure the integrity of their research.
doi:10.1111/j.1547-5069.2012.01439.x
PMCID: PMC3366028  PMID: 22458928
Longitudinal research; participant retention; tracking; compliance
21.  Evolution of Encephalopathy during Whole Body Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy 
The Journal of Pediatrics  2011;160(4):567-572.e3.
Objective
To examine the predictive ability of stage of hypoxic-ischemic encephalopathy (HIE) for death or moderate/severe disability at 18 months among neonates undergoing hypothermia.
Study design
Stage of encephalopathy was evaluated at <6 hr of age, during study intervention and at discharge among 204 participants in the NICHD Neonatal Research Network Trial of whole body hypothermia for HIE. HIE was examined as a predictor of outcome by regression models.
Results
Moderate and severe HIE occurred at <6 hrs of age among 68% and 32% of 101 hypothermia group infants and 60% and 40% of 103 control group infants, respectively. At 24 and 48 hrs of study intervention, infants in the hypothermia group had less severe HIE than infants in the control group. Persistence of severe HIE at 72 hrs increased the risk of death or disability after controlling for treatment group. The discharge exam improved the predictive value of stage of HIE at < 6hrs for death/disability.
Conclusions
On serial neurological examinations, improvement in stage of HIE was associated with cooling. Persistence of severe HIE at 72 hours and an abnormal neurological exam at discharge was associated with a greater risk of death or disability.
doi:10.1016/j.jpeds.2011.09.018
PMCID: PMC3299861  PMID: 22050871
Neurological examinations; neonates; clinical biomarker; death; disability
22.  Technical Implementation of a Multi-Component, Text Message–Based Intervention for Persons Living with HIV 
JMIR Research Protocols  2012;1(2):e17.
Background
Men who have sex with men (MSM) continue to be severely and disproportionately affected by the HIV/AIDS (human immunodeficiency virus/acquired immune deficiency syndrome) epidemic in the United States. Effective antiretroviral therapy has altered the HIV epidemic from being an acute disease to a chronic, manageable condition for many people living with HIV. The pervasiveness, low cost, and convenience of Short Message Service (SMS) suggests its potential suitability for supporting the treatment of conditions that must be managed over an extended period.
Objective
The purpose of this proof-of-concept study was to develop, implement, and test a tailored SMS-based intervention for HIV-positive MSM. Prior studies do not routinely provide sufficiently detailed descriptions of their technical implementations, restricting the ability of subsequent efforts to reproduce successful interventions. This article attempts to fill this gap by providing a detailed description of the implementation of an SMS-based intervention to provide tailored health communication messages for HIV-positive MSM.
Methods
We used archives from the SMS system, including participant responses to messages and questions sent via SMS, as the data sources for results reported in this article. Consistent with the purpose of this article, our analysis was limited to basic descriptive statistics, including frequency distributions, means and standard deviations.
Results
During the implementation period, we sent a total of 7,194 messages to study participants, received 705 SMS responses to our two-way SMS questions of participants, and 317 unprompted SMS message acknowledgements from participants. Ninety two percent of participants on antiretroviral therapy (ART) responded to at least one of the weekly medication adherence questions administered via SMS, and 27% of those had their medication adherence messages changed over the course of the study based on their answers to the weekly questions. Participants who responded to items administered via SMS to assess satisfaction with and use of the messages reported generally positive perceptions, although response rates were low overall.
Conclusions
Results confirm the technical feasibility of deploying a dynamically tailored, SMS-based intervention designed to provide ongoing behavioral reinforcement for HIV-positive MSM. Lessons learned related to text programming, message delivery and study logistics will be helpful to others planning and implementing similar interventions.
doi:10.2196/resprot.2017
PMCID: PMC3626151  PMID: 23612237
short message service; SMS; text message; mobile phone; mHealth; HIV; tailored messaging
23.  Serial Pediatric Symptom Checklist Screening in Children with Prenatal Drug Exposure 
Objective
To examine screening results obtained by serial annual behavioral assessment of children with prenatal drug exposure.
Method
The Maternal Lifestyle Study enrolled children with prenatal cocaine exposure (PCE) at birth for longitudinal assessments of developmental, behavioral, and health outcomes. At 8, 9, 10, 11, and 12 years of age, caregivers rated participants on the Pediatric Symptom Checklist (PSC). Serial PSC results were compared to an established broad-based behavioral measure at 9, 11, and 13 years. PSC results were analyzed for 1,081 children who had at least 2 annual screens during the 5-year time span. Most subjects (87%) had 4 or more annual screens rated by the same caregiver (80%). PSC scores (and Positive screens) over time were compared at different time points for those with and without PCE. Covariates, including demographic factors and exposures to certain other substances, were controlled.
Results
Children with PCE had significantly higher scores overall, with more Positive screens for behavior problems than children without PCE. Children with PCE had more externalizing behavior problems. Children exposed to tobacco pre- and post-natally also showed higher PSC scores. Over time, PSC scores differed slightly from the 8-year scores, without clear directional trend. Earlier PSC results predicted later behavioral outcomes.
Conclusion
Findings of increased total PSC scores and Positive PSC screens for behavioral concerns in this group of children with prenatal substance exposure support the growing body of evidence that additional attention to identification of mental health problems may be warranted in this high-risk group.
doi:10.1097/DBP.0b013e318208ee3c
PMCID: PMC3069136  PMID: 21200328
Behavior disorder; child behavior; mental health; screening; prenatal cocaine exposure; Pediatric Symptom Checklist
24.  Preadolescent behavior problems after prenatal cocaine exposure: Relationship between teacher and caretaker ratings (Maternal Lifestyle Study) 
Neurotoxicology and teratology  2010;33(1):78-87.
Background
We previously reported an association between prenatal cocaine exposure (PCE) and childhood behavior problems as observed by the parent or caretaker. However, these behavior problems may not manifest in a structured environment, such as a school setting.
Objective
We determined whether there is an association between PCE and school behavior problems and whether ratings of behavior problems from the teacher differ from those noted by the parent or caretaker.
Methods
The Maternal Lifestyle Study, a multicenter study, enrolled 1388 children with and without PCE at one month of age for longitudinal assessment. Teachers masked to prenatal drug exposure status completed the Teacher Report Form (TRF/6-18) when children were 7, 9, and 11 years old. We also administered the Child Behavior Checklist-parent report (CBCL) to the parent/caretaker at same ages and then at 13 years. We performed latent growth curve modeling to determine whether high PCE will predict externalizing, internalizing, total behavior, and attention problems at 7 years of age and whether changes in problems' scores over time differ between those exposed and non-exposed from both teacher and parent report. Besides levels of PCE as predictors, we controlled for the following covariates, namely: site, child characteristics (gender and other prenatal drug exposures), family level influences (maternal age, depression and psychological symptomatology, continuing drug use, exposure to domestic violence, home environment, and socioeconomic status), and community level factors (neighborhood and community violence).
Results
The mean behavior problem T scores from the teacher report were significantly higher than ratings by the parent or caretaker. Latent growth curve modeling revealed a significant relationship between intercepts of problem T scores from teacher and parent ratings; i.e., children that were rated poorly by teachers were also rated poorly by their parent/caretaker or vice versa. After controlling for covariates, we found high PCE to be a significant predictor of with higher externalizing behavior problem T scores from both parent and teacher report at 7 years (p=0.034 and p=0.021, respectively) in comparison to non-PCE children. These differences in scores from either teacher or caregiver were stable through subsequent years or did not change significantly over time. Boys had higher T scores than girls on internalizing and total problems by caretaker report; they also had significantly higher T scores for internalizing, total, and attention problems by teacher ratings; the difference was marginally significant for externalizing behavior (p=0.070). Caretaker postnatal use of tobacco, depression, and community violence were significant predictors of all behavior problems rated by parent/caretaker, while lower scores on the home environment predicted all behavior outcomes by the teacher report.
Conclusions
Children with high PCE are likely to manifest externalizing behavior problems; their behavior problem scores at 7 years from either report of teacher or parent remained higher than scores of non-exposed children on subsequent years. Screening and identification of behavior problems at earlier ages could make possible initiation of intervention, while considering the likely effects of other confounders.
doi:10.1016/j.ntt.2010.06.005
PMCID: PMC3011027  PMID: 20600844
25.  Prenatal Cocaine Exposure and Body Mass Index and Blood Pressure at 9 Years of Age 
Journal of hypertension  2010;28(6):1166-1175.
Background
Prenatal cocaine exposure has been linked to intrauterine growth retardation and poor birth outcomes; little is known about the effects on longer-term medical outcomes, such as overweight status and hypertension in childhood. Our objective was to examine the association between prenatal cocaine exposure and body mass index and blood pressure at 9 years of age among children followed prospectively in a multi-site longitudinal study evaluating the impact of maternal lifestyle during pregnancy on childhood outcome.
Design/Methods
This analysis includes 880 children (277 cocaine exposed and 603 with no cocaine exposure) with blood pressure, height, and weight measurements at 9 years of age. Regression analyses were conducted to explore the relationship between prenatal cocaine exposure and body mass index and blood pressure at 9 years of age after controlling for demographics, other drug exposure, birth weight, maternal weight, infant postnatal weight gain, and childhood television viewing, exercise and dietary habits at 9 years. Path analyses were used to further explore these relationships.
Results
At 9 years of age, 15% of the children were pre-hypertensive and 19% were hypertensive; 16% were at risk for overweight status and 21% were overweight. A small percentage of women were exposed to high levels of prenatal cocaine throughout pregnancy. Among children born to these women, a higher body mass index was noted. Path analysis suggested that high cocaine exposure has an indirect effect on systolic and diastolic blood pressure that is mediated through its effect on body mass index.
Conclusion
High levels of in-utero cocaine exposure are a marker for elevated body mass index and blood pressure among children born full term.
PMCID: PMC2874425  PMID: 20486281
Prenatal cocaine exposure; Body mass index; Childhood hypertension; Overweight; Obesity

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