Associations of prenatal stress with 5-year-old children's executive function in a low socioeconomic status population.

Prenatal stress has a significant, but small, negative effect on children's executive function (EF) in middle and high socioeconomic status (SES) households. Importantly, rates and severity of prenatal stress are higher and protective factors are reduced in lower SES households, suggesting prenatal stress may be particularly detrimental for children's EF in this population. This study examined whether prenatal stress was linked to 5-year-old's EF in a predominantly low SES sample and child sex moderated this association, as males may be more vulnerable to adverse prenatal experiences. Participants were 132 mother-child dyads drawn from a prospective prenatal cohort. Mothers reported on their depression symptoms, trait anxiety, perceived stress, everyday discrimination, and sleep quality at enrollment and once each trimester, to form a composite prenatal stress measure. Children's EF was assessed at age 5 years using the parent-report Behavior Rating Inventory of Executive Function - Preschool (BRIEF-P) Global Executive Composite subscale and neuropsychological tasks completed by the children. Mixed models revealed higher prenatal stress was associated with lower BRIEF-P scores, indicating better EF, for females only. Higher prenatal stress was associated with lower performance on neuropsychological EF measures for both males and females. Results add to the limited evidence about prenatal stress effects on children's EF in low SES households.

The timing and quality of sleep was associated with dietary quality and anthropometry in toddlers born preterm.

AIM: The aim of the study was to examine prospective associations of sleep characteristics (duration, timing, quality) with dietary and anthropometric measures among toddlers born preterm (<35 weeks). METHODS: Children participated in the Omega Tots trial at 10-17 months' corrected age (Ohio, USA; 26 April 2012 to 6 April 2017). Caregivers reported toddlers' sleep at baseline using the Brief Infant Sleep Questionnaire. After 180 days, caregivers reported toddlers' past month diet in a food frequency questionnaire, and anthropometry was measured using standardised protocols. The toddler diet quality index (TDQI: higher scores indicating better quality), and weight-for-length, triceps skinfold and subscapular skinfold z-scores were calculated. Linear and logistic regression assessed adjusted associations with dietary and anthropometric outcomes at 180-day follow-up (n = 284), and linear mixed models assessed changes in anthropometry. RESULTS: Daytime sleep was associated with lower TDQI (ßadj per hour = -1.62 (95% CI: -2.71, -0.52)) whereas night-time sleep was associated with higher TDQI (ßadj  = 1.01 (95% CI: 0.16, 1.85)). Night-time awakenings and caregiver-reported sleep problems were also associated with lower TDQI. Night awakening duration and sleep-onset latency were associated with higher triceps skinfold z-score. CONCLUSION: Daytime and night-time caregiver-reported sleep showed opposite associations with diet quality, suggesting that sleep timing may be important.

Effects of Omega-3-6-9 fatty acid supplementation on behavior and sleep in preterm toddlers with autism symptomatology: Secondary analysis of a randomized clinical trial.

BACKGROUND: Children born extremely preterm disproportionately experience sequelae of preterm birth compared to those born at later gestational ages, including higher prevalence of autism spectrum disorder (ASD) and associated behaviors. AIM: Explore effects of combined dietary docosahexaenoic acid, eicosapentaenoic acid, gamma-linolenic acid, and oleic acid (omega 3-6-9) on caregiver-reported behavior and sleep in toddlers born at ≤29 weeks' gestation who were exhibiting symptoms commonly seen with ASD. STUDY DESIGN: 90-day randomized (1:1), double blinded, placebo-controlled trial. SUBJECTS: Thirty-one children aged 18-38 months received omega 3-6-9 (n = 15) or canola oil placebo (n = 16). OUTCOME MEASURES: Mixed effects regression analyses followed intent to treat and explored treatment effects on measures of caregiver-reported behavior (Child Behavior Checklist 1.5-5, Toddler Behavior Assessment Questionnaire - Short Form, Vineland Adaptive Behavior Scales, 2nd Edition) and sleep (Children's Sleep Habits Questionnaire, Brief Infant Sleep Questionnaire). RESULTS: Twenty-nine of 31 (94%; ntx = 13, nplacebo = 16) children randomized had data available for at least one outcome measure, 27 (87%; ntx = 12, nplacebo = 15) had complete outcome data. Children randomized to omega 3-6-9 experienced a medium magnitude benefit of supplementation on anxious and depressed behaviors (ΔDifference = -1.27, d = -0.58, p = 0.049) and internalizing behaviors (ΔDifference = -3.41, d = -0.68, p = 0.05); and a large magnitude benefit on interpersonal relationship adaptive behaviors (ΔDifference = 7.50, d = 0.83, p = 0.01), compared to placebo. No effects were observed on other aspects of behavior or sleep. CONCLUSIONS: Findings provide preliminary support for further exploration of omega 3-6-9 during toddlerhood to improve socioemotional outcomes among children born preterm, especially for those showing early symptoms commonly seen with ASD. Results need to be replicated in a larger sample. TRIAL REGISTRATION: Registered with ClinicalTrials.gov: NCT01683565.

Early childhood growth trajectories in a Medicaid population.

BACKGROUND: Evidence on the role of early growth trajectories and later obesity risk is primarily based on privately insured or universally insured samples. OBJECTIVES: We aimed to characterize and determine factors associated with early growth trajectories and estimate associations with overweight/obesity risk in a Medicaid-insured and uninsured cohort. METHODS: Infants seen at a large pediatric academic centre in 2010-2016 were included. Weight and length/height measurements were converted to age and sex-specific BMI z-scores (BMIz) based on the World Health Organization (WHO) Growth Standards. Group-based trajectories were modelled using BMIz created groups. Logistic and log-binomial regression models estimated associations between membership in trajectories and maternal/child factors and overweight or obesity at 36, 48, and 60 months, separately. Analyses were performed between 2019 and 2021. RESULTS: The best-fitting model identified five BMIz trajectories among 30 189 children and 310 113 clinical encounters; two trajectories showed rapid rise in BMIz. Lower maternal education, pre-pregnancy maternal overweight/obese status, and maternal smoking were positively associated with both rapid-rising BMIz trajectories. Children in either of the two rapid-rising trajectories were 3.00 (95% CI: 2.85, 3.25), 2.97 (95% CI: 2.77, 3.18) and 2.76 (95% CI: 2.53, 3.01) times more likely to have overweight or obesity at 36, 48, and 60 months, respectively compared to children in the stable trajectory groups. CONCLUSIONS: Among Medicaid insured and uninsured children, several maternal and child characteristics were associated with early rapid-rise in BMIz. Clinical monitoring of early rapidly rising BMI may be important to address modifiable risk factors for obesity in families from low-income households.

Behavioral and Cognitive Differences in Early Childhood related to Prenatal Marijuana Exposure.

Prenatal marijuana exposure (PME) negatively impacts child development and behavior; however, few studies have examined these associations at early ages among children exposed to today's highly potent marijuana. Using a prospective prenatal cohort (Columbus, Ohio, USA), PME was determined from maternal self-report, medical chart abstraction, and urine toxicology from prenatal visits and delivery. At age 3.5 years, 63 offspring children completed tasks assessing executive function (EF), visual spatial ability, emotion regulation, and aggressive behavior. Caregivers reported on children's EF and problem behaviors. Logistic regressions and analyses of covariance controlling for key variables were used to examine associations between PME and child outcomes. Compared to non-exposed children, children with PME had more sleep-related problems, withdrawal symptoms, and externalizing problems, including aggressive behaviors and oppositional defiant behaviors. Children with and without PME did not differ in terms of executive functioning. Findings suggest behavioral problems associated with PME may manifest by age 3.5.

Underdiagnosis of obesity in pediatric clinical care settings among children born preterm: a retrospective cohort study.

BACKGROUND: Neonatal care of preterm infants may include dietary approaches such as high calorie formulas to promote physical growth. However, continuing growth-promoting strategies beyond the point of necessity, coupled with poverty and food insecurity which are more common among families of children born preterm, may increase the risk of obesity. Because children born preterm tend to have more pressing health conditions that require ongoing care, obesity may go undiagnosed by providers. METHODS: This retrospective cohort study included 38,849 children (31,548 term, 7301 preterm) born from 2010 to 2015, who received clinical care at a large pediatric medical center (Ohio, USA). Electronic medical record data, linked to Ohio birth certificates, were used to identify children with measured obesity (≥2 weight-for-length values ≥95th percentile before 24 months of age or BMI values ≥95th percentile at or after 24 months of age). Children were considered to have diagnosed obesity if their medical record had an obesity-related phrase or billing code recorded. Modified Poisson regression was used to compare risk of obesity undiagnosis among obese children born preterm versus at term. RESULTS: In total, 13,697 children had measured obesity, 10,273 (75%) of which were undiagnosed. Children born preterm with measured obesity were 8% more likely to be undiagnosed compared to children born at term (adjusted relative risk = 1.08 95% CI 1.05, 1.11). The risk was slightly higher for preterm children born to white women or born to women with higher educational attainment. For both groups, Primary Care and subspecialist clinics were the most common settings for undiagnosed obesity (74.9% and 16.8% of undiagnosed cases, respectively). CONCLUSIONS AND RELEVANCE: Preterm birth was associated with increased risk of undiagnosed obesity in early childhood. This highlights the need to enhance obesity screening in the preterm population and to further explore reasons for this disparity.

Association of Infant Feeding Methods and Excess Weight from Birth to Age 6.

Objective: To examine the associations between human milk feeding method (at the breast versus bottle) and measures of child adiposity during the first 6 years of life. Study Design: Women 12 months' postpartum who delivered a singleton, liveborn infant at >24 weeks gestation completed a survey assessing infant feeding methods and sociodemographics. Mothers were recontacted when the child was 6 years old for a follow-up study assessing growth (N = 269). Children were categorized as ever or never having excess weight using weight-for-age z-scores (WAZ), weight-for-height z-scores (WHZ), and body mass index-for-age z-scores (BMIZ) from birth to 6 years. Modified Poisson regression estimated associations between the duration of each feeding method (exclusive and combined) with excess weight status. Mixed-effect models estimated associations between feeding methods and trajectories of the outcomes. Results: For all feeding practices, increasing duration (in months) was unassociated with the risk of ever having excess weight by age 6 years. Based on mixed models, longer duration of feeding human milk by any method was associated with lower BMIZ (adj ß for 6-12 months versus 0-3 months = -0.50, 95% CI: -0.99 to -0.01) and also with the shape of the BMIZ trajectory curve. No other associations between feeding methods and excess weight outcomes were observed. Conclusions: Longer duration of feeding human milk was associated with lower average BMIZ in early childhood but feeding at the breast and feeding expressed milk were not clearly associated with the outcomes when considered separately. Larger studies would help clarify the associations between these specific feeding methods and outcomes. IRB17-00876.

Feeding Infants at the Breast or Feeding Expressed Human Milk: Long-Term Cognitive, Executive Function, and Eating Behavior Outcomes at Age 6 Years.

OBJECTIVE: To examine how expressed milk feeding diverges from feeding at the breast in its association with neurodevelopment and behavior. We hypothesized that longer and exclusive feeding at the breast only (ie, no formula, no feeding expressed milk) would be associated with the optimal cognitive developmental, executive function, and eating behaviors and that expressed milk feeding would be associated with less-optimal outcomes. STUDY DESIGN: The Moms2Moms cohort (Ohio, US) reported infant feeding practices at 12 months postpartum and children's global cognitive ability, executive function, and eating behaviors at 6 years. Linear and log-binomial regression models estimated associations with durations of feeding at the breast, expressed milk, human milk (modes combined), and formula. RESULTS: Among 285 participants, each month of exclusive feeding at the breast only was associated with a decreased risk of clinically meaningful executive function (working memory) deficit (adjusted relative risk [RR] 0.78, 95% CI 0.63-0.96) but was unassociated with inhibition (adjusted RR 0.92, 95% CI 0.85-1.01). Feeding expressed milk was not clearly related to executive function outcomes. No associations with global cognitive ability were observed. Weak associations were observed with eating behaviors for some feeding practices. CONCLUSIONS: Feeding at the breast may offer advantages to some aspects of executive function that expressed milk may not. Large, prospective studies exploring mechanisms could further distinguish the effect of feeding mode from that of nutrients.

Fatty Acid Supplementation and Socioemotional Outcomes: Secondary Analysis of a Randomized Trial.

BACKGROUND AND OBJECTIVES: Children born preterm experience socioemotional difficulties, including increased risk of autism spectrum disorder (ASD). In this secondary analysis, we tested the effect of combined docosahexaenoic acid (DHA) and arachidonic acid (AA) supplementation during toddlerhood on caregiver-reported socioemotional outcomes of children born preterm. We hypothesized that children randomly assigned to DHA + AA would display better socioemotional outcomes compared with those randomly assigned to a placebo. METHODS: Omega Tots was a single-site randomized, fully masked, parallel-group, placebo-controlled trial. Children (N = 377) were 10 to 16 months at enrollment, born at <35 weeks' gestation, and assigned to 180 days of daily 200-mg DHA + 200-mg AA supplementation or a placebo (400 mg corn oil). Caregivers completed the Brief Infant-Toddler Social and Emotional Assessment and the Pervasive Developmental Disorders Screening Test-II, Stage 2 at the end of the trial. Liner mixed models and log-binomial regression compared socioemotional outcomes between the DHA + AA and placebo groups. RESULTS: Outcome data were available for 83% of children (n treatment = 161; n placebo = 153). Differences between DHA + AA and placebo groups on Brief Infant-Toddler Social and Emotional Assessment scores were of small magnitude (Cohen's d ≤ 0.15) and not statistically significant. Children randomly assigned to DHA + AA had a decreased risk of scoring at-risk for ASD on the Pervasive Developmental Disorders Screening Test-II, Stage 2 (21% vs 32%; risk ratio = 0.66 [95% confidence interval: 0.45 to 0.97]; risk difference = -0.11 [95% confidence interval: -0.21 to -0.01]) compared with children randomly assigned to a placebo. CONCLUSIONS: No evidence of benefit of DHA + AA supplementation on caregiver-reported outcomes of broad socioemotional development was observed. Supplementation resulted in decreased risk of clinical concern for ASD. Further exploration in larger samples of preterm children and continued follow-up of children who received DHA + AA supplementation as they approach school age is warranted.

Lifestyle and Early Achievement in Families (LEAF) study: Design of an ambidirectional cohort study of prenatal marijuana exposure and child development and behaviour.

BACKGROUND: Marijuana is the most-used illicit substance during pregnancy in the USA, but only two cohort studies, begun over 30 years ago, were specifically established to assess the association of pregnancy use with childhood outcomes. They found use to be associated with specific deficits in executive function at 8+ years, but did not focus on these outcomes earlier in life when intervention may be more successful. Two general purpose cohorts found increased aggression in exposed female toddlers and increased behavioural problems and tic disorders in exposed school-age children. OBJECTIVES: The Lifestyle and Early Achievement in Families (LEAF) study assesses the association of in utero marijuana exposure, documented prospectively by biomarker, self-report, and medical records, with executive function and aggression at age 3½-7 years. METHODS: This ambidirectional cohort (historical cohort with continued follow-up) includes women enrolled in the Perinatal Research Repository during prenatal care at Ohio State University Wexner Medical Center and their children, recontacted 3½-7 years post-birth. Children complete 1-2 study visits including cognitive testing, behavioural observation, and maternal and teacher report of behaviour. Family and social environmental factors are assessed. RESULTS: Child follow-up began in September 2016; visits continue through August 2020. There are 362 eligible children; 32% had mothers who used marijuana during pregnancy, 10% of mothers completed college, and 23% did not complete high school. Mean maternal age at study registration in pregnancy was 26.4 years, and 63% of mothers were African American. To date, 268 children have completed at least 1 study visit. CONCLUSIONS: The LEAF Study will document the association of prenatal marijuana exposure with development and behaviour in the current era when marijuana is more potent than when previous cohorts were studied. The results may inform policy and interventions to counsel reproductive-aged women about the risks of use during pregnancy and guide prevention and treatment of adverse effects among children.

To attend, or not to attend: Examining caregiver intentions and study compliance in a pediatric, randomized controlled trial.

BACKGROUND/AIMS: The Intent to Attend is a brief questionnaire recommended by the National Research Council to address dropout concerns and improve prediction of missing data in clinical trials, although implementation has been very limited. As a formative study in pediatric research, the relationship between caregiver intentions and study compliance was investigated in a 180-day trial of dietary supplementation of preterm toddlers. Treatment effect estimation in the context of missing data was also explored. METHODS: Study compliance (i.e. study completion, supplement adherence, and diary completion) was tracked over three study visits. Baseline questionnaires asked caregivers about intentions concerning study completion via the Intent to Attend, screened for mental health symptoms (depression, trait anxiety), and captured family demographics. Simple and multiple logistic regression models were built to examine associations between caregiver intent and compliance outcomes. The Intent to Attend was also employed as an auxiliary variable to account for missing data within mixed models estimating the treatment effect on the primary outcomes. RESULTS: Of the 316 caregiver-child dyads included, 95% of caregivers with low intentions had a child complete the study, but only 87% of caregivers with high intentions had a child complete the study. Low intentions to complete the study were associated with a more than 60% lower odds of study non-completion, but the confidence interval included the null (odds ratio: 0.36; 95% confidence interval: 0.11, 1.20). No effect measure modification by caregiver mental health, child sex, or annual income was detected. Income was the only significant predictor of study non-completion; the lowest income group was almost four times more likely to be study non-completers compared with the highest income group, even after adjustment for child sex and caregiver mental health (adjusted odds ratio = 3.59, 95% confidence interval: 1.38, 9.31). When using Intent to Attend as an auxiliary variable, similar results were obtained when compared with the original treatment effect estimates on the primary outcomes. CONCLUSION: Contrary to prior adult studies, there is no clear relationship between caregiver intentions and study compliance. Findings elucidate the complexities of caregiver-child interactions during pediatric trial participation.

Parental Perceptions and Behaviors Regarding Child Weight Status among Toddlers Born Preterm.

OBJECTIVE: Childhood obesity is a significant determinant of adult obesity. Among children born preterm, rapid "catch-up growth" in infancy increases the risk of later obesity. Parental perceptions of their child's weight status may compound the child's biologically heightened risk of obesity. STUDY DESIGN: We performed a secondary analysis of data on parental perceptions of child weight status from a randomized controlled trial (2012-2017, n = 331 toddlers born preterm). We used the Child Feeding Questionnaire (CFQ) to measure parental child feeding behaviors and beliefs. We calculated the prevalence of incorrect weight estimation, and used t-tests and chi-square tests to compare sample characteristics by correct versus incorrect weight estimation. We calculated odds ratios (ORs) for factors associated with parental underestimation of child weight status. RESULTS: Most (90%) children were of normal weight, whereas 3% were underweight and 7% were overweight. A majority (75%) of parents correctly estimated their child's weight status. Incorrect weight estimation was only associated with child's actual weight. Parents of overweight children were more likely to underestimate their child's weight status than parents of normal weight children (OR: 2.23, 95% confidence interval: 2.00-2.49). Mean CFQ scores differed by the child's actual weight status but not by the child's estimated weight status. CONCLUSION: Among these toddlers born preterm, significantly higher proportions of parents with underweight and overweight children incorrectly estimated their child's weight status relative to parents of normal weight children. Our findings suggest that weight underestimation could be a problem in this population, although it was not associated with changes in feeding practices.

Docosahexaenoic Acid and Arachidonic Acid Supplementation and Sleep in Toddlers Born Preterm: Secondary Analysis of a Randomized Clinical Trial.

STUDY OBJECTIVES: This secondary analysis characterized sleep patterns for toddlers born preterm and tested effects of docosahexaenoic acid (DHA)+ arachidonic acid (AA) supplementation on children's caregiver-reported sleep. Exploratory analyses tested whether child sex, birth weight, and caregiver depressive symptomatology were moderators of the treatment effect. METHODS: Omega Tots was a single-site 180-day randomized (1:1), double-blinded, placebo-controlled trial. Children (n = 377) were age 10 to 16 months at enrollment, born at less than 35 weeks' gestation, assigned to 180 days of daily 200 mg DHA + 200 mg AA supplementation or placebo (400 mg corn oil), and followed after the trial ended to age 26 to 32 months. Caregivers completed a sociodemographic profile and questionnaires about their depressive symptomatology (Center for Epidemiologic Studies Depression Scale) and the child's sleep (Brief Infant Sleep Questionnaire). Analyses compared changes in sleep between the DHA+AA and placebo groups, controlling for baseline scores. Exploratory post hoc subgroup analyses were conducted. RESULTS: Eighty-one percent (ntx = 156; nplacebo = 150) of children had 180-day trial outcome data; 68% (ntx = 134; nplacebo = 122) had postintervention outcome data. Differences in change between the DHA+AA and placebo groups after 180 days of supplementation were not statistically significant for the entire cohort. Male children (difference in nocturnal sleep change = 0.44, effect size = 0.26, P = .04; sleep problems odds ratio = 0.36, 95% confidence interval = 0.15, 0.82) and children of depressed caregivers (difference in nocturnal sleep change = 1.07, effect size = 0.65, P = .006; difference in total sleep change = 1.10, effect size = 0.50, P = .04) assigned to the treatment group showed improvements in sleep, compared to placebo. CONCLUSIONS: Although there is no evidence of an overall effect of DHA+AA supplementation on child sleep, exploratory post hoc analyses identified important subgroups of children born preterm who may benefit. Future research including larger samples is warranted. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Identifier: NCT01576783. CITATION: Boone KM, Rausch J, Pelak G, Li R, Turner AN, Klebanoff MA, Keim SA. Docosahexaenoic acid and arachidonic acid supplementation and sleep in toddlers born preterm: secondary analysis of a randomized clinical trial. J Clin Sleep Med. 2019;15(9):1197-1208.

Improved Estimation of Breastfeeding Rates Using a Novel Breastfeeding and Milk Expression Survey.

Background: Increasing the proportion of infants who are breastfed and extending breastfeeding duration are high-priority U.S. goals. Evaluation of progress is based on federal survey data, but federal survey questions do not reflect contemporary feeding practices. Materials and Methods: Our objective was to evaluate the Brief Breastfeeding and Milk Expression Recall Survey (BaByMERS) in estimating breast milk feeding and milk expression practices and compare to estimates from simultaneously administered federal survey questions. We surveyed women with child(ren) younger than the age of 6 years attending a large children's hospital for urgent or primary care. We estimated the proportions who participated in various breast milk feeding and milk expression practices and the durations of each and examined agreement between the surveys. We compared respondents with high versus low disagreement using log-binomial regression. Results: Of 225 respondents, 51% had less than a Bachelor's degree, and 44% identified as a race other than white. Similar proportions on each survey reported ever having breastfed or fed breast milk (84%). Proportions still breastfeeding or feeding breast milk at 6 and 12 months differed slightly by survey. Dyads (9%) who fed at the breast and fed expressed milk for nonidentical periods had estimates for the duration of breastfeeding or feeding breast milk that were lower per the federal survey. Respondents who answered the federal survey before the BaByMERS were more likely to provide discrepant responses (risk ratio = 3.40, 95% confidence interval: 1.18-9.80). Conclusions: This study offers further validation of brief interviewer-administered questions to collect quality data recalled about infant feeding and lactation for research purposes.

Docosahexaenoic and Arachidonic Acid Supplementation of Toddlers Born Preterm Does Not Affect Short-Term Growth or Adiposity.

BACKGROUND: Dietary DHA intake among US toddlers is low. Healthy physical growth is an important objective for the clinical care of children born preterm. OBJECTIVES: The aim of the trial was to examine the effects of supplementing toddlers born preterm with DHA and arachidonic acid (AA) for 180 d on growth and adiposity. METHODS: Omega Tots, a randomized placebo-controlled trial, was conducted between April 2012 and March 2017. Children born at <35 wk gestation who were 10-16 mo in corrected age were assigned to receive daily oral supplements of DHA and AA (200 mg each, "DHA + AA") or corn oil (placebo) for 180 d. Prespecified secondary outcomes included weight, length, head circumference, mid-upper arm circumference, triceps and subscapular skinfolds, BMI, and their respective z scores, and body fat percentage, which were measured at baseline and trial completion. Mixed-effects regression was used to compare the change in outcomes between the DHA + AA and placebo groups, controlling for baseline values. RESULTS: Among 377 children included in the analysis (median corrected age = 15.7 mo, 48.3% female), 348 (92.3%) had growth or adiposity data at baseline and trial end. No statistically significant differences between the DHA + AA and placebo groups in growth or adiposity outcomes were observed. For instance, the change in weight-for-age z scores was 0.1 for the DHA + AA group and 0.0 for the placebo group (effect size = 0.01, P = 0.99). However, post-hoc subgroup analyses revealed a statistically significant interaction between treatment group and sex, suggesting somewhat slower linear growth for females assigned to the DHA + AA group compared with the placebo group. CONCLUSIONS: Among toddlers born preterm, daily supplementation with DHA + AA for 180 d resulted in no short-term differences in growth or adiposity compared with placebo. If DHA supplementation is implemented after the first year of life, it can be expected to have no effect on short-term growth or adiposity. This trial is registered with clinicaltrials.gov as NCT02199808.

Gaps and Factors Related to Receipt of Care within a Medical Home for Toddlers Born Preterm.

OBJECTIVE: To characterize gaps and factors related to receipt of care within a medical home for toddlers born preterm. STUDY DESIGN: Participants were 202 caregivers of children born at <35 weeks of gestation. At 10-16 months of corrected age, caregivers completed the National Survey of Children's Health (2011/2012) medical home module and a sociodemographic profile. Care within a medical home comprised having a personal doctor/nurse, a usual place for care, effective care coordination, family-centered care, and getting referrals when needed. Gestational age and neonatal follow-up clinic attendance were abstracted from the medical record. The Bayley Scales of Infant and Toddler Development, Third Edition assessed developmental status. Log-binomial regression examined factors related to receiving care within a medical home. RESULTS: Fifty-three percent (n = 107) of the children received care within a medical home. Low socioeconomic status (young caregiver: risk ratio [RR] = 0.73; 95% CI 0.55, 0.97; low education: RR= 0.69; 95% CI 0.49, 0.98) and delayed language (RR = 0.63; 95% CI 0.42, 0.95) were associated with a lower likelihood of receiving care within a medical home. Degree of prematurity and neonatal clinic follow-up participation were unrelated to receipt of care within a medical home. CONCLUSIONS: Receipt of care within a medical home was lacking for nearly one-half of preterm toddlers, especially those with lower socioeconomic status and poorer developmental status. Discharge from a neonatal intensive care unit may be an optimal time to facilitate access to a primary care medical home and establish continuity of care. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01576783.

Associations between parenting behavior and executive function among preschool-aged children born very preterm.

The objective of the current study was to determine whether three domains of observed parenting behavior were associated with executive function in preschool-aged children born very preterm (<30 completed weeks' gestation). Executive function of 41 preschool-aged (3.5 to 4.5 years) children was assessed using a standardized protocol (gift delay) and by parent-report (Behavior Rating Inventory of Executive Function-Preschool, BRIEF-P). Observational protocols were used to determine parental sensitivity, harsh intrusiveness, and dyadic mutuality in a semi-structured play task. Parental sensitivity and mutuality were rated as higher, and harsh intrusiveness was rated as lower for children high in executive function on the gift delay task. Similarly, correlations between the three parenting scales and the BRIEF-P Global Executive Composite t-score were in the expected direction though not always statistically significant. Findings suggest that very preterm children who experienced sensitive parenting and were rated as having greater mutuality in their interactions with their caregivers scored higher on executive function tasks. These findings add to the growing literature on the key role that sensitive parenting and mutually responsive, harmonious interactions between caregivers and children may play in the development of executive function in very preterm children.

Effect of Docosahexaenoic Acid Supplementation vs Placebo on Developmental Outcomes of Toddlers Born Preterm: A Randomized Clinical Trial.

Importance: Intake of dietary docosahexaenoic acid (DHA) among toddlers is low. Supplementation may benefit developmental outcomes of toddlers who were born preterm. Objective: To determine whether 6 months of daily DHA supplementation improves developmental outcomes of toddlers who were born preterm. Design, Setting, and Participants: A randomized, fully masked, placebo-controlled trial was conducted from April 26, 2012, to March 24, 2017, at a large US pediatric academic center with 9 neonatal intensive care units. Children born at less than 35 weeks' gestation who were 10 to 16 months corrected age underwent 6 months of intervention. Of 2363 children assessed, 982 were eligible, 605 declined, and 377 enrolled and were randomized. Analyses were according to intent to treat. Interventions: One-to-one allocation to receive daily microencapsulated DHA, 200 mg, and arachidonic acid (AA), 200 mg (DHA+AA), or microencapsulated corn oil (placebo). Main Outcomes and Measures: The primary outcome specified a priori was Bayley Scales of Infant and Toddler Development, third edition (Bayley-III), cognitive composite score at 16 to 22 months corrected age. Secondary outcomes were Bayley-III language and motor composite scores and Infant Behavior Questionnaire-Revised and Early Childhood Behavior Questionnaire effortful control and activity level scores. Subgroup analyses defined a priori were by income, sex, and birth weight. Results: Among 377 children randomized and included in the analysis (182 girls and 195 boys; median corrected age, 15.7 months), 338 children (89.7%) had complete data on the primary outcome. Bayley-III cognitive scores did not differ between the DHA+AA and placebo groups (difference in change, 0.5 [95% CI, -1.8 to 2.8]; effect size, 0.05; P = .66). Assignment to the DHA+AA group had a small to medium negative effect on Bayley-III language scores among children with lower birth weights (eg, a child with a birth weight of 1000 g assigned to receive DHA+AA experienced a 4.1-point relative decrease, while a child assigned to placebo did not; P = .03 for interaction). Supplementation had a similar negative effect on effortful control scores among children with annual household incomes greater than $35 000 (difference in change, -0.3 [95% CI, -0.4 to -0.1]; effect size, -0.37; P = .01). Bayley-III motor scores and activity level scores were unaffected. Conclusions and Relevance: Daily supplementation with 200 mg of DHA and 200 mg of AA for 6 months resulted in no improvement in cognitive development and early measures of executive function vs placebo, and may have resulted in negative effects on language development and effortful control in certain subgroups of children. These findings do not support DHA supplementation in the second year of life for children who are born preterm. Trial Registration: ClinicalTrials.gov Identifier: NCT01576783.

ω-3 and ω-6 Fatty Acid Supplementation May Reduce Autism Symptoms Based on Parent Report in Preterm Toddlers.

Background: Children born preterm are at increased risk of autism spectrum disorder (ASD). n-3 (ω-3) Combined with n-6 (ω-6) fatty acids including γ-linolenic acid (GLA) may benefit children born preterm showing early signs of ASD. Previous trials have reported that docosahexaenoic acid (DHA) promotes cognitive development in preterm neonates and n-3 fatty acids combined with GLA improve attention-deficit-hyperactivity disorder. Objectives: The objectives of the pilot Preemie Tots Trial were 1) to confirm the feasibility of a full-scale trial in toddlers born very preterm and exhibiting ASD symptoms and 2) to explore the effects of supplementation on parent-reported ASD symptoms and related behaviors. Methods: This was a 90-d randomized, fully blinded, placebo-controlled trial in 31 children 18-38 mo of age who were born at ≤29 wk of gestation. One group was assigned to daily Omega-3-6-9 Junior (Nordic Naturals, Inc.) treatment (including 338 mg eicosapentaenoic acid, 225 mg DHA, and 83 mg GLA), and the other group received canola oil (124 mg palmitic acid, 39 mg stearic acid, 513 mg linoleic acid, 225 mg α-linolenic acid, and 1346 mg oleic acid). Mixed-effects regression analyses followed intent-to-treat analysis and explored effects on parent-reported ASD symptoms and related behaviors. Results: Of 31 children randomly assigned, 28 had complete outcome data. After accounting for baseline scores, those assigned to treatment exhibited a greater reduction in ASD symptoms per the Brief Infant Toddler Social Emotional Assessment ASD scale than did those assigned to placebo (difference in change = - 2.1 points; 95% CI: - 4.1, - 0.2 points; standardized effect size = - 0.71). No other outcome measure reflected a similar magnitude or a significant effect. Conclusions: This pilot trial confirmed adequate numbers of children enrolled and participated fully in the trial. No safety concerns were noted. It also found clinically-significant improvements in ASD symptoms for children randomly assigned to receive Omega-3-6-9 Junior, but effects were confined to one subscale. A future full-scale trial is warranted given the lack of effective treatments for this population. This trial was registered at www.clinicaltrials.gov as NCT01683565.