Prenatal choline, cannabis, and infection, and their association with offspring development of attention and social problems through 4 years of age.

BACKGROUND: Prenatal choline is a key nutrient, like folic acid and vitamin D, for fetal brain development and subsequent mental function. We sought to determine whether effects of higher maternal plasma choline concentrations on childhood attention and social problems, found in an initial clinical trial of choline supplementation, are observed in a second cohort. METHODS: Of 183 mothers enrolled from an urban safety net hospital clinic, 162 complied with gestational assessments and brought their newborns for study at 1 month of age; 83 continued assessments through 4 years of age. Effects of maternal 16 weeks of gestation plasma choline concentrations ⩾7.07 µM, 1 s.d. below the mean level obtained with supplementation in the previous trial, were compared to lower levels. The Attention Problems and Withdrawn Syndrome scales on Child Behavior Checklist 1½-5 were the principal outcomes. RESULTS: Higher maternal plasma choline was associated with lower mean Attention Problems percentiles in children, and for male children, with lower Withdrawn percentiles. Higher plasma choline concentrations also reduced Attention Problems percentiles for children of mothers who used cannabis during gestation as well as children of mothers who had gestational infection. CONCLUSIONS: Prenatal choline's positive associations with early childhood behaviors are found in a second, more diverse cohort. Increases in attention problems and social withdrawal in early childhood are associated with later mental illnesses including attention deficit disorder and schizophrenia. Choline concentrations in the pregnant women in this study replicate other research findings suggesting that most pregnant women do not have adequate choline in their diets.

Maternal prenatal choline and inflammation effects on 4-year-olds' performance on the Wechsler Preschool and Primary Scale of Intelligence-IV.

Maternal gestational inflammation from infection, obesity, depression, and adverse childhood experiences negatively affects offspring cognitive development. Choline is a key nutrient in fetal brain development. We investigated whether higher maternal plasma choline concentrations have a positive association with offspring cognition, specifically processing speed, in the presence of inflammation. Forty-eight children were evaluated at 4 years of age. Processing Speed Composite Score on the Wechsler Preschool & Primary Scales of Intelligence was the principal outcome. Maternal C-reactive protein (CRP), a marker of inflammation, and choline plasma concentration had been measured at 16 weeks' gestation. Choline concentrations >7.07µM were compared to lower levels. Mothers with lower choline levels reported more depression and stress. Head circumference was larger for neonates of mothers with higher choline levels. In analyses with maternal CRP, higher maternal choline was associated with higher offspring Processing Speed Composite Scores for both sexes. For males, higher maternal choline competed with the negative association of maternal CRP on Processing Speed. Higher Processing Speed was related to the child's behavioral ratings, with fewer Withdrawn Problems on the Child Behavior Checklist 1 ½-5 years at 4 years and higher Infant Behavior Questionnaire Orienting/Regulation at 3 months of age, consistent with persistent developmental effects. Higher processing speed and decreased problems in social withdrawal are positively associated with prenatal maternal choline. Both lower processing speed and social withdrawal problems are precursors to later mental difficulties. Choline supplementation in pregnancy may mitigate effects of maternal inflammation that contribute to problems in offspring's' cognition and behavior.

Targeting Treatments to Health Disparities.

These initial data suggest that with prenatal vitamins and choline supplements, we might decrease one risk factor associated with poorer health outcomes disproportionally affecting Black families, ie, preterm birth. Dissemination of this research fulfills the principle of Justice in the Belmont Report, to ensure that participants from different racial, ethnic and socioeconomic groups receive benefits from research directed to their specific problems.

Male fetus susceptibility to maternal inflammation: C-reactive protein and brain development.

BACKGROUND: Maternal inflammation in early pregnancy has been identified epidemiologically as a prenatal pathogenic factor for the offspring's later mental illness. Early newborn manifestations of the effects of maternal inflammation on human fetal brain development are largely unknown. METHODS: Maternal infection, depression, obesity, and other factors associated with inflammation were assessed at 16 weeks gestation, along with maternal C-reactive protein (CRP), cytokines, and serum choline. Cerebral inhibition was assessed by inhibitory P50 sensory gating at 1 month of age, and infant behavior was assessed by maternal ratings at 3 months of age. RESULTS: Maternal CRP diminished the development of cerebral inhibition in newborn males but paradoxically increased inhibition in females. Similar sex-dependent effects were seen in mothers' assessment of their infant's self-regulatory behaviors at 3 months of age. Higher maternal choline levels partly mitigated the effect of CRP in male offspring. CONCLUSIONS: The male fetal-placental unit appears to be more sensitive to maternal inflammation than females. Effects are particularly marked on cerebral inhibition. Deficits in cerebral inhibition 1 month after birth, similar to those observed in several mental illnesses, including schizophrenia, indicate fetal developmental pathways that may lead to later mental illness. Deficits in early infant behavior follow. Early intervention before birth, including prenatal vitamins, folate, and choline supplements, may help prevent fetal development of pathophysiological deficits that can have life-long consequences for mental health.

Maternal Prenatal Depression in Pregnancies With Female and Male Fetuses and Developmental Associations With C-reactive Protein and Cortisol.

BACKGROUND: Prenatal depression has lasting effects on development in offspring, including later mental illness risk. Maternal responses to depression include inflammation and hypothalamic-pituitary-adrenal axis stimulation. Effects on development of cerebral inhibitory neurocircuits may differ for female and male fetuses. METHODS: Mothers (N = 181) were assessed periodically, beginning at 16 weeks' gestation, using the Center for Epidemiologic Studies-Depression Scale. Maternal prenatal C-reactive protein and hair cortisol and cortisone levels were determined. Cortisone was determined in neonatal hair. Development of cerebral inhibitory neurocircuits was assessed in 162 1-month-old newborns by inhibition of P50 electrophysiological responses to repeated sounds. RESULTS: Maternal depression was associated with decreased newborn P50 inhibition in both sexes. Maternal C-reactive protein levels were significantly associated with depression only in pregnancies with male fetuses and with decreased newborn P50 inhibition only in male newborns. Maternal cortisol levels were significantly associated with depression only in pregnancies with female fetuses and with decreased newborn P50 inhibition only in female newborns. In pregnancies with male fetuses compared with pregnancies with female fetuses, cortisol was more robustly metabolized to cortisone, which does not activate cortisol receptors. CONCLUSIONS: This study finds sex-specific associations of C-reactive protein and cortisol levels with prenatal depression in women and with decreased development of newborn P50 inhibition. Sex-based differences in maternal response to depression with inflammation or cortisol and their developmental effects may reflect evolutionary influences to promote survival in adversity. Decreased newborn P50 inhibition is associated with later childhood behavioral problems, and decreased P50 inhibition is a pathophysiological feature of several mental illnesses.

Black American Maternal Prenatal Choline, Offspring Gestational Age at Birth, and Developmental Predisposition to Mental Illness.

Black Americans have increased risk for schizophrenia and other mental illnesses with prenatal origins. Prenatal choline promotes infant brain development and behavioral outcomes, but choline has not been specifically assessed in Black Americans. Pregnant women (N = 183, N = 25 Black Americans) enrolled in a study of prenatal stressors and interactions with prenatal choline. Black American women had lower 16-week gestation plasma choline than Whites. Lower choline was not related to obesity, income, or metabolic genotypes. Pregnant women in rural Uganda have higher choline levels than Black American women. Black Americans' lower choline was associated with higher hair cortisol, indicative of higher stress. Lower maternal choline was associated with offsprings' lower gestational age at birth and with decreased auditory P50 inhibition, a marker of inhibitory neuron development. Behavioral development was assessed on the Infant Behavior Questionnaire-R-SF (IBQ-R) at 3 months. Lower Black American maternal gestational choline was associated with lower infant IBQ-R Orienting/Regulation, indicating decreased attention and relation to caregivers. Additional evidence for developmental effects of choline in Black Americans comes from a randomized clinical trial of gestational phosphatidylcholine supplementation versus placebo that included 15 Black Americans. Phosphatidylcholine increased gestational age at birth and newborn P50 inhibition and decreased Social Withdrawn and Attention problems at 40 months of age in Black Americans' offspring compared to placebo. Inhibitory and behavioral deficits associated with lower prenatal choline in offspring of Black American women indicate potential developmental predispositions to later mental illnesses that might be ameliorated by prenatal choline or phosphatidylcholine supplementation.

Maternal choline and respiratory coronavirus effects on fetal brain development.

Prenatal COVID-19 infection is anticipated by the U.S. Centers for Disease Control to affect fetal development similarly to other common respiratory coronaviruses through effects of the maternal inflammatory response on the fetus and placenta. Plasma choline levels were measured at 16 weeks gestation in 43 mothers who had contracted common respiratory viruses during the first 6-16 weeks of pregnancy and 53 mothers who had not. When their infants reached 3 months of age, mothers completed the Infant Behavior Questionnaire-Revised (IBQ-R), which assesses their infants' level of activity (Surgency), their fearfulness and sadness (Negativity), and their ability to maintain attention and bond to their parents and caretakers (Regulation). Infants of mothers who had contracted a moderately severe respiratory virus infection and had higher gestational choline serum levels (≥7.5 mM consistent with U.S. Food and Drug Administration dietary recommendations) had significantly increased development of their ability to maintain attention and to bond with their parents (Regulation), compared to infants whose mothers had contracted an infection but had lower choline levels (<7.5 mM). For infants of mothers with choline levels ≥7.5 µM, there was no effect of viral infection on infant IBQ-R Regulation, compared to infants of mothers who were not infected. Higher choline levels obtained through diet or supplements may protect fetal development and support infant early behavioral development even if the mother contracts a viral infection in early gestation when the brain is first being formed.

Interaction of maternal choline levels and prenatal Marijuana's effects on the offspring.

BACKGROUND: This study investigated whether higher maternal choline levels mitigate effects of marijuana on fetal brain development. Choline transported into the amniotic fluid from the mother activates α7-nicotinic acetylcholine receptors on fetal cerebro-cortical inhibitory neurons, whose development is impeded by cannabis blockade of their cannabinoid-1(CB1) receptors. METHODS: Marijuana use was assessed during pregnancy from women who later brought their newborns for study. Mothers were informed about choline and other nutrients, but not specifically for marijuana use. Maternal serum choline was measured at 16 weeks gestation. RESULTS: Marijuana use for the first 10 weeks gestation or more by 15% of mothers decreased newborns' inhibition of evoked potentials to repeated sounds (d' = 0.55, p < 0.05). This effect was ameliorated if women had higher gestational choline (rs = -0.50, p = 0.011). At 3 months of age, children whose mothers continued marijuana use through their 10th gestational week or more had poorer self-regulation (d' = -0.79, p < 0.05). This effect was also ameliorated if mothers had higher gestational choline (rs = 0.54, p = 0.013). Maternal choline levels correlated with the children's improved duration of attention, cuddliness, and bonding with parents. CONCLUSIONS: Prenatal marijuana use adversely affects fetal brain development and subsequent behavioral self-regulation, a precursor to later, more serious problems in childhood. Stopping marijuana use before 10 weeks gestational age prevented these effects. Many mothers refuse to cease use because of familiarity with marijuana and belief in its safety. Higher maternal choline mitigates some of marijuana's adverse effects on the fetus.

Higher Gestational Choline Levels in Maternal Infection Are Protective for Infant Brain Development.

OBJECTIVE: To assess whether maternal choline decreases effects of mothers' infections on fetal brain circuit development and on expression of infant behavior at 1 year of age. STUDY DESIGN: A cross-sectional study was conducted in a public hospital obstetrics and midwifery service, with prenatal assessments of maternal infection, C-reactive protein, and choline level and postnatal assessments of cerebral neuronal inhibition in 162 newborns. At 1 year, 136 parents completed reports of their child's behavior. RESULTS: Maternal infection at 16 weeks of gestation, experienced by 41% of mothers, raised mean maternal C-reactive protein (d' = 0.47, P = .002) and decreased the development of cerebral inhibition of auditory response at 1 month of age (d' = 0.39, P < .001). Decreased newborn cerebral inhibition manifested as decreased behavioral self-regulation at 1 year. Greater choline levels in mothers with infections were associated with improved newborn inhibition of auditory cerebral response, mitigating the effect of infection (ß = -0.34 [95% CI, -5.35 to -0.14], P = .002). At 1 year of age, children of mothers with infection and greater gestational choline levels had improved development of self-regulation, approaching the level of children of mothers without infection (ß = 0.29 [95% CI 0.05-0.54], P = .03). CONCLUSIONS: Greater maternal choline, recommended by the American Medical Association as a prenatal supplement, is associated with greater self-regulation among infants who experienced common maternal infections during gestation. Behavioral problems with diminished self-regulation often lead to referrals to pediatricians and might lead to later mental illness.

Low-Income Working Families With Employer-Sponsored Insurance Turn To Public Insurance For Their Children.

Many families rely on employer-sponsored health insurance for their children. However, the rise in the cost of such insurance has outpaced growth in family income, potentially making public insurance (Medicaid or the Children's Health Insurance Plan) an attractive alternative for affordable dependent coverage. Using data for 2008-13 from the Medical Expenditure Panel Survey, we quantified the coverage rates for children from low- or moderate-income households in which a parent was offered employer-sponsored insurance. Among families in which parents were covered by such insurance, the proportion of children without employer-sponsored coverage increased from 22.5 percent in 2008 to 25.0 percent in 2013. The percentage of children with public insurance when a parent was covered by employer-sponsored insurance increased from 12.1 percent in 2008 to 15.2 percent in 2013. This trend was most pronounced for families with incomes of 100-199 percent of the federal poverty level, for whom the share of children with public insurance increased from 22.8 percent to 29.9 percent. Among families with incomes of 200-299 percent of poverty, uninsurance rates for children increased from 6.0 percent to 9.2 percent. These findings suggest a movement away from employer-sponsored insurance and toward public insurance for children in low-income families, and growth in uninsurance among children in moderate-income families.

Adoption of a Portal for the Primary Care Management of Pediatric Asthma: A Mixed-Methods Implementation Study.

BACKGROUND: Patient portals may improve communication between families of children with asthma and their primary care providers and improve outcomes. However, the feasibility of using portals to collect patient-reported outcomes from families and the barriers and facilitators of portal implementation across diverse pediatric primary care settings have not been established. OBJECTIVE: We evaluated the feasibility of using a patient portal for pediatric asthma in primary care, its impact on management, and barriers and facilitators of implementation success. METHODS: We conducted a mixed-methods implementation study in 20 practices (11 states). Using the portal, parents of children with asthma aged 6-12 years completed monthly surveys to communicate treatment concerns, treatment goals, symptom control, medication use, and side effects. We used logistic regression to evaluate the association of portal use with child characteristics and changes to asthma management. Ten clinician focus groups and 22 semistructured parent interviews explored barriers and facilitators of use in the context of an evidence-based implementation framework. RESULTS: We invited 9133 families to enroll and 237 (2.59%) used the portal (range by practice, 0.6%-13.6%). Children of parents or guardians who used the portal were significantly more likely than nonusers to be aged 6-9 years (vs 10-12, P=.02), have mild or moderate/severe persistent asthma (P=.009 and P=.04), have a prescription of a controller medication (P<.001), and have private insurance (P=.002). Portal users with uncontrolled asthma had significantly more medication changes and primary care asthma visits after using the portal relative to the year earlier (increases of 14% and 16%, respectively). Qualitative results revealed the importance of practice organization (coordinated workflows) as well as family (asthma severity) and innovation (facilitated communication and ease of use) characteristics for implementation success. CONCLUSIONS: Although use was associated with higher treatment engagement, our results suggest that achieving widespread portal adoption is unlikely in the short term. Implementation efforts should include workflow redesign and prioritize enrollment of symptomatic children. CLINICALTRIAL: Clinicaltrials.gov NCT01966068; https://clinicaltrials.gov/ct2/show/NCT01966068 (Archived by WebCite at http://www.webcitation.org/6i9iSQkm3).

Quality of Health Insurance Coverage and Access to Care for Children in Low-Income Families.

IMPORTANCE: An increasing diversity of children's health coverage options under the US Patient Protection and Affordable Care Act, together with uncertainty regarding reauthorization of the Children's Health Insurance Program (CHIP) beyond 2017, merits renewed attention on the quality of these options for children. OBJECTIVE: To compare health care access, quality, and cost outcomes by insurance type (Medicaid, CHIP, private, and uninsured) for children in households with low to moderate incomes. DESIGN, SETTING, AND PARTICIPANTS: A repeated cross-sectional analysis was conducted using data from the 2003, 2007, and 2011-2012 US National Surveys of Children's Health, comprising 80,655 children 17 years or younger, weighted to 67 million children nationally, with household incomes between 100% and 300% of the federal poverty level. Multivariable logistic regression models compared caregiver-reported outcomes across insurance types. Analysis was conducted between July 14, 2014, and May 6, 2015. EXPOSURES: Insurance type was ascertained using a caregiver-reported measure of insurance status and each household's poverty status (percentage of the federal poverty level). MAIN OUTCOMES AND MEASURES: Caregiver-reported outcomes related to access to primary and specialty care, unmet needs, out-of-pocket costs, care coordination, and satisfaction with care. RESULTS: Among the 80,655 children, 51,123 (57.3%) had private insurance, 11,853 (13.6%) had Medicaid, 9554 (18.4%) had CHIP, and 8125 (10.8%) were uninsured. In a multivariable logistic regression model (with results reported as adjusted probabilities [95% CIs]), children insured by Medicaid and CHIP were significantly more likely to receive a preventive medical (Medicaid, 88% [86%-89%]; P < .01; CHIP, 88% [87%-89%]; P < .01) and dental (Medicaid, 80% [78%-81%]; P < .01; CHIP, 77% [76%-79%]; P < .01) visits than were privately insured children (medical, 83% [82%-84%]; dental, 73% [72%-74%]). Children with all insurance types experienced challenges in access to specialty care, with caregivers of children insured by CHIP reporting the highest rates of difficulty accessing specialty care (28% [24%-32%]), problems obtaining a referral (23% [18%-29%]), and frustration obtaining health care services (26% [23%-28%]). These challenges were also magnified for privately insured children with special health care needs, whose caregivers reported significantly greater problems accessing specialty care (29% [26%-33%]) and frustration obtaining health care services (36% [32%-41%]) than did caregivers of children insured by Medicaid, and a lower likelihood of insurance always meeting the child's needs (63% [60%-67%]) than children insured by Medicaid or CHIP. Caregivers of privately insured children were also significantly more likely to experience out-of-pocket costs (77% [75%-78%]) than were caregivers of children insured by Medicaid (26% [23%-28%]; P < .01) or CHIP (38% [35%-40%]; P < .01). CONCLUSIONS AND RELEVANCE: This examination of caregiver experiences across insurance types revealed important differences that can help guide future policymaking regarding coverage for families with low to moderate incomes.

Policy Perspective: Ensuring Comprehensive Care and Support for Gender Nonconforming Children and Adolescents.

Despite recent notable advances in societal equality for lesbian, gay, bisexual, and transgender (LGBT) individuals, youth who identify as trans* or gender nonconforming, in particular, continue to experience significant challenges accessing the services they need to grow into healthy adults. This policy perspective first offers background information describing this population, their unique healthcare needs, and obstacles when seeking care, including case study examples. The authors then provide recommendations for medical education, health systems, and insurance payers, as well as recommendations for school systems and broader public policy changes to improve the health and well-being of gender nonconforming youth.

Mandates for Collaboration: Health Care and Child Welfare Policy and Practice Reforms Create the Platform for Improved Health for Children in Foster Care.

Improving the health of children in foster care requires close collaboration between pediatrics and the child welfare system. Propelled by recent health care and child welfare policy reforms, there is a strong foundation for more accountable, collaborative models of care. Over the last 2 decades health care reforms have driven greater accountability in outcomes, access to care, and integrated services for children in foster care. Concurrently, changes in child welfare legislation have expanded the responsibility of child welfare agencies in ensuring child health. Bolstered by federal legislation, numerous jurisdictions are developing innovative cross-system workforce and payment strategies to improve health care delivery and health care outcomes for children in foster care, including: (1) hiring child welfare medical directors, (2) embedding nurses in child welfare agencies, (3) establishing specialized health care clinics, and (4) developing tailored child welfare managed care organizations. As pediatricians engage in cross-system efforts, they should keep in mind the following common elements to enhance their impact: embed staff with health expertise within child welfare settings, identify long-term sustainable funding mechanisms, and implement models for effective information sharing. Now is an opportune time for pediatricians to help strengthen health care provision for children involved with child welfare.

Mental Health, Behavioral and Developmental Issues for Youth in Foster Care.

Youth in foster care represent a unique population with complex mental and behavioral health, social-emotional, and developmental needs. For this population with special healthcare needs, the risk for adverse long-term outcomes great if needs go unaddressed or inadequately addressed while in placement. Although outcomes are malleable and effective interventions exist, there are barriers to optimal healthcare delivery. The general pediatrician as advocate is paramount to improve long-term outcomes.

The ACA's pediatric essential health benefit has resulted in a state-by-state patchwork of coverage with exclusions.

The Affordable Care Act (ACA) establishes essential health benefits as the coverage standard for health plans sold in the individual and small-group markets for all fifty states and the District of Columbia, including the health insurance Marketplaces. "Pediatric services" is one of the required classes of coverage under the ACA. However, other than oral health and vision care, neither the act nor the regulations for implementing it define what these services should be. We investigated how state benchmark plans-the base plan chosen in each state as the standard or benchmark of coverage in that state under ACA rules-address pediatric coverage in plans governed by the essential health benefits standard. Our review of summaries of all the state benchmark plans found that no state specified a distinct pediatric services benefit class. Furthermore, although benchmark plans explicitly included multiple pediatric conditions, many plans also specifically excluded services for children with special health care needs. The Department of Health and Human Services has made a commitment in the essential health benefits regulations to review its approach for the 2016 plan year. Thus, our findings have implications for future regulations regarding the essential health benefits standard for pediatric services.

A procurement-based pathway for promoting public health: innovative purchasing approaches for state and local government agencies.

Through their purchasing powers, government agencies can play a critical role in leveraging markets to create healthier foods. In the United States, state and local governments are implementing creative approaches to procuring healthier foods, moving beyond the traditional regulatory relationship between government and vendors. They are forging new partnerships between government, non-profits, and researchers to increase healthier purchasing. On the basis of case examples, this article proposes a pathway in which state and local government agencies can use the procurement cycle to improve healthy eating.