Maternal early-pregnancy ferritin and offspring neurodevelopment: A prospective cohort study from gestation to school age.

BACKGROUND: Iron plays a role in many key processes in the developing brain. During pregnancy, iron supplementation is widely recommended to prevent and treat iron deficiency; however, the prevalence of iron deficiency and the risk of iron overload vary greatly between populations. Evidence on the role of high levels of maternal ferritin, a storage iron marker during pregnancy in relation to offspring neurodevelopment is lacking. OBJECTIVE: Our main objective was to examine if maternal ferritin levels during pregnancy are associated with child cognitive and motor abilities. METHODS: We included Dutch mother-child dyads from the prospective population-based Generation R Study, born in 2002-2006. We compared children whose mothers had high (standard deviation score >+1) or low (standard deviation score <-1) early-pregnancy ferritin to children whose mothers had intermediate ferritin (reference group) using linear regression. Children underwent non-verbal intelligence and language tests at 4-9 years (cognitive abilities), finger-tapping and balancing tests at 8-12 years (motor abilities), and structural magnetic resonance imaging at 8-12 years (brain morphology). Covariates were child age, sex, maternal intelligence quotient estimate, age, body-mass-index, education, parity, smoking and alcohol use. RESULTS: Of the 2479 mother-child dyads with data on maternal ferritin and at least one child neurodevelopmental outcome, 387 mothers had low (mean = 20.6 µg/L), 1700 intermediate (mean = 64.6 µg/L) and 392 high (mean = 170.3 µg/L) early-pregnancy ferritin. High maternal ferritin was associated with 2.54 points (95% confidence interval -4.16, -0.92) lower child intelligence quotient and 16.02 cm3 (95% confidence interval -30.57, -1.48) smaller brain volume. Results remained similar after excluding mothers with high C-reactive protein. Low maternal ferritin was not associated with child cognitive abilities. Maternal ferritin was unrelated to child motor outcomes. CONCLUSION: High maternal ferritin during pregnancy was associated with poorer child cognitive abilities and smaller brain volume. Maternal iron status during pregnancy may be associated with offspring neurodevelopment.

Maternal folate levels during pregnancy and offspring brain development in late childhood.

BACKGROUND: Cumulative evidence shows that low maternal folate levels during pregnancy are associated with offspring neuropsychiatric disorders even in the absence of neural tube defects. However, the relationship between prenatal exposure to folate and brain development in late childhood has been rarely investigated. METHODS: In 2095 children from a prospective population-based cohort in Rotterdam, the Netherlands, we examined the association of maternal folate levels during pregnancy with downstream brain development in offspring. Maternal folate concentrations were measured from venous blood in early gestation. Child structural neuroimaging data were measured at age 9-11 years. In addition, measures of child head circumference using fetal ultrasound in the third trimester and total brain volume using magnetic resonance imaging at age 6-8 years were used for analyses with repeated assessments of brain development. RESULTS: Maternal folate deficiency (i.e., <7 nmol/L) during pregnancy was associated with smaller total brain volume (B = -18.7 cm3, 95% CI -37.2 to -0.2) and smaller cerebral white matter (B = -7.2 cm3, 95% CI -11.8 to -2.6) in children aged 9-11 years. No differences in cortical thickness or surface area were observed. Analysis of the repeated brain assessments showed that children exposed to deficient folate concentrations in utero had persistently smaller brains compared to controls from the third trimester to childhood (ß = -0.4, 95% CI -0.6 to -0.1). CONCLUSIONS: Low maternal folate levels during pregnancy are associated with altered offspring brain development in childhood, suggesting the importance of essential folate concentrations in early pregnancy.

Eye movement desensitization and reprocessing (EMDR) in children and adolescents with subthreshold PTSD after medically related trauma: design of a randomized controlled trial.

Background: Three in every 10 children and adolescents admitted to a hospital or undergoing medical treatment develop subthreshold symptoms of posttraumatic stress disorder (PTSD). When untreated, subthreshold PTSD can have a serious impact on psychosocial functioning, quality of life and long-term psychopathology. However, research investigating subthreshold PTSD and its treatment following paediatric medical interventions and/or hospitalization is scarce. Eye Movement Desensitization and Reprocessing (EMDR) is a fast and non-invasive psychosocial treatment for posttraumatic stress complaints. However, the effectiveness of EMDR in paediatric patients with subthreshold PTSD has not previously been systematically investigated. Objective: Describing the design of a randomized controlled trial (RCT) set up to evaluate the effectiveness of EMDR in children with subthreshold PTSD after hospitalization. Method: Children aged 4-15 years who have undergone a one-time (trauma type I) or repeated (trauma type II) hospitalization up to five years ago will be included. Participating children will be first screened with a standardized questionnaire for PTSD-symptoms. Subsequently, children with subthreshold PTSD will be randomly assigned to (1) approximately six sessions of standardized EMDR or (2) care as usual (CAU). Children with full diagnostic PTSD do not participate in the RCT, but are referred for direct treatment. Follow-up measurements will take place after eight weeks and eight months. Discussion: Considering the scarce evidence for the effectiveness of EMDR in children with medically related trauma, clinicans, researchers and children treated in hospitals can benefit from this study. Potential strengths and limitations of this study are discussed. Trial Registration: Netherlands Trial Register NTR5801.

Antecedentes: Alrededor de 3 de cada 10 niños y adolescentes ingresados en un hospital o sometidos a tratamiento médico desarrollan síntomas subumbrales de trastorno de estrés postraumático (TEPT). Cuando no se trata, el TEPT subumbral puede tener un impacto grave en el funcionamiento psicosocial, la calidad de vida, y la psicopatología a largo plazo. Sin embargo, la investigación sobre el TEPT subumbral y su tratamiento después de las intervenciones médicas pediátricas y/o la hospitalización es escasa. La desensibilización y reprocesamiento por movimientos oculares (EMDR) es un tratamiento psicosocial rápido y no invasivo para las quejas de estrés postraumático. Sin embargo, la efectividad del EMDR en pacientes pediátricos con TEPT subumbral no ha sido previamente investigada de manera sistemática.Objetivo: Describir el diseño de un ensayo controlado aleatorizado (RCT, en sus siglas en inglés) establecido para evaluar la efectividad de EMDR en niños con TEPT subumbral después de una hospitalización.Método: Se incluirán niños de 4 a 15 años que hayan sido sometidos a una hospitalización única (trauma tipo I) o repetida (trauma tipo II) hasta en los 5 años previos. Los niños participantes serán evaluados inicialmente con un cuestionario estandarizado para síntomas de TEPT. Posteriormente, los niños con TEPT subumbral serán asignados aleatoriamente a (1) seis sesiones de EMDR estandarizado o (2) cuidados usuales (CAU, por sus siglas en inglés). Los niños con diagnóstico completo de TEPT no participan en el RCT, pero serán derivados para tratamiento directo. Las mediciones de seguimiento se llevarán a cabo después de ocho semanas y ocho meses.Discusión: Teniendo en cuenta la escasa evidencia de la efectividad de EMDR en niños con trauma médico, los clínicos, los investigadores y los niños tratados en hospitales pueden beneficiarse de este estudio. Se discuten las fortalezas y limitaciones potenciales de este estudio.

Associations of maternal folic acid supplementation and folate concentrations during pregnancy with foetal and child head growth: the Generation R Study.

PURPOSE: Folic acid supplementation during pregnancy has been associated with a reduced risk of common neurodevelopmental delays in the offspring. However, it is unclear whether low folate status has effects on the developing brain. We evaluated the associations of maternal folic acid supplementation and folate concentrations during pregnancy with repeatedly measured prenatal and postnatal head circumference in the offspring. METHODS: Within a population-based prospective cohort, we measured maternal plasma folate concentrations at approximately 13 weeks of gestation (90 % range 10.5-17.2) and assessed folic acid supplementation by questionnaire (2001-2005). Up to 11 repeated measures of head circumference were obtained during foetal life (20 and 30 weeks of gestation) and childhood (between birth and age 6 years) in 5866 children (2002-2012). RESULTS: In unadjusted models, foetal head growth was 0.006 SD (95 % CI 0.003; 0.009, P < 0.001) faster per week per 1-SD higher maternal folate concentration. After adjustment for confounders, this association was attenuated to 0.004 SD per week (95 % CI 0.000; 0.007, P = 0.02; estimated absolute difference at birth of 2.7 mm). The association was independent of overall foetal growth. No associations were found between maternal folate concentrations and child postnatal head growth. Preconceptional start of folic acid supplementation was associated with larger prenatal head size, but not with prenatal or postnatal head growth. CONCLUSIONS: Our results suggest an independent, modest association between maternal folate concentrations in early pregnancy and foetal head growth. More research is needed to identify whether specific brain regions are affected and whether effects of folate on foetal head growth influence children's long-term functioning.

No association between hair cortisol or cortisone and brain morphology in children.

Little is known about the relationship between the long-term hypothalamic-pituitary-adrenal (HPA) axis functioning and brain structure in children. Glucocorticoid in hair has emerged as an important biomarker of HPA activity. In this study, we investigated the associations of hair cortisol and cortisone concentrations with brain morphology in young children. We included 219 children aged 6-10 years from the Generation R Study in Rotterdam, the Netherlands. We examined cortisol and cortisone concentrations by hair analysis using liquid chromatography-tandem mass spectrometry, and assessed brain morphometric measures with structural magnetic resonance imaging. The relationships of hair cortisol and cortisone concentrations with brain volumetrics, cortical thickness, cortical surface area and gyrification were analyzed separately after adjustment for several potential confounding factors. We observed a positive association between cortisol concentrations and cortical surface area in the parietal lobe, positive associations of cortisone concentrations with thalamus volume, occipital lobe volume and cortical surface area in the parietal lobe, and a negative association between cortisone concentrations and cortical surface area in the temporal lobe in the regions of interest analyses. A negative association between cortisol or cortisone concentrations and hippocampal volume was observed in children with behavioral problems. The whole brain vertex-wise analyses did however not show any association between cortisol or cortisone concentration and brain morphometric measures after correction for multiple testing. Although some associations are noted in region of interest analyses, we do not observe clear association of hair cortisol or cortisone with brain morphometric measures in typically developing young children.