Judith K. Eckerle

Choline supplementation in children with fetal alcohol spectrum disorders: a randomized, double-blind, placebo-controlled trial

BACKGROUND Fetal alcohol spectrum disorders (FASDs) are conditions characterized by physical anomalies, neurodevelopmental abnormalities, and neurocognitive deficits, including intellectual, executive, and memory deficits. There are no specific biological treatments for FASDs, but rodent models have shown that prenatal or postnatal choline supplementation reduces cognitive and behavioral deficits. Potential mechanisms include phospholipid production for axonal growth and myelination, acetylcholine enhancement, and epigenetic effects. OBJECTIVE Our primary goal was to determine whether postnatal choline supplementation has the potential to improve neurocognitive functioning, particularly hippocampal-dependent memory, in children with FASDs. DESIGN The study was a double-blind, randomized, placebo-controlled pilot trial in children (aged 2.5-5 y at enrollment) with FASDs (n = 60) who received 500 mg choline or a placebo daily for 9 mo. Outcome measures were Mullen Scales of Early Learning (primary) and the elicited imitation (EI) memory paradigm (secondary). RESULTS The administration proved feasible, and choline was well tolerated. Participants received a dose on 88% of enrolled days. The only adverse event linked to choline was a fishy body odor. Choline supplementation improved the secondary outcome (EI) only after immediate recall performance was controlled for, and the outcome was moderated by age. The treatment effect on EI items recalled was significant in the younger participants (2.5- to ≤4.0-y-olds); the young choline group showed an increase of 12-14 percentage points greater than that of the young placebo group on delayed recall measures during treatment. However, there was a marginal baseline difference in delayed item recall between the young choline and placebo groups as well as a potential ceiling effect for item recall, both of which likely contributed to the observed treatment effect. We also observed a trend toward a negative effect of choline supplementation on the immediate EI recall of ordered pairs; the young placebo group showed an increase of 8-17 percentage points greater than that of the choline group during treatment. There was an inverse relation between choline dose (in mg/kg) and memory improvement (P = 0.041); the data suggest that weight-adjusted doses may be a better alternative to a fixed dose in future studies. Limitations included trend-level baseline differences in performance, the post-hoc determination of age moderation, and potential ceiling effects for the memory measure. CONCLUSIONS This pilot study suggests that an additional evaluation of choline supplementation as an intervention for memory functioning in children with FASDs is warranted. The observed interaction between age and cholines effect on EI suggests that potential sensitive periods should be considered in future work. This trial was registered at clinicaltrials.gov as NCT01149538.

Choline supplementation in children with fetal alcohol spectrum disorders has high feasibility and tolerability.

There are no biological treatments for fetal alcohol spectrum disorders (FASDs), lifelong conditions associated with physical anomalies, brain damage, and neurocognitive abnormalities. In preclinical studies, choline partially ameliorates memory and learning deficits from prenatal alcohol exposure. This phase I pilot study evaluated the feasibility, tolerability, and potential adverse effects of choline supplementation in children with FASD. We hypothesized that choline would be well tolerated with minimal adverse events. The study design was a double-blind, randomized, placebo-controlled trial. Participants included 20 children aged 2.5 to 4.9 years with prenatal alcohol exposure and FASD diagnoses. Participants were randomly assigned to 500 mg choline or placebo daily for 9 months (10 active, 10 placebo). Primary outcome measures included feasibility, tolerability, adverse effects, and serum choline levels. Seventeen participants completed the study. Compliance was 82% to 87%, as evidenced by parent-completed log sheets and dose counts. Periodic 24-hour dietary recalls showed no evidence of dietary confounding. Adverse events were minimal and were equivalent in the active and placebo arms with the exception of fishy body odor, which occurred only in the active group. There were no serious adverse events to research participants. This phase I pilot study demonstrates that choline supplementation at 500 mg/d for 9 months in children aged 2 to 5 years is feasible and has high tolerability. Further examination of the efficacy of choline supplementation in FASD is currently underway.

Executive functioning deficits in preschool children with Fetal Alcohol Spectrum Disorders

Executive function (EF) deficit is a hallmark of Fetal Alcohol Spectrum Disorders (FASD), but the vast majority of available evidence comes from school-age children and adolescents. Very little is known about EF during the critical developmental period prior to 6 years of age in FASD. We evaluated EF in 39 children with FASD (3.0–5.5 years) and a comparison group of 50 age-matched, nonexposed controls. Measures included the EF Scale for Early Childhood and a Delay of Gratification task. Compared to age-matched controls, preschool children with FASD had impairments on the EF Scale and showed more impulsivity on the Delay of Gratification task. To confirm the EF Scale finding, FASD group performance was compared to a separate normative dataset (N = 1,400). Those with FASD performed below normal (M = –0.57, SD = 0.92). Within the FASD group, IQ was correlated with the EF Scale (partial r = .60, p = .001) and Delay of Gratification (partial r = .58, p = .005). EF Scale performance did not differ significantly across levels of FASD severity (fetal alcohol syndrome [FAS], partial FAS, or alcohol-related neurobehavioral disorder [ARND]). However, compared to normative data, those with FAS had the largest deficits (M = –0.91 SD from the mean, SE = 0.23), followed by partial FAS (M = –0.66 SD from the mean, SE = 0.26), then ARND (M = –0.36 SD from the mean, SE = 0.20). These novel data show that EF deficits manifest well before the age of 6 years in children with FASD, that they occur across the spectrum, and that EF may be most impaired in children with more severe forms of FASD and/or lower IQs.

Inadequate intake of nutrients essential for neurodevelopment in children with fetal alcohol spectrum disorders (FASD).

This study evaluated dietary intake in children with fetal alcohol spectrum disorders (FASD). Pre-clinical research suggests that nutrient supplementation may attenuate cognitive and behavioral deficits in FASD. Currently, the dietary adequacy of essential nutrients in children with FASD is unknown. Dietary data were collected as part of a randomized, double-blind controlled trial of choline supplementation in FASD. Participants included 31 children with FASD, ages 2.5-4.9 years at enrollment. Dietary intake data was collected three times during the nine-month study via interview-administered 24-hour recalls with the Automated Self-Administered 24-hour Recall. Dietary intake of macronutrients and 17 vitamins/minerals from food was averaged across three data collection points. Observed nutrient intakes were compared to national dietary intake data of children ages 2-5 years (What we Eat in America, NHANES 2007-2008) and to the Dietary Reference Intakes. Compared to the dietary intakes of children in the NHANES sample, children with FASD had lower intakes of saturated fat, vitamin D, and calcium. The majority (>50%) of children with FASD did not meet the Recommended Dietary Allowance (RDA) or Adequate Intake (AI) for fiber, n-3 fatty acids, vitamin D, vitamin E, vitamin K, choline, and calcium. This pattern of dietary intake in children with FASD suggests that there may be opportunities to benefit from nutritional intervention. Supplementation with several nutrients, including choline, vitamin D, and n-3 fatty acids, has been shown in animal models to attenuate the cognitive deficits of FASD. These results highlight the potential of nutritional clinical trials in FASD.

Infections in Internationally Adopted Children

Thousands of international adoptees join families in the United States every year. Many have been in institutional care and are from countries or areas with a high risk of several infectious diseases. Focused infectious disease testing is important to ensure the health of the adoptee, as well as their new family and the larger community in which they now live. Newly arrived internationally adopted children should be screened for specific infections, including viral, bacterial, and parasitic infections. They should ideally be seen shortly after arrival by a multidisciplinary team at a center specializing in international adoption.

Overweight and obesity among children and adolescents with fetal alcohol spectrum disorders.

BACKGROUND Because prenatal alcohol exposure is associated with growth deficiency, little attention has been paid to the potential for overweight and obesity in children with fetal alcohol spectrum disorders (FASD). This study examined the prevalence of overweight/obesity (body mass index [BMI]) in a large clinical sample of children with FASD. METHODS Children, aged 2 to 19 years, who were evaluated for FASD at University Clinics, included 445 with an FASD diagnosis and 171 with No-FASD diagnosis. Prevalence of overweight/obesity (BMI ≥ 85 percentile) was compared to national and state prevalence. BMI was examined in relation to FASD diagnosis, gender, and age. Dietary intake data were examined for a young subsample (n = 42). RESULTS Thirty-four percent with any FASD diagnosis were overweight or obese, which did not differ from the No-FASD group or U.S. prevalence. Underweight was prevalent in those with fetal alcohol syndrome (FAS) (17%). However, increased rates of overweight/obesity were seen in those with partial FAS (40%). Among adolescents, those with any FASD diagnosis had increased overweight/obesity (42%), particularly among females (50%). The rate in adolescent females with FASD (50%) was nearly 3 times higher than state prevalence for adolescent females (17 to 18%), p < 0.001. In the young subsample, those who were overweight/obese consumed more calories, protein, and total fat per day than those who were not overweight or obese. CONCLUSIONS Rates of overweight/obesity are increased in children with partial FAS. In adolescents, rates are increased for any FASD diagnosis (particularly in females). Results are suggestive of possible metabolic/endocrine disruption in FASD-a hypothesis for which there is evidence from animal models. These data suggest that clinicians may consider prenatal alcohol exposure as a risk factor for metabolic/endocrine disruption, should evaluate diet as a risk in this population, and may need to target interventions to females prior to puberty to effect changes in overweight-related outcomes.

Hepatitis A Screening for Internationally Adopted Children From Hepatitis A Endemic Countries

Screening for hepatitis A virus (HAV) infection is not currently routinely recommended in internationally adopted children. International adoptees seen at the University of Minnesota International Adoption Clinic from 2006 to 2010 were assessed for acute HAV infection (positive HAV immunoglobulin M). Thirty of the 656 children screened (4.6%) were acutely HAV infected. HAV-infected children emigrated from Ethiopia (16), Guatemala (4), China (2), Colombia (2), Haiti (2), Philippines (2), Liberia (1), and Nepal (1). Infection was most frequent among children younger than 2 years (6.7%). No symptoms distinguished children with acute HAV infection from uninfected children. HAV infection caused significant social disruption, including separation of children from their ill adoptive parents during the initial weeks postarrival, a period important for postadoption adjustment and attachment. All international adoptees arriving from countries with high or intermediate HAV endemicity should be screened for HAV infection on arrival to the United States.

Prevalence of Vitamin D Deficiency in International Adoptees Within the First 6 Months After Adoption

Background. Vitamin D deficiency impairs bone health and development. Objective. To determine the prevalence of and risk factors for vitamin D deficiency in pediatric international adoptees. Methods. A prospective cohort (N = 189) study from a single international adoption clinic was conducted. Total 25-hydroxy vitamin D [25(OH)D] level was measured at the initial clinical assessment (within 6 months of adoption). Vitamin D deficiency was defined as a 25(OH)D <20 ng/mL (<8 nmol/L) and insufficiency as 25(OH)D <30 ng/mL (<12 nmol/L). Results. Vitamin D deficiency was diagnosed in 8% and insufficiency in 27% of the cohort. Lower body mass index and longer time in an institution were associated with vitamin D deficiency and insufficiency independent of age. Conclusions. Vitamin D insufficiency was common in our cohort of international adoptees. The significance of vitamin D insufficiency on bone development during the typical “catch-up” growth following international adoption needs to be determined.

Asymptomatic malaria and other infections in children adopted from Ethiopia, United States, 2006–2011

We screened 52 children adopted from Ethiopia for malaria because they had previously lived in a disease-endemic region or had past or current hepatomegaly or splenomegaly. Seven (13.5%) children had asymptomatic malaria parasitemia by microscopy (n = 2) or PCR (n = 5). Our findings suggest that adoptees at risk for asymptomatic malaria should be screened, preferably by PCR.