Vitamin B12 and Folate Status in Pregnant Females and Their Infants in Norway: Secondary Analysis from the Mommy's Food Study.

BACKGROUND: Vitamin B12 and folate are essential micronutrients important for normal infant growth and development. OBJECTIVES: The aims were to describe vitamin B12 and folate status in pregnant females and their infants according to commonly used status cutoffs and examine the associations between maternal status, maternal supplement use, and breastfeeding and infant status. METHODS: Pregnant females were recruited at 18 wk gestation in Bergen, Norway. Maternal vitamin B12 and folate status were measured at gestational weeks 18 (n = 136) and 36 (n = 116), and infant status was measured at ages 3 (n = 73) and 6 (n = 74) mo. RESULTS: At gestational weeks 18 and 36, respectively, 4.4% and 2.6% of the mothers had plasma cobalamin concentrations <148 pmol/L, 0.7% and 6.9% had methylmalonic acid (MMA) concentrations >0.26 µmol/L, and 3.7% and 30% had folate concentrations <10 nmol/L. None of the females had total homocysteine (t-Hcy) concentrations >13 µmol/L or 3 combined indicator of vitamin B12 (cB12) < -0.5. At 3 and 6 mo, respectively, 4.1% and 5.4% of the infants had cobalamin concentrations <148 pmol/L, 63% and 74% had t-Hcy concentrations >6.5 µmol/L, 59% and 66% had MMA concentrations >0.26 µmol/L, and 47% and 60% had cB12 > -0.5. None of the infants had folate concentrations <10 nmol/L. Several of the vitamin B12 biomarkers in infants were associated with maternal vitamin B12 status during pregnancy. Breastfed infants had lower vitamin B12 status (as indicated by plasma cobalamin, t-Hcy, and cB12) than nonbreastfed infants at both 3 and 6 mo. Use of supplements during pregnancy was associated with better vitamin B12 status among infants at 3 and 6 mo, as indicated by infants' cobalamin and t-Hcy concentrations. CONCLUSIONS: Subclinical vitamin B12 deficiency among infants was common and associated with maternal vitamin B12 status during pregnancy and breastfeeding. Among the mothers, an increase in biochemical folate deficiency was discovered toward the end of gestation. Further studies are needed to investigate clinical consequences. This trial was registered at clinicaltrials.gov as NCT02610959.

Salivary cortisol levels relate to cognitive performance in children prenatally exposed to methadone or buprenorphine.

Opioid maintenance therapy (OMT) is generally recommended for pregnant opioid-dependent women. However, much is still unknown about the potential long-term effects of prenatal methadone and buprenorphine exposure. This study explored the long-term effects of prenatal methadone and buprenorphine exposure in a cohort (n = 41) of children, aged 9-11 years, using the Wechsler Abbreviated Scale of Intelligence (WASI) to measure cognitive development and salivary cortisol samples to measure HPA-axis activity. Prenatally exposed children scored significantly lower on all four subtests of WASI (vocabulary, similarities, block design, and matrix reasoning), compared to a comparison group (all p < .05). No group differences were found for salivary cortisol levels or cortisol reactivity levels (all p > .05). Cortisol levels significantly predicted matrix reasoning scores for the OMT group, ß = -65.58, t(20) = 15.70, p = .02. Findings suggest that prenatal exposure to methadone or buprenorphine does not have long-term effects on children's HPA-axis functioning. However, since children of women in OMT scored significantly lower on tasks of cognitive function, careful follow-up throughout the school years and across adolescence is recommended.

The effects of a school-based physical activity intervention programme on children's executive control: The Health Oriented Pedagogical Project (HOPP).

AIMS: To assess the effects of a large school-based physical activity intervention on children's ability to resist distractions and maintain focus, known as executive control. METHODS: A quasi-experimental design with seven intervention and two control primary schools. The Health Oriented Pedagogical Project (HOPP) intervention consisted of 45 min of physical activity a day during school time for 6-8 months in addition to the regular weekly physical education lessons. A total of 1173 children, spanning from second grade (age 7 years) to sixth grade (age 12 years) were included in the analysis. Main outcome measures were executive control was measured at baseline and 1 year after using a modified Eriksen flanker task for the younger children (second and third grades) and a computerised Stroop task for the older children (fourth, fifth, and sixth grades). RESULTS: Both the intervention and control group showed improvements in executive control after 1 year. However, the children in the intervention group did not improve their performance more than those in the control group. CONCLUSIONS: No positive effect of the physical activity intervention programme on children's task performance was found, suggesting that the intervention did not affect children's executive control.

The developmental trajectory of pointing perception in the first year of life.

The present study investigated the development of the neural basis of pointing perception in 6-month- and 13-month-old infants. In a spatial-cueing paradigm, infants were presented with a peripheral target followed by a hand pointing toward (congruent condition) or away (incongruent condition) from the previously cued location. EEG responses to the presentation of the hand were measured. Thirteen-month-olds demonstrated larger amplitudes of ERP component P400 to incongruent compared to congruent pointing gestures over posterior temporal areas; 6-month-olds did not show any differential activation. This result suggests that the neural correlates of pointing perception undergo substantial development between 6 and 13 months of age.

Visual selective attention is impaired in children prenatally exposed to opioid agonist medication.

AIMS: To examine whether prenatal exposure to opioid agonist medication is associated with visual selective attention and general attention problems in early childhood. METHOD: Twenty-two children (mean age = 52.17 months, SD = 1.81) prenatally exposed to methadone, 9 children (mean age = 52.41 months, SD = 1.42) prenatally exposed to buprenorphine and 25 nonexposed comparison children (mean age = 51.44 months, SD = 1.31) were tested. Visual selective attention was measured with a Tobii 1750 Eye Tracker using a spatial negative priming paradigm. Attention problems were measured using the Child Behavior Checklist. RESULTS: The comparison group demonstrated a larger spatial negative priming effect (mean = 23.50, SD = 45.50) than the exposed group [mean = -6.84, SD = 86.39, F(1,50) = 5.91, p = 0.019, η(2) = 0.11]. No difference in reported attention problems was found [F(1,51) = 1.63, p = 0.21, η(2) = 0.03]. Neonatal abstinence syndrome and prenatal exposure to marijuana were found to predict slower saccade latencies in the exposed group (b = 54.55, SE = 23.56, p = 0.03 and b = 88.86, SE = 32.07, p = 0.01, respectively). CONCLUSION: Although exposed children did not appear to have attention deficits in daily life, lower performance on the SNP task indicates subtle alteration in the attention system.

Vitamin B12 status in infancy and the effect of a vitamin B12 injection in infants with subclinical vitamin B12 deficiency: study protocol for a register-based randomised controlled trial.

INTRODUCTION: Vitamin B12 (cobalamin) is crucial for optimal child development and growth, yet deficiency is common worldwide. The aim of this study is twofold; (1) to describe vitamin B12 status and the status of other micronutrients in Norwegian infants, and (2) in a randomised controlled trial (RCT), investigate the effect of vitamin B12 supplementation on neurodevelopment in infants with subclinical vitamin B12 deficiency. METHODS AND ANALYSIS: Infant blood samples, collected at public healthcare clinics, are analysed for plasma cobalamin levels. Infants with plasma cobalamin <148 pmol/L are immediately treated with hydroxocobalamin and excluded from the RCT. Remaining infants (cobalamin ≥148 pmol/L) are randomly assigned (in a 1:1 ratio) to either a screening or a control group. In the screening group, baseline samples are immediately analysed for total homocysteine (tHcy), while in the control group, the baseline samples will be analysed after 12 months. Screening group infants with plasma tHcy >6.5 µmol/L, are given an intramuscular injection of hydroxocobalamin (400 µg). The primary outcomes are cognitive, language and motor development assessed using the Bayley Scales of Infant and Toddler Development at 12 months of age. ETHICS AND DISSEMINATION: The study has been approved by the Regional Committee for Medical and Health Research Ethics (ref: 186505). Investigators who meet the Vancouver requirements will be eligible for authorship and be responsible for dissemination of study findings. Results will extend current knowledge on consequences of subclinical vitamin B12 deficiency during infancy and may inform future infant feeding recommendations. TRIAL REGISTRATION NUMBER: NCT05005897.

Children born to women in opioid maintenance treatment: A longitudinal study of child behavioral problems and parenting stress.

In the wake of the "opioid epidemic", there is considerable concern regarding potential harmful long-term effects of prenatal opioid exposure. Opioid misuse and addiction confer increased exposure to lifestyle stressors and health burdens. Accordingly, it is challenging to disentangle effects of prenatal opioid exposure per se from factors related to maternal stress. In this study, we followed 36 women enrolled in comprehensive opioid maintenance treatment (OMT) program and their children alongside 36 age-matched mother-child dyads from a community sample (COMP) from pregnancy until child-age 8 years. Across five sessions, we used a battery of well-established questionnaires to investigate trajectories of parenting stress and mental health symptoms as well as child behavior problems. The 8-year retention was relatively high (OMT: 72%, COMP: 67%), and the OMT sample remarkably stable and well-functioning, with minimal concomitant illicit drug use. Mixed effects regressions showed significantly different trajectories of child behavior problems (F = 3.8, p = 0.024) and parenting stress (F = 3.1, p = 0.016) in the two groups. Differences in experienced stress were largely explained by more distress specifically related to the parenting role in the OMT group (F = 9.7, p = 0.003). The OMT sample also reported higher psychological distress (F = 15.6, p < 0.001) than the comparison group, but notably few participants presented with problems that warranted clinical intervention. The results underscore the benefits of tailored follow-up of children prenatally exposed to opioids and their families beyond infancy and toddlerhood. Long-term direct effects of prenatal opioid exposure on behavior problems are likely modest, given an otherwise stable caregiving environment conducive to healthy development.

ERP correlates of cognitive control in children prenatally exposed to methadone or buprenorphine.

Much is still unknown about the potential long-term effects of prenatal methadone and buprenorphine exposure. We examined neural correlates of cognitive control in 19 prenatally methadone and buprenorphine exposed and 21 nondrug exposed children, aged 9-11 years. Children performed a modified version of the Eriksen Flanker task, which taps into selective attention, conflict response, and response inhibition mechanisms. We investigated behavioral responses and the ERP components N1, P2, N2, P3, and the late positive component (LPC). Children in the exposed group showed normal cognitive control function. However, an atypical ERP response related to perceptual and attention allocation processes was found in the exposed group.

Mother-child interaction and cognitive development in children prenatally exposed to methadone or buprenorphine.

OBJECTIVE: To assess the influence of mother-child interaction on children's cognitive development in a group of children prenatally exposed to methadone or buprenorphine. STUDY DESIGN: The study is part of a prospective longitudinal project investigating the development of children born to women in opioid maintenance therapy (OMT). The sample includes 67 children born between 2005 and 2007, 35 of which prenatally exposed to either methadone or buprenorphine and 32 non-exposed comparison children. RESULTS: Both groups scored within the normal range of development. However, the OMT group scored significantly lower on measures of cognitive development and mother-child interaction compared to the comparison group. Cognitive development was found to be affected by both group status, F(1,54)=5.65, p=0.02, η(2)=0.10 and mother-child interaction F(1,54)=5.26, p=0.03, η(2)=0.09. Behavioral inhibition (statue), sensorimotor function (imitating hand positions), and short-term memory (sentences) was influenced by group status while narrative memory and vocabulary were found to be more influenced by mother-child interaction. CONCLUSIONS: Different risk factors may influence different cognitive functions in children of women in OMT. Specifically, language-related cognitive skills may be more related to mother-child interaction while performance in higher cognitive functions requiring precise control over sensorimotor responses may be more sensitive to other factors such as prenatal OMT exposure, genetics, and/or prenatal exposure to other substances.

Methodological Issues in Assessing the Impact of Prenatal Drug Exposure.

Prenatal drug exposure is a common public health concern that can result in perinatal complications, birth defects, and developmental disorders. The growing literature regarding the effects of prenatal exposure to specific drugs such as tobacco, alcohol, cocaine, and heroin is often conflicting and constantly changing. This review discusses several reasons why the effects of prenatal drug exposure are so difficult to determine, including variations in dose, timing, duration of exposure, polydrug use, unreliable measures of drug exposure, latent or "sleeper" effects, genetic factors, and socioenvironmental influences. In addition to providing research guidelines, this review also aims to help clinicians and policy makers to identify the strengths and weaknesses in studies investigating the effects of prenatal drug exposure. This knowledge may be used to make better informed decisions regarding the appropriate treatment for pregnant, drug-dependent women and their children.

Executive function in preschool children prenatally exposed to methadone or buprenorphine.

Although an increasing number of children are born with prenatal methadone or buprenorphine exposure, little is still known about the potential long-term effects of these opioids. The aim of this study was to investigate executive function (EF) in children of women in opioid maintenance therapy (OMT). A total of 66 children (aged 48-57 months) participated in the study, 35 of which had histories of prenatal methadone or buprenorphine exposure. EF was measured using a battery of neuropsychological tests and the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P). Results showed that children of women in OMT perform lower on tasks of short-term memory and inhibition compared to nonexposed children, which was mainly associated with lower maternal education and employment rate. The OMT group scored significantly lower on all EF tasks compared to the nonexposed group, although scores fell within the average range on all measures. The development of these children should be monitored to assess for the possible problem behaviors and to promote optimal outcomes.

Neurodevelopmental investigation of the mirror neurone system in children of women receiving opioid maintenance therapy during pregnancy.

AIMS: Opioid maintenance therapy (OMT) is generally recommended for pregnant opioid-dependent women. Previous studies investigating the long-term effects of OMT on children's cognitive development found that children of women in OMT have an increased risk of developing deficits in motor and visual perceptual skills, which are important aspects of the mirror neurone system (MNS), a complex neural circuit involved in learning and social interactions. The aim of the current study was to investigate aspects of the MNS in children of women in OMT. DESIGN: A 2 (control group versus OMT group) × 2 (human versus mechanic) mixed factorial design. SETTING: The Cognitive Developmental Research Unit at the University of Oslo, Norway. PARTICIPANTS: Fifteen children of women in OMT and 15 non-exposed children participated. MEASUREMENTS: Goal-directed eye movements were recorded using a Tobii 1750 eye tracker. Neurocognitive tests were employed to map children's cognitive development. FINDINGS: The OMT group made fewer proactive goal-directed eye movements [mean = -37.73, standard deviation (SD) = 208.56] compared to the control group (mean = 181.47, SD = 228.65), F((1,28)) = 7.53, P = 0.01, η(2) = 0.21. No differences were found on tests of visual perception or goal understanding. CONCLUSIONS: Use of opioid maintenance therapy during pregnancy appears to be associated with impaired goal-directed eye movements in the 4-year-old infant which may affect later social adjustment adversely.

Deviant smooth pursuit in preschool children exposed prenatally to methadone or buprenorphine and tobacco affects integrative visuomotor capabilities.

BACKGROUND AND AIMS: Although an increasing number of children are born to mothers in opioid maintenance therapy (OMT), little is known about the long-term effects of these opioids. Previous studies suggest an association between prenatal OMT exposure and difficulties in eye movement control. Also, the effects of tobacco smoking on eye movements have been reported. The present study examined the influence of eye movements, i.e. smooth pursuit, on visuomotor capabilities in children of smoking mothers in OMT. DESIGN: The study comprised a 2 (OMT versus contrast group) × 2 (slow versus fast smooth pursuit) between-subject factorial design. SETTING: The cognitive developmental research unit at the University of Oslo, Norway. PARTICIPANTS: Participants were 26 4-year-old children of tobacco-smoking women in OMT and 23 non-exposed 4-year-old children, with non-smoking mothers, matched by gender and age. MEASUREMENT: Eye movements and smooth pursuit were recorded using a Tobii 1750 eyetracker. Visuomotor functions were examined by Bender test. FINDINGS: The OMT group tracked slowly moving objects with smooth pursuit in a similar manner to their non-exposed peers. When fast smooth pursuit was measured, the OMT group of children tracked the object more slowly than the contrast group, P = 0.02, ηp(2) = 0.11. A regression analysis showed that fast smooth pursuit predicted children's performance on a visuomotor task, R(2) = 0.37. CONCLUSION: Impaired eye-tracking skills in 4-year-old children exposed to methadone or buprenorphine and tobacco prenatally could inhibit the development of some cognitive functions in later life.

Prenatal exposure to methadone and buprenorphine: a review of the potential effects on cognitive development.

The amount of opioid users receiving opioid maintenance therapy has increased significantly over the last few years. As a result, an increasing number of children are prenatally exposed to long-lasting opioids such as methadone and buprenorphine. This article reviews the literature on the cognitive development of children born to mothers in opioid maintenance therapy. Topics discussed are the effects of prenatal exposure on prematurity, somatic growth, brain volume, myelination, and the endocrine and neurotransmitter system. Social-environmental factors, including parental functioning, as well as genetic factors are also described. Areas requiring further research are identified.