The Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study: rationale and methods.

The Alberta Pregnancy Outcomes and Nutrition (APrON) study is an ongoing prospective cohort study that recruits pregnant women early in pregnancy and, as of 2012, is following up their infants to 3 years of age. It has currently enrolled approximately 5000 Canadians (2000 pregnant women, their offspring and many of their partners). The primary aims of the APrON study were to determine the relationships between maternal nutrient intake and status, before, during and after gestation, and (1) maternal mood; (2) birth and obstetric outcomes; and (3) infant neurodevelopment. We have collected comprehensive maternal nutrition, anthropometric, biological and mental health data at multiple points in the pregnancy and the post-partum period, as well as obstetrical, birth, health and neurodevelopmental outcomes of these pregnancies. The study continues to follow the infants through to 36 months of age. The current report describes the study design and methods, and findings of some pilot work. The APrON study is a significant resource with opportunities for collaboration.

The relationship between the motor system activation during action observation and adaptation in the motor system following repeated action observation.

Repeated action observation has been shown to alter the cortical representation of the observed movement in the motor system. This change in cortical representation is thought to reflect a motor adaptation to observational training (observational training effect). One factor that may impact the observational training effect is the degree of motor system activation that occurs during the observation of the action (i.e., individual differences in the responsiveness of the motor system during action observation). The present study was conducted to test this hypothesis by assessing the relationship between the change in motor system activity during action observation and the change in cortical representation of action following repeated action observation. To this end, transcranial magnetic stimulation (TMS) was used to evoke contractions of thumb muscles in two different protocols: 1) during the observation of thumb movements to assess the responsiveness of each individual's corticospinal system during action observation; and, 2) after the observation of 1800 thumb movements to assess the amount of adaptation in the representation of the thumb following repeated action observation. The key finding was the significant positive relationship between the level of corticospinal system activation during action observation and the amount of change in the direction of TMS evoked thumb movements. These data support the hypothesized relationship between motor system activation during action observation and the motor systems adaptation following observational training. They are also consistent with the notion that a common neural mechanism underlies these effects.

Psychological distress and salivary cortisol covary within persons during pregnancy.

The mechanisms whereby maternal stress during pregnancy exerts organizational effects on fetal development require elaboration. The aim of this study was to assess the plausibility of cortisol as a biological link between maternal psychological distress during pregnancy and fetal development. Previous research has resulted in equivocal findings for between-persons differences in stress and cortisol. Ecological momentary assessment was used to simultaneously assess mood and cortisol 5 times daily for 3 days in 83 women (gestational ages 6-37 weeks). Results from multilevel analysis indicated a robust within-person association between negative mood and cortisol. For each 1.0% increase in negative mood there was a corresponding 1.9% increase in cortisol. This association was unaffected by advancing gestational age. The results suggest that cortisol is a plausible biological mechanism for transducing the effects of maternal psychological distress during pregnancy to fetal development.

Comparing Attentional Networks in fetal alcohol spectrum disorder and the inattentive and combined subtypes of attention deficit hyperactivity disorder.

The Attention Network Test (ANT) was used to examine alerting, orienting, and executive control in fetal alcohol spectrum disorder (FASD) versus attention deficit hyperactivity disorder (ADHD). Participants were 113 children aged 7 to 10 years (31 ADHD-Combined, 16 ADHD-Primarily Inattentive, 28 FASD, 38 controls). Incongruent flanker trials triggered slower responses in both the ADHD-Combined and the FASD groups. Abnormal conflict scores in these same two groups provided additional evidence for the presence of executive function deficits. The ADHD-Primarily Inattentive group was indistinguishable from the controls on all three ANT indices, which highlights the possibility that this group constitutes a pathologically distinct entity.

Are balance problems connected to reading speed or the familial risk of dyslexia?

AIM: The aim of this study was to examine the connection between balance problems and reading speed in children with and without a familial risk of dyslexia by controlling for the effects of attention, hyperactivity, and cognitive and motor functioning. METHOD: The prevalence of balance problems was studied in 94 children (48 females, 46 males) with a familial risk of dyslexia (at-risk group) and 85 children (38 females, 47 males) without a risk of dyslexia (comparison group). Further, the relationships between balance problems (at age 8y 6mo), reading proficiency (at age 9y), attention-deficit-hyperactivity disorder (at age 8y), and cognitive (at age 8y 6mo) and motor functioning (at age 6y 6mo) were examined. Inclusion criteria for the at-risk group were that at least one parent had a confirmed reading problem and one or more of the parents' close relatives also had a reading problem. The Good Balance System was used to assess static standing balance, word-list and text reading tasks were used to measure reading proficiency. The Behavioural Assessment System for Children - Parent Rating Scale was used to assess attention-deficit-hyperactivity disorder, the Wechsler Intelligence Scale for Children was used to assess cognitive functioning, and the Movement Assessment Battery for Children was used to measure motor functioning. RESULTS: Balance (F((1,177)) =4.82; p=0.029; =0.027) and reading (F((1,176)) =11.95; p=0.001; =0.064) problems were more common in the at-risk group than in the comparison group. Furthermore, attention, hyperactivity, IQ, and motor functioning were not related to balance problems. However, attention (F((1,154)) =10.80; p=0.001; =0.066) and IQ (F((1,170)) =22.08; p<0.001; =0.115) were individually connected to reading speed. INTERPRETATION: Balance problems alone could not produce any differences in reading skills. Instead, both balance problems and reduced reading skills were mainly associated separately with a familial risk of dyslexia. This indicates that there may be a shared genetic mechanism between balance and reading problems.

Validation of the Edinburgh Depression Scale during pregnancy.

BACKGROUND: Untreated depression during pregnancy may have adverse outcomes for the mother and her child. Screening for depression in the general pregnant population is thus recommended. The Edinburgh Depression Scale (EDS) is widely used for postpartum depression screening. There is no consensus on which EDS cutoff values to use during pregnancy. The aim of the current study was to examine the predictive validity and concurrent validity of the EDS for all three trimesters of pregnancy. METHODS: In a large unselected sample of 845 pregnant women, the sensitivity, specificity, and validity of the EDS were evaluated. The Composite International Diagnostic Interview (depression module) was used to examine the predictive validity of the EDS. The anxiety and somatization subscales of the Symptom Checklist 90 (SCL-90) were used to examine its concurrent validity. Only women with a major depressive episode were considered as cases. RESULTS: The prevalence of depression decreased toward end term: 5.6%, 5.4%, and 3.4%. The EDS scores also decreased toward end term, while the SCL-90 subscale anxiety scores increased. The EDS showed high test-retest reliability and high concurrent validity with the SCL-90 anxiety and somatization subscales. The area under the receiver operating characteristic curve was high and varied between 0.93 and 0.97. A cutoff value of 11 in the first trimester and that of 10 in the second and third trimesters gave the most adequate combination of sensitivity, specificity, and positive predictive value. CONCLUSIONS: The EDS is a reliable instrument for screening depression during pregnancy. A lower cutoff than commonly applied in the postpartum period is recommended.

The relation between umbilical cord characteristics and the outcome of external cephalic version.

BACKGROUND: Umbilical cords of fetuses in breech presentation differ in length and coiling from their cephalic counterparts and it might be hypothesised that these cord characteristics may in turn affect ECV outcome. AIM: To investigate the relation between umbilical cord characteristics and the outcome of external cephalic version (ECV). STUDY DESIGN: Prospective cohort study. SUBJECTS: Women (>35 weeks gestation) with a singleton fetus in breech presentation, suitable for external cephalic version. Demographic, lifestyle and obstetrical parameters were assessed at intake. ECV success was based on cephalic presentation on ultrasound post-ECV. Umbilical cord length (UCL) and umbilical coiling index (UCI) were measured after birth. OUTCOME MEASURE: The relation between umbilical cord characteristics (cord length and coiling) and the success of external cephalic version. RESULTS: ECV success rate was overall 79/146 (54%), for multiparas 37/46(80%) and for nulliparas 42/100 (42%). Multiple logistic regression showed that UCL (OR: 1.04, CI: 1.01-1.07), nulliparity (OR: 0.20, CI: 0.08-0.51), frank breech (OR: 0.37, 95% CI: 0.15-0.90), body mass index (OR: 0.85, CI: 0.76-0.95), placenta anterior (OR: 0.27, CI: 0.12-0.63) and birth weight (OR: 1.002, CI: 1.001-1.003) were all independently related to ECV success. CONCLUSIONS: Umbilical cord length is independently related to the outcome of ECV, whereas umbilical coiling index is not.

Maternal selenium status during early gestation and risk for preterm birth.

BACKGROUND: Preterm birth occurs in 5%-13% of pregnancies. It is a leading cause of perinatal mortality and morbidity and has adverse long-term consequences for the health of the child. Because of the role selenium plays in attenuating inflammation, and because low concentrations of selenium have been found in women with preeclampsia, we hypothesized that low maternal selenium status during early gestation would increase the risk of preterm birth. METHODS: White Dutch women with a singleton pregnancy (n = 1197) were followed prospectively from 12 weeks' gestation. Women with thyroid disease or type 1 diabetes were excluded. At delivery, 1129 women had complete birth-outcome data. Serum concentrations of selenium were measured during the 12th week of pregnancy. Deliveries were classified as preterm or term, and preterm births were subcategorized as iatrogenic, spontaneous or the result of premature rupture of the membranes. RESULTS: Of the 60 women (5.3%) who had a preterm birth, 21 had premature rupture of the membranes and 13 had preeclampsia. The serum selenium concentration at 12 weeks' gestation was significantly lower among women who had a preterm birth than among those who delivered at term (mean 0.96 [standard deviation (SD) 0.14] µmol/L v. 1.02 [SD 0.13] µmol/L; t = 2.9, p = 0.001). Women were grouped by quartile of serum selenium concentration at 12 weeks' gestation. The number of women who had a preterm birth significantly differed by quartile (χ² = 8.01, 3 degrees of freedom], p < 0.05). Women in the lowest quartile of serum selenium had twice the risk of preterm birth as women in the upper three quartiles, even after adjustment for the occurrence of preeclampsia (adjusted odds ratio 2.18, 95% confidence interval 1.25-3.77). INTERPRETATION: Having low serum selenium at the end of the first trimester was related to preterm birth and was independent of the mother having preeclampsia. Low maternal selenium status during early gestation may increase the risk of preterm premature rupture of the membranes, which is a major cause of preterm birth.

Maternal thyroid function and the outcome of external cephalic version: a prospective cohort study.

BACKGROUND: To investigate the relation between maternal thyroid function and the outcome of external cephalic version (ECV) in breech presentation. METHODS: Prospective cohort study in 141 women (≥ 35 weeks gestation) with a singleton fetus in breech. Blood samples for assessing thyroid function were taken prior to ECV. Main outcome measure was the relation between maternal thyroid function and ECV outcome indicated by post ECV ultrasound. RESULTS: ECV success rate was 77/141 (55%), 41/48 (85%) in multipara and 36/93 (39%) in primipara. Women with a failed ECV attempt had significantly higher TSH concentrations than women with a successful ECV (p < 0.001). Multiple logistic regression showed that TSH (OR: 0.52, 95% CI: 0.30-0.90), nulliparity (OR: 0.11, 95% CI: 0.03-0.36), frank breech (OR: 0.30, 95% CI: 0.10-0.93) and placenta anterior (OR: 0.31, 95% CI: 0.11-0.85) were independently related to ECV success. CONCLUSIONS: Higher TSH levels increase the risk of ECV failure. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT00516555.

Preliminary fMRI findings on the effects of event rate in adults with ADHD.

Inhibition problems in attention deficit hyperactivity disorder (ADHD) are sensitive to stimulus event rate. This pilot study explores the neural basis of this increased susceptibility to event rate in ADHD. Event-related functional magnetic resonance imaging was used in conjunction with the administration of a fast (1.5 s) and a slow (7 s) Go/No-Go task. Brain activity patterns and reaction times of ten young male adults with ADHD (two of whom were in partial remission) and ten healthy male controls were compared. The ADHD group responded slower than controls with greater variability but with similar number of errors. Accurate response inhibition in the ADHD group in the slow condition was associated with widespread fronto-striatal activation, including the thalamus. For correct Go trials only, the ADHD group compared with controls showed substantial under-activation in the slow condition. The observed abnormal brain activation in the slow condition in adults with ADHD supports a fronto-striatal etiology, and underlines a presumed activation regulation deficit. Larger sample sizes to further validate these preliminary findings are needed.

Differentiating attention deficits in children with fetal alcohol spectrum disorder or attention-deficit-hyperactivity disorder.

AIM: The attention and inhibition problems found in children with attention-deficit-hyperactivity disorder (ADHD) are also common in children with fetal alcohol spectrum disorders (FASDs). Attempts to distinguish ADHD from FASDs in terms of these deficits are rare and were pursued in this study. METHOD: A total of 116 children (47 with ADHD, 31 males, 16 females; 30 with FASDs, 17 males, 13 females; and 39 comparison children, 20 males, 19 females) participated. The mean age was 9 years 4 months (SD 1y 8mo) in the ADHD groups, 8 years 10 months (SD 1y 2mo) in the FASD group, and 9 years 1 month (SD 1y 1mo) in the comparison group. Sustained attention was tested with a slow event rate continuous performance task (CPT). Inhibitory control was tested with both a slow and fast event rate Go/No-Go task. RESULTS: On the CPT task, children with ADHD, combined type (ADHD-C), ADHD, primarily inattentive type (ADHD-PI), and FASDs showed greater declines in task performance as a function of time than comparison children, suggesting sustained attention problems in all clinical groups. Children's Go/No-Go performance was event-rate dependent, with the ADHD-C group being affected in the slow condition and the ADHD-PI and FASD groups having problems with the fast condition. INTERPRETATION: Children with ADHD-C are typically impaired in handling understimulation, while children with FASDs may have problems with overstimulation. The dissociation in responsivity to event rate between groups may have significant differential diagnostic value.

Can attention deficit hyperactivity disorder and fetal alcohol spectrum disorder be differentiated by motor and balance deficits?

There is an ongoing debate regarding the diagnostic overlap between Attention Deficit Hyperactivity Disorder (ADHD) and Fetal Alcohol Spectrum Disorder (FASD). Differential diagnosis is important because of treatment implications. Children aged 7-10years (47 ADHD, 30 FASD, 39 controls) participated. The Movement Assessment Battery for Children (M-ABC) and the Clinical Observations of Motor and Postural Skills (COMPS) were used. Force plate and electromyography data were collected during static balance and balance perturbation. On the M-ABC both children with ADHD and FASD had more motor problems than controls. The ADHD-Combined and the ADHD-Predominantly Inattentive subgroups were similarly affected in their fine motor skills. On the COMPS, the majority of children in both groups performed in the normal range, but for those children clinically affected, it was the children with ADHD who were more likely to be severely impaired. The children with ADHD were characterized by early onset latencies of the tibialis anterior muscles and increased amplitudes of the gastrocnemius muscles. Difficulty scaling muscle force reflecting medial cerebellar involvement may be the key problem in ADHD. Cerebellar involvement in the postural instability in FASD awaits further study.

Maternal thyroid hormone concentration during late gestation is associated with foetal position at birth.

OBJECTIVE: To evaluate whether there is an association between maternal thyroid hormone and foetal cephalic head position at term gestation. CONTEXT: Rotation and flexion of the head enables the foetus to negotiate the birth canal. Low-normal range thyroid hormone concentrations in euthyroid pregnant women constitute a risk of infant motor abnormality. We hypothesized that low normal maternal thyroid hormone levels are associated with increased risk of abnormal foetal position at delivery. DESIGN: In 960 healthy Dutch women with term gestation and cephalic foetal presentation, thyroid parameters [foetal T4 (FT4), TSH and thyroid peroxidase antibody] were assessed at 36 weeks of gestation, and related to foetal head position (anterior cephalic vs. abnormal cephalic) and delivery mode (spontaneous vs. assisted delivery). RESULTS: Women presenting in anterior position (n = 891) had significantly higher FT4 levels at 36 weeks of gestation than those with abnormal cephalic presentation (n = 69). There were no between-group differences for TSH. Regression analyses indicated that the risk of abnormal head position decreased as a function of increasing FT4 [single odds ratio (OR) = 0.87, 95% confidence intervals (CI) 0.77-0.98; multivariate OR = 0.88, 95% CI 0.72-0.99)]. A similar inverse relationship between maternal FT4 and risk of assisted delivery was obtained (OR = 0.86, 95% CI 0.79-0.95; OR = 0.91, 95% CI 0.84-0.98). CONCLUSION: The lower the maternal FT4 concentration at 36 weeks of gestation, the higher the risk of abnormal cephalic foetal presentation and assisted delivery.

Neonatal screening for congenital hypothyroidism in the Netherlands: cognitive and motor outcome at 10 years of age.

CONTEXT: Patients with thyroidal congenital hypothyroidism (CH-T) born in The Netherlands in 1981-1982 showed persistent intellectual and motor deficits during childhood and adulthood, despite initiation of T(4) supplementation at a median age of 28 d after birth. OBJECTIVE: The present study examined whether advancement of treatment initiation to 20 d had resulted in improved cognitive and motor outcome. DESIGN/SETTING/PATIENTS: In 82 Dutch CH-T patients, born in 1992 to 1993 and treated at a median age of 20 d (mean, 22 d; range, 2-73 d), cognitive and motor outcome was assessed (mean age, 10.5 yr; range, 9.6-11.4 yr). Severity of CH-T was classified according to pretreatment free T(4) concentration. MAIN OUTCOME MEASURE: Cognitive and motor outcome of the 1992-1993 cohort in comparison to the 1981 to 1982 cohort was the main outcome measure. RESULTS: Patients with severe CH-T had lower full-scale (93.7), verbal (94.9), and performance (93.9) IQ scores than the normative population (P < 0.05), whereas IQ scores of patients with moderate and mild CH-T were comparable to those of the normative population. In all three severity subgroups, significant motor problems were observed, most pronounced in the severe CH-T group. No correlations were found between starting day of treatment and IQ or motor outcome. CONCLUSIONS: Essentially, findings from the 1992-1993 cohort were similar to those of the 1981-1982 cohort. Apparently, advancing initiation of T(4) supplementation from 28 to 20 d after birth did not result in improved cognitive or motor outcome in CH-T patients.

Vagal and sympathetic activity in burnouts during a mentally demanding workday.

OBJECTIVE: We study differences in task performance and related sympathetic-vagal reaction patterns between burnouts and controls during a mentally demanding workday. METHOD: Thirty-nine adults with burnout and 40 healthy controls performed mental tasks during a simulated workday. At pretest, just before lunch (lunch test) and at the end of the day (posttest), a Stroop color word task was administered as a probe task. Efficiency (the relation between performance and effort during the probe task), performance (reaction time and errors), and effort (self-report) were measured, as well as cardiovascular indices of sympathetic (blood pressure) and vagal (respiratory sinus arrhythmia) activity. RESULTS: Performance and effort investment of both burnouts and controls did not differ during pretest. As the day progressed the performance of controls improved more than the performance of burnouts. Moreover, the control group showed a decrease of blood pressure in response to mental task demands, a decrease in respiratory sinus arrhythmia activity, and no change in experienced effort. In the burnout group, no change could be demonstrated in blood pressure, suggesting a sympathetic predominance in the sympathetic-vagal balance. Burnouts experienced an increase in effort and were more tired at the end of the workday. CONCLUSION: Burnouts and healthy controls differ in their pattern of sympathetic-vagal activity only after long-lasting work demands. Findings give limited support to Porges's view that in healthy subjects, the vagal system is more responsive to challenging task situations than in chronically stressed individuals. The distinction between two phases in the burnout on the basis of behavioral and physiological characteristics is discussed.

Neonatal effects of maternal hypothyroxinemia during early pregnancy.

OBJECTIVE: We sought to examine the neurobehavioral profile of neonates who are born to women with hypothyroxinemia during early pregnancy. METHODS: Examined were 108 neonates who were born to mothers with low maternal free thyroid hormone (fT4 concentrations; <10th percentile) at 12 weeks' gestation (case patients) and 96 neonates who were born to women whose fT4 values were between the 50th and 90th percentiles, matched for parity and gravidity (control subjects). Newborn development was assessed at 3 weeks of age using the Neonatal Behavioral Assessment Scale. Maternal thyroid function (fT4 and thyrotropin hormone) was assessed at 12, 24, and 32 weeks' gestation. RESULTS: Infants of women with hypothyroxinemia at 12 weeks' gestation had significantly lower scores on the Neonatal Behavioral Assessment Scale orientation index compared with subjects. Regression analysis showed that first-trimester maternal fT4 but not maternal TSH or fT4 later in gestation was a significant predictor of orientation scores. CONCLUSIONS: This study confirms that maternal hypothyroxinemia constitutes a serious risk factor for neurodevelopmental difficulties that can be identified in neonates as young as 3 weeks of age.

Intraindividual validation of heart rate variability indexes to measure vagal effects on hearts.

Heart rate variability (HRV) has been widely used as a measure of vagal activation in physiological, psychological, and clinical examinations. We studied the within-subject quantitative relationship between HRV and vagal effects on the heart in different body postures during a gradually decreasing vagal blockade. Electrocardiogram and respiratory frequency were measured in subjects (8 endurance athletes and 10 participants of nonendurance sports) in supine, sitting, and standing postures before the blockade, under vagal blockade (atropine sulfate, 0.04 mg/kg), and four times during a 150-min recovery from the blockade. Fast Fourier transform was used to calculate low-frequency power (LFP, 0.04-0.15 Hz), high-frequency power (HFP, 0.15-0.40 Hz), and total power (TP, 0.04-0.40 Hz). A within-subject linear regression analysis of recovery time on each HRV index was conducted. Complete vagal blockade decreased all HRV significantly, particularly HFP (P < 0.001). A linear fit explained a large portion of the within-subject variance between recovery time and natural log-transformed (ln) HRV indexes in every posture, with coefficients of determination (R2) in the supine posture [means (SD)]: 98 (SD 2)% for mean R-R interval, 87 (SD 10)% for lnLFP, 87 (SD 13)% for lnHFP, and 91 (SD 10)% for lnTP. Neither body posture nor endurance-training background had an impact on R2 values. There was marked between-subject variation in the R2 values, slopes, and intercepts. In conclusion, all HRV, particularly HFP, is predominantly under vagal control. Within subjects, lnLFP, lnHFP, and lnTP increased linearly with the gradually decreasing vagal blockade in all postures.

Motor correlates of ADHD: contribution of reading disability and oppositional defiant disorder.

This study investigated whether the likelihood of motor impairment in children with attention-deficit/hyperactivity disorder (ADHD) increases with the presence of other disorders, and whether the co-occurring diagnoses of reading disability (RD) and oppositional defiant disorder (ODD) account for the motor deficits seen in ADHD. A total of 291 children (218 boys, 73 girls) participated. Six groups of children were compared: ADHD only (n = 29); RD only (n = 63); ADHD and RD (n = 47); ADHD and ODD (n = 19); ADHD, RD, and ODD (n = 21); and typically developing control children (n = 112). Motor skills were assessed with the Bruininks-Oseretsky Test of Motor Proficiency and the Beery Test of Visual-Motor Integration. We found that the motor skills of the ADHD-only group did not differ from the typical control group. Furthermore, motor impairment in ADHD increased as a function of co-occurring disorders, and the presence of RD rather than ADHD predicted motor impairment.

An investigation of impulsivity in children with early-treated congenital hypothyroidism.

The main feature of congenital hypothyroidism (CH) is a total or partial absence of thyroid hormone, caused by a developmental disorder of the thyroid gland. Introduction of neonatal thyroid screening allows early treatment with replacement hormone. As a result the prognosis of CH has greatly improved but neuropsychological problems do still occur. Claims that early-treated CH is associated with impulsivity were tested with a memory search task comprising 2 response probability conditions: a baseline condition in which "yes" and "no" responses were equally probable and a response bias condition in which the probability of a "no" response was raised to 70%. Impulsivity was defined as the ability to stop and change a response set and was assessed from the amount of inaccurate "no" responses made. Comparisons were made between 47 children with early-treated CH and 35 controls at the age of 7.5 years. Children with early-treated CH were notably slow and variable in their overall task performance but, most important, did not show signs of poor impulse control. Suggested short-term memory problems in these children could not be confirmed. Performance could not be attributed to early disease-related factors or lowered intelligence.