The relationship between growth, development and social milieu - a longitudinal study involving preschool Coloured children in Cape Town

A prospective longitudinal study was carried out to establish the relationship between growth, development and social milieu in Coloured pre-school children in Cape Town. This population was selected because, on the basis of previous studies, a wide range of nutritional status as well as a spectrum of socio-economic conditions were known to exist. A pilot study was conducted to establish the feasibility of obtaining information about factors to be included in the study as well as to determine the most suitable sampling methods. A cohort of 1 000 consecutive Coloured infants born in the Cape Town municipal area and notified to the Cape Town City Council was identified. A random sample of 187 was selected from the cohort for long-term study. Anthropometric data were documented from birth until 5 years and compared to the NCHS reference values. Developmental data consisted of milestones recorded during infancy, language assessment on the Reynell Language Scale at 2½ years carried out by the Logopaedics Department, University of Cape Town, and at 5 years, a specially constructed developmental assessment designed to assess gross motor function, fine motor development including visuo-motor skills and language, both comprehension and expression as well as basic colour and number concepts. Social data were collected during home visits by two experienced, full-time research social workers, who were both integrally involved in the planning of the study. At birth infants were relatively light and short for gestational age. Size at birth correlated with social class. A rapid post-natal weight gain rendered them relatively overweight between 3 and 6 months. Thereafter they again became lighter and shorter than the NCHS reference values and this persisted during the pre-school period. Mother's weight was related to weight at birth, 12 months and 30 months. The genetic influence on growth was reflected in a correlation between parental height and child's length from 12 months onwards. Environmental influences as assessed by social class by occupational grading of the breadwinner, income and family stability were also correlated with growth from 12 months onwards. Infant development as indicated by milestones was very similar to internationally reported studies. Motor development was not associated with social class by occupational grading of the breadwinner but with father's education, mother's personality and family stability. It was also highly correlated with growth during infancy. Early language milestones were associated with the child's micro-environment as indicated by marital status, family unit, setting and stability. Language development at 30 months reflected a general lag in verbal skills and was correlated with parental education and family stability. At five years there was a good correlation between growth, development and social milieu, although the social variables accounted for far more of the variation in development than did growth. Social class by occupation grading of the breadwinner and income reflected the general socio-economic status and there was a good cross-correlation between the social variables. Approximately one third of the families lived in a middle cl ass environment. However, poor maternal education, low incomes and over-crowding were prevalent and must constitute risk factors in child rearing. Sixty five percent of the mothers were not educated further than primary school level and over half of the families were living below an effective minimum level of income. Similarly, over half the families lived in grossly overcrowded conditions. In conclusion, therefore, during infancy developmental milestones were similar to those reported in the literature. Later, however, there was a fall-off in development and this coincided with a greater association with social circumstances. Just prior to school entry social factors far outweighed growth indices as predictors of developmental variation. Social stability of the family a composite evaluation based on a number of social characteristics, was most consistently associated with development. The implications for intervention are that this would need to be broad based and aimed at improving incomes, housing, family cohesion and child centredness and eliminating social pathology. Such intervention would require a concerted effort from a variety of sources which should include administrators, community workers and health professionals

Mediating and Moderating Effects of Iron Homeostasis Alterations on Fetal Alcohol-Related Growth and Neurobehavioral Deficits

We have previously demonstrated prenatal alcohol exposure (PAE)-related alterations in maternal and infant iron homeostasis. Given that early iron deficiency and PAE both lead to growth restriction and deficits in recognition memory and processing speed, we hypothesized that PAE-related iron homeostasis alterations may mediate and/or moderate effects of PAE on growth and neurobehavior. We examined this hypothesis in a prenatally recruited, prospective longitudinal birth cohort [87 mother-infant pairs with heavy prenatal alcohol exposure (mean = 7.2 drinks/occasion on 1.4 days/week); 71 controls], with serial growth measures and infant neurobehavioral assessments. PAE was related to growth restriction at 2 weeks and 5 years, and, in infancy, poorer visual recognition memory, slower processing speed, lower complexity of symbolic play, and higher emotionality and shyness on a parental report temperament scale. Lower maternal hemoglobin-to-log(ferritin) ratio, which we have shown to be associated with PAE, appeared to exacerbate PAE-related 2-week head circumference reductions, and elevated maternal ferritin, which we have shown to be associated with PAE, appeared to exacerbate PAE-related visual recognition memory deficits. In causal inference analyses, PAE-related elevations in maternal ferritin and hemoglobin:log(ferritin) appeared to statistically mediate 22.6–82.3% of PAE-related growth restriction. These findings support potential mechanistic roles of iron homeostasis alterations in fetal alcohol spectrum disorders (FASD)

Development and validation of a quantitative choline food frequency questionnaire for use with drinking and non-drinking pregnant women in Cape Town, South Africa

Background Although animal and human studies have demonstrated interactions between dietary choline and fetal alcohol spectrum disorders, dietary choline deficiency in pregnancy is common in the US and worldwide. We sought to develop and validate a quantitative food frequency questionnaire (QFFQ) to estimate usual daily choline intake in pregnant mothers. Methods A panel of nutrition experts developed a Choline-QFFQ food item list, including sources with high choline content and the most commonly consumed choline-containing foods in the target population. A data base for choline content of each item was compiled. For reliability and validity testing in a prospective longitudinal cohort, 123 heavy drinking Cape Coloured pregnant women and 83 abstaining/light-drinking controls were recruited at their first antenatal clinic visit. At 3 prenatal study visits, each gravida was interviewed about alcohol, smoking, and drug use, and administered a 24-hour recall interview and the Choline-QFFQ. Results Across all visits and assessments, > 78% of heavy drinkers and controls reported choline intake below the Dietary Reference Intakes adequate intake level (450 mg/day). Women reported a decrease in choline intake over time on the QFFQ. Reliability of the QFFQ across visits was good-to-acceptable for 2 of 4 group-level tests and 4 of 5 individual-level tests for both drinkers and controls. When compared with 24-hr recall data, validity of the QFFQ was good-to-acceptable for 3 of 4 individual-level tests and 3 of 5 group-level tests. For controls, validity was good-to-acceptable for all 4 individual-level tests and all 5 group-level tests. Conclusions To our knowledge, this is the first quantitative choline food frequency screening questionnaire to be developed and validated for use with both heavy and non-drinking pregnant women and the first to be used in the Cape Coloured community in South Africa. Given the high prevalence of inadequate choline intake and the growing evidence that maternal choline supplementation can mitigate some of the adverse effects of prenatal alcohol exposure, this tool may be useful for both research and future clinical outreach programs

Prenatal Alcohol Exposure is Associated with Regionally Thinner Cortex During the Preadolescent Period

Children with fetal alcohol spectrum disorders (FASD) may exhibit craniofacial dysmorphology, neurobehavioral deficits, and reduced brain volume. Studies of cortical thickness in FASD have yielded contradictory findings, with 3 reporting thicker cerebral cortex in frontal and temporal brain regions and 2 showing thinner cortex across multiple regions. All 5 studies included subjects spanning a broad age range, and none have examined continuous measures of prenatal alcohol exposure. We investigated the relation of extent of in utero alcohol exposure to cortical thickness in 78 preadolescent children with FASD and controls within a narrow age range. A whole-brain analysis using FreeSurfer revealed no significant clusters where cortical thickness differed by FASD diagnostic group. However, alcohol dose/occasion during pregnancy was inversely related to cortical thickness in 3 regions-right cuneus/pericalcarine/superior parietal lobe, fusiform/lingual gyrus, and supramarginal/postcentral gyrus. The effect of prenatal alcohol exposure on IQ was mediated by cortical thickness in the right occipitotemporal region. It is noteworthy that a continuous measure of maternal alcohol consumption during pregnancy was more sensitive than FASD diagnosis and that the effect on cortical thickness was most evident in relation to a measure of maternal binge drinking

Prospective memory impairment in children with prenatal alcohol exposure

Background Prenatal alcohol exposure (PAE) is linked to impaired performance on tests of retrospective memory, but prospective memory (PM; the ability to remember and act on delayed intentions) has not been examined in alcohol-exposed children. We investigated event-based PM in children with heavy PAE and the degree to which associations between PAE and PM are influenced by IQ, executive functioning (EF), retrospective memory, and attention deficit/hyperactivity disorder (ADHD). Methods We administered a computerized PM task to 89 children (Mage = 11.1 years) whose mothers were recruited prenatally: 29 with fetal alcohol syndrome (FAS) or partial FAS (PFAS), 32 nonsyndromal heavily exposed (HE), and 28 Controls. We examined effects of diagnostic group, cue focality, and task difficulty on PM performance. The association between a continuous measure of alcohol exposure and PM performance was also examined after controlling for sociodemographic confounders. Mediation of alcohol effects on PM by IQ, EF, and retrospective memory scores was assessed as was the effect of ADHD on PM performance. Results Children with FAS/PFAS made more PM errors than either HE or Control children. PAE was negatively related to PM performance even after adjusting for sociodemographic confounders, EF, and retrospective memory. This relation was only partially mediated by IQ. PAE was related to ADHD, but ADHD was not related to PM performance. Conclusions Fetal alcohol-related impairment in event-based PM was seen in children with FAS/PFAS. The effect of PAE on PM was not attributable to impaired EF and retrospective memory and was not solely attributable to lower IQ. Consistent with previous studies, we found no effect of ADHD on event-based PM performance at this age. This is the first study documenting PM impairment in children with heavy PAE and identifies a new domain of impairment warranting attention in diagnosis and management of fetal alcohol spectrum disorders

Neural correlates of cerebellar-mediated timing during finger tapping in children with fetal alcohol spectrum disorders

Objectives: Classical eyeblink conditioning (EBC), an elemental form of learning, is among the most sensitive indicators of fetal alcohol spectrum disorders. The cerebellum plays a key role in maintaining timed movements with millisecond accuracy required for EBC. Functional MRI (fMRI) was used to identify cerebellar regions that mediate timing in healthy controls and the degree to which these areas are also recruited in children with prenatal alcohol exposure. Experimental design: fMRI data were acquired during an auditory rhythmic/non-rhythmic finger tapping task. We present results for 17 children with fetal alcohol syndrome (FAS) or partial FAS, 17 heavily exposed (HE) nonsyndromal children and 16 non- or minimally exposed controls. Principal observations: Controls showed greater cerebellar blood oxygen level dependent (BOLD) activation in right crus I, vermis IV–VI, and right lobule VI during rhythmic than non-rhythmic finger tapping. The alcohol-exposed children showed smaller activation increases during rhythmic tapping in right crus I than the control children and the most severely affected children with either FAS or PFAS showed smaller increases in vermis IV–V. Higher levels of maternal alcohol intake per occasion during pregnancy were associated with reduced activation increases during rhythmic tapping in all four regions associated with rhythmic tapping in controls. Conclusions: The four cerebellar areas activated by the controls more during rhythmic than non-rhythmic tapping have been implicated in the production of timed responses in several previous studies. These data provide evidence linking binge-like drinking during pregnancy to poorer function in cerebellar regions involved in timing and somatosensory processing needed for complex tasks requiring precise timing