Prospective, longitudinal assessment of developmental neurotoxicity.

Abstract

Methodological issues in the design of prospective, longitudinal studies of developmental neurotoxicity in humans are reviewed. A comprehensive assessment of potential confounding influences is important in these studies because inadequate assessment of confounders can threaten the validity of causal inferences drawn from the data. Potential confounders typically include demographic background variables, alcohol and smoking during pregnancy, the quality of parental stimulation, the child's age at test, and the examiner. Exposure to other substances is assessed where significant exposure is expected in the target population. In most studies, control variables even weakly related to outcome are included in all multivariate statistical analyses, and a toxic effect is inferred only if the effect of exposure is significant after controlling for the potential confounders. Once a neurotoxic effect has been identified, suspected mediating variables may be added to the analysis to examine underlying processes or mechanisms through which the exposure may impact on developmental outcome. Individual differences in vulnerability may be examined in terms of either an additive compensatory model or a synergistic "risk and resilience" approach. Failure to detect real effects (Type 11 error) is of particular concern in these studies because public policy considerations make it likely that negative findings will be interpreted to mean that the exposure is safe. Important sources of Type 11 error include inadequate representation of highly exposed individuals, overcontrol for confounders, and inappropriate correction for multiple comparisons. Given the high cost and complexity of prospective, longitudinal investigations, cross-sectional pilot studies focusing on highly exposed individuals can be valuable for the initial identification of salient domains of impairment. Environ Health Perspect 1 04(Suppl 2): 275-283 (1996)

Neuropsychological Measures of Attention and Impulse Control among 8-Year-Old Children Exposed Prenatally to Organochlorines

“…Our study also found associations between PCBs and Processing Speed, a subscale of the WISC-III, among males only. Although associations between PCBs and Processing Speed have not been previously reported, associations were found with Freedom from Distractibility, another WISC-III subscale, in the Michigan study ( Jacobson and Jacobson 1996 ), with suggestive associations for Digit Span, a subtest of Freedom from Distractibility ( Jacobson and Jacobson 2003 ). Null associations were found between PCBs and Digit Span in the Faroes cohort ( Grandjean et al 2001 ) and the present study (data not shown).…”

Polychlorinated biphenyls (PCBs) and neurological development in children: a systematic review

“…Socioeconomic status, prenatal maternal alcohol consumption, maternal smoking during pregnancy, maternal age, dietary habits, gender, the caregiving environment as measured by the HOME inventory69 and breast feeding itself are strongly associated with neurodevelopment,70 and adjustment for these factors was heterogeneous among studies and not comparable. Besides, humans are exposed to PCBs that are quite frequently present in mixtures with other organochlorine compounds or other chemical products, but only a few of the studies measured other compounds.…”

Pharmacological Treatment of Neonatal Opiate Withdrawal: Between the Devil and the Deep Blue Sea

“…This includes, but is not limited to, confounders such as, maternal age, nutrition status, IQ and psychiatric history, neonatal birth weight, gestational age, perinatal complications and congenital and developmental anomalies, and sources of bias, such as selection bias, for example, selecting children who are already suspected of developmental delay [57]. Unfortunately, the majority of available studies are limited or incomplete in their analysis and control for these potential confounders [5, 33, 49, 53–56, 60–63].…”

“…In addition to social variables, there are numerous other potential maternal and neonatal confounders to match or statistically control for in order to make valid comparisons between exposed and nonexposed groups [ 44 , 46 , 47 , 57 – 59 ]. This includes, but is not limited to, confounders such as, maternal age, nutrition status, IQ and psychiatric history, neonatal birth weight, gestational age, perinatal complications and congenital and developmental anomalies, and sources of bias, such as selection bias, for example, selecting children who are already suspected of developmental delay [ 57 ]. Unfortunately, the majority of available studies are limited or incomplete in their analysis and control for these potential confounders [ 5 , 33 , 49 , 53 – 56 , 60 – 63 ].…”