Neonatal outcome measures

Various investigators have reported an association of low-level lead exposure in the foetal period and neonatal outcome measures. These studies differ, of course, with respect to the populations sampled and other procedural features. What is striking, however, in reviewing these is the lack of consistency between studies in the specific outcome measures related to foetal lead exposure. Several features of the research designs that could account for some... 

First, the possibility will be considered that some unmeasured or undermeasured confounding conditions may be particularly crucial to gestational lead exposure and to neonatal outcome measures. The second possibility to be considered is whether discrepancies between studies with respect to correction of blood lead level (PbB) for haematocrit percent (Hct%) may be related to discrepant results. Data from our Cleveland study will be used to illustrate some of these issues. While this commentary is limited to neonatal outcome measures, the issues raised are also relevant to prospective analyses relating foetal lead exposure to later development. 

Table 1 Neonatal outcome measures related to one or more indicators of foetal lead exposure in one or more studies... 

Transdermal glyceryl trinitrate 5 mg for 16 hours each day has been compared with placebo in 25 mothers bearing intrauterine growth-retarded fetuses (86). It was applied from week 27 to week 35 of gestation until delivery. Three mothers were excluded from the analysis because they did not use the glyceryl trinitrate correctly. Placental flow, measured by Doppler, was improved by glyceryl trinitrate, and there was a better short-term neonatal outcome. Moreover, a biochemical marker of brain distress, the protein SIOOB, was normalized after glyceryl trinitrate, without an excess of adverse events in either the neonates or the mothers. 

Economic and humanistic outcome evaluations are now made as part of healthcare governance. The information gained from valid outcome measures can be used on a national level to allocate expenditures for treating various sectors of the population (e.g. the elderly, neonates, etc.) or to determine which programs will receive financial resources (e.g. vaccine programs vs. acute influenza treatments). Outcome information can be used to help make decisions regarding the inclusion or exclusion of drugs on formularies. Complete information about the economic, humanistic... 

OBJECTIVES To determine whether a universal ISP or an lOP targeted at a high risk group is more economically efficient from a Societal viewpoint to prevent IDD. The primary outcome measure is prevention of irreversible IDD (endemic cretinism, mild motor and mental impairment, stillbirths and neonatal deaths). The secondary outcome measure is prevention of reversible IDD (endemic goiter). 

Table 1 includes neonatal outcome variables reported to be significantly related to low-level maternal, placental, cord, or very early infancy PbB in one or more studies. Case reports and some older studies that include additional adverse outcomes, usually as a result of high-level exposure (Rom, 1976), have been excluded. To save space. Table I excludes reports of assessed outcome measures not significantly related to PbB in any study in the review. These variables are pre-eclampsia, spontaneous abortion, foetal distress, ponderal index, intrauterine growth retardation, meconium staining, Apgar scores, jaundice, blood type, sex of infant and most scales of the Brazelton Newborn Assessment Scale. 

Chlorpyrifos provides an example of the utility of human pharmacokinetic models to estimate daily dose from biomonitoring data for a rapidly cleared pesticide. The urinary metabolite trichloro-2-pyridinol (TCP) is used in the NHANES study to monitor population exposure to chlorpyrifos (CDC 2005). Several epidemiologic studies have linked chlorpyrifos exposure to adverse birth outcomes through associations between urinary and blood biomarkers and have demonstrated maternal exposure and physiologic measurements in the neonate (Berkowitz et al. 2003, 2004 Whyatt et al. 2004 Needham 2005). 

Effects of maternal blood lead at 36 weeks and birth, and of umbilical cord lead, upon trend of development in the first 30 days of life, as measured by the Brazelton Neonatal Behavioural Assessment Scale, were assessed by multiple regression techniques. Much of the significant bivariate effect of cord lead upon abnormal reflex trend could be accounted for by control variables. However, the difference between maternal lead at birth and cord lead remained significant in the multivariate model, accounting for 6.2% additional variance in outcome. Change in maternal lead between 36 weeks and birth was a significant predictor of abnormal reflex trend and trend in regulation of states. 

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