In this study we found a modest but significant association between very small increases in umbilical cord blood lead and elevations in SBP and DBP during labor and delivery. This association was observed at blood lead concentrations well below the current CDC recommended action level of 10 μg/dL for children and below the recommended level of 5 μg/dL for pregnant women (CDC 2007
). Average blood lead concentrations in this study are lower than in prior studies of lead and blood pressure in pregnant women with the exception of the EDEN cohort study (Yazbeck et al. 2009
Our findings are consistent with previous studies on blood lead levels and blood pressure during pregnancy (Magri et al. 2003
; Rabinowitz et al. 1987
; Rothenberg et al. 1999
). Unlike other studies (Chen et al. 2006
; Dawson et al. 2000
; Magri et al. 2003
; Sowers et al. 2002
), we did not observe an association between lead and GH, preeclampsia, or clinically diagnosed hypertension as noted in the medical record. Except for that of Rabinowitz et al. (1987)
, these studies differed from ours in that they used maternal venous blood lead measurements and blood pressure taken before labor and delivery. Our measurements, blood pressure during labor and delivery as well as umbilical cord blood lead concentrations, have some limitations (as discussed below) but may still represent the relative lead exposure and blood pressure status of these women.
Studies of blood pressure customarily use the average of three measurements on a seated, resting subject. We did not collect, and therefore could not average, multiple blood pressure measurements for each individual; this may have introduced some nondifferential misclassification, which would be expected to attenuate results. Additionally, in our study, like Rabinowitz et al. (1987)
, we used blood pressure measurements taken during labor and delivery, a time of additional stress. Our blood pressure measures are therefore not equivalent to the standardized measures that one would obtain in a more controlled setting. However, because all of our blood pressure measures were taken during similar conditions for all women, they are likely to be similarly skewed. Supporting the validity of our blood pressure measures, women with previous hypertension diagnosis during or before pregnancy had higher admission and maximum blood pressure levels, and neither admission nor maximum pressures were correlated with the length of the hospital stay.
An important strength of this study was the quality of cord blood exposure measurements. Through obtaining clean samples and our use of high-quality analytic methods, we were able to obtain quantitative lead measurements for most of this population, despite the fact that their lead exposures were very low. Because of constraints of the study design, we were unable to measure maternal blood lead levels. Umbilical cord metal measurements, however, may serve as a proxy for maternal exposure. Indeed, umbilical cord blood lead is highly correlated with maternal venous blood lead [reported at r2
= 0.82 (Chuang et al. 2001
)]; thus, use of cord blood lead will reasonably differentiate among different blood lead concentrations among mothers. Recognizing this, previous studies have also used cord blood lead to evaluate associations with maternal hypertension or preeclampsia (Rabinowitz et al. 1987
; Vigeh et al. 2006
). Several investigators report that umbilical cord blood lead concentrations are generally lower than maternal blood lead concentrations (Chuang et al. 2001
; Harville et al. 2005
; Rothenberg et al. 1996
). In > 500 mother–infant pairs, the ratio of mean cord blood lead to mean maternal blood lead was 0.78 (Chuang et al. 2001
). Assuming that this ratio holds in the present study, the geometric mean and 75th percentile of maternal blood lead would be approximately 0.86 and 1.24 μg/dL, respectively. These estimates for maternal venous blood in the present study are lower than concurrent estimates among adult women in the National Health and Nutrition Examination Survey, where geometric mean and 75th percentile were 1.22 and 1.80 μg/dL in 2003–2004 and 1.11 and 1.73 μg/dL in 2005–2006 (CDC 2010
Bone lead is considered to be a better marker of long-term lead exposure, and blood lead a more precise estimate of short-term lead exposure (Hu et al. 2007
). However, during pregnancy there is potentially a greater release of lead from bone into blood (Gulson et al. 1997
), and maternal blood may be derived from mobilization of lead in bone. Nevertheless, if the mechanism(s) by which lead affects maternal blood pressure levels is heavily influenced by long-term lead exposure, bone lead could be a better biomarker for describing a relationship of lead exposure with blood pressure. Rothenberg et al. (2002)
found associations of maternal hypertension and elevations in blood pressure levels with maternal bone (calcaneous) lead but not with maternal venous blood lead. On the other hand, short-term or transient lead effects on blood pressure might be better assessed with biomarkers of recent lead dose such as blood lead (Navas-Acien et al. 2008
). Knowledge of the mechanism by which lead exerts effects on blood pressure would be helpful in determining whether blood or bone lead is a better biomarker for studying this relationship; although mechanisms have been suggested (Vaziri 2008
), more work is ongoing.
Although maternal venous and umbilical cord blood lead are highly correlated, this correlation is not equivalent. If factors influencing the ratio of maternal blood lead to cord blood were not related to blood pressure, this would result in random misclassification of exposure, and as a result, our findings would be biased toward the null. In contrast, Harville et al. (2005)
reported that higher maternal blood pressure is related to a lower ratio of maternal blood lead to cord blood lead; in that situation, our results could have been biased away from the null. However, evidence supporting this conclusion is somewhat limited because Harville et al. (2005)
observed this relationship only in the subset of women > 30 years of age or with > 40 pounds of weight gain. Meanwhile, our findings are consistent with prospective evidence among nonpregnant adults, where placental transfer of lead would not influence results (Glenn et al. 2003
), providing additional support for an association between lead exposure and subsequent elevations in blood pressure.
Prior work has evaluated the influence of measurements of hematocrit or hemoglobin, stress, calcium, or zinc on the relationship between lead exposure and blood pressure levels (Hense et al. 1993
; Nawrot et al. 2002
; Peters et al. 2007
; Rabinowitz et al. 1987
; Rothenberg et al. 1999
). These data were not available for this study. Although hematocrit and hemoglobin have been associated with low lead concentrations (Harville et al. 2005
), their role as a confounders has been proposed to be more important among older women (> 50 years) (Hense et al. 1993
). Moreover, the association between blood lead levels and GH was only slightly decreased and remained statistically significant after further adjustment for hematocrit in a study during the third trimester of pregnancy (Magri et al. 2003
). Stress has been identified as an effect modifier of the lead–blood pressure relationship; those with higher stress had a higher risk of developing hypertension after lead exposure (Peters et al. 2007
). The observation that women in our population with higher cord blood leads had higher maximum blood pressure levels during labor and delivery is consistent with that work.
Our BMD analysis of these data provides a different perspective of the relationship we observed between lead exposure and blood pressure increase. In terms of estimated maternal blood lead levels from cord blood levels (calculated as described above), we found a BMDL of roughly 1.4 μg/dL venous blood lead for all blood pressure outcomes. The BMDL, again, is an exposure level that, with 95% confidence, corresponds to the prespecified response (1 SD of blood pressure) (Sand et al. 2008
). Although BMD analysis is frequently used in the process of creating regulatory exposure standards, our use of it here should not be interpreted in a regulatory context, but rather as a description of an exposure level in this study where we observed measurable effects.
No threshold effect of lead has been identified. Action levels for lead are based in part on our ability to create and invest in effective interventions for lead exposure, while recognizing that the goal is to reduce exposures to the greatest extent possible (Bernard 2003
). There is initial evidence that calcium supplementation may be related to lower blood lead levels in pregnancy by reducing the release of lead from bone lead stores (Ettinger et al. 2009
), although this needs replication. Better still would be primary prevention, or preventing lead exposure in the first place; this could occur, for example, by limiting the amount of lead released to the environment by implementing safer work practices (U.S. EPA 2010
In this work, we show that the previously established association of blood lead levels with elevations in blood pressure can be replicated among pregnant women at the time of labor and delivery, extending previous findings to even lower lead exposure levels. Because even small reductions in population blood pressure could result in substantial public health benefits (Whelton et al. 2002
), this work suggests that continued reductions in lead exposure remain an important public health goal.