Changes in serial blood lead levels during pregnancy.

Abstract

The first step in modli lead kinetics during pregnancy includes a description of sequential matenal blood lead (PbB) Cross-sectional studies of groups of women at different stages of pregnancy present conflicting results (1-3), and the design is inadequate to study serial changes of lead during pregnancy. Case studies with serial measurements of PbB in pregnant women are interesting (4-6), but these are usually of women suffering frank lead intoxication.The only detailed work prospectively studying PbB in pregnant women is that of Barltrop (7) A priori exclusion criteria for the study were: 1) younger than 15, older than 42; 2) active diabetes, German measles, hepatitis, or toxoplasmosis, as determined by laboratory test, 3) habitual use of alcohol or drugs, 4) use of prescription medications, 5) hypertension controlled with medication, 6) active psychosis. Women not excluded by these criteria were informed of the purpose of the study and the procedures involved. They read, or were read, a statement of informed consent approved by the institutional review board, and signed it.A total of 532 women passed the exclusion criteria and were enrolled in the study. Of this total, 30 never arrived at the project office for their first or following appointments. One case developed hypoglycemia and 27 developed conditions described by the above exclusion criteria during their pregnancy; 22 spontaneously aborted, and 16 were stillbirths. We will report these data elsewhere. The exclusion of these subjects left 436 participants.Some of the remaining women gave birth to babies meeting the following a priori exclusion criteria, and these 22 pregnancies were also removed from the present data set: 1) birth weight under 2000 g, 2) gestation age under 36 weeks, 3) 5-min Apgar score under 6, 4) multiple birth, and 5) major congenital anomaly. An additional 41 babies suffered from hyperbilirubinemia, high lead level [one baby was born with a cord level of 69 pg/dl (3.33 pmol/l); see Rothenberg et al. (6) for description of this case], minor congenital anomaly, severe infection, birth trauma, asphyxia, respiratory difficulty, or early infant death, and these cases were also excluded from the data set. Table 1 summarizes data on 159 patients who were excluded or who dropped out of the study and compares them to 373 patients retained in the study. Excluded patients were significantly older, had more pregnancies and abortions, and gave birth to lower birth-weight and lower

The evidence that lead increases the risk for spontaneous abortion

“…The rationale for this study lies in the fact that lead is stored in bone tissue for decades, and the possibility, supported by several studies, that demineralization of the skeleton takes place during certain physiologic states such as pregnancy [Silbergeld et al, 1988;Rothenberg et al, 1994;Hertz-Picciotto et al, 2000] and menopause [Symanski and Hertz-Picciotto, 1995]. The cases of childhood plumbism were identi®ed from hospital records, traced in the 1980s, and interviewed regarding their pregnancy histories.…”

“…Since the gestational age distribution for blood lead measurements is heavily weighted after 14 weeks, it is probable that on average, the blood specimens from surviving pregnancies were drawn later in pregnancy than those who spontaneously aborted. Several reports now demonstrate that blood lead levels change throughout pregnancy [Rothenberg et al, 1994;Hertz-Picciotto et al, 2000], indicating the need for cases and surviving pregnancies to have blood drawn at comparable gestational ages. Of further concern is the small number of cases (n 22), of which not all had a blood lead measurement, resulting in very low statistical power.…”

“…The third line represents a noncase who would not be eligible to serve as a control for the case shown, due to later entry into prenatal care (a noncase entering too early would also have been ineligible). In light of changes in blood lead over the course of pregnancy documented in other studies [e.g., Rothenberg et al, 1994;Hertz-Picciotto et al, 2000], this matching also prevented bias due to noncomparable times for the measurement of the exposure. Other matching factors included maternal age, calendar time of entry, and public vs. private clinic.…”

Changes in low levels of lead over the course of pregnancy and the association with birth outcomes

“…There is a significant drop from the first trimester to the second and then a gradual increase until delivery [1][2][3]. This rise is thought to occur because of the increased demand for calcium during the latter months of pregnancy and the subsequent mobilization of lead from maternal bone stores into the blood stream [4,5].…”

“…Adverse birth outcomes, including pre-term delivery and lower birth weight, have also been associated with exposure to lead in utero [15][16][17][18][19]. Knowledge of lead's effects on birth outcomes is based on populations with moderate to high levels where study cohorts typically include either women in developing countries where current exposure to environmental lead is much greater than in the U.S. or lower income women living in the inner-city of the U.S., a demographic with higher average blood lead due to the well-established disparity in exposure during childhood [2,10,17,20]. Two factors make the study of general population levels of maternal blood lead of importance.…”