Posted by admin on March 2nd, 1995 — in newsletter
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Lead Exposure in Pregnancy
Vol 3#3, March 1995
Eugene Pergament, MD, PhD; Amy Schechtman, MS; Carrie Koval
Lead has long been suspected to be a teratogen. The main sources of lead are lead-based paint, contaminated soil, and occupational exposure. Lead is transferred freely through the placenta as early as 12 weeks gestation and a maternal-fetal barrier to lead is not known. (O’Halloran et. al., 1992).
Recent data indicate that lead is toxic at levels which were previously thought to be safe. Today, levels of 10-15 ug/dL are of concern when just a few years ago, a blood lead level of 25 ug/dL was the lowest level for concern (O’Halloran et. al., 1992). According to the Center for Disease Control (CDC), the acceptable blood lead level is <10 ug/dL. However, even low level of lead in the blood is thought to carry a risk for subtle CNS damage (West et. al., 1992). In 1984 it was estimated that half a million pregnant women were at increased risk due to lead exposure (Landrigan, 1990). Although these numbers seem to be decreasing, lead exposure during pregnancy continues to be a serious problem. This RISK||NEWSLETTER will address the issue of lead exposure in pregnancy.
MOBILIZATION OF LEAD
Lead is stored in bone where it accumulates throughout an individual’s lifetime. Mobilization of these lead stores may occur during pregnancy and lactation due to bone demineralization. Theoretically, a significant history of childhood lead poisoning could lead to adverse pregnancy outcome later in life. Animal studies support this theory, lead mobilization, however has not been directly studied in human pregnancies. The possibility of childhood lead poisoning leading to adverse pregnancy outcome is based on secondary data. However, there are studies that have shown no increase in lead levels during pregnancy (O’Halloran et. al., 1992).
CONGENITAL MALFORMATIONS
A variety of minor malformations associated with an increased maternal blood lead level during pregnancy. These malformations include skin tags and papillae, hydroceles, hemangiomas, lymphangiomas, and undescended testicles in males. There is, however, no particular pattern of malformations that is associated with lead exposure. Nor have major malformations been associated with an increased maternal lead level (Needleman et. al., 1984; Wong et. al., 1992). Needleman et. al. (1994) did not find an association between lead levels and decreased birth weight, shortened gestation, apgar scores, respiratory distress, or jaundice. Wong et. al. (1992), however, reviewed two studies in which shortened gestation and low birth weight were associated with maternal lead levels. One study of 192 pregnancies showed a 1/2 week reduction in gestation for every 10 ug/dL increase in maternal blood lead levels. Also, low-level lead exposure was associated with a 114 g decrease in birth weight for every 10 ug/dL increase in maternal blood lead levels. A second study of infants with increased cord blood lead levels found that their gestational age was significantly decreased when compared with infants whose cord blood levels were not elevated. Even though the studies of Needleman (1984) and Wong (1992) do not agree as to whether lead levels are associated with a decrease in gestational age or birth weight, all the studies consistently find an increased incidence of miscarriage and stillbirth among women with increased lead levels.
NEUROLOGICAL IMPAIRMENT
Wong et. al. (1992) reviewed four prospective studies on the neurologic effects of low-level in-utero exposure to lead. The studies used the Bayley Mental Development Index scores (MDI) as measurement of neurobehavioral development in infants. The first study followed 249 children from birth until two years old. Prenatal lead exposure was estimated at birth from cord blood. These children were categorized into two groups: low lead levels with a mean level of 1.8 ug/dL and high lead levels with a mean level of 14.6 ug/dL. When the MDI was given at 12, 18, and 24 months of age, the high level group consistently showed a deficit ranging from 4 to 8 points when compared to the low level group. This was statistically significant at the 95% confidence interval with a probability of p=.0001.
The second study followed 132 infants for the first year of life. Lead levels were estimated by maternal blood lead levels and cord blood levels. The mean maternal blood level was 6.5 ug/dL, with the highest lead level being 14.7 ug/dL. The mean umbilical cord blood level was slightly lower, 5.8 ug/dL. Even at this seemingly low exposure, the infants showed abnormal reflexes, decreased muscle tone, and abnormal neurological soft signs at birth. At 12 months of age, the lead exposed infants had a statistically significant lower MDI score when compared to non-exposed infants.
The MDI scores were also lower in lead exposed infants in the third study. In 192 pregnancies that were exposed to low lead levels, infants had an average decrease of 2.25 in their MDI scores for each 10 ug/dL increase in in-utero lead levels. The fourth study evaluated 2 year old children and showed similar results. Every 10 ug/dL increase in lead levels produced a 2.0 point decrease in MDI scores.
Children whose cord blood lead levels were increased (10-25 ug/dL) and who also showed lower MDI scores until 24 months of age showed no difference in the McCarthy Scales of Children’s Abilities when compared to non-exposed children at 57 months of age. One possibility is that the two scales (MDI and McCarthy) evaluate different abilities and lead exposure does not affect those abilities measured on the second test (McCarthy). Another possibility is that these children recovered and compensated for their deficits sometime between 24 and 57 months of age (Bellinger et. al., 1990). Over 2,600 children were followed prospectively. Their cord lead levels were taken at birth to determine prenatal lead exposure and lead levels were measured in shed deciduous teeth to determine postnatal lead exposure. Any behavior problems identified when these children were 8 years old was associated with the postnatal lead exposure rather than the prenatal exposure (Bellinger et. al., 1994). This indicated that behavior problems in school-aged children are more likely due to postnatal lead exposure and not low-level prenatal lead exposure.
OCCUPATIONAL EXPOSURES
Lead is the third most common occupational exposure in women (Bentur et. al., 1991). As stated earlier, past studies have shown that women who have occupational exposure to lead tend to have more preterm deliveries, miscarriages, and stillbirths. There is also an increased risk for minor anomalies. The World Health Organization (WHO) recommends that the expressed limit for women who work with lead should not exceed 30 ug/dL (O’Halloran et. al., 1992). However, if a woman does have an occupational exposure, her mean lead levels should not exceed other women’s levels in the same geographic location.
There has been no evidence of adverse fetal outcome among pregnancies with paternal lead exposure. Among males who work with lead, there have been chromosome alterations and abnormalities in sperm count, vigor, and morphologic features observed. These effects, however, tend to cause infertility rather than adverse fetal effects (Bentur et. al., 1991). Previous reports have show a higher frequency of stillbirths and miscarriages in pregnancies with paternal exposure to lead. It is now believed that lead brought into the home on contaminated work clothes, thereby elevating maternal lead levels, was responsible.
RECOMMENDATIONS
Women who are at risk for having increased lead levels during pregnancy should have their blood levels monitored. If their levels are elevated, every attempt should be made to reduce their exposure. Chelating agents which reduce lead levels are not recommended for use during pregnancy because their teratogenic effects are unknown.
Three hundred forty-nine African American women who took prenatal vitamins generally had lower lead levels than women not taking prenatal vitamins. Specifically, an inverse association between lead levels and antioxidants such as vitamin E and ascorbic acid was observed (West et. al., 1994). Deficiencies in iron, calcium, and zinc can lead to increased lead absorption. Therefore it is important that at-risk women have good nutrition (O’Halloran et. al., 1992).
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Posted by admin on March 1st, 1995 — in newsletter
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Organic Solvents and Pregnancy
VOL3#4, March 1995
Eugene Pergament, MD, PhD; Amy Schechtman, MS, CGC; Charli Loebl, BS
Exposures to organic solvents may occur in a variety of settings, including occupational exposure in the workplace, non-occupational or incidental exposure in the home, or exposure as the result of solvent abuse.
There are numerous organic solvents, therefore, this issue of RISK||NEWSLETTER will focus on those organic solvents commonly found in the workplace or home, or are frequently abused.
OCCUPATIONAL EXPOSURES
Occupational exposure is defined as chronic exposure in amounts less than the threshold limit value causing maternal symptoms. As with many teratogens, critical parameters, which determine the level of the exposure, include duration of exposure, route of exposure, and dosage of exposure. Occupational exposures may involve exposure by inhalation or by skin contact. The dosage of the solvent exposure, measured by airborne concentration or blood level, is often difficult to assess accurately. Therefore, precautions such as wearing protective clothing and gloves and working in an adequately ventilated environment are strongly recommended.
TOLUENE
Toluene, also called methylbenzene, is the most commonly used organic solvent. It is a volatile, aromatic hydrocarbon metabolized differently in the adult than in the fetus or neonate. In the adult, half of inhaled toluene is converted to hippuric acid, while the other half is excreted as toluene in the urine. The fetus or newborn does not make the conversion of toluene to hippuric acid (Goodwin, 1988).
Occupational exposure to toluene occurs in many industrial settings, including shoe manufacturers, painting, printing and adhesive industries, as well as laboratory exposure. The threshold limit value for toluene is 50 to 100 ppm.
In a retrospective study of 535 laboratory workers exposed to toluene, Taskinen et. al. (1994) found a significant association with spontaneous abortion. A study, which monitored worker’s biologic levels of six solvents by the same investigators found the highest risk for spontaneous abortion in printing workers, exposed to toluene and other organic solvents. This study also found an increased frequency of spontaneous abortion in toluene-exposed shoe workers (Lindbohm, 1990). One hundred sixty-eight women working with varnishes containing toluene at a level of 55 ppm were reported to have children with a higher incidence of fetal asphyxia and low birth weight (Syrovadko, 1977).
BENZENE
Benzene is an aromatic hydrocarbon whose composition differs from toluene by the absence of a methyl group attached to the benzene ring. This industrial organic solvent has an occupational exposure limit of 0.1 ppm. Chronic exposure to benzene has been found to cause chromosomal abnormalities in white blood cells, bone marrow hypoplasia, and aplastic anemia (National Academy of Sciences, 1976). However, this finding does not appear to be relevant to the risk of teratogenicity in typical industrial level exposures. A cohort study of 41 pregnant laboratory workers exposed in the first trimester did not find an increased rate of miscarriage (Axelsson et. al., 1984). In another study, 150 women with occupational exposure to benzene had a slightly increased risk of stillbirth but no increased association was found for premature delivery, low birth weight or length (Savitz et. al., 1989).
In a study of eight hundred and twenty-three men occupationally exposed to approximately 5 ppm of benzene, the risk of spontaneous abortion was not increased in 1739 pregnancies (Strucker et. al., 1994).
XYLENE
Xylene, also called dimethylbenzene or xylol, is an aromatic hydrocarbon solvent commonly found in paints, lacquers and adhesives and also in laboratories. After toluene, it is the most common solvent encountered in the workplace (Brown-Woodman, 1991). A study of women working in pathology or histology laboratories showed an association of xylene exposure with an increased risk of spontaneous abortion (Taskinen et. al., 1994). No association with congenital malformation was found, however. Other studies report that unless there are signs of maternal toxicity, e.g., irritation of the skin, mucous membrane, or respiratory tract, xylene is not embryotoxic (Von Burg, 1982). The threshold limit value for Xylene is 100 ppm.
HOUSEHOLD EXPOSURE
Under normal circumstances, household use of solvent-containing products does not exceed the threshold limit value applied to occupational exposures. Most exposures to organic solvents in the home are typically episodic and at low airborne levels, rather than chronic or at high concentrations. Therefore, household use of organic solvents is usually not associated with spontaneous abortion and this type of exposure does not confound data on occupational exposure. However, because measurements of airborne levels of solvents are difficult to interpret, precautions to reduce household exposure to solvents are advisable.
SOLVENT ABUSE
Abuse of solvents refers to intentional sniffing of vapors of solvents in order to obtain a feeling of euphoria, light-headedness or dizziness. As with other chemical abuses, it is difficult to determine the exact level or pattern of exposure. The air concentration of the solvent is very likely to be greater with abuse than with an occupational or accidental exposure, otherwise the desired euphoric effect in the mother would not be sought after. Due to higher concentrations with abuse, teratogenic effects may be more likely.
TOLUENE
Since toluene is the main component found in spray paints, glues and lacquers, the typical method of abuse is spraying a material with the aerosol, placing the material over the nose and mouth, and then inhaling. A phenotype of toluene embryopathy had been described in pregnancies in which women reported chronic toluene abuse. This toluene embryopathy includes a spectrum of features similar to those present in the fetal alcohol syndrome. Pearson et. al. (1994) proposed a common mechanism for the craniofacial features: a deficiency of craniofacial neuroepithelium and mesodermal components due to increased embryonic cell death. these facial characteristics include a narrow bifrontal diameter, short palpebral fissures, hypoplastic midface, and wide nasal bridge (Wilkins-Haug et. al., 1994). Other features include premature delivery, low birth weight, microcephaly, growth retardation, development delay, abnormal palmar creases, blunt fingertips, small fingernails, deep-set eyes, micrognathia, and abnormal auricles (Pearson et. al., 1994; Arnold et. al., 1994). Pearson et. al. (1994) examined eighteen pregnancies in which there was known maternal toluene abuse and did follow-up evaluations of 9 of these infants 3 to 36 months after an initial neonatal examination. Thirty-nine percent of the infants were born premature and 9% of the pregnancies experienced perinatal death. Eighty-three percent of the newborns displayed the craniofacial features similar to those seen in fetal alcohol syndrome and of these patients, 89% had other minor anomalies. Fifty-four percent were small for gestational age and 52% displayed continued growth retardation. Developmental delay was the most common finding, occurring in 80% of the pregnancies.
Lindemann (1991) reported two cases of solvent abuse in which mothers had been sniffing paint thinner containing toluene, ethanol and butylacetate. The infants were premature and displayed dysmorphic features similar to the toluene embryopathy phenotype. In addition, they exhibited transient hyperchloraemic acidosis and aminoaciduria, suggesting renal tubular dysfunction. The proposed mechanism is that sniffing toluene during pregnancy may change membrane permeability in the tubules of the kidney and enhance liver enzyme activity (Lindermann, 1991).
FETAL SOLVENT SYNDROME
Other forms of solvent abuse include sniffing paints, lacquers, glues and gasoline to achieve a “high”. These solvents are known to contain variable proportions of many solvents, the most common components being toluene, benzene and xylene. Gasoline also contains methanol and petroleum ether. Case reports of mothers who sniffed these substances described a syndrome of birth defects analogous to the fetal alcohol syndrome. This fetal solvent syndrome or fetal gasoline syndrome has also been associated with hypotonia, mental retardation, and poor postnatal head growth. In these instances, it is difficult to determine whether there is a primary solvent responsible for the effects or if a combination of solvents were the cause for the embryopathy.
SUMMARY
There are a number of recommendations common to many solvents, which, if followed, are likely to reduce the level of risk associated with prenatal exposure. Duration, route, and dosage of exposure are characteristic elements, which define the nature of any exposure. In general, an exposure that is sporadic or short in duration and without maternal effects typically does not cause fetal anomalies or pregnancy complications. An exposure that is lower than the threshold limit value is also unlikely to be teratogenic. However, because many solvent exposures occur by inhalation, it is difficult to assess the exact concentration of an airborne solvent. Women are often advised to take added precautions if an exposure is unavoidable. Wearing gloves, masks and protective clothing is advisable. Reducing the airborne concentration of a solvent by providing good ventilation is also recommended. The Occupational Safety and Health Association (OSHA) can be useful by evaluating questionable workplace exposures. In Chicago, OSHA can be reached at (312) 353-2220. The telephone number of the National Office of OSHA, Section of Risk Standards, is (202) 219-7157.
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