Table 3:
Developmental Pb exposure and cardiovascular health
| Exposure details | Window of exposure | Model | Epigenetic/molecular effect | Phenotype | Sex specificity | Reference |
|---|---|---|---|---|---|---|
| 0.2% Pb acetate in drinking water | Gestation until adulthood (12, 20, and 28 weeks) | Rat | Not investigated | Elevated blood pressure, respiratory frequency, hyperactive baro- and chemoreflexes in adulthood in both sexes | Effects observed in both males and females | [96] |
| 500 ppm of Pb acetate in drinking water | Gestation and lactation | Rat | Not investigated | Elevated systolic blood pressure, increased reactivity to noradrenaline in adolescent and adult male offspring | Only male offspring were evaluated | [97] |
| 0.05% Pb acetate in drinking water | 1 week prior to mating until day 11.5 gestation | Mouse | Not investigated | Abnormal angiogenesis in yolk sac of embryos | Not investigated | [98] |
| 2.1 (low), 16 (medium), or 32 (high) ppm Pb acetate in drinking water | 2 weeks prior to mating through gestation and lactation | Mouse | Not investigated | Increased food intake and energy expenditure in both sexes in adulthood, increased body weight, body fat, and insulin response in males | Yes | [100] |
| 12 mg of Pb acetate per ml or sodium acetate control in drinking water | 30 days prior to breeding until 21 days of age | Rat | Not investigated | Delayed timing of puberty | Only female offspring were evaluated | [101] |
| 300 mg/l Pb acetate in drinking water | Gestation and lactation | Rat | Not investigated | Elevated blood glucose at 12 and 21 days post-natal | Not reported | [102] |
| 100 mg Pb/kg diet | 8 weeks treatment starting at 35 days of age | Rabbit | Not investigated | Reduced relative heart weight, increased creatine phosphokinase | Only males were evaluated | [103] |
| 1% Pb acetate in drinking water | 12 and 40 day treatments starting at 4-5 weeks of age | Rat | Increased levels of acetylated histone H3 in abdominal and thoracic aortas and cardiac tissue | Increased proliferating cell nuclear antigen in cardiac tissue, enlarged cardiac cells after 40 days, elevated blood pressure during first 17 days, altered internal elastic lamina of aorta | Not reported | [104] |
| 60 ppm of Pb acetate in drinking water | Weaning until 10 months of age | Rat | Not investigated | Increased diastolic and systolic blood pressure, increased cardiac inotropy | Only males were evaluated | [105] |
| Blood Pb levels in preschool | Early childhood | Human | Not investigated | Smaller left ventricle (interventricular septum, left ventricular posterior wall, and left ventricular mass index); impaired left ventricular systolic function (fractional shortening and ejection fraction); increased inflammatory cell counts in both sexes | Effects observed in both males and females | [109] |
| Maternal hair Pb levels | Gestation | Human | Not investigated | Increased risk of congenital heart defects (septal, conotruncal, right-sided obstructive, left-sided obstructive, anomalous venous return, and others) | Not reported | [110] |
| Parental hair, toenail, and tooth Pb levels | Gestation | Human | Not investigated | Increased Pb levels in parents of children with congenital heart defects | Not reported | [111] |
| Blood Pb levels in pregnant women at 17–40 weeks gestation | Gestation | Human | Not investigated | Increased blood Pb levels in mothers of children with congenital heart defects (conotruncal defects, right ventricle outflow tract obstructions, and septal defects) | Not reported | [112] |
| Pb levels in first meconium samples of newborns | Gestation | Human | Not investigated | Increased Pb levels in meconium of infants with conotruncal heart defects | Not reported | [113] |
| Pb levels in blood of mothers with infants under 6 months of age | Gestation | Human | Not investigated | Increased blood Pb levels in mothers of infants with congenital heart defects | Effects observed in both males and females | [114] |
| Pb levels in prenatal cord blood and early childhood | Gestation and early childhood | Human | Not investigated | Elevated cord blood Pb associated with increased systolic blood pressure; elevated early childhood Pb associated with increased peripheral vascular resistance and decreased stroke volume in response to acute stress | Not reported | [115] |
| Blood Pb levels in childhood (9–11 years of age) | Early childhood | Human | Not investigated | Impaired response to cardiovascular stress (reduced stroke volume and increased peripheral vascular resistance) | Not reported | [116] |
| Pb levels in maternal toenail samples collected at ∼28 weeks gestation and/or 6 weeks postpartum | Early and late prenatal periods | Human | Not investigated | Early prenatal Pb exposure associated with significantly higher systolic blood pressure in children (mean age 5.5 years), with stronger effects among boys compared to girls | Yes | [47] |
| Blood Pb levels in pregnant women in second trimester | Gestation | Human | Not investigated | Higher maternal blood Pb associated with higher risk of elevated systolic blood pressure in children 4–6 years of age who had short gestation | Not reported | [117] |
| Pb in maternal urine at ∼12 weeks gestation | Gestation | Human | Not investigated | Increased risk of elevated blood pressure in early childhood (4–11 years of age), particularly in combination with molybdenum | Not reported | [118] |
| Maternal blood Pb concentrations at gestational weeks 14 and 30 | Gestation | Human | Not investigated | Late gestation Pb associated with reduced kidney volume in children ∼4.5 years of age, with a stronger association in girls | Yes | [120] |
| Maternal blood Pb levels | Gestation | Human | Not investigated | Lower Z-scores for total cholesterol, LDL and HDL in boys with maternal blood Pb levels ≥ 5 µg/dl | Yes—No effects noted in girls | [121] |