Canonical correlation analysis between heavy metal levels in umbilical cord blood and fetal growth and development

Background Environmental exposure to heavy metals during pregnancy can affect the growth and development of fetuses at different pregnancy stages. However, few studies have been conducted to evaluate which pregnancy stage is most affected and what are the correlations between fetal growth and development during pregnancy and the levels of heavy metals in umbilical cord blood.

Objective This study is conducted to investigate the correlation between fetal growth and development during pregnancy and heavy metal levels in umbilical cord blood under heavy metal exposure.

Methods A heavy metal contaminated area (pollution area) in Gansu Province and another adjacent area (control area) on the windward side of the polluted area were selected as study areas from January 2013 to December 2016. With informed consent, pregnant women with a single fetus, aged 22-35 years, and who volunteered to cooperate the study and lived in the study areas for more than two years were included. Through a questionnaire survey the basic information of the pregnant women were collected. Fetal double top diameter, femur length, and fetal heart rate at different stages were measured by ultrasonic examination. The levels of nickle (Ni), copper (Cu), and arsenic (As) in newborns' umbilical cord blood were measured during delivery with inductively coupled plasma mass spectrometer. The correlations between fetal growth and development indicators (double top diameter, femoral length, and fetal heart rate) and heavy metal levels in umbilical cord blood (Ni, Cu, and As) were analyzed by canonical correlation.

Results During the second trimester, the third trimester, and delivery, there were respectively 42, 58, and 71 pregnant women from the pollution area and 58, 91, and 169 pregnant women from the control area recruited in the study. Except that the pregnant women's passive smoking rates during the third trimester and delivery in the pollution area (84.5% and 85.9%, respectively) were higher than those in the control area (44.0% and 47.3%, respectively) (Ps < 0.001), the complication rates during the second trimester and delivery in the pollution area (40.5% and 38.0%, respectively) were higher than those in the control area (19.0% and 17.8%, respectively) (P=0.018, P=0.001), and the rates of women's residential address ≤ 300 m away from streets and women taking medicine during pregnancy in the pollution area (60.6% and 29.6%, respectively) were higher than those in the control area (45.0% and 12.4%, respectively) (P=0.027, P=0.001), there were no significant differences in other aspects of general information between the women in the two study areas. The levels of umbilical cord blood As of subjects during the second trimester, the third trimester, and delivery in the pollution area (0.77, 0.75, and 0.73 μg·L^-1, respectively) were higher than those in the control area (0.29, 0.34, and 0.35 μg·L^-1, respectively) (P < 0.001). The femoral lengths of fetuses during the second trimester, the third trimester, and delivery in the pollution area (35.0, 60.0, and 70.0 mm, respectively) were less than those in the control area (41.5, 63.0, and 72.0 mm, respectively) (P < 0.01). Fetal growth and development in the second trimester was canonically correlated with heavy metal levels in umbilical cord blood:U₁=0.617X₁+0.349X₂-0.430X₃ (X_1-3 were double top diameter, femoral length, and fetal heart rate, respectively); W₁=-0.545Y₁-0.109Y₂-0.897Y₃ (Y_1-3 were Ni, Cu, and As levels, respectively). In other words, double top diameter and femoral length were negatively correlated with Ni, Cu, and As levels in umbilical cord blood, fetal heart rate was positively correlated with Ni, Cu, and As levels in umbilical cord blood, and fetal double top diameter and femoral length were most correlated with As level in umbilical cord blood.

Conclusion Heavy metal levels in umbilical cord blood as internal exposure doses are negatively correlated with double top diameter and femoral length of the second-trimester fetuses, indicating that metal exposure during pregnancy have a strong adverse health effect on the second-trimester fetuses.