Table 1 Main characteristics of studies included in the systematic review

1

Liu et al. [32]

Wuhan,

China

Pregnant women at the first trimester

2026

24–28 weeks

OGTT based on IADPSG criteria

Urinary sample of cadmium concentration

The median value (interquartile range (IQR)) of urinary Cd concentrations among all women was 0.62 (0.33–1.08) µg/L

Cohort

Poisson regression

Top tertile vs. bottom tertile:

Cd RR = 1.36 [95% CI 0.98, 1.90]

2

[41]

Japan

Pregnant women at the second trimester

16,955

22–28 weeks

OGTT based on JSOG and JAOG criteria

Blood cadmium and lead concentrations

The geometric mean (GM) concentrations of Cd and Pb in

maternal blood was 0.677 (range 0.0951–4.73) and 6.05

(range 1.50–70.9) ng/g, respectively

Cross-sectional

logistic regression

High vs. low category

Nulliparous group

Cd OR: 0.76 [95% CI 0.28–2.08]

Pb OR; 2.51 [95% CI 0.72–8.72]

Parous group

Cd OR: 0.64 [95% CI 0.29–1.44]

Pb OR; 0.31 [95% CI 0.04–2.29]

3

Romano et al. [54]

New Hampshire, USA

Pregnant women at the second trimester

917

24–28 weeks

GCT based on ACOG criteria

Urinary cadmium concentration

Urinary Cd levels among women with glucose intolerance or GDM (geometric mean = 0.09 μg/L,

IQR = 0.05–0.16) and women with normal glucose results (geometric

mean = 0.06 μg/l, IQR = 0.03–0.13)

Cross-sectional

logistic regression

Double vs. normal category

OR; 0.86[ 95% CI 0.51–1.44]

4

[62]

Poitiers

and Nancy, France

Pregnant women at the second trimester

623

24–28 weeks

OGTT based on Carpenter

and Coustan criteria

Blood cadmium and lead

concentrations

Geometric mean of Cd = 0.75

Geometric mean of Pb = 16.2

Cross-sectional

logistic regression

Cd OR: 1.81 [95% CI 0.93–3.50]

Pb OR: 1.65 [95% CI 0.82–3.34]

5

[70]

Taiyuan, China

Pregnant women at the second trimester

1552

24–28 weeks

OGTT based on ACOG criteria

Blood nickel (Ni), arsenic (As), Cd antimony (Sb),

thallium (Tl), mercury (Hg) and Pb concentrations

Median (IQR):

Ni = 6.484 (1.500e12.706),

As = 16.188 (8.533e23.823),

Cd = 1.076 (0.503e4.287),

Sb = 1.249 (0.150e10.727),

Tl = 0.157 (0.005e0.973),

Hg = 1.339 (0.935e2.185),

Pb = 27.968 (20.544e35.981)

Cross-sectional

Logistic Regression

High vs. low category

Ni OR: 0.94 [95% CI 0.72, 1.21]

As OR: 1.08 [95% CI 0.83, 1.40]

Cd OR: 0.83 [95% CI 0.64, 1.08]

Sb OR: 0.84 [95% CI 0.64, 1.11]

Tl OR: 0.82 [95% CI 0.63, 1.07]

Hg OR: 1.38 [95% CI 1.07, 1.78]

Pb OR: 1.01 [95% CI 0.78, 1.30]

6

Li et al. [31]

Wuhan, China

Pregnant women at the first trimester

610

24–28 weeks

75-g OGTT based on IADPSG criteria

Urinary cadmium concentration

The median of Cd = 0.64 μg/L

Cohort

Multiple

linear Regression

High vs. low category

Cd OR: 2.09 [95% CI 1.32, 3.33]

7

Wang, et al. [69]

Tongji, China

Pregnant women at the first trimester

2090

24–28 weeks

75-g OGTT based on IADPSG criteria

Urinary Ni, As, Cd

, antimony (Sb), cobalt (Co), and vanadium (V) concentration

The mean (range):

Ni = 1.74(1.10,2.79),

Sb = 0.30(0.17, 0.48),

As = 29.64(18.87, 46.67),

Cd = 0.62(0.35, 1.08),

Co = 0.33(0.22, 0.50),

V = 0.47(0.34, 0.60)

μg/L

Cohort

Poisson regression

High vs. low category

Ni OR: 1.61 [95% CI 1.20, 2.17]

Sb OR: 1.95 [95% CI 1.46, 2.61]

As OR: 1.39 [95% CI 1.04, 1.84]

Cd OR: 1.05 [95% CI 0.77, 1.41]

Co OR: 1.43 [95% CI 1.07, 1.92]

V OR: 1.53 [95% CI 1.16, 2.02]

8

Jia et al. [27]

Beijing, China

Pregnant women at the second trimester

678

24–28 weeks

75-g OGTT based on IADPSG criteria

As, Cd, Pb, Hg, and tin (Sn), in maternal hair

Median (IQR):

As = 0.503 (0.230–0.840)

Cd = 0.015 (0.010–0.024)

Pb = 0.352 (0. 230–0.542)

Hg = 0.419 (0.279–0.663)

Sn = 0.153 (0.098–0.259)

μg/L

nested case–control

Log-binomial regression

High vs. low category

As OR: 0.91 [95% CI 0.77–1.07]

Cd OR: 1.03 [95% CI 0.85–1.24]

Pb OR: 1.07 [95% CI 0.89–1.29]

Hg OR: 1.27 [95% CI 1.05–1.53]

Sn OR: 1.25 [95% CI 1.04–1.52]

9

[42]

Yozgat, Turkey

Pregnant women at the second trimester

112

24–28 weeks

100-g OGTT

Blood Cd, Pb, Sb, Hg, and As concentrations

Median (IQR) and mean ± SD of:

Cr III (μg/L)

Case: 0.19 (0.03), Control: 0.29 (0.08)

Cr VI (μg/L)

Case:3.62 (0.49), Control: 3.75 (0.42)

Se (μg/L)

Case: 29.48 ± 9.87, Control: 38.21 ± 11.56

Zn (μg/L)

Case:474.07 (141.70), Control: 545.29 (142.17)

Cu (μg/L)

Case:1483.69 (1062.04), Control: 1352.67 (329.69)

Cd (μg/L)

Case:1.33 (0.42), Control: 1.20 (0.23)

Pb (μg/L)

Case:19.76 (15.82), Control: 11.30 (5.24)

Hg (μg/L)

Case: 1.12 (0.52), Control: 1.03 (0.63)

Sb (μg/L)

Case: 2.51 ± 0.98, Control: 2.11 ± 0.71

As (μg/L)

Case: 5.92 (0.93), Control: 6.18 (1.78)

Case–control study

Student t-test, Mann–Whitney U test

Case

Cd (μg/L):1.33 (0.42)

Pb (μg/L): 19.76 (15.82)

Hg (μg/L): 1.12 (0.52)

Sb (μg/L): 2.51 ± 0.98

As (μg/L): 5.92 (0.93)

Control

Cd (μg/L): 1.20 (0.23)

Pb (μg/L): 11.30 (5.24)

Hg (μg/L): 1.03 (0.63)

Sb (μg/L): 2.11 ± 0.71

As (μg/L): 6.18 (1.78)

10

[53]

Birjand, Iran

Pregnant women at the second trimester

102

24–28 weeks

75-g OGTT based on IADPSG criteria

Blood Cd, As, Hg, Ni, Cu, Zn and V concentrations

Mean of elements in GMD group vs. non-GDM (μg/L):

As (8.58 vs. 3.15),

Cd (6.75 vs. 0.52),

Hg (2.6 vs. 0.9)

Cu (418.3 vs. 415.4)

V (0.96 vs. 1.24)

Zn (706.1 vs. 664.9)

Cross-sectional

Multiple

linear Regression

As RD: 0.48 [95% CI 0.32, 0.64]

Cd RD: 0.65, [95% CI 0.47, 0.83]

Cu RD: 0.02 [95% CI − 0.14, 0.18]

Hg DR: 0.46 [95% CI 0.21, 0.72]

Ni DR: 0.09 [95% CI − 0.04, 0.22]

V DR:− 0.14 [95% CI − 0.22, − 0.05]

Zn DR:− 0.06 [95% CI −  0.06, −  0.19]

11

Zheng, et al. [77]

Boston, USA

Pregnant women at the first trimester

1311

26–28 weeks

100-g OGTT

based on IADPSG criteria

Blood Cd, As, Hg, Cu, Zn, Se, barium (Ba), cesium (Cs), and Pb concentrations

the median (IQR):

0.84 (0.44, 1.53) ng/g for As, 3.18 (1.99, 5.90) ng/ g for Ba, 0.40 (0.28, 0.56) ng/g for Cd, 0.53 (2.03, 3.18) ng/g for Cs, 563 (515, 617) ng/g for Cu, 3.25 (1.64, 6.39) ng/g for Hg, 41.1 (37.0, 46.1) μg/g for Mg, 16.1 (13.1, 20.3) ng/g for Mn, 17.6 (13.5, 23.6) ng/g for Pb, 248 (220, 282) ng/g for Se, and 10.4 (9.27, 11.6) μg/g for Zn

multivariable linear regression

Ba tertile 2 vs. 1 = 3.32 (− 0.16, 6.80)

Ba tertile 3 vs. 1 = 1.86 (− 1.63, 5.36)

As in Ba tertile 1 =− 0.82 (− 3.98, 2.35)

As in Ba tertile 2 vs. 1 = 1.53 (− 2.76, 5.81)

As in Ba tertile 3 vs. 1 = 3.01 (− 1.35, 7.37)

Hg in Ba tertile 1 =− 1.88 (− 4.68, 0.92)

Hg in Ba tertile 2 vs. 1 = 0.67 (− 3.37, 4.71)

Hg in Ba tertile 3 vs. 1 = 0.01 (− 4.11, 4.14)

Mg in Ba tertile 1 = 1.19 (− 1.54, 3.91)

Mg in Ba tertile 2 vs. 1 =− 0.33 (− 4.39, 3.72)

Mg in Ba tertile 3 vs. 1 =− 1.82 (− 5.89, 2.26) Pb in Ba tertile 1 =− 2.64 (− 5.30, 0.00)

Pb in Ba tertile 2 vs. 1 = 0.24 (− 3.39, 3.87)

Pb in Ba tertile 3 vs. 1 = 3.95 (0.28, 7.61)

Se in Ba tertile 1 = 2.50 (− 0.74, 5.74)

Se in Ba tertile 2 vs. 1 =− 2.84 (− 7.52, 1.85)

Se in Ba tertile 3 vs. 1 =− 2.40 (− 6.80, 2.01)

12

Zhou, et al. [78]

Foshan, China

Pregnant women at the first trimester

8169

24–28 weeks

75-g OGTT based on IADPSG criteria

Blood Cu, Pb and Zn concentrations

Cu (μmol/L) = 20.50 (16.20–25.40)

Pb (μg/L) = 26.80 (17.00–41.55)

Zn (μmol/L) = 114.20 (104.35–124.80)

Cohort

Logistic Regression

High vs. low category

Cu OR: 0.94 [95% CI 0.81–1.09]

Zn OR: 1.04 [95% CI 0.89–1.20]

Pb OR: 0.89 [95% CI 0.76–1.03]

13

[79]

Wuhan, China

Pregnant women at the first trimester

610

24–28 weeks

75-g OGTT based on IADPSG criteria

Blood Cu, Zn, Se, and Cr concentrations

Median (IQR):

Cu (mg/L) = Case: 1.44 (1.27–1.59) vs. control: 1.34 (1.19–1.49)

Zn (mg/L) = case: 1.12 (0.86–1.68) vs. control: 1.57 (1.06–2.36)

Se (µg/L) = case: 29.43 (24.27–34.72) vs. control: 30.89 (25.71–36.46)

Cr (µg/L) = 2.65 (1.26–5.74) vs. control: 3.20 (1.53–5.80)

case–control

Logistic Regression

High vs. low category

Cu OR: 2.48 [95% CI 1.48,4.16]

Zn OR: 0.30[ 95% CI 0.18,0.50]

Se OR: 0.63 [95% CI 0.38,1.04]

Cr OR: 0.95 [95% CI 0.58, 1.55]

14

[66]

Japan

Pregnant women at the second trimester

610

24–28 weeks

75-g OGTT based on JSOG and JAOG criteria

Blood lead, mercury, cadmium selenium concentrations

Median and 5–95 percentile:

Hg (ng/g) = 3.6, 1.5–8.7

Pb (ng/g) = 5.9, 3.5–10.6

Cd (ng/g) = 0.7, 0.3–1.5

Se (ng/g) = 168, 141–205

Cross-sectional

Logistic Regression

High vs. low category

Hg OR: 1.21 [95% CI 1.02,1.44]

Pb OR: 0.97 [95% CI 0.82, 1.15]

Cd OR: 0.73 [95% CI 0.61, 0.87]

Se OR: 1.34 [95% CI 1.13, 1.59]

15

[71]

Shanghai, China

first trimester of gestation

403 GDM patients and 763 controls

24–28 weeks

an oral glucose tolerance test (OGTT) was implemented by a 75 g glucose challenge

Blood Vanadium; Chromium; Manganese; Cobalt; Nickel;

Selenium

V (µg/L) = 6.25 (3.71–9.06)

Cr (µg/L) = 372.40 (250.75–531.44)

Mn (µg/L) = 5.79 (3.51–8.90)

Co (µg/L) = 56.82 (40.24–81.94)

Ni (µg/L) = 30.67 (17.34–48.57)

Se (µg/L) = 87.80 (60.33–120.72)

Case–control

logistic regression

OR

V: 1.39 (1.14, 1.69)

Cr:0.81 (0.63, 1.03)

Mn: 1.22 (0.99, 1.51)

Co: 1.14 (0.91, 1.43)

Ni: 0.86 (0.77, 0.97)

Se: 0.85 (0.67, 1.07)

16

[72]

Chongqing, China

the first trimester of gestation

GDM = 224, non-GDM = 619

between 22 and

28 weeks gestation

Plasma glucose was measured during a

75-g oral glucose tolerance test (OGTT)

Maternal hair and cord blood

GDM group:

Cr (µg/L) = 0.589 (0.325, 0.690)

Co(µg/L) = 0.008 (0.006, 0.014)

Ni (µg/L) = 0.348 (0.209, 0.901)

As(µg/L) = 0.073 (0.054, 0.107)

Se(µg/L) = 0.290 (0.235, 0.336)

Cd(µg/L) = 0.022 (0.014, 0.062)

Hg (µg/L) = 0.700 (0.521, 1.006)

Pb(µg/L) = 0.307 (0.214, 0.839)

Non-GDM group:

Cr (µg/L) = 1.852 (0.469, 8.665)

Co(µg/L) = 0.015 (0.013, 0.024)

Ni (µg/L) = 0.430 (0.160, 1.269)

As(µg/L) = 0.075 (0.067, 0.088)

Se(µg/L) = 0.275 (0.233, 0.307)

Cd(µg/L) = 0.014 (0.013, 0.015)

Hg (µg/L) = 0.686 (0.221, 0.702)

Pb(µg/L) = 0.469 (0.352, 0.704)

Case–control

logistic regression

OR:

Cr: 1.02 (0.85, 1.21)

Co: 1.07 (0.93, 1.23)

Ni: 1.20 (1.02, 1.40)

As: 1.28 (1.01, 1.64)

Se: 5.37 (3.48, 8.28)

Cd: 1.02 (0.89, 1.18)

Hg: 1.09 (0.92, 1.29)

Pb: 0.94 (0.80, 1.11)