Abnormal peripheral cellular immune profiles in gestational diabetes mellitus: A meta-analysis

Table 1 Description of eligible studies reporting the profile of maternal immune status in gestational diabetes mellitus

No	Ref.	Country	Population of outcomes	BMI of GDM women	Location of immune cells	Period of pregnancy	Type of immune cells	Age	Type of study	Sample size	NOS
1	Lapolla et al[24]	Italy	Maternal and fetal outcomes	23 ± 5	Peripheral venous blood	At third trimester of pregnancy	Lymphocyte subsets and cytokines: Total lymphocytes, T lymphocyte subsets CD3 and CD8	33 ± 4	Cross-section	62 GDM patients and 74 women with normal glucose tolerance	7
2	Mahmoud et al[25]	Kuwait	Maternal outcomes	NA	Peripheral venous blood	At third trimester of pregnancy	Naïve T cells were decreased and memory T-cells and activated T cells (CD4+HLA-DR+, CD4+CD29+)	Maternal age was matched without detail information	Cohort	63 GDM and 16 pregnant women with Type 2 diabetes and 48 healthy, women	6
3	Schober et al[26]	Germany	Maternal outcomes	NA	Peripheral venous blood	At third trimester of pregnancy	Four different Treg subsets: Naïve Treg cells, memory Treg cells, the highly differentiated and activated Treg cells	31 (21-44)	Cohort	64 healthy pregnant women, 121 pregnant women with dietary-adjusted gestational diabetes	7
4	Pendeloski et al[27]	Brazil	Maternal outcomes	25.7 (23.4-29.0)	Peripheral venous blood	At third trimester of pregnancy	T subpopulations (CD4+ and CD8+), the expression of immunoregulatory molecules (CD28, ICOS, CTLA-4, and PD-1) and activation markers (CD69 and HLA-DR)	23–36	Case-control study	30 healthy pregnant women and 20 GDM patients	6
5	Gomes Fagundes et al[28]	Brazil	Maternal and fetal outcomes	BMI was divided into < 25 and > 25	Maternal blood, cord blood and colostrum	At third trimester of pregnancy	The subsets of cells (both CD3+ and CD4+ populations, the ‘naıve’ cells were CD45RA+ and the ‘memory’ cells were CD45RO+) and cytokine profile	18-45 years old	Cross-section	15 healthy pregnant women, 13diabetes mellitus gestational women	8
6	Friebe-Hoffmann et al[12]	Germany	Maternal outcomes	NA	Peripheral venous blood	At third trimester	CD3-, CD4-, CD8- and γδ T-cells as well as B-, NK-, NKT- and dendritic cells	19-44 years old	Cross-section	24 pregnant controls, 18 women with GDM	6
7	Lobo et al[29]	Brazil	Maternal outcomes	Overweight (pre- pregnancy BMI ≥ 25 kg/m2)	Peripheral venous blood	At third trimester of pregnancy	Treg and NK cells	34.14 ± 1.99	Case-control study	27 glucose- tolerant (controls) and 31 GDM overweight pregnant women	6
8	Sheu et al[16]	Australia	Maternal outcomes	25.4 ± 6.0	Peripheral venous blood	At third trimester of pregnancy and 7 weeks postpartum	Th17, Th2, Th1 and Treg cells	33.6 ± 3.4	Cohort	55 women with GDM (cases) and 65 healthy controls	7
9	Sifnaios et al[30]	Greece	Maternal outcomes	NA	Peripheral venous blood	At third trimester of pregnancy and 6 months postpartum	Th17, Th2, Th1 and Treg cells	≥ 18 years old	Cross-section	26 women with GDM (cases) and 23 healthy controls	6
10	Zhao et al[31]	China	Maternal outcomes	NA	Maternal Blood, Cord Blood and Placenta	At third trimester of pregnancy	CD3+, CD4+, and CD8+ T cells	27.45 ± 1.25	Cohort	28 women with GDM (cases) and 28 healthy controls	7
11	Schliefsteiner et al[19]	Austria	Maternal outcomes	32.8 ± 7.6	Placenta	The second trimester	M1 or M2 phenotype macrophages	NA	Pilot-study	Healthy women (n = 5) and women with GDM (n = 6)	6
12	Huang et al[11]	China	Maternal outcomes	23.28 ± 3.37	Peripheral venous blood	At third trimester of pregnancy	Lymphocyte, neutrophils, inflammatory cytokines, placenta-derived macrophages, and their products	29.26 ± 4.65	A case-control and cohort study	214 women with GDM and 926 women without	7
13	Angelo et al[32]	Brazil	Maternal outcomes	29.65 ± 4.58	Peripheral venous blood	At third trimester of pregnancy	Flow cytometry was used to assess peripheral blood monocytes subsets (classical, intermediate, non-classical)	34.74 ± 1.64	Case-control study	18 women with GDM (cases) and 20 healthy controls	6
14	Xiong et al[21]	China	Maternal outcomes	21.08 ± 2.60	Peripheral venous blood	At third trimester of pregnancy	NK cell subsets	32.9 ± 3.21	Cross-section	10 women with GDM (cases) and 10 healthy controls	6
15	Ye et al[33]	China	Maternal outcomes	24.54 ± 4.49	Peripheral venous blood	At third trimester of pregnancy	PD-1 expressed on T-cell subsets	29.91 ± 4.43	Cross-section	55 women with GDM (cases) and 55 healthy controls	8
16	Wang et al[34]	China	Maternal outcomes	28.42 ± 3.26	Peripheral venous blood	At third trimester of pregnancy	Leukocyte, neutrophil, monocyte, and lymphocyte counts	29.13 ± 4.39	Case-control study	147 women with GDM (cases) and 161 healthy controls	8
17	Yang et al[35]	China	Maternal outcomes	BMI ≥ 25 kg/m2	Peripheral venous blood	At first trimester of pregnancy	CD4+CD25+FOXP3+	Cohort	21 women with GDM (cases) and 34 healthy controls	7
18	Wang et al[36]	China	Maternal outcomes	Second 23.1 ± 1.3; Third 26.1 ± 1.6	Peripheral venous blood	Second and third trimesters	Treg cells	26.8 ± 1.7	Cohort	GDM: 45 (17 = 2nd.28 = 3rdT); Control: 104 (28 in the first trimester, 43 in the second trimester,	6
19	Fagninou et al[37]	Benin	Maternal outcomes	NA	Peripheral venous blood	At third trimester of pregnancy	Serum IL-10 and Th1 and Th2ratio measured. NK cells and monocytes	30.6 ± 3.04	Case control	15 women with GDM (cases) and 25 healthy controls	6

GDM: Gestational diabetes mellitus; NOS: Newcastle-Ottawa Scale; BMI: Body mass index; NK: Natural killer.