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Preplanned Studies: Hematological Parameters in the First Trimester and the Risk of Gestational Diabetes Mellitus — Beijing, China, 2017–2020

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  • Summary

    What is already known about this topic?

    Hematological parameters may indicate the presence of chronic low-grade inflammation and increasing viscosity, which are involved in the pathological processes of gestational diabetes mellitus (GDM). However, the association between several hematological parameters in early pregnancy and GDM has yet to be elucidated.

    What is added by this report?

    Hematological parameters in the first trimester, particularly red blood cell (RBC) count and systematic immune index, have a significant impact on GDM incidence. The neutrophils (NEU) count in the first trimester was particularly pronounced for GDM. The upward trend of RBC, white blood cell (WBC), and NEU counts was consistent across all GDM subtypes.

    What are the implications for public health practice?

    Early pregnancy hematological parameters are associated with the risk of GDM.

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  • Funding: Supported by the National Key Research and Development Program of China (NKPs) [Grant no. 2021YFC2700705]
  • [1] Ye WR, Luo C, Huang J, Li CL, Liu ZX, Liu FK. Gestational diabetes mellitus and adverse pregnancy outcomes: systematic review and meta-analysis. BMJ 2022;377:e067946. http://dx.doi.org/10.1136/bmj-2021-067946CrossRef
    [2] McElwain CJ, McCarthy FP, McCarthy CM. Gestational diabetes mellitus and maternal immune dysregulation: what we know so far. Int J Mol Sci 2021;22(8):4261. http://dx.doi.org/10.3390/ijms22084261CrossRef
    [3] Hanley AJG, Retnakaran R, Qi Y, Gerstein HC, Perkins B, Raboud J, et al. Association of hematological parameters with insulin resistance and β-cell dysfunction in nondiabetic subjects. J Clin Endocrinol Metab 2009;94(10):3824 − 32. http://dx.doi.org/10.1210/jc.2009-0719CrossRef
    [4] Tan PC, Chai JN, Ling LP, Omar SZ. Maternal hemoglobin level and red cell indices as predictors of gestational diabetes in a multi-ethnic Asian population. Clin Exp Obstet Gynecol 2011;38(2):150-4. https://www.imrpress.com/journal/CEOG/38/2/pii/1630488777430-1613358224.https://www.imrpress.com/journal/CEOG/38/2/pii/1630488777430-1613358224
    [5] O’Malley EG, Reynolds CME, Killalea A, O’Kelly R, Sheehan SR, Turner MJ. Comparison of ultrasound with biomarkers to identify large-for-gestational age in women screened for gestational diabetes mellitus. J Matern Fetal Neonatal Med 2022;35(25):6306 − 11. http://dx.doi.org/10.1080/14767058.2021.1911993CrossRef
    [6] Shaarbaf Eidgahi E, Nasiri M, Kariman N, Safavi Ardebili N, Salehi M, Kazemi M, et al. Diagnostic accuracy of first and early second trimester multiple biomarkers for prediction of gestational diabetes mellitus: a multivariate longitudinal approach. BMC Pregnancy Childbirth 2022;22(1):13. http://dx.doi.org/10.1186/s12884-021-04348-6CrossRef
    [7] Hassan B, Rayis DA, Musa IR, Eltayeb R, ALhabardi N, Adam I. Blood groups and hematological parameters do not associate with first trimester gestational diabetes mellitus (institutional experience). Ann Clin Lab Sci 2021;51(1):97-101. http://www.annclinlabsci.org/content/51/1/97.long.http://www.annclinlabsci.org/content/51/1/97.long
    [8] Kvist-Hansen A, Kaiser H, Krakauer M, Gørtz PM, Wang X, Becker C, et al. Neutrophil-to-lymphocyte ratio and the systemic immune-inflammation index as potential biomarkers of effective treatment and subclinical atherosclerotic cardiovascular disease in patients with psoriasis. J Eur Acad Dermatol Venereol 2023. http://dx.doi.org/10.1111/jdv.18860.http://dx.doi.org/10.1111/jdv.18860
    [9] Obstetrics Group, Obstetrics and Gynecology Branch, Chinese Medical Association, Collaborative Group of Pregnancy with Diabetes, Perinatal Medicine Branch, Chinese Medical Association. Diagnosis and therapy guideline of pregnancy with diabetes mellitus. Chin J Obstetrics Gynecol 2014;49(8):561 − 9. http://dx.doi.org/10.3760/cma.j.issn.0529-567x.2014.08.001 (In Chinese). CrossRef
    [10] Kotzaeridi G, Blätter J, Eppel D, Rosicky I, Linder T, Geissler F, et al. Characteristics of gestational diabetes subtypes classified by oral glucose tolerance test values. Eur J Clin Invest 2021;51(9):e13628. http://dx.doi.org/10.1111/eci.13628CrossRef
    [11] Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol 2009;114(6):1326 − 31. http://dx.doi.org/10.1097/AOG.0b013e3181c2bde8CrossRef
    [12] Herder C, Færch K, Carstensen-Kirberg M, Lowe GD, Haapakoski R, Witte DR, et al. Biomarkers of subclinical inflammation and increases in glycaemia, insulin resistance and beta-cell function in non-diabetic individuals: the Whitehall II study. Eur J Endocrinol 2016;175(5):367 − 77. http://dx.doi.org/10.1530/EJE-16-0528CrossRef
    [13] Gauer JS, Ajjan RA, Ariëns RAS. Platelet–neutrophil interaction and thromboinflammation in diabetes: considerations for novel therapeutic approaches. J Am Heart Assoc 2022;11(20):e027071. http://dx.doi.org/10.1161/JAHA.122.027071CrossRef
    [14] Tamariz LJ, Young JH, Pankow JS, Yeh HC, Schmidt MI, Astor B, et al. Blood viscosity and hematocrit as risk factors for type 2 diabetes mellitus: the atherosclerosis risk in communities (ARIC) study. Am J Epidemiol 2008;168(10):1153 − 60. http://dx.doi.org/10.1093/aje/kwn243CrossRef
  • TABLE 1.  Characteristics among participants in the cohort according to GDM status (n=5,529).

    VariableOverall (N=5,529)non-GDM (n=4,512)GDM (n=1,017)P value*
    Age, years [median (IQR)]31.00 (29.00, 34.00)31.00 (29.00, 33.00)32.00 (29.00, 35.00)<0.001
    Parity (%)
     ≥11,966 (35.6)1,565 (34.7)401 (39.4)0.005
    BMI, kg/m2, n (%)<0.001
     <18.5190 (3.4)154 (3.4)36 ( 3.5)
     18.5–23.93,548 (64.2)2,998 (66.4)550 (54.1)
     24.0–27.91,450 (26.2)1,129 (25.0)321 (31.6)
     ≥28.0341 (6.2)231 (5.1)110 (10.8)
    Gestational weeks (mean±SD)12.01±0.9812.01±0.9812.02±0.960.868
    Adverse pregnancy history, n (%)456 (8.2)330 (7.3)126 (12.4)<0.001
    Fasting plasma glucose, mmol/L (mean±SD)4.91±0.344.88±0.335.02±0.33<0.001
    OGTT fasting, mmol/L (mean±SD)4.63±0.384.54±0.305.01±0.46<0.001
    OGTT 1 hour, mmol/L (mean±SD)7.69±1.617.29±1.329.45±1.59<0.001
    OGTT 2 hour, mmol/L (mean±SD)6.63±1.246.32±0.957.99±1.43<0.001
    Hematological parameters
     RBC, 1012/L (mean±SD)4.20±0.314.19±0.314.25±0.31<0.001
     HB, g/L (mean±SD)127.78±8.27127.47±8.22129.20±8.38<0.001
     WBC, 109/L [median (IQR)]8.60 (7.40, 9.90)8.50 (7.30, 9.80)9.00 (7.70, 10.40)<0.001
     PLT, 109/L (mean±SD)237.77±49.62236.32±49.49244.20±49.71<0.001
     LYM, 109/L [median (IQR)]1.70 (1.40, 2.00)1.70 (1.40, 2.00)1.70 (1.50, 2.00)0.001
     NEU, 109/L [median (IQR)]6.30 (5.20, 7.40)6.20 (5.20, 7.30)6.60 (5.50, 7.90)<0.001
     NLR [median (IQR)]3.72 (3.00, 4.58)3.71 (3.00, 4.56)3.80 (3.13, 4.69)0.005
     SII [median (IQR)]872.14 (678.57, 1113.60)860.50 (672.19, 1099.820)914.52 (709.71, 1186.67)<0.001
    Abbreviation: GDM=gestational diabetes mellitus; BMI=body mass index; OGTT=oral glucose tolerance test; RBC=red blood cell count; Hb=hemoglobin concentration; WBC=white blood cell count; PLT=platelet; LYM=lymphocytes; Neu=neutrophil; NLR=Neutrophil-to-lymphocyte ratio; SII=systemic immune-inflammation index, IQR=interquartile range; SD=standard deviation.
    * Data are presented as mean±SD, and P values were from 2-sample independent t-tests; or presented as median (interquartile range), and P values were from Mann–Whitney U test; or presented as number (percent), and P values were from Chi-squared tests.
    OGTT was tested at 24–28 gestational weeks, and other variables were collected or measured in early pregnancy.
    Download: CSV

    TABLE 2.  Odds ratio and 95% confidence intervals for GDM according to quartiles of hematological markers in early pregnancy.

    VariableORs (95% CIs) for GDMPtrend*
    Quartile 1Quartile 2Quartile 3Quartile 4
    SII<680680–872873–1,110≥1,111 
     Cases/total (%)211/1,383 (15.26)229/1,382 (16.57)277/1,382 (20.04)300/1,382 (21.71)
     Model 11 (ref.)1.11 (0.90, 1.36)1.4 (1.15, 1.70)***1.55 (1.27, 1.88)***<0.001
     Model 2§1 (ref.)1.11 (0.90, 1.36)1.35 (1.10, 1.64)***1.48 (1.22, 1.81)***<0.001
     Model 31 (ref.)1.12 (0.91, 1.38)1.35 (1.11, 1.65)***1.51 (1.24, 1.84)***<0.001
    NLR<3.013.01–3.723.73–4.58≥4.59
     Cases/total (%)218/1,390 (15.68)268/1,383 (19.38)253/1,376 (18.39)278/1,380 (20.14)
     Model 11 (ref.)1.29 (1.06, 1.58)*1.22 (1.00, 1.50)*1.37 (1.12, 1.66)***0.002
     Model 21 (ref.)1.29 (1.06, 1.57)*1.21 (0.99, 1.48)1.39 (1.14, 1.69)***0.001
     Model 31 (ref.)1.31 (1.07, 1.60)**1.24 (1.01, 1.52)*1.42 (1.17, 1.74)***0.001
    RBC<4.004.00–4.194.20–4.39≥4.40
     Cases/total (%)203/1,397 (14.53)253/1,427 (17.73)253/1,340 (18.88)308/1,365 (22.56)
     Model 11 (ref.)1.27 (1.04, 1.56)*1.39 (1.13, 1.70)**1.73 (1.43, 2.11)***<0.001
     Model 21 (ref.)1.24 (1.01, 1.52)*1.31 (1.07, 1.61)**1.56 (1.28, 1.91)***<0.001
     Model 31 (ref.)1.25 (1.02, 1.54)*1.32 (1.07, 1.62)**1.56 (1.28, 1.91)***<0.001
    HB<124124–128129–133≥134
     Cases/total (%)252/1,600 (15.75)219/1,346 (16.27)234/1,255 (18.65)312/1,328 (23.49)
     Model 11 (ref.)1.04 (0.86, 1.27)1.24 (1.02, 1.51)*1.67 (1.38, 2.01)***<0.001
     Model 21 (ref.)1.01 (0.83, 1.23)1.16 (0.95, 1.41)1.52 (1.26, 1.84)***<0.001
     Model 31 (ref.)1.02 (0.83, 1.24)1.16 (0.95, 1.41)1.52 (1.26, 1.84)***<0.001
    WBC<7.57.5–8.68.7–9.9≥10.0
     Cases/total (%)205/1,448 (14.16)237/1,436 (16.5)252/1,307 (19.28)323/1,338 (24.14)
     Model 11 (ref.)1.20 (0.98, 1.47)1.46 (1.19, 1.78)***1.96 (1.61, 2.38)***<0.001
     Model 21 (ref.)1.18 (0.97, 1.45)1.39 (1.14, 1.71)***1.79 (1.47, 2.19)***<0.001
     Model 31 (ref.)1.20 (0.98, 1.47)1.41 (1.16, 1.71)***1.81 (1.48, 2.21)***<0.001
    PLT<205205–234235–269≥270
     Cases/total (%)213/1,416 (15.04)247/1,367 (18.07)266/1,393 (19.10)291/1,353 (21.51)
     Model 11 (ref.)1.25 (1.02, 1.53)*1.33 (1.09, 1.62)**1.53 (1.26, 1.86)***<0.001
     Model 21 (ref.)1.23 (1.01, 1.51)*1.25 (1.03, 1.53)*1.37 (1.12, 1.67)**0.001
     Model 31 (ref.)1.23 (1.01, 1.51)*1.25 (1.02, 1.53)*1.36 (1.12, 1.67)**0.001
    LYM<1.411.41–1.701.80–2.00≥2.01
     Cases/total (%)243/1,498 (16.22)298/1,664 (17.91)249/1,295 (19.23)227/1,072 (21.18)
     Model 11 (ref.)1.14 (0.94, 1.37)1.23 (1.01, 1.50)1.39 (1.13, 1.70)***0.002
     Model 21 (ref.)1.12 (0.93, 1.35)1.17 (0.96, 1.43)1.25 (1.01, 1.53)*0.074
     Model 31 (ref.)1.12 (0.93, 1.35)1.16 (0.96, 1.42)1.23 (1.00, 1.51)*0.102
    NEU<5.215.21–6.306.40–7.40≥7.41
     Cases/total (%)196/1,399 (14.01)252/1,472 (17.12)248/1,323 (18.75)321/1,335 (24.04)
     Model 11 (ref.)1.28 (1.04, 1.56)*1.43 (1.17, 1.76)***1.99 (1.63, 2.42)***<0.001
     Model 21 (ref.)1.26 (1.02, 1.54)*1.37 (1.12, 1.69)**1.85 (1.51, 2.26)***<0.001
     Model 31 (ref.)1.27 (1.03, 1.56)*1.39 (1.13, 1.71)**1.87 (1.53, 2.29)***<0.001
    Abbreviation: GDM=gestational diabetes mellitus; RBC=red blood cell count; Hb=hemoglobin concentration; WBC=white blood cell count; PLT=platelet; LYM=lymphocyte; Neu=neutrophils; NLR=Neutrophil-to-lymphocyte ratio; SII=systemic immune-inflammation index; CIs=confidence intervals; ORs=odds ratios; ref.=reference.
    * P value <0.05.
    Model 1: adjusted for age.
    § Model 2: adjusted for age and body mass index.
    Model 3: adjusted for age, body mass index, gestational week, parity, adverse pregnancy history, and fasting plasma glucose.
    ** P value <0.01.
    †† P trend values were obtained from the logistic regression models by using individual hematological parameters treated as continuous variables, where standard deviation (SD) was used as a unit to quantify the elevation of each parameter.
    *** P value <0.001.
    Download: CSV

    TABLE 3.  Associations of hematological markers with different gestational diabetes mellitus status.

    VariableGDM-IPH vs. NGTGDM-IFH vs. NGTGDM-CH vs. NGT
    Model 1Model 2§Model 3Model 1Model 2Model 3Model 1Model 2Model 3
    OR (95% CI)OR (95% CI)OR (95% CI)OR (95% CI)OR (95% CI)OR (95% CI)OR (95% CI)OR (95% CI)OR (95% CI)
    SII
    Quartile 1ref.ref.ref.ref.ref.ref.ref.ref.ref.
    Quartile 21.26 (0.95, 1.67)1.27 (0.96, 1.69)1.29 (0.97, 1.71)1.03 (0.74, 1.44)1.02 (0.73, 1.43)1.02 (0.73, 1.44)0.88 (0.55, 1.38)0.88 (0.55, 1.39)0.89 (0.56, 1.40)
    Quartile 31.47 (1.12, 1.93)**1.46 (1.11, 1.93)**1.47 (1.12, 1.94)**1.43 (1.04, 1.97)*1.35 (0.99, 1.87)1.36 (0.99, 1.87)1.17 (0.76, 1.80)1.06 (0.69, 1.64)1.06 (0.68, 1.64)
    Quartile 41.71 (1.31, 2.24)***1.71 (1.31, 2.25)***1.75 (1.34, 2.30)***1.46 (1.07, 2.01)*1.37 (1.00, 1.89)1.38 (1.00, 1.90)*1.32 (0.87, 2.02)1.17 (0.77, 1.79)1.20 (0.78, 1.84)
    Ptrend<0.001<0.001<0.0010.0020.0070.0080.0260.1260.125
    NLR
    Quartile 1ref.ref.ref.ref.ref.1 ref.ref.ref.ref.)
    Quartile 21.30 (0.99, 1.71)1.31 (1.00, 1.72)1.32 (1.01, 1.74)*1.18 (0.85, 1.63)1.18 (0.85, 1.63)1.19 (0.86, 1.64)1.48 (0.98, 2.26)1.53 (1.00, 2.35)1.54 (1.01, 2.37)*
    Quartile 31.33 (1.02, 1.75)*1.32 (1.01, 1.74)*1.35 (1.03, 1.78)*1.17 (0.85, 1.62)1.16 (0.84, 1.6)1.18 (0.85, 1.63)1.03 (0.65, 1.62)1.05 (0.66, 1.67)1.07 (0.67, 1.71)
    Quartile 41.43 (1.10, 1.88)**1.43 (1.10, 1.88)**1.47 (1.12, 1.92)**1.36 (1.00, 1.87)1.39 (1.01, 1.90)*1.42 (1.04, 1.95)*1.18 (0.76, 1.84)1.25 (0.80, 1.96)1.28 (0.81, 2.01)
    Ptrend0.0060.0060.0050.0390.0240.0260.5860.3890.405
    RBC
    Quartile 1ref.ref.ref.ref.ref.ref.ref.ref.ref.
    Quartile 21.16 (0.88, 1.52)1.15 (0.88, 1.51)1.17 (0.89, 1.53)1.23 (0.88, 1.72)1.19 (0.86, 1.67)1.21 (0.87, 1.69)1.83 (1.15, 2.97)*1.72 (1.08, 2.80)*1.74 (1.09, 2.84)*
    Quartile 31.28 (0.98, 1.69)1.28 (0.98, 1.69)1.30 (0.99, 1.71)1.41 (1.02, 1.96)*1.31 (0.94, 1.83)1.31 (0.94, 1.83)1.72 (1.07, 2.82)*1.44 (0.89, 2.37)1.46 (0.89, 2.40)
    Quartile 41.62 (1.25, 2.11)***1.61 (1.24, 2.11)***1.62 (1.24, 2.11)***1.70 (1.24, 2.35)***1.48 (1.07, 2.05)*1.49 (1.08, 2.06)*2.22 (1.41, 3.58)***1.62 (1.02, 2.64)*1.64 (1.02, 2.67)*
    Ptrend<0.001<0.001<0.0010.0010.0240.027<0.0010.0590.063
    HB
    Quartile 1ref.ref.ref.ref.ref.ref.ref.ref.ref.
    Quartile 20.98 (0.75, 1.29)0.99 (0.75, 1.30)1.00 (0.76, 1.31)1.10 (0.80, 1.51)1.05 (0.76, 1.44)1.05 (0.76, 1.44)1.11 (0.70, 1.75)0.99 (0.63, 1.58)1.00 (0.63, 1.59)
    Quartile 31.12 (0.85, 1.46)1.11 (0.85, 1.46)1.12 (0.85, 1.46)1.39 (1.02, 1.89)*1.25 (0.92, 1.72)1.25 (0.91, 1.71)1.31 (0.84, 2.06)1.05 (0.66, 1.66)1.06 (0.67, 1.69)
    Quartile 41.71 (1.34, 2.19)***1.72 (1.34, 2.21)***1.73 (1.35, 2.23)***1.43 (1.05, 1.94)*1.26 (0.92, 1.72)1.25 (0.91, 1.71)2.00 (1.33, 3.03)**1.49 (0.98, 2.28)1.52 (1.00, 2.34)
    Ptrend<0.001<0.001<0.0010.0070.0740.0860.0040.1970.161
    WBC
    Quartile 1ref.ref.ref.ref.ref.ref.ref.ref.ref.
    Quartile 21.28 (0.98, 1.68)1.28 (0.98, 1.68)1.30 (0.99, 1.70)1.01 (0.72, 1.41)0.98 (0.71, 1.37)0.98 (0.70, 1.37)1.46 (0.87, 2.49)1.40 (0.83, 2.39)1.42 (0.84, 2.42)
    Quartile 31.39 (1.06, 1.83)*1.39 (1.06, 1.83)*1.41 (1.07, 1.86)*1.27 (0.92, 1.77)1.20 (0.87, 1.67)1.21 (0.87, 1.68)2.29 (1.42, 3.79)***2.01 (1.24, 3.36)**2.03 (1.24, 3.39)**
    Quartile 41.72 (1.32, 2.25)***1.72 (1.31, 2.25)***1.73 (1.32, 2.27)***1.80 (1.33, 2.45)***1.60 (1.17, 2.19)**1.59 (1.17, 2.18)**3.37 (2.14, 5.47)***2.62 (1.65, 4.28)***2.68 (1.68, 4.39)***
    Ptrend<0.001<0.001<0.001<0.001<0.001<0.001<0.001<0.001<0.001
    PLT
    Quartile 1ref.ref.ref.ref.ref.ref.ref.ref.ref.
    Quartile 21.38 (1.05, 1.82)*1.40 (1.07, 1.86)*1.41 (1.07, 1.86)*1.17 (0.85, 1.61)1.14 (0.83, 1.57)1.14 (0.83, 1.57)1.09 (0.68, 1.74)1.03 (0.64, 1.65)1.03 (0.64, 1.66)
    Quartile 31.45 (1.10, 1.90)**1.45 (1.11, 1.91)**1.46 (1.11, 1.92)**1.12 (0.81, 1.55)1.03 (0.75, 1.43)1.03 (0.74, 1.43)1.44 (0.93, 2.25)1.21 (0.78, 1.90)1.21 (0.77, 1.90)
    Quartile 41.62 (1.24, 2.12)***1.62 (1.23, 2.13)***1.62 (1.23, 2.13)***1.36 (1.00, 1.86)1.17 (0.85, 1.61)1.15 (0.84, 1.59)1.66 (1.09, 2.58)*1.21 (0.78, 1.90)1.22 (0.78, 1.91)
    Ptrend<0.001<0.001<0.0010.0440.3690.3620.0010.1400.106
    LYM
    Quartile 1ref.ref.ref.ref.ref.ref.ref.ref.ref.
    Quartile 21.08 (0.84, 1.38)1.09 (0.85, 1.39)1.09 (0.85, 1.40)1.16 (0.86, 1.58)1.13 (0.84, 1.54)1.13 (0.84, 1.54)1.32 (0.84, 2.11)1.26 (0.79, 2.02)1.25 (0.79, 2.01)
    Quartile 31.09 (0.84, 1.42)1.09 (0.84, 1.42)1.09 (0.83, 1.41)1.26 (0.92, 1.73)1.19 (0.87, 1.64)1.17 (0.85, 1.62)1.74 (1.10, 2.77)*1.52 (0.96, 2.43)1.51 (0.95, 2.42)
    Quartile 41.14 (0.87, 1.50)1.13 (0.85, 1.49)1.11 (0.84, 1.46)1.37 (0.99, 1.91)1.20 (0.86, 1.68)1.19 (0.85, 1.67)2.42 (1.55, 3.83)***1.82 (1.16, 2.91)*1.83 (1.16, 2.92)**
    Ptrend0.5130.5980.6780.0740.4000.458<0.0010.0090.010
    NEU
    Quartile 1ref.ref.ref.ref.ref.ref.ref.ref.ref.
    Quartile 21.16 (0.88, 1.52)1.15 (0.88, 1.52)1.16 (0.88, 1.53)1.13 (0.81, 1.59)1.11 (0.79, 1.56)1.11 (0.79, 1.56)2.33 (1.42, 3.94)***2.25 (1.37, 3.82)**2.29 (1.39, 3.89)**
    Quartile 31.4 (1.07, 1.83)*1.39 (1.06, 1.83)*1.41 (1.07, 1.85)*1.32 (0.95, 1.85)1.25 (0.90, 1.76)1.26 (0.90, 1.77)1.91 (1.13, 3.32)*1.73 (1.02, 3.01)*1.75 (1.03, 3.06)*
    Quartile 41.64 (1.26, 2.14)***1.62 (1.25, 2.13)***1.65 (1.26, 2.16)***1.99 (1.46, 2.72)***1.81 (1.32, 2.49)***1.81 (1.32, 2.5)***3.64 (2.26, 6.08)***2.99 (1.84, 5.02)***3.07 (1.89, 5.18)***
    Ptrend<0.001<0.001<0.001<0.001<0.001<0.001<0.001<0.001<0.001
    Abbreviation: OGTT=oral glucose tolerance test; RBC=red blood cell count; Hb=hemoglobin concentration; WBC=white blood cell count; PLT=platelet; LYM=lymphocytes; Neu=neutrophils; NLR=Neutrophil-to-lymphocyte ratio; SII=systemic immune-inflammation index; NGT=normoglycaemia; GDM-IFH, fasting glucose values ≥5.1 mmol/L with normal post-load glucose values, GDM-IPH, post-load glucose values ≥10.0 mmol/L at 1 h and/or ≥8.5 mmol/L at 2 h with normal fasting glucose values; GDM-CH, fasting blood glucose values ≥5.1 mmol/L and post-load glucose values ≥10.0 mmol/L at 1 h and/or ≥8.5 mmol/L at 2 h.
    * P value <0.05.
    Model 1: adjusted for age.
    § Model 2: adjusted for age and body mass index.
    Model 3: adjusted for age, body mass index, gestational week, parity, adverse pregnancy history, and fasting plasma glucose.
    ** P value <0.01.
    *** P value <0.001.




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Hematological Parameters in the First Trimester and the Risk of Gestational Diabetes Mellitus — Beijing, China, 2017–2020

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Summary

What is already known about this topic?

Hematological parameters may indicate the presence of chronic low-grade inflammation and increasing viscosity, which are involved in the pathological processes of gestational diabetes mellitus (GDM). However, the association between several hematological parameters in early pregnancy and GDM has yet to be elucidated.

What is added by this report?

Hematological parameters in the first trimester, particularly red blood cell (RBC) count and systematic immune index, have a significant impact on GDM incidence. The neutrophils (NEU) count in the first trimester was particularly pronounced for GDM. The upward trend of RBC, white blood cell (WBC), and NEU counts was consistent across all GDM subtypes.

What are the implications for public health practice?

Early pregnancy hematological parameters are associated with the risk of GDM.

  • 1. Graduate School of Peking Union Medical College, Beijing Municipality, China
  • 2. National Research Institute for Family Planning, Beijing Municipality, China
  • 3. National Human Genetic Resources Center, Beijing Municipality, China
  • 4. Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Municipality, China
  • 5. Haidian Maternal&Child Health Hospital, Beijing Municipality, China
  • Corresponding authors:

    Xiaoxuan Zou, xiaoxuanzou@126.com

    Ying Yang, angela-yy65@hotmail.com

  • Funding: Supported by the National Key Research and Development Program of China (NKPs) [Grant no. 2021YFC2700705]
  • Online Date: March 03 2023
    Issue Date: March 03 2023
    doi: 10.46234/ccdcw2023.035
  • Gestational diabetes mellitus (GDM) is a prevalent high-risk disorder during pregnancy, increasing the risk of adverse pregnancy outcomes (1). Previous studies have documented that abnormalities in hematological cells reflect the increasing level of maternal immune dysregulation and viscosity, which may play a role in the pathophysiology of GDM (2-3). However, reports of the association between several hematological parameters in early pregnancy and GDM are equivocal. Although some epidemiological studies have demonstrated a positive association between red blood cell (RBC) (4), white blood cell (WBC) (5), or hemoglobin (Hb) (6) in early pregnancy and GDM, inconsistent results were observed in other studies (7). To our knowledge, previous studies have not included certain novel immune blood parameters, such as the neutrophil-lymphocyte ratio (NLR). We conducted a retrospective study and used adjusted logistic regression models to assess the association between increased hematological parameters in early pregnancy and incident GDM, collecting data from the Haidian District Maternal and Child Health Care Hospital on pregnant women between 2017 and 2020. All analyses were performed using the R software (version 4.1.2;R Foundation for Statistical Computing, Vienna, Austria). The results showed that a quartile increment in Hb, RBC, WBC, platelet (PLT), neutrophils (NEU), NLR, and systemic immune-inflammation index (SII) was positively associated with GDM incident (Ptrend<0.05) after multivariable adjustment.

    This retrospective cohort study was conducted among 29,570 reproductive-aged women with singleton pregnancies who were registered in the obstetric archives between January 2017 and April 2020 and completed their routine prenatal visits in the Maternal and Child Health Care Hospital of Haidian District, Beijing. After excluding participants with chronic diseases (e.g., hypertension, diabetes, or chronic nephritis), infectious diseases [e.g., syphilis, clap, or acquired immune deficiency syndrome (AIDS)], missing values of hematological parameters before 13 gestational weeks, or women who did not undergo a standard oral glucose tolerance test (OGTT) at 24 to 28 gestational weeks, a total of 5,529 participants were finally included (Supplementary Figure S1).

    Hematological parameters included blood cell counts [RBC, PLT, and WBC, including neutrophil (NEU) and lymphocyte (LYM)] and hemoglobin concentration, which were tested from fasting blood samples collected in the first trimester and immediately stored at 4–8 °C for 24 h. We further calculated NLR and SII [(neutrophil × platelet)/lymphocyte], indicating the degree of individual inflammatory burden (8). Both NLR and SII reflect the balance of adaptive immune and inflammatory factors in the human body. Physical examinations, previous obstetric history, laboratory parameters, and diagnoses were extracted from the electronic medical record system. Information on physical examinations contained height and weight.

    GDM was diagnosed if at least one value of plasma glucose concentration was equal to or exceeded the thresholds of 5.1, 10.0, and 8.5 mmol/L for fasting, 1 h, and 2 h post-glucose load values, respectively, after performing a 75 g OGTT at gestational 24–28 weeks according to the Guidelines for Diagnosis and Treatment of Diabetes in Pregnancy (2014) in China (9). We further distinguished the impact of three subtypes of GDM: isolated fasting hyperglycemia (GDM-IFH), isolated post-load hyperglycemia (GDM-IPH), and combined hyperglycemia (GDM-CH) (10). This study used age-adjusted and multivariable-adjusted logistic regression models to examine the associations between hematological parameters and GDM. The odds ratio (OR) and 95% confidence interval (CI) of having GDM were used to quantify the association. We categorized participants into four groups based on quartile cutoff values of hematological parameters. A linear trend was tested by recoding individual hematological parameters as a continuous variable into the regression model. To provide clinical recommendation (11), the normal ranges of RBC, Hb, WBC, PLT, NEU, and LYM in the first trimester were defined as 3.42–4.55 (×1012/L), 116–139 (g/L), 5.7–13.6 (×109/L), 174–391 (×109/L), 3.61–10.19 (×1012/L), and 1.1–3.6 (×1012/L), respectively. All the regression models were adjusted for the following covariates: age (categorical, <30, ≥30), gestational week (categorical, <9, ≥9), parity (categorical, 0, ≥1), body mass index (BMI) before 20 gestational weeks (categorical, <18.5, 18.5–23.9, 24.0–27.9, ≥28.0), history of adverse pregnancy outcomes (categorical, have, not have), and fasting blood glucose (categorical, <6.1, ≥6.1). All analyses were conducted using R software 4.1.2, and two-sided P<0.05 values were considered statistically significant.

    Among the 5,529 participants, 1,017 incident GDM cases (18.4%, including 503 GDM-IPH, 339 GDM-IFH, and 175 GDM-CH) were identified. Table 1 shows the baseline characteristics of the pregnant women. The median age of participants was 31 (29 to 34) years, and the median gestational week at enrollment was 12.01. Participants with GDM were more likely to be older, parous, have an abnormal pregnancy history, and have higher levels of fasting plasma glucose and BMI in the first trimester (P<0.05). The hematological parameters in the first trimester, including RBC, Hb, WBC, PLT, LYM, NEU, NLR, and SII, were higher in GDM than in non-GDM women (P<0.05). Results from multivariable-adjusted logistic regressions revealed that, compared with the first quartile, the odds ratios (95% CI) of GDM across the highest quartile of NEU, WBC, RBC, Hb, SII, NLR, and PLT were 1.87 (1.53, 2.29), 1.81 (1.48, 2.21), 1.56 (1.28, 1.91), 1.52 (1.26, 1.84), 1.51 (1.24, 1.84), 1.42 (1.17, 1.74), and 1.36 (1.12, 1.67), respectively (all Ptrend<0.01, Table 2). For GDM subtypes, increased risks of GDM-IFH, GDM-IPH, and GDM-CH were associated with an increase in RBC, WBC, and NEU count. Elevated LYM, rather than SII or NLR, was only significantly associated with GDM-CH. In addition, Hb and PLT were only significantly associated with GDM-IPH (Table 3). In summary, the results verified that a high level of each hematological parameter was a significant predictor of GDM. According to clinical classification, the risk for GDM was significantly increased with higher WBC [OR=2.03 (1.21, 3.31) for WBC ≥13.7×1012/L], NEU [OR=2.01 (1.33, 2.98) for NEU ≥10.2×1012/L], RBC [OR=1.55 (1.28, 1.87) for RBC ≥4.56×1012/L], and Hb [OR=1.7 (1.34, 2.14) for Hb ≥140 g/L] levels in the first trimester (Supplementary Table S1).

    VariableOverall (N=5,529)non-GDM (n=4,512)GDM (n=1,017)P value*
    Age, years [median (IQR)]31.00 (29.00, 34.00)31.00 (29.00, 33.00)32.00 (29.00, 35.00)<0.001
    Parity (%)
     ≥11,966 (35.6)1,565 (34.7)401 (39.4)0.005
    BMI, kg/m2, n (%)<0.001
     <18.5190 (3.4)154 (3.4)36 ( 3.5)
     18.5–23.93,548 (64.2)2,998 (66.4)550 (54.1)
     24.0–27.91,450 (26.2)1,129 (25.0)321 (31.6)
     ≥28.0341 (6.2)231 (5.1)110 (10.8)
    Gestational weeks (mean±SD)12.01±0.9812.01±0.9812.02±0.960.868
    Adverse pregnancy history, n (%)456 (8.2)330 (7.3)126 (12.4)<0.001
    Fasting plasma glucose, mmol/L (mean±SD)4.91±0.344.88±0.335.02±0.33<0.001
    OGTT fasting, mmol/L (mean±SD)4.63±0.384.54±0.305.01±0.46<0.001
    OGTT 1 hour, mmol/L (mean±SD)7.69±1.617.29±1.329.45±1.59<0.001
    OGTT 2 hour, mmol/L (mean±SD)6.63±1.246.32±0.957.99±1.43<0.001
    Hematological parameters
     RBC, 1012/L (mean±SD)4.20±0.314.19±0.314.25±0.31<0.001
     HB, g/L (mean±SD)127.78±8.27127.47±8.22129.20±8.38<0.001
     WBC, 109/L [median (IQR)]8.60 (7.40, 9.90)8.50 (7.30, 9.80)9.00 (7.70, 10.40)<0.001
     PLT, 109/L (mean±SD)237.77±49.62236.32±49.49244.20±49.71<0.001
     LYM, 109/L [median (IQR)]1.70 (1.40, 2.00)1.70 (1.40, 2.00)1.70 (1.50, 2.00)0.001
     NEU, 109/L [median (IQR)]6.30 (5.20, 7.40)6.20 (5.20, 7.30)6.60 (5.50, 7.90)<0.001
     NLR [median (IQR)]3.72 (3.00, 4.58)3.71 (3.00, 4.56)3.80 (3.13, 4.69)0.005
     SII [median (IQR)]872.14 (678.57, 1113.60)860.50 (672.19, 1099.820)914.52 (709.71, 1186.67)<0.001
    Abbreviation: GDM=gestational diabetes mellitus; BMI=body mass index; OGTT=oral glucose tolerance test; RBC=red blood cell count; Hb=hemoglobin concentration; WBC=white blood cell count; PLT=platelet; LYM=lymphocytes; Neu=neutrophil; NLR=Neutrophil-to-lymphocyte ratio; SII=systemic immune-inflammation index, IQR=interquartile range; SD=standard deviation.
    * Data are presented as mean±SD, and P values were from 2-sample independent t-tests; or presented as median (interquartile range), and P values were from Mann–Whitney U test; or presented as number (percent), and P values were from Chi-squared tests.
    OGTT was tested at 24–28 gestational weeks, and other variables were collected or measured in early pregnancy.

    Table 1.  Characteristics among participants in the cohort according to GDM status (n=5,529).

    VariableORs (95% CIs) for GDMPtrend*
    Quartile 1Quartile 2Quartile 3Quartile 4
    SII<680680–872873–1,110≥1,111 
     Cases/total (%)211/1,383 (15.26)229/1,382 (16.57)277/1,382 (20.04)300/1,382 (21.71)
     Model 11 (ref.)1.11 (0.90, 1.36)1.4 (1.15, 1.70)***1.55 (1.27, 1.88)***<0.001
     Model 2§1 (ref.)1.11 (0.90, 1.36)1.35 (1.10, 1.64)***1.48 (1.22, 1.81)***<0.001
     Model 31 (ref.)1.12 (0.91, 1.38)1.35 (1.11, 1.65)***1.51 (1.24, 1.84)***<0.001
    NLR<3.013.01–3.723.73–4.58≥4.59
     Cases/total (%)218/1,390 (15.68)268/1,383 (19.38)253/1,376 (18.39)278/1,380 (20.14)
     Model 11 (ref.)1.29 (1.06, 1.58)*1.22 (1.00, 1.50)*1.37 (1.12, 1.66)***0.002
     Model 21 (ref.)1.29 (1.06, 1.57)*1.21 (0.99, 1.48)1.39 (1.14, 1.69)***0.001
     Model 31 (ref.)1.31 (1.07, 1.60)**1.24 (1.01, 1.52)*1.42 (1.17, 1.74)***0.001
    RBC<4.004.00–4.194.20–4.39≥4.40
     Cases/total (%)203/1,397 (14.53)253/1,427 (17.73)253/1,340 (18.88)308/1,365 (22.56)
     Model 11 (ref.)1.27 (1.04, 1.56)*1.39 (1.13, 1.70)**1.73 (1.43, 2.11)***<0.001
     Model 21 (ref.)1.24 (1.01, 1.52)*1.31 (1.07, 1.61)**1.56 (1.28, 1.91)***<0.001
     Model 31 (ref.)1.25 (1.02, 1.54)*1.32 (1.07, 1.62)**1.56 (1.28, 1.91)***<0.001
    HB<124124–128129–133≥134
     Cases/total (%)252/1,600 (15.75)219/1,346 (16.27)234/1,255 (18.65)312/1,328 (23.49)
     Model 11 (ref.)1.04 (0.86, 1.27)1.24 (1.02, 1.51)*1.67 (1.38, 2.01)***<0.001
     Model 21 (ref.)1.01 (0.83, 1.23)1.16 (0.95, 1.41)1.52 (1.26, 1.84)***<0.001
     Model 31 (ref.)1.02 (0.83, 1.24)1.16 (0.95, 1.41)1.52 (1.26, 1.84)***<0.001
    WBC<7.57.5–8.68.7–9.9≥10.0
     Cases/total (%)205/1,448 (14.16)237/1,436 (16.5)252/1,307 (19.28)323/1,338 (24.14)
     Model 11 (ref.)1.20 (0.98, 1.47)1.46 (1.19, 1.78)***1.96 (1.61, 2.38)***<0.001
     Model 21 (ref.)1.18 (0.97, 1.45)1.39 (1.14, 1.71)***1.79 (1.47, 2.19)***<0.001
     Model 31 (ref.)1.20 (0.98, 1.47)1.41 (1.16, 1.71)***1.81 (1.48, 2.21)***<0.001
    PLT<205205–234235–269≥270
     Cases/total (%)213/1,416 (15.04)247/1,367 (18.07)266/1,393 (19.10)291/1,353 (21.51)
     Model 11 (ref.)1.25 (1.02, 1.53)*1.33 (1.09, 1.62)**1.53 (1.26, 1.86)***<0.001
     Model 21 (ref.)1.23 (1.01, 1.51)*1.25 (1.03, 1.53)*1.37 (1.12, 1.67)**0.001
     Model 31 (ref.)1.23 (1.01, 1.51)*1.25 (1.02, 1.53)*1.36 (1.12, 1.67)**0.001
    LYM<1.411.41–1.701.80–2.00≥2.01
     Cases/total (%)243/1,498 (16.22)298/1,664 (17.91)249/1,295 (19.23)227/1,072 (21.18)
     Model 11 (ref.)1.14 (0.94, 1.37)1.23 (1.01, 1.50)1.39 (1.13, 1.70)***0.002
     Model 21 (ref.)1.12 (0.93, 1.35)1.17 (0.96, 1.43)1.25 (1.01, 1.53)*0.074
     Model 31 (ref.)1.12 (0.93, 1.35)1.16 (0.96, 1.42)1.23 (1.00, 1.51)*0.102
    NEU<5.215.21–6.306.40–7.40≥7.41
     Cases/total (%)196/1,399 (14.01)252/1,472 (17.12)248/1,323 (18.75)321/1,335 (24.04)
     Model 11 (ref.)1.28 (1.04, 1.56)*1.43 (1.17, 1.76)***1.99 (1.63, 2.42)***<0.001
     Model 21 (ref.)1.26 (1.02, 1.54)*1.37 (1.12, 1.69)**1.85 (1.51, 2.26)***<0.001
     Model 31 (ref.)1.27 (1.03, 1.56)*1.39 (1.13, 1.71)**1.87 (1.53, 2.29)***<0.001
    Abbreviation: GDM=gestational diabetes mellitus; RBC=red blood cell count; Hb=hemoglobin concentration; WBC=white blood cell count; PLT=platelet; LYM=lymphocyte; Neu=neutrophils; NLR=Neutrophil-to-lymphocyte ratio; SII=systemic immune-inflammation index; CIs=confidence intervals; ORs=odds ratios; ref.=reference.
    * P value <0.05.
    Model 1: adjusted for age.
    § Model 2: adjusted for age and body mass index.
    Model 3: adjusted for age, body mass index, gestational week, parity, adverse pregnancy history, and fasting plasma glucose.
    ** P value <0.01.
    †† P trend values were obtained from the logistic regression models by using individual hematological parameters treated as continuous variables, where standard deviation (SD) was used as a unit to quantify the elevation of each parameter.
    *** P value <0.001.

    Table 2.  Odds ratio and 95% confidence intervals for GDM according to quartiles of hematological markers in early pregnancy.

    VariableGDM-IPH vs. NGTGDM-IFH vs. NGTGDM-CH vs. NGT
    Model 1Model 2§Model 3Model 1Model 2Model 3Model 1Model 2Model 3
    OR (95% CI)OR (95% CI)OR (95% CI)OR (95% CI)OR (95% CI)OR (95% CI)OR (95% CI)OR (95% CI)OR (95% CI)
    SII
    Quartile 1ref.ref.ref.ref.ref.ref.ref.ref.ref.
    Quartile 21.26 (0.95, 1.67)1.27 (0.96, 1.69)1.29 (0.97, 1.71)1.03 (0.74, 1.44)1.02 (0.73, 1.43)1.02 (0.73, 1.44)0.88 (0.55, 1.38)0.88 (0.55, 1.39)0.89 (0.56, 1.40)
    Quartile 31.47 (1.12, 1.93)**1.46 (1.11, 1.93)**1.47 (1.12, 1.94)**1.43 (1.04, 1.97)*1.35 (0.99, 1.87)1.36 (0.99, 1.87)1.17 (0.76, 1.80)1.06 (0.69, 1.64)1.06 (0.68, 1.64)
    Quartile 41.71 (1.31, 2.24)***1.71 (1.31, 2.25)***1.75 (1.34, 2.30)***1.46 (1.07, 2.01)*1.37 (1.00, 1.89)1.38 (1.00, 1.90)*1.32 (0.87, 2.02)1.17 (0.77, 1.79)1.20 (0.78, 1.84)
    Ptrend<0.001<0.001<0.0010.0020.0070.0080.0260.1260.125
    NLR
    Quartile 1ref.ref.ref.ref.ref.1 ref.ref.ref.ref.)
    Quartile 21.30 (0.99, 1.71)1.31 (1.00, 1.72)1.32 (1.01, 1.74)*1.18 (0.85, 1.63)1.18 (0.85, 1.63)1.19 (0.86, 1.64)1.48 (0.98, 2.26)1.53 (1.00, 2.35)1.54 (1.01, 2.37)*
    Quartile 31.33 (1.02, 1.75)*1.32 (1.01, 1.74)*1.35 (1.03, 1.78)*1.17 (0.85, 1.62)1.16 (0.84, 1.6)1.18 (0.85, 1.63)1.03 (0.65, 1.62)1.05 (0.66, 1.67)1.07 (0.67, 1.71)
    Quartile 41.43 (1.10, 1.88)**1.43 (1.10, 1.88)**1.47 (1.12, 1.92)**1.36 (1.00, 1.87)1.39 (1.01, 1.90)*1.42 (1.04, 1.95)*1.18 (0.76, 1.84)1.25 (0.80, 1.96)1.28 (0.81, 2.01)
    Ptrend0.0060.0060.0050.0390.0240.0260.5860.3890.405
    RBC
    Quartile 1ref.ref.ref.ref.ref.ref.ref.ref.ref.
    Quartile 21.16 (0.88, 1.52)1.15 (0.88, 1.51)1.17 (0.89, 1.53)1.23 (0.88, 1.72)1.19 (0.86, 1.67)1.21 (0.87, 1.69)1.83 (1.15, 2.97)*1.72 (1.08, 2.80)*1.74 (1.09, 2.84)*
    Quartile 31.28 (0.98, 1.69)1.28 (0.98, 1.69)1.30 (0.99, 1.71)1.41 (1.02, 1.96)*1.31 (0.94, 1.83)1.31 (0.94, 1.83)1.72 (1.07, 2.82)*1.44 (0.89, 2.37)1.46 (0.89, 2.40)
    Quartile 41.62 (1.25, 2.11)***1.61 (1.24, 2.11)***1.62 (1.24, 2.11)***1.70 (1.24, 2.35)***1.48 (1.07, 2.05)*1.49 (1.08, 2.06)*2.22 (1.41, 3.58)***1.62 (1.02, 2.64)*1.64 (1.02, 2.67)*
    Ptrend<0.001<0.001<0.0010.0010.0240.027<0.0010.0590.063
    HB
    Quartile 1ref.ref.ref.ref.ref.ref.ref.ref.ref.
    Quartile 20.98 (0.75, 1.29)0.99 (0.75, 1.30)1.00 (0.76, 1.31)1.10 (0.80, 1.51)1.05 (0.76, 1.44)1.05 (0.76, 1.44)1.11 (0.70, 1.75)0.99 (0.63, 1.58)1.00 (0.63, 1.59)
    Quartile 31.12 (0.85, 1.46)1.11 (0.85, 1.46)1.12 (0.85, 1.46)1.39 (1.02, 1.89)*1.25 (0.92, 1.72)1.25 (0.91, 1.71)1.31 (0.84, 2.06)1.05 (0.66, 1.66)1.06 (0.67, 1.69)
    Quartile 41.71 (1.34, 2.19)***1.72 (1.34, 2.21)***1.73 (1.35, 2.23)***1.43 (1.05, 1.94)*1.26 (0.92, 1.72)1.25 (0.91, 1.71)2.00 (1.33, 3.03)**1.49 (0.98, 2.28)1.52 (1.00, 2.34)
    Ptrend<0.001<0.001<0.0010.0070.0740.0860.0040.1970.161
    WBC
    Quartile 1ref.ref.ref.ref.ref.ref.ref.ref.ref.
    Quartile 21.28 (0.98, 1.68)1.28 (0.98, 1.68)1.30 (0.99, 1.70)1.01 (0.72, 1.41)0.98 (0.71, 1.37)0.98 (0.70, 1.37)1.46 (0.87, 2.49)1.40 (0.83, 2.39)1.42 (0.84, 2.42)
    Quartile 31.39 (1.06, 1.83)*1.39 (1.06, 1.83)*1.41 (1.07, 1.86)*1.27 (0.92, 1.77)1.20 (0.87, 1.67)1.21 (0.87, 1.68)2.29 (1.42, 3.79)***2.01 (1.24, 3.36)**2.03 (1.24, 3.39)**
    Quartile 41.72 (1.32, 2.25)***1.72 (1.31, 2.25)***1.73 (1.32, 2.27)***1.80 (1.33, 2.45)***1.60 (1.17, 2.19)**1.59 (1.17, 2.18)**3.37 (2.14, 5.47)***2.62 (1.65, 4.28)***2.68 (1.68, 4.39)***
    Ptrend<0.001<0.001<0.001<0.001<0.001<0.001<0.001<0.001<0.001
    PLT
    Quartile 1ref.ref.ref.ref.ref.ref.ref.ref.ref.
    Quartile 21.38 (1.05, 1.82)*1.40 (1.07, 1.86)*1.41 (1.07, 1.86)*1.17 (0.85, 1.61)1.14 (0.83, 1.57)1.14 (0.83, 1.57)1.09 (0.68, 1.74)1.03 (0.64, 1.65)1.03 (0.64, 1.66)
    Quartile 31.45 (1.10, 1.90)**1.45 (1.11, 1.91)**1.46 (1.11, 1.92)**1.12 (0.81, 1.55)1.03 (0.75, 1.43)1.03 (0.74, 1.43)1.44 (0.93, 2.25)1.21 (0.78, 1.90)1.21 (0.77, 1.90)
    Quartile 41.62 (1.24, 2.12)***1.62 (1.23, 2.13)***1.62 (1.23, 2.13)***1.36 (1.00, 1.86)1.17 (0.85, 1.61)1.15 (0.84, 1.59)1.66 (1.09, 2.58)*1.21 (0.78, 1.90)1.22 (0.78, 1.91)
    Ptrend<0.001<0.001<0.0010.0440.3690.3620.0010.1400.106
    LYM
    Quartile 1ref.ref.ref.ref.ref.ref.ref.ref.ref.
    Quartile 21.08 (0.84, 1.38)1.09 (0.85, 1.39)1.09 (0.85, 1.40)1.16 (0.86, 1.58)1.13 (0.84, 1.54)1.13 (0.84, 1.54)1.32 (0.84, 2.11)1.26 (0.79, 2.02)1.25 (0.79, 2.01)
    Quartile 31.09 (0.84, 1.42)1.09 (0.84, 1.42)1.09 (0.83, 1.41)1.26 (0.92, 1.73)1.19 (0.87, 1.64)1.17 (0.85, 1.62)1.74 (1.10, 2.77)*1.52 (0.96, 2.43)1.51 (0.95, 2.42)
    Quartile 41.14 (0.87, 1.50)1.13 (0.85, 1.49)1.11 (0.84, 1.46)1.37 (0.99, 1.91)1.20 (0.86, 1.68)1.19 (0.85, 1.67)2.42 (1.55, 3.83)***1.82 (1.16, 2.91)*1.83 (1.16, 2.92)**
    Ptrend0.5130.5980.6780.0740.4000.458<0.0010.0090.010
    NEU
    Quartile 1ref.ref.ref.ref.ref.ref.ref.ref.ref.
    Quartile 21.16 (0.88, 1.52)1.15 (0.88, 1.52)1.16 (0.88, 1.53)1.13 (0.81, 1.59)1.11 (0.79, 1.56)1.11 (0.79, 1.56)2.33 (1.42, 3.94)***2.25 (1.37, 3.82)**2.29 (1.39, 3.89)**
    Quartile 31.4 (1.07, 1.83)*1.39 (1.06, 1.83)*1.41 (1.07, 1.85)*1.32 (0.95, 1.85)1.25 (0.90, 1.76)1.26 (0.90, 1.77)1.91 (1.13, 3.32)*1.73 (1.02, 3.01)*1.75 (1.03, 3.06)*
    Quartile 41.64 (1.26, 2.14)***1.62 (1.25, 2.13)***1.65 (1.26, 2.16)***1.99 (1.46, 2.72)***1.81 (1.32, 2.49)***1.81 (1.32, 2.5)***3.64 (2.26, 6.08)***2.99 (1.84, 5.02)***3.07 (1.89, 5.18)***
    Ptrend<0.001<0.001<0.001<0.001<0.001<0.001<0.001<0.001<0.001
    Abbreviation: OGTT=oral glucose tolerance test; RBC=red blood cell count; Hb=hemoglobin concentration; WBC=white blood cell count; PLT=platelet; LYM=lymphocytes; Neu=neutrophils; NLR=Neutrophil-to-lymphocyte ratio; SII=systemic immune-inflammation index; NGT=normoglycaemia; GDM-IFH, fasting glucose values ≥5.1 mmol/L with normal post-load glucose values, GDM-IPH, post-load glucose values ≥10.0 mmol/L at 1 h and/or ≥8.5 mmol/L at 2 h with normal fasting glucose values; GDM-CH, fasting blood glucose values ≥5.1 mmol/L and post-load glucose values ≥10.0 mmol/L at 1 h and/or ≥8.5 mmol/L at 2 h.
    * P value <0.05.
    Model 1: adjusted for age.
    § Model 2: adjusted for age and body mass index.
    Model 3: adjusted for age, body mass index, gestational week, parity, adverse pregnancy history, and fasting plasma glucose.
    ** P value <0.01.
    *** P value <0.001.




    Table 3.  Associations of hematological markers with different gestational diabetes mellitus status.

    • This study found that several high-level hematological parameters (Hb concentration, RBC, PLT, and WBC, including NEU count, NLR, and SII) in the first trimester were significantly associated with an increased risk of gestational diabetes mellitus (GDM). Notably, elevated Hb concentration and PLT count, as well as elevated LYM count, could be used as potential biomarkers to identify isolated post-load hyperglycemia and GDM with fasting hyperglycemia, respectively. Our results also provide clinical evidence that elevated RBC and NEU counts in early pregnancy could be novel risk factors and biomarkers of GDM in addition to Hb concentration. To our knowledge, this is the first study to assess the impact of SII, RBC, and other hematological indices in early pregnancy on GDM and to discuss their impact on different GDM subtypes with a moderate sample size. Given that the discovery of symptoms or signs at the early stage of GDM is difficult, combining elevated hematological parameters in the first trimester with clinical risk factors or laboratory indicators may be able to identify women at higher risk as early as possible.

      Research evidence suggests that subclinical inflammation may lead to insulin resistance by impairing β cell function and affecting insulin signaling directly (12). This may explain why classical inflammatory markers, such as WBC count and NLR, as well as the novel inflammation marker, SII, are correspondingly increased in early pregnancy among women with GDM. Additionally, platelet aggregation and glycated platelets have been reported in diabetes, which is correlated to a setting of acute and chronic inflammation with a similar cytokine milieu as that implicated in increased WBC count (13). In terms of surrogacy for nutritional improvement, higher RBC and Hb levels are often accompanied by higher blood viscosity, which has been demonstrated to be associated with insulin resistance (14). Furthermore, GDM-IFH and GDM-CH reveal impaired β-cell function and a high risk of maternal and neonatal outcomes, rather than GDM-IPH. However, the mechanisms underlying the link between elevated lymphocytes, rather than NLR or SII, and GDM-CH still need to be established in the future.

      This study had several limitations. The participants were recruited from one hospital in China, which may have introduced selection bias and limited the generalizability of our findings. Additionally, this observational study cannot explain the causal relationship between parameters in the early trimester and the risk of GDM, nor can it explain the mechanisms between hematological parameters and the risk of GDM. Further experiments or research are needed to explore these mechanisms. Overall, our results provide evidence that abnormally high routine first-trimester complete blood test results are positively associated with the risk of GDM.

    • No conflicts of interest.

    • All dedicated health workers in the Haidian District Maternal and Child Health Care Hospital, and all participants who took part in the construction of this medical database.

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