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Journal of Peking University (Health Sciences) ›› 2023, Vol. 55 ›› Issue (6): 1045-1052. doi: 10.19723/j.issn.1671-167X.2023.06.014

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Analysis of pregnancy outcomes, disease progression, and risk factors in patients with undifferentiated connective tissue disease

Fang-ning YOU1,2,Liang LUO3,Xiang-jun LIU1,Xue-wu ZHANG1,Chun LI1,*()   

  1. 1. Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing 100044, China
    2. Department of Nephropathy and Rheumatology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400011, China
    3. Department of Chinese Medicine, the People's Hospital of Yubei District of Chongqing City, Chongqing 401120, China
  • Received:2023-08-11 Online:2023-12-18 Published:2023-12-11
  • Contact: Chun LI E-mail:13811190098@163.com
  • Supported by:
    China International Medical Foundation(Z-2018-40-2101);Beijing Municipal Science and Technology Projects(Z191100006619110)

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Abstract:

Objective: To investigate the fetal and maternal outcomes, risk factors of disease progression and adverse pregnancy outcomes (APOs) in patients with undifferentiated connective tissue disease (UCTD). Methods: This retrospective study described the outcomes of 106 pregnancies in patients with UCTD. The patients were divided into APOs group (n=53) and non-APOs group (n=53). The APOs were defined as miscarriage, premature birth, pre-eclampsia, premature rupture of membranes (PROM), intrauterine growth restriction (IUGR), postpartum hemorrhage (PPH), and stillbirth, small for gestational age infant (SGA), low birth weight infant (LBW) and birth defects. The differences in clinical manifestations, laboratory data and pregnancy outcomes between the two groups were compared. Logistic regression analysis was performed to analyze the risk factors for APOs and the progression of UCTD to definitive CTD. Results: There were 99 (93.39%) live births, 4 (3.77%) stillbirths and 3 (2.83%) miscarriage, 20 (18.86%) preterm delivery, 6 (5.66%) SGA, 17 (16.03%) LBW, 11 (10.37%) pre-eclampsia, 7 (6.60%) cases IUGR, 19 (17.92%) cases PROM, 10 (9.43%) cases PPH. Compared with the patients without APOs, the patients with APOs had a higher positive rate of anti-SSA antibodies (73.58% vs. 54.71%, P=0.036), higher rate of leukopenia (15.09% vs. 3.77%, P=0.046), lower haemoglobin level [109.00 (99.50, 118.00) g/L vs. 124.00 (111.50, 132.00) g/L, P < 0.001].Multivariate Logistic regression analysis showed that leucopenia (OR=0.82, 95%CI: 0.688-0.994) was an independent risk factors for APOs in UCTD (P=0.042). Within a mean follow-up time of 5.00 (3.00, 7.00) years, the rate of disease progression to a definite CTD was 14.15%, including 8 (7.54%) Sjögren's syndrome, 4 (3.77%) systemic lupus erythematosus (SLE), 4 (3.77%) rheumatoid arthritis and 1 (0.94%) mixed connective tissue disease. Multivariate Cox proportional risk regression analysis showed that Raynaud phenomenon (HR=40.157, 95%CI: 3.172-508.326) was an independent risk factor for progression to SLE. Conclusion: Leukopenia is an independent risk factor for the development of APOs in patients with UCTD. Raynaud's phenmon is a risk factor for the progression of SLE. Tight disease monitoring and regular follow-up are the key measures to prevent adverse pregnancy outcomes and predict disease progression in UCTD patients with pregnancy.

Key words: Undifferentiated connective tissue disease, Adverse pregnancy outcomes, Risk factor

CLC Number: 

  • R593.2

Table 1

Comparison of clinical characteristics and laboratory indexes between the two groups"

Items Total patients (n=106) APOs (n=53) Non-APOs (n=53) Z/t/χ2 P value
Age at conception/years, ${\bar x}$±s 31.00±0.38 30.03±0.54 31.96±0.51 -2.570 0.012*
Birth weight/g, ${\bar x}$±s 2 901.43±67.30 2 693.41±104.78 3 158.26±52.11 -4.113 0.000*
Disease duration/weeks, M (P25, P75) 48.00 (23.50, 144.00) 96.00 (32.00, 144.00) 48.00 (12.00, 144.00) -1.222 0.222
Mode of delivery
  Vaginal, n (%) 56 (52.83) 23 (43.39) 33 (62.26) 2.457 0.117
  Cesarean section, n (%) 45 (42.45) 25 (47.16) 20 (37.73) 2.099 0.147
Clinical manifestations of the disease
  Arthritis, n (%) 12 (11.32) 9 (16.98) 3 (5.66) 3.383 0.066
  Cutaneous manifestations, n (%) 14 (13.20) 8 (15.09) 6 (11.32) 0.329 0.566
  Photosensitive, n (%) 5 (4.71) 4 (7.54) 1 (1.88) 1.889 0.169
  RP, n (%) 6 (5.66) 3 (5.66) 3 (5.66) 0.001 0.981
Haematological 38 (35.84) 24 (45.28) 14 (26.41) 4.102 0.043*
  Leukopenia, n (%) 10 (9.43) 8 (15.09) 2 (3.77) 3.975 0.046*
  Thrombocytopaenia, n (%) 27 (25.47) 16 (30.18) 11 (20.75) 1.242 0.265
  Haemolytic anaemia, n (%) 5 (4.71) 4 (7.54) 1 (1.88) 1.889 0.169
  PLT/(×109/L), M (P25, P75) 172.00 (103.50, 216.75) 171.00 (41.00, 234.50) 132.50 (132.50, 195.00) -0.082 0.935
  Hb/(g/L), M (P25, P75) 114.00 (106.75, 127.25) 109.00 (99.50, 118.00) 124.00 (111.50, 132.00) 11.999 0.001*
  Proteinuria, n (%) 18(16.98) 12(22.64) 6(11.32) 3.261 0.071
Laboratory features
  ANA positive, n (%) 106 (100.00) 53(50.00) 53 (50.00) 0.913 0.339
  Anti-ENA positive, n (%) 77 (72.64) 44 (83.01) 33 (62.26) 6.411 0.011*
  Anti-SSB antibodies, n (%) 11 (10.37) 8 (15.09) 3 (5.66) 2.547 0.110
  Anti-SSA antibodies, n (%) 68 (64.15) 39 (36.79) 29 (27.35) 4.412 0.036*
  Anti-RNP antibodies, n (%) 8 (7.54) 5 (9.43) 3 (5.66) 0.543 0.461
  Anti-U1RNP antibodies, n (%) 3 (2.83) 2 (3.77) 1 (1.88) 0.343 0.558
  Anti-Ro52 antibodies, n (%) 29 (27.35) 16 (30.18) 13 (24.52) 0.434 0.510
  Anti-ribosomal P protein antibodies, n (%) 5 (4.71) 4 (7.54) 1 (1.88) 1.893 0.169
  Anti-nucleosome antibodies, n (%) 5 (4.71) 2 (3.77) 3 (5.66) 0.210 0.647
  Anti-Sm antibodies, n (%) 1 (0.94) 0 (0.00) 1 (1.88) 1.010 0.315
  Anti-cell membrane DNA antibodies 2 (1.88) 2 (3.77) 0 (0.00) 1.010 0.315
  Anti-M2 antibodies, n (%) 2 (1.88) 2 (3.77) 0 (0.00) 2.040 0.153
  Anti-dsDNA antibodies, n (%) 5 (4.71) 1 (1.88) 4 (7.54) 1.891 0.169
  Low C3，n (%) 26 (24.52) 14 (26.41) 12 (22.64) 0.159 0.690
  Low C4，n (%) 3 (2.83) 0 (0.00) 3 (5.66) 3.263 0.071
  Low C3/C4, n (%) 26 (24.52) 1 4(26.41) 12 (22.64) 0.106 0.744
  IgA positive, n (%) 1 (0.94) 0 (0.00) 1 (1.88) 1.138 0.286
  IgG positive, n (%) 14 (13.20) 9 (16.98) 5 (9.43) 1.385 0.239
  IgM positive, n (%) 4 (3.77) 3 (5.66) 2 (3.77) 0.104 0.747
  LA positive, n (%) 17 (16.03) 6 (11.32) 11 (20.75) 1.426 0.232
  aCL (IgG/IgM) positive, n (%) 10 (9.43) 4 (7.54) 6 (11.32) 0.212 0.645
  Anti-β2GPⅠ(IgG/IgM) antibodies positive, n (%) 12 (11.32) 5 (9.43) 7 (13.20) 0.096 0.757
  Coombs test positive, n (%) 6 (5.66) 4 (7.54) 2 (3.77) 2.649 0.104
  D-diemer/(μg/L), M (P25, P75) 659 (346.25, 1 103.75) 747.00 (403.00, 1 603.00) 559.00 (337.00, 853.00) -0.252 0.211
  APTT/s, M (P25, P75) 27.80 (26.00, 30.00) 27.80 (26.30, 29.00) 27.35 (25.90, 30.12) 0.018 0.986
  ESR/(mm/h), M (P25, P75) 16.00 (10.00, 34.00) 14.50 (9.25, 35.50) 21.00 (11.00, 40.00) -0.674 0.500
  CRP/(mg/L), M (P25, P75) 4.92 (1.82, 11.42) 8.09 (2.49, 22.00) 3.20 (1.66, 10.00) -1.190 0.234
  RF/(IU/mL), M (P25, P75) 15.00 (15.00, 21.15) 15.00 (15.00, 29.20) 15.00 (15.00, 15.00) -0.985 0.325

Table 2

Binary Logistic analysis results of of factors related to APOs in UCTD patients"

Variables Univariate Multivariate
B Wald P OR(95%CI) B Wald P OR(95%CI)
Anti-SSA positive -0.902 4.311 0.038* 0.406 (0.173-0.951)
Anti-ENA positive -1.232 6.038 0.014* 0.292 (0.109-0.779)
Leucopenia -0.239 6.786 0.009* 0.788 (0.658-0.943) -0.190 4.119 0.042* 0.827(0.688-0.994)
Anemia -0.051 12.497 0.000* 0.950 (0.923-0.977)

Table 3

Therapy undertaken by the patients before, during and after pregnancy"

Therapy Before pregnancy, n(%) During pregnancy, n(%) Postpartum, n(%)
Low-dose aspirin 13 (12.26) 32 (30.18) 1 (0.94)
Low molecular weight heparin 6 (5.66) 29 (27.35) 3 (2.83)
Glucocorticosteroids 27 (25.47) 19 (17.92) 27 (25.47)
HCQ 51 (48.11) 78 (73.58) 61 (57.54)
Intravenous immunoglobulin 0 (0.00) 3 (2.83) 0 (0.00)
MMF 0 (0.00) 0 (0.00) 2 (1.88)
Ciclosporin 3 (2.83) 6 (5.66) 7 (6.60)
Iguratimod 0 0 3 (2.83)
Tacrolimus 1 (0.94) 2 (1.88) 2 (1.88)

Table 4

The related factor analysis of definite CTD envolved from UCTD"

CTD Variables CTD group Control group Z/t/χ2 P
SLE RP, n (%) 3 (75.00) 3 (2.94) 37.427 0.000*
Anti-RNP, n (%) 2 (50.00) 6 (5.88) 10.237 0.030*
SS Anti-SSA, n (%) 8 (100.0) 60 (61.22) 4.340 0.037*
Arthritis, n (%) 3 (37.50) 11 (11.22) 4.455 0.025*
Salivary gland ultrasound, n (%) 3 (37.50) 0 (0.00) 101.00 0.000*
RA Arthritis, n (%) 3 (75.00) 11 (10.78) 13.846 0.007*

Figure 1

Kaplan-Meier survival curve of UCTD envolved into definite CTD UCTD, undifferentiated connective tissue disease; SS, Sjögren' s syndrome; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; RP, Raynaud phenomenon."

Table 5

Cox proportional risk regression analysis results of factors related to definite CTD envolved from UCTD"

CTD Variables Univariate Multivariate
B SE Wald P HR(95% CI) B SE Wald P HR(95% CI)
SLE RP 3.894 1.155 11.360 0.001* 49.120 (5.102－472.877) 3.693 1.295 8.130 0.004* 40.157 (3.172-508.326)
Anti-RNP 2.751 1.052 6.832 0.009* 15.652 (1.990－123.117)
SS Salivary gland ultrasound 3.417 0.736 21.537 0.000* 30.487 (7.200－129.095)
RA Arthritis -3.101 1.157 7.182 0.007* 0.045 (0.005－0.435)
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