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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)
1 Mosca M , Tani C , Neri C , et al. Undifferentiated connective tissue diseases (UCTD)[J]. Autoimm Rev, 2006, 6 (1): 1- 4.
doi: 10.1016/j.autrev.2006.03.004
2 García-González M , Rodríguez-Lozano B , Bustabad S , et al. Undifferentiated connective tissue disease: Predictors of evolution into definite disease[J]. Clin Exp Rheumatol, 2017, 35 (5): 739- 745.
3 Mecacci F , Pieralli A , Bianchi B , et al. The impact of autoimmune disorders and adverse pregnancy outcome[J]. Semin Perinatol, 2007, 31 (4): 223- 226.
doi: 10.1053/j.semperi.2007.05.005
4 Mosca M , Neri R , Bombardieri S . Undifferentiated connective tissue diseases (UCTD): A review of the literature and a proposal for preliminary classification criteria[J]. Clin Exp Rheumatol, 1999, 17 (5): 615- 620.
5 Practice Committee of the American Society for Reproductive Medicine . Evaluation and treatment of recurrent pregnancy loss: A committee opinion[J]. Fertil Steril, 2012, 98 (5): 1103- 1111.
doi: 10.1016/j.fertnstert.2012.06.048
6 Vogel JP , Chawanpaiboon S , Moller AB , et al. The global epidemiology of preterm birth[J]. Best Pract Res Clin Obstet Gynaecol, 2018, 52, 3- 12.
doi: 10.1016/j.bpobgyn.2018.04.003
7 Tyas BD , Lestari P , Akbar MIA . Maternal perinatal outcomes related to advanced maternal age in preeclampsia pregnant women[J]. J Family Reprod Health, 2019, 13 (4): 191- 200.
8 Sharma D , Shastri S , Farahbakhsh N , et al. Intrauterine growth restriction: Part 1[J]. J Matern Fetal Neonatal Med, 2016, 29 (24): 3977- 3987.
doi: 10.3109/14767058.2016.1152249
9 American College of Obstetricians and Gynecologists' Committee on Practice Bulletins-Obstetrics . Practice bulletin No.172: Premature rupture of membranes[J]. Obstet Gynecol, 2016, 128 (4): 165- 177.
doi: 10.1097/AOG.0000000000001712
10 Sheldon WR , Blum J , Vogel JP , et al. Postpartum haemorrhage management, risks, and maternal outcomes: Findings from the World Health Organization Multicountry Survey on Maternal and Newborn Health[J]. BJOG, 2014, 121 (Suppl 1): 5- 13.
11 Robinson GE . Pregnancy loss[J]. Best Pract Res Clin Obstet Gynaecol, 2014, 28 (1): 169- 178.
doi: 10.1016/j.bpobgyn.2013.08.012
12 Bertino E , Spada E , Occhi L , et al. Neonatal anthropometric charts: The Italian neonatal study compared with other European studies[J]. J Pediatr Gastroenterol Nutr, 2010, 51 (3): 353- 361.
doi: 10.1097/MPG.0b013e3181da213e
13 Krasevec J , Blencowe H , Coffey C , et al. Study protocol for UNICEF and WHO estimates of global, regional, and national low birthweight prevalence for 2000 to 2020[J]. Gates Open Res, 2022, 6, 80- 93.
doi: 10.12688/gatesopenres.13666.1
14 World Health Organization (WHO). Sixty-third world health assembly. Birth defects[R]. Geneva: WHO, 2010.
15 Ostensen M , Andreoli L , Brucato A , et al. State of the art: Reproduction and pregnancy in rheumatic diseases[J]. Autoimmun Rev, 2015, 14 (5): 376- 386.
doi: 10.1016/j.autrev.2014.12.011
16 Goldenberg RL , Culhane JF , Iams JD , et al. Epidemiology and causes of preterm birth[J]. Lancet, 2008, 371 (9606): 75- 84.
doi: 10.1016/S0140-6736(08)60074-4
17 Radin M , Schreiber K , Cecchi I , et al. A Multicentre study of 244 pregnancies in undifferentiated connective tissue disease: Maternal/fetal outcomes and disease evolution[J]. Rheumatology (Oxford), 2020, 59 (9): 2412- 2418.
doi: 10.1093/rheumatology/kez620
18 Muñoz Muñoz1 C , Ahmed K , Thomas M , et al. Comparing pregnancy outcomes in patients with criteria and non-criteria autoimmune disease: A systematic review[J]. Lupus, 2022, 31 (1): 5- 18.
doi: 10.1177/09612033211061850
19 Haase I , Fischer-Betz R . State of the art: Fertility and pregnancy in rheumatic diseases[J]. Z Rheumatol, 2021, 80 (8): 699- 706.
doi: 10.1007/s00393-021-01073-5
20 Luo L , Li XR , Li C , et al. Risk factors for adverse pregnancy outcomes in women with rheumatoid arthritis and follow-up of their offspring[J]. Clin Rheumatol, 2022, 41 (10): 3135- 3141.
doi: 10.1007/s10067-022-06233-9
21 Erden A , Apaydın H , Fanouriakis A , et al. Performance of the systemic lupus erythematosus risk probability index in a cohort of undifferentiated connective tissue disease[J]. Rheumatology (Oxford), 2022, 61 (9): 3606- 3613.
doi: 10.1093/rheumatology/keac005
22 张晓英, 温鸿雁, 陈俊伟, 等. 未分化结缔组织病合并骨髓增生异常综合征1例[J]. 北京大学学报(医学版), 2012, 44 (2): 316- 319.
doi: 10.3969/j.issn.1671-167X.2012.02.033
23 Lin L , Wei Y , Zhu W , et al. Prevalence, risk factors and associated adverse pregnancy outcomes of anaemia in Chinese pregnant women: A multicentre retrospective study[J]. BMC Pregnancy Childbirth, 2018, 18 (1): 111- 118.
doi: 10.1186/s12884-018-1739-8
24 Li M , Huang SJ . Innate immunity, coagulation and placenta related adverse pregnancy outcomes[J]. Thromb Res, 2009, 124 (6): 656- 662.
doi: 10.1016/j.thromres.2009.07.012
25 孔德璇, 张志坤, 李慧东. 系统性红斑狼疮与孕产妇不良妊娠结局的相关性[J]. 中国妇幼保健, 2022, 37 (10): 1865- 1868.
26 Klein A , Molad Y . Hematological manifestations among patients with rheumatic diseases[J]. Acta Haematol, 2021, 144 (4): 403- 412.
doi: 10.1159/000511759
27 Wang F , Jia W , Fan M , et al. Single cell immune landscape of human recurrent miscarriage[J]. Genomics Proteomics Bioinformatics, 2021, 19 (2): 208- 222.
doi: 10.1016/j.gpb.2020.11.002
28 Cavazzana I , Franceschini F , Belfiore N , et al. Undifferentiated connective tissue disease with antibodies to Ro/SSa: Clinical features and follow-up of 148 patients[J]. Clin Exp Rheumatol, 2001, 19 (4): 403- 409.
29 Tektonidou MG , Andreoli L , Limper M , et al. EULAR recommendations for the management of antiphospholipid syndrome in adults[J]. Ann Rheum Dis, 2019, 78 (10): 1296- 1304.
doi: 10.1136/annrheumdis-2019-215213
30 Duan JN , Ma D , Wen XT , et al. Hydroxychloroquine prophylaxis for preeclampsia, hypertension and prematurity in pregnant patients with systemic lupus erythematosus: A meta-analysis[J]. Lupus, 2021, 30 (7): 1163- 1174.
doi: 10.1177/09612033211007199
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