未分化结缔组织病患者的妊娠结局、疾病演变及其影响因素

doi:10.19723/j.issn.1671-167X.2023.06.014

Abstract

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

Fang-ning YOU,Liang LUO,Xiang-jun LIU,Xue-wu ZHANG,Chun LI. Analysis of pregnancy outcomes, disease progression, and risk factors in patients with undifferentiated connective tissue disease[J].Journal of Peking University (Health Sciences), 2023, 55(6): 1045-1052.

Figures/Tables 6

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 1

Table 2

Table 3

Table 4

Figure 1

Table 5

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Variables	Univariate				Multivariate
Variables	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)

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)

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^*

CTD	Variables	Univariate					Multivariate
CTD	Variables	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)

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

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