Clinical Features and Outcomes of Twin Pregnancies with Antiphospholipid Antibodies Positivity: A Retrospective Study

Figures & data

Figure 1 The flow diagram for patient selection.

Table 1 Demographics and Baseline Characteristics of twin-pregnant women with negative and positive aPL

Characteristics	Entire Cohort of Twin Pregnancies				PSM Cohort of Twin Pregnancies
	aPL Negative (n=747)	aPL Positive (n=26)	P value	SMD	aPL Negative (n=48)	aPL Positive (n=24)	P value	SMD
Maternal age, years	32.66 ± 4.16	33.69 ± 2.71	0.07	0.29	33.92 ± 3.68	33.63 ± 2.72	0.71	0.09
Maternal age ≥35, n (%)	234 (31.33)	10 (38.46)	0.44	—	15 (31.25)	9 (37.50)	0.73	—
BMI, kg/m^2	29.44 ± 4.68	29.12 ± 3.40	0.65	—	28.24 ± 4.28	29.10 ± 3.50	0.37	—
Weight gain, kg	16.33 ± 6.29	15.79 ± 6.37	0.69	0.08	15.44 ± 6.16	15.79 ± 6.37	0.83	0.056
Parity	0 (0,1)	0 (0,1)	0.31	0.43	1 (1,2)	2 (1,3)	0.03*	0.09
Primiparity, n (%)	624 (83.53)	25 (96.15)	0.09	—	45 (93.75)	23 (95.83)	0.72	—
Multiparity, n (%)	123 (16.47)	1 (3.85)	0.09	—	3 (6.25)	1 (4.17)	0.72	—
SBP, mm Hg	126.12 ± 14.62	127.23 ± 15.54	0.72	—	124.42 ± 11.75	127.33 ± 14.57	0.40	—
DBP, mm Hg	75.84 ± 10.77	77.46 ± 12.76	0.53	—	76.92 ± 8.39	76.58 ± 12.56	0.91	—
Chorionicity
Monochorionic, n (%)	157 (21.02)	2 (7.69)	0.08	0.42	5 (10.42)	2 (8.33)	0.78	0.07
Dichorionic, n (%)	545 (72.96)	24 (92.31)	0.08	—	43 (89.58)	22 (91.67)	0.78	0.07
Mode of conception
Spontaneous, n (%)	303 (40.56)	2 (7.69)	0.001*	—	4 (8.33)	2 (8.33)	1.00	—
ART, n (%)	444 (59.44)	24 (92.31)	0.001*	0.83	44 (91.67)	22 (91.67)	1.00	0.00
Mode of delivery
Vaginal, n (%)	42 (5.62)	0 (0)	0.81	—	1 (2.08)	0 (0)	0.50	—
Caesarean, n (%)	679 (90.90)	24 (92.31)	0.81	—	47 (97.92)	22 (91.67)	0.50	—
Comorbidities
PCOS, n (%)	50 (6.69)	3 (12.50)	0.34	0.17	5 (10.42)	2 (8.33)	0.78	0.07
Preeclampsia, n (%)	131 (17.54)	6 (25.00)	0.47	—	8 (16.67)	5 (20.83)	0.67	—
Diabetes mellitus, n (%)	203 (27.18)	8 (33.33)	0.69	0.08	14 (29.17)	7 (29.17)	1.00	0.00
Thyroid diseases, n (%)	135 (18.07)	6 (25.00)	0.52	0.12	10 (20.83)	6 (25.00)	0.69	0.09
Platelet count, ×10^9/L	192.52 ± 58.26	191.08 ± 47.84	0.88	0.03	185.63 ± 52.81	190.04 ± 43.20	0.71	0.09

Notes: All data are presented as mean ± standard deviation, median, interquartile range, or n (%). *P < 0.05.

Abbreviations: aPL, antiphospholipid antibodies; ART, Assisted reproductive technology; BMI, body mass index; DBP, diastolic blood pressure; PCOS, polycystic ovary syndrome; SBP, systolic blood pressure.

Figure 2 Distribution of pregnancy outcomes of twin pregnancy with aPL positivity.

Table 2 Maternal and Fetal Outcomes of Control and Twin Pregnancy with aPL Positivity in PSM Cohort

	Control in Twin Pregnancies (n=48)	Twin Pregnancy with aPL Positivity (n=24)	P value^a	aOR	P value^b
Adverse pregnancy outcomes, n (%)	36 (75.00)	19 (79.17)	0.70	0.51 (−0.89, 1.91)	0.48
Abortion, n (%)	0 (0)	2 (8.33)	0.043*	—	—
Stillbirth^#, n (%)	0 (0)	1 (4.17)	0.15	—	—
Preterm birth < 37 weeks, n (%)	25 (52.08)	14 (58.33)	0.61	0.37 (−0.79, 1.53)	0.54
Preterm birth < 34 weeks, n (%)	4 (8.33)	8 (33.33)	0.007*^c	2.76 (0.83, 4.70)	0.005*
PROM, n (%)	9 (18.75)	5 (20.83)	0.83	0.37 (−0.97, 1.71)	0.58
PPROM, n (%)	6 (12.50)	5 (20.83)	0.35	0.82 (−0.59, 2.23)	0.26
Low birthweight (<2500 g)^#, n (%)	27 (56.25)	15 (62.50)	0.34	0.97 (−0.36, 2.30)	0.15
Very low birthweight (<1500 g)^#, n (%)	2 (4.17)	5 (20.83)	0.016*^d	2.40 (0.18, 4.67)	0.034*
SGA^#, n (%)	16 (33.33)	12 (50.00)	0.09	1.66 (0.22, 3.10)	0.024*
Preeclampsia, n (%)	8 (16.67)	5 (20.83)	0.66	0.13 (−1.30, 1.55)	0.86
Thrombocytopenia, n (%)	5 (10.42)	3 (12.50)	0.79	0.22 (−1.49, 1.93)	0.80
ICU admission, n (%)	1 (2.08)	3 (12.50)	0.06	2.03 (−0.56, 4.61)	0.13

Notes: All data are presented as the mean ± standard deviation or n (%). ^#The number of pregnancies in which at least one fetus in the twin pregnancy had this outcome. ^aP value was calculated for the difference in the percentage of pregnancy outcomes between control and twin pregnancies with aPL positivity. ^bP value was calculated for the aOR of pregnancy outcomes. Multivariate analysis was adjusted for maternal age, gravidity, weight at admission, BMI, thyroid diseases and diabetes mellitus. ^cSignificant in the univariate analysis, P = 0.012 (OR = 1.70, 95% CI 0.38–3.03). ^dSignificant in the univariate analysis, P = 0.03 (OR = 1.91, 95% CI 0.18–3.64). *P < 0.05.

Abbreviations: aPL, antiphospholipid antibodies; ICU, intensive care unit; PROM, premature rupture of membrane; PPROM, preterm premature rupture of membranes; SGA, small for gestational age.

Figure 3 Forest plot of risk factors for preterm birth < 34 weeks (A), very low birthweight (<1500 g) (B) and SGA (C).

Table 3 Clinical Characteristics and Treatments of Twin-Pregnant Women with aPL Positivity

Characteristics	Non-Adverse Pregnancy Outcomes (n=5)	Adverse Pregnancy Outcomes (n=19)	P value
Maternal age, years	33.20 ± 1.48	33.73 ± 2.98	0.58
Maternal age ≥ 35, n (%)	1 (20.00)	8 (42.11)	0.36
BMI, kg/m^2	29.55 ± 3.63	28.98 ± 3.57	0.76
Weight gain, kg	18.00 ± 5.87	15.21 ± 6.52	0.39
Parity	0 (0,1)	0 (0,1)	0.21
Primiparity, n (%)	4 (80.00)	19 (100.00)	0.046*
Multiparity, n (%)	1 (20.00)	0 (0)	0.046*
Chorionicity
Monochorionic, n (%)	1 (20.00)	1 (5.26)	0.29
Dichorionic, n (%)	4 (80.00)	18 (94.74)	0.29
Mode of conception
Spontaneous, n (%)	0 (0)	2 (10.53)	0.45
ART, n (%)	5 (100.00)	17 (89.47)	0.45
Mode of delivery
Vaginal, n (%)	0 (0)	0 (0)	—
Caesarean, n (%)	5 (100.00)	17 (89.47)	0.57
Comorbidities
PCOS, n (%)	0 (0)	2 (10.53)	0.45
Preeclampsia, n (%)	0 (0)	5 (26.32)	0.20
Diabetes mellitus, n (%)	1 (20.00)	6 (31.58)	0.61
Thyroid diseases, n (%)	0 (0)	6 (31.58)	0.15
Thrombocytopenia, n (%)	2 (40.00)	1 (5.26)	0.037*
Treatment
No treatment, n (%)	0 (0)	2 (10.53)	0.45
LDA, n (%)	1 (20.00)	12 (63.16)	0.08
LMWH, n (%)	5 (100.00)	14 (73.68)	0.20
LDA+LMWH, n (%)	1 (20.00)	6 (31.58)	0.61
Hydroxychloroquine, n (%)	0 (0)	4 (21.05)	0.26
Corticosteroids, n (%)	1 (20.00)	5 (26.32)	0.77

Note: *P < 0.05.

Abbreviations: aPL, antiphospholipid antibodies; ART, Assisted reproductive technology; BMI, body mass index; PCOS, polycystic ovary syndrome; LDA, low-dose aspirin; LMWH, low-molecular-weight heparin.

Table 4 aPL Profile in Twin-Pregnant Women with or Without Adverse Pregnancy Outcomes

Serological Profile	Non-Adverse Pregnancy Outcomes (n=5)	Adverse Pregnancy Outcomes (n=19)	P value
LA positivity, n (%)	4 (80.00)	14 (73.68)	0.88
aCL positivity, n (%)	1 (20.00)	7 (36.84)	0.36
Anti-β2GPI positivity, n (%)	0 (0)	2 (10.53)	0.16
Single aPL positivity, n (%)	4 (100.00)	17 (89.47)	0.91
Single LA positivity, n (%)	4 (80.00)	12 (63.16)	0.89
Single aCL positivity, n (%)	1 (20.00)	5 (26.32)	0.65
Triple aPL positivity, n (%)	0 (0)	2 (10.53)	0.16

Abbreviations: aCL, anticardiolipin; aPL, antiphospholipid antibody; anti-β2GPI, anti-β2 glycoprotein I; LA, lupus anticoagulant.

Table 5 Coagulation Function of Control and Twin Pregnancy with aPL Positivity in PSM Cohort

	Control Group in Twin Pregnancies				Twin Pregnancies with aPL Positivity
	Non-Adverse Pregnancy Outcomes (n=12)	Adverse Pregnancy Outcomes (n=36)	t	P value	Non-Adverse Pregnancy Outcomes (n=5)	Adverse Pregnancy Outcomes (n=19)	t	P value
PT	10.26 ± 0.56	10.26 ± 0.67	<0.01	1.00	10.26 ± 0.93	10.20 ± 0.80	0.13	0.90
APTT	27.23 ± 2.04	27.4 ± 2.14	−0.27	0.79	28.30 ± 1.55	27.50 ± 2.98	0.82	0.43
TT	17.48 ± 1.32	18.35 ± 1.74	−1.82	0.08	17.26 ± 1.04	18.77 ± 1.77	−2.44	0.03*
FIB	4.61 ± 0.71	4.40 ± 0.83	0.83	0.41	4.05 ± 3.43	5.02 ± 1.41	−2.49	0.02*
D-dimer	4520.58 ± 1810.40	3436.97 ± 1660.12	1.83	0.08	3501.20 ± 1375.82	2916.05 ± 1912.47	0.77	0.46

Note: *P < 0.05.

Abbreviations: aPL, antiphospholipid antibodies; APTT, activated thromboplastin time; FIB, fibrinogen; PT, prothrombin time; TT, thrombin time.