New Benefits of Hydroxychloroquine in Pregnant Women with Systemic Lupus Erythematosus: A Retrospective Study in a Tertiary Centre

Rahman, Rahana Abd; Tun, Kyaw Min; Atan, Ixora Kamisan; Said, Mohd Shahrir Mohamed; Mustafar, Ruslinda; Zainuddin, Ani Amelia

doi:10.1055/s-0040-1715140

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Original Article • Rev. Bras. Ginecol. Obstet. 42 (11) • Nov 2020 • https://doi.org/10.1055/s-0040-1715140 copy

New Benefits of Hydroxychloroquine in Pregnant Women with Systemic Lupus Erythematosus: A Retrospective Study in a Tertiary Centre

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective:

To determine pregnancy outcomes in women with systemic lupus erythematosus (SLE) who were treated with hydroxychloroquine in a tertiary center.

Methods:

A retrospective study involving pregnant women with SLE who had antenatal follow-up and delivery in between 1 January 2007 and 1 January 2017. All participants were retrospectively enrolled and categorized into two groups based on hydroxychloroquine treatment during pregnancy.

Results:

There were 82 pregnancies included with 47 (57.3%) in the hydroxychloroquine group and 35 (42.7%) in the non-hydroxychloroquine group. Amongst hydroxychloroquine users, there were significantly more pregnancies with musculoskeletal involvement (p = 0.03), heavier mean neonatal birthweight (p = 0.02), and prolonged duration of pregnancy (p = 0.001). In non-hydroxychloroquine patients, there were significantly more recurrent miscarriages (p = 0.003), incidence of hypertension (p = 0.01) and gestational diabetes mellitus (p = 0.01) and concurrent medical illness (p = 0.005). Hydroxychloroquine use during pregnancy was protective against hypertension (p = 0.001), and the gestational age at delivery had significant effect on the neonatal birthweight (p = 0.001). However, duration of the disease had a significant negative effect on the neonatal birthweight (p = 0.016).

Conclusion:

Hydroxychloroquine enhanced better neonatal outcomes and reduced adverse pregnancy outcomes and antenatal complications such as hypertension and diabetes.

Keywords:
hydroxychloroquine; systemic lupus erythematosus; pregnancy

	HCQn = 47 (57.3%)	Non HCQn = 35 (42.7%)	OR (95%CI)p-value
Mean age ± SD (years old)	32.03 ± 3.92	31.50 ± 3.54	0.82^a a Student’s t-test.
Ethnicity, n (%)			0.99^b b Contingency coefficient, df = 2.
Malay	35 (74.5)	26 (74.3)
Chinese	9 (19.1)	7 (20.0)
Indian	3 (6.4)	2 (5.7)
Parity, n (%)			0.47 (0.18–1.21)
Primipara	20 (42.6)	9 (25.7)	0.12^c c Chi-square test.
Multipara	27 (57.4)	26 (74.3)

	HCQn = 47	Non HCQn = 35	OR (95%CI)p-value
Presence of antiphospholipid antibody, n (%)			0.11^a a Student's t-test.
No	36 (76.6)	21 (60.0)
Yes	11 (23.4)	14 (40.0)
Mean disease duration ± SD (years)	7.06 ± 4.24	6.57 ± 3.56	0.44^a a Student's t-test.
System involvement, n (%)
Musculoskeletal	29 (61.7)	13 (37.1)	2.63 (1.06–6.51)
			0.03^c c Chi-square test, difference expressed in odds ratio (95% CI), ITP-idiopathic thrombcytopenic purpura.
Lupus nephritis	23 (48.9)	22 (62.9)	0.54 (0.22–1.33)
			0.18^c c Chi-square test, difference expressed in odds ratio (95% CI), ITP-idiopathic thrombcytopenic purpura.
Hematology	24 (51.1)	12 (34.3)	2.09 (0.85–5.18)
			0.11^c c Chi-square test, difference expressed in odds ratio (95% CI), ITP-idiopathic thrombcytopenic purpura.
CNS	0	3 (8.6)	0.91 (0.83–1.01)
			0.07^c c Chi-square test, difference expressed in odds ratio (95% CI), ITP-idiopathic thrombcytopenic purpura.
Recurrent miscarriage, n (%)	0	6 (17.1)	0.83 (0.71–0.96)
			0.003^c c Chi-square test, difference expressed in odds ratio (95% CI), ITP-idiopathic thrombcytopenic purpura.
Concurrent medical illness, n (%)	7 (14.9)	15 (42.9)	0.23 (0.08–0.66)
Secondary hypertension	2 (4.3)	6 (15.8)	0.005^c c Chi-square test, difference expressed in odds ratio (95% CI), ITP-idiopathic thrombcytopenic purpura.
Chronic kidney disease	0	4 (10.5)
Thyroid disease	1 (2.1)	2 (5.3)
Heart disease	1 (2.1)	5 (13.2)
ITP	2 (4.3)	1 (2.6)
Steroids use pre pregnancy, n (%)	45 (95.7)	29 (82.9)	0.05^b b contingency coefficient, df = 2.
5–10 mg	32 (71.1)	20 (68.9)
10–20 mg	5 (11.1)	4 (13.9)
> 20 mg	8 (17.8)	5 (17.2)
Steroids use during pregnancy, n (%)	45 (95.7)	31 (88.6)	0.22^b b contingency coefficient, df = 2.
5–10 mg	28 (62.2)	19 (61.3)
10–20 mg	11 (24.4)	7 (22.6)
> 20 mg	6 (13.6)	5 (16.1)
Immunosuppressive drugs prepregnancy, n(%)	23(48.9)	20(57.1)	0.46^b b contingency coefficient, df = 2.
Azathioprine	16 (34.0)	13 (37.1)
Cyclosporin A	7 (14.9)	2 (5.7)
Both	0	4 (11.4)
Immunosuppressive drugs during pregnancy, n (%)	25 (53.2)	23 (67.7)	0.26^b b contingency coefficient, df = 2.
Azathioprine	17 (36.2)	18 (51.4)
Cyclosporin A	6 (12.8)	2 (5.7)
Both	2 (4.3)	3 (8.6)

	HCQn = 47	Non HCQn = 35	OR (95% CI)p value
Antenatal complication
Hypertension in pregnancy	3 (6.4)	15 (42.9)	0.09 (0.02–0.35)
			0.01^c c Chi-squared test, difference expressed in odds ratio (95% CI).
Gestational diabetes mellitus	0	5 (14.3)	0.86 (0.75–0.98)
			0.01^c c Chi-squared test, difference expressed in odds ratio (95% CI).
Mean duration of pregnancy ± SD (week)	36.74 ± 2.01	34.79 ± 4.21	0.001^a a Student's t-test.
Fetal loss ≥ 24 weeks, n (%)	2 (5.3)	2 (7.1)	0.72 (0.09–5.47)
			0.75^c c Chi-squared test, difference expressed in odds ratio (95% CI).
Gestational age at birth, n (%)			0.25^b b Contingency coefficient, df = 2.
Term livebirth (≥ 37 weeks)	26 (55.3)	14 (40.0)
Preterm livebirth (< 37 weeks)	11 (23.4)	14 (40.0)
Miscarriage (< 24 weeks)	10 (21.3)	7 (20.0)
Mean birthweight (kg) ± SD (range)	2.52 ± 0.56	2.13 ± 0.79	0.02^a a Student's t-test.
Intrauterine growth restriction, n (%)	6 (16.7)	10 (35.7)	0.36 (0.11–1.16)
			0.08^c c Chi-squared test, difference expressed in odds ratio (95% CI).
Mode of delivery, n (%)
Vaginal	18 (47.9)	13 (43.3)	0.91^b b Contingency coefficient, df = 2.
Assisted vaginal	3 (7.9)	2 (6.7)
Caesarean section	17 (44.7)	15 (50.0)
Apgar score
≥ 7 in 5 minutes	34 (94.4)	22 (78.6)	0.22 (0.04–1.17)
< 7 in 5 minutes	2 (5.6)	6 (21.4)	0.06^c c Chi-squared test, difference expressed in odds ratio (95% CI).
NICU admission	4 (11.1)	5 (19.2)	0.53 (0.13–2.18)
			0.37^c c Chi-squared test, difference expressed in odds ratio (95% CI).
Indication for LSCS			0.53^b b Contingency coefficient, df = 2.
Preeclampsia	2 (11.8)	5 (33.3)
Fetal Distress	7 (5.9)	2 (13.3)
Worsening Lupus	1 (5.9)	2 (13.3)
Failed IOL/ Poor Progress	2 (11.8)	2 (13.3)
Maternal Request/ Refuse TOS	4 (23.5)	1 (6.7)
Breech	1 (5.9)	1 (6.7)

	Multivariate Model I		Multivariate Model II
	aOR (95% CI)	p-value	aß (95% CI)	p-value
HCQ usage	0.08 (0.02–0.36)	0.001	0.002 (−0.45–0.45)	0.67
Maternal age (years old)	1.04 (0.88–1.23)	0.63	0.01 (−0.02–0.03)	0.33
Concurrent medical illness	0.65 (0.15–2.91)	0.58	−0.12 (−0.30–0.07)	0.21
Immunosuppressive treatment	4.48 (0.92–21.88)	0.06	0.002 (−0.17–0.17)	0.98
Lupus nephritis	1.53 (0.34–6.77)	0.58	0.07 (−0.11–0.24)	0.45
Gestational age at delivery (week)	–		0.19 (0.16–0.21)	0.001
Duration of SLE (years)	–		−0.03 (−0.05 to −0.01)	0.016

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[1] Address for correspondence Rahana Abd Rahman, PhD Universiti Kebangsaan Malaysia Medical Centre Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur Malaysia drrahana@ppukm.ukm.edu.my