Increased risk of early-onset preeclampsia in pregnant women with COVID-19

Figures & data

Table 1. Stratification of pregnant women with SARS-CoV-2 infection.

Maternal characteristics & clinical factors (N = 1929)	Severity of COVID-19			P value ^#	P value ^≠
	Asymptomatic (n = 1450)	Mild (n = 371)	Moderate–severe (n = 108)
Maternal age (years) [median (IQR)]	27 (24–30)	27 (24–30.5)	31 (27–33.25)	0.4549	<0.001
Gestational age (weeks) at the time of admission [median [IQR)]	39 (37–39)	37 (34–39)	32 (28–36)	<0.001	<0.001
≤28 weeks	24 (1.7)	45 (12.1)	28 (25.9)	<0.001^a	<0.001^†
28–34 weeks	71 (4.9)	67 (18.1)	46 (42.6)	<0.001^†	<0.001^†
>34 weeks	1355 (93.4)	259 (69.8)	34 (31.5)	Reference	Reference
Nulliparous	681 (47.0)	190 (51.2)	50 (46.3)	0.1439	0.8930
Multiple gestation	33 (2.3)	9 (2.4)	3 (2.8)	0.8636	0.7346
In vitro fertilization	29 (2.0)	7 (1.9)	3 (2.8)	0.8888	0.4826
Diabetes mellitus	9 (0.6)	1 (0.3)	4 (3.7)	0.6973	0.0096
Gestational diabetes mellitus	41 (2.8)	12 (3.2)	8 (7.4)	0.6774	0.0169
Chronic hypertension	11 (0.8)	6 (1.6)	3 (2.8)	0.1329	0.0673
Bronchial asthma	12 (0.8)	1 (0.3)	2 (1.9)	0.4865	0.2526
Severe anemia (Hb <7 gm %)	13/1366 (1.0)	3/359 (0.8)	4/108 (3.7)	>0.999	0.0308
Cardiac disease	11 (0.8)	4 (1.1)	3 (2.8)	0.5232	0.0673
de novo hypertension in pregnancy	185 (12.8)	49 (13.2)	13 (12.0)	0.8176	0.8280
Gestational hypertension	96 (6.6)	20 (5.4)	6 (5.6)	0.3867	0.6659
Preeclampsia/Eclampsia	89 (6.1)	29 (7.8)	7 (6.5)	0.2411	0.8861
Preterm birth^a	125/1170 (10.7)	35/222 (15.8)	14/71 (19.7)	0.0295	0.0191
Intrauterine fetal death^a	17/1170 (1.5)	9/222 (4.1)	4/71 (5.6)	0.0148	0.0281
Maternal death^a	0	1/222 (0.5)	43/71 (60.6)	-	-
Comparison between three waves of COVID-19
First wave	950 (65.5)	128 (34.5)	25 (23.1)	Reference	Reference
Second wave	331 (22.8)	123 (33.2)	81 (75.0)	<0.001	<0.001
Third wave	169 (11.7)	120 (32.3)	2 (1.9)	<0.001	0.4112

^aTotal pregnancy outcome includes all deliveries, abortions beyond 20 weeks and maternal mortality (n = 1463).

#Comparison was made between mild versus asymptomatic.

≠Comparison was made between moderate-severe versus asymptomatic.

†Gestational weeks>34 was considered as a reference category for<28 weeks and 28–34 weeks.

Mild COVID-19 was defined as patients with uncomplicated upper respiratory tract infection with mild symptoms such as fever, cough, sore throat, nasal congestion, malaise, headache without shortness of breath or Hypoxia [10].

Moderate COVID-19 was defined as pneumonia with no signs of severe disease. It included patients with presence of clinical features of dyspnea and or hypoxia, fever, cough, including SpO2 90 to≤93% on room air, respiratory rate more or equal to 24 per minute [10].

Severe COVID-19 was defined as patients with severe pneumonia, acute respiratory distress syndrome, sepsis or septic shock. It included women with clinical signs of pneumonia plus one of the following; respiratory rate>30 breaths/min, severe respiratory distress, SpO2 < 90% on room air[10].

Table 2. Association of maternal and clinical characteristics of women with COVID-19 who developed early and late-onset preeclampsia.

Maternal characteristic & clinical factors	Early onset preeclampsia	Late-onset preeclampsia	Early onset^a preeclampsia	Late-onset preeclampsia
n = 1929	n = 32%)	n = 93%)	uOR (95% CI)	uOR (95% CI)	P value
Incidence rate per 100	11.4^†	5.6^††	2.15 (1.41–3.28)	0.47 (0.31–0.71)	0.0003
Maternal age (years) >35	5 (15.6)	10 (10.8)	1.54 (0.48–4.89)	0.65 (0.20–2.07)	0.530
Severity of COVID-19 disease
Asymptomatic	18 (56.3)	71 (76.3)	Reference	Reference
Symptomatic	14 (43.8)	22 (23.7)	2.51 (1.08–5.85)	0.40 (0.17–0.93)	0.0304
Pregnancy characteristics
Nulliparous	19 (59.4)	52 (55.9)	1.15 (0.51–2.61)	0.87 (0.38–1.96)	0.7332
Multiple gestation	2 (6.3)	3 (3.2)	2.00 (0.32–12.55)	0.50 (0.08–3.14)	0.6016
IVF conception	3 (9.4)	4 (4.3)	2.30 (0.49–10.89)	0.43 (0.09–2.06)	0.3708
Previous spontaneous abortion	6 (18.8)	13 (14.0)	1.42 (0.49–4.11)	0.70 (0.24–2.04)	0.5707
Previous still birth	4 (12.5)	2 (2.2)	6.50 (1.13–37.38)	0.15 (0.03–0.89)	0.0370
Gestational diabetes mellitus	2 (6.3)	3 (3.2)	2.00 (0.32–12.55)	0.50 (0.08–3.14)	0.6016
Comorbidities/Co-infections
Chronic hypertension	0	8 (8.6)	-	-	-
Bronchial asthma	0	1 (1.1)	-	-	-
Hypothyroidism	2 (6.3)	12 (12.9)	0.45 (0.10–2.13)	2.22 (0.47–10.52)	0.5160
Tuberculosis	3 (9.4)	1 (1.1)	9.52 (0.95–95.1)	0.11 (0.01–1.05)	0.0513
Malaria/Dengue	1 (3.1)	1 (1.1)	2.97 (0.18–48.9)	0.34 (0.02–5.55)	0.448
Anemia (Hb <11 gm %)	19/32 (59.4)	42/91 (46.2)	1.71 (0.75–3.86)	0.59 (0.26–1.33)	0.1982
Comparison between three waves
First wave	13 (40.6)	51 (54.8)	Reference	Reference
Second wave	8 (25.0)	28 (30.1)	1.12 (0.41–3.03)	0.89 (0.33–2.41)	0.8219
Third wave	11 (34.4)	14 (15.1)	3.08 (1.14–8.36)	0.32 (0.12–0.88)	0.0236
Pregnancy complications & Adverse outcomes (n = 1463) ^a	n = 30	n = 88
Cesarean birth	12 (40.0)	47 (53.4)	0.58 (0.25–1.35)	1.72 (0.74–3.99)	0.2046
Abruption placentae	1 (3.3)	2 (2.3)	1.48 (0.13–16.9)	0.67 (0.6–7.72)	>0.999
Intrauterine fetal death	5 (16.7)	4 (4.5)	4.20 (1.05–16.84)	0.24 (0.06–0.96)	0.0454
Postpartum hemorrhage	1 (3.3)	5 (5.7)	0.57 (0.06–5.11)	1.75 (0.20–15.6)	>0.999
Maternal mortality	3 (10.0)	1 (1.1)	9.67 (0.97–96.8)	0.10 (0.01–1.04)	0.0501

^aTotal pregnancy outcome includes all deliveries, abortions beyond 20 weeks and maternal mortality.

^bEarly onset PE rate per 100 was calculated from pregnant women who had gestational weeks of < 34 (n = 281) and ^††Late-onset PE rate per 100 from pregnant women who had gestational weeks≥34 (n = 1648).

^cThe post-partum hemorrhage was defined as intrapartum or post-partum (within 24 hours) accompanied by signs and symptoms of hypovolemia within 24 hours of birth process regardless of route of delivery.

Table 3. Association of severity of COVID-19 disease and preeclampsia (early onset and late-onset PE).

Total pregnant women	PE	Without PE	Women with PE				Early onset PE	Late-onset PE	Early onset PE
(N = 1929)	(n = 125)	(n = 1804)	uOR (95% CI)	P value	aOR * (95% CI)	P value	(n = 32)	(n = 93)	uOR (95% CI)	P value	aOR # (95% CI)	P value
Asymptomatic	89 (71.2)	1361 (75.4)	Reference		Reference		18 (56.3)	71 (76.3)	Reference		Reference
Mild	29 (23.2)	342 (19.0)	1.30 (0.84–2.00)	0.2423	1.20 (0.77–1.88)	0.4242	10 (31.3)	19 (20.4)	2.08 (0.82–5.23)	0.1213	1.99 (0.72–5.45)	0.1834
Moderate to severe	7 (5.6)	101 (5.6)	1.06 (0.48–2.35)	0.8861	0.83 (0.36–1.91)	0.6544	4 (12.5)	3 (3.2)	5.26 (1.08–25.63)	0.0399	8.13 (1.56–42.46)	0.0129

*Adjusted with maternal age>35 years, chronic hypertension, bronchial asthma, GDM, multiple gestation, nulliparous, IVF conception, previous history of abortion and still birth.

#Adjusted with maternal age>35 years,GDM, multiple gestation, nulliparous, IVF conception, previous history of abortion and still birth.

PE- Preeclampsia; uOR- unadjusted odds ratio; aOR- adjusted odds ratio.