Clinical and Obstetric Aspects of Pregnant Women with COVID-19: A Systematic Review

Bastos, Sarah Nilkece Mesquita Araújo Nogueira; Barbosa, Bárbara Louise Freire; Cruz, Larisse Giselle Barbosa; Souza, Rayza Pereira de; Melo, Simone Santos e Silva; Luz, Caroline Camargo Bandeira da Silveira

doi:10.1055/s-0041-1733913

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Review Article, Gynecological Endocrinology • Rev Bras Ginecol Obstet. 43 (12) • Oct 2021 • https://doi.org/10.1055/s-0041-1733913 linkcopy

Clinical and Obstetric Aspects of Pregnant Women with COVID-19: A Systematic Review

Aspectos clínicos e obstétricos de gestantes com COVID-19: Uma revisão sistemática

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective To analyze the clinical and obstetric aspects of pregnant women with COVID-19.

Methods A systematic literature review in the MEDLINE/PubMed, LILACS, SCIELO, and CNKI databases was performed from March to May 2020, with the descriptors: Pregnancy; 2019-nCov; Coronavirus; SARS-Cov-2, Covid-19. Of those chosen were original titles, without language and period restriction and that addressed pregnant women with a clinical and/or laboratory diagnosis of COVID-19. Revisions, editorials, and duplicate titles were excluded. The Newcastle-Ottawa (NOS) and Murad et al. scales were used to assess the quality of the studies.

Results We included 34 articles with 412 pregnant women infected with severe acute respiratory syndrome (SARS-Cov-2), with an average age of 27.5 years of age and 36.0 gestational weeks. The most common symptom was fever (205 [49.7%]), and 89 (21.6%) pregnant women progressed to severe viral pneumonia. Laboratory tests showed an increase in C-reactive protein (154 [37.8%]), and radiological tests showed pneumonia with peripheral ground-glass pattern (172 [51.4%]). Emergency cesarean delivery was indicated for most pregnant women, and the most common gestational complication was premature rupture of ovarian membranes (14 [3.4%;]). We detected 2 (0.5%) neonatal deaths, 2 (0.5%) stillbirths, and 1 (0.2%) maternal death.

Conclusion Pregnant women with COVID-19 presented a clinical picture similar to that of non-infected pregnant women, with few obstetric or neonatal repercussions. There was a greater indication of cesarean deliveries before the disease aggravated, and there was no evidence of vertical transmission of the infection.

Keywords
pregnancy; coronavirus infections; severe acute respiratory syndrome; SARS virus; betacoronavirus

PICO	MEANING	DESCRIPTORS
Population (P):	Pregnant women of any age	(("Pregnant Women" [MeSH Terms]))
Intervention (I):	COVID-19 infection	(("coronavirus" [MeSH Terms] OR "coronavirus" [All Fields]) OR ("COVID-19" [All Fields] OR"2019-nCoV" [All Fields] OR "SARS-CoV-2" [All Fields]).
Comparison (C):	Non-pregnant women	Not applicable
Outcomes (O):	COVID-19 interference in the pregnancy	(("Pregnancy" [MeSH Terms]))

Art	Author/ year/ country;	N	Diagnostic method	Maternal age	Trimester average GA	Main signs and symptoms	Radiological/laboratory manifestations	Maternal/gestational/fetal repercussions
1	Xiong et al. (2020)¹²; China	1	RT-PCR	(25)	2^nd (26 GW)	38°C fever, dry cough, and tremor	Radiological: pulmonary opacity Laboratory: neutrophilia and lymphocytopenia	Without repercussions
2	Li et al. (2020)¹⁵; China	16	RT-PCR	(31,5)26–37	3^rd (35 GW)	Fever (4;25.0%)	Radiological: bilateral pneumonia 43.75% (7) and unilateral pneumonia 50% (8) Laboratory: leukopenia and neutrophilia	14 (87.5%) Cesarean deliveries 3 (18.75%) Premature births, of which: 2 (66.67%) premature rupture of ovarian membranes (RPMO) and 1 (33.3%) bleeding 2 (12.5%) fetal distress
3	Chen et al. (2020)²⁷; China	5	RT-PCR	(28) 25–31	3^rd (39 GW)	Fever (after delivery) and dry cough (2;40.0%)	Radiological: bilateral pneumonia 60% (3) and 40% (2) unilateral Laboratory: increased CRP (4; 80.0%) and alkaline phosphates (4; 80.0%); leukopenia 40% (2)	2 (40.0%) Cesarean deliveries
4	Yu et al. (2020)¹³; China	7	RT-PCR	(32) 29–34	3^rd (39 GW)	Fever (86%;6), cough, dyspnea, and diarrhea (14%;1,each)	Radiological: 86% (6) bilateral pneumonia and 14% (1) unilateral Laboratory: neutrophilia (71%; 5), lymphopenia (71%; 5), thrombocytopenia (29%; 2) and elevation of D-dimer (100%; 7), alanine aminotransferase (29%; 2) and CRP (100%; 7)	Infected NB 36h after delivery
5	Kang et al. (2020)¹⁶; China	1	RT-PCR	30	3^rd (35 GW).	Cough	Radiological: pneumonia and bilateral pleural effusion Laboratory: Without changes	Emergency cesarean delivery Fetal bradycardia
6	Liu et al. (2020)⁴⁵; China	15	RT-PCR	32 (23–40)	1^st to 3^rd (12 to 38 GW).	Fever (86.6%; 13); Cough (60.0%; 9); fatigue (26.7%; 4); myalgia (20.0%; 3); dyspnea, odynophagia, and diarrhea (6.6%; 1, each)	Radiological: ground-glass opacity and late pulmonary consolidations Laboratory: lymphocytopenia (80.0%; 12) and increased value of C-reactive protein (66.6%; 10)	10 (66.6%) cesarean deliveries 3 (20.0%) premature births
7	Chen et al. (2020)¹⁴; China	9	RT-PCR	30 (26–40)	3^rd (37 GW)	Fever (77.7%; 7); Cough (44.4%; 4); myalgia (33.3%; 3); odynophagia and malaise (22.2%; 2, each)	Radiological: ground-glass opacity (88.8%; 8) Laboratory: lymphocytopenia (55.5%; 5), elevation of aminotransferases (33.3%; 3) and C-reactive protein-PCR (66.6%; 6)	9 (100.0%) cesarean deliveries 4 (44.4%) newborns had birth weight less than 2500 g 1 (11.1%) PROM
8	Liu et al. (2020)¹⁷; China	13	RT-PCR	29 (22–36)	2 patients in the 2^nd (26 GW); 11 patients in the 3^rd (35 GW)	Fever and fatigue (10; 77%); Dyspnea (3; 23%)	NR	10 (77%) cesarean deliveries, 5 (38.4%) of which were emergency 6 (46%) premature birth 3 (23%) fetal distress. 1 (7.6%) PROM 1 (7.6%) stillborn 1 (7.6%) maternal multiple organ dysfunction syndrome (MODS)
9	Li et al. (2020)¹⁸; China	1	RT-PCR	30	3^rd (35 GW)	Dry cough, fever, and dyspnea	Radiological: bilateral irregular pulmonary infiltrates Laboratory: slightly abnormal.	Emergency cesarean delivery Fetal bradycardia
10	Chen et al. (2020)¹⁹; China	3	RT-PCR	29,6 (23–34)	3^rd (36.6 GW)	Pre or postnatal fever (100%, 3) and chest pain (33.3%; 1).	Radiological: bilateral ground-glass opacities and bronchiectasis (100%, 3) Laboratory: significant increase in CRP (100%, 3)	3 (100.0%) cesarean deliveries 1 (33.3%) premature birth 1 (33.3%) premature placental displacement 1 (33.3%) placenta previa 1 (33.3%) NB with LBW
11	Zhang et al. (2020)²⁰; China	16	RT-PCR	29 (24–34)	3^rd (38 GW)	Cough; Chest pain; dyspnea, and diarrhea	NR	16 (100%) emergency cesarean section 3 (18.7%) premature births 2 (12.5%) fetal distress 3 (18.7%) rupture of membranes 1 (6.25%) fetal distress and fetal bradycardia 1 (6.25%) severe maternal pneumonia
12	Yan et al. (2020)²¹; China	116	RT-PCR	31 (24-41)	3^rd (38 GW) 1^st (4;3.4%) 2^nd (6;5.2%) 3^rd (96;91.4%)	27 (23.3%) asymptomatic Fever (50.9%; 59), cough (28.4%; 33), fatigue (12.9%; 15), dyspnea (7.8%; 9); odynophagia (8.6%; 10); myalgia (5.3%; 6); diarrhea (0.9%; 1)	Radiological: bilateral ground-glass pneumonia (96.3%; 104) Laboratory: lymphopenia and increased CRP (44.0%; 51), leukopenia (24.1%; 28)	99 deliveries, 85 (85.9%) of which were cesarean and 33 (38.8) indications due to COVID-19 21 (21.2%) premature births 6 (6.0%) PROM 1 abortion 1 neonatal death from asphyxiation. 8 (6.9%) severe pneumonia with ventilatory support
13	Ferrazzi et al. (2020)²²; Itália	42	RT-PCR	NR	NR	Dyspnea (20; 48%)	Radiological: interstitial pneumonia (20; 48.0%) Laboratory: NR	18 (43%) cesarean deliveries 2 (4.7%) premature births 7 (35%) severe pneumonia with ventilatory support
14	Kalafat et al. (2020)²³; Turquia	1	RT-PCR	32	3^rd (35 GW and 3 days)	Cough (1; 100%), dyspnea (1; 100%)	Radiological: bilaterally thick pulmonary B lines, located in the posterior basal segments of the lung Laboratory: NR	Premature cesarean delivery Reduced fetal movements
15	Wen et al. (2020)²⁴; China	1	RT-PCR	31	3^rd (30 GW)	Diarrhea. (1; 100%)	Radiological: irregular consolidation and bilateral ground-glass opacities, mainly distributed in the sub-plastic regions. Left pleural effusion Laboratory: NR	Without gestational changes
16	Fan et al. (2020)²⁵; China	2	RT-PCR	31 (29-34)	3^rd (36.5 GW)	Chills, fever (37.6±38.5°C), nasal congestion and odynophagia	Radiological: irregular consolidation and bilateral opacities Laboratory: lymphopenia (1; 50.0%)	2 (100%) Emergency cesarean delivery 2 (100%) NB had mild neonatal pneumonia
17	Pierce-Williams et al. (2020)²⁶; EUA	64	RT-PCR	33	3^rd (29.9 GW)	Fever, dyspnea	Radiological: NR Laboratory: elevation of ferritin, liver enzymes, CRP, interleukin-6, d-dimer, LDH, creatine phosphokinase (CPK)	44 (69.0%) severe pneumonia 20 (31.0%) critical illness 14(22.0%)SARS 24 cesarean deliveries 31 (48.4%) premature births, 15 in critical patients 19 (30.0%) invasive mechanical ventilation 1 cardiorespiratory arrest, without maternal mortality 3 (9.0%) postpartum hemorrhage 1 neonatal COVID-19 infection
18	Blauvelt et al.(2020)²⁸; EUA	01	RT-PCR	34	3^rd (28 GW)	Asthenia, fever, myalgia, cough, and dyspnea	Radiological: bilateral opacities in the lower lobes Laboratory: lymphopenia and lactate elevation, D-dimer, and CRP	Cesarean and premature delivery SARS, with the need to undergo invasive mechanical ventilation NB with respiratory distress
19	Hong et al. (2020)²⁹; China	01	RT-PCR e laboratorial	36	2^nd (23 weeks)	Fever, myalgia and dyspnea, cough, tachycardia	Radiological: opacities in pulmonary bases. Laboratory: lymphopenia and elevation of transaminases, CPK, and CRP	SARS, with the need to undergo invasive mechanical ventilation
20	Li et al. (2020)³⁰; China	01	RT-PCR	31	3^rd (35 GW)	Odynophagia, dry cough, fever, and dyspnea	Radiological: diffuse opacity in bilateral ground glass Laboratory: lymphopenia, respiratory acidosis and abnormal coagulogram, elevated CRP and interleukin 6	Premature cesarean delivery SARS with multiple organ dysfunction Neonatal death
21	Schnettler et al. (2020)³¹; EUA	01	RT-PCR	39	3^rd (31 GW)	Cough, dyspnea, fever, and asthenia	Radiological: peripheral diffuse opacities in bilateral ground glass Laboratory: leukopenia, lymphopenia, thrombocytopenia, elevated transaminases	Emergency and premature cesarean delivery. SARS, with the need to undergo invasive mechanical ventilation
22	Wu et al. (2020)³²; China	08	RT-PCR	29	(26–35)	3^rd (38 GW)	Fever on admission (1 ;12.5%), and fever in the postpartum period (3; 37.5%)	Radiological: peripheral diffuse opacities in bilateral ground glass (6; 75.0%) Laboratory: leukocytosis (6; 75.0%); lymphopenia (5; 62.5%), elevation of D-dimers and creatine kinase (CK) and creatine kinase-MB (CK-MB) in 4 (50.0%) in the postpartum period	6 (75.0%) Cesarean delivery 1 fetal distress
23	Peng et al. (2020)³³; China	01	RT-PCR	25	3^rd (35 SG)	Fever, fatigue and dyspnea	Radiological: peripheral diffuse opacities in bilateral ground-glass pattern Laboratory: NR	Emergency cesarean and premature delivery Fetal distress
24	Breslin et al. (2020)³⁴; EUA	43	RT-PCR	27 (20–39)	3^rd (37 SG)	Cough (19; 65.6%); fever (14; 48.3%); myalgia (11; 37.9%). headache (8; 27.6%); dyspnea (7; 24.1%); chest pain (5; 17.2%)	Radiological: peripheral diffuse opacities in bilateral ground-glass pattern (1; 2.32%) Laboratory: NR	Cesarean delivery (8; 44.4%) Premature birth (4; 13.8%) 1 PROM 2 (4.6%) severe maternal pneumonia 1 newborn with respiratory distress
25	Karami et al. (2020)³⁵; Irã	01	RT-PCR	27	3^rd (30 SG)	Dyspnea, fever, cough, myalgia, and tachypnea	Radiological: bilateral diffuse peripheral ground-glass opacities and pleural effusion Laboratory: leukopenia, thrombocytopenia, elevated CRP, lactic dehydrogenase (LDH) Echocardiogram: severe systolic dysfunction right	Maternal death from severe acute respiratory syndrome (SARS) and MODS; stillborn
26	Iqba et al. (2020)³⁶; EUA	01	RT-PCR	34	3^rd (39 GW)	Fever, cough, chills, and myalgia	Radiological: diffuse pulmonary opacities Laboratory: lymphopenia	NR
27	Xia et al. (2020)³⁷; China	01	RT-PCR	27	3^rd (36 GW)	Fever, cough, drop in oxygen saturation (92%)	Radiological: bilateral diffuse peripheral ground-glass opacities Laboratory: neutrophilia, lymphopenia, and elevated CRP	Cesarean delivery Fetal distress
28	Buonsenso et al. (2020)³⁸; Itália	07	RT-PCR	40	3^rd (36 GW)	Cough	Radiological: diffuse interstitial lung disease Laboratory: NR	2 (28.5%) Cesarean delivery 1 Premature Birth 1 Abortion 2 Neonatal COVID-19 infections
29	Qiancheng et al. (2020)³⁹; China	28	RT-PCR	30 (18–41)	3^rd (38 GW)	Fever (5; 17.9%), asthenia (1; 3.6%), cough (7; 25%), dyspnea (2; 7.1%), abdominal pain (5; 17.9%)	Radiological: bilateral peripheral diffuse ground-glass opacities (26; 92.9%) Laboratory: Leukocytosis (10; 35.7%), increased CRP (17; 68.0%), lymphopenia (8; 28.6)	17 (60.0%) Cesarean delivery 1 (4.3%) Premature birth 4 (14.2%) Induced abortion 2 (7.1%) Severe pneumonia
30	Lyra et al.(2020)⁴⁰; Portugal	01	RT-PCR	35	3^rd (39 GW)	Cough	NR	Cesarean delivery
31	Kelly et al. (2020)⁴¹; EUA	01	RT-PCR	–	3^rd (33 GW)	Vomiting, cough, and tachycardia	Radiological: Radiography showed subsegmental atelectasis without consolidation Laboratory: lymphopenia and mild elevation of liver enzymes	Cesarean and premature delivery 1 SARS, with the need to undergo invasive mechanical ventilation
32	Browne et al. (2020)⁴²; EUA	01	RT-PCR e Serological (IgG/lgM)	33	2^nd (23 GW)	Fever, cough, and myalgia	Radiological: NR Laboratory: leukocytosis	Premature cesarean delivery
33	Indraccolo (2020)⁴³; Itália	01	RT-PCR	NR	3^rd (32 GW)	Cough, epigastric pain, and chest pain	NR	NR
34	Lu et al. (2020)⁴⁴; China	01	RT-PCR	22	3^rd (38 GW)	Asymptomatic	Radiological: bilateral pleural effusion Laboratory: hyperproteinemia, elevated transaminases and LDH	Cesarean delivery
Total	N 412	Diagnostic method RTC-PCR (412;100%)	Average age 27.5		GA 36.0	Symptoms Fever (49.7%; 205); dyspnea (31.5%; 130); cough (26.5%; 109), fatigue (8.2%; 34); myalgia (7.0%; 29); chest pain (5.5%; 23), diarrhea (4.8%; 20); odynophagia (3.6%; 15)	Main radiological findings Pneumonia/ground-glass pattern (51.4%; 212), 51.5% (172) of which were bilateral Main laboratory findings Increased CRP (37.8%; 154); lymphopenia (20.3%; 84); leukopenia (14.2%; 58); neutrophilia (5.5%; 23);	Maternal and Gestacional repercussions Cesarean delivery (36.2%; 149); premature birth (18.4%; 76); abortion (1.0%; 4); PROM (3.4%; 14); hemorrhage (1.0%; 4); placental abruption (0.2%; 1);p previa (0.2%; 1); severe maternal pneumonia (21.6%; 89); maternal death (0.2%; 1); Fetal repercussions Stillborn (0.5%; 2); neonatal death (0.5%; 2); fetal distress (2.7%; 11); fetal bradycardia (0.7%; 3); LBW (1.0%; 4); neonatal COVID infection (1.0%; 4)

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[TFN1] Abbreviations: CRP, C-reactive protein; GA, gestational age; GW, gestational week; LBW, low birth weight; NB, newborn; NR, not reported; PROM, premature rupture of ovarian membranes; RT-PCR, reverse transcription polymerase chain reaction; SARS, severe acute respiratory syndrome.