WHO REGIONAL OFFICE FOR AFRICA COVID-19 RAPID POLICY BRIEF SERIES

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WHO REGIONAL OFFICE FOR AFRICA COVID-19 RAPID POLICY BRIEF SERIES SERIES 4: COVID-19 AND THE PREGNANCY PROCESS

NUMBER 004-01: Labour and delivery outcomes of pregnant women diagnosed with COVID-19

Based on information as at 25 May 2020

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Labour and delivery outcomes of pregnant women diagnosed with COVID-19

WHO/AF/ARD/DAK/10/2020

© WHO Regional Office for Africa 2020

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RAPID POLICY BRIEF

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NUMBER: 004-01 RESEARCH DOMAIN: COVID-19 COVID-19 & Pregnancy

TITLE: Labour and delivery outcomes of pregnant women diagnosed with COVID-19 RAPID POLICY BRIEF NUMBER: 004-01

1 RAPID POLICY BRIEF NUMBER: 004-01

2 RESEARCH DOMAIN:

COVID-19 & Pregnancy

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TITLE: Labour and delivery outcomes of pregnant women diagnosed with COVID-19

4 DATE OF PUBLICATION: 22/06/2020

5 BACKGROUND

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world, provoking disruption well beyond loss of life and livelihood in over 200 countries and territories. The coronavirus disease 2019 (COVID-19) caused by this pathogen has affected many vulnerable people, including pregnant women. Susceptibility of pregnant women to COVID-19 is believed to result from the physiological changes associated with pregnancy, such as altered cell immunity, decreased pulmonary capacity, and variations in blood flow [1,2]. In previous outbreaks of coronaviruses, mortality rates among pregnant women were higher than in the general population, between 18 and 25% for Severe Acute Respiratory Syndrome (SARS) and as high as 37% for Middle East respiratory syndrome (MERS) [3,4]. Similarly, a large proportion of pregnant patients required mechanical ventilation, with up to 35% during the SARS outbreak and 41%

during MERS [4,5]. Some studies also suggest that coronavirus infection may be associated with spontaneous miscarriage, preterm delivery, and foetal growth restriction [6]. This policy brief summarises evidence on the impact of COVID-19 on pregnancy and its outcomes.

6 SEARCH STRATEGY / RESEARCH METHODS

A systematic search of the following databases was conducted to obtain peer-review literature published between 1 December 2019 and 25 May 2020: WHO COVID-19 database; PubMed, and IRIS (WHO Institutional Repository for Information Sharing), using search terms to denote pregnancy and outcomes of obstetric delivery in COVID-19 patients. As different databases apply different index terms, the searches corresponded to: “pregnancy OR pregnant” AND “delivery OR childbirth OR labor OR labour”; (covid 19 pregnancy) AND ((delivery) OR (childbirth)); and ("COVID-19"[MeSH] OR "Covid19"[MeSH]) AND ("Pregnancy"[MeSH] OR "Pregnant Women"[MeSH]) AND ("Delivery, Obstetric"[MeSH]). Adding the search term: “Africa OR African” to the key concepts of pregnancy and obstetric delivery did not generate any results. The initial search yielded 349 publications. Relevant studies were retained based on predefined inclusion criteria; others were systematically removed based on exclusion criteria and duplication of results across the databases. Finally, full texts of 34 papers were retrieved and reviewed to inform this policy brief.

7 SUMMARY OF GLOBALLY PUBLISHED LITERATURE RELATED TO THE SUBJECT

As early adaptive immune system responses project less severe manifestations of disease, there is evidence to suggest that pregnant women infected with SARS-CoV-2 are less likely to suffer severe outcomes than those who had been infected with SARS and MERS [2,7]. However, studies on the impact of COVID-19 on pregnancy and its outcomes present a mixed picture. Four studies show that the recovery rate among pregnant COVID-19 patients is good, and few of these patients and their newborns have presented with severe disease requiring intensive care measures such as ventilation or oxygen therapy [8–11]. Additionally, some research suggests a low rate of severe disease in women who initially present without symptoms and that most asymptomatic women will remain asymptomatic [12,13]. In contrast, two studies show deterioration of the maternal condition and adverse effects of peri-natal SARS-CoV-2 [14,15]. It is

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RAPID POLICY BRIEF NUMBER: 004-01

therefore important to err on the side of caution and ensure that all pregnant women and their newborns receive appropriate care and counselling during the COVID-19 pandemic [16].

In an analysis of 38 pregnant women by Schwartz, no maternal deaths were shown to have occurred – a different result than SARS and MERS – and no cases of intrauterine transmission of SARS-CoV-2 from mother to neonate were confirmed – a similar finding to SARS and MERS [8]. In one study within the analysis, 9 livebirths took place by caesarean section, including 4 preterm deliveries, the earliest of which occurred at 36 weeks of gestation [17]. No severe disease or death were reported. Neonatal bacterial pneumonia developed in 3 newborns, but resolved with treatment. Maternal patients suffered from no pre-existing chronic conditions; however, 3 out of 9 women developed co-morbid conditions, which were identified as being obstetrical in aetiology and not considered risk factors for neonatal infection.

Furthermore, any clinical, radiologic, hematologic, or biochemical abnormalities observed corresponded to similar characteristics in non-pregnant adults with COVID-19 [8,18,19]. Such abnormalities include the onset of fever and/or cough, lymphocytopenia [9], and chest computer tomography (CT) imaging of patchy shadowing and ground glass-like opacities [20] – observed to different extents in all 34 publications retained for this brief.

In another study, onset of symptoms occurring before delivery in 4 cases, the same day as delivery in 2 cases, and after delivery in 3 cases [14]. All the mothers presented with the typical clinical symptoms of COVID-19 and viral pneumonia, as described by the abnormalities cited above. 7 caesarean sections and 2 vaginal deliveries took place, resulting in 10 neonates (including one set of twins) – 4 full-term and 6 premature infants. None of the women experienced severe pneumonia or maternal death. One neonatal death occurred in a premature delivery at 35 weeks and 5 days, after developing shortness of breath with fluctuating oxygenation and decreased platelets [14]. In a comparison study between pregnant women with SARS-CoV-2 infection and uninfected pregnant women, Zhang et al. found no significant differences between pregnant women with or without COVID-19 in terms of prevalence of co-morbid obstetrical conditions such as foetal distress, preterm delivery, premature rupture of membranes, and intraoperative blood loss [21].

In the sixteen remaining population studies identified by the search for this policy brief, there was an overwhelming trend towards caesarean section – 209 caesarean deliveries versus 122 vaginal deliveries, among the 331 women who delivered during the publications’ respective study periods [7,9–

12,15,18,19,22–29]. It is suggested that caesarean section may help with dyspnea, though not a conclusive finding [21]. There has been some concern about surgical stress to the delivering mother; however, no significant adverse effects have been observed. This mode of delivery shortens the process, thus reducing maternal cardiopulmonary burden and improving lung ventilation, which is considered to reduce the risk of foetal intrauterine infection [21]. The evidence is mixed, however, as analyses of vaginal delivery outcomes demonstrate that, under strict protection measures, vaginal delivery neither exacerbates COVID-19 in mothers, nor does it conclusively increase the risk of SARS-CoV-2 infection in neonates [22,28]. Though the medical team in Alzamora et al. opted for a caesarean section, authors explained that vaginal delivery is not necessarily contra-indicated with COVID-19, pointing out a “lack of convincing evidence”[4] that caesarean section is protective. According to Liao et al., if vaginal delivery can be achieved safely, it should be chosen [22].

Among the 4 neonates delivered vaginally in a sample of fourteen individual case reports included in the search [30–33], 1 was briefly shown to be infected by SARS-CoV-2 (37 hours after the positive result, a new RT-PCR assay demonstrated SARS-CoV-2-negativity) [33] – while the other 3 remained uninfected, regardless of severity of disease in the mothers. According to Carosso et al., this uncertain case of infection was due to possible mother-to-child transmission by faecal contamination through the vaginal canal, as

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positive antibodies (Immunoglobulin G) were also observed in cord blood [33]. Amid the retained case reports, 13 out of 14 COVID-19-positive women survived labour and delivery despite 5 of these involving recovery from relatively severe or critical disease [4,30,34–36].

Premature infants tend to suffer more from respiratory distress than their full -term peers. In a study of clinical characteristics and risk assessment for neonatal infection, 2 late preterm infants required non- invasive continuous positive airway pressure (nCPAP) ventilation [23]. They presented mild neonatal respiratory distress syndrome, which resolved with the respiratory therapy. Full-term infants in this and other studies [9,10,19] face a lower risk of respiratory distress; older gestational age is likely protective.

According to Yang et al., SARS-CoV-2 in late pregnancy does not cause adverse outcomes in neonates [23];

however, one key to infection prevention is the strict use of personal protective equipment throughout the process [37–39]. Moreover, neonates are seemingly resilient in the face of their mothers’ medical adversity related to COVID-19. In Zhang et al., even when pregnant women showed diminished lung capacity due to COVID-19, there was no significant impact on the neonates [21]. In one case of severe ARDS in the mother, foetal heart rate remained “reassuring” when maximal ventilatory support was provided during delivery [36]. The neonate transitioned to extra-uterine life with no complications, and was extubated two days after birth.

8 SUMMARY OF AFRICA-SPECIFIC LITERATURE ON THE SUBJECT

No literature specific to the African Region was identified.

9 POLICY FINDINGS

1. SARS-CoV-2 infection caused generally mild respiratory symptoms in pregnant women [26]. A case-control study by Li et al., found no pregnant patients (either confirmed or suspected COVID- 19) to have developed severe respiratory complications requiring critical care. Furthermore, evidence suggests, in some study cohorts, that the clinical characteristics of the pregnant women are mild compared to the general population [25]. However, Huang et al. demonstrated that severe maternal and neonatal outcomes do arise with SARS-CoV-2, including infant death, but that this possibility is amplified in women of older age and/or with medical histories of hypertension and cardiovascular disease [15]. As a result, systematic screening should be employed given the changes (mainly physiological and immunological) in pregnancy and their potential impact on the maternal-neonatal dyad.

2. In severe and critical cases, hospitalisation may be shorter in pregnant women (median 6 days for severe, 10.5 days for critical) than in non-pregnant persons (median 12 days) [15,29]. Additionally, certain risk factors drive the course of disease towards more serious forms. For example, in a U.S.

cohort study, critically ill pregnant women (ages: 35.9 +/- 4.3 years) were significantly older than severely ill pregnant women (32.0 +/- 6.0 years old) [29]. In an Italian study, BMI was found to also increase the likelihood of severe onset of disease [24].

3. Diagnosis of this novel coronavirus infection is not an indication for the premature end of a pregnancy; rather, the severity of the course of disease is a factor that would determine this choice, as seen in the many cases of iatrogenic preterm birth observed in the available literature.

Moreover, COVID-19 is not an intrinsic indication for caesarean section [16]. One recommendation is to deliver in negative-pressure isolation regardless of the mode of delivery, completing the procedure in as short a timeframe as possible.

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4. There was no significant difference in the incidence of preterm delivery and neonatal asphyxia between pregnant women with or without COVID-19. Moreover, preterm delivery is more likely to do with obstetric complications than COVID-19-related illness.

5. Neonates are stronger than expected, not necessarily as affected by severe disease as their SARS- CoV-2-infected mothers, especially those born at later gestational ages.

10 ONGOING RESEARCH IN THE AFRICAN REGION None identified

11 AFRO RECOMMENDATIONS FOR FURTHER RESEARCH

WHO AFRO encourages researchers to scientifically document the obstetric delivery of pregnant women with suspected or confirmed COVID-19 in the African Region, particularly as the evidence on impact of SARS-CoV-2 infection on pregnancy and its outcomes are not strongly conclusive in other parts of the world.

It also calls for further research to ascertain the safety of different modes of delivery (caesarean versus vaginal) with respect to the health and well-being of mothers and neonates, as well as the impact of different therapies on the course of delivery. AFRO welcomes any scientificall y rigorous research related to all aspects of case management in COVID-19-positive pregnant women that is specific to the Region, and invites all COVID-19 response committees to make optimal use of their scientific committees and extend collaboration to academics and other related partners to undertake robust evidence-informed studies on the subject.

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12 REFERENCES

1 Sina BJ. Pregnancy and the global disease burden. Reprod Health 2017;14:170. doi:10.1186/s12978-017- 0420-4

2 Dashraath P, Wong JLJ, Lim MXK, et al. Coronavirus disease 2019 (COVID-19) pandemic and pregnancy. Am J Obstet Gynecol Published Online First: March 2020.https://dx.doi.org/10.1016/j.ajog.2020.03.021

3 Wang S, Guo L, Chen L, et al. A case report of neonatal COVID-19 infection in China. Clin Infect Dis Published Online First: March 2020.https://dx.doi.org/10.1093/cid/ciaa225

4 Alzamora MC, Paredes T, Caceres D, et al. Severe COVID-19 during Pregnancy and Possible Vertical Transmission. Am J Perinatol Published Online First: April 2020.https://dx.doi.org/10.1055/s-0040- 1710050

5 Schwartz DA, Graham AL. Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections.

2020;12.https://dx.doi.org/10.3390/v12020194

6 Wong SF, Chow KM, Leung TN, et al. Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome. Am J Obstet Gynecol 2004;191:292–7. doi:10.1016/j.ajog.2003.11.019 7 Yang H, Hu B, Zhan S, et al. Effects of SARS-CoV-2 infection on pregnant women and their infants: A

retrospective study in Wuhan, China. Arch Pathol Lab Med 2020;:arpa.2020-0232-SA.

doi:10.5858/arpa.2020-0232-SA

8 Schwartz DA. An Analysis of 38 Pregnant Women with COVID-19, Their Newborn Infants, and Maternal- Fetal Transmission of SARS-CoV-2: Maternal Coronavirus Infections and Pregnancy Outcomes. Arch Pathol Lab Med 1976 Published Online First: March 2020.https://dx.doi.org/10.5858/arpa.2020-0901-SA

9 Liu D, Li L, Wu X, et al. Pregnancy and Perinatal Outcomes of Women With Coronavirus Disease (COVID-19) Pneumonia: A Preliminary Analysis. AJR Am J Roentgenol 2020;:1–6.

10 Liu W, Wang J, Li W, et al. Clinical characteristics of 19 neonates born to mothers with COVID-19. Front Med 2020;14:193–8. doi:10.1007/s11684-020-0772-y

11 Xu L, Yang Q, Shi H, et al. Clinical presentations and outcomes of SARS-CoV-2 infected pneumonia in pregnant women and health status of their neonates. Published Online First: April

2020.https://dx.doi.org/10.1016/j.scib.2020.04.040

12 London V, McLaren R, Atallah F, et al. The Relationship between Status at Presentation and Outcomes among Pregnant Women with COVID-19. Am J Perinatol 2020;:s-0040-1712164. doi:10.1055/s-0040- 1712164

13 Sharma KA, Kumari R, Kachhawa G, et al. Management of the first patient with confirmed COVID‐19 in pregnancy in India: From guidelines to frontlines. Int J Gynecol Obstet 2020;:ijgo.13179.

doi:10.1002/ijgo.13179

14 Zhu H, Wang L, Fang C, et al. Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia.

Transl Pediatr Published Online First: 2020. doi:10.21037/tp.2020.02.06

15 Huang W, Zhao Z, He Z, et al. Unfavorable outcomes in pregnant patients with COVID-19 outside Wuhan, China. J Infect Published Online First: 2020. doi:10.1016/j.jinf.2020.05.014

16 Clinical management of COVID-19: Interim guidance. 27 May 2020. World Health Organization https://www.who.int/publications/i/item/clinical-management-of-covid-19

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17 Chen H, Guo J, Wang C, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet 2020;395:809–15.

18 Chen R, Zhang Y, Huang L, et al. Sécurité et efficacité de différents modes d’anesthésie pour des parturientes infectées par la COVID-19 accouchant par césarienne : une série de 17 cas. Can J Anaesth 2020;67:655–63.

19 Yu N, Li W, Kang Q, et al. Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study. Lancet Infect Dis

2020;20:559–64.

20 Xia H, Zhao S, Wu Z, et al. Emergency Caesarean delivery in a patient with confirmed COVID-19 under spinal anaesthesia. Br J Anaesth 2020;124:e216–8.

21 Zhang L, Jiang Y, Wei M, et al. Analysis of the pregnancy outcomes in pregnant women with COVID-19 in Hubei Province. Chin J Obstet Gynecol 2020;55:E009–E009. doi:10.3760/cma.j.cn112141-20200218-00111 22 Liao J, He X, Gong Q, et al. Analysis of vaginal delivery outcomes among pregnant women in Wuhan, China

during the COVID-19 pandemic. Int J Gynaecol Obstet Published Online First: May 2020.https://dx.doi.org/10.1002/ijgo.13188

23 Yang P, Wang X, Liu P, et al. Clinical characteristics and risk assessment of newborns born to mothers with COVID-19. J Clin Virol 2020;127:104356–104356.

24 Savasi VM, Parisi F, Patanè L, et al. Clinical Findings and Disease Severity in Hospitalized Pregnant Women With Coronavirus Disease 2019 (COVID-19): Obstet Gynecol 2020;:1. doi:10.1097/AOG.0000000000003979 25 Wu Y, Liu C, Dong L, et al. Coronavirus disease 2019 among pregnant Chinese women: Case series data on

the safety of vaginal birth and breastfeeding. BJOG Published Online First: May 2020.https://dx.doi.org/10.1111/1471-0528.16276

26 Li N, Han L, Peng M, et al. Maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia: a case-control study. Clin Infect Dis Published Online First: April

2020.https://dx.doi.org/10.1093/cid/ciaa352

27 Buonsenso D, Costa S, Sanguinetti M, et al. Neonatal Late Onset Infection with Severe Acute Respiratory Syndrome Coronavirus 2. Am J Perinatol Published Online First: May 2020.https://dx.doi.org/10.1055/s- 0040-1710541

28 Ferrazzi E, Frigerio L, Savasi V, et al. Vaginal delivery in SARS-CoV-2 infected pregnant women in Northern Italy: a retrospective analysis. BJOG Published Online First: April 2020.https://dx.doi.org/10.1111/1471- 0528.16278

29 Pierce-Williams RAM, Burd J, Felder L, et al. Clinical course of severe and critical COVID-19 in hospitalized pregnancies: a US cohort study. Am J Obstet Gynecol MFM 2020;:100134–100134.

30 Yu Y, Fan C, Bian J, et al. Severe COVID‐19 in a pregnant patient admitted to hospital in Wuhan. Int J Gynecol Obstet 2020;:ijgo.13232. doi:10.1002/ijgo.13232

31 Iqbal SN, Overcash R, Mokhtari N, et al. An Uncomplicated Delivery in a Patient with Covid-19 in the United States. N Engl J Med 2020;382:e34–e34.

32 Xiong X, Wei H, Zhang Z, et al. Vaginal delivery report of a healthy neonate born to a convalescent mother with COVID--19. J Med Virol Published Online First: April 2020.https://dx.doi.org/10.1002/jmv.25857

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33 Carosso A, Cosma S, Borella F, et al. Pre-labor anorectal swab for SARS-CoV-2 in COVID-19 pregnant patients: is it time to think about it? Eur J Obstet Gynecol Reprod Biol Published Online First: April 2020.https://dx.doi.org/10.1016/j.ejogrb.2020.04.023

34 Zamaniyan M, Ebadi A, Aghajanpoor Mir S, et al. Preterm delivery in pregnant woman with critical COVID- 19 pneumonia and vertical transmission. Prenat Diagn Published Online First: April

2020.https://dx.doi.org/10.1002/pd.5713

35 Li J, Wang Y, Zeng Y, et al. Critically ill pregnant patient with COVID-19 and neonatal death within two hours of birth. Int J Gynaecol Obstet Published Online First: May

2020.https://dx.doi.org/10.1002/ijgo.13189

36 Schnettler WT, Al Ahwel Y, Suhag A. Severe ARDS in COVID-19-infected pregnancy: obstetric and intensive care considerations. Am J Obstet Gynecol MFM 2020;:100120–100120.

37 Lyra J, Valente R, Rosário M, et al. Cesarean Section in a Pregnant Woman with COVID-19: First Case in Portugal. Acta Med Port Published Online First: May 2020.https://dx.doi.org/10.20344/amp.13883 38 Lee DH, Lee J, Kim E, et al. Emergency cesarean section on severe acute respiratory syndrome coronavirus

2 (SARS- CoV-2) confirmed patient. Published Online First: April 2020.https://dx.doi.org/10.4097/kja.20116

39 Du Y, Wang L, Wu G, et al. Anesthesia and protection in an emergency cesarean section for pregnant woman infected with a novel coronavirus: case report and literature review. J Anesth Published Online First: 2020. doi:10.1007/s00540-020-02796-6

BRIEF PRODUCED BY: Aminata Binetou-Wahebine Seydi, Humphrey Cyprian Karamagi, Kwami Dadji, Regina Titi-Ofei, Jean Claude Nshirimana, Pascal Mouhouelo, Juliet Nabyonga, Benson Droti, Hillary Kipruto, James Avoka Asamani, Monde Mambimongo, John Appia, Assumpta Muriithi, Nancy Kidula, Prosper Tumusiime, and Felicitas Zawaira.