Clinical care of pregnant and postpartum women with COVID19: Living recommendations from the National COVID19 Clinical Evidence Taskforce

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.To date, 18 living recommendations for the clinical care of pregnant and postpartum women with COVID-19 have been issued by the National COVID-19 Clinical Evidence Taskforce. This includes recommendations on mode of birth, delayed umbilical cord clamping, skin-to-skin contact, breastfeeding, rooming-in, antenatal corticosteroids, angiotensin-converting enzyme inhibitors, disease-modifying treatments (including dexamethasone, remdesivir and hydroxychloroquine), venous thromboembolism prophylaxis and advanced respiratory support interventions (prone positioning and extracorporeal membrane oxygenation). Through continuous evidence surveillance, these living recommendations are updated in near real-time to ensure clinicians in Australia have reliable, evidence-based guidelines for clinical decision-making. Please visit https://covid 19evi dence.net.au/ for the latest recommendation updates.

# Introduction
commonly presents with fever and respiratory symptoms including cough and shortness of breath; other symptoms (such as myalgia, sore throat, fatigue, diarrhoea and anosmia) are less common.An estimated 15% of infected individuals will develop severe disease (requiring oxygen support) and 5% will progress to critical disease.Critical COVID-19 disease is characterised by respiratory failure, acute respiratory distress syndrome (ARDS), thromboembolism, sepsis, shock or multiorgan failure. After recovery from acute illness, some individuals may experience longer-term sequelae, particularly respiratory complications. [bib_ref] Long term respiratory complications of covid-19, Fraser [/bib_ref] Experience from previous pandemics (H1N1) and coronavirus outbreaks (SARS and MERS) raised concerns that pregnant women may be particularly vulnerable to more severe COVID-19 disease. [bib_ref] Coronavirus disease 2019 (COVID-19) and pregnancy: what obstetricians need to know, Rasmussen [/bib_ref] [bib_ref] 2019-nCoV epidemic: what about pregnancies?, Favre [/bib_ref] While current data are limited, pregnant and recently pregnant women with COVID-19 are less likely to experience fever and myalgia, compared with non-pregnant women of reproductive age. [bib_ref] Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease..., Allotey [/bib_ref] However, they have higher rates of intensive care unit admission or invasive ventilation, and their babies are more likely to be born preterm or require neonatal unit admission. [bib_ref] Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease..., Allotey [/bib_ref] Epidemiological data from the Latin American region suggest maternal deaths may be increasing due to COVID-19.Vertical transmission appears possible although probably rare. [bib_ref] Transplacental transmission of SARS-CoV-2 infection, Vivanti [/bib_ref] [bib_ref] COVID-19 and pregnancy: a review of clinical characteristics, obstetric outcomes and vertical..., Pettirosso [/bib_ref] In response to the COVID-19 pandemic, state, national and international organisations rapidly developed clinical guidelines on how best to care for pregnant and postpartum women with Ideally, clinical guidelines are developed using systematic reviews of available evidence to address pre-specified questions, with expert panels formulating recommendations based on this evidence. However, many such recommendations become outdated as new evidence emerges. [bib_ref] The validity of recommendations from clinical guidelines: a survival analysis, Garcia [/bib_ref] [bib_ref] Validity of the agency for healthcare research and quality clinical practice guidelines:..., Shekelle [/bib_ref] This is a particular challenge in the COVID-19 context, where the volume of COVID-19-related literature is increasing dramatically. 15 Living guideline methodologies were developed to meet such challenges. [bib_ref] Living systematic reviews: 4. living guideline recommendations, Akl [/bib_ref] In living guidelines, digital technologies and continuous evidence surveillance are used to continually update systematic reviews and recommendations, so as to reflect the latest available evidence. [bib_ref] Living systematic review: 1. Introduction-the why, what, when, and how, Elliott [/bib_ref] This approach has been used successfully in stroke, diabetes, maternal health and other topics. [bib_ref] Bringing stroke clinical guidelines to life, English [/bib_ref] [bib_ref] Breathing life into Australian diabetes clinical guidelines, White [/bib_ref] [bib_ref] Developing and applying a 'living guidelines' approach to WHO recommendations on maternal..., Vogel [/bib_ref] The National COVID-19 Clinical Evidence Taskforce was established in March 2020 to produce living recommendations on the clinical care of people with COVID-19 in Australia.

# Methods

## Identification and formulation of clinical questions
We conducted a systematic mapping of available guidelines on the

## Literature searching, data collection and synthesis
An information specialist oversees the evidence surveillance process, which combines daily searches of COVID-19-related articles and preprints across broad topic areas (such as pregnancy and newborn care) with targeted searches for specific clinical questions as they are proposed by the expert panels. The evidence review team uses Covidence, 27 a collaborative online software for managing and streamlining systematic reviews, for screening literature.
Titles and abstracts are initially screened by two reviewers independently, with full texts of potentially eligible studies retrieved and also reviewed in duplicate. Disagreements are resolved through discussion or consultation with a third member of the evidence review team. Eligible articles are primary research (typically trials) or systematic reviews relating to the clinical questions of interest. Systematic reviews (particularly living systematic reviews that are kept up-to-date) of reasonable quality are the preferred evidence source. If required, a limited update may be used to integrate findings from more recent primary studies into an existing systematic review. Where no such systematic review exists, the evidence review team initiates a new systematic review. For some clinical questions where direct trial evidence is unlikely to be available for pregnant and postpartum women, lower quality evidence such as observational studies or studies from related topics (eg, studies of women with ARDS due to other causes) are considered.
Data on study characteristics and priority outcomes are extracted in duplicate using standardised data collection forms, with disagreements resolved through discussion or consulting a third reviewer.Included studies are assessed using an appropriate quality assessment tool, such as AMSTAR 2 for systematic reviews and the Cochrane Risk of Bias 2.0 assessment tool for randomised trials. [bib_ref] RoB 2: a revised tool for assessing risk of bias in randomised..., Sterne [/bib_ref] [bib_ref] AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised..., Shea [/bib_ref] Developing and updating recommendations May 2020, the panel convened on a weekly basis to review the evidence, develop and update recommendations. Where necessary, assistance is sought from additional expert advisory groups (eg, haematology, critical care). The panel reviews evidence profiles on the benefits, harms and certainty of the evidence for priority questions, as well as considering the resource requirements, cost-effectiveness, feasibility, acceptability and equity of each intervention. This is done systematically using GRADE evidence to decision frameworks. [bib_ref] GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to..., Alonso-Coello [/bib_ref] Recommendations are formulated in line with established Australian maternity care principles, including the need for evidence-based, person-centred care that is responsive to women's needs and preferences.

# Results
The following recommendations are current as of 17 September 2020, with any subsequent updates freely available at https:// covid 19evi dence.net.au/. Classifications of disease severity used by the Taskforce are described in [fig_ref] TABLE 1: Classification of COVID-19 disease severity  Occurrence of severe respiratory failure [/fig_ref].

## Pregnancy and perinatal care of women with covid-19
Seven recommendations on mode of birth, delayed umbilical cord clamping, skin-to-skin contact, breastfeeding, rooming-in, antenatal corticosteroids and angiotensin-converting enzyme (ACE)inhibitors support continuing with the provision of usual care, although the need for masks and hand hygiene when mothers are caring and feeding their babies, is emphasised [fig_ref] TABLE 2: Pregnancy and perinatal care recommendations for women with COVID-19  Mode of... [/fig_ref].
While systematic reviews on the risks of vertical transmission by mode of birth, rooming-in status and different infant feeding approaches have been published, only very low certainty evidence (predominantly case reports and case series) is currently available. [bib_ref] Maternal transmission of SARS-COV-2 to the neonate, and possible routes for such..., Walker [/bib_ref] [bib_ref] Transmission of SARS-CoV-2 through breast milk and breastfeeding: a living systematic review, Centeno-Tablante [/bib_ref] Additional evidence is available from a US multi-centre cohort study of 106 neonates born to mothers who were positive for COVID-19. [bib_ref] Neonatal management and outcomes during the COVID-19 pandemic: an observation cohort study, Salvatore [/bib_ref] In this study, mode of birth, skinto-skin contact and breastfeeding were managed as per usual care, although maternal use of surgical masks, hand hygiene and breast cleansing were encouraged. Newborns roomed-in with mothers, except for 17 newborns who were separated at parental request or due to medical complications. Newborns were tested by nasopharyngeal polymerase chain reaction at 12-24 h (n = 106), 5-7 days (n = 79) and 14 days (n = 72) of life, with all newborns testing negative at all timepoints. While the possibility of vertical transmission cannot be excluded based on this evidence, this must be weighed against the known, substantial benefits of these interventions. [bib_ref] Effect of timing of umbilical cord clamping of term infants on maternal..., Mcdonald [/bib_ref] [bib_ref] Effect of timing of umbilical cord clamping and other strategies to influence..., Rabe [/bib_ref] [bib_ref] Early skin-to-skin contact for mothers and their healthy newborn infants, Moore [/bib_ref] [bib_ref] Interventions to prevent hypothermia at birth in preterm and/or low birth weight..., Mccall [/bib_ref] [bib_ref] Rooming-in for new mother and infant versus separate care for increasing the..., Jaafar [/bib_ref] [bib_ref] Hospital practices that increase breastfeeding duration: results from a population-based study, Murray [/bib_ref] [bib_ref] Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of..., Roberts [/bib_ref] No direct evidence was identified on delayed cord clamping in women with COVID-19, or on antenatal corticosteroids or use of ACE inhibitors for postpartum women with hypertension requiring drug treatment. Hence, these recommendations are aligned with current Australian pregnancy and perinatal care guidance on use of these interventions.Use of disease-modifying treatments in women with COVID-19

## Corticosteroids
Evidence on corticosteroids compared with standard care for COVID-19 in adults comes from eight randomised trials (over 5700 patients), including the multi-centre RECOVERY trial that evaluated dexamethasone against usual care in 2104 patients. 46,47 Pregnant women were specifically excluded from all trials, except for RECOVERY (six pregnant women enrolled) and REMAP-CAP (the number of pregnant women enrolled has not been reported). [bib_ref] Dexamethasone in hospitalized patients with Covid-19 -preliminary report, Horby [/bib_ref] [bib_ref] Effect of hydrocortisone on mortality and organ support in patients with severe..., Angus [/bib_ref] Corticosteroids reduce mortality for adult patients with severe or critical COVID-19 (relative risk (RR) 0.86 95% Ci 0.77-0.97), and probably also reduce the need for mechanical ventilation or death, and time to discharge from hospital. However, in patients who do not require oxygen, corticosteroids may increase mortality (RR 1.27 95% CI 1.00-1.61). Considering these benefits and the likely acceptability of the intervention, using dexamethasone 6 mg daily (IV or oral) for up to ten days is recommended in pregnant or breastfeeding women with COVID-19 who are receiving oxygen [fig_ref] TABLE 3: Recommendations on use of disease-modifying treatments for pregnant or postpartum women with... [/fig_ref]. While the RECOVERY Trial specified that enrolled pregnant women receive oral prednisolone or intravenous hydrocortisone,dexamethasone is preferred as it is used for other clinical indications in pregnancy.Corticosteroids should not be used in women with COVID-19 who do not require oxygen, due to the lack of benefit and possible harms in this subgroup.

## Remdesivir
Four trials have compared remdesivir with standard care in hospitalised, non-pregnant adults with COVID-19. [bib_ref] Remdesivir for the treatment of Covid-19 -preliminary report, Beigel [/bib_ref] [bib_ref] Remdesivir for 5 or 10 days in patients with severe Covid-19, Goldman [/bib_ref] [bib_ref] Effect of remdesivir vs standard care on clinical status at 11 days..., Spinner [/bib_ref] [bib_ref] Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial, Wang [/bib_ref] As pregnant and breastfeeding women were excluded from these trials, there is no direct evidence on the impact of remdesivir for COVID-19 in these women, as well as a lack of safety data on its use in pregnancy. [bib_ref] Placental transfer and safety in pregnancy of medications under investigation to treat..., Louchet [/bib_ref] In non-pregnant adults, remdesivir may decrease time to recovery

## Skin-to-skin contact
Early skin-to-skin contact after birth and during the postnatal period is supported, irrespective of the presence of COVID-19. However, parents with COVID-19 should use infection prevention and control measures (mask and hand hygiene) (consensus recommendation) - Early skin-to-skin contact refers to placing the naked baby prone on the parent's bare chest immediately after birth.
- Skin-to-skin contact should be encouraged and continue as per usual practice in other postnatal and neonatal settings, such as neonatal intensive care unit and postnatal wards, providing infection prevention and control measures are maintained.

## Breastfeeding
Breastfeeding is supported irrespective of the presence of COVID-19. However, women with COVID-19 who are breastfeeding should use infection prevention and control measures (mask and hand hygiene) while infectious (conditional recommendation, very low certainty evidence) - There is currently no evidence to indicate that breastfeeding increases the risk of vertical transmission to the newborn. As there are substantial known benefits for breastfeeding, women should be supported to initiate or continue breastfeeding. If the baby is being fed with expressed breastmilk or formula, these same infection prevention and control measures should be used.

## Rooming-in
For women with COVID-19 who have given birth, support rooming-in of mother and newborn in the birth suite and on the postnatal ward when both mother and baby are well. However, women with COVID-19 should use infection prevention and control measures (mask and hand hygiene) (conditional recommendation, very low certainty evidence) - There is currently no evidence to indicate that a woman with a known COVID-19 infection should be separated from her newborn to prevent transmission. As there are substantial known benefits for keeping mother and newborn together postpartum, women should be supported to be with their newborn as per usual care. - Women with COVID-19 should be encouraged and supported in using good hand hygiene before and after handling their baby, and using a mask while in close contact with their baby. To the extent possible, these women should practice physical distancing when not feeding or caring for the baby.

## Antenatal corticosteroids
The use of antenatal corticosteroids for women at risk of preterm birth is supported as part of standard care, independent of the presence of COVID-19 (consensus recommendation) - There are clear benefits to using antenatal corticosteroids for women at risk of preterm birth at less than 34 weeks gestation. There is currently no evidence to suggest that antenatal corticosteroids cause additional maternal or fetal harm in the setting of COVID-19 when used for this indication. They should therefore be given where indicated. - The Taskforce has separate recommendations regarding the use of dexamethasone as a disease-modifying treatment in pregnant or breastfeeding women for COVID-19. Women with COVID-19 who are on oxygen and receiving dexamethasone do not require additional doses of corticosteroids for fetal lung maturation.

## Ace inhibitors
for postpartum women with hypertension requiring drug treatment
In postpartum women with COVID-19 who have hypertension requiring treatment with ACE inhibitors, there is currently no evidence to deviate from usual care. These medications should be initiated or continued unless otherwise contraindicated (consensus recommendation) - ACE inhibitors are contraindicated in the antenatal period due to risk of fetal and neonatal harm. Recommendations were current at the time of writing. Please visit The National COVID-19 Clinical Evidence Taskforce (https://covid 19evi dence. net.au/) for the latest updates to the recommendations. ACE, angiotensin-converting enzyme by a few days (hazards ratio (HR) 1.24, 95% CI 1.08-1.42) and time to improvement only slightly (HR 1.17, 95% CI 1.00-1.38). Its effect on mortality is uncertain, and it is currently unclear which regimen (five days or ten days) provides the most benefit. However, the panel noted that severity of disease is an important factor -for pregnant women with severe or critical COVID-19, the harm-tobenefit ratio may differ compared to pregnant women with mild or moderate disease. The Taskforce therefore made a conditional recommendation against the routine use of remdesivir in pregnant and breastfeeding women outside of a trial setting [fig_ref] TABLE 3: Recommendations on use of disease-modifying treatments for pregnant or postpartum women with... [/fig_ref].

## Hydroxychloroquine for treatment or for post-exposure prophylaxis
There are currently 11 trials (over 6300 patients) comparing hydroxychloroquine with standard care in the treatment of patients with COVID-19. [bib_ref] Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open..., Tang [/bib_ref] [bib_ref] Hydroxychloroquine for early treatment of adults with mild Covid-19: a randomized-controlled trial, Mitja [/bib_ref] [bib_ref] Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19, Cavalcanti [/bib_ref] [bib_ref] Hydroxychloroquine in the treatment of COVID-19: a multicenter randomized controlled study, Abd-Elsalam [/bib_ref] In all trials, pregnant women were either excluded or their eligibility was not specified. Meta-analyses indicate that hydroxychloroquine is potentially harmful and no more effective than standard care, leading to a strong recommendation against its use for COVID-19 treatment [fig_ref] TABLE 3: Recommendations on use of disease-modifying treatments for pregnant or postpartum women with... [/fig_ref]. Separately, hydroxychloroquine for post-exposure prophylaxis has been evaluated in two trials (3135 participants), both of which excluded pregnant and breastfeeding women; however, there is currently insufficient evidence to assess benefits. [bib_ref] A randomized trial of hydroxychloroquine as postexposure prophylaxis for Covid-19, Boulware [/bib_ref] The Taskforce recommends that hydroxychloroquine for post-exposure prophylaxis should not be used outside of randomised trials with appropriate ethical approval, emphasising that further trials (including in pregnant and breastfeeding women) are needed.

## Other disease-modifying treatments
The Taskforce has issued a further 19 recommendations on a wide range of disease-modifying treatments [fig_ref] TABLE 3: Recommendations on use of disease-modifying treatments for pregnant or postpartum women with... [/fig_ref] , including: 1. Use dexamethasone 6 mg daily intravenously or orally for up to ten days in pregnant or breastfeeding women with COVID-19 who are receiving oxygen (including mechanically ventilated patients) (strong recommendation, low certainty evidence).

## Do not routinely use dexamethasone to treat covid-19 in pregnant or breastfeeding women who do not require oxygen (strong recommendation, low certainty evidence).
- Antenatal corticosteroids should still be used for fetal lung maturation in pregnant women at risk of preterm birth who also have COVID-19. Dexamethasone should still be used for other evidence-based indications in pregnant and breastfeeding women who have COVID-19.

## Remdesivir as treatment for covid-19
Use of remdesivir for pregnant or breastfeeding women with COVID-19 outside of a trial setting should not be considered routinely (conditional recommendation, very low certainty evidence).
- As pregnant and breastfeeding women are often excluded from clinical trials, use of remdesivir in this population would be outside a clinical trial setting. Pregnant and breastfeeding women receiving remdesivir should nonetheless be enrolled in national COVID-19 registries. Currently, there is no direct evidence of the effects of remdesivir in pregnant and breastfeeding women. Information about the patients and the intervention (dosages, duration) in the trials used for this recommendation can be found in the Practical info tab. - Due to antagonism observed in vitro, concomitant use of remdesivir with chloroquine or hydroxychloroquine is not recommended.Hydroxychloroquine as treatment for COVID-19
Do not use hydroxychloroquine for the treatment of COVID-19 (strong recommendation, moderate certainty evidence).
- This recommendation applies to adults, children and adolescents, pregnant and breastfeeding women, older people living with frailty and those receiving palliative care. - Use of hydroxychloroquine may still be considered in the context of randomised trials with appropriate ethical approval, such as combination therapies that include hydroxychloroquine.
Hydroxychloroquine for post-exposure prophylaxis For people exposed to individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, do not use hydroxychloroquine for post-exposure prophylaxis outside of randomised trials with appropriate ethical approval (strong recommendation, low certainty evidence). Trials are needed in special populations, including children and adolescents, pregnant and breastfeeding women, older people living with frailty and those receiving palliative care. Until further evidence is available, do not use hydroxychloroquine for post-exposure prophylaxis in these populations unless they are eligible to be enrolled in trials.

## Other disease-modifying treatments
For people with COVID-19, do not use the other disease-modifying treatments  outside of randomised trials with appropriate ethical approval (strong recommendation, very low certainty evidence).
- Trials are needed in special populations, including children and adolescents, pregnant and breastfeeding women, older people living with frailty and those receiving palliative care. Until further evidence is available, do not use in these populations unless they are eligible to be enrolled in trials. Recommendations were current at the time of writing. Please visit The National COVID-19 Clinical Evidence Taskforce (https://covid 19evi dence. net.au/) for the latest updates to the recommendations. The treatments include: aprepitant, baloxavir marboxil, calcifediol, chloroquine, colchicine, convalescent plasma, darunavir-cobicistat, favipiravir, human mesenchymal stem cells, immunoglobulin plus methylprednisolone, interferon -1a, interferon -1b, interferon gamma, lopinavir-ritonavir, ruxolitinib, sofosbuvir-daclatasvir, telmisartan and umifenovir. aprepitant, azithromycin, baloxavir marboxil, calcifediol, chloroquine, colchicine, convalescent plasma, darunavir-cobicistat, favipiravir, human mesenchymal stem cells, immunoglobulin plus methylprednisolone, interferon -1a, interferon -1b, interferon gamma, lopinavir-ritonavir, ruxolitinib, sofosbuvir-daclatasvir, telmisartan and umifenovir. These treatments have typically been evaluated in one or two trials with a small number of non-pregnant participants, resulting in low or very low certainty evidence from which no conclusions can be drawn. For some of these treatments (such as baloxavir marboxil or favipiravir), no pregnancy safety data are available, whereas others (such as azithromycin or lopinavir-ritonavir) have a well-described safety profile. [bib_ref] Placental transfer and safety in pregnancy of medications under investigation to treat..., Louchet [/bib_ref] The Taskforce therefore recommends that these treatments should not be used outside of randomised trials, with emphasis that trials enrolling pregnant and breastfeeding women are needed.

## Venous thromboembolism (vte) prophylaxis
While COVID-19 infection appears to increase the risk of VTE, there is currently no direct evidence on the exact duration of this increased risk, or which prophylactic anticoagulant regimen is optimal. [bib_ref] COVID-19 coagulopathy in pregnancy: critical review, preliminary recommendations and ISTH Registry -communication..., Kadir [/bib_ref] The consensus recommendations were formulated based on a review of available international guidelines [bib_ref] COVID-19 coagulopathy in pregnancy: critical review, preliminary recommendations and ISTH Registry -communication..., Kadir [/bib_ref] [bib_ref] A critical review of the pathophysiology of thrombotic complications and clinical practice..., D&apos;souza [/bib_ref] and consultation with expert haematologists. Recognising that TABLE 4 Venous thromboembolism (VTE) prophylaxis in pregnant and postpartum women  Pregnant women in general are at an increased risk of venous thromboembolism (VTE). Hospitalised pregnant women with an acute infective illness (such as are at even greater risk of VTE. However, the exact duration of increased risk of VTE in association with COVID-19 infection is not yet established. All pregnant and postpartum women should undergo a documented assessment of risk factors for VTE on admission to hospital, if COVID-19 is diagnosed, if COVID-19 severity changes, and postpartum. The use of pharmacological prophylaxis in women should be accompanied by other measures to prevent VTE, such as anti-embolism stockings and sequential compression devices.
For pregnant or postpartum women who are admitted to hospital (for any indication) and who have COVID-19, use prophylactic doses of anticoagulants, preferably low-molecular weight heparin (LMWH: eg, enoxaparin 40 mg once daily or dalteparin 5000 IU once daily) unless there is a contraindication, such as risk for major bleeding or imminent birth. Prophylactic anticoagulants should be continued for at least 14 days after discharge or until COVID-19-related morbidity (including immobility, dehydration and/or shortness of breath) has resolved (consensus recommendation).
- Dosing of LMWH is dependent on pre-pregnancy body weight and current renal function. - For women with early pregnancy body weight outside of 50-90 kg, consider adjusted LMWH dosing. - There is limited evidence to guide the most appropriate dose in obese patients but standard dosing may be inadequate.
For pregnant women with severe or critical COVID-19, or where there are additional risk factors for VTE, consider using increased prophylactic dosing of anticoagulants, preferably LMWH (eg, enoxaparin 40 mg twice daily or dalteparin 5000 IU twice daily) unless there is a contraindication, such as risk for major bleeding or platelet count < 30  109/L. Prophylactic anticoagulants should be continued for at least four weeks after discharge or until COVID-19-related morbidity (including immobility, dehydration and/or shortness of breath) has resolved (consensus recommendation).
- Dosing is dependent on pre-pregnancy body weight and current renal function. For women with early pregnancy body weight outside of 50-90 kg, consider adjusted LMWH dosing. - There is limited evidence to guide the most appropriate dose in obese patients but standard dosing may be inadequate. - Clinicians should refer to their local or jurisdictional guidance on additional VTE risk factors. - In some situations, continuation of LMWH throughout the rest of pregnancy and postpartum may be required. Involvement of specialist obstetricians, obstetric medicine physicians, haematologists or other physicians with expertise in VTE in pregnant women would be warranted.
For pregnant or postpartum women who are self-isolating at home with mild COVID-19 and where additional risk factors for VTE are present, consider using prophylactic doses of anticoagulants, preferably LMWH (eg, enoxaparin 40 mg once daily or dalteparin 5000 IU once daily) unless there is a contraindication, such as risk for major bleeding or imminent birth. Prophylactic anticoagulants should be continued for at least 14 days or until COVID-19-related morbidity (including immobility, dehydration and/or shortness of breath) has resolved. For pregnant or postpartum women who are self-isolating at home with mild COVID-19 and who have no additional risk factors for VTE, routine pharmacological prophylaxis is not recommended (consensus recommendation) - Dosing of LMWH is dependent on pre-pregnancy body weight and current renal function. For women with early pregnancy body weight outside of 50-90 kg, consider adjusted LMWH dosing. - There is limited evidence to guide the most appropriate dose in obese patients but standard dosing may be inadequate. - Clinicians should refer to their local or jurisdictional guidance on additional VTE risk factors.
For postpartum women who have had COVID-19 during pregnancy, consider using at least 14 days of prophylactic dosing of anticoagulants, preferably LMWH (eg, enoxaparin 40 mg once daily or dalteparin 5000 IU once daily) unless there is a contraindication, such as risk for major bleeding. Increased duration of six weeks should be considered if severe or critical COVID-19 and/or additional risk factors for VTE are present (consensus recommendation) - Dosing of LMWH is dependent on pre-pregnancy body weight and current renal function. For women with early pregnancy body weight outside of 50-90 kg, consider adjusted LMWH dosing. - There is limited evidence to guide the most appropriate dose in obese patients but standard dosing may be inadequate.

# Discussion
The treatment of COVID-19 is a rapidly expanding area of research, with an unprecedented global effort underway. However, with more than 53 000 COVID-19 articles in PubMed, as well as 2100 systematic review protocols and 1600 trial protocols registered online in less than eight months, it is increasingly difficult for clinicians to remain up-to-date on important developments. 15,There is also a growing recognition that a portion of the COVID-19 literature is of poor quality, further complicating its interpretation and application in clinical care. [bib_ref] Waste in covid-19 research, Glasziou [/bib_ref] - Current reports suggest prone ventilation in adult patients is effective in improving hypoxia associated with COVID-19. This should be done in the context of a hospital guideline that includes suitable personal protective equipment for staff, and that minimises the risk of adverse events, e.g. accidental extubation. - Proning of a pregnant woman should avoid abdominal compression and ensure a woman's hips and chest are supported. In the absence of specialised equipment, proning can be performed using pillows and blankets. - Proning can be challenging in late gestation and delivery of the baby may be warranted.
[formula] Extracorporeal membrane oxygenation (ECMO) [/formula]
Consider referral to an ECMO centre for venovenous ECMO in mechanically ventilated pregnant women with COVID-19 and refractory respiratory failure (despite optimising ventilation, including proning). Delivery of the baby prior to ECMO to enhance maternal resuscitation should be considered on a case-by-case basis (consensus recommendation).
- Due to the resource-intensive nature of ECMO and the need for experienced centres, healthcare workers and infrastructure, ECMO should only be considered in selected pregnant women with COVID-19 and severe ARDS. - The decision on whether to use ECMO should be taken in consultation with the woman's family, as well as obstetric and intensive care specialists. Key considerations include gestational age, fetal viability, fetal well-being and the risks and benefits to mother and baby. - Early referral to an ECMO centre is preferred. - As pregnant and postpartum women may have haemostatic alterations, anticoagulation regimens may need to be modified appropriately. Recommendations were current at the time of writing. Please visit The National COVID-19 Clinical Evidence Taskforce (https://covid 19evi dence. net.au/) for the latest updates to the recommendations.
A key finding from these recommendations is the lack of direct evidence specific to pregnant and breastfeeding women with COVID-19. Historically, women (and particularly pregnant and breastfeeding women) have been excluded from adult clinical trials, despite repeated calls from professional associations, regulatory agencies and researchers for their inclusion. [bib_ref] An ethics call to include pregnant women in research: reflections from the..., Saenz [/bib_ref] This trend has continued in the era of COVID-19, with pregnant and breastfeeding women excluded from large multi-centre trials of COVID-19 therapeutics. [bib_ref] Consider pregnancy in COVID-19 therapeutic drug and vaccine trials, Whitehead [/bib_ref] and perinatal living recommendations, which will be updated as necessary in response to new, important evidence. We encourage clinicians in Australia's maternity services to freely subscribe to Taskforce updates (covid19evidence.net.au) to ensure they remain abreast of guideline updates.
[table] TABLE 1: Classification of COVID-19 disease severity  Occurrence of severe respiratory failure (PaO2/FiO2 < 200), respiratory distress or acute respiratory distress syndrome (ARDS). This includes patients deteriorating despite advanced forms of respiratory support (noninvasive ventilation, high-flow nasal oxygen) OR patients requiring mechanical ventilation. OR other signs of significant deterioration  hypotension or shock  impairment of consciousness  other organ failure Recommendations were current at the time of writing. Please visit The National COVID-19 Clinical Evidence Taskforce (https://covid 19evi dence. net.au/) for the latest updates to the recommendations. [/table]
[table] TABLE 2: Pregnancy and perinatal care recommendations for women with COVID-19  Mode of birth For pregnant women with COVID-19, mode of birth should remain as per usual care (conditional recommendation, very low certainty evidence)  There is currently no evidence to indicate that caesarean section for women with COVID-19 reduces the risk of vertical transmission to the newborn. Mode of birth should continue as per usual care. Respiratory deterioration due to COVID-19 may prompt urgent delivery on an individual basis.Delayed umbilical cord clamping is supported as part of standard care, independent of the presence of COVID-1 (consensus recommendation)  There is currently no evidence that delayed umbilical cord clamping affects the risk of vertical transmission of COVID-19. [/table]
[table] TABLE 3: Recommendations on use of disease-modifying treatments for pregnant or postpartum women with COVID-19  [/table]
[table] TABLE 5: Respiratory support for pregnant and postpartum women with severe or critical COVID-19  Prone positioning 1. For mechanically ventilated pregnant women with COVID-19 and hypoxaemia despite optimising ventilation, consider prone positioning for more than 12 h a day (consensus recommendation). 2. For pregnant and postpartum women with COVID-19 and respiratory symptoms who are receiving any form of supplemental oxygen therapy and have not yet been intubated, consider prone positioning. When positioning a pregnant woman in prone, care should be taken to support the gravid uterus to reduce aorta-caval compression. Women who are deteriorating should be considered for early endotracheal intubation and invasive mechanical ventilation. Birth of the baby should be considered when it may enhance maternal resuscitation or be beneficial to the fetus (consensus recommendation). [/table]