Covid Effect on Pregnant Ladies

The CDC recommends that everyone take the same precautions to prevent the spread of COVID-19. However, there may be some additional risks for pregnant people. Pregnant people who have symptoms of COVID-19 should be tested as soon as possible; however, they are not prioritized for testing over other people.

pregnant women have just as much risk of getting covid as anyone else.

Pregnancy is not a risk factor for covid. Women are at the same risk of getting covid as the general population, and pregnant women are more likely to get severe symptoms. Covid 19 can cause severe illness in infants and older children.

pregnant women are also at a greater risk of developing severe symptoms of covid 19 than non-pregnant people.

It is important to note that pregnant women are also at a greater risk of developing severe symptoms of covid 19 than non-pregnant people.

This is because the immune system changes during pregnancy. The higher level of estrogen and progesterone in the body during pregnancy can make it more difficult for your body to fight off viruses and infections that you may be exposed to. This is why pregnant women should take extra precautions during this time. It’s best not to go outside or travel if you feel like you might get sick; instead, stay home until your symptoms go away (or even longer).

Pregnant women with covid 19 may be at increased risk of having an adverse pregnancy outcome including preterm birth.

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covid 19 can cause transient neonatal illness in newborns and serious illness in older children.

Transient Neonatal Illness

Transient neonatal illness refers to the newborns experiencing a fever, rash and vomiting. Transient neonatal illness is not a serious illness. Children with this condition usually recover without any complications within a few days. Serious Illness

Children who are older than one month can experience serious illness from their immune response to covid 19 infection. This type of reaction causes fever, rash, vomiting and jaundice (yellowing of the skin or eyes). In some cases it can cause liver damage that can be life threatening if left untreated (hepatic failure).

you should see a doctor if you experience any symptoms of covid19

You should see a doctor as soon as possible if you experience any symptoms of covid19. If you are pregnant, it is especially important to seek treatment. You should also see a doctor if you have not been vaccinated against covid19 and are not sure whether or not you are pregnant.

Conclusion

It is important that you take precautions to avoid contracting covid 19 during your pregnancy. If you are pregnant and have any of the symptoms listed above, it is important that you see a doctor immediately as this can be very serious.

Covid Effect on Pregnant Ladies

The overall risk of COVID-19 to pregnant women is low. However, women who are pregnant or were recently pregnant are at increased risk of severe illness with COVID-19. Severe illness means that you might need to be hospitalized, have intensive care or be placed on a ventilator to help with breathing. Pregnant women with COVID-19 are also more likely to deliver a baby before the start of the 37th week of pregnancy (premature birth). Pregnant women with COVID-19 might also be at increased risk of problems such as stillbirth and pregnancy loss.

Pregnant women who are Black or Hispanic are more likely to be affected by infection with the COVID-19 virus. Pregnant women who have other medical conditions, such as diabetes, also might be at even higher risk of severe illness due to COVID-19.

Contact your health care provider right away if you have COVID-19 symptoms or if you’ve been exposed to someone with COVID-19. It’s recommended that you get tested for the COVID-19 virus. Before going to your appointment, call ahead of time to tell your health care provider about your symptoms and possible exposure.

If you have COVID-19 and are pregnant, your health care provider might recommend treatment with a monoclonal antibody medication. Treatment with a monoclonal antibody medication involves a single infusion given by needle in the arm (intravenously) in an outpatient setting. Monoclonal antibody medications are most effective when given soon after COVID-19 symptoms start.

Your treatment may also include getting plenty of fluids and rest. You may also take medication to reduce fever, relieve pain or lessen coughing. If you’re very ill, you may need to be treated in the hospital.

Impact on prenatal care

Talk to your health care provider about precautions that will be taken to protect you during appointments or whether virtual prenatal care is an option for you. Ask if there are any tools that might be helpful to have at home, such as a blood pressure monitor or a device to monitor your oxygen levels (pulse oximeter). To make the most of any virtual visits, prepare a list of questions ahead of time and take detailed notes. Online childbirth classes also may be an option.

If you have certain high-risk conditions during pregnancy, virtual visits might not be an option. Ask your health care provider about how your care might be affected.

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Labor and delivery recommendations

If you are healthy as you approach the end of pregnancy, some aspects of your labor and delivery might proceed as usual. But be prepared to be flexible.

If you are scheduled for labor induction or a C-section, you and your support person might be screened for COVID-19 symptoms before your arrival at the hospital. You might be screened again before entering the labor and delivery unit. If you have symptoms of the virus that causes COVID-19, your induction or C-section might be rescheduled.

To protect the health of you and your baby, some facilities might limit the number of people you can have in the room during labor and delivery. Visits after delivery might be affected too. Also, during your stay in the hospital, you and your support person might be screened for symptoms every day. Talk to your health care provider about any restrictions that might apply.

If you have COVID-19 or are waiting for test results due to symptoms during your stay in the hospital after childbirth, wear a well-fitting face mask and have clean hands when caring for your newborn. Stay a reasonable distance from your baby when possible. When these steps are taken, the risk of a newborn becoming infected with the COVID-19 virus is low.

However, if you are severely ill with COVID-19, you might need to be temporarily separated from your newborn.

Postpartum guidance

It’s recommended that postpartum care after childbirth be an ongoing process. Talk to your health care provider about virtual visit options for checking in after delivery, as well as your need for an office visit.

During this stressful time, you might have more anxiety about your health and the health of your family. Pay attention to your mental health. Reach out to family and friends for support while taking precautions to reduce your risk of infection with the COVID-19 virus.

If you experience severe mood swings, loss of appetite, overwhelming fatigue and lack of joy in life shortly after childbirth, you might have postpartum depression. Contact your health care provider if you think you might be depressed. For example, if your symptoms don’t fade on their own, you have trouble caring for your baby or completing daily tasks, or you have thoughts of harming yourself or your baby.

Breastfeeding considerations

Research suggests that breast milk isn’t likely to spread the COVID-19 virus to babies. The bigger concern is whether an infected mother can spread the virus to the baby through respiratory droplets during breastfeeding.

If you have COVID-19, take steps to avoid spreading the virus to your baby. Wash your hands before breastfeeding and wear a well-fitting face mask during breastfeeding and whenever you are within 6 feet of your baby. If you’re pumping breast milk, wash your hands before touching any pump or bottle parts and follow recommendations for proper pump cleaning. If possible, have someone who is well give the baby the expressed breast milk.

COVID-19 vaccines during pregnancy and breastfeeding

If you are pregnant or breastfeeding, it’s recommended that you get a COVID-19 vaccine. Getting a COVID-19 vaccine can protect you from severe illness due to COVID-19. Vaccination can also help pregnant women build antibodies that might protect their babies. Research shows that infants born to mothers who receive two doses of an mRNA COVID-19 vaccine — such as the Pfizer-BioNTech or Moderna COVID-19 vaccine — might have a lower risk of hospitalization due to COVID-19 infection in their first six months of life.

COVID-19 vaccines don’t cause infection with the COVID-19 virus, including in pregnant women or their babies. None of the COVID-19 vaccines contain the live virus that causes COVID-19. Also, keep in mind that mRNA COVID-19 vaccines don’t alter your DNA or cause genetic changes.

Findings from a large study of more than 40,000 women show that getting a COVID-19 vaccine during pregnancy poses no serious risks for pregnant women who were vaccinated or their babies. Most of the women in the study received an mRNA vaccine, such as the Pfizer-BioNTech or Moderna COVID-19 vaccine.

The study adds to evidence that COVID-19 vaccination during pregnancy isn’t associated with an increased risk of premature birth. Also, babies born to pregnant women who received a COVID-19 vaccine aren’t at increased risk of low birth weight.

It’s also recommended that you get a COVID-19 vaccine if you are trying to get pregnant or might become pregnant in the future. There is currently no evidence that any COVID-19 vaccines cause fertility problems.

If you haven’t yet received a COVID-19 vaccine or if you’re due for a booster shot, an mRNA vaccine, such as the Pfizer-BioNTech or Moderna COVID-19 vaccine, is preferred in most situations.

If you become pregnant after receiving the first dose of a COVID-19 vaccine that requires two doses, it’s recommended that you get your second shot. It’s also recommended that pregnant women receive a COVID-19 booster shot when it’s time to get one. If possible, people who live with you also should be vaccinated against COVID-19. If you have concerns, talk to your health care provider about the risks and benefits.

What you can do

There are many steps you and people in your household can take to reduce your risk of infection from the COVID-19 virus and reduce the risk of spreading it to others.

  • Get vaccinated.
  • Avoid close contact with anyone who is sick or has symptoms.
  • Keep distance between yourself and others (within about 6 feet, or 2 meters) when you’re in indoor public spaces if you’re not fully vaccinated. This is especially important if you have a higher risk of serious illness.
  • Wear a well-fitting face mask in indoor public spaces if you’re in an area with a high number of people with COVID-19 in the hospital and new COVID-19 cases, whether or not you’re vaccinated. The CDC recommends wearing the most protective mask possible that you’ll wear regularly, fits well and is comfortable.
  • Wash your hands often with soap and water for at least 20 seconds, or use an alcohol-based hand sanitizer that contains at least 60% alcohol.
  • Avoid crowds and indoor spaces that have poor airflow.
  • Cover your mouth and nose with your elbow or a tissue when you cough or sneeze. Throw away the used tissue. Wash your hands right away.
  • Avoid touching your eyes, nose and mouth.
  • Clean and disinfect high-touch surfaces, such as doorknobs, light switches, electronics and counters, regularly.
  • Stay home from work, school and public areas and stay home in isolation if you’re sick, unless you’re going to get medical care. Avoid public transportation, taxis and ride-hailing services if you’re sick.

Above all, focus on taking care of yourself and your baby. Contact your health care provider to discuss any concerns. If you’re having trouble managing stress or anxiety, talk to your health care provider or a mental health counselor about coping strategies.

Treatment of Covid in Pregnancy

The following document provides summary information for healthcare professionals, and describes the available evidence regarding the fetal risks associated with medications that are being used in patients with COVID-19.

This document is not intended to act as a clinical guideline for the pharmacological management of pregnant patients with COVID-19. The UK Royal College of Obstetricians and Gynaecologists (RCOG) are regularly updating their clinical advice to both healthcare professionals and pregnant women regarding COVID-19 in pregnancy; this information can be found here.

Owing to the potential for COVID-19 to cause significant disease and mortality in pregnant women, the benefits of maternal treatment should be carefully considered against the fetal/neonatal risks discussed below. In the context of COVID-19, pregnancy is not a contraindication to any of the treatment options discussed below. However, safety data and efficacy are yet to be established for some treatments.

Given that the scientific understanding of the coronavirus pandemic is constantly changing, this document will be updated as new information becomes available.

Background

The current outbreak of coronavirus disease 2019 (COVID-19) was declared a global pandemic by the World Health Organization (WHO) on 11th March 2020.[1]

COVID-19 is acquired following infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen, a novel enveloped RNA betacoronavirus which infects host epithelial cells via angiotensin-converting enzyme 2 (ACE2). As ACE2 is predominantly expressed on type II alveolar cells of the lung, [1] patients with COVID-19 manifest a spectrum of upper and lower respiratory tract symptoms.[1]

Pregnant women do not appear to be more likely to contract SARS-CoV-2 than the general population.[2] Most women who are infected during pregnancy will be asymptomatic (70-80%)[3], and the majority of those who do become symptomatic will only ever experience mild to moderate symptoms.[3] However, natural physiological adaptations to pregnancy result in changes to the immune and respiratory systems, cardiovascular function, and coagulation, which may in turn affect the progression of COVID-19. Intensive care admission and invasive ventilation have been shown to be more common among pregnant women with COVID-19 than in infected non-pregnant women of the same age.[4, 5] The UK Obstetric Surveillance Survey (UKOSS) identified increased rates of intensive care admission among pregnant women with COVID-19 in comparison with uninfected pregnant women.[6] Risk factors associated with severe COVID-19, ICU admission or invasive ventilation during pregnancy include: maternal age ≥35, BMI ≥30, and pre-existing maternal comorbidity, specifically chronic hypertension and pre-pregnancy diabetes.[4] Pregnant women also appear to be at increased risk of complications in their third trimester when compared to earlier in pregnancy.[3]

COVID-19 vaccination has proven highly effective at decreasing hospitalisation and ICU admission in pregnancy, with UKHSA data demonstrating that a very small proportion (<1%) of pregnant women admitted to hospital with COVID-19 had received two doses of the vaccine.[7] More information about COVID-19 vaccination in pregnancy can be found on the ‘Use of non-live vaccines in pregnancy’ summary.

The available data do not currently demonstrate an association between COVID-19 infection in pregnancy and an increased risk of congenital anomalies, and limited evidence has not shown any association with an increased risk of miscarriage. However, COVID-19 in pregnancy has been associated with impaired fetal growth and an approximate 2-fold increased risk of stillbirth. Symptomatic COVID-19 has been associated with an approximate 3-fold increased risk of preterm birth (likely influenced by iatrogenic deliveries). Excluding complications which arise as a result of prematurity, the risk of neonatal complications does not appear to be increased with COVID-19 infection in pregnancy.[3]

Imaging

Diagnostic chest X-rays and chest CT scans may be required when investigating pregnant patients with COVID-19.

The UKTIS monograph ‘Exposure to Ionising Radiation in Pregnancy’ provides an overview of the fetal risks following maternal exposure to diagnostic radiation in pregnancy. In summary, national guidelines state that pregnant women should not be exposed to doses of radiation in excess of 50mGy, and a single chest X-ray or cross-sectional chest CT scan would not be expected to exceed this dose. Furthermore, results from preclinical animal studies and epidemiological human surveillance together provide evidence that exposure to total absorbed doses of less than 100mGy is unlikely to result in increased risks of dose-dependent effects (including fetal loss, malformation growth restriction or neurodevelopmental impairment). Very small increased risks of non-dose-dependent effects may exist, but these are likely to be very small and minimally raised above the background rate.

Chest X-ray and cross-sectional imaging (CT scanning or MRI) should not be withheld on fetal grounds (since the risk to the fetus is minimal) if there is a clinical need to image pregnant women.

Treatment guidelines

Treatment guidelines for the general populations are provided by the National Institute for Health and Care Excellence.[8] Pregnancy specific treatment guidelines are provided jointly by the Royal College of Midwives and the Royal College of Obstetricians and Gynaecologists.[9] Readers are encouraged to check the latest recommendations provided in these treatment guidelines, and use these in conjunction with the safety information provided below.

Treatment options for patients with COVID-19

The following therapies have either been identified as possible treatment options by the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) or have been listed as investigational medicinal products in COVID-19 clinical trials that are recorded on the EU register.

Additional treatment options are likely to emerge as the scientific and clinical understanding of COVID-19 improve; these will be added to future updates of this document.

If there are any treatment options which this document does not discuss please contact the telephone service (0344 892 0909 – available Monday to Friday, excl. bank holidays, 9am to 5pm) for more information.

Aspirin

There is no specific information on malformation rates following use of low-dose aspirin (75-300mg/day) in pregnancy but in most cases this treatment is initiated after 12 weeks of pregnancy when fetal organogenesis is complete and there is little risk of medication-induced structural malformation. Increased risks of gastroschisis, cleft lip and palate, and neural tube defects have been reported following maternal use of aspirin during pregnancy (mainly at analgesic doses); however, data are conflicting and may also be confounded, and a causal association with aspirin has not been proven. Data relating to risk of cardiac malformations are reassuring.

The majority of evidence suggests that there is no association between the use of low-dose aspirin and miscarriage, fetal growth restriction, or preterm delivery. Stillbirth data are limited to one small randomised-controlled trial that found no increased risk following exposure to low-dose aspirin. No data are available on pregnancy outcomes following aspirin use at analgesic doses, and data on neurodevelopmental outcomes following in utero aspirin exposure at any dose are too limited to facilitate an evidence-based assessment of risk.

Please refer to the UKTIS monograph ‘Use of Aspirin in Pregnancy’ for further information regarding the use of low dose aspirin in pregnancy.

Corticosteroids

The interim results of the RECOVERY trial have demonstrated a significant reduction in 28-day mortality for individuals with COVID-19 requiring oxygen who were given steroid (dexamethasone) therapy (age-adjusted rate ratio 0.83; 95% CI 0.75–0.93; P<0.001).[10] Corticosteroids are recommended for treating COVID-19 if patients require supplementary oxygen.[8]

The RCOG recommends prednisolone 40mg orally once daily (or methylprednisolone 32 mg once daily), and, in women unable to take oral medicine, hydrocortisone 80mg intravenously twice daily instead of dexamethasone treatment.[3] Hydrocortisone and prednisolone are extensively metabolised by the placenta, whilst dexamethasone crosses the placenta. It is reasonable to assume that prednisolone or methylprednisolone are as equally effective as hydrocortisone at treating the inflammation associated with COVID-19 and these substitutions are reasonable to prevent unnecessary fetal exposure to dexamethasone. The RECOVERY trial has recently initiated a comparison of high dose corticosteroids (prednisolone 130 mg or hydrocortisone 540 mg in four divided doses or intravenous methylprednisolone 100mg IV for five days; followed by prednisolone 65 mg or hydrocortisone 270 mg in four divided doses or intravenous methylprednisolone 50 mg for five days).[11]

The UKTIS monograph ‘Use of Systemic Corticosteroids in Pregnancy’ describes approximately 7,000 exposed pregnancies reported in the literature. Many of the studies reporting pregnancy outcomes following gestational exposure to systemic corticosteroids are limited by a lack of stratification to account for differing doses, treatment duration and steroid potencies. The available data may therefore be inadequate to assess the fetal risks posed by maternal high dose/potency corticosteroid exposure, or use for extended periods during pregnancy.

Although data regarding malformation risks following first trimester exposure are conflicting, the majority of the best quality evidence does not suggest increased risks in either the overall malformation rate, or for specific malformations (including orofacial clefts and cardiac anomalies). The small number of methodologically limited studies investigating miscarriage and intrauterine death risks do not provide reliable evidence of increased risks, and similarly there is no reliable evidence indicating use of systemic corticosteroids impairs fetal growth. Some studies have shown increased risks of preterm delivery, but the evidence is likely confounded by the underlying condition for which corticosteroids were administered.

Tocilizumab

Tocilizumab is a humanised monoclonal IgG1 antibody which binds and inhibits both soluble and membrane-bound IL-6 receptors, thereby inhibiting the pro-inflammatory activity of IL-6.[12] Randomised clinical trials have demonstrated that tocilizumab given to hospitalised patients with severe COVID-19 reduces the risk of death, lessens the need for mechanical ventilation, and decreases time spent in hospital.[13]

Evidence relating to the fetal effects following maternal use in pregnancy are limited, currently consisting of uncontrolled case reports/series’ which together describe approximately 600 exposed pregnancies.[14] Although adverse pregnancy outcomes have been described (including cases of congenital anomaly, miscarriages and preterm deliveries), the crude rates of these events do not generally appear to be notably increased above the background rate. The largest case series published to date is provided from a review of the manufacturer’s global safety database, describing 180 prospective exposed pregnancies with a crude malformation rate of 4.5% (95% CI 1.50 to 10.2%) and a crude miscarriage rate of 21.6% (95% CI 16.0 to 28.5%).[15] Although these crude rates are increased in comparison to the background risks (malformation 2-3%, miscarriage 10-20%), the findings are based on small numbers of exposed and affected pregnancies which produced wide confidence limits that overlap the expected rates. Furthermore, no pattern of malformation was observed, concomitant methotrexate exposure (a known teratogen and abortifacient) was described, and methodological biases likely exist. Controlled studies are therefore required before any meaningful assessment of the teratogenic risk can be provided.

Tocilizumab should be strongly considered for pregnant women with severe COVID who have a CRP>75 or are in, or may be going to, an intensive care unit.[9]

Whilst there are no m

ajor concerns about the use of tocilizumab in pregnancy, discussion with UKTIS is recommended. Due to high demand, tocilizumab may be subject to availability issues. The UK Department of Health and Social Care have recommended that sarilumab may be given in place of tocilizumab for adult patients hospitalised due to COVID-19, who meet the criteria for interleukin-6 receptor inhibitor treatment.

Sarilumab

Sarilumab is a human monoclonal antibody (IgG1 subtype) that specifically binds to both soluble and membrane-bound IL-6 receptors (IL-6Rα), and inhibits IL-6-mediated signalling, thereby inhibiting the pro-inflammatory activity of IL-6.[16]

There are currently no published data regarding the safety of sarilumab use in human pregnancy. Preclinical reproductive toxicity studies (using animal models) undertaken by the manufacturer have not been published in the peer-reviewed literature. Product literature states that pregnant Cynomolgus monkeys given intravenous sarilumab once-weekly from early gestation to birth experienced AUC plasma concentrations 83 times those seen in human therapy.[16] No adverse effects on the mother, embryo, fetus or neonate (up to 1 month after birth) were described.[16]

Given that monoclonal antibodies have highly selective pharmacological effects, it is anticipated that sarilumab will have a pregnancy safety profile similar to that of tocilizumab. In instances where tocilizumab is unavailable, the benefits of sarilumab treatment in hospitalised pregnant patients with severe COVID-19 who meet the requirements for IL-6 receptor inhibitor treatment will likely outweigh the unknown risks. As no human pregnancy data are currently available for sarilumab, careful collation of pregnancy outcome data is advised. To aid this data collection, healthcare professionals are encouraged to report cases of sarilumab exposure in pregnancy to UKTIS.

Sarilumab should be considered in place of tocilizumab (in women with COVID who have CRP>75 and are in, or need ICU admission).[8]

Ronapreve (REGN-COV2)

Ronapreve (REGN-COV2) is a mixture of two monoclonal antibodies (mAbs; casirivimab (REGN10933) and imdevimab (REGN10987) targeting non-overlapping epitopes on the SARS-CoV-2 spike protein[17]. The spike protein is a key mediator of viral infectivity required for attachment and entry into target cells by binding the ACE2 receptor.[18]

Results from a double blind, placebo controlled trial of 799 non-hospitalised adults with mild to moderate COVID-19 symptoms showed viral load reduction in patients treated with Ronapreve versus placebo at day seven.[19] Another randomised controlled trial described decreased mortality among hospitalised seronegative COVID-19 patients treated with Ronapreve in comparison with those allocated to standard care.[17]

The available pregnancy safety data are highly limited. Six case reports of exposure in pregnancy describe successful single dose administration of Ronapreve. Progression of COVID-19 symptoms (from mild to moderate – shortness of breath) beyond those observed at initial administration was only observed in one patient. Two of the women were exposed in the first trimester, one in the second trimester, and three in the third.[20, 21]Pregnancy outcome information has been described for three of the exposed pregnancies (one second trimester exposed, two third trimester exposed); (i) an uneventful labour with uncomplicated spontaneous vaginal delivery; (ii) preterm delivery (36 weeks) of a healthy fetus; and (iii) term delivery (37 weeks) of a healthy fetus.[20, 21] One of the neonates was admitted to the neonatal intensive care unit owing to intermittent tachypnea and presumed transient tachypnea of the newborn (COVID-19 test result was negative) with discharge on day 2 after delivery.[20] Of the remaining pregnancies, no adverse pregnancy events were reported at the time of the case report publications.

Ronapreve should be considered for women with COVID-19 and no SARS-CoV2 antibodies.[9]

Whilst the target for the monoclonal antibodies are unique to viral proteins and therefore unlikely to affect fetal development, minimal pregnancy exposure data (human or animal) are available for Ronapreve to establish safety. Discussion with UKTIS is encouraged, in order to collect pregnancy outcome data.

Sotrovimab

Sotrovimab is an IgG1 monoclonal antibody that binds to a conserved epitope on the spike protein receptor binding domain of SARS-CoV-2.[22] In the UK it is licensed for the treatment of symptomatic adults and adolescents with acute COVID-19 infection who do not require oxygen supplementation, and who are at increased risk of progressing to severe COVID infection.

Preclinical animal studies have not evaluated the risk of reproductive toxicity. However, the manufacturer reports no off-target binding in a cross-reactive binding assay that used a protein array enriched for human embryofetal proteins.[22]

As the binding target for sotrovimab is likely unique to COVID-19 viral proteins, it is not expected that the administration of sotrovimab in pregnancy would affect fetal development. Therefore, sotrovimab could be considered for use in women with COVID-19 where the benefits are expected to outweigh the risks. Discussion with UKTIS is encouraged, in order to collect pregnancy outcome data.

COVID-19 antivirals

A number of COVID-19 antiviral medications are under development. As these are newly developed medications, there is a lack of human pregnancy safety information for all these treatment options.

Molnupiravir is licensed for the treatment of mild to moderate COVID-19 in adults with a positive SARS-COV-2 diagnostic test, who have at least one risk factor for developing severe illness.[23] Preclinical animal reproductive toxicity studies have indicated possible teratogenic effects[23], and as such, molnupiravir is not recommended for use in pregnancy until further studies have established its effectiveness and safety. The manufacturer of molnupiravir recommends that women of childbearing potential should use effective contraception for the duration of treatment and for four days after the final dose. Pregnant women who have received molnupiravir at any stage in pregnancy, or became pregnant shortly after taking it, should be referred to UKTIS for further counselling and follow-up of the pregnancy outcome. Please see the UKTIS monograph, ‘Use of molnupiravir in pregnancy,’ for more information.

Paxlovid (nirmatrelvir/ritonavir) is licensed for the treatment of COVID-19 in adults who do not require supplemental oxygen, but who are at increased risk of developing severe illness.[24] Nirmatrelvir is a peptidomimetic inhibitor of the coronavirus 3C-like (3CL) protease which prevents viral replication.[24] Ritonavir is included in the formulation as a pharmacokinetic enhancer, to inhibit CYP3A mediated metabolism of nirmatrelvir, and does not possess pharmacodynamic activity against SARS-CoV-2 3CL protease.[24] Preclinical animal reproductive toxicity studies have not identified adverse effects on fetal morphology or embryo-fetal viability in rat or rabbit models with doses of nirmatrelvir up to 12 times the human dose (equivalence based on predicted AUC concentrations).The offspring of pregnant rabbits administered 24 times the equivalent human dose, lower fetal body weights were observed but evidence of maternal toxicity was described (impact on weight gain/food consumption).[24] There is a large amount of published evidence relating to the safety of ritonavir in human pregnancy, collected from antiretroviral and HIV/AIDS pregnancy registries. Overall, these data do not provide evidence that ritonavir use in the first trimester is associated with an increased risk of malformation above the expected background rate of 2-3%.[25] There is also no evidence that liponavir/ritonavir combination therapy in pregnancy had any detectable impact on postnatal development.[26] Data investigating other adverse pregnancy outcomes (such as miscarriage, preterm delivery, fetal growth impairment or stillbirth risks) are lacking. Due to a lack of human pregnancy safety data, the manufacturer of Paxlovid does not recommend use in pregnancy. However, the benefits of use could outweigh the risks in some circumstances (see paragraph below). As CYP3A4 metabolic activity and glomerular filtration increase during pregnancy, it is unclear whether pregnancy may impact the pharmacokinetics of Paxlovid. Further research into the efficacy of this medication in pregnancy is required.

Despite the lack of human pregnancy safety data for COVID-19 antivirals, there may be specific circumstances where the benefits of use during pregnancy could outweigh the risks. Such circumstances may include the use in women at high risk of developing severe disease (due to non-vaccination status or clinical vulnerabilities), or in women experiencing severe symptoms of COVID-19 where other more established treatments have failed. However, the efficacy of these treatments may not have been proven in all such clinical scenarios. Where COVID-19 antivirals are being considered for use during pregnancy, the risks and benefits should be discussed on an individual patient basis. Alternative early treatment options that do not pose theoretical risks of fetal harm, such as casirivimab/imdevimab (Ronapreve) or sotrovimab monoclonal antibodies may be preferred for pregnant women. Discussion with UKTIS is recommended in all cases where COVID-19 antiviral treatment is being considered in pregnancy.

In collaboration with the MHRA, UKTIS is currently conducting enhanced safety monitoring of pregnancies exposed to COVID-19 antiviral medications (including molnupiravir and Paxlovid). If you are aware of any women who have used COVID-19 antivirals during pregnancy, or became pregnant shortly after finishing treatment, please report these pregnancies to UKTIS (telephone 0344 892 0909, available Monday to Friday excluding Bank Holidays, 9am to 5pm).

Remdesivir

Remdesivir is a novel, broad-acting antiviral nucleotide prodrug which effectively inhibits replication of SARS-CoV-2 in vitro and that of related coronaviruses including MERS-CoV in non-human primates.[1] A 2020 NICE evidence review concluded that there was some evidence to support the benefit of remdesivir use in decreasing the need for supportive measures, including mechanical ventilation, and reducing the time to recovery in patients with mild/moderate to severe COVID-19 receiving supplemental oxygen.[27] A 2021 study has also shown that use of remdesivir within seven days of symptom onset among patients at high risk for severe disease progression resulted in an 87% reduction in risk of hospitalisation or death.[28]

Remdesivir is not considered highly effective in the treatment of acute COVID-19. Clinical guidelines for the UK state that remdesivir may be used in patients requiring low-flow supplemental oxygen.[27] Remdesivir may also be used as a prophylactic treatment in patients with hospital onset of COVID-19, where treatment is being initiated within seven days of symptom onset and where a neutralising monoclonal antibody (nMAB) is either contraindicated or otherwise unavailable.[29]

There are very limited animal or human pregnancy exposure data available. A single small case series of six pregnant women exposed at various (unreported) stages of pregnancy whilst being treated for Ebola did not describe any adverse pregnancy outcomes.[30]

More recent case reports have not identified any particular concerns,[31-33] but it should be noted that remdesivir was given outside of the first trimester in all these case reports. A case series of 86 women (67 were pregnant, 19 immediate postpartum) were given remdesivir on a compassionate basis for severe COVID-19 infection. Although rates of pre-term delivery were high (likely related to severe COVID-19) the study demonstrated a high rate of clinical recovery.[34]

Remdesivir can be given in pregnancy if the benefits outweigh the potential risks. Discussion with UKTIS is recommended to discuss the clinical circumstances around each individual case.

Anakinra

Anakinra is a recombinant selective IL-1 receptor antagonist. It blocks the biologic activity of natural IL-1 by competitively inhibiting the binding of IL-1 to the interleukin-1 type receptor.[35] No observed effects were seen on embryo-fetal development in rats and rabbits at doses up to 100 time the human dose (2mg/kg/day).[35] The limited human pregnancy exposure data consist of 57 pregnancies from a number of case reports, case series and registry data; with 23 using anakinra throughout pregnancy.[36-42] Two cases of renal anomalies in exposed infants were reported, one renal agenesis in a twin with a genetic mutation[37] and one renal agenesis and ectopic neuropophysis with growth hormone deficiency in an infant exposed in utero from 9/40 until delivery at 38/40.[40] In addition, two cases of oligohydramnios were also seen in five pregnancies from a registry.[39] However, one patient was also exposed to three other DMARDs and celecoxib, a drug previously associated with low amniotic fluid levels.

Pregnancy data are currently limited, and although renal agenesis and oligohydramnios have been described in exposed infants, controlled studies are lacking, therefore any meaningful assessment of the teratogenic risk cannot currently be provided. Discussion with UKTIS is recommended prior to treatment.

Bamlanivimab

Bamlanivimab, also known as LY-CoV555 and LY3819253, is a neutralising monoclonal antibody that targets the receptor-binding domain of the spike protein of SARS-CoV2. Bamlanivimab has been found to be ineffective in treating hospitalised patients with COVID-19.[43][30] There are limited data available to determine bamlanivimab’s effectiveness in outpatients with mild to moderate COVID-19. Interim results from the BLAZE-1 trial in the United States indicate a potential clinical benefit but further data are required to draw conclusions.[44]

Bamlanivimab remains an investigational drug and is not licensed. No pregnancy exposure data (human or animal) are currently available. Discussion with UKTIS is recommended prior to treatment.

Hydroxychloroquine

Hydroxychloroquine has not shown to be effective for the treatment of COVID-19[10, 45] and is therefore not recommended for treating COVID-19 in pregnancy. Please refer to the UKTIS monograph ‘Use of Chloroquine in Pregnancy‘ for further information regarding the use of hydroxychloroquine in pregnancy.

Azithromycin

Azithromycin has not been shown to benefit clinical outcome including clinical status or mortality, when added to standard care (which included hydroxychloroquine) in treating patients admitted to hospital with COVID-19.[46]

Please refer to the UKTIS monograph ‘Use of Macrolide Antibiotics in Pregnancy’ for further information regarding the use of azithromycin in pregnancy.

Lopinavir/ritonavir

Lopinavir/ritonavir has not been shown to be effective for the treatment of COVID-19[10, 45] and is therefore not recommended for treating COVID-19 in pregnancy.

Lopinavir and ritonavir are both HIV-protease inhibitors. Typically, ritonavir is administered alongside other protease inhibitors to act as a competitive inhibitor of CYP3A4, thereby enhancing bioavailability and prolonging pharmacodynamic activity.[47]]

Evidence relating to the fetal effects following maternal use in pregnancy is mainly provided from large uncontrolled case series collected from antiretroviral pregnancy registries. Together these data provide outcomes for approximately 3,000 exposed pregnancies and do not suggest an increased risk of malformation.[47] Studies investigating neurodevelopmental outcomes have also provided reassuring findings.[47] However, data concerning other adverse pregnancy outcomes are lacking.

Interferon beta-1a

The SOLIDARITY trial showed no reduction in mortality (in unventilated patients or any other subgroup), initiation of ventilation or hospitalisation duration in COVID-19 patients treated with interferon beta-1a (n=1,412) or with interferon beta -1a and lopinavir (n=651) when compared to 4,088 receiving standard care.[45] Beta interferon is not currently recommended by the NHS.

Interferons are a family of naturally occurring cytokines that are produced in response to viral infection, and mediate antiviral, antiproliferative and immunomodulatory activities.[48] Studies assessing teratogenic or fetotoxic risks have typically assessed exposure to any interferon beta (including 1a and 1b subtypes) in the treatment of multiple sclerosis.

The UKTIS monograph ‘Use of Interferon Beta in Pregnancy’ describes approximately 2,750 exposed pregnancies reported in the literature.

Colchicine

Colchicine is a mitotic spindle fibre inhibitor that induces metaphase arrest in cells undergoing mitosis.[49] Its anti-inflammatory effect has been attributed to the disruption of microtubules in neutrophils, which in turn inhibit migration toward the chemotactic factors.[50] Pregnancy exposure data are mainly provided from uncontrolled case reports of patients treated for Familial Mediterranean Fever and together describe approximately 2,100 exposed pregnancies.[49] These data do not currently indicate an increased risk of miscarriage, congenital malformation or chromosomal anomalies.

Imatinib

Imatinib is a tyrosine kinase inhibitor that potently inhibits the activity of the Bcr-Abl tyrosine kinase, as well as several receptor tyrosine kinases, and is typically used in the treatment of haematological malignancies.[51] A clinical trial is under way in the Netherlands investigating whether early imatinib use can prevent hypoxemic respiratory failure through preventing extensive vascular leakage and pulmonary oedema in patients with COVID-19.[52]

Data regarding imatinib use in human pregnancy are limited to retrospective case reports and case series describing approximately 300 pregnancies exposed in the treatment of CML, with around half exposed in the first trimester.[53] Although malformations including combinations of exomphalos, renal agenesis,[54, 55] scoliosis and hemivertebrae[55] have been described in exposed infants, controlled studies are lacking, therefore any meaningful assessment of the teratogenic risk cannot currently be provided.

Baricitinib

Baricitinib is a Janus kinase inhibitor which machine learning has identified as a potential drug for the treatment of COVID-19 by inhibiting the endocytosis of SARS-CoV-2 into pulmonary cells.[1] A case report was located in the literature which described a patient with rheumatoid arthritis who was exposed to baricitinib from conception to 17 weeks. The outcome was a healthy infant born at 38 weeks.[56] Tofacitinib is another Janus kinase inhibitor; although data are limited with approximately 60 exposed pregnancies published in a small number of uncontrolled case series[57, 58] and a case report[59], crude rates of adverse pregnancy outcomes do not appear to be increased in comparison with their respective expected background rates.

Other treatment options

Clinical trials of several other treatment options are recorded in the EU register, including camostat mesilate (a serine protease inhibitor) and sargramostim (a recombinant human granulocyte-macrophage colony stimulating growth factor). No pregnancy exposure data (human or animal) were located for these medications.

Pregnant With Covid When To Go To Hospital

Experts are still studying COVID-19 and pregnancy. From what they know so far, pregnant people do not seem more likely than other people to get the infection.

However, compared with females of the same age who are not pregnant, pregnant people with COVID-19 seem to be more likely to get very sick and need to stay in the ICU. (“ICU” is short for “intensive care unit.”) In pregnant people, the risk of getting very sick or dying is highest in those who are age 35 or older, or have certain health conditions like obesity, high blood pressure, or diabetes. But most people recover before having their baby, and do not need to stay in the hospital.

What should I do if I have symptoms?If you have a fever, cough, trouble breathing, runny nose, or other symptoms of COVID-19, call your doctor, nurse, or midwife. They can tell you what to do and whether you need to be seen in person. They will also tell you if you should be tested for the virus that causes COVID-19.

If I am pregnant and get infected, can I pass the virus to my baby?Experts think it might be possible for a baby to get the infection while still in the uterus. But this seems to be very uncommon. And when it does happen, most babies do not get very sick.

It is also possible to pass the virus to the baby during childbirth or after the baby is born. If you have COVID-19 when you give birth, there are ways to lower this risk.

Can COVID-19 cause problems with pregnancy?From what experts know so far, most people who get COVID-19 during pregnancy will not have serious problems. But problems can happen if the mother becomes seriously ill.

Pregnant people who get COVID-19 might have an increased risk of preterm birth. This is when the baby is born before 37 weeks of pregnancy. This seems to be more of a risk in people who get very sick and have pneumonia. Preterm birth can be dangerous, because babies who are born too early can have serious health problems.

Getting COVID-19 during pregnancy might also increase the risk of stillbirth. This is when a baby dies before it is born. The risk of preterm birth is much higher than the risk of stillbirth.

How is COVID-19 treated?Most people with mild illness will be able to stay home while they get better. Mild illness means you might have symptoms like fever and cough, but you do not have trouble breathing. Ask your doctor, nurse, or midwife about ways to relieve these symptoms.

People with serious symptoms or other health problems might need to go to the hospital. If you need to be treated in the hospital, the doctors and nurses will also monitor your baby’s health.

In certain cases, doctors might recommend medicines that seem to help people who are severely ill. But some of these medicines are not safe to take if you are pregnant.

Can COVID-19 be prevented?The best way to prevent COVID-19 is to get vaccinated.

In the United States, the first vaccines became available in late 2020. Since then, experts have been studying their safety in people who are pregnant or breastfeeding. Many pregnant people have gotten the vaccine without any problems. The vaccine does not increase the risk of miscarriage (pregnancy loss) or harm the baby. Based on the available evidence, experts recommend that pregnant people get the vaccine. They also recommend getting a “booster” shot for extra protection. Ask your doctor, nurse, or midwife about the best time to get the booster shot.

Vaccines work very well to prevent serious illness and death from COVID-19. Because pregnant people seem to be at high risk for getting very sick if they do get infected, vaccination is especially important. There is also evidence that people who are vaccinated have a lower risk of problems that affect the baby, like stillbirth. More information about COVID-19 vaccines and boosters is available separately. (See “Patient education: COVID-19 vaccines (The Basics)”.)

You can also protect yourself and others by “social distancing” (staying at least 6 feet, or 2 meters, away from other people) and wearing a face mask when you are around other people (figure 1). You should also be sure to wash your hands often.

Will my regular prenatal appointments change?Your doctor, nurse, or midwife will work with you to make a plan for your visits during pregnancy. If you live in an area where there are a lot of cases of COVID-19, there will likely be some changes. For example:

●Your partner might not be able to join you for appointments

●If you have any symptoms of COVID-19, you will probably need to wear a medical mask during your appointments

●Your doctor, nurse, or midwife might group certain tests together so you don’t need to go in as often

●Your doctor, nurse, or midwife might suggest replacing some visits with a phone or video call

These changes can feel stressful. It can help to keep in mind that the goal is to help protect you and others.

What will my delivery be like?Different hospitals and birth centers have different rules to help keep people safe. These might include guidelines for things like wearing a mask and how many visitors you can have. Your doctor, nurse, or midwife will talk to you about what to expect.

You will be checked for fever and other symptoms of COVID-19 when you arrive to give birth. This might happen earlier if you are scheduled to be “induced” or have a cesarean birth (“c-section”). You might be tested for the virus, too.

If you have COVID-19 when you go into labor, the doctors and nurses will take steps to protect others around you. For example, you will need to wear a medical mask. You will still be able to have a vaginal birth, if that is what you planned. You don’t need a c-section just because you are sick.

If you have COVID-19, your doctor or nurse might suggest staying apart from your baby until you get better. This will depend on how sick you are, whether your baby has been tested for the virus, and other factors. Most people are not separated from their babies. You will need to wear a face mask to lower the risk of spreading the infection. You might need to take other precautions, too. These things can be hard. But they are important in order to protect your baby.

What if I want to breastfeed?Breastfeeding has many benefits for both you and your baby. If you have COVID-19, there might be a very small chance of passing the infection to your baby through breast milk. But no babies have become very sick in this way.

Whether or not you breastfeed, it’s important to be extra careful when feeding or holding your baby. You could pass the virus to your baby through close contact. You can protect your baby by washing your hands often and wearing a face mask while you feed them.

You might choose to pump breast milk for your baby. If you are sick, wash your hands carefully before pumping, and wear a mask while you pump. If possible, have a healthy person clean your pump thoroughly between uses.

If you are planning to breastfeed, experts recommend getting the COVID-19 vaccine if you haven’t already. Vaccines work by causing your immune system to make “antibodies,” which are proteins that fight against the virus. These antibodies enter your breast milk, which might help protect your baby in addition to protecting you.

What can I do to cope with stress and anxiety?It’s normal to feel anxious or worried about COVID-19. If you are pregnant, you might feel sad about having to cancel celebrations or limit contact with relatives and friends.

You can take care of yourself by:

●Getting vaccinated and boosted

●Taking breaks from the news

●Getting regular exercise and eat healthy foods

●Trying to find activities that you enjoy and can do in your home

●Staying in touch with your friends and family members

Keep in mind that most pregnant people do not get severely ill from COVID-19. It helps to be prepared, and it’s important to do what you can to lower your risk. But try not to panic.

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