Caring for Pregnant Patients With Asthma During the COVID-19 Pandemic

Updated August 6, 2021

There is increasing information about COVID-19 and pregnancy. We hope the following information will be useful to practicing allergists and their patients.

Does pregnancy increase the need for critical care in the setting of COVID-19 infection?

Historically, pregnant individuals have been thought to be at increased risk of severe morbidity and mortality from specific respiratory infections, such as flu and SARS. As of October 13, 2020, a total of 26,364 cases of COVID-19 in pregnant women were reported to the Centers for Disease Control and Prevention (CDC) with a total of 45 deaths.

A recent prospective cohort study from Italy found that the cumulative incidence of COVID-19 infection during the first trimester was 10.1% with a high prevalence of asymptomatic patients (Cosma). In another prospective cohort study of 137 pregnant women infected with SARS-CoV2 on admission for delivery, 75% were asymptomatic on admission and 63.5% of these women remained asymptomatic throughout hospitalization. Only 3.6% developed a severe infection (Hcini).

In an analysis of approximately 400,000 women aged 15–44 years with symptomatic COVID-19, intensive care unit (ICU) admission, invasive ventilation, extracorporeal membrane oxygenation, and death were more likely in pregnant women than in nonpregnant women.

Risk of receiving invasive ventilation in pregnant women aged 35-44 was 3.6 times that of non-pregnant women (Zambrano). However, the data did not distinguish hospitalizations for COVID-19 from hospital admissions for pregnancy-related conditions or for delivery. A recent meta-analysis of 77 studies from China, Europe and the United States reported that high body mass index, chronic hypertension, and pre-existing diabetes were associated with severe COVID-19 in pregnancy. Pre-existing comorbidity was a risk factor for admission to the ICU [odds ratio (OR) 4.21, 95% confidence interval (CI) 1.06-16.72] and invasive ventilation (OR 4.48, 95% CI 1.40-14.37) (Allotey). Pregnant women should be counseled about the potential risk for severe illness from COVID-19 and conscientiously take the same precautions as the general public to prevent infection, particularly if they have comorbid conditions mentioned above. If they do become sick, prompt management of symptoms is important. 

Is timing of delivery affected by COVID-19?

Having severe symptoms or complications from any illness might affect timing of delivery. Reports of women hospitalized with symptoms of COVID-19 during the second and third trimesters of pregnancy have included preterm deliveries, but it is not clear if these were due to the mother’s infection or other reasons (Rasmussen). For women with suspected or confirmed COVID-19 in the third trimester who recover, it is reasonable to attempt to postpone elective delivery until a negative test result is obtained in an attempt to avoid transmission to the neonate. 

Does COVID-19 present an increased risk of adverse perinatal and fetal outcomes?

Maternal SARS-CoV-2 infection may lead to perinatal complications directly or indirectly through placental dysfunction. Placental abnormalities such as malperfusion and functional impairment have been reported in pregnant women with COVID-19, potentially leading to outcomes such as preterm birth, intrauterine growth restriction, low birth weight and possibly early pregnancy loss (Cavalcante). As noted above, some pregnant women with COVID-19 have had preterm births, and early reports showed a higher rate of delivery by caesarean sections. This was supported by a prospective cohort study of 675 pregnant patients from three New York City hospitals. Caesarean delivery rates were 46.7% in symptomatic COVID-19 and 45.5% in asymptomatic COVID-19 versus 30.9% in patients without COVID-19 (Prabhu).

A U.K. study compared rates of stillbirth and preterm delivery in pre-pandemic and pandemic cohorts. The incidence of stillbirth was significantly higher during the pandemic period (9.31 per 1,000 births) versus the pre-pandemic period (2.38 per 1,000 births). There was no increase in the incidence of preterm births. Interestingly, none of the women who experienced stillbirths had symptoms suggestive of SARS-CoV-2 infection, so the reasons for this increase remain unclear (Khalil). In a prospective study of over 20,000 pregnant women in Nepal, there was a significant increase in neonatal mortality during the pandemic (40 per 1,000 births) versus the pre-pandemic period (13 per 1,000 births), and stillbirths during the pandemic (21 per 1,000 births) versus pre-pandemic (14 per 1,000 births), highlighting the need for access to care for those in fragile healthcare systems (Ashish). A recent meta-analysis reported that pregnant women with COVID-19 are at increased risk of delivering a preterm birth (OR 3.01, 95% CI 1.16-7.85). However, this is based on a small number of studies with significant heterogeneity (Allotey).

A recent multinational cohort study from 73 centers in 22 different countries found that earlier gestational age at infection (first trimester), maternal ventilator support and low birth weight are risk factors associated with adverse perinatal outcomes (DiMascio). A cross-sectional study of pregnant women with severe COVID-19 in Brazil found that the main risk factors for maternal death by COVID-19 were obesity, diabetes, cardiovascular disease, and presence of ARDS (Takemoto). A U.S. matched case control study of 61 cases of pregnant women with COVID-19 infection found that odds of adverse outcomes such as preeclampsia, venous thromboembolism, maternal ICU admission, and maternal death, were 3.4 times more likely in the case group compared to uninfected matched comparison pregnancies. In addition, neonatal outcomes such as respiratory distress syndrome, intraventricular hemorrhage and neonatal death were 1.7 times more likely in the case group. This was largely driven by those patients with severe disease. In fact, those patients with mild COVID-19 had outcomes similar to matched controls (Brandt).

PRIORITY, a prospective U.S. cohort study, recently reported early findings in 263 infants born to mothers with confirmed SARS-CoV-2 during pregnancy. NICU admission, preterm birth and pneumonia or respiratory tract infection through 6-8 weeks of age did not differ between those born to mothers testing positive to SARS-CoV-2 and those born to mothers testing negative. However, infants born to mothers who first tested positive 0–14 days prior to delivery were also born earlier (Flaherman).

Among 3,912 infants with known gestational age born to women with SARS-CoV-2 infection in another study, 12.9% were preterm (<37 weeks), which was higher than a national estimate of 10.2% (Woodworth).

In a recent study where all women presenting in labor underwent COVID-19 testing, 65% of women with positive tests were asymptomatic, and those who tested positive were more likely to have preeclampsia (7.7% versus 4.3%; prevalence ratio, 1.84; 95% CI, 1.004-3.36). COVID-19 illness severity may also affect pregnancy outcome (Ahlberg). In a cohort study of 252 SARS-CoV-2 positive pregnant women, severe or critical illness prior to 37 weeks gestation was associated with pregnancy loss and preterm birth (Adhikari).

In a U.S. retrospective cohort study of 1,856 births, there was a two-fold increased risk of hypertensive disorders of pregnancy in women with COVID-19 infection. In addition, early infection seemed to be more associated with hypertensive disorders developing (Rosenbloom). Similarly, in a prospective, observational study of 42 pregnancies, 75% of those women with severe COVID-19 presented with signs and symptoms of preeclampsia (Mendoza). A multi-center study including over 18,000 pregnancies across 3 years found no change in the rates of third trimester stillbirth during the first five months of the COVID-19 pandemic (Bunnell).

Another study looked at the association of early gestational infection with adverse fetal and perinatal outcomes. They found that infection during first or second trimesters was not associated with adverse perinatal outcomes such as growth restriction or placental dysfunction (Rosen).

Can maternal SARS-CoV-2 infection be transmitted to the fetus?

In reports of a limited number of infants born to women with COVID-19 around the time of delivery, most newborns have not had evidence of infection. However, a small number of newborns have tested positive for the virus soon after delivery. This suggests the possibility that the virus could pass from a mother to a baby during pregnancy. A recent study measured viral load in COVID-19 positive pregnant mothers and found that it was not associated with COVID-19 positivity in neonates (Anand). In fact, risk of transmission to neonate by rooming-in and breastfeeding was low. In a meta-analysis including 230 women with COVID-19 and 156 newborns, the vertical transmission rate calculated by SARS-CoV-2 nucleic acid tests was 3.91% (Chi). In the PRIORITY study described above of 263 infants born to mothers with confirmed SARS-CoV-2 during pregnancy, the estimated incidence of a positive infant SARS- CoV-2 test was low at 1.1%. In another study, among 610 (21.3%) infants with testing results, 2.6% had positive SARS-CoV-2 results, primarily those born to women with infection at delivery (Woodworth). A retrospective cohort analysis of 100 neonates born to 100 mothers with SARS-CoV-2 infection in New York hospitals found that there was no evidence of vertical transmission (Dumitriu).

Are there special considerations for pregnant women with asthma?

Few data exist to indicate that having asthma is associated with an increased risk of becoming infected with COVID-19 or a more severe course in the non-pregnant infected patient. Recent reassuring data show that having asthma was not associated with an increased risk of hospitalization or even mortality in COVID-19 hospitalized patients (Chhiba). There are even fewer data for pregnant asthmatic women with COVID-19. However, the CDC does indicate that those with moderate to severe asthma might be at a higher risk for severe illness from COVID-19. In one study of 46 pregnant women with COVID-19 infection, four had asthma. Of the six women with severe disease in that study, two had asthma, but one was overweight and the other was obese with hypertension (Lokken). Current recommendations emphasize the need to maintain asthma control during pregnancy. Reducing controller therapy could put pregnant women with asthma at increased risk of an asthma exacerbation necessitating medical care, which could then put them at an increased risk of being exposed to COVID-19. 

Is breastfeeding safe during COVID-19 infection?

Breast milk provides protection against serious childhood infections. Women are often encouraged to continue breastfeeding or provide breast milk even when they are sick with a virus, such as the flu. Information about COVID-19 in breastfeeding women is limited at this time. Most case reports have not detected virus in the breastmilk of infected mothers. In a study of 18 women with confirmed SARS-CoV-2 infection, one breast milk sample had detectable SARS-CoV-2 RNA, but the viral culture for that sample was negative (Chambers). No other breast milk samples from the 18 women had an evidence of infectious virus. In another study that included 24 mothers confirmed with COVID-19 and 19 with suspected infection, no breast milk samples tested positive for the SARS-Co-V-2 nucleic acid (Peng). In a review of 46 COVID-19 positive mothers whose breast milk samples were tested for SARS-CoV-2, 43 samples tested negative and only three tested positive. Of the three mothers whose breast milk samples tested positive, only one infant tested positive for the virus (Centeno-Tablante). This suggests that breast milk may not be a potential source of infection for the infant. In fact, one group found that there was no clinical evidence of infections in infants who were breastfed with mothers wearing masks, appropriate hand and breast hygiene, and with newborns kept six feet away from mothers (Kyle).

Are there any data on the safety of remdesivir in the management of critically ill pregnant COVID-19 patients?

Remdesivir was recently given emergency use authorization (EUA) by the Food and Drug Administration (FDA). Data on the use in pregnancy is limited. Manufacturer safety data indicate no reproductive developmental toxicity in animals at clinically relevant doses. Embryonic toxicity was only noted when systemically toxic doses were administered to female animals before conception. A recent case report describes one pregnant patient who received compassionate use of remdesivir and developed transaminitis, which is a noted side effect of remdesivir (Malderelli).

Should pregnant and lactating women receive the COVID-19 vaccine?

On December 11, 2020, the FDA issued the first EUA for a vaccine for the prevention of COVID-19 in individuals 16 years of age and older. The EUA allows the Pfizer-BioNTech COVID-19 vaccine to be distributed in the United States. However, the vaccine was not specifically tested in pregnant women or in those who were breastfeeding. Developmental and reproductive studies in animals to assess the potential effects on the fetus are underway. However, the FDA encourages vaccine companies to collect long-term data on how the vaccine performs in pregnant and lactating women. Without data, having a shared decision making dialogue with the pregnant patient regarding receiving the vaccine that considers exposure risk and underlying conditions will be essential. This is supported by the American College of Obstetricians and Gynecologists (ACOG) who recommends that COVID-19 vaccines should not be withheld from pregnant individuals who meet criteria for vaccination based on Advisory Committee on Immunization Practices (ACIP)-recommended priority groups and that pregnant individuals should be free to make their own decision in conjunction with their clinical care team.

Global vaccine acceptance by pregnant women is largely unknown. A recent study using Pregristry, surveyed pregnant women from 16 countries and found that 52.0% of pregnant women (n = 2,747/5,282) and 73.4% of non-pregnant women (n = 9,214/12,562) indicated an intention to receive the vaccine. Vaccine acceptance was lowest in Russia, the United States and Australia (Skiefte).

A U.S. survey of 662 pregnant women found that 77.9% reported having already been vaccinated against influenza during the 2020-2021 season, and 58.3% said they would accept the COVID-19 vaccine while pregnant. Concern for the fetus and vaccine side effects were most common reasons for those declining vaccination (Levy).

Is there safety data on the use of COVID-19 vaccines in pregnancy?

Using data from the V-safe program, the CDC reviewed preliminary data on over 35,000 women who identified as pregnant after their vaccine. Data on almost 4,000 who participated in the pregnancy registry did not show any safety signals of concern, and outcomes were similar to studies on pregnant women before the pandemic. The CDC now recommends that all pregnant women be vaccinated (Shimabukuro).

Using data from 131 reproductive age vaccine recipients, the authors found that pregnant and lactating women elicited comparable vaccine-induced humoral immune responses to non-pregnant controls and generated higher antibody titers than those observed following SARS-CoV-2 infection in pregnancy. Vaccine-generated antibodies were present in umbilical cord blood and breast milk after maternal vaccination (Gray).

Are there ongoing studies to which pregnant women could be referred?

Researchers are still learning how COVID-19 affects pregnant women. As part of their pregnancy studies, the organization MotherToBaby is interested in examining the short and long-term effects of COVID-19 in pregnancy and breastfeeding, as well as COVID-19 vaccination in pregnancy or during breastfeeding. This study will consist of phone calls over the course of the pregnancy and post-delivery or while breastfeeding, release of medical records related to the pregnancy and infant’s development, and collection of breast milk samples. If you have a pregnant or breastfeeding patient with COVID-19, or who has been vaccinated please consider enrolling them at mothertobaby.org or by calling (877) 311-8972.

Women diagnosed with COVID-19 from all countries may enroll in the International Registry of Coronavirus Exposure in Pregnancy (IRCEP). Women can enroll and provide information to the IRCEP via its website and mobile app. The study will collect data on reproductive history, COVID-19 infection test and symptoms. Women will complete monthly modules until post-partum, and medical records from the mother and neonate will be requested. If you have a pregnant patient with COVID-19, consider enrolling them at ircep.preregistry.com

The Vaccines and Medications in Pregnancy Surveillance System (VAMPSS) also is continuing to study asthma medications during pregnancy. VAMPSS is a nationwide post-marketing surveillance system established to comprehensively monitor the use and safety of vaccines and medications during pregnancy, coordinated by the AAAAI. You can learn more about VAMPSS at the AAAAI website. If you have a pregnant patient with asthma, please consider enrolling them in the VAMPSS studies at mothertobaby.org or by calling (877) 311-8972.

References

1. Adhikari et al. Pregnancy outcomes among women with and without severe acute respiratory syndrome coronavirus 2 infection. JAMA Netw Open. 2020

2. Ahlberg et al. Association of SARS-CoV-2 Test Status and Pregnancy Outcomes. JAMA. 2020

3. Allotey et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis.BMJ 2020

4. Anand et al. Clinical profile, viral load, management and outcome of neonates born to COVID 19 positive mothers: a tertiary care centre experience form India. Eur J Pediatr 2020

5. Ashish,et al. Effect of the COVID-19 pandemic response on intrapartum care, stillbirth, and neonatal mortalityoutcomes in Nepal: a prospective observational study.Lancet Glob Health.2020

6. Brandt et al. Epidemiology of coronavirus disease 2019 in pregnancy risk factors and associations with adverse maternal and neonatal outcomes. Am J Obstet Gynecol 2020

7. Bunnell, et al. Thirs trimester stillbirth during the first wave of the SARS-CoV-2 pandemic: similar rates with increase in placental vasculopathic pathology. Placenta 2021

8. Cavalcante, et al. Maternal immune responses and obstetrical outcomes of pregnant women with COVID-19 and possible health risks of offspring. J Reprod Immunol.2021

9. Centeno_Tablante, et al. WHO. Breastfeeding and COVID-19. Scientific Brief. 23 June 2020. https://www.who.int/publications/i/item/10665332639.

10. Chambers et al. Evaluation for SARS-CoV-2 in breast milk from 18 infected women. JAMA 2020

11. Chhiba et al. Prevalence and characterization of asthma in hospitalized and non-hospitalized patients with COVID-19. J Allergy and Clin Immunol.2020

12. Chi et al. Clinical characteristics and outcomes of pregnant women with COVID-19 and the risk of vertical transmission: a systematic review. Arch Obstet gynecol.2020.

13. Cosma et al. The “scar” of a pandemic:cumulative incidence of COVID-19 during the first trimester of pregnancy.J Med Virol. 2021

14. Di Mascio et al. Risk factors associated with adverse fetal outcomes in pregnancies affected by coronavirus disease 2019; a secondary analysis of the WAPM study on COVID-19. JPerinat Med 2020

15. Dumitriu et al. outcomes of neonates born to mothers with severe acute respiraotry syndrome coronavirus 2 infection at a large medical center in New York City.JAMA Ped.2021

16. Flaherman et al. Infant Outcomes Following Maternal Infection With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): First Report From the Pregnancy Coronavirus Outcomes Registry (PRIORITY) Study.Clin Infect Dis.2020

17. Hcini et al. Maternal,fetal and neonatal outcomes of large series of SARS-CoV-2 positive pregnancies in peripartum period:a single-center prospective comparative study.Eur J of Obstet Gynecol.2021

18. Gray et al. COVID-19 vaccine response in pregnant and lactating women: a cohort study. AJOG 2021

19. Khalil et al. Change in the incidence of stillbirth and preterm delivery during the COVID-19 pandemic. JAMA.2020

20. Kyle et al. A review of newborn outcomes during the COVID-19 pandemic. Sem in Perinatol 2020

21. Levy et al. Accepatance of COVID-19 vaccination in pregnancy: a survey study. AJOG.2021

22. Lokken, et al. Clinical characteristics of 46 pregnant women with SARS-CoV-2 infection in Washington state. AJOG.2020

23. Malderelli et al. Remdesivir treatment for severe COVID-19 in third –trimester pregnancy: case report and management discussion. Open Forum ID 2020

24. Mendoza, et al. Preeclampsia-like syndrome induced by severe COVID-19: a prospective observational study. BJOG.2020

25. Peng et al. A study if breastfeeding practices, SARS Co-V-2 and its antibodies in the breast milk of mothers confirmed with COVID-19

26. Prabhu et al. Pregnancy andpostpartum outcomes in a universally tested population for SARS-CoV-2 in New York City: A prospective cohort study. BJOG 2020.

27. Rasmussen et al. Coronavirus disease 2019 (COVID-19) and pregnancy: what obstetricians need to know. ACOG.2020

28. Rosen et al. Fetal and perinatal outcome following first and second trimester COVID-19 infection: evidence from a prospective cohort study.J Clin Med.2021

29. Rosenbloom et al. COVID-19 infection and hypertensive disorders of pregnancy. AJOG.2021

30. Shimabukuro et al. Preliminary findings of mRNA covid-19 vaccine safety in pregnant persons. NEJM.2021

31. Skjefte et al. COVID-19 vaccine acceptance among pregnant women and mothers of young children: results of a survey in 16 countries. Eur J Epidemiol. 2021

32. Takemoto et al. Maternal mortality and COVID-19. J Matern Fetal Neonatal Med.2020

33. Woodworth et al. Birth and Infant Outcomes Following Laboratory-Confirmed SARS-CoV-2 Infection in Pregnancy — SET-NET, 16 Jurisdictions, March 29–October 14, 2020. MMWR. Oct 2020

34. Zambrano et al. Update: Characteristics of Symptomatic Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status — United States, January 22–October 3, 2020. MMWR. Oct 2020

ACOG: https://www.acog.org/clinical-information/physician-faqs/covid-19-faqs-for-ob-gyns-obstetrics

MotherToBaby: https://mothertobaby.org//?s=covid

CDC: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/pregnant-people.html