Pregnancy, Lactation, and COVID-19 Therapeutics

General Considerations

The COVID-19 Treatment Guidelines Panel (the Panel) recommends against withholding COVID-19 treatments or vaccination from pregnant or lactating individuals specifically because of pregnancy or lactation (AIII).

The decision to feed the infant breast milk while the lactating patient is receiving therapeutic agents for COVID-19 should be a collaborative effort between the patient and the clinical team, including infant care providers. The patient and the clinical team should consider the benefits of breastfeeding, the postnatal age of the infant, the need for the medication, any underlying risks of infant exposure to the drug, and the potential adverse outcomes of COVID-19.

If a patient is receiving a treatment for COVID-19 that prevents them from feeding breast milk to their infant for a limited time, the clinical team should still encourage pumping breast milk and provide lactation support. This ensures that lactation can resume after the patient stops receiving the treatment.

While a person with COVID-19 is breastfeeding, prevention measures should be taken to avoid transmitting SARS-CoV-2 to the infant. These measures include practicing good hand hygiene, wearing face coverings, and performing proper pump cleaning before and after breast milk expression.

For the Panel’s recommendations on when to use the medications listed below, refer to Therapeutic Management of Nonhospitalized Adults With COVID-19 and Therapeutic Management of Hospitalized Adults With COVID-19.

Rationale

Baricitinib

Pregnancy

When deciding whether to prescribe baricitinib to a pregnant individual, clinicians need to consider the severity of the patient's COVID-19, the patient's comorbidities, and the gestational age of the infant.

Baricitinib is a Janus kinase (JAK) inhibitor. As a small-molecule drug, baricitinib is likely to pass through the placenta; therefore, fetal risk cannot be ruled out.² In animal studies, baricitinib doses that exceeded the therapeutic human dose were associated with embryofetal developmental abnormalities. Pregnancy registries provide some outcome data on the use of tofacitinib, another JAK inhibitor, during pregnancy for other conditions (e.g., ulcerative colitis, rheumatoid arthritis, psoriasis). Among the cases reported, pregnancy outcomes were similar to those among the general population.^3-5

Lactation

There is no information on the use of baricitinib in lactating people or on the effects of baricitinib on breastfed infants; however, baricitinib has been detected in the breast milk of lactating rats.⁶ Feeding breast milk should be avoided for 4 days (approximately 5–6 elimination half-lives) after baricitinib is discontinued.

Dexamethasone

Pregnancy

A short course of betamethasone or dexamethasone, which are both known to cross the placenta, is routinely used to decrease neonatal complications of prematurity in people with threatened preterm delivery.^7,8 Treating COVID-19 with a short course of dexamethasone can lower the risk of death in pregnant individuals. In addition, there is a low risk of fetal adverse effects with dexamethasone.

Lactation

Dexamethasone should be offered to lactating patients with COVID-19 who qualify for this therapy. Breast milk can be fed to the infant while the lactating patient is receiving dexamethasone. Although there are limited data on dexamethasone and lactation, some published reports about a related antenatal corticosteroid (betamethasone) reported a time-limited decrease in the volume of milk production.^9,10 Given the benefits of breast milk, additional lactation support has been recommended if needed.

Low-Molecular-Weight Heparin and Unfractionated Heparin

Pregnancy

In general, the preferred anticoagulants during pregnancy are heparin compounds. Because of its reliability and ease of administration, low-molecular-weight heparin (LMWH) is recommended over unfractionated heparin (UFH) for the prevention and treatment of venous thromboembolism (VTE) in pregnant people.

The use of anticoagulation therapy during labor and delivery requires specialized care and planning. The management of anticoagulation therapy in pregnant patients with COVID-19 should be similar to the management used for pregnant patients with other conditions.

Lactation

LMWH, UFH, and warfarin do not accumulate in breast milk and do not induce an anticoagulant effect in the newborn; therefore, they can be used by breastfeeding individuals who require VTE prophylaxis or treatment.

Molnupiravir

Pregnancy

The Panel recommends against the use of molnupiravir for the treatment of COVID-19 in pregnant patients unless there are no other options and therapy is clearly indicated (AIII).

The Food and Drug Administration (FDA) Emergency Use Authorization (EUA) states that molnupiravir is not recommended for use in pregnant patients because fetal toxicity has been reported in animal studies of molnupiravir. However, when other therapies are not available, pregnant people with COVID-19 who are at high risk of progressing to severe disease may reasonably choose molnupiravir therapy after being fully informed of the potential risks, particularly if they are beyond the time of embryogenesis (i.e., >10 weeks’ gestation). The patient should also be informed about the pregnancy surveillance program and offered the opportunity to participate.

Lactation

There is no data on the use of molnupiravir in lactating people, though molnupiravir has been detected in the offspring of lactating rats. Molnupiravir is not authorized for use in children aged <18 years. Because the risk of adverse effects in infants is currently unknown, the FDA EUA fact sheet does not recommend feeding an infant breast milk from a patient who is taking molnupiravir for the duration of the treatment course and until 4 days after the final dose.

Remdesivir

Pregnancy

While pregnant individuals were excluded from the clinical trials that evaluated the safety and efficacy of remdesivir for the treatment of COVID-19, subsequent reports on the use of remdesivir in pregnant individuals have been reassuring. Among 95 pregnant patients with moderate, severe, or critical COVID-19 who were included in a secondary analysis of data from a COVID-19 pregnancy registry in Texas, the composite maternal and neonatal outcomes were similar between those who received remdesivir (n = 39) and those who did not.¹¹

A systematic review of 13 observational studies that included 113 pregnant people also reported few adverse effects of remdesivir in pregnant patients with COVID-19. The most common adverse effect was a mild elevation in transaminase levels.¹²

Lactation

Remdesivir is approved by the FDA for use in pediatric patients aged ≥28 days and weighing ≥3 kg. Limited data have suggested that the drug is poorly absorbed via the oral route; therefore, the levels of the drug that are absorbed when the infant ingests breast milk are low.^13,14 One case report described a patient with COVID-19 who received remdesivir during the immediate postpartum period.¹⁴ Based on the concentration of remdesivir in the maternal serum and breast milk, the calculated milk-to-serum ratio was low. Therefore, the levels of remdesivir that would have reached a breastfed infant were estimated to be low.

Ritonavir-Boosted Nirmatrelvir (Paxlovid)

Pregnancy

Ritonavir has been used extensively during pregnancy in people with HIV and has a favorable safety profile during pregnancy. The mechanisms of action for both nirmatrelvir and ritonavir and the results of animal studies and case series suggest that this regimen can be used safely in pregnant individuals.

Two descriptive case series evaluated outcomes among pregnant patients with COVID-19 who received ritonavir-boosted nirmatrelvir. One case series included 47 patients with COVID-19 and a median gestational age of 28.4 weeks. These patients started taking ritonavir-boosted nirmatrelvir after a median duration of 1 day of COVID-19 symptoms. Thirty (64%) patients in the cohort had clinical characteristics in addition to pregnancy that increased their risk of progressing to severe COVID-19. The patients tolerated ritonavir-boosted nirmatrelvir well, with no serious adverse effects noted in either the pregnant patients or the neonates during the study period.¹⁵ The other case series included 7 patients with a mean gestational age of 26.4 weeks who initiated ritonavir-boosted nirmatrelvir after approximately 2 days of COVID-19 symptoms. One patient developed dysgeusia and stopped treatment, but the remaining 6 patients completed 5 days of treatment. Six of the patients were fully vaccinated, and 4 of these patients had also received a booster dose. All the patients reported resolution of their COVID-19 symptoms, and no fetal or neonatal adverse effects were observed during the study period.¹⁶

Ritonavir-boosted nirmatrelvir should be offered to pregnant and recently pregnant patients with COVID-19 who qualify for this therapy based on the results of a risk-benefit assessment. The risk-benefit assessment may include factors such as medical comorbidities, body mass index, vaccination status, and the number and severity of the risk factors for severe disease.

Obstetricians should be aware of potential drug-drug interactions when prescribing this agent. See Drug-Drug Interactions Between Ritonavir-Boosted Nirmatrelvir (Paxlovid) and Concomitant Medications for more information.

Lactation

Studies of infants who were exposed to ritonavir through breast milk suggest that the amount of ritonavir that transfers through breast milk is negligible and not considered clinically significant.²⁴

There are no data on the use of nirmatrelvir in lactating people. However, a prebirth-to-lactation study performed in rats reported an 8% decrease in body weight on Postnatal Day 17 in the offspring of rats that received nirmatrelvir and had systemic exposures that were 8 times higher than the clinical exposures at the authorized human dose. This reduction in body weight was not seen in the offspring of rats that had exposures that were 5 times higher than the clinical exposures at the authorized human dose.³ Because the overall oral absorption of nirmatrelvir is poor, it is unlikely that the levels of nirmatrelvir absorbed from breast milk ingestion would be clinically relevant or expected to cause adverse effects in an infant.¹⁷

Tocilizumab

Pregnancy

Pregnant individuals have been excluded from clinical trials that evaluated the use of the anti-interleukin-6 receptor monoclonal antibody tocilizumab for the treatment of COVID-19. An analysis of data from a global safety database reported pregnancy outcomes from 288 women who were exposed to tocilizumab during their pregnancies. Eighty-nine percent of these women received tocilizumab as ongoing treatment for rheumatoid arthritis, and most were exposed to tocilizumab during their first trimester. The rates of congenital abnormalities among the infants born to these women were not higher than the rates seen in the general population. However, an increased rate of preterm birth was observed among these individuals when compared with the general population. A retrospective report of 61 pregnant women who were exposed to tocilizumab at conception or during their first trimesters showed no increased rates of congenital abnormalities or spontaneous abortion.¹⁸

As pregnancy progresses, monoclonal antibodies are actively transported across the placenta, with the greatest transfer occurring during the third trimester. This may affect immune responses in the exposed fetus. If a pregnant patient receives tocilizumab after 20 weeks’ gestation, clinicians should delay administering live viral vaccines to the infant for at least 6 months.

Lactation

There is limited information on tocilizumab and breastfeeding. Based on case report data, the amount of tocilizumab transferred to the infant via breast milk appears to be very low, with no reports of adverse effects.¹⁹