INTRODUCTION — Pregnant and recently postpartum persons with influenza are more likely to develop severe illness and to die than the general population, based on data from seasonal influenza and from the influenza pandemics of 1918 to 1919, 1957 to 1958, and 2009 to 2010. The increased severity of influenza in pregnant and recently postpartum patients is thought to be related to normal physiologic changes that occur during pregnancy. For example, heart rate and oxygen consumption increase, lung capacity decreases, and there is a shift away from cell-mediated immunity.

Because of the increased severity of influenza in pregnancy and postpartum, inactivated influenza vaccine is recommended for these patients, regardless of trimester of pregnancy. In addition, pregnant and postpartum patients with suspected or confirmed influenza should receive prompt empiric treatment with an appropriate antiviral medication.

This topic will discuss issues specific to seasonal influenza in pregnant and postpartum patients. Detailed general information on seasonal influenza in the nonpregnant population can be found separately.

●(See "Seasonal influenza in adults: Clinical manifestations and diagnosis".)

●(See "Seasonal influenza in adults: Clinical manifestations and diagnosis".)

●(See "Seasonal influenza in adults: Treatment".)

●(See "Influenza: Epidemiology, pathogenesis, and outcomes".)

●(See "Seasonal influenza vaccination in adults".)

●(See "Prevention of seasonal influenza with antiviral drugs in adults".)

●(See "Antiviral drug resistance among seasonal influenza viruses".)

CLINICAL MANIFESTATIONS — Clinical manifestations of influenza in pregnant and postpartum patients are similar to those in the general population and include fever (usually 37.8 to 40.0°C [100 to 104°F]), headache, myalgia, shortness of breath, nonproductive cough, rhinorrhea, sore throat, and malaise. These clinical features overlap substantially with other respiratory viral illnesses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; the virus that causes coronavirus disease 2019 [COVID-19]), and there is no way to distinguish between them without testing. In addition, coinfection with influenza and SARS-CoV-2 can occur. (See "Seasonal influenza in adults: Clinical manifestations and diagnosis" and 'Diagnosis' below and "COVID-19: Clinical features", section on 'Initial presentation' and "COVID-19: Diagnosis", section on 'Testing for other pathogens'.)

DIAGNOSIS — The diagnosis of influenza should be made clinically since it is critical to initiate appropriate treatment promptly in pregnant and recently postpartum patients. (See "Seasonal influenza in adults: Clinical manifestations and diagnosis".)

Diagnostic influenza laboratory tests in pregnant and postpartum patients are the same as those for other high-risk patients. (See "Seasonal influenza in adults: Clinical manifestations and diagnosis".)

Postdiagnosis — The American College of Obstetricians and Gynecologists considers pregnant and postpartum patients with the inability to retain fluids, signs of dehydration, difficulty breathing/shortness of breath, chest pain or pressure, mental status changes, comorbidities, obstetric complications, worsening symptoms after previous improvement, or inability for self-care as moderate or high risk [1]. These patients should be referred immediately to an emergency department or equivalent setting for evaluation, possible admission, and treatment. (See 'Treatment' below.)

Respiratory compromise is assessed by physical examination and testing (eg, pulse oximetry, chest radiograph, arterial blood gas). Low-risk symptomatic patients may be evaluated and treatment initiated via phone or other electronic communication, unless other issues warrant an office visit. Ambulatory patients should receive follow-up in 24 to 48 hours to assess change in status.

CLINICAL COURSE IN PREGNANCY

Maternal effects — During the 2009 H1N1 pandemic, pregnant patients had a more severe clinical course and higher mortality compared with nonpregnant patients [2,3]. Although this excess risk has not been confirmed during nonpandemic time periods, the available evidence has limitations and should not reduce concern about influenza during pregnancy [3,4]. Comorbidities, such as chronic cardiac or pulmonary disease, diabetes mellitus, chronic renal disease, malignancy, and immunosuppression, do increase the risk of complications from influenza (seasonal or pandemic) in pregnant patients [3,5].

The clinical course of influenza in pregnancy has become difficult to study because pregnant patients are encouraged to be immunized against influenza, and, if symptomatic, they are likely to be identified early and treated empirically with antiviral medications. The clinical course of influenza in pregnant patients is illustrated by the following examples:

●During the 1918 to 1919 and 1957 to 1958 pandemics, pregnant patients had high mortality rates [6-9].

●Before the 2009 H1N1 pandemic, pregnant patients had increased rates of hospitalization for acute respiratory disease during influenza season compared with nonpregnant patients [10,11].

●During the 2009 H1N1 pandemic, a disproportionate number of deaths occurred among pregnant patients, who accounted for 5 percent of all deaths even though they comprised only 1 percent of the United States general population [12]. Twelve percent of pregnancy-related deaths were attributed to confirmed or possible H1N1 infection during this pandemic [13]. Pregnant patients had a more severe course once infected, but there was no evidence that they were more susceptible to infection with 2009 H1N1 influenza virus [14].

●Cumulative data including both the 2009 H1N1 pandemic and subsequent years show that pregnant patients with influenza are more likely to be hospitalized and to be admitted to an intensive care unit compared with the general population [2,15,16]. Severe illness (defined as admission to an intensive care unit or death) is seen more often among patients in whom treatment with antiviral medications is delayed.

Fetal effects — The fetal effects of influenza have not been well-studied. Transplacental transmission of influenza virus appears to be rare [17], but has been documented in a case of fatal avian influenza (H5N1) in a pregnant patient [18]. However, maternal influenza during pregnancy might have adverse effects on the fetus even in the absence of transplacental transmission.

In a 2013 systematic review and meta-analysis of observational studies, influenza or influenza-like illness in the first trimester was associated with an increased risk of congenital abnormalities (adjusted odds ratio [aOR] for any anomaly 2.00, 95% CI 1.62-2.48), including cleft lip (OR 3.2), neural tube defects (OR 3.3), hydrocephaly (OR 5.7), and congenital heart defects (OR 1.6) [19]. Hyperthermia (including fever) is a common clinical manifestation of influenza and a risk factor for certain birth defects and other adverse infant outcomes [20]. This risk appears to be attenuated by use of antipyretics. (See 'Antipyretics' below and "Open neural tube defects: Risk factors, prenatal screening and diagnosis, and pregnancy management", section on 'Fever/hyperthermia'.)

There are also reports that maternal influenza infection during pregnancy is associated with an increased risk for spontaneous abortion, preterm delivery, low birth weight, birth of a small for gestational age infant, and fetal death [2,8,21-27]. In the 2009 H1N1 pandemic, only severely ill pregnant patients (ie, those admitted to an intensive care unit) had a substantially increased risk of poor infant outcomes (eg, preterm labor, low birth weight) [28].

PREVENTION

Vaccination

Administration — The Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices (ACIP) recommends that all patients who are pregnant or might be pregnant or postpartum during influenza season receive any licensed, age-appropriate, recommended inactivated influenza vaccine (IIV) or recombinant influenza vaccine quadrivalent, regardless of trimester [29]. Annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications, including pregnant and postpartum patients. The CDC's ACIP does not preferentially recommend a specific formulation of influenza vaccine as comparative effectiveness data in large populations are not available to support a specific recommendation.

In general, for most individuals, influenza vaccination should be offered before community onset of influenza activity (by the end of October in the northern hemisphere and by April in the southern hemisphere). However, for pregnant patients in the third trimester, earlier vaccination (July/August in the northern hemisphere, or January/February in the southern hemisphere) may reduce the risk of maternal influenza illness and early infant influenza [27]. (See 'Clinical course in pregnancy' above and 'Infant protection' below.)

Pregnant patients should not receive a live-attenuated influenza vaccine due to concerns about the safety of a live vaccine administered during pregnancy [29]. Pregnant and postpartum patients do not need to avoid contact with individuals who have recently received the live-attenuated influenza vaccine, and it is safe for use postpartum. (See "Immunizations during pregnancy", section on 'Live vaccines' and "Seasonal influenza vaccination in adults", section on 'Live attenuated vaccine (LAIV)'.)

Pregnant patients with a history of egg allergy of any severity may receive any licensed, recommended, and age-appropriate influenza vaccine (not live-attenuated vaccine). However, if the allergy is severe, then administration should be supervised by a health care provider who is able to recognize and manage anaphylaxis [29]. Egg-free quadrivalent cell-culture based and recombinant vaccines (Flucelvax and Flublok, respectively) are also available. (See "Seasonal influenza vaccination in adults" and "Influenza vaccination in individuals with egg allergy".)

Despite recommendations for influenza vaccination of pregnant patients, which have been published annually since 2004 and supported and promoted by key professional groups such as the American College of Obstetricians and Gynecologists (ACOG) [30], coverage rates have remained low for many years, especially in patients with adverse socioeconomic factors [31]. In response to the 2009 H1N1 pandemic and broad educational efforts to target pregnant patients and their providers, national estimates of influenza coverage rates for pregnant patients in the United States had increased to approximately 54 percent [32]. However, in 2017 to 2018, influenza vaccination coverage was only 49 percent among pregnant and postpartum patients [33]. In one study among pregnant patients in the United States, the most commonly reported primary reason for not receiving influenza vaccination was believing the vaccine is not effective [34].

Rates of influenza vaccination during pregnancy are higher in patients whose providers specifically recommend it and highest when the provider both recommends and offers the vaccine. These findings highlight the importance of provider involvement to increase influenza vaccination of pregnant patients. Health care providers may find the health care provider script developed by ACOG helpful for talking with patients about the importance of influenza vaccination during pregnancy [35].

Benefits

Reduction in maternal influenza illness — Influenza vaccination plays a key role in reducing the risk of maternal influenza illness. Multiple clinical studies and surveillance data have demonstrated the benefits of influenza vaccination for pregnant patients, including those with HIV infection [36]. Pregnant patients achieve seroprotection at rates similar to nonpregnant patients [26,37], although there may be some differences in the antibody response of pregnant patients to influenza vaccine compared with nonpregnant patients [38].

In a 2014 systematic review and meta-analysis of cohort studies of vaccination for preventing influenza in healthy adults, H1N1 vaccines reduced the risk of influenza-like illness in pregnant patients by 89 percent (95% CI 79-94) and the seasonal vaccine reduced the risk of influenza-like illness in pregnant patients by 24 percent (95% CI 11-35) [39]. Newborns of vaccinated patients had a 41 percent (95% CI 6-63) reduction in laboratory-confirmed influenza. The systematic review did not include a randomized trial [40] or a large case-control study [41]; the latter was published just prior to the review. In a large trial in which pregnant patients were randomly assigned to receive either IIV or pneumococcal vaccine, those who received the influenza vaccine had a 36 percent (95% CI 4-57) reduction in febrile respiratory illness and their infants had a 63 percent (95% CI 5-85) reduction in laboratory-confirmed influenza [40]. In the large case-control study, influenza vaccination reduced the risk of laboratory-confirmed influenza by approximately one-half [41].

Reduction in maternal influenza hospitalization — Between 2010 and 2016, influenza vaccine was 40 percent effective (adjusted vaccine effectiveness 40 percent, 95% CI 12-59 percent) against laboratory-confirmed influenza-associated hospitalization during pregnancy, in one study of hospitals in Australia, Canada, Israel, and the United States [42].

Improvement in pregnancy outcome — In a 2016 systematic review and meta-analysis of observational studies on the effect of maternal influenza immunization on stillbirth and miscarriage, influenza vaccination was associated with a reduction in risk of stillbirth (relative risk [RR] 0.73, 95% CI 0.55-0.96) but had no significant effect on risk of miscarriage (RR 0.91, 95% CI 0.68-1.22) [43]. Others have reported influenza vaccination is associated with a reduced risk for small for gestational age infants and preterm delivery [40,44-48] and an increase in birth weight [44].

Infant protection — In addition to protecting the pregnant patient, influenza vaccination during pregnancy protects the infant for several months after birth [36,40,49-55]. Antenatal maternal immunization induces substantial levels of anti-influenza-specific serum immunoglobulin G (IgG), which are actively transferred across the placenta to the fetus [56], and anti-influenza-specific IgA in breast milk, which is transferred to the infant during lactation [57]. Thus, antenatal maternal vaccination is an effective strategy for reducing influenza-related morbidity and mortality among infants, who are at increased risk for severe influenza illness and not eligible for vaccination until six months of age because they fail to mount an adequate immune response [58,59]. Maternal vaccine may also reduce hospitalizations for all-cause acute lower respiratory tract infection before three months of age [60].

However, passive protection afforded by maternal influenza vaccination appears to decline significantly before the infant is eligible for vaccination. In a randomized trial of 1026 infants of patients who received trivalent IIV during pregnancy and 1023 infants of patients who received a placebo, the vaccine's efficacy against polymerase chain reaction (PCR)-confirmed influenza illness was approximately 86 percent in infants ≤8 weeks of age and 25 to 30 percent in infants 8 to 24 weeks of age [53]. The percentage of infants with hemagglutination inhibition antibody titers ≥1:40 to the influenza vaccine strains targeted by the vaccine was ≥56 percent in the first week and fell to <10 percent at 24 weeks of age. Others have observed similar decreases in vaccine efficacy [54].

It is possible that maternal immunization in the third trimester would improve passive protection for the newborn [61], as with Tdap; however, delaying maternal immunization places the mother at risk for influenza and its sequelae (maternal and fetal) and is not recommended.

Safety — Although pregnant patients often have concerns about the safety of vaccines for their fetuses, multiple studies have not shown an increased risk of complications associated with administration of IIVs to pregnant patients compared with the general population. Although rare, all vaccines, including influenza vaccine, have some background risk of adverse effects, such as Guillain-Barré syndrome [62] (see "Standard immunizations for nonpregnant adults", section on 'Safety'). However, no specific concerns for pregnant patients, their fetuses, infants, or school-age children have been identified from multiple research studies and monitoring systems worldwide that have collected information on the safety of all types of influenza vaccination (eg, monovalent H1N1, seasonal trivalent) [26,39,40,63-79]. However, data are limited regarding first-trimester administration and use of quadrivalent and cell culture based vaccines and even more limited for recombinant influenza vaccines. Although a case-control study found an association between spontaneous abortion and vaccination with a pH1N1-containing vaccine in the subgroup of patients who received two consecutive pH1N1-containing vaccines [80], these findings were not replicated in larger and more carefully designed follow-up studies from the same monitoring system [81,82].

Although influenza vaccines that contain adjuvants (substances that boost the immune response and potentially provide longer-lasting and broader protection against antigenically-drifted viruses) are only approved in the United States for use in individuals ≥65 years of age, experience from Europe provides limited but reassuring data on the safety of adjuvant-containing influenza vaccines administered to pregnant patients [83-85].

There is no evidence that vaccines that contain thimerosal are harmful to the children of patients who received thimerosal-containing vaccines during pregnancy. However, thimerosal-free formulations of the seasonal influenza vaccine are available. (See "Standard childhood vaccines: Parental hesitancy or refusal", section on 'Influenza'.)

Antiviral prophylaxis

Candidates — Decisions regarding antiviral prophylaxis need to take into consideration whether the exposure was significant and the host's risk for developing a complicated infection. Antiviral prophylaxis within 48 hours of the most recent exposure is a reasonable option for pregnant and postpartum patients with a significant exposure up to two weeks after delivery (including those who have had a pregnancy loss). Early empiric treatment, once signs or symptoms of influenza develop, is an alternative to prophylaxis.

Detailed information about significant exposure and close contacts and assessment of the host's risk are discussed separately. (See "Prevention of seasonal influenza with antiviral drugs in adults", section on 'Target populations for prevention' and "Prevention of seasonal influenza with antiviral drugs in adults", section on 'Indications for chemoprophylaxis'.)

Drug regimen — For chemoprophylaxis in pregnancy, zanamivir may be a good choice given its limited systemic absorption. However, respiratory complications may be associated with zanamivir because of its inhaled route of administration and need to be considered, especially in patients at risk for respiratory problems, such as those with asthma [86]. Oral oseltamivir is an alternative agent.

The doses of influenza antiviral medications recommended for chemoprophylaxis of influenza A and B are [87]:

●Zanamivir 10 mg (two 5 mg inhalations) once daily or

●Oseltamivir 75 mg orally once daily

The recommended duration of prophylaxis is seven days after the last known exposure [87]. For control of outbreaks in long-term care facilities and hospitals, the CDC recommends chemoprophylaxis for a minimum of two weeks and up to one week after the most recent known case was identified.

No adverse events have been associated with oseltamivir or zanamivir among patients who received these drugs during pregnancy or among infants exposed in utero or through breast milk. Evidence of the safety of these drugs in pregnancy is discussed separately. (See "Pharmacology of antiviral drugs for influenza", section on 'Use in pregnancy' and 'Breastfeeding' below.)

Infection control measures

Standard precautions — Standard precautions for reducing the transmission of influenza include hand hygiene (eg, washing with soap and water, use of alcohol-based disinfectant), and respiratory hygiene/cough etiquette (covering the nose and mouth when coughing, disposing of used tissues promptly, and practicing hand hygiene after contact with respiratory secretions). Health care workers should use gloves, gowns, masks, and eye protection, as appropriate, when in contact with infected patients (table 1). (See "Infection prevention: Precautions for preventing transmission of infection", section on 'Standard precautions'.)

Symptomatic patients — Pregnant patients with confirmed or suspected influenza infection who come to the hospital for delivery should be placed in a private room and cared for using the same infection control precautions for influenza that are used for other patient populations [88]. They should be treated with appropriate antiviral therapy immediately; treatment should not be delayed while awaiting the results of diagnostic testing. (See 'Antiviral medications' below and "Infection control measures for prevention of seasonal influenza".)

In outpatient settings, patients should be screened for respiratory symptoms and signs and triaged appropriately. When scheduling appointments and at office check-in, patients and the persons who accompany them can be instructed to inform office staff if they have symptoms of a respiratory infection. Symptomatic patients should be given face masks and supplies and instructions for hand hygiene. They should wait in a separate waiting area or be asked to sit as far away from others as possible [89].

Healthy term newborns of symptomatic mothers — Healthy term newborns of mothers with confirmed or suspected influenza infection should be considered exposed, not infected, if they are born in the hospital using the recommended infection control guidelines. Asymptomatic healthy term newborns can be cared for in the well-born nursery using Standard Precautions and should be observed for signs of infection.

Given the risk of severe complications of influenza in newborns, the CDC recommends considering temporary separation of a mother with suspected or confirmed influenza from the newborn. The length of temporary separation needs to be made on a case-by-case basis. Although there are no data on which to formulate evidence-based recommendations about the length of separation, CDC guidelines developed during the 2009 H1N1 pandemic may provide a reasonable approach. These guidelines recommended separating a mother with 2009 H1N1 from the infant until three criteria were met: The mother had received antiviral medications for 48 hours, was afebrile without antipyretics for >24 hours, and was able to control coughing and respiratory secretions. During temporary separation, all feedings should be provided by a healthy caregiver. Mothers who intend to breastfeed should be encouraged to express their milk. (See 'Breastfeeding' below.)

If temporary separation is not feasible or acceptable, then environmental controls should be considered, such as physical barriers and keeping the newborn >6 feet away from the ill mother.

Oral oseltamivir is approved by the US Food and Drug administration (FDA) for chemoprophylaxis in persons 1 year of age and older and treatment of acute uncomplicated influenza within 2 days of illness onset in persons 14 days of age and older. Although not stated as an FDA-approved indication, the CDC and the American Academy of Pediatrics recommend use of oral oseltamivir for chemoprophylaxis in infants 3 months to 1 year of age and treatment of influenza in infants less than 14 days old. If a child is younger than 3 months old, use of oseltamivir for chemoprophylaxis is not recommended unless the situation is judged critical, given limited data of safety and efficacy in this age group. Prophylactic and therapeutic dosing in infants is reviewed separately (see "Seasonal influenza in children: Management", section on 'Antiviral agent administration' and "Seasonal influenza in children: Prevention with antiviral drugs"). Influenza vaccines are recommended for children ≥6 months of age. (See "Seasonal influenza in children: Prevention with vaccines".)

Infant caregivers and household contacts — All individuals who live with or provide care for infants younger than 6 months of age should be vaccinated against influenza. Ideally, caregivers and household contacts should be vaccinated before the infant is discharged home from the hospital [90]. Otherwise, those who are unvaccinated and eligible for vaccination (ie, >6 months of age) should be strongly encouraged to be vaccinated in a timely way. (See "Seasonal influenza vaccination in adults".)

Infant caregivers and household contacts of the infant who have significant contact with an individual with influenza should be considered for postexposure prophylaxis. (See "Prevention of seasonal influenza with antiviral drugs in adults", section on 'Postexposure prophylaxis'.)

Breastfeeding — Patients with suspected or confirmed influenza who are breastfeeding should be encouraged to continue breastfeeding if possible. During temporary separation, mothers with confirmed or suspected influenza infection who intend to breastfeed should be encouraged to express their breast milk, which a healthy caregiver can use to bottle feed the newborn.

Although data on the safety of antiviral medications during lactation are limited, use of oseltamivir by breastfeeding mothers appears to pose no harm to their infants [91,92]. The drug and its active metabolite are poorly excreted into breast milk [93]. We are not aware of any studies on the safety of zanamivir or baloxavir marboxil during breastfeeding.

Protection of pregnant health care workers — Although pregnant health care workers should observe the same infection control procedures as all health care personnel, they may be offered some accommodations (eg, avoiding involvement with aerosol-generating procedures on patients with suspected or confirmed influenza) to avoid potentially high-risk exposures.

TREATMENT

Key principles

●Since the influenza vaccine is not 100 percent effective [94], pregnant patients and postpartum patients (within two weeks of delivery or pregnancy loss [95]) who meet current case definitions for suspected or confirmed influenza should receive empiric treatment with appropriate influenza antiviral medications as early as possible regardless of vaccination status, and treatment should not be withheld while awaiting results of diagnostic testing (including testing for SARS-CoV-2 [ie, COVID-19]) or in situations in which testing is not performed [96] (see 'Clinical manifestations' above and 'Diagnosis' above). Furthermore, during periods when influenza viruses are circulating in the community, a negative test cannot rule out infection, especially if the test used does not have high sensitivity to detect influenza viruses or if the specimen was collected more than four days after illness onset. Therefore, decisions about antiviral therapy should be based on the clinical picture and information on local influenza activity in the community [97].

Available data suggest that the benefits outweigh any theoretical risks. Studies from the 2009 to 2010 season demonstrated that initiating treatment of pregnant patients early (generally <2 days) after onset of influenza symptoms was associated with less severe disease and fewer deaths compared with treatment begun later [12,21,98-101]. A study from the 2010 to 2014 influenza seasons demonstrated a markedly shorter median length of hospital stay among patients with severe influenza receiving early antiviral treatment compared with those who received treatment >2 days after symptom onset (2.2 versus 7.8 days) [102].

●Although the benefits of antiviral therapy are greatest when initiated within the first 48 hours following symptom onset, treatment should still be administered to patients who present >48 hours after illness onset and have not begun to improve. The risk of treatment is believed to be low, and there may be some benefit even after a prolonged delay, particularly in severely ill pregnant and postpartum patients [99].

●Antiviral treatment can be prescribed over the phone or in person for patients with mild symptoms and no medical or obstetric comorbidities, but this decision should take individual circumstances into account (eg, inability for self-care or follow-up) [1]. All other patients should be seen promptly for evaluation, and those with respiratory compromise or complications should be admitted for treatment. (See 'Candidates' above.)

●Health care providers can facilitate early treatment by informing pregnant and postpartum patients about signs and symptoms of influenza, emphasizing the need to contact their health care provider for early treatment, and ensuring rapid access to telephone consultation and clinical evaluation.

Antiviral medications — Treatment decisions, especially those involving empiric treatments, should be informed by knowledge of influenza activity in the community. The vast majority of currently circulating influenza viruses have been susceptible to the neuraminidase inhibitors, oseltamivir, zanamivir, and peramivir (updated resistance information is available at www.cdc.gov/flu). (See "Antiviral drug resistance among seasonal influenza viruses".)

Although information on the safety of oseltamivir, zanamivir, and peramivir during pregnancy, especially the first trimester, is limited, the benefits of treatment outweigh the potential risks [103]. Two 2019 studies of the use of oseltamivir during pregnancy were reassuring [104,105]; however, earlier reports have described some potentially increased risks to offspring following prenatal exposure to influenza antiviral medications [99,106-110].

Oseltamivir is generally preferred over inhaled zanamivir and intravenous peramivir for treatment of pregnant patients, assuming that prevalence of oseltamivir resistance is low among circulating influenza viruses. Oseltamivir is the drug of choice because of its systemic absorption and the greater clinical experience using this drug in pregnancy, but pregnancy is not a contraindication to use of zanamivir or peramivir. Zanamivir is relatively contraindicated in patients with asthma or chronic obstructive pulmonary disease. (See "Pharmacology of antiviral drugs for influenza", section on 'Zanamivir'.)

Based on limited data, the dose of antiviral therapy for treatment of influenza during pregnancy is the same as in nonpregnant adults [1,87,103]:

●Oseltamivir 75 mg twice daily (preferred) for five days or

●Zanamivir 10 mg (two 5 mg inhalations) twice daily for five days or

●Peramivir 600 mg intravenously (infused over a minimum of 15 minutes) administered as a single dose

While the usual duration of treatment with oseltamivir and zanamivir is five days, longer treatment courses can be considered for patients who remain severely ill after five days of treatment. Some clinicians have recommended that severely ill patients be treated with double-dose oseltamivir (ie, 150 mg twice daily); however, no data are available to suggest that higher doses are more effective [87]. The oral formulation of oseltamivir appears to be adequately absorbed following nasogastric administration. (See "Seasonal influenza in adults: Treatment", section on 'Neuraminidase inhibitors'.)

There is evidence from phase 2 and 3 randomized trials that a single dose of baloxavir marboxil has similar clinical benefit to oseltamivir in alleviating symptoms. However, pregnant patients were excluded from these trials. Until more safety data on baloxavir marboxil use in pregnancy are available, oseltamivir remains the preferred drug for use in pregnancy [103].

Antipyretics — Use of acetaminophen for treatment of fever may be important, since hyperthermia during the first trimester has been associated with neural tube defects and possibly other birth defects. In addition, fever during labor is a risk factor for neonatal seizures, encephalopathy, cerebral palsy, and neonatal death [20,111,112]. Other antipyretics (eg, aspirin, ibuprofen) have been associated with adverse pregnancy and infant outcomes; therefore, acetaminophen appears to be the best option [86]. (See "Prenatal care: Patient education, health promotion, and safety of commonly used drugs", section on 'Acetaminophen'.)

Symptomatic therapy — Many pregnant patients will seek advice about symptomatic therapy for cough, rhinorrhea, sore throat, headache, and myalgia. Symptomatic therapy is similar to that for the common cold and reviewed separately. (See "Treatment of respiratory infections in pregnant patients", section on 'The common cold'.)

Role of antibiotics — Antibiotics are indicated only for bacterial complications of acute influenza, such as bacterial pneumonia, otitis media, or sinusitis. Treatment is similar to that in nonpregnant adults (see "Seasonal influenza in adults: Treatment", section on 'Antibiotics for secondary bacterial pneumonia'), except for avoidance of antibiotics with potentially harmful effects in pregnant patients or the fetus. (See "Prenatal care: Patient education, health promotion, and safety of commonly used drugs", section on 'Antibiotics'.)

Management of ARDS — (See "Seasonal influenza in adults: Treatment", section on 'Management of ARDS'.)

OBSTETRIC MANAGEMENT — There are no published guidelines for monitoring the fetus during or after maternal influenza infection. The type and frequency of fetal surveillance should be guided by the health care provider's judgment on a case-by-case basis. (See "Overview of antepartum fetal assessment", section on 'Indications for fetal assessment'.)

SOCIETY ALGORITHM LINK — The American College of Obstetricians and Gynecologists and Society for Maternal-Fetal Medicine have jointly published an algorithm for assessment and treatment of pregnant patients with influenza-like illness.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Immunizations in adults" and "Society guideline links: Seasonal influenza vaccination" and "Society guideline links: Respiratory disease in pregnancy".)

SUMMARY AND RECOMMENDATIONS

●Pregnant patients with seasonal influenza are at increased risk for serious complications requiring hospitalization and intensive care unit admission, and death. Severe maternal illness increases the risk of adverse pregnancy outcome. (See 'Clinical course in pregnancy' above.)

●The diagnosis of seasonal influenza should be made clinically, without waiting for results from diagnostic testing. (See 'Diagnosis' above.)

●Infection control measures are indicated in outpatient and inpatient settings to reduce the risk for transmission of virus among mothers, newborns, staff, and non-staff (eg, infant caregivers, household contacts) in contact with mothers and newborns. (See 'Infection control measures' above.)

●All patients who are pregnant or will be pregnant or postpartum during influenza season should receive the quadrivalent inactivated influenza vaccine, regardless of pregnancy trimester (Grade 1A). (See 'Vaccination' above.)

●We base the decision to use antiviral prophylaxis on whether the exposure was significant and the host's risk for developing a complicated infection. Early treatment, once signs or symptoms of influenza develop, is an alternative to prophylaxis. (See 'Candidates' above.)

●For chemoprophylaxis in pregnancy, zanamivir may be a good choice given its limited systemic absorption. However, respiratory complications may be associated with zanamivir because of its inhaled route of administration and need to be considered, especially in patients at risk for respiratory problems, such as those with asthma. Oral oseltamivir is an alternative agent. (See 'Antiviral prophylaxis' above.)

●For pregnant and postpartum patients (within two weeks of delivery or pregnancy loss) who meet current case definitions for suspected or confirmed influenza, we recommend empiric treatment with appropriate influenza antiviral medications as early as possible regardless of vaccination status (Grade 2B). Treatment should not be withheld while awaiting results of diagnostic testing or in situations in which testing is not performed.

Early treatment (within two days of symptom onset) has been associated with a lower risk for admission to an intensive care unit and death, when compared with treatment initiated later. However, beginning treatment >2 days after symptom onset also has benefits if the patient has not yet improved. (See 'Key principles' above.)

●Oseltamivir is generally preferred over inhaled zanamivir and intravenous peramivir for treatment of influenza in pregnant patients, assuming that prevalence of oseltamivir resistance is low among circulating influenza viruses. (See 'Antiviral medications' above.)

●Fever should be treated with acetaminophen. (See 'Antipyretics' above.)