Characteristics and Outcomes of Pregnant Women Hospitalized With Laboratory-Confirmed Respiratory Syncytial Virus Before and During the COVID-19 Pandemic

Abstract

Background

Respiratory syncytial virus (RSV) can cause severe disease among infants and older adults. Less is known about RSV among pregnant women.

Methods

To analyze hospitalizations with laboratory-confirmed RSV among women aged 18 to 49 years, we used data from the RSV Hospitalization Surveillance Network (RSV-NET), a multistate population-based surveillance system. Specifically, we compared characteristics and outcomes among (1) pregnant and nonpregnant women during the pre–COVID-19 pandemic period (2014–2018), (2) pregnant women with respiratory symptoms during the prepandemic and pandemic periods (2021–2023), and (3) pregnant women with and without respiratory symptoms in the pandemic period. Using multivariable logistic regression, we examined whether pregnancy was a risk factor for severe outcomes (intensive care unit admission or in-hospital death) among women aged 18 to 49 years who were hospitalized with RSV prepandemic.

Results

Prepandemic, 387 women aged 18 to 49 years were hospitalized with RSV. Of those, 350 (90.4%) had respiratory symptoms, among whom 33 (9.4%) were pregnant. Five (15.2%) pregnant women and 74 (23.3%) nonpregnant women were admitted to the intensive care unit; no pregnant women and 5 (1.6%) nonpregnant women died. Among 279 hospitalized pregnant women, 41 were identified prepandemic and 238 during the pandemic: 80.5% and 35.3% had respiratory symptoms, respectively (P < .001). Pregnant women were more likely to deliver during their RSV-associated hospitalization during the pandemic vs the prepandemic period (73.1% vs 43.9%, P < .001).

Conclusions

Few pregnant women had severe RSV disease, and pregnancy was not a risk factor for a severe outcome. More asymptomatic pregnant women were identified during the pandemic, likely due to changes in testing practices for RSV.

Severe outcomes among pregnant women hospitalized with RSV infection were rare, and mild/asymptomatic infection was more frequently identified in pregnant women. In addition, more pregnant women delivered during their RSV-associated hospitalization during the COVID-19 pandemic vs before the pandemic.

Respiratory syncytial virus (RSV) causes respiratory infections resulting in hospitalization of children aged <5 years and older adults in the United States each year [1–4], and it is the leading cause of hospitalizations among infants in the United States annually [5]. A maternal RSV vaccination was recently approved and recommended as an approach to prevent severe RSV illness among infants through maternal antibody transfer [6, 7]. However, less is known about RSV in pregnant women, including whether maternal RSV vaccination may have the added benefit of clinically significant protection for mothers during and following pregnancy. The few studies examining RSV among pregnant women revealed that infections were uncommon [8–13], included limited hospitalizations among those infected with RSV, and found mixed results related to increased risk for adverse pregnancy outcomes among women infected with RSV when compared with those who did not have an RSV infection during pregnancy [11, 14, 15]. In addition, testing practices for RSV have changed in recent years due to broader availability of multipathogen testing and routine SARS-CoV-2 screening at hospital admission with tests that often include RSV. Most published data on pregnant women with RSV occurred prior to the COVID-19 pandemic, and observational studies do not account for recent changes in testing practices.

We used data collected through the Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET)—a large, geographically diverse population-based surveillance system—to describe characteristics of pregnant women hospitalized with laboratory-confirmed RSV during the prepandemic (2014–2018) and pandemic (2021–2023) periods. Our objectives were as follows: (1) to compare characteristics and outcomes between pregnant and nonpregnant women aged 18 to 49 years with acute respiratory infection (ARI) symptoms with RSV-associated hospitalizations during the prepandemic periods and examine risk factors for severe outcomes, (2) to compare characteristics and clinical outcomes of pregnant women with ARI symptoms with RSV-associated hospitalizations between the prepandemic and pandemic periods, and (3) to compare characteristics and outcomes between pregnant women with and without ARI symptoms with RSV-associated hospitalizations in the pandemic period.

METHODS

RSV-NET conducts active, population-based surveillance of laboratory-confirmed RSV-associated hospitalizations. An RSV-NET case was defined as hospitalization of a resident of the catchment area with a positive laboratory-confirmed RSV test result in the 14 days preceding or during hospitalization. RSV testing was performed at the discretion of the health care providers or through facility-based screening policies and included all commercially available types of RSV tests. Surveillance was conducted annually from October through April during each of the following seasons: 2014–2015, 2015–2016, 2016–2017, 2017–2018, 2021–2022, and 2022–2023. The network covered approximately 3.4% of the US population in 6 states in 2014 and expanded to 8.6% of the US population in 12 states in the 2021–2023 seasons: California, Colorado, Connecticut, Georgia, Maryland, Michigan, Minnesota, New Mexico, New York, Oregon, Tennessee, and Utah (Supplementary Table 1). This analysis included pregnant and nonpregnant women aged 18 to 49 years (childbearing age) with RSV-associated hospitalizations during the surveillance seasons of 2014–2015 through 2017–2018 (prepandemic period) and pregnant women with RSV-associated hospitalizations during the surveillance seasons of 2021–2022 through 2022–2023 (pandemic period). Pregnant women were included if they were pregnant at the time of hospital admission. The 2019–2020 and 2020–2021 seasons were excluded, as data collection and RSV circulation were interrupted due to the COVID-19 pandemic.

Detailed clinical and demographic information was abstracted from medical records by trained surveillance officers using a standardized case report form for all pregnant and nonpregnant women aged 18 to 49 years during the 2014–2018 seasons and for pregnant women during the 2021–2023 seasons. Among pregnant women who delivered during their RSV-associated hospitalization, data on pregnancy outcomes were captured for all surveillance years. Additional details on pregnancy complications and gestation of pregnancy were available only for the 2021–2023 surveillance seasons.

The first stage of our analysis was performed to assess whether there were differences between symptomatic pregnant and nonpregnant women aged 18 to 49 years with RSV-associated hospitalizations. Symptomatic women were defined as those who had the presence of any respiratory symptom (congestion/runny nose, cough, shortness of breath/respiratory distress, upper respiratory tract infection/influenza-like illness, hemoptysis/bloody sputum, sore throat, or wheezing) that began or worsened within the 2 weeks prior to admission according to data available in the medical chart. Because RSV-NET had limited data from nonpregnant women in this age group during the pandemic period, we compared clinical characteristics and severe outcomes (defined as intensive care unit [ICU] admission or in-hospital death) between symptomatic pregnant and nonpregnant women during the prepandemic period only. We used multivariable logistic regression with generalized estimating equations and exchangeable correlation matrix to assess whether pregnancy during a prepandemic RSV-associated hospitalization was associated with severe outcomes. Age, race/ethnicity, respiratory season, and underlying medical conditions were included as covariates in the model. Adjusted risk ratios (aRRs) with 95% CIs are presented for all multivariable associations.

The second stage of our analysis was performed to assess the impact of the COVID-19 pandemic and resulting changes in testing practices on the detection of RSV among hospitalized pregnant women. We examined differences in clinical severity and pregnancy outcomes among symptomatic pregnant women hospitalized with RSV during the prepandemic and pandemic periods. We compared clinical characteristics, severe outcomes, and pregnancy outcomes among symptomatic pregnant women during the prepandemic and pandemic surveillance periods.

The final stage of our analysis was performed to determine if there were differences in clinical course or pregnancy outcomes between symptomatic and asymptomatic pregnant women with RSV-associated hospitalizations during the pandemic period. We compared clinical characteristics, severe outcomes, and pregnancy outcomes between symptomatic and asymptomatic pregnant women in the pandemic period.

A chi-square test was used to compare proportions and a Wilcoxon rank sum test for medians, based on an alpha of .05 to indicate statistical significance. Small sample sizes <4 were suppressed due to privacy considerations. SAS (version 9.4; SAS Institute) was used for all analyses. This activity was reviewed, considered exempt from institutional review board approval, and conducted in accordance with applicable federal law and Centers for Disease Control and Prevention policy (45 CFR part 46, 21 CFR part 56; 42 USC §241d; 5 USC §552a; 44 USC §3501 et seq).

RESULTS

During the 2014–2018 and 2021–2023 surveillance seasons, 11 309 adults aged ≥18 years were hospitalized with RSV infection. Among these, 1042 (9.2%) were women aged 18 to 49 years: 387 women during the prepandemic period and 655 during the pandemic period. There were 41 pregnant women (10.6% of women of childbearing age) identified in the prepandemic period and 238 (36.7% of women of childbearing age) in the pandemic period. The proportion of women in this age group who were pregnant increased each season, from 4% in 2014–2015 to 16% in 2017–2018 (prepandemic seasons) to 38% in 2021–2022 and 36% in 2022–2023 (pandemic seasons). Among 41 pregnant women prepandemic, 18 (43.9%) were no longer pregnant at discharge, and among 238 pregnant women during the pandmic, 174 (73.1%) were no longer pregnant at discharge.

Comparison of Symptomatic Pregnant and Nonpregnant Women Aged 18 to 49 Years in the Prepandemic Period

Among 387 women aged 18 to 49 years with RSV-associated hospitalizations in the prepandemic period, 350 (90.4%) had at least 1 ARI symptom recorded in the medical record in the 2 weeks prior to or at hospital admission, among whom 33 (9.4%) were pregnant at admission (Table 1). When compared with symptomatic pregnant women, symptomatic nonpregnant women were older (median, 37.6 vs 31.6 years; P = .005) and were more likely to have shortness of breath (70.3% vs 42.4%, P = .001), non-ARI symptoms (67.8% vs 48.5%, P = .026), or an underlying medical condition (87.4% vs 42.4%, P < .001). Cardiovascular disease, chronic lung disease, diabetes, immunosuppressive conditions, and neurologic disorders were more common among nonpregnant women. The median hospital length of stay was longer among nonpregnant women (3.6 vs 2.4 days, P = .006). Five (15.2%) pregnant women and 74 (23.3%) nonpregnant women were admitted to the ICU. Five nonpregnant women died during their hospitalization; no pregnant women died. Among pregnant women, 12 (36.4%) delivered during their RSV-associated hospitalization. All deliveries resulted in premature deliveries or ill newborns requiring additional time in the hospital after birth and/or ventilation after birth, miscarriages, or stillbirths.

Table 1.

Demographic and Clinical Characteristics Among Women Aged 18–49 Years With Laboratory-Confirmed RSV With Respiratory Symptoms Stratified by Pregnancy Status, RSV-NET, 2014–2018

	Women, Median (IQR) or No. (%)
	Pregnant (n = 33)	Nonpregnant (n = 317)	Total (n = 350)	P Value
Age, y	31.6 (28.8–35.8)	37.6 (27.8–45.0)	36.8 (27.9–44.4)	.0046
Age group, y				<.0001
18–29	7 (21.2)	88 (27.8)	95 (27.1)
30–39	21 (63.6)	88 (27.8)	109 (31.1)
40–49	5 (15.2)	141 (44.5)	146 (41.7)
Race/ethnicitya				.0298
White, non-Hispanic	18 (60.0)	144 (47.4)	162 (48.5)
Black, non-Hispanic	6 (20.0)	123 (40.5)	129 (38.6)
Hispanic	<4	25 (8.2)	…
Other	4 (13.3)	12 (3.9)	16 (4.8)
Signs and symptoms
Cough	30 (90.9)	285 (89.9)	315 (90.0)	.8549
Wheezing	7 (21.2)	133 (35.6)	120 (34.3)	.0964
Sore throat	7 (21.2)	75 (23.7)	82 (23.4)	.7521
Upper respiratory infection	5 (15.2)	43 (13.6)	48 (13.7)	.8009
Congestion	16 (48.5)	132 (41.6)	148 (42.3)	.4488
Shortness of breath	14 (42.4)	223 (70.3)	237 (67.7)	.0011
Non-ARI symptomsb	16 (48.5)	215 (67.8)	231 (66.0)	.0256
Underlying conditionsc
Asthma	12 (36.4)	112 (35.3)	124 (35.4)	.9061
Cardiovascular disease	<4	65 (20.5)	…	.0146
Chronic lung disease	<4	53 (16.7)	…	.0383
Diabetes	<4	75 (23.7)	…	.0062
Immunosuppressive conditions	<4	108 (34.1)	…	.0033
Neurologic disorders	<4	67 (21.1)	68 (19.4)	.0124
Other conditions	5 (15.2)	143 (45.1)	8 (42.3)	.0009
Any underlying condition	14 (42.4)	277 (87.4)	291 (83.1)	<.0001
Outcomes
ICU admission	5 (15.2)	74 (23.3)	79 (22.6)	.284
In-hospital death	0	5 (1.6)	5 (1.4)
Length of stay, d	2.4 (1.0–4.0)	3.6 (2.0–6.4)	3.4 (1.9–6.2)	.0057
No longer pregnant at discharge	12 (36.4)		12 (36.4)
Pregnancy outcome
Healthy, term newborn	0	NA
Premature ill newborn, miscarriage, neonatal death, stillbirth	12 (100)	NA

Sample sizes <4 are suppressed and totals not shown throughout all analyses due to privacy considerations.

Abbreviations: ARI, acute respiratory infection; ICU, intensive care unit; NA, not applicable; RSV, respiratory syncytial virus; RSV-NET, RSV Hospitalization Surveillance Network.

^aIf individuals did not have ethnicity information, they were categorized as non-Hispanic. Other includes non-Hispanic persons reported as American Indian, Alaska Native, Asian, Pacific Islander, other, or multiple races; 16 (4.6%) had missing or unknown race and ethnicity.

^bNon-ARI symptoms include any of the following: abdominal pain, altered mental status/confusion, anosmia/decreased smell, chest pain, conjunctivitis, diarrhea, dysgeusia/decreased taste, fatigue, fever/chills, headache, muscle aches/myalgias, nausea/vomiting, rash, or seizures.

^cCardiovascular disease does not include hypertension, and chronic lung disease does not include asthma. Other conditions include chronic metabolic disease (excluding diabetes), blood disorder/hemoglobinopathy, renal disease, gastrointestinal/liver disease, rheumatologic/autoimmune/inflammatory condition, and other conditions.

On multivariable analysis, pregnancy was not a risk factor for ICU admission or in-hospital death among women aged 18 to 49 years after controlling for covariates (Figure 1). The presence of underlying medical conditions—specifically, diabetes (aRR, 1.78 [95% CI, 1.16–2.74]; P = .008) and neurologic disorders (aRR, 1.57 [95% CI, 1.24–1.98]; P < .001)—was associated with an increased risk of severe outcomes among all women aged 18 to 49 years regardless of pregnancy status.

Figure 1.

Risk factors for severe outcomes (intensive care unit admission or in-hospital death) among women 18 to 49 years of age with laboratory-confirmed respiratory syncytial virus (RSV Hospitalization Surveillance Network, 2014–2018). Other race category includes non-Hispanic persons reported as American Indian, Alaska Native, Asian, Pacific Islander, other, or multiple races. Total number of women 18 to 49 years of age, n = 350; total with severe outcome, n = 80. aRR, adjusted risk ratio; NH, non-Hispanic.

Comparison of Symptomatic Pregnant Women Between the Prepandemic and Pandemic Periods

Among 41 pregnant women who were hospitalized prepandemic and 238 who were hospitalized during the pandemic, there were 33 (80.5%) and 84 (35.3%) symptomatic pregnant women, respectively. They did not significantly differ by median age, race, or ethnicity (Table 2). The distribution of age groups differed between the periods with a higher proportion symptomatic pregnant women in older groups reported during the prepandemic periods (P = .025). Cough was the only symptom that differed between periods; cough was more frequent among symptomatic pregnant women prepandemic as compared with during the pandemic (90.9% vs 63.1%, P < .003). Length of hospital stay and presence of any underlying condition did not differ between the periods. Almost all symptomatic pregnant women (96.6%) had additional testing for viral codetections, and among those tested, approximately 12% had a known viral codetection; the proportion did not differ between the periods. Five symptomatic pregnant women were admitted to the ICU prepandemic, and none were admitted to the ICU in the pandemic period.

Table 2.

Demographic and Clinical Characteristics Among Pregnant Persons With Laboratory-Confirmed RSV With Respiratory Symptoms Stratified by the Prepandemic (2014–2018) and Pandemic (2021–2023) Periods, RSV-NET

	Pregnant Women, Median (IQR) or No. (%)
	Prepandemic, 2014–2018 (n = 33)	Pandemic, 2021–2023 (n = 84)	Total (n = 117)	P Value
Age, y	31.6 (28.8–35.8)	29.6 (26.1–34.2)	30.5 (26.7–34.5)	.0616
Age group, y
18–29	7 (21.2)	39 (46.4)	46 (39.3)	.0254
30–39	21 (63.6)	40 (47.6)	61 (52.1)
40–49	5 (15.2)	5 (6.0)	10 (8.5)
Race/ethnicitya				.3476
White, non-Hispanic	18 (60.0)	35 (44.3)	53 (48.6)
Black, non-Hispanic	6 (20.0)	18 (22.8)	24 (22.0)
Hispanic	<4	15 (19.0)	…
Other	4 (13.3)	11 (13.9)	15 (13.8)
Signs and symptoms
Cough	30 (90.9)	53 (63.1)	83 (70.9)	.0029
Wheezing	7 (21.2)	10 (11.9)	17 (14.5)	.1986
Sore throat	7 (21.2)	14 (16.7)	21 (17.9)	.5643
Upper respiratory infection	5 (15.2)	21 (25.0)	26 (22.2)	.2489
Congestion	16 (48.5)	43 (51.2)	59 (50.4)	.7922
Shortness of breath	14 (42.4)	24 (28.6)	38 (32.5)	.1499
Non-ARI symptomsb	16 (48.5)	40 (47.6)	56 (47.9)	.9328
Underlying conditions
Asthma	12 (36.4)	23 (27.4)	4 (3.4)	.3396
Cardiovascular disease	<4	6 (2.5)	…	.8848
Chronic lung disease	<4	5 (2.1)	…	.6769
Diabetes	<4	9 (3.8)	…	.8415
Immunosuppressive conditions	<4	<4	…	.0343
Neurologic disorders	<4	<4	…	.8415
Other conditions	<4	<4	…	.1337
Any underlying condition	14 (42.4)	35 (41.7)	49 (41.9)	.9404
Viral testing	33 (93.9)	81 (97.6)	112 (96.6)	.3309
Any viral codetectionsc	4 (12.1)	10 (11.9)	14 (12.0)	.9741
Outcomes
ICU admission	5 (15.2)	<4	…	.0255
Length of stay	2.4 (1.0–4.0)	1.9 (1.0–2.8)	1.9 (0.9–3.0)	.1933
No longer pregnant at discharged	12 (36.4)	45 (54.9)	57 (50.4)	.0545
Pregnancy outcomed
Healthy, term newborn	0	35 (77.8)	35 (61.4)
Premature, ill newborn, miscarriage, neonatal death, stillbirth	12 (100.0)	10 (22.2)	22 (38.6)

Sample sizes <4 are suppressed and totals not shown throughout all analyses due to privacy considerations.

Abbreviations: ARI, acute respiratory infection; ICU, intensive care unit; RSV, respiratory syncytial virus; RSV-NET, RSV Hospitalization Surveillance Network.

^aIf individuals did not have ethnicity information, they were categorized as non-Hispanic. Other includes non-Hispanic persons reported as American Indian, Alaska Native, Asian, Pacific Islander, other, or multiple races; 18 (6.5%) had missing or unknown race and ethnicity.

^bNon-ARI symptoms include any of the following: abdominal pain, altered mental status/confusion, anosmia/decreased smell, chest pain, conjunctivitis, diarrhea, dysgeusia/decreased taste, fatigue, fever/chills, headache, muscle aches/myalgias, nausea/vomiting, rash, or seizures.

^cViral codetections include the following: prepandemic influenza, n = 4 (12.9%); pandemic influenza, n = 5 (6.2%); rhinovirus/human metapneumovirus, n = 5 (6.2%).

^dTwo cases were removed for pregnancy status at discharge and pregnancy outcome due to missing information.

A similar proportion of symptomatic pregnant women delivered (54.9% vs 36.4%, P = .055) during their RSV-associated hospitalization in the prepandemic and pandemic periods. Pregnancy outcomes among those who delivered differed between the periods: during the pandemic, 10 (22.2%) infants were born premature or ill, resulted in a miscarriage or neonatal death, or were stillborn, whereas 12 (100%) of prepandemic deliveries had 1 of these outcomes.

Comparison of Pregnant Women With and Without Respiratory Symptoms During the Pandemic

Among the 238 pregnant women hospitalized with laboratory-confirmed RSV during the 2021–2023 pandemic period, 84 (35.3%) were symptomatic in the 2 weeks prior to or at admission, and 154 (64.7%) pregnant women did not have any respiratory symptoms (Table 3). The presence of any underlying medical condition (41.7% vs 27.9%, P = .031) and specifically asthma (27.4% vs 15.6%, P = .029) was more common among symptomatic pregnant women when compared with asymptomatic pregnant women. Median length of stay did not differ between those with and without respiratory symptoms. Pregnant symptomatic women were earlier in gestation than asymptomatic pregnant women (median gestation, 35.8 vs 38.0 weeks; P < .001) at the time of admission for their RSV-associated hospitalization. Pregnancy outcomes did not differ between symptomatic and asymptomatic pregnant women who delivered during their RSV-associated hospitalization in the pandemic period. Fewer than 4 women were admitted to the ICU, and all were among symptomatic pregnant women; none died in the hospital regardless of the presence of symptoms. Almost all asymptomatic pregnant women (83.7%) delivered during their RSV-associated hospitalization as compared with only 54.9% of symptomatic women (P < .001). There were no differences in pregnancy outcomes between the groups.

Table 3.

Demographic and Clinical Characteristics Among Pregnant Women With Laboratory-Confirmed RSV Stratified by Presence of Respiratory Symptoms, RSV-NET, 2021–2023

	ARI Symptoms, Median (IQR) or No. (%)
	Yes (n = 84)	No (n = 154)	Total (n = 238)	P Value
Age, y	29.6 (26.1–34.2)	29.2 (23.4–33.1)	29.3 (24.2–33.4)	.1325
Age group, y				.6095
18–29	39 (46.4)	74 (48.1)	113 (47.5)
30–39	40 (47.6)	75 (48.7)	115 (48.3)
40–49	5 (6.0)	5 (3.2)	10 (4.2)
Race/ethnicitya
White, non-Hispanic	35 (44.3)	69 (47.6)	104 (46.4)	.3658
Black, non-Hispanic	18 (22.8)	21 (14.5)	39 (17.4)
Hispanic	15 (19.0)	37 (25.5)	52 (23.2)
Other	11 (13.9)	18 (12.4)	29 (12.9)
Signs and symptoms
No signs/symptoms reported	0	120 (77.9)	120 (50.4)
No ARI symptoms	0	154 (100.0)	154 (64.7)
Any ARI symptomsb	84 (100)	0	84 (35.3)
Cough	53 (63.1)	0	53 (22.3)
Wheezing	10 (11.9)	0	10 (4.2)
Sore throat	14 (16.7)	0	14 (5.9)
Upper respiratory infection	21 (25.0)	0	21 (8.8)
Congestion	43 (51.2)	0	43 (18.1)
Shortness of breath	24 (28.6)	0	24 (10.1)
Non-ARI symptomsc	40 (47.6)	34 (22.1)	74 (31.1)	<.0001
Underlying conditions
Asthma	23 (27.4)	24 (15.6)	47 (19.7)	.0289
Cardiovascular disease	<4	<4	6 (2.5)	.4452
Chronic lung disease	4 (4.8)	<4	…	.0345
Diabetes	<4	7 (4.5)	…	.4028
Immunosuppressive conditions	<4	<4	…	.943
Neurologic disorders	<4	4 (2.6)	…	.9189
Other conditionsd	<4	<4	…	.943
Any underlying condition	35 (41.7)	43 (27.9)	78 (32.8)	.0309
Outcomes
ICU admission	<4	0	…
Length of stay	1.9 (1.0–2.8)	1.7 (1.2–2.5)	1.8 (1.1–2.6)	.6736
No longer pregnant at dischargee	45 (54.9)	129 (83.7)	174 (73.1)	<.0001
Pregnancy complication
Gestational diabetes	7 (8.3)	17 (11.0)	24 (10.1)	.5077
Preeclampsia	11 (13.1)	14 (9.1)	25 (10.5)	.3356
Pregnancy induced hypertension	15 (17.9)	16 (10.4)	31 (13.0)	.1019
Intrauterine growth restriction	<4	<4	…	.5348
Gestational age, wk	35.8 (29.8–38.2)	38.0 (36.2–39.0)	37.5 (34.1–38.8)	.00002
Pregnancy outcomee
Healthy, term newborn	35 (74.5)	108 (83.7)	143 (82.2)	.3697
Premature, ill born, miscarriage, neonatal death, stillbirth	10 (25.5)	21 (16.3)	31 (17.8)

Sample sizes <4 are suppressed and totals not shown throughout all analyses due to privacy considerations.

Abbreviations: ARI, acute respiratory infection; ICU, intensive care unit; RSV, respiratory syncytial virus; RSV-NET, RSV Hospitalization Surveillance Network.

^aIf individuals did not have ethnicity information, they were categorized as non-Hispanic. Other includes non-Hispanic persons reported as American Indian, Alaska Native, Asian, Pacific Islander, other, or multiple races; 14 (5.9%) had missing or unknown race and ethnicity.

^bARI symptoms include any of the following: congested/runny nose, cough, hemoptysis/bloody sputum, shortness of breath/respiratory distress, sore throat, upper respiratory tract infection/influenza-like illness, and wheezing.

^cNon-ARI symptoms include any of the following: abdominal pain, altered mental status/confusion, anosmia/decreased smell, chest pain, conjunctivitis, diarrhea, dysgeusia/decreased taste, fatigue, fever/chills, headache, muscle aches/myalgias, nausea/vomiting, rash, or seizures.

^dOther underlying conditions include blood disorder, chronic metabolic disease other than diabetes, renal disease, gastrointestinal/liver disease, rheumatologic/autoimmune/inflammatory condition, and other underlying condition.

^eSix cases were removed for pregnancy status at discharge and pregnancy outcome due to missing information.

DISCUSSION

In a large, geographically diverse, population-based surveillance system that contained data from >11 000 adults with laboratory-confirmed RSV-associated hospitalizations, a small proportion (n = 279, 2.5%) of all adult hospitalizations occurred in pregnant women, and pregnant women hospitalized with RSV rarely experienced severe outcomes. These findings are consistent with smaller studies with limited numbers of RSV infections and hospitalizations among pregnant women [8, 9, 11, 13  16].

During the COVID-19 pandemic, asymptomatic RSV infections were more frequently identified in pregnant women, and a higher proportion of pregnant women delivered during their RSV-associated hospitalization when compared with the prepandemic time frame, likely due to changes in testing practices.

Our finding that severe outcomes are rare among pregnant women hospitalized with RSV is consistent with other studies, although most studies that include data on pregnant women are limited to smaller cohort studies with few RSV infections, of which very few or no infections resulted in hospitalization [8, 9, 11, 13, 16, 17].

In one large study across 4 high-income countries, hospitalized pregnant women were rarely tested for RSV, and among those tested, it was not frequently detected. However, in that study, 40% of women hospitalized with RSV were diagnosed with pneumonia [15]. Women in our analysis were not systematically tested for RSV, and there are likely biases in who was tested. Given similar testing biases in other studies, the addition of routine RSV testing into COVID-19 or influenza studies among pregnant women could help quantify underdetection of RSV in this population.

We identified several important differences in RSV-associated hospitalizations among pregnant women between the prepandemic and pandemic periods. As compared with prepandemic seasons, asymptomatic RSV infections during the pandemic period were more frequently identified in pregnant women; pregnant women were more likely to deliver healthy term infants during their RSV-associated hospitalization; and severe clinical outcomes, such as ICU admission or in-hospital death, were infrequent or absent. It is likely that in the pandemic period, healthy pregnant women with asymptomatic or mild RSV were incidentally identified through routine COVID-19 respiratory virus screening with multipathogen tests upon admission to the labor and delivery ward. Universal screening for SARS-CoV-2 in women admitted for labor and delivery began early in the pandemic and in many settings included all women admitted regardless of the presence of ARI symptoms [18]. These findings support other limited studies suggesting that mild or asymptomatic RSV in pregnant women may be more frequent than previously thought. Such studies identified mild RSV-associated ARI among 10% to 13% of pregnant women receiving routine prenatal care during the respiratory season; the studies also found evidence of a recent RSV infection among 32% of healthy pregnant women, which indicated an unidentified RSV infection in the current or prior RSV season [10].

In contrast, in the prepandemic period, more poor birth outcomes occurred among pregnant women with RSV-associated hospitalizations than during the pandemic period. This likely reflects testing biases and should be interpreted with caution, as hospitalized cases were identified by clinician-driven testing or screening. Unlike the pandemic period, when RSV testing likely occurred as a result of routine SARS-CoV-2 multipathogen screening, clinicians in the prepandemic period may have tested for RSV when pregnant women were more severely ill or had underlying medical conditions, pregnancy complications, or other risk factors, leading to a bias in detecting RSV among hospitalized pregnant women with preterm births or infants who were ill at birth. The role of RSV during pregnancy and its impact on pregnancy outcomes remain unclear; however, there is some evidence that it may be harmful to the fetus. Regan et al found an association with preterm birth among pregnant women who were admitted to the hospital with an ARI or febrile illness during their pregnancy but did not deliver during that admission; however, there was no overall difference in preterm births between those who were RSV positive and negative [15]. Similarly, Kenmoe et al found higher odds of preterm birth among pregnant individuals who were RSV positive [14]. Other studies have not identified an association of preterm birth among women who were positive for RSV during their pregnancy [11, 13, 15], and Trinh et al found that prenatal infection with RSV was associated with a lower birth weight and postnatal growth [19]. Our study was not designed to assess potential harm to the fetus resulting from viral infection during pregnancy, nor could we follow pregnant women to assess outcomes among infants born after their RSV-associated hospitalization.

Maternal RSV vaccination is intended to prevent disease in infants through vertical transmission of antibodies from the mother; this approach has been effective in reducing infant risk for pertussis, COVID-19, and influenza [20, 21]. Clinical data from the vaccine approved in August 2023 suggested that vaccine efficacy, in preventing severe medically attended RSV-associated lower respiratory tract illness in infants in the first 6 months of life, is >75% when vaccination occurs at a gestational age between 32 and 36 weeks [6]. However, for influenza and SARS-CoV-2, studies have shown that pregnant women are at higher risk for hospitalization and severe disease as compared with nonpregnant women [22–26]. COVID-19 and influenza vaccines are thus recommended for pregnant women without regard to timing during pregnancy [27–29] to decrease their risk of severe disease and hospitalization and to provide protection for the infant through maternal antibody transfer. In contrast, the Tdap vaccine, which is administered during pregnancy to protect infants from pertussis, and the RSV maternal vaccine are approved for administration during pregnancy in a specific gestational period to optimize maternal antibody transfer to the infant [6, 7, 30]. Our study suggests that, while RSV vaccine is effective in preventing disease in infants, more data are needed to determine if the maternal RSV vaccine provides clinically meaningful protection to the mother given that severe RSV disease in pregnant women appears to be infrequent.

This cross-sectional study has several limitations. First, data are based on clinician-driven testing practices, and pregnant women who were severely ill or in the ICU were probably more likely to be tested for RSV prior to the pandemic than those who presented with mild or no respiratory symptoms. There are many reasons why some clinicians may choose not to test an individual, and we do not know what proportion of pregnant women present to the hospital with RSV infection but are not tested. Second, women with high-risk pregnancies or underlying medical conditions may be more likely to be hospitalized for monitoring and subsequently tested out of concern for pregnancy complications, and complete data were not available on pregnancy complications. Third, changes in testing practices and the expansion of the catchment area over time make it difficult to interpret trends. Fourth, we do not know if women were admitted for labor and delivery or for other reasons. Fifth, we are unable to assess infant outcomes for those who delivered after their RSV-associated hospitalization and are limited to assessing only those who delivered at the same time as their RSV infection. Last, signs and symptoms on admission are abstracted from the medical record, and case patients may have had symptoms that were not recorded.

Our study indicates that asymptomatic RSV infection may be more common among pregnant women than previously thought, as demonstrated by the high proportion of asymptomatic pregnant women with RSV identified in the pandemic period when testing increased. However, pregnant women are not likely at higher risk for severe RSV outcomes when compared with nonpregnant women of the same age. Although the direct maternal benefit of maternal RSV vaccination may be low in preventing RSV-related hospitalizations in pregnant women, RSV vaccination of pregnant women could play an important role in preventing severe RSV disease in infants through maternal antibody transfer [6].

Supplementary Data

Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.

Notes

Acknowledgments. We thank the surveillance officers, staff, and participating health care facilities and laboratories for their support in data collection. We thank Kendra Delk for her support in preparing the manuscript for submission.

Disclaimer. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the US Department of Health and Human Services, the US Public Health Service Commissioned Corps, the Centers for Disease Control and Prevention, or the authors’ institutions.

Patient consent statement. This activity was reviewed, considered exempt from institutional review board approval, and conducted in accordance with applicable federal law and Centers for Disease Control and Prevention policy (45 CFR part 46, 21 CFR part 56; 42 USC §241[d]; 5 USC §552a; 44 USC §3501 et seq). Patient consent is not required for this activity.

RSV-NET Surveillance Team . Shua J. Chai, MD, MPH (California Emerging Infections Program, Career Epidemiology Field Officer Program, Centers for Disease Control and Prevention); Isaac Armistead, MD, MPH (Colorado Department of Public Health and Environment); Kimberly Yousey-Hindes, MPH (Connecticut Emerging Infections Program, Yale School of Public Health); Kyle P. Openo, DrPH (Emory University School of Medicine, Georgia Emerging Infections Program, Georgia Department of Public Health, Atlanta Veterans Affairs Medical Center); Justin Henderson, MPH (Michigan Department of Health and Human Services); Erica Bye, MPH (Minnesota Department of Health); Francesca Pacheco, MPH (New Mexico Department of Health); Jemma V. Rowlands, MPH (New York State Department of Health); Nancy M. Bennett, MD, MS (University of Rochester School of Medicine and Dentistry); M. Andraya Hendrick, MPH (Public Health Division, Oregon Health Authority); William Schaffner, MD (Vanderbilt University Medical Center); Mary Hill, MPH (Salt Lake County Health Department)

Financial support. This work was supported by the Centers for Disease Control and Prevention through an Emerging Infections Program cooperative agreement (grant CDC-RFA-CK17-1701) and through a Council of State and Territorial Epidemiologists cooperative agreement (grant NU38OT000297-02-00).