Maternal and Infant Outcomes Among Severely Ill Pregnant and Postpartum Women with 2009 Pandemic Influenza A (H1N1) --- United States, April 2009--August 2010

Pregnant women with influenza are at increased risk for hospitalization and death (1,2). Since 2004, the Advisory Committee on Immunization Practices (ACIP) has recommended inactivated influenza vaccine for all women who are pregnant during influenza season, regardless of trimester (3). Nonetheless, after the 2004 recommendation, estimated annual influenza vaccination coverage among pregnant women was approximately 15%, before increasing to nearly 50% during the 2009 influenza A (H1N1) pandemic (4). Since April 2009, CDC has collaborated with state and local health departments to conduct enhanced surveillance for severe influenza among pregnant and postpartum women. To assess maternal and infant outcomes among severely ill pregnant and postpartum women with 2009 H1N1 during the 2009 H1N1 pandemic, CDC analyzed data for the period April 15, 2009 to August 10, 2010. This report summarizes the results of that analysis, which found that, among 347 severely ill pregnant women, 75 died from 2009 H1N1, and 272 were admitted to an intensive-care unit (ICU) and survived. Women who survived received antiviral treatment sooner after symptom onset than women who died. Pregnant women with severe influenza who delivered during their influenza hospitalization were more likely to deliver preterm and low birth weight infants than those in the general U.S. population; infants born after their mother's influenza hospitalization discharge were more likely to be small for gestational age. These data document the severe effects of 2009 H1N1 on pregnant women and their infants, emphasize the importance of vaccinating pregnant women against influenza (3,5), and demonstrate the value of prompt administration of antivirals to pregnant women with suspected or confirmed influenza (5,6).

CDC initially requested reporting of all pregnant women with influenza illness who had been reported to state/local health departments with illness onset from April 15, 2009, to August 21, 2009. In October 2009, CDC established the CDC Pregnancy Flu Line as a dedicated, ongoing mechanism for reporting severely ill pregnant and postpartum women with onset during August 21, 2009--August 10, 2010. Surveillance data with illness onset from April 15, 2009, to December 31, 2009, and reported to CDC by January 31, 2010, were reported previously (2). Health departments used existing public health surveillance infrastructure to identify women who were pregnant or postpartum (≤6 weeks) at illness onset, were admitted to an ICU or died, and had laboratory-confirmed influenza as defined by a positive rapid influenza diagnostic test, real-time reverse transcriptase--polymerase chain reaction, or viral culture. Requested data included demographic and clinical information on infected pregnant women and, for the Flu Line, their newborns. The initial CDC data request elicited responses from 50 of the 53 state and local health departments contacted; the Flu Line received responses from 50 states, three localities, and one territory. Flu Line staff members followed up on incomplete case reports until final outcomes were obtained for mother and infant, when possible. Surveillance mechanisms among states varied. Women were assumed to be infected with 2009 H1N1 when influenza type was not available, based on U.S. virologic surveillance data that suggested nearly all influenza activity during this time was 2009 H1N1 (2,7).

Although the initial data request included pregnant women who were not severely ill with influenza, the Flu Line only included severely ill women, and this analysis of the entire pandemic period (April 15, 2009--August 10, 2010) includes only women with severe illness (i.e., death or ICU admission). Similarly, because data on postpartum women were not requested as part of the initial data request, totals are reported separately for pregnant and postpartum women, and differences in categorical variables for the entire period are presented for pregnant women only. Demographic and clinical factors were compared using Fisher's exact tests and corresponding p values. Small for gestational age was calculated by comparing the 2005 standard 10th percentiles for birth weight (8) to weight for gestational age at birth as reported in the Flu Line case report.

From April 15, 2009, to August 10, 2010, a total of 347 severely ill pregnant women, including 272 who were admitted to the ICU and survived and 75 pregnant women who died from 2009 H1N1, were reported to the surveillance systems. Fifteen severely ill postpartum women, including nine who died, also were reported.

Of the 307 pregnant women for whom information regarding the presence of underlying medical conditions was available, 153 (49.8%) had underlying conditions. Comparing pregnant women who died with those who were admitted to an ICU and survived, the women who died were significantly more likely to have underlying conditions (61.5%) than those who survived (46.7%) (p=0.04) (Table 1). The underlying conditions (generally indicated by checked boxes on the case report form) included asthma, pregestational/gestational diabetes, obesity, immune suppression, cancer, pregestational/gestational hypertension, hemoglobinopathy, and chronic lung, autoimmune, neurologic, renal, thyroid, and cardiovascular diseases. No statistically significant differences between the women who died and the ICU survivors were observed by age, race, or trimester of illness onset.

Among women who died, 86.1% received antiviral treatment with a neuraminidase inhibitor, compared with 94.8% of women who survived (p=0.02) (Table 1). Treatment timing was significantly different for women who died, compared with those who survived (p<0.01); only four (7.0%) of the pregnant women who died received treatment with a neuraminidase inhibitor within 2 days of illness onset, compared with 76 (40.6%) of the women who survived. The Flu Line requested reports of any severe influenza illness with onset after August 21, 2009; however, the first shipments of 2009 H1N1 vaccine did not occur until approximately 2 months after this date, and only 105 (48%) of the 218 Flu Line reports included vaccination status. Of the 105, three women who were admitted to an ICU reported receiving the 2009 H1N1 vaccine at least 2 weeks before onset of illness; none of the women who died were reported to have received the 2009 H1N1 vaccine.

Data on pregnancy outcomes were requested for Flu Line reports only, and pregnancy outcome data were available for 168 (77%) of the 218 Flu Line reports. Of the 168 pregnancy outcomes, 148 (88%) were live births, 11 (7%) were spontaneous abortions, seven (4%) were fetal deaths, one was an ectopic pregnancy, and one was a 15-week elective abortion secondary to intrauterine growth restriction. Among 85 liveborn singleton infants born during their mothers' hospitalization for influenza, 63.6% were born preterm or very preterm (<37 weeks gestation), 4.1% were small for gestational age; 43.8% had low birth weight, 69.4% were admitted to the neonatal intensive care unit, and 29.2% had a low 5-minute Apgar score (defined as ≤6) (Table 2). Of 54 liveborn singleton infants born 5--187 days (median: 85 days) after their mother's discharge from influenza hospitalization, 20.8% were born preterm, 25.0% were small for gestational age, 19.2% had low birth weight, 22.0% were admitted to the neonatal intensive care unit, and 2.0% had a low 5-minute Apgar score (Table 2).

Reported by

Kimberly Newsome, MPH, Jennifer Williams, MSN, Shannon Way, MPH, Margaret Honein, PhD, Holly Hill, MD, National Center on Birth Defects and Developmental Disabilities; Sonja Rasmussen, MD, Influenza Coordination Unit, Anne F McIntyre, PhD, Lyn Finelli, DrPH, National Center for Immunization and Respiratory Diseases; Denise Jamieson, MD, William Callaghan, MD, Marianne Zotti, DrPH, National Center for Chronic Disease Prevention and Health Promotion, CDC. Corresponding contributor: Kimberly Newsome, kan3@cdc.gov.

Editorial Note

These data underscore the severe effects of influenza on pregnant women and their infants. Although previous reports have noted similar maternal findings, national influenza pandemic pregnancy data have heretofore not included infant outcomes. Among women who delivered while hospitalized for influenza, 63.6% delivered preterm or very preterm and 43.8% delivered low birth weight infants compared with U.S. averages of 12.3% for preterm birth and 8.2% for low birth weight (9). Similarly, 25.0% of infants born after their mothers' influenza hospitalization discharge were small for gestational age, compared with 10.0% of the general population (8).

The findings in this report are subject to at least four limitations. First, reporting requirements and case identification are not standardized across states and localities. Second, since August 2009, CDC has only collected and this report is only presenting data on severely ill pregnant women, and this analysis is not representative of the burden of influenza illness among all pregnant women. Third, because many women do not know they are pregnant early in pregnancy, illness in the first trimester might be more likely to be underreported. Finally, 49.8% of the pregnant women had underlying medical conditions in addition to severe influenza; although the presence of an underlying medical condition is common among reproductive-aged women (e.g., 34% of reproductive aged women in the United States are obese) (10), the degree to which adverse infant outcomes can be attributed to 2009 H1N1 or to the underlying conditions is unknown.

These data reaffirm recommendations that pregnant and postpartum women receive prompt, empiric treatment with antiviral medications for suspected or confirmed influenza (5,6). In addition, the severe impact of 2009 H1N1 influenza among pregnant women and their infants emphasizes the importance of prevention in this group. The cornerstone of influenza prevention among pregnant women remains promotion of influenza vaccination; ACIP recommends vaccination for women regardless of trimester (3). Despite this recommendation and the recent increase in influenza vaccination among pregnant women, coverage remains lower than optimal and increasing vaccination coverage in this group continues to be a key public health priority (5).

Acknowledgments

State and local health department staff members who collected data for CDC on maternal and infant outcomes among severely ill pregnant and postpartum women. Listing available at http://www.cdc.gov/ncbddd/birthdefects/acknowlegements.html.

References

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