Influenza A/H1N1 (2009) infection in pregnancy an Asian perspective

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1 DOI: /j x Maternal medicine Influenza A/H1N1 (2009) infection in pregnancy an Asian perspective ML Lim, a CY Chong, b WSN Tee, c WY Lim, a JJ Chee a a Department of Maternal Fetal Medicine, b Department of Paediatric Medicine & Infectious Disease Service and c Department of Pathology and Laboratory Medicine, KK Women s & Children s Hospital, Singapore Correspondence: Dr ML Lim, Department of Maternal Fetal Medicine, KK Women s & Children s Hospital, 100 Bukit Timah Road, Singapore lim.may.li@kkh.com.sg Accepted 16 January Published Online 10 February Objective To describe the characteristics of an obstetric population with influenza A/H1N1 (2009) infection, with a focus on the need for hospitalisation and complications. Design Cohort study. Setting Tertiary referral centre. Population Two hundred and eleven pregnant women with influenza A/H1N1 (2009) infection diagnosed by nasopharyngeal swab polymerase chain reaction (PCR). Methods Obstetric patients presenting to our centre were recruited and followed up. Data collected included demographic and clinical information. Main outcome measures H1N1 and pregnancy complications, and hospitalisation needs. Results The median age of the cohort was 29.0 years (range years), the median gestation at referral was 23.0 weeks (range 4 38 weeks), the median time interval between illness onset and presentation was 2.0 days (range 1 7 days), and the median time interval between illness onset and commencement of oseltamivir was 2.0 days (range 1 11 days). Hospital admission was significantly associated with the presence of co-morbidity (OR 4.14, 95% CI , P = ), breathlessness (OR 5.2, 95% CI , P = ) and sore throat (OR 0.35, 95% CI , P = 0.005). There were two cases of pneumonia complicating H1N1 infection, but no mortality. Nine cases developed pregnancy complications. All women recovered. Conclusions The need for hospitalisation was significantly associated with breathlessness and co-morbidity. There was minimal morbidity and no mortality observed. We attribute this to early presentation, diagnosis and treatment. Keywords H1N1, influenza, pregnancy. Please cite this paper as: Lim M, Chong C, Tee W, Lim W, Chee J. Influenza A/H1N1 (2009) infection in pregnancy an Asian perspective. BJOG 2010;117: Introduction The influenza A/H1N1 (2009) pandemic has affected many communities in the world, with a gradually increasing mortality. 1 Singapore has been no exception. To date, there have been over 7000 confirmed cases (Singapore Ministry of Health, pers. comm.) and 18 H1N1-related deaths. 2 Identification of this virus in humans in April 2009 attracted due attention because the viral gene segments are a triple-reassortant derived from avian, human and swine lineages. 3 Following the declaration by the World Health Organization of the global threat from the A/H1N1 (2009) virus, 4 our hospital swiftly introduced measures to contain and prevent the spread of infection, as well as to mitigate against possible complications of the infection, particularly in the population deemed to be at increased risk. Observations from past seasonal influenza epidemics and pandemics have identified pregnant women to be a vulnerable group for mortality and morbidity. During the Asian influenza epidemic of , 10% of deaths from influenza in New York City involved pregnant women, whereas in Minnesota, 50% of deaths among women of childbearing age occurred during pregnancy. 5,6 The current A/H1N1 (2009) outbreak appears to be no less severe, with 13% of mortality reported to the US Centres for Disease Control and Prevention in the first 2 months of outbreak occurring in pregnant women. 7 Since the diagnosis of the index case on our shores on 26 May 2009, our centre has managed a large number of ª 2010 The Authors Journal compilation ª RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology 551

2 Lim et al. pregnant women with A/H1N1 (2009) infection. The aim of our paper is to characterise the obstetric population with A/H1N1 (2009) infection presenting to our hospital in the early period of the outbreak, with an emphasis on outcomes and features relating to hospital admission. Methods KK Women s & Children s Hospital, a tertiary referral centre, is responsible for over deliveries per annum, which accounts for 30% of births in Singapore. Our centre has a Women s 24-hour clinic that provides service to patients presenting via self-referral, general practitioners or private hospitals. In our study, we included all pregnant women with A/H1N1 (2009) diagnosed between 26 May 2009 (the date of diagnosis of the first case in Singapore) and 14 September 2009 in our centre. Cases were defined as pregnant women presenting with fever and/or acute respiratory illness, and confirmed positive for A/H1N1 (2009) by a nasopharyngeal swab. A real-time polymerase chain reaction (PCR) assay was set up on the Rotor-Gene Q (Qiagen, using primers and a probe that target the haemagglutinin gene of A/H1N1 (2009). The assay was adapted from the primers and probe used by the National Public Health Laboratory, Singapore. Priority was given to obstetric patients to ensure that swab results were reported within 12 hours. Data were recorded prospectively on demographics such as age, parity and gestational age. Other data recorded pertained to clinical characteristics such as contact history (contact with a confirmed H1N1 case), travel history, presence of co-morbidity, clinical presentation, duration of respiratory illness prior to presentation, temperature on admission (with fever defined as a tympanic temperature above 37.5 C), interval between onset of illness and antiviral therapy, whether the patient was admitted or not and reason for admission (whether mandatory, for clinical indication or for non-clinical indication, such as patient request and unsuitable home environment because of the presence of family members with medical conditions considered as being high risk). Admission for clinical indication was made based on the severity of signs or symptoms at the discretion of the consultant on the day, or because of the presence of respiratory or pregnancy complications. Regarding admission for clinical indication, we also wanted to determine which sample characteristics were associated with an increased likelihood of admission. Patients who were confirmed to have A/H1N1 (2009) were offered treatment with oseltamivir (75 mg twice daily for 5 days) in the first instance, with inhaled zanamivir being offered as a second-line drug. In cases presenting with severe symptoms, empirical treatment was offered pending the results of the nasopharyngeal swab. Institution strategy for the influenza A/H1N1 (2009) outbreak In our institution, strict measures had been implemented to safeguard our patients against A/H1N1 (2009) infection. In the initial containment phase of the outbreak, we set up triaging at entry points into the hospital to identify patients and visitors who had a fever and/or acute respiratory illness. Health personnel were also screened, with body temperatures taken and recorded on a twice-daily basis. Full personal protective equipment (N95 mask, goggles, gloving and gowning) were used when attending to suspected or confirmed A/H1N1 (2009) cases. Registers were put in place to log movements in and out of all wards and departments, in anticipation of the need for contact tracing in the event of positive cases being detected. All pregnant women with a fever and/or acute respiratory illness were assessed carefully. Nasopharyngeal swabs were taken to confirm or exclude A/H1N1 (2009) infection. Each case was co-managed with the infectious disease physicians, and antiviral treatment was instituted immediately if infection was confirmed. Admission into isolation rooms was initially mandatory for all suspected and confirmed cases. Negative cases were discharged if clinically well. All positive cases were treated with oseltamivir and kept in isolation rooms until they had recovered clinically and their nasopharyngeal swabs were negative. In order to cater for the surge in numbers of cases requiring isolation (both obstetric as well as paediatric), five isolation wards were converted from other facilities used as private rooms, family rooms and outpatient areas. As community spread of the virus became more evident in mid-july 2009, there was a transition into a mitigation phase, and we altered our strategy, with admission criteria being based on the patient s clinical condition. There was no mandatory home quarantine or isolation during the mitigation phase, although patients with confirmed A/H1N1 (2009) infection were advised to self-isolate at home. Positive cases were offered treatment with oseltamivir. If the women were clinically well, they were offered outpatient therapy, with advice to return if symptoms intensified or persisted for more than 5 days. Statistical analysis Using STATA 9.2 (Statacorp LP, College Station, TX, USA), results were reported in proportions when describing the sample characteristics. Odds ratios with 95% confidence intervals were used to describe the associations between sample characteristics and the outcomes of interest. The level of statistical significance was set at 5%. The statistical 552 ª 2010 The Authors Journal compilation ª RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology

3 A/H1N1 (2009) infection in pregnancy an Asian perspective methods used involved the use of logistic regression to adjust for multivariate analysis, as well as for confounding factors. Results Between 26 May 2009 and 14 September 2009, 211 cases of A/H1N1 (2009)-positive pregnant women presented to our hospital. The characteristics of these women are shown in Table 1. The median age of the cohort was 29.0 years (range years). In terms of parity, there was an almost equal distribution between nulliparous and multiparous groups (50.7% versus 49.3%). The median gestational age was 23.0 weeks (range 4 38 weeks). The ethnic distribution of the cohort was as follows: 51.1% Chinese (108/211), 29.9% Malay (63/211) and 9.0% Indian (19/211), with a combination of other ethnic groups making up the last 10.0% (21/211). The majority of patients reported having developed a fever at home (176/211; 83.4%). However, fever was recorded in only 132 women (62.6%) at the time of presentation to hospital. Cough was present in 191 women (90.5%). Other reported symptoms included rhinorrhoea (n = 131; 62.1%), sore throat (n = 124; 58.8%), breathlessness (n = 28; 13.3%), headache (n = 38; 18.0%) and myalgia (n = 68; 32.2%). Co-morbidity seen included asthma (n = 27), hypertension (n = 1), gestational diabetes mellitus (n = 4), type-ii diabetes (n = 1) and a combination of heart disease/diabetes mellitus/asthma (n = 2). Twenty-two women (10.4%) reported a positive travel history. Contact history with confirmed H1N1-positive cases was elicited in ten women (4.7%). The median time interval between onset of acute respiratory illness and presentation to hospital was 2.0 days (range 1 7 days), and the median time interval between onset of illness and commencement of treatment was 2.0 days (range 1 11 days). Treatment was accepted by 208 women (98.6%). Three women declined treatment as there was already perceived clinical improvement. All of the treated women were given oseltamivir, with the exception of one woman who requested inhaled zanamivir. Outpatient management was instituted in 149 women (70.6%). The remaining 62 women were admitted for the following reasons: mandatory admission without clinical indication during the containment phase (n = 11), clinical indication [presence of severe symptoms/signs (n = 25), respiratory complication (n = 2), pregnancy complication (n = 8)] and non-clinical indication (n = 16). Table 2 lists the variables that were significantly associated with admission for clinical indication: presence of co-morbidity (OR 4.14, 95% CI , P = ), breathlessness (OR 5.22, 95% CI , P = ) and sore throat (OR 0.35, 95% CI , P = 0.005). Table 1. Characteristics of pregnant women with influenza A/ H1N1 (2009) infection from 26 May 2009 to 14 September 2009 Frequency (%) Maternal age (years) <18 3 (1.4) (56.9) >29 88 (41.7) Parity Nulliparous 107 (50.7) Multiparous 104 (49.3) Gestation at presentation (weeks) (23.7) (46.9) >28 62 (29.4) Race Chinese 108 (51.1) Malay 63 (29.9) Indian 19 (9.0) Others 21 (10.0) Travel history Yes 22 (10.4) No 189 (89.6) Contact history Yes 10 (4.7) No 201 (95.3) Co-morbidity Yes 35 (16.6) No 176 (83.4) Temperature on admission 37.5 C 79 (37.4) >37.5 C 132 (62.6) Interval between onset of illness and presentation (days) 1 59 (28.0) 2 81 (38.4) 3 71 (33.6) Interval between onset of illness and commencement of treatment (days) 1 36 (17.1) 2 70 (33.2) (48.3) Declined treatment 3 (1.4) Duration of hospital stay (days) 1 16 (7.6) 2 19 (9.0) 3 10 (4.7) >3 17 (8.1) Not admitted 149 (70.6) Body temperature had shown a significant linear association (OR 1.62, 95% CI , P = ), with an insignificant test for departure from linearity. From these crude associations, we selected co-morbidity, breathlessness, sore throat and body temperature at admission for the multivariate analysis, as these were the factors that were significant in univariate analysis. They were then fitted into ª 2010 The Authors Journal compilation ª RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology 553

4 Lim et al. Table 2. Crude associations between sample characteristics and hospitalisation for clinical indication in pregnant women with influenza A/H1N1 (2009) infection Variable Category OR 95% CI Likelihood ratio test P value Age <18-years old years old 0.37 ( ) years old 0.41 ( ) Gestation* 13 weeks weeks 1.21 ( ) >28 weeks 2.34 ( ) Race Chinese Malay 1.58 ( ) Indian 1.16 ( ) Others 1.55 ( ) Parity Nulliparous Multiparous 0.84 ( ) Contact history No Yes 2.26 ( ) Co-morbidity No Yes 4.14 ( ) Temperature* C C 1.56 ( ) >38.5 C 2.99 ( ) Cough No Yes 0.56 ( ) Rhinorrhoea No Yes 0.9 ( ) Sore throat No Yes 0.35 ( ) Breathlessness No Yes 5.22 ( ) Headache No Yes 0.54 ( ) Myalgia No Yes 0.1 ( ) Symptomatic days *Significant linear trend. 1 days days 0.56 ( ) >3 days 0.47 ( ) a multivariate logistic regression model to determine the final model associated with hospital admission based on clinical indication, using a forward-fitting technique (Table 3). In our final model, we found that women with co-morbidity and breathlessness had three and four times higher odds ratios for hospital admission, respectively, compared with those without co-morbidity or breathlessness. Similarly, the odds of hospital admission showed a linear increase with body temperature, rising 1.9 times for each 1 C increase. We found no evidence of confounding between these factors. Looking at the length of hospital stay, the median for those admitted (with or without clinical indication; Table 3. Odds ratios for the association with hospital admission for clinical indication mutually adjusted for variables in the model Variables Adjusted OR 95% CI Wald s test P value Co-morbidity Temperature* Breathlessness *Significant linear trend. n = 15) during the containment phase was 4 days (range 1 6 days). During the mitigation phase, 31 of a total of 196 cases were admitted for clinical indication, with a median length of hospital stay of 2 days (range 1 13 days). We had two cases of A/H1N1 (2009) infection complicated by pneumonia. The first was a primigravida at 23 weeks of gestation, with no history of co-morbidity. She had presented to her private obstetrician with a 24-hour history of upper respiratory tract symptoms. A nasopharyngeal swab was taken then. She was confirmed to be H1N1- positive 48 hours later, and was referred to our unit for further management. On admission, she had complained of breathlessness, cough and runny nose. She was pyrexial, tachypnoeic and had reduced oxygen saturation. A chest radiograph showed right-sided pleural effusion with right lower lobe consolidation. She was treated with intravenous ceftriaxone and oral oseltamivir, and admitted into an intensive care unit (ICU) for close monitoring and intensive physiotherapy, during which time her symptoms subsided. She was subsequently transferred to a general isolation ward 48 hours later. A repeat nasopharyngeal swab on day 5 of admission after completion of a 5-day course of oseltamivir was negative, and she was then deisolated. She made an uneventful recovery and was discharged from hospital 13 days post-admission. The second case was a 22-year-old healthy, multiparous woman at 15 weeks of gestation, presenting with a 4-day history of fever, cough, myalgia, breathlessness and vomiting. On admission, her oxygen saturation was normal in room air. A/H1N1 (2009) was confirmed on nasopharyngeal swab within 24 hours of admission. A chest radiograph showed patchy changes in the left lower zone that were suspicious for pneumonia. Intravenous antibiotic and oral oseltamivir therapy were commenced. She recovered uneventfully, and was discharged from hospital 4 days after admission. In our cohort, pregnancy complications included hyperemesis (n = 2), first-trimester miscarriage (n = 3), preterm labour (n = 2), hypertension (n = 1) and suspicious cardiotocograph (n = 1). Of the preterm labour cases, one progressed to delivery at 25 weeks of gestation within 24 hours of admission. 554 ª 2010 The Authors Journal compilation ª RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology

5 A/H1N1 (2009) infection in pregnancy an Asian perspective Complete recovery from A/H1N1 (2009) was seen in all patients. Discussion The A/H1N1 (2009) pandemic has affected Singapore, notwithstanding its geographical distance from the origin of the infection, as a result of the influx of travellers. As this is a new viral strain, there is no prior knowledge of its pathogenicity. As such, our response to the H1N1 crisis was shaped by our experience in 2003, of severe acute respiratory syndrome (SARS), when stringent measures of unprecedented scale were imposed for the containment of the outbreak. 8 Our initial response to news of the evolving pandemic was one of surveillance, isolation and quarantine of all suspected and confirmed cases (containment phase). As the situation evolved, with evidence of community spread, we made the transition towards a mitigation phase, where efforts were targeted towards the high-risk groups, including the pregnant population. The susceptibility of the pregnant woman to viral infections lies in the fact that pregnancy is associated with an immunologic shift from cell-mediated immunity to humoral immunity. Although this physiological change is necessary to facilitate tolerance to paternally-derived fetal antigens, it renders the pregnant woman more vulnerable to intracellular pathogens such as viruses. 9 This increased susceptibility was also seen in previous pandemics: during the influenza pandemic of 1918, pregnant women appeared to have a higher mortality rate compared with non-pregnant women, and pneumonia was a common complication, with 50% of these women dying. 10 Similarly, a study by Mullooly and colleagues also attests to the potential for increased morbidity resulting from influenza in pregnancy: looking at influenza A epidemics over a 5-year period ( ), they found a significant excess of acute respiratory diseases among pregnant women. Notably, this excess was attributable to the period when there was a new strain of virus. 11 To date, there has been no report of a single unit with as large a cohort of H1N1-positive pregnant cases as our centre. We managed 211 cases between 26 May 2009 and 14 September Jamieson and co-workers published the only series of pregnant women with A/H1N1 (2009) infection, comprising 34 women recruited from 13 states in the USA. There was one case of maternal mortality and ten cases of morbidity. 7 Our series had no mortality, although there were 11 cases of morbidity. Our observation of a better outcome may be because of the inclusion of a larger cohort with milder disease. Strict surveillance measures were put in place to detect A/H1N1 (2009) infection in all pregnant women. There was also heightened public awareness as a result of media reporting and strategically placed visual signage within hospitals and family practice clinics, highlighting prior travel, presence of fever or flu-like illness and our past experience with SARS. These factors are likely to have contributed to early presentation and diagnosis allowing early institution of treatment. Almost 70% of our cohort presented within 48 hours of the onset of illness, and over 50% received treatment within this time interval. The prevention of disease progression with early treatment may account for our cohort of milder cases. Randomised controlled studies have demonstrated benefit in commencing antiviral therapy early in acute influenza illness. Nicholson et al. found oseltamivir to result in a significantly shorter duration of illness when the antiviral medication is used for the treatment of acute influenza. 12 Treanor et al. and Kaiser et al. also found oseltamivir to be efficacious in reducing the severity of acute influenza illness, and in reducing the incidence of secondary complications such as bronchitis and pneumonia. 13,14 Mortality has also been shown to be significantly reduced when antiviral treatment is given, as seen in a cohort study of laboratoryconfirmed cases of influenza. 15 In spite of this, A/H1N1 (2009) infection may be a benign illness in pregnancy, as evident in the short length of hospital stay in the cases admitted for clinical indication. Looking at admissions for clinical indication, multivariate analysis found a significant association with variables such as presence of co-morbidity, maternal fever on admission and breathlessness. Cox et al., using a national database on hospitalisations and discharges, found that pregnant women admitted with respiratory complications were more likely to have associated co-morbidities (such as diabetes, chronic renal disease and chronic cardiac disease). 16 Epidemiologic data on fatal cases of A/H1N1 (2009) have also demonstrated a significant proportion of deaths occurring in those with underlying diseases. 17 Breathlessness, a symptom associated with pulmonary complications, was shown to increase the odds of hospital admission by four-fold. The significance of this feature was confirmed in a report by Jain and colleagues, in which shortness of breath was more likely to be seen in A/H1N1 (2009) patients admitted to an ICU and in those who died, than in patients not admitted into an ICU. 18 Notably, we found a disproportionate representation of women of Malay ethnicity in the cohort. The Malays account for about 14% of the general population in Singapore, yet almost a third of our cohort were from this ethnic group. The ascribed ethnicity is often a self-reported demographic. This observation raises the question of whether certain ethnic groups may be more susceptible to A/H1N1 (2009) infection. In addition, could the racial factor explain the disparity between the observed outcomes in our cohort and those in the series by Jamieson et al. 7 Although there are no epidemiological studies on links between race and susceptibility to ª 2010 The Authors Journal compilation ª RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology 555

6 Lim et al. A/H1N1 (2009) infection, it is plausible to hypothesise a link, as it is known that certain diseases are seen more commonly in some ethnic or racial groups. La Ruche et al. found that indigenous populations in some countries of the Americas and the Pacific seemed to be at greater risk of severe A/H1N1 (2009) infection. Although genetic susceptibility was considered to be a contributory factor, other factors such as cultural differences in approach to health, family size, crowding and poor access to health care may play a role. 19 We speculate that these factors may be applicable in our cohort. We recognise some limitations in our study. Firstly, our admission criteria, which included the severity of clinical signs/symptoms at the discretion of the admitting consultant, is open to bias and subjectivity. Secondly, despite the large cohort of A/H1N1 (2009)-infected women, the proportion of severe cases is too small to allow any meaningful subgroup analysis. Conclusion Our experience of A/H1N1 (2009) in pregnancy suggests that the infection is mild in nature. Due consideration should be given to the potential benefit of early diagnosis and treatment. However, its novelty and the limited literature currently available on the subject indicate the need for a cautionary approach when managing an obstetric patient with this infection. Disclosure of interests None. Contribution to authorship MLL was responsible for the study design, data collection, data analysis and the writing of the manuscript. CYC reviewed the manuscript. WSNT contributed details on laboratory test and reviewed manuscript. WYL was responsible for statistical analysis. JJC analysed the data and reviewed the manuscript. Details of ethics approval Not applicable. Funding None. j References 1 World Health Organisation. Global alert and response (GAR). Pandemic (H1N1) 2009 update 62 [ 2009_08_21/en/index.html]. Accessed 20 September Singapore: Ministry of Health. 18th influenza A (H1N1-2009) related death press release [ aspx?id=22990]. Accessed 20 September Smith GJD, Vijaykrishna D, Bahl J, Lycett SJ, Worobey M, Pybus OG, et al. Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature 2009;459: World Health Organisation. Global alert and response (GAR). Swine flu illness in the United States and Mexico update 2 [ Accessed 20 September Greenberg M, Jacobziner H, Pakter J, Weisl BAG. Maternal mortality in the epidemic of Asian influenza, New York City, Am J Obstet Gynecol 1958;76: Freeman DW, Barno A. Deaths from Asian influenza associated with pregnancy. Am J Obstet Gynecol 1959;78: Jamieson DJ, Honein MA, Rasmussen SA, Williams JL, Swerdlow DL, Biggerstaff MS, et al. H1N influenza virus infection during pregnancy in the USA. Lancet 2009;374: James L, Shindo N, Cutter J, Ma S, Chew SK. Public health measures implemented during SARS outbreak in Singapore Public Health 2006;120: Jamieson DJ, Theiler RN, Rasmussen SA. Emerging infections and pregnancy. Emerg Infect Dis 2006;12: Harris JW. Influenza occurring in pregnant women. JAMA 1919;72: Mullooly JP, Barker WH, Nolan TF. Risk of acute respiratory disease among pregnant women during influenza A epidemics. Public Health Rep 1986;101: Nicholson KG, Aoki FY, Osterhaus ADME, Trottier S, Carewicz O, Mercier CH, et al. Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Lancet 2000;355: Treanor JT, Hayden FG, Vrooman PS, Barbarash R, Bettis R, Riff D, et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza a randomized controlled trial. JAMA 2000;283: Kaiser L, Wat C, Mills T, Mahoney P, Ward P, Hayden F. Impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations. Arch Intern Med 2003;163: McGeer A, Green KA, Plevneshi A, Shigayeva A, Siddiqi N, Raboud J, et al. Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada. Clin Infect Dis 2007;45: Cox S, Posner SF, McPheeters M, Jamieson DJ, Kourtis AP, Meikle S. Hospitalizations with respiratory illness among pregnant women during influenza season. Obstet Gynecol 2006;107: Vaillant L, La Ruche G, Tarantola A, Barboza P. Epidemiology of fatal cases associated with pandemic H1N1 influenza Euro Surveill 2009;14:pii= Jain S, Kamimoto L, Bramley AM, Schmitz AM, Benoit SR, Louie J, et al. Hospitalised patients with 2009 H1N1 influenza in the United States, April June N Engl J Med 2009;361: La Ruche G, Tarantola A, Barboza P, Vaillant L, Gueguen J, Gastellu- Etchegorry M. The 2009 pandemic H1N1 influenza and indigenous populations of the Americas and the Pacific. Euro Surveill 2009;14:pii= ª 2010 The Authors Journal compilation ª RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology