Executive summary of HTA journal
Health Technol Assess 2010;14(34):109–182
Influenza A/H1N1v in pregnancy: an investigation of the characteristics and managementof affected women and the relationship to pregnancy outcomes for mother and infant.
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L Yates,1 M Pierce,2 S Stephens,1 AC Mill,3 P Spark,2 JJ Kurinczuk,2 M Valappil,4 P Brocklehurst,2 SHL Thomas1,5* and M Knight2
1United Kingdom Teratology Information Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Wolfson Unit, Newcastle upon Tyne, UK
2National Perinatal Epidemiology Unit, University of Oxford, UK
3School of Biology, Institute of Research on the Environment and Sustainability, Newcastle University, Newcastle upon Tyne, UK
4Health Protection Agency Newcastle Laboratory, Institute of Pathology, Newcastle General Hospital, Newcastle upon Tyne, UK
5Wolfson Unit of Clinical Pharmacology, Institute of Cellular Medicine and Medical Toxicology Centre, Newcastle University, Newcastle upon Tyne, UK
April 2009 saw the emergence of a novel influenza A virus of swine origin (swine flu), subsequently subtyped (and referred to in this document) as AH1N1v. This spread rapidly, achieving pandemic status in June 2009. Pregnant women were identified as being at high risk of severe influenza-related complications, requiring early assessment and treatment of flu-like symptoms, and as a priority group for vaccination against AH1N1v. There was, however, limited information available about the maternal and fetal risks of AH1N1v infection or of antiviral drug or AH1N1v vaccine use in pregnancy. This study was therefore designed to assess rates of and risk factors for adverse outcomes following AH1N1v infection in pregnancy and to assess the adverse effects of the antiviral drugs and vaccines used in prevention and management.
The objectives of this research were to:
- estimate the incidence of AH1N1v influenza in pregnancy during the ‘second wave’
- determine the effect of AH1N1v infection and/or treatment with neuraminidase antiviral drugs in pregnant women and/or AH1N1v vaccination (timing of use, dose and agent) on pregnancy outcome, including specific adverse or beneficial effects of antiviral treatment or AH1N1v vaccination on eventual maternal and fetal outcome
- ascertain the influence of demographic or pregnancy characteristics and additional aspects of pregnancy management on outcomes for mother and infant
- produce guidance on the management of AH1N1v infection in pregnancy: initially following systematic review and updated subsequently by monthly review of emerging data from this study such that outcomes for women and infants could be optimised during the current pandemic.
Prospective national cohort studies were conducted using different sources to identify women in three specific groups:
- pregnant women suspected of being infected with AH1N1v or treated with antiviral medication and managed in the community
- pregnant women vaccinated against AH1N1v
- pregnant women admitted to hospital with confirmed AH1N1v.
Information about pregnancy management and outcomes was collected directly from health professionals caring for infected women in secondary care settings, and from health professionals as well as women themselves, with consent, where infection was managed in primary care.
Women were identified through the following sources:
- The UK Teratology Information Service (UKTIS) collected data from general practices within and outside the Primary Care Research Networks (PCRNs), as well as from self-notifications from affected women. Some practices acted as ‘sentinel’ sites, providing data on all presentations, antiviral prescriptions and vaccinations.
- The UK Obstetric Surveillance System (UKOSS) collected data through its network of collaborating clinicians in all consultant-led maternity units in the UK.
Characteristics of women with influenza-like illness (ILI) in primary care were compared with those of women without symptoms accepting or declining immunisation. Characteristics of women admitted to hospital with confirmed AH1N1v infection in pregnancy were compared with a historical cohort of over 1200 women giving birth in the UK, identified from the same hospitals as the cohort women and uninfected with AH1N1v.
The incidences of suspected AH1N1v infection, use of antiviral drugs and AH1N1v vaccination were estimated from presentation data provided by sentinel general practices. Characteristics of women with ILI were compared with asymptomatic women who were offered vaccination. Use and timing of antiviral agents and uptake of AH1N1v vaccines were also determined.
The incidence of hospitalisation with confirmed AH1N1v influenza in pregnancy was estimated with 95% confidence intervals (CIs) using the most recently available birth data (2007) as a proxy for September 2009 to January 2010. Outcomes examined in hospitalised women included maternal death, admission to an intensive care unit, perinatal mortality and preterm birth. In addition, risk factors for hospital and intensive care unit admission were examined in a full regression model, which was developed by including both potential explanatory and confounding factors in a core model if there was a pre-existing hypothesis or evidence to suggest that they were causally related to admission with AH1N1v influenza in pregnancy.
The weekly incidence of ILI amongst pregnant women in 24 sentinel practices averaged 51/100,000 over the period of study. In the 23 practices providing these data, antiviral drugs were offered to 4.8% (95% CI 4.0% to 5.9%) and vaccination to 64.8% (95% CI 64.7% to 68.9%) of registered pregnant women.
A total of 90 pregnant women with ILI presenting in primary care were reported to the research team: 55 were prescribed antiviral drugs and in 42 (76%) cases this was within 2 days of symptom onset. After comparison with 1329 uninfected pregnant women who were offered vaccination, the only maternal factor identified as increasing odds of ILI presentation was pre-existing asthma [adjusted odds ratio (aOR) 2.0, 95% CI 1.0 to 3.9]. In this small data set there was no significant effect of other comorbid conditions or of age, racial group, body mass index (BMI), index of multiple deprivation (IMD) or smoking status. The data suggest that vaccination occurred in 56% of pregnant women who were offered it, although information on whether or not vaccination was offered was not always provided.
Overall, 241 pregnant women were admitted to hospital with laboratory-confirmed AH1N1v infection. Eighty-three per cent of women who were hospitalised with AH1N1v influenza were treated with antiviral agents, but only 6% received antiviral treatment before hospital admission.
Women hospitalised with AH1N1v influenza in pregnancy were more likely to be overweight (aOR 1.7, 95% CI 1.2 to 2.4) or obese (aOR 2.0, 95% CI 1.3 to 3.0) than the comparison cohort. They were also more likely to have asthma requiring inhaled or oral steroids (aOR 2.3, 95% CI 1.4 to 3.9), to be multiparous (aOR 1.6, 95% CI 1.1 to 2.2), to have a multiple pregnancy (aOR 5.2, 95% CI 1.9 to 13.8) and to be from a black or other minority ethnic group (aOR 1.6, 95% CI 1.1 to 2.3). Younger smokers had a raised odds of admission with confirmed AH1N1v influenza (aOR 4.2, 95% CI 2.0 to 8.9) when compared with older non-smokers.
Treatment within 2 days of symptom onset was associated with an 84% reduction in the odds of admission to an intensive therapy unit (ITU) (OR 0.16, 95% CI 0.08 to 0.34); women admitted to ITU were more likely to be obese (aOR 3.4, 95% CI 1.2 to 9.2) than women who were not admitted to an ITU.
Sixty-three per cent of hospitalised women had completed their pregnancies at the time of reporting. Women admitted to hospital with AH1N1v infection were more likely to deliver preterm; a conservative estimate accounting for the high proportion of women who are undelivered suggests a three times increased risk compared with an uninfected population cohort (OR 3.1, 95% CI 2.1 to 4.5).
Earlier treatment with antiviral agents is associated with improved outcomes for pregnant women. Further actions are needed in future pandemics to ensure that antiviral agents and vaccines are provided promptly to pregnant women, particularly in the primary care setting.
Maternal obesity during pregnancy is associated with both admission to hospital with confirmed infection and critical illness from AH1N1v infection. This highlights the importance of ongoing work to support obesity prevention at a community level.
Maternal smoking, particularly in younger mothers, is also associated with admission with AH1N1v infection in pregnancy. Smoking in pregnancy is associated with a number of risks to both mother and fetus and thus prevention programmes continue to be important.
Women with asthma and other comorbidities are more likely to present in primary care or be admitted to hospital with AH1N1v infection in pregnancy. Clinicians should be aware of this association and work to ensure that women with coexisting illnesses in pregnancy are treated appropriately.
Data on outcomes of pregnancy in women admitted to hospital with confirmed AH1N1v influenza are, as yet, incomplete. However, there appears to be a significantly increased risk of preterm delivery, which may impact on service provision in a future pandemic.
Further research is needed on longer-term outcomes for infants exposed to AH1N1v influenza, antiviral drugs or vaccines during pregnancy. This includes studies of the effects of these factors on:
- fetal development and congenital malformations
- postnatal development
- potentially associated conditions, such as childhood leukaemia.
Yates L, Pierce M, Stephens S, Mill A, Spark P, Kurinczuk J, et al. Influenza A/H1N1v in pregnancy: an investigation of the characteristics and managementof affected women and the relationship to pregnancy outcomes for mother and infant. Health Technol Assess 2010;14(34):109–182.
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