The effects of influenza on pregnancy

1. The effects of influenza on pregnancy Pat O’Brien

2. Seasonal flu • A respiratory illness  No viraemia • No transplacental transmission • Fetal abnormalities very unlikely • 11% of all mothers have proven infection • More complications of pregnancy • HT, bleeding, breech! • No single complication significantly  • Pregnancy outcomes are the same Ramphal et al, AJOG, 1980 Irving et al, BJOG, 2000

3. Pandemic flu • More invasive and more virulent • Viraemia common • ? Possibly reaches placenta +/- fetus • Evidence lacking

4. Pregnancy and H5N1 infection • Case report Gu et al, Lancet, 2007(post-mortem pregnant woman) • Virus detected in placenta and fetus • Lungs, liver macrophages, circulating monocytes • Mild acute interstitial pneumonitis • Why the difference? • Maternal viraemia more common • Different virus receptor expression • Lungs • High number of infected cells, but • No evidence of severe damage • ? Due to naive immune status (less cytokines)

5. Effect on baby: virus(if transplacental spread) • 1st trimester • Miscarriage/birth defects • 2nd trimester • Miscarriage/IUFD • ? Neuropsychiatric morbidity • Japan 1957: flu in 2nd trimester  risk of schizophrenia in children  x 3 • Close to delivery • Neonatal influenza infection

6. Effect on fetus - fever • Uncertain (epidemiological studies), but... • Episodes of hyperthermia common • 18% in 1st trimester • Miscarriage • No Andersen et al, Lancet, 2002 • Yes (OR 5.5) Kline et al, Am J Epid, 1985 • Fetal abnormalities • Animals: Yes (Brain, NTD, clefts, heart) Edwards, Birth Defects Research, 2006 • Humans: Perhaps (NTD, heart) Milunsky et al, JAMA, 1992 Tikkanen et al, Eur J Epid, 1991

7. Effect on fetus: maternal condition • Severe maternal illness • hypoxia • hypotension • Hypoxia + pyrexia  increased risk of hypoxic brain damage

8. Any evidence from previous flu pandemics? • Little good evidence • Stillbirth figures from past 80 years: • No changes that could be attributed to pandemic flu

9. Effect on mother • Viral pneumonia • +/- secondary bacterial pneumonia • Are pregnant women more susceptible to seasonal flu virus? • Evidence conflicting, but probably yes • CDC believes so  recommends vaccination

10. Effect on mother • Is seasonal flu pneumonia more severe/fatal in pregnant women? • Again, evidence conflicting, but probably yes • Chickenpox pneumonia: case fatality rate  x 5 • 3rd trimester •  immune function Likely to  respiratory •  body water dysfunction caused by • Splinting of diaphragm pneumonia

11. Effect of pandemic flu virus on mother • 500,000 women pregnant • 250,000 infected • 2.5% case fatality rate • 6,250 maternal deaths • Maternal mortality rate • 1.25% • 1250 per 100,000 (not counting deaths in puerperium)

12. H1N1: Swine Flu - Australia • Population 21 million • 27,000 cases • 95 deaths (1 in 20,000) • 3,281 hospital admissions • 1918-9 pandemic: 1 in 400 died • More seriously affected: • Pregnant • Obese • Diabetes

13. H1N1: Swine Flu DH/RCOG recommends: • Do not need to take swabs • Do not give post-exposure prophylaxis • Do treat pregnant women with flu symptoms • Choice of drug • Zanamivir (Relenza) in pregnancy • Severe Asthma → consider using Tamiflu • Encourage breast-feeding (use Tamiflu)

14. Key messages • Paradox: most mild, but some very severe • Younger age group • Obese, pregnant, diabetes • Treat pregnant women • DON’T PANIC! But don’t be complacent

15. Next steps • Second wave • Resistance • Genetic re-assortment or recombination • Vaccination • High risk groups • Front-line staff • Mechanism