The effects of influenza on pregnancy Pat O’Brien

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

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

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

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

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

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

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

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

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

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

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

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)

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

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