The effects of influenza The effects of influenza on pregnancy on pregnancy

Pat O’BrienPat O’Brien

Seasonal flu Seasonal flu • A A respiratoryrespiratory illness illness No viraemia No viraemia

• No transplacental transmissionNo transplacental transmission

• Fetal abnormalities very unlikelyFetal abnormalities very unlikely– 11% of all mothers have proven infection11% of all mothers have proven infection

• More complications of pregnancyMore complications of pregnancy– HT, bleeding, breech!HT, bleeding, breech!– No single complication significantly No single complication significantly

• Pregnancy outcomes are the samePregnancy outcomes are the same Ramphal et al, AJOG, 1980Ramphal et al, AJOG, 1980

Irving et al, BJOG, 2000Irving et al, BJOG, 2000

Pandemic fluPandemic flu

• More invasive and more virulentMore invasive and more virulent

• Viraemia commonViraemia common

• ? Possibly reaches placenta +/- fetus? Possibly reaches placenta +/- fetus

• Evidence lackingEvidence lacking

Pregnancy and H5N1 Pregnancy and H5N1 infectioninfection• Case report Case report Gu et al, Lancet, 2007Gu et al, Lancet, 2007

((post-mortem pregnant womanpost-mortem pregnant woman))– Virus detected in placenta and fetusVirus detected in placenta and fetus

•Lungs, liver macrophages, circulating Lungs, liver macrophages, circulating monocytesmonocytes

•Mild acute interstitial pneumonitisMild acute interstitial pneumonitis

– Why the difference?Why the difference?•Maternal viraemia more commonMaternal viraemia more common

•Different virus receptor expressionDifferent virus receptor expression

– LungsLungs•High number of infected cells, butHigh number of infected cells, but

•No evidence of severe damageNo evidence of severe damage

•? Due to naive immune status (less cytokines)? Due to naive immune status (less cytokines)

Effect on baby: virusEffect on baby: virus((if transplacental spreadif transplacental spread))

• 11stst trimester trimester– Miscarriage/birth defectsMiscarriage/birth defects

• 22ndnd trimester trimester– Miscarriage/IUFDMiscarriage/IUFD– ? Neuropsychiatric morbidity? Neuropsychiatric morbidity

• Japan 1957: flu in 2Japan 1957: flu in 2ndnd trimester trimester risk of schizophrenia in children risk of schizophrenia in children x 3 x 3

• Close to deliveryClose to delivery– Neonatal influenza infectionNeonatal influenza infection

Effect on fetus - feverEffect on fetus - fever• Uncertain (epidemiological studies), Uncertain (epidemiological studies), butbut......

– Episodes of hyperthermia commonEpisodes of hyperthermia common•18% in 118% in 1stst trimester trimester

– MiscarriageMiscarriage•NoNo Andersen et al, Lancet, 2002Andersen et al, Lancet, 2002

•Yes (OR 5.5)Yes (OR 5.5) Kline et al, Am J Epid, 1985Kline et al, Am J Epid, 1985

– Fetal abnormalitiesFetal abnormalities•Animals: Yes (Brain, NTD, clefts, heart)Animals: Yes (Brain, NTD, clefts, heart)

Edwards, Birth Defects Research, 2006Edwards, Birth Defects Research, 2006

•Humans: Perhaps (NTD, heart)Humans: Perhaps (NTD, heart)

Milunsky et al, JAMA, 1992Milunsky et al, JAMA, 1992

Tikkanen et al, Eur J Epid, 1991Tikkanen et al, Eur J Epid, 1991

Effect on fetus: maternal Effect on fetus: maternal conditioncondition

• Severe maternal illnessSevere maternal illness– hypoxiahypoxia– hypotensionhypotension

• Hypoxia + pyrexiaHypoxia + pyrexia

increased risk of hypoxic brain increased risk of hypoxic brain damagedamage

Any evidence from Any evidence from previous flu pandemics? previous flu pandemics?

• Little good evidenceLittle good evidence

• Stillbirth figures from past 80 years:Stillbirth figures from past 80 years:– NoNo changes that could be attributed to changes that could be attributed to

pandemic flupandemic flu

Effect on motherEffect on mother

• Viral pneumoniaViral pneumonia

• +/- secondary bacterial pneumonia+/- secondary bacterial pneumonia

• Are pregnant women more Are pregnant women more susceptible to seasonal flu virus?susceptible to seasonal flu virus?– Evidence conflicting, but probably yesEvidence conflicting, but probably yes– CDC believes so CDC believes so recommends recommends

vaccinationvaccination

Effect on motherEffect on mother

• Is seasonal flu pneumonia more Is seasonal flu pneumonia more severe/fatal in pregnant women?severe/fatal in pregnant women?– Again, evidence conflicting, but probably yesAgain, evidence conflicting, but probably yes– Chickenpox pneumonia: case fatality rate Chickenpox pneumonia: case fatality rate x 5 x 5

• 33rdrd trimester trimester– immune function Likely to immune function Likely to respiratory respiratory– body waterbody water dysfunction caused by dysfunction caused by– Splinting of diaphragm pneumonia Splinting of diaphragm pneumonia

Effect of pandemic flu virus Effect of pandemic flu virus on mother on mother• 500,000 women pregnant500,000 women pregnant

• 250,000 infected250,000 infected

• 2.5% case fatality rate2.5% case fatality rate

• 6,250 maternal deaths6,250 maternal deaths

• Maternal mortality rateMaternal mortality rate– 1.25%1.25%– 1250 per 100,000 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

• 1918-9 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 messagesKey messages

• Paradox: most mild, but some very Paradox: most mild, but some very severesevere

• Younger age groupYounger age group

• Obese, pregnant, diabetesObese, pregnant, diabetes

• Treat pregnant womenTreat pregnant women

• DON’T PANIC! But don’t be DON’T PANIC! But don’t be complacentcomplacent

Next stepsNext steps

• Second wave Second wave

• ResistanceResistance

• Genetic re-assortment or Genetic re-assortment or recombinationrecombination

• VaccinationVaccination– High risk groupsHigh risk groups– Front-line staffFront-line staff– MechanismMechanism