Kambhampati L*, More V**.
(* Third Year Resident, ** Assistant Professor, Department of Obstetrics and Gynecology, Seth G.S. Medical College and K.E.M. Hospital, Mumbai, India.)
H1N1 infection is a subtype of Influenza A which is a RNA virus primarily causing acute respiratory illness. It has emerged as a pandemic in 2009 affecting all populations. The normal physiological changes that occur in pregnancy causing altered immune status lead to higher rate of serious complications due to H1N1 infection in pregnancy. Herewith, presenting a case of twin pregnancy with eclampsia complicated by H1N1 infection managed successfully with focus on clinical manifestations, complications and management.
H1N1 infection, also called as swine flu is a subtype of Influenza A which causes flu like symptoms such as fever, sore throat, rhinorrhea and sometimes diarrhea. In pregnancy and other immune-compromised conditions there are 4 to 5 times increased risk of serious illness leading to severe pneumonia causing hospitalization and intensive care unit admissions. Most swine flu infections in pregnancy occur in second or third trimester. Although initial presentation is with mild to moderate symptoms, rapid clinical deterioration is seen in most patients especially if treatment is started after more than 48 hours.
A 27-year-old patient G3 P0 A2 with dichorionic diamniotic twin gestation was referred to us from a peripheral hospital in view of twin gestation with threatened preterm labor. On examination patient’s general condition was fair. She was afebrile, pulse 90/ min, blood pressure 120/ 80 mm Hg. Per abdominal examination showed over-distended uterus with multiple fetal parts, fetal heart sounds of both twins was around 140 bpm with minimal uterine activity, per vaginal examination showed cervical os one finger loose and poorly effaced with vertex presentation, station -3 and intact membranes. She was given two doses of injection betamethasone 12 mg, 24 hours apart and capsule nifedipine 20 mg followed by 10 mg 6 hourly for 2 days.
On 4th day of admission patient had sudden onset of breathlessness NYHA Class II/ III with tachycardia and tachypnea and fever with chills. In view of this, physician was consulted. Arterial blood gas was done which showed decreased oxygen saturation, chest x ray showed mid and lower lung opacities. Throat swab for H1N1 infection was sent. Patient was started on nasal oxygen, antibiotics, tab oseltamavir 75 mg 12 hourly and shifted to ICU. In view of breathlessness with tachypnea, cardiology reference was taken and 2 D echo was done which was normal. D dimer assay was done and it was normal, lower limb Doppler was done and deep vein thrombosis was ruled out. Patient was suspected to have acute respiratory distress syndrome secondary to H1N1 infection. Throat swab was positive for H1N1 infection. Patient was started on non invasive ventilation with positive pressure ventilation. Patient then had premature rupture of membranes after which she spontaneously progressed and delivered uneventfully by normal vaginal delivery at 33 weeks gestation, both twins delivered by vertex presentation. Both babies needed neonatal intensive care in view of prematurity. Patient then improved post-partum, and was weaned off from respiratory support in two days.
During intrapartum period, patient developed hypertension for which blood pressure monitoring was done. On day 3 post-delivery she had one episode of general tonic clonic convulsion. Injection magnesium sulphate loading dose was given according to Pritchard regimen but was discontinued due to rising creatinine levels. She was then switched to loading dose of 1g followed by maintenance dose of 500 mg of injection leveteracetam, followed by oral doses. She had uncontrolled hypertension for which she was started on nifedipine which was increased till 30 mg 6 hourly, telmisartan 40 mg once a day, clonidine 0.1 mg twice a day, prazocin 1 mg 6 hourly. BP monitoring was done and anti hypertensives were tapered gradually, till she was normotensive. In view of convulsion, MRI was done and it was suggestive of posterior reversible encephalopathy syndrome. Patient gradually improved and was discharged along with both babies on day 20 postpartum.
Influenza is an enveloped RNA virus belonging to orthomyxidae family of viruses. It causes acute respiratory illness ranging from mild flu like illness to severe pneumonia which can be fatal. Influenza virus can be divided into 3 types A, B and C. Influenza A can be further divided into multiple subtypes based on the two viral antigen H (hemagglutinin) and N (neuraminidase). Hemagglutinin helps in viral attachment by binding to the sialic acid receptors on cell surface and neuraminidase helps in viral release by degrading the receptor in infected cells after cell replication is done. The newest antiviral drugs manufactured specifically for H1N1 infection have neuroaminidase receptors as target. Influenza infection is a seasonal infection. According to a study conducted in Chennai, highest level of influenza infection is found in the month of June.
In the most recent pandemic, the first case of H1N1 infection was detected in April 2009 in Mexico, it shortly spread to over 74 countries infecting over 30,000 people by June 2009. The first case of H1N1 infection was reported from Hyderabad on May 16, 2009. By 2015 around 31000 people were infected with H1N1, of which 1800 deaths were recorded.
Pregnancy does not lead to an increased risk of acquiring H1N1 infection but due to the physiological changes which occur in pregnancy it becomes a high risk for developing complications, leading to increased maternal morbidity and mortality especially in women with co- morbidities. Pregnancy also leads to decreased tolerance to hypoxemia thereby increasing maternal and perinatal morbidity. Apart from the changes in immune system, decrease in oncotic pressure especially in third trimester causes hemodynamic changes which affect lung function and can lead to development of pneumonia and acute pulmonary edema.
H1N1 is routinely diagnosed by rapid antigen tests using rRT – PCR, from specimens collected from throat or nasal swabs. As H1N1 has more predilection to lower respiratory tract, specimens can also be collected by broncho- alveolar lavage and endotracheal secretions.
The most common presentation of H1N1 infection is with mild flu like illness having cough, rhinorrhea and fever with chills, general malaise and body aches. Occasionally gastrointestinal symptoms like vomiting and diarrhea can be seen. Symptoms are commonly seen within a week of acquiring infection and patients are contagious till 7 days after acquiring the infection. Rapid progression to severe pneumonia, acute respiratory distress syndrome can be seen with pregnant women especially with co morbidities like bronchial asthma, tuberculosis, pre -eclampsia and eclampsia.
According to previous studies pregnant women are most commonly affected in second or third trimester. H1N1 infection,when it occurs in first trimester can lead to higher incidence of neural tube defects most likely due to hyperthermia. During labor, hypothermia due to H1N1 infection can cause neonatal seizures, encephalopathy, cerebral palsy and even death. Studies have showed that presence of co morbidities like pre- eclampsia, eclampsia, tuberculosis, bronchial asthma increases the risk of complications by more than 50%.
Treatment of H1N1 is by newer neuroaminidase inhibitors like oseltamivir and zanamivir which focus on the early phase of infection. Hence delay in initiation of treatment by more than 48 hours leads to increased complications. CDC guidelines emphasize the importance of starting antiviral medication even on just clinical suspicion of H1N1 infection.
Several studies conducted have proven that these antiviral drugs are safe in pregnancy and lactation. The concentration of the drug in breast milk is found to be lesser than the pediatric dosage of the drug. Oseltamivir is administered orally and zanamivir by inhalational route. Oseltamivir is preferable in pregnant patient especially in patients with respiratory illnesses due to better tolerability. The therapeutic dosage of oselatamivir is 75 mg twice daily for 5 days and for zanamivir is 10 mg twice daily for 5 days by inhalational route. For chemoprophylaxis the same dosage is given for 10 days once daily.
Immunization with inactivated trivalent vaccine has been recommended in pregnancy as live vaccine is contraindicated in this pregnancy. The inactivated vaccine currently available protects against two subtypes of Influenza A virus namely H1N1 and H1N3 and Influenza B virus and it is administered subcutaneously. As opposed to live vaccine, antivirals can be given simultaneously with inactivated vaccine.
Posterior reversible encephalopathy syndrome is a rare clinico-radiological syndrome most often associated with severe pre -eclampsia or eclampsia as seen in our patient. It can present clinically with headache, seizures, altered sensorium or even visual abnormalities like cortical blindness. Most accepted cause for this syndrome is vasogenic edema in the brain. Mostly with the control of hypertension the clinical symptoms also subside. Hence early initiation of treatment is essential to prevent any long lasting sequelae.
Pregnant women in second and third trimesters and with associated co morbidities are at especially high risk for severe manifestations of H1N1 infection. High clinical suspicion and early initiation of treatment within 48 hours of onset of symptoms can prevent morbidity and mortality in these women.
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Kambhampati L, More V. Successful Management Of H1N1 Infection Complicating A Case Of Twin Pregnancy With Eclampsia. JPGO 2017. Volume 4 No.10. Available from: http://www.jpgo.org/2017/10/successful-management-of-h1n1-infection.html