H1N1 Infection in Pregnancy; A Retrospective Study of Feto-Maternal Outcome and Impact of the Timing of Antiviral Therapy
Naser Al-Husban1, Nathir Obeidat2, Oqba Al-Kuran1, Khaled Al Oweidat2 and Faris Bakri3.
Received: November 11, 2018
Accepted: January 16, 2019
Mediterr J Hematol Infect Dis 2019, 11(1): e2019020 DOI 10.4084/MJHID.2019.020
This is an Open Access article distributed
under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Abstract Background and Objective:
H1N1 infection carries an increased risk in pregnancy. Our aim was to
study the feto-maternal outcome and the effect of early initiation of
therapy. |
Introduction
Data obtained from many countries revealed that old patients seemed to be relatively protected from getting infected. There are, however, certain other vulnerable groups of patients.[2,3,4,5] They are the same groups that are more vulnerable during seasonal influenza—those with underlying heart disease, lung disease, etc. The unexpected, much higher risk group was pregnancy. Pregnant women had a hospitalization and death rate up to 10 times higher compared to other females in the same age group.[3,5,6] These data lend support to the present recommendation to promptly treat pregnant women with H1N1 influenza virus infection with anti-influenza drugs.[5]
Reports from the past pandemics (1918-1919) and 2009 outbreaks showed that pregnant women are at risk of complications from the disease.[7] Pregnancy stage also modified the association between influenza activity and influenza-like illness episodes. Findings estimate that 20-43 pregnant/postpartum women need to be vaccinated with an 80% effective vaccine to prevent one influenza-like illness episode.[7] In addition, pregnant women are prone to complications such as pneumonia and adult respiratory distress syndrome (ARDS) because the maternal immune system is modified to accommodate the developing fetus, the gravid uterus elevates the diaphragm, and they have congestion and local edema.[8]
There was a 4- times higher rate of hospital admissions in pregnant women compared to the general population.[5] Among patients with H1N1 virus infection, pregnant women accounted for 6-9% of the intensive care unit (ICU) admissions and 6-10% of patients who died. The risk of death is particularly increased in infected women during the third trimester.[5,9,10] The excess risk may be limited to women infected in the third trimester and the first four weeks postpartum; however, available data are of low quality.[11]
Our study is a retrospective descriptive case series that evaluates the clinical course, the effects of various maternal characteristics, and the impact of the timing of antiviral therapy on feto-maternal outcome in H1N1 infected pregnant patients.
Materials and Methods
Results
A total of 243 non-pregnant patients and a total of 68 pregnant patients were tested for H1N1 influenza A based on their presenting symptoms. Among the pregnant population, 27 patients (39.70%) were found to be positive for the H1N1.
None of the confirmed cases received the seasonal flu vaccine or specific A/H1N1 2009 influenza vaccine that season (starting September 2017). There were five patients who missed their antenatal care and/or did not deliver at our unit. Every effort was done to obtain further information about their antenatal course, delivery and neonatal outcome, including telephone calls. Besides, there were three patients who, after obtaining the positive result for H1N1 infection in the second trimester, denied and refused admission and treatment. We could not obtain any further data concerning their pregnancy and delivery.
A total of nine of our patients (47.37%) are of age 31 years or older. Only one patient was less than 20 years of age. The vast majority (14 patients, 73.68%) were multiparous patients. There was one case of twin pregnancy. Eleven patients (57.89%) were infected in the third trimester (57.89%), six patients (31.6%) in the second trimester, one patient (5.3%) in the first trimester and one (5.3%) in the postpartum period. (Table 1).
Table 1. Patients’ characteristics, maternal age, parity and gestational age at diagnosis and presentation. |
Most of our patients presented with cough, fever, and chills; 17, 16 and 13 patients, respectively. Other causes of fever were excluded by urinalysis and urine and blood cultures. There were also a variety of symptoms including a runny nose, generalized fatigue, shortness of breath, sore throat, sputum, headache, myalgia, and vomiting. Documented fever at presentation was a prominent sign in our patients (14 patients, 73.68%). There are also other physical signs including tachycardia, pharyngitis, wheezes, hypoxia and decreased air entry. One patient had sinus bradycardia (at a rate of 36-40 beats/minute with normal echocardiogram and thyroid function) which was relieved two days after starting antiviral therapy, and another patient had hemoptysis (Table 2). Chest radiographs were deemed necessary in 3 patients dictated by their clinical situation. The first of them had mild atelectasis, the second had diffuse bilateral ground-glass opacification and pleural effusion, and was admitted to the ICU. She later underwent an urgent cesarean section due to severe respiratory distress and hypoxia. The third patient had severe infiltration and opacification, and she passed away in the ICU.
Table 2. Presenting symptoms and signs. |
Eight patients (42.10%) were started on Oseltamivir therapy, 75 mg twice daily, only one day after the clinical onset of symptoms and they were the patients with no feto-maternal complications. Two patients started antiviral therapy five days after the onset of symptoms (Table 3). Both were admitted to the ICU, and one of them passed away. The deceased patient was on Zanamivir inhalation instead of Oseltamivir because she was ventilated.
Table 3. Time between onset of symptom and starting therapy. |
Fifteen patients (78.95%) completed a 5-day course of Oseltamivir. Two patients received six days of therapy. Another two patients received seven days of Oseltamivir. At the discretion of the respiratory and infectious consultants, one of them received the last two days as an outpatient at home.
Six patients (31.58%) needed oxygen therapy, and 2 (10.53%) were admitted to the intensive care unit (ICU).
Except the two patients who were admitted to the ICU, the earliest delivery was two weeks after the confirmed H1N1 infection.
The first ICU admission was the case of a 41-year-old lady who had essential hypertension, and a history of ICU admission due to a penicillin allergy. She had three children and one miscarriage, P3+1(previous three caesareans). She presented at 38+1 weeks for urgent cesarean section due to a non-reassuring CTG. The cesarean section went uneventfully with the delivery of a healthy male fetus weighing 3.7 kg with 1-minute APGAR score of 8/9. On the first postoperative day, she started to complain of SOB, cough, and a fever. She was started on antibiotics and went home on the second postoperative day. She presented on the 3rd postoperative day with severe respiratory distress and hypoxia. Her chest radiograph showed severe infiltration and opacification (chest radiographs 1-4, shown). She was admitted to the ICU and intubated. H1N1 influenza infection was suspected, so a tracheal aspirate was taken and was positive for H1N1 (she was the first case in the hospital to be diagnosed with H1N1 infection). A total of 6 days were between the initial presentation and the initiation of therapy. She was then intubated, and over a deteriorating course of 15 days with multi-organ failure, she passed away.
Chest radiograph 1 of the deceased patient. |
Chest radiograph 2 of the deceased patient. |
Chest radiograph 3 of the deceased patient |
Chest radiograph 4 of the deceased patient. |
The second patient admitted to the ICU was a 32-year-old lady, P3 (all were NVD). She has a history of seasonal allergy and angioedema. She was also admitted to the ICU and intubated ten months before her current pregnancy due to pulmonary hemorrhage, implying a probable residual lung disease or damage. She was confirmed to have H1N1 infection at 30 weeks +3 days gestation. She presented with a dry cough, shortness of breath, palpitations, headache, chills, generalized fatigue, myalgia, and hemoptysis. Her physical examination revealed tachycardia (130 beats/minute), wheezes and hypoxia. She was diagnosed to have H1N1 infection with a secondary bacterial infection and started on Oseltamivir, nebulizers, and antibiotics three days after her onset of symptoms. Her CXR showed diffuse bilateral ground-glass opacification and pleural effusion. In the ICU she developed anemia and was given a blood transfusion. She developed severe respiratory distress with hypoxia at 33 weeks and underwent urgent cesarean section under epidural anesthetic with an outcome of an alive baby weighing 2 kilograms (Kg) and an APGAR score of 8/9. The baby was admitted to the NICU due to prematurity. She was kept in the ICU. Her respiratory condition started to improve and continued improving over the postoperative course. She recovered well and was discharged with her baby in good condition.
Except these two patients, all other patients delivered 2 or more weeks after their infection; babies were not separated from them and they were encouraged to breastfeed. A total of 5 patients (26.31%) delivered before the 37 weeks were completed. Most of our patients (73.68%) delivered beyond term. 36.84% of our patients delivered vaginally while 12 patients (63.16%) were delivered by cesarean section, most of them were elective caesareans (Table 4).
Table 4. Gestational age at delivery and mode of delivery. |
Nine babies out of 20, (45%) weighed more than 3 kg. Four babies (20%), 2 of which were twins, weighed less than 2 kg. 18 babies (90%) had APGAR scores more than 8 at 1 and 5 minutes after delivery. Five babies (25%) were admitted to the NICU (Table 5).
Table 5. Birth weight, APGAR score, preterm delivery and NICU admission. |
One patient was pregnant with twins and delivered three weeks after H1N1 admission (admitted at 28+6 weeks, delivered at 35+4 weeks) by cesarean section due to intra-uterine growth restriction (IUGR), decreased liquor and decreased fetal movement and spontaneous decelerations on CTG. She started therapy three days after the onset of her symptoms. The babies weighed 1.5, and 1.51 kg and both were admitted to the NICU. The 4th baby who was admitted to the NICU was delivered at 34 weeks due to fetal distress during induction of labor because of oligohydramnios. The mother was H1N1 infected at 28+3 weeks, with 2 days between onset and therapy. The baby weighed 1.7 kg and was admitted for one week. The same baby was admitted again 2 weeks after discharge due to a chest infection. One term baby, who was delivered at 38 weeks, vaginally, in a private hospital, weighing 2.6 kg with an APGAR score of 5, was admitted to the NICU for 5 days due to hypoxia and wheezes. The detailed diagnostic workup is not available. The baby was discharged and now is doing very well. The mother was infected at 19 +2 weeks, with 3 days between onset and therapy.
Discussion
The three most common clinical symptoms in our patients were cough, fever, and chills. These were moderate symptoms. Jamieson DJ et al.,[5] Louie JK, et al.[10] and Hewagama S et al.[16] reported similar results.
Shortness of breath, hemoptysis, hypoxia, wheezes, tachypnea, and decreased air entry were found in patients with severe symptoms who required chest radiographs with positive findings, oxygen therapy and intubation with intensive management. Liu L et al.,[17] reported that in a general population, critical cases were associated with severe hypoxemia, multisystem organ failure, and a requirement for mechanical ventilation.
94.73% of our patients were hospitalized to complete their minimum of a 5-day course, and two patients (10.53%) were admitted to the ICU. One patient with mild symptoms declined hospitalization and completed her therapy at home with no complications. There was only one maternal death (5.26%). She deteriorated very quickly and, because of the low index of suspicion of the H1N1 infection, 6 days passed before confirming a diagnosis and starting therapy. The delay in initiating therapy, the urgent cesarean delivery due to fetal distress, and the postpartum status were the most probable contributing factors to her death, as she had only a history of essential hypertension and penicillin allergy as co-existing clinical conditions. After that case, and because of public and medical staff fear and awareness, particularly in pregnant women, the threshold to test patients for the H1N1 was lowered, and therefore most our patients (42.10%) were diagnosed and started on therapy within one day of their disease onset. The rest of our patients started therapy within 5 days of onset of symptoms, except the maternal mortality case and the other patient who was admitted to the ICU (more than 5 days). Meijer WJ et al.[18] reviewed and judged 294 reports according to the STROBE guidelines or CONSORT statement. In all, 100 studies, published between 1961 and 2015, were included and reported that, compared to the general population, pregnant women are more often hospitalized and admitted to an intensive care unit due to influenza virus infection. Our approach of early testing and initiation of therapy in confirmed cases contributed significantly to the good outcome, a lower rate of ICU admissions, less need for oxygen (only 4 excluding the ICU patients) and low complications in our series. Early treatment with Oseltamivir is associated with a reduced risk of severe disease.[18] Heba V et al.[19] found that initiation of oseltamivir within 48 hours of symptom onset was associated with fewer complications in patients hospitalized with 2009 influenza A (H1N1). Viasus D et al.[20] reported that timely oseltamivir administration has a beneficial effect on outcomes in hospitalized adults with A (H1N1), even in those who are admitted beyond 48 h after onset of symptoms. Higuera Iglesias AL et al.[21] found that earlier initiation of Oseltamivir therapy, even when initiated more than 48 hours after the onset of symptoms, significantly reduced occurrence and severity of pneumonia and shortened hospitalization in pandemic H1N1 2009. Based on these results, patients affected by future influenza pandemics would benefit from early therapy.
In a systematic review and meta-analysis of observational studies, Dominik Mertz et al.,[22] found that in influenza infection, pregnancy is associated with a higher risk of hospital admission than non-pregnant individuals with similar risk of mortality. This increased susceptibility was described for various pathogens including H1N1 influenza virus.[5] Changes in the immune, cardiac and respiratory systems are the likely reasons that pregnant women are at increased risk for severe illness with influenza.[14,15] These facts were taken into account during the management approach of our patients.
The only patient with significant co-existing medical diseases was the previously mentioned 2nd ICU patient. No other cases had significant medical problems. This fact could have contributed to the good outcome. Jamieson DJ et al.[5] mentioned the reporting of six deaths in pregnant women to the CDC. All were in women who had developed pneumonia and subsequent acute respiratory distress syndrome requiring mechanical ventilation.[5] Among the 788 pregnant patients in the USA with 2009 Influenza A (H1N1) infection, 30 died (3.8%). Patients who started their therapy more than 4 days after disease onset were more likely to be admitted to an ICU. Authors concluded that early treatment was associated with fewer ICU admissions and fewer deaths.[23] Fatima S Dawood et al.[24] found that the estimate of respiratory and cardiovascular mortality associated with the 2009 pandemic was 15 times higher than the reported laboratory-confirmed deaths. There are several risk factors and medical conditions that increase the severity, complications, admission to the ICU and death among H1N1 infection.[10,25,26,27]
Although 31.58% of our patients were infected in the second trimester and 5.26% in the first trimester, only 5.26% delivered before 34 weeks. Only 21.05% delivered between 34 and 37 weeks and most patients (73.68%) delivered after 37 weeks. The increased overall prematurity rate of 26.31% could be caused by H1N1 infection. Two patients who were infected around 28 weeks (one at 28 weeks plus 3 days and the other at 28 weeks plus 6 days) developed decreased liquor and IUGR and underwent cesarean section due to fetal distress at 34 weeks and 35 weeks plus 4 days. This rate is much higher than reported in the general population.[28] There were no cases of intra-uterine fetal death (IUFD) or stillbirths in our cases. NICU admission in our series was 25%. Pierce M et al.,[29] found that perinatal mortality is increased due to an increased rate of stillbirth, increased prematurity, increased rate of NICU admission due to secondary pneumonia. Overall around two-thirds of our patients were delivered by cesarean section mostly elective obstetric indications. The mode of delivery was dictated by obstetric reasons except one patient who underwent a caesarean section because of severe respiratory compromise.
Forty-five percent of babies weighed more than 3 kg. Four babies (20%), 2 of them were twins, weighed less than 2 kg. The newborn babies were well off as indicated by an APGAR score of more than 8 at 1 and 5 minutes after delivery in 90% of babies. Fell DB et al.[30] in a systematic meta-analysis of comparative studies found that in the subgroup of the highest-quality studies two reported significantly increased preterm birth following severe 2009 pandemic H1N1 (pH1N1) influenza illness, whereas those assessing mild-to-moderate pH1N1 or seasonal influenza found no association. They found no association with small for gestational age (SGA). They concluded that comparative studies of preterm birth, SGA birth and fetal death following maternal influenza disease are limited in number and quality. An association between severe pH1N1 disease and preterm birth and fetal death was reported by several studies; however, these limited data do not permit firm conclusions on the magnitude of any association.[30] There was one case of mortality in our report. William L Callaghan et al.,[31] found that 12 pregnancy-related deaths could be due to possible or confirmed H1N1 infection in the 2009-2010 pandemic. A CDC study of 347 pregnant women found that prompt use of antiviral drugs during the 2009 H1N1 influenza pandemic improved survival among severely ill pregnant women.[32] Neuraminidase inhibitors (NI) are likely to reduce mortality in hospitalized patients and are effective at reducing secondary symptomatic influenza transmission.[33] Because pregnancy is a high rather risk situation, all our patients were given NI, even with the potential significant side effects. The US Centres for Disease Control and Prevention recommend chemoprophylaxis with either Oseltamivir or Zanamivir against H1N1 influenza
For people at risk of complications, including pregnant women.[34] The use of NIs is reassuring to pregnant and lactating women as they aren’t associated with adverse outcomes or congenital malformations even with early pregnancy exposures.[35,36] Although cardiac side effects (1.8%) and transient neonatal hypoglycemia in the newborns were reported,[37,38] we did not encounter such side effects in our newborns.
None of our patients had received influenza vaccination prior to or during the current pregnancy. Antenatal influenza vaccination can enhance fetal growth and can reduce preterm birthrate.[39,40] Maternal influenza immunization is a strategy with substantial benefits for both mothers and infants.[41] Mark G. Thompson et al.,[42] found that pregnant women vaccinated against flu had a 40% lower risk for hospitalization if they became ill with the infection compared with unvaccinated pregnant women. We, therefore, would expect a reduction in the preterm birth rate, IUGR and NICU admissions should our patients be vaccinated. This is particularly important in our series since we had a very low threshold for testing suspected cases and early initiation of antiviral therapy.
Our one case of twin pregnancy was complicated by oligohydramnios, IUGR and urgent cesarean section due to fetal distress. Soydinc et al.,[43] reported that H1N1 influenza infection caused significant fetal and maternal complications and they had a maternal death of a twin pregnancy infected at 32 weeks gestation. Hein Bogers et al.,[44] reported 2 cases with severe perinatal complications, one with fetal demise at 24 weeks gestation.
Our case series are limited in number. We recommend studying all cases of H1N1 infection at a national level to reach more solid conclusions.
Conclusions
References
- Centers for Disease Control and Prevention (CDC)
Hospitalized patients with novel influenza A (H1N1) virus
infection-California, April-May, 2009; MMWR Morb Mortal Wkly Rep; 2009.
pp. 536-41. PMid:19478723
- Collignon P. Swine flu-lessons learnt in Australia; Med J Aust; 2010. pp. 364–5. PMid:20367578
- Kelly HA. A pandemic response to a disease of predominantly seasonal intensity; Med J Aust; 2010. pp. 81–3 PMid:20078407
- Australian influenza surveillance summary report no. 26, 2009, reporting period: 31 October 2009–6 November 2009
- Jamieson
DJ, Honein MA, Rasmussen SA, Williams JL, Swerdlow DL, Biggerstaff MS,
Lindstrom S, Louie JK, Christ CM, Bohm SR, Fonseca VP, Ritger KA,
Kuhles DJ, Eggers P, Bruce H, Davidson HA, Lutterloh E, Harris ML,
Burke C, Cocoros N, Finelli L, MacFarlane KF, Shu B, Olsen SJ. Novel
Influenza A (H1N1) Pregnancy Working Group. H1N1 2009 influenza virus
infection during pregnancy in the USA. Lancet. 2009 Aug 8;
374(9688):451–8. https://doi.org/10.1016/S0140-6736(09)61304-0
- New
South Wales public health network Progression and impact of the first
winter wave of the 2009 pandemic H1N1 influenza in New South Wales,
Australia. Euro Surveill. 2009; 14(42):pii = 19365
- Lindsay
L, Jackson LA, Savitz DA. Community influenza activity and risk of
acute influenza like illness episode among healthy unvaccinated
pregnant and postpartum women. A J Epidemiol 2006;163:838-848 https://doi.org/10.1093/aje/kwj095 PMid:16554352
- Lim
Boon H, Mahmood Tahir AJ. Influenza A H1N1 2009 (swine flu) and
pregnancy. Obstet Gynecol India 2011; 61(4):386-393.
https://doi.org/10.1007/s13224-011-0055-2 PMid:22851818 PMCid:PMC3295877
- Kumar
A, Zarychanski R, Pinto R, Cook DJ, Marshall J, Lacroix J, et al.
Critically ill patients with 2009 influenza A (H1N1) infection in
Canada. JAMA 2009;302:1872-1879. https://doi.org/10.1001/jama.2009.1496 PMid:19822627
- Louie
JK, Acosta M, Jamieson DJ, Honein MA. Severe 2009 H1N1 influenza in
pregnant and postpartum women in California . N Engl J Med 2010;
262:27-35. https://doi.org/10.1056/NEJMoa0910444 PMid:20032319
- Mertz,
D., Kim, T. H., Johnstone, J., Lam, P. P., Science, M., Kuster, S. P.,
Fadel, S. A., Tran, D., Fernandez, E., Bhatnagar, N., Loeb, M. (2014).
Populations at risk for severe or complicated Avian Influenza H5N1: a
systematic review and meta-analysis. PloS one, 9(3), e89697. https://doi.org/10.1371/journal.pone.0089697
- Prabhu T.R. H1N1 influenza virus infection in pregnancy: A study of 32 cases. Journal of SAFOG 2014;6(2):93-97. https://doi.org/10.5005/jp-journals-10006-1279
- Brabin B.J. Epidemiology of infection in pregnancy. Rev. Infect. Dis.1985;7:579-603 https://doi.org/10.1093/clinids/7.5.579 PMid:3903938
- Goodnight WH, Soper DE. Pneumonia in pregnancy. Crit Care Med. 2005; 33(10 Suppl):S390-7. https://doi.org/10.1097/01.CCM.0000182483.24836.66 PMid:16215363
- Jamieson DJ, Theiler RN, Rasmussen SA. Emerging infections and pregnancy. Infect Dis. 2006 Nov; 12(11):1638-43. https://doi.org/10.3201/eid1211.060152 PMid:17283611 PMCid:PMC3372330
- Hewagama
S, Walker SP, Stuart RL, Gordon C, Johnson PDR, Friedman ND, O' Reilly
M, Cheng AC, Giles ML. 2009 H1N1 influenza A and pregnancy outcome in
Victoria, Australia. Clin Infect. Diseases 2010; 50:686-690. https://doi.org/10.1086/650460 PMid:20100064
- Liu
L, Zhang RF, Lu HZ, Lu SH, Huang Q, Xiong YY, Xi XH, Zhang ZY.
Sixty-two severe and critical patients with 2009 influenza A (H1N1) in
Shanghai, China. Chin Med J (Engl) 2011; 124(11):1662-1666
- Meijer
WJ, van Noortwijk AG, Bruinse HW, Wensing AM. Influenza virus infection
in pregnancy: a review. Acta Obstet Gynecol Scand 2015; 94(8):797-819. https://doi.org/10.1111/aogs.12680 PMid:26012384
- Hiba
V, Chowers M, Levi-Vinograd I, Rubinovitch B, Leibovici L, Paul M.
Benefit of early treatment with Oseltamivir in hospitalized patients
with documented 2009 influenza A (H1N1): a retrospective cohort study.
J Antimicrob Chemother 2011; 66(5):1150-1155 https://doi.org/10.1093/jac/dkr089 PMid:21393197
- Viasus
D, Pano-Pardo JR, Pachon J, Riera M, Lopez-Medrano F, Paveras A, et al.
Timing of Osetlamivir administration and outcomes in hospitalized adult
patients with pandemic 2009 influenza A (H1N1) virus infection. Chest
2011; 140(4):1025-1032. https://doi.org/10.1378/chest.10-2792 PMid:21415133
- Higuera
Iglesias AL, Kudo K, Manabe T, Corcho Berdugo AE, Corrales Baeza A,
Alfaro Ramos L, et al. Reducing recurrence and severity of pneumonia
due to pandemic H1N1 2009 by early oseltamivir administration: a
retrospective study in Mexico. PLoS One. 2011; 6(7):e21838. doi:
10.1371/journal.pone.0021838. Epub 2011 Jul 8. https://doi.org/10.1371/journal.pone.0021838
- Mertz
D, Geraci J, Winkup J, Gessner B D, Ortiz J R, Loeb M. Pregnancy as a
risk factor for severe outcomes from influenza virus infection: A
systematic review and meta-analysis of observational studies. Vaccine
2017; 35(4):421-428. https://doi.org/10.1016/j.vaccine.2016.12.012 PMid:28024955 PMCid:PMC5359513
- Siston
AM, Rasmussen SA, Honein MA, Fry AM, Seib K, Callaghan WM, et al.
Pandemic 2009 influenza A (H1N1) virus illness among pregnant women in
the United States. JAMA 2010; 303(15):1517-1527. https://doi.org/10.1001/jama.2010.479 PMid:20407061 PMCid:PMC5823273
- Dawood
FS, Luliano AD, Reed C, Meltzer MI, Shay DK, Cheng PY, et al. Estimated
global mortality associated with the first 12 months of 2009 pandemic
influenza A H1N1 virus circulation: a modelling study. Lancet Infect
Dis.2012; 12(9):687-695 https://doi.org/10.1016/S1473-3099(12)70121-4
- ANZIC
influenza Investigators., Webb SA, Pettila V, Seppelt I, Bellomo R,
Bailey M, Cooper DJ, et al. Critical care services and 2009 H1N1
influenza in Australia and New Zealand Engl J Med. 2009;
361(20):1925-34.
- The ANZIC Influenza
Investigators. Critical care services and the H1N1 (2009) influenza
epidemic in Australia and New Zealand in 2010: the impact of the second
winter epidemic. Crit care 2011; 15(3):R143. https://doi.org/10.1186/cc10266 PMid:21658233 PMCid:PMC3219015
- Viasus
D, Pa-o-Pardo JR, Pachón J, Campins A, López-Medrano F, Villoslada A,
Fari-as MC, Moreno A, Rodríguez-Ba-o J, Oteo JA, Martínez-Montauti J,
Torre-Cisneros J, Segura F, Gudiol F, Carratalà J. Factors associated
with severe disease in hospitalized adults with pandemic (H1N1) 2009 in
Spain. Clin Microbiol Infect 2011; 17(5):738-746. https://doi.org/10.1111/j.1469-0691.2010.03362.x PMid:20825436
- Changchang
Li Zhijiang Liang, Michael S Bloom, Qiong Wang, Xiaoting Shen, Huanhuan
Zhang, Suhan Wang, Weigin Chen, Yan Lin, Qingguo Zhao, Cunrui Huang.
Temporal trends of preterm birth in Shenzhen, China: a retrospective
study. Reprod Health 2018; 15:47 https://doi.org/10.1186/s12978-018-0477-8 PMid:29534760 PMCid:PMC5851155
- Pierce
M, Kurinczuk JJ, Spark P, Brocklehurst P, Knight M; UKOSS. Perinatal
outcomes after maternal 2009/H1N1 infection: national cohort study. BMJ
2011; 14:342:d3214. https://doi.org/10.1136/bmj.d3214
- Fell
DB, Savitz DA, Kramer MS, Gessner BD, Katz MA, Knight M, Luteijn JM,
Marshall H, Bhat N, Gravett MG, Skidmore B, Ortiz JR. maternal
influenza and birth outcomes: systematic review of comparative studies.
BJOG 2017; 124(1):48-59 https://doi.org/10.1111/1471-0528.14143 PMid:27264387 PMCid:PMC5216449
- William
L Callaghan, Andreea A Creanga, Denise Jamieson. Pregnancy-related
mortality resulting from influenza in the United States during the
2009-2010 Pandemic. Obstet Gynecol 2015; 126(3):486-490. https://doi.org/10.1097/AOG.0000000000000996 PMid:26244541 PMCid:PMC4557717
- Maternal
and infant outcomes among severely ill pregnant and postpartum women
with 2009 pandemic influenza A (H1N1)--United States, April 2009-August
2010. MMWR Morb Mortal Wkly Rep. 2011; 60(35):1193-6(ISSN:
1545-861X)
- Doll Mk,
Winters N, Boikos C, Kraicer-Melamed H, Gore G, Quach C. Safety and
effectiveness of neuraminidase inhibitors for influenza treatment,
prophylaxis, and outlook control: a systematic review of systematic
reviews and/or meta-analysis. J Antimicrob Chemother 2017;
72(11):2990-3007 https://doi.org/10.1093/jac/dkx271 PMid:28961794
- Centres for Disease Control and Prevention. What pregnant women should know aboutH1N1 (formerly called swine flu) virus. http://www.cdc.gov/h1n1flu/guidance/pregnant.htm (accessed May 27, 2009).
- Graner
S et al. Neuraminidase inhibitors during pregnancy and risk of adverse
neonatal outcomes and congenital malformations: Population based
European register study. BMJ 2017 Feb 28; 356:j629. https://doi.org/10.1136/bmj.j629 PMid:28246106 PMCid:PMC5421412
- Tanaka
T, Nakajima K, Murashima A, Garcia-Bournissen F, Koren G, Ito S. Safety
of neuraminidase inhibitors against novel influenza A (H1N1) in
pregnant and breastfeeding women. CMAJ : Canadian Medical Association
Journal. 2009; 181(1-2):55-58. https://doi.org/10.1503/cmaj.090866
- Ehrenstein
V, Kristensen NR, Monz BU, Clinch B, Kenwright A, Sorensen HT.
Oseltamivir in pregnancy and birth outcomes. BMC Infect Dis. 2018;
18(1):519 https://doi.org/10.1186/s12879-018-3423-z PMid:30326840 PMCid:PMC6192366
- Svensson
T, Granath F, Stephansson O, Kieler H. Birth outcomes among women
exposed to neuraminidase inhibitors during pregnancy. Pharmacoepidemiol
Drug Saf. 2011; 20(10):1030-4. https://doi.org/10.1002/pds.2194 PMid:21774030
- Steinhoff
M. C., Omer S. B. A review of fetal and infant protection associated
with antenatal influenza immunization. AJOG 2012; S21-S27 https://doi.org/10.1016/j.ajog.2012.06.071 PMid:22920054
- Steinhoff
MC, Omer SB, Roy E, Arifeen SE, Raqib R, Dodd C, Breiman RF, Zaman K.
"Neonatal outcomes after influenza immunization during pregnancy: a
randomized controlled trial," Canadian Medical Association Journal,
vol. 184, no. 6, pp. 645–653, 2012. https://doi.org/10.1503/cmaj.110754 PMid:22353593 PMCid:PMC3314035
- Zaman
K, Roy E, Arifeen S. E, Rahman M, Raqib R, Wilson E, Omer SB, Shahid
NS, Breiman RF, Steinhoff MC. Effectiveness of maternal influenza
immunization in mothers and infants. N Engl J Med 2008;
359(15):1555-1564. https://doi.org/10.1056/NEJMoa0708630 PMid:18799552
- Thompson
MG, Kwong JC, Regan AK, Katz MA, Drews SJ, Azziz-Baumgartner E, et al.
Influenza Vaccine Effectiveness in Preventing Influenza-associated
Hospitalizations During Pregnancy: A Multi-country Retrospective Test
Negative Design Study, 2010-2016.Clin Infect Dis. 2018 Oct 11. https://doi.org/10.1093/cid/ciy737.42
- Soydinc
HE, Celen MK, Yildiz B, Sak ME, Evsen MS, Gul T. Pregnancy and H1N1
infection in Southeast Turkey. J Infect Dev Ctries 2012; 6(8):644-649 https://doi.org/10.3855/jidc.1956 PMid:22910572
- Bogers
H, Bos D, Schoenmakers S, Duvekot JJ. Postpandemic Influenza
A/H1N1pdm09 is still Causing Severe Perinatal Complications. Mediterr J
Hematol Infect Dis. 2015;7(1):e2015007. https://doi.org/10.4084/mjhid.2015.007 PMid:25574366 PMCid:PMC4283922
[TOP]