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2009 A/H1N1 influenza vaccination in pregnancy: uptake and pregnancy outcomes – a historical cohort study
European Journal of Obstetrics & Gynecology and Reproductive Biology 178 (2014) 163–168
To describe the uptake of 2009 A/H1N1 influenza vaccination among pregnant women and determine if vaccination was associated with adverse pregnancy outcomes.
A historical cohort study was performed using booking, delivery suite and neonatal unit discharge records from the Coombe Women and Infants University Hospital, Dublin, Ireland. Singleton deliveries to women pregnant before (December 2008–September 2009) and during the pandemic (December 2009–September 2010) were included.
Information on vaccination status and type of vaccine was collected on admission to the delivery suite. Logistic regression analyses were used to determine maternal characteristics associated with vaccination. Pregnancy outcomes were compared for vaccinated and unvaccinated women, with adjustment for differing maternal characteristics. Outcomes included vaccination status, preterm birth, size for gestational age, neonatal intensive care admission, congenital anomalies and perinatal death.
Of 6894 women pregnant during the pandemic, 2996 [43.5%] reported vaccination at delivery. In the early weeks of the vaccination programme rates of over 70% were achieved. Of those vaccinated, 246 [8.2%], 1709 [57.0%] and 1034 [34.5%] were vaccinated in the first, second and third trimesters respectively. Vaccination was less likely in younger age groups, those who were not in the professional/manager/employer socioeconomic group, women from Eastern Europe, Africa and Asia/Middle East, those who reported an unplanned pregnancy, women who booked late for antenatal care and recipients of publicly-funded obstetric care. Irish nationality was associated with reporting vaccination. There was no association between vaccination during pregnancy and adverse pregnancy outcomes. Women who were vaccinated were less likely to have a preterm delivery than unvaccinated women.
2009 A/H1N1 influenza vaccination uptake was influenced by maternal sociodemographic factors. High vaccination uptake can be achieved in a pandemic situation. Future public health campaigns should provide clear information on vaccination safety in pregnancy, ensure consistent vaccination recommendations from healthcare professionals and provide easy access to vaccination in order to optimise uptake rates in subgroups of the population who less likely to be vaccinated. There was no association between vaccination and adverse pregnancy outcomes.
Keywords: 2009 A/H1N1 influenza, Vaccine, Pregnancy, Uptake, Congenital anomaly, Perinatal death.
Pandemic 2009 A/H1N1 influenza infection appeared to increase the risk of severe maternal morbidity and mortality and was associated with adverse pregnancy outcomes , , , and , including perinatal death  . Previous pandemics also demonstrated the risk of serious adverse maternal and fetal outcomes  . In order to reduce the risk of such adverse outcomes vaccinations against pandemic 2009 A/H1N1 influenza were licensed and recommended for use during pregnancy  . In Ireland two vaccines were commercially available and recommended for use in the national immunisation campaign: Pandemrix®, an egg-derived vaccine containing thiomersal and the AS03 adjuvant (dl-α-tocopherol, squalene and polysorbate); and Celvapan®, a cell-line-derived, thiomersal free, non-adjuvanted alternative.
Seasonal influenza vaccines have been administered to pregnant women since the late 1950s  , and the US Advisory Committee on Immunization Practices (ACIP) has, since 2004, encouraged pregnant women to be vaccinated against seasonal influenza regardless of gestation  . Uptake rates of 2009 A/H1N1 influenza vaccine varied internationally during the pandemic with studies reporting rates in pregnant women from as low as 4.7% to as high as 85% , , and . Variations in international recommendations relating to the optimal timing of vaccination in pregnancy, the selection of non-adjuvanted vaccines for pregnant women and the need for seasonal influenza vaccination in pregnancy led to media commentaries, speculation on vaccine safety and public anxiety.
Available data support the use of the inactivated influenza vaccine during all stages of pregnancy, particularly for women with medical conditions that may increase the risk of complications. Reassuring pharmacoepidemiological studies have indicated that 2009 A/H1N1 influenza vaccination is not associated with adverse pregnancy outcomes including fetal death, preterm birth and congenital anomalies , , , , , and . Vaccination may have reduced the risk of influenza-related fetal death during the pandemic  .
It is important to study the determinants of vaccination uptake in pregnant women in a variety of settings, given the regional variations that have been previously reported  . It is also essential that extensive data are available on pregnancy outcomes after gestational vaccine exposure in order to inform decisions on vaccination by pregnant women and health professionals, particularly during a pandemic situation. This study has two main objectives. The first objective is to describe the uptake and determinants of 2009 A/H1N1 influenza vaccination in pregnant women during the pandemic. The second objective is to determine if there is an association between vaccination and adverse pregnancy outcomes.
Materials and methods
The Irish pandemic flu vaccination programme began in early November 2009 and ended on the 31st of March 2010  . In the initial phase high risk groups, including pregnant women, were offered prioritised access to the vaccine. Vaccination was offered in vaccination centres set up by the Health Service Executive, in vaccination clinics run by the maternity hospital to coincide with antenatal clinics and in primary care. Details of vaccination provider were not available for this study.
All singleton deliveries during the study period were eligible for inclusion. Data on maternal characteristics, medical and obstetric history recorded at the antenatal booking interview and perinatal outcomes recorded in the delivery suite and neonatal intensive care unit were extracted from electronic hospital records at the Coombe Women and Infants University Hospital in Dublin (CWIUH). CWIUH is a tertiary referral maternity hospital serving a diverse urban/suburban catchment area and delivering approximately 12% of all Irish births. The majority of women (approximately 85%) receive antenatal care in the public system. Antenatal care may be delivered by an obstetric team within the hospital or it may involve combined care delivered by an obstetrician and a primary care doctor. The hospital also offers midwifery-led antenatal care to low risk women.
Data on vaccination status was recorded at delivery from the beginning of December 2009. The following questions were added to the delivery suite admission form:
- (1) H1N1 vaccine this pregnancy? (Yes/No)
- (2) When given (1st dose) (1st trimester, 2nd trimester, 3rd trimester).
- (3) Vaccine used? (Celvapan 1 dose, Celvapan 2 doses, Pandemrix, unknown)
Preterm and very preterm deliveries were defined as delivery prior to 37 and 32 weeks gestation respectively. Gestational age is routinely determined from the first day of the last menstrual period (LMP). The booking visit ultrasound scan estimate is used if there is uncertainty of the LMP date or if there is a discrepancy of more than seven days between the LMP and ultrasound estimates. Birthweight is measured by a midwife or paediatrician on the delivery suite using electronic scales. Small for gestational age was defined as a birthweight determined to be less than the 10th centile customised for maternal weight, height, gestation and infant sex  . Congenital anomalies were ascertained from electronic records of any anomalies identified by midwifery or paediatric staff on the delivery suite or from congenital anomaly, body system or discharge diagnoses fields in the neonatal unit electronic discharge records.
Descriptive statistics were used as appropriate to describe maternal characteristics of vaccinated and unvaccinated women. Univariable logistic regression analyses were used to determine odds ratios and 95% confidence intervals for associations between maternal characteristics and vaccination. Cases with missing data were excluded from the logistic regression analyses. The levels of missing data for each maternal characteristic and pregnancy outcome are indicated in Table 1 and Table 2.
|N = 6894||Vaccinated n = 2996 [43.5%]||Unvaccinated n = 3898 [56.5%]||OR||95% CI|
|Age at delivery||6894|
|<20 years||97 [37.7]||160 [62.3]||0.92||0.70–1.21|
|20–24 years||353 [40.3]||522 [59.7]||1.03||0.87–1.22|
|25–29 years||686 [39.6]||1045 [60.4]||1||–|
|30–34 years||1015 [44.9]||1248 [55.1]||1.24||1.09–1.41|
|35–39 years||719 [48.8]||753 [51.2]||1.45||1.26–1.67|
|>40 years||126 [42.6]||170 [57.4]||1.13||0.88–1.45|
|Home duties||481 [37.1]||815 [62.9]||0.61||0.52–0.70|
|Professional/manager /employer||910 [49.3]||934 [50.7]||1||–|
|Non-manual||1115 [44.2]||1406 [55.8]||0.81||0.72–0.92|
|Manual||110 [34.4]||210 [65.6]||0.54||0.42–0.69|
|Unemployed||240 [42.9]||319 [57.1]||0.77||0.64–0.93|
|Non-classifiable||140 [40.2]||208 [59.8]||0.69||0.55–0.87|
|Nationality – Irish||6838|
|Yes||2352 [49.2]||2431 [50.8]||1||–|
|No||618 [30.1]||1437 [69.9]||0.44||0.40–0.49|
|Western Europe||2460 [48.6]||2598 [51.4]||1||–|
|Eastern Europe||144 [16.6]||724 [83.4]||0.21||0.17–0.25|
|Africa||128 [39.1]||199 [60.9]||0.68||0.54–0.85|
|South America||16 [50.0]||16 [50.0]||1.05||0.53–2.11|
|North America||14 [53.8]||12 [46.2]||1.23||0.57–2.67|
|Asia/Middle East||201 [39.4]||309 [60.6]||0.69||0.57–0.83|
|Australia and New Zealand||7 [41.2]||10 [58.8]||0.74||0.28–1.94|
|Yes||1815 [43.4]||2365 [56.6]||1||–|
|No||1140 [43.6]||1472 [56.4]||1.00||0.91–1.11|
|Yes||1248 [42.8]||1669 [57.2]||1||–|
|No||1748 [44.0]||2229 [56.0]||1.04||0.95–1.15|
|Yes||2055 [44.6]||2557 [55.4]||1||–|
|No||934 [41.7]||1304 [58.3]||0.89||0.80–0.99|
|Booking gestation (weeks)||6832|
|<12 weeks||1317 [46.9]||1493 [53.1]||1.18||1.06–1.30|
|12–20 weeks||1547 [42.8]||2065 [57.2]||1||–|
|>20 weeks||110 [26.8]||300 [73.2]||0.49||0.39–0.62|
|Publicly-funded obstetric care||6894|
|Yes||2444 [43.5]||3366 [57.9]||1||–|
|No||552 [50.9]||532 [49.1]||1.43||1.25–1.63|
|Smoked during pregnancy a||6891|
|No||2527 [43.6]||3270 [56.4]||1||–|
|Yes||469 [42.9]||625 [57.1]||0.97||0.85–1.10|
a Smoking status ascertained at the antenatal booking interview.
OR – odds ratio; CI – confidence interval.
|n = 13938||Vaccinated n = 2996||Unvaccinated n = 3898||Pre-vaccination
n = 7044
|OR a||95% CI||OR b||95% CI|
|Mode of delivery||13938|
|SVD||1768 [59.0]||2220 [57.0]||4105 [58.3]||1||–||1||–|
|Elective LSCS||208 [6.9]||496 [12.7]||760 [10.8]||0.53||0.44–0.63||0.64||0.54–0.75|
|Emergency LSCS||420 [14.0]||548 [14.1]||919 [13.0]||0.96||0.83–1.11||1.06||0.93–1.21|
|Forceps||247 [8.2]||296 [7.6]||522 [7.4]||1.05||0.88–1.26||1.10||0.93–1.29|
|Ventouse||353 [11.8]||338 [8.7]||738 [10.5]||1.31||1.12–1.54||1.11||0.97–1.28|
|Preterm birth <37 weeks||13824||141 [4.7]||252 [6.5]||371 [5.3]||0.71||0.58–0.88||0.89||0.73–1.08|
|Spontaneous birth <37 weeks||13824||73 [2.5]||127 [3.3]||198 [2.8]||0.74||0.55–0.99||0.86||0.66–1.13|
|Very preterm birth <32 weeks||13824||26 [0.9]||60 [1.6]||73 [1.0]||0.56||0.35–0.89||0.84||0.53–1.31|
|Spontaneous birth <32 weeks||13824||15 [0.5]||25 [0.6]||30 [0.4]||0.78||0.41–1.48||1.17||0.63–2.19|
|Small for gestational age <10th centile c||13824||368 [12.4]||485 [12.6]||862 [12.3]||0.98||0.85–1.13||1.00||0.88–1.14|
|Apgar score <3 at 1 min||13911||27 [0.9]||42 [1.1]||57 [0.8]||0.83||0.51–1.35||1.11||0.70–1.76|
|Apgar score <7 at 5 min||13853||21 [0.7]||33 [0.9]||50 [0.7]||0.82||0.47–1.43||0.98||0.59–1.64|
|Admitted to neonatal unit||13938||507 [16.9]||652 [16.7]||942 [13.4]||1.01||0.89–1.15||1.32||1.17–1.48|
|Congenital anomaly||13938||66 [2.2]||110 [2.8]||181 [2.6]||0.78||0.57–1.05||0.85||0.64–1.14|
|Perinatal death d||13938||11 [0.4]||22 [0.6]||39 [0.6]||0.65||0.31–1.34||0.66||0.34–1.29|
a Vaccinated versus unvaccinated (unadjusted odds ratio).
b Vaccinated versus pre-vaccination (unadjusted odds ratio).
c Birth weight centiles were calculated using GROW-centile, a customised weight centile calculator.
d Includes stillbirths and neonatal deaths. Stillbirth was defined as delivery of a baby showing no signs of life at or after 24 weeks gestation. Neonatal death was defined as the death of a baby within the first seven days of life.
OR – odds ratio; CI – confidence interval; SVD – spontaneous vaginal delivery; LSCS – lower segment caesarean section.
Pregnancy outcomes were compared between vaccine-exposed women delivering between December 2009 and September 2010 and two comparison groups. The first comparison group included women delivering from the beginning of December 2009 to the end of September 2010 who reported that they had not been vaccinated at the time of delivery (unvaccinated group). The second comparison group included women delivering from the beginning of December 2008 to the end of September 2009, representing a time period prior to the mass vaccination programme and the main wave of the pandemic (prevaccination group). Univariable and multivariable logistic regression analyses were used to generate unadjusted and adjusted odds ratios examining the association between vaccination and adverse perinatal outcomes. The multivariable analysis included adjustment for age band at delivery, socioeconomic group, region, planning of pregnancy, booking gestation, public obstetric care and smoking in pregnancy.
A separate univariable logistic regression analysis was carried out to determine if vaccination was associated with congenital anomalies after first trimester exposure with comparison to the unvaccinated group.
The study was approved by the Hospital’s Research Ethics Committee on 16th May 2012 (Study No. 3–2012).
Of 6894 women delivering between the beginning of December 2009 and the end of the following September, 2996 women [43.5%] reported vaccination at delivery. The temporal distribution of vaccination during pregnancy is represented in Fig. 1 . Vaccination in the first, second and third trimesters was reported by 246 [8.2%], 1709 [57.0%] and 1034 [34.5%] vaccinated women, respectively. Celvapan® was received by 1692 [56.5%] women, with approximately half receiving a single dose and half receiving two. A single dose of Pandemrix® was received by 698 [23.3%] women, with a further 606 [20.2%] women unsure of the specific vaccine used.
Maternal characteristics of vaccinated and unvaccinated women are outlined in Table 1 . Compared with women in the 25–29 age group, those between 30–39 years were more likely to report vaccination. Vaccination was most likely in the professional, manager and employer socioeconomic group compared to all other groupings. There were regional variations in vaccination uptake with women from Eastern Europe less likely to report vaccination than those from Western Europe (odds ratio 0.21, 95% Confidence Interval 0.17–0.25). Women from Africa and Asia/Middle East were also less likely to report vaccination. Irish nationality was associated with reporting vaccination (OR 2.25, 95% CI 2.01–2.51). Women who reported an unplanned pregnancy were less likely to be vaccinated. Those booking after 20 weeks were less likely to be vaccinated (OR 0.49, 95% CI 0.39–0.62) compared to those booking between 12 and 20 weeks’ gestation. Women who received privately-funded obstetric care were more likely to report vaccination (OR 1.43, 95% CI 1.25–1.63).
Maternal and perinatal outcomes for the vaccinated and unvaccinated groups are compared in Table 2 . Adverse perinatal outcomes did not appear to differ significantly between the vaccinated group and the two comparison groups. In the unadjusted analyses, vaccinated women were less likely to have an elective caesarean section than the unvaccinated group. Preterm birth (<37 and <32 weeks’ gestation) was also less likely in the vaccinated women compared to the unvaccinated group. This association was not found when the prevaccination group were used for comparison. Adjustment for maternal characteristics that differed significantly between the vaccinated and unvaccinated groups including age, socioeconomic group, region, planning of pregnancy, booking gestation, funding of obstetric care and smoking with multivariable logistic regression analyses did not alter the results. The adjusted OR for the association between vaccination and preterm delivery before 37 and 32 weeks’ gestation were 0.72, 95% CI 0.58–0.89 and 0.56, 95% CI 0.35–0.90, when the vaccinated group were compared with the unvaccinated group.
There were nine congenital anomalies among 246 pregnancies where women reported vaccination in the first trimester and 110 among 3897 pregnancies in unvaccinated women (3.7% vs. 2.8%; OR 1.31, 95% CI 0.65–2.61). The congenital anomalies recorded for the nine neonates were: duplication of left ureter (history of duplicate kidneys in siblings), atrophic right kidney (maternal history of atrophic kidney also), unspecified chromosomal anomaly, mild pyelectasis on antenatal ultrasound, subcutaneous dermoid cyst, hydronephrosis on antenatal ultrasound, bilateral hydrocele, albinism and cardiomyopathy (maternal cardiomyopathy also).
This study demonstrated that 43.5% of women delivering between December 2009 and September 2010 had received at least one dose of pandemic 2009 A/H1N1 influenza vaccine, with vaccination rates of over 70% in the weeks after the initiation of the vaccination programme. Of the women with known vaccine type, the majority [70.7%] received the cell-line-derived, thiomersal free, non-adjuvanted product Celvapan®. Women who were less likely to be vaccinated included those in younger age groups, those who were not in the professional/manager/employer socioeconomic group, women from Eastern Europe, Africa and Asia/Middle East, women who booked late for antenatal care, those who reported an unplanned pregnancy and those who received publicly-funded obstetric care. Vaccination was not associated with adverse pregnancy outcomes.
Strengths and limitations
This study was conducted in a large tertiary referral maternity hospital that delivers approximately 9000 babies annually. Data on maternal characteristics, medical history, vaccination status and pregnancy outcomes were routinely collected by midwives using structured computer-guided and paper questionnaires. Data were available on a diverse group of women from a broad range of socio-economic groupings. Virtually all deliveries during the study period were included in the analysis, reducing the risk of selection bias. This study also provided information on both adjuvanted and unadjuvanted vaccines. The study results are likely to be generalisable to women receiving antenatal care in similar hospital settings worldwide, though international variations in vaccine uptake are likely.
This study was limited by the inclusion of only one maternity hospital. Current constraints imposed by the Irish Data Protection Act precluded a planned study including the three main Dublin maternity hospitals which deliver 4 in 10 Irish babies. Data were not available on the vaccination provider or the model of antenatal care. Pregnancy outcomes were ascertained after information on vaccination status was collected, this may have potentially led to biased assessment of outcomes, however there is no evidence to suggest that this occurred. The study was also limited by the constraint of ascertainment of vaccination status at delivery as this prevented any analysis of the relationship between vaccination and early pregnancy loss and also introduced the risk of recall bias. Reliance on maternal self-report of vaccination status, vaccine used and timing of vaccination is a potential limitation, however, the high profile nature of the pandemic vaccination recommendations meant that most women knew this information. Congenital anomalies were ascertained from routine hospital records up to the time of hospital discharge. There was limited recording of clinical details of anomalies and it is possible that misclassification led to an underestimation of congenital anomalies for all neonates. Although multivariable logistic regression was used to adjust for differing maternal characteristics between the comparison groups, it is possible that residual confounding remained. This residual confounding may have explained the apparent differences in the elective caesarean section rate between the vaccinated and unvaccinated groups.
There are a number of factors that may have an impact on vaccination uptake rates in the pregnant population. Maternal characteristics associated with vaccination include working outside the home, being multiparous and having a higher level of education  . Other factors include the safety concerns of both patients and healthcare workers and also a lack of recommendation of vaccination by medical professionals  . A US survey of postpartum women, which reported a vaccination rate of 34%, indicated that the strongest determinants of vaccination were awareness of vaccine safety and health professional recommendations  . Some studies identified that pandemic 2009 A/H1N1 influenza vaccination was actually offered to a minority of women during pregnancy  and . Maternal co-morbidities have also been demonstrated to affect the likelihood of vaccination along with regional variations in uptake  .
Several similar studies in a variety of international settings have reported uptake rates in pregnancy below 15% , , , and . Vaccine availability issues early in the pandemic may have reduced uptake in some studies. Higher rates of 37–85% have been reported in other studies from the US and UK , , and . In a Dutch online survey with a 20.6% response rate, 63% of pregnant women reported vaccination  . An EU survey reported that for pregnant women, Ireland had the second highest vaccination coverage at 32% after the Netherlands at 58%  . In line with the findings of this study, vaccination was much less likely in Eastern European countries. Low uptake of the vaccine in pregnancy has also been reported in an Australian study  .
The higher estimates from some patient surveys may be caused by sampling bias. Uptake rates will also vary between studies depending on the time period included. In this study, vaccination rates of up to 70% were achieved in women delivering in the weeks after the initiation of the vaccination campaign. These uptake rates may be explained by clear public health messages given in antenatal clinics along with specific vaccination clinics run in the hospital to coincide with antenatal clinics. Vaccination was also available through national vaccination programmes run in the community by public health services.
This study adds to previous findings of regional variations in vaccination uptake  and . Maternal characteristics associated with not being vaccinated were similar in several international studies. A Canadian study also reported variations in vaccination rates related to maternal age, socio-economic status and late booking  . A French study had similar findings with higher vaccination rates in women who were older, employed and born in France  .
Ressuring data are provided on the safety of pandemic 2009 A/H1N1 influenza vaccination in pregnancy. Previous studies support the current findings of no association between pandemic 2009 A/H1N1 influenza vaccination in pregnancy and adverse pregnancy outcomes including fetal death, preterm birth and congenital anomalies , , , , , and . One previous study also noted an association between vaccination and a marginal risk reduction for caesarean section  .
There was some evidence of a possible protective effect of vaccination with regard to preterm birth. The unadjusted and adjusted analyses indicated that preterm birth below 37 and 32 weeks’ gestation was less likely in the vaccinated group compared to the unvaccinated. There was no evidence of a significant difference in preterm birth rates when the vaccinated group were compared to the prevaccination group. Maternal 2009/H1N1 infection has been associated with preterm birth, particularly with infection in the third trimester  . Confounding by unmeasured maternal characteristics may explain this difference. Alternatively the association may be indicative of a protective effect of vaccination, reducing febrile illness and associated preterm delivery. The protective effect of the vaccine may have prevented preterm birth within the vaccinated group which had preterm birth rates that were similar to rates in the prevaccination comparison group. A lower likelihood of preterm birth after pandemic 2009 A/H1N1 influenza vaccination in pregnancy has previously been reported  and , though this finding was not consistent across all studies  and .
Women with an underlying health condition are more likely to be vaccinated during pregnancy  . These underlying health conditions may predispose a proportion of the vaccinated group to adverse pregnancy outcomes, however, there was no evidence of an increased risk of adverse outcomes for the vaccinated group in this study.
This study demonstrates that high influenza vaccine uptake rates can be achieved for pregnant women in a pandemic situation. Future public health campaigns should provide clear information on vaccination safety in pregnancy, ensure consistent advice and vaccination recommendations from healthcare professionals and provide easy access to vaccination e.g. through integration with antenatal care to optimise uptake rates in subgroups of the population who are less likely to be vaccinated.
Reassuring data from geographically diverse locations on the relationship between maternal vaccination and pregnancy outcomes will aid future vaccination campaigns. This wealth of safety data will attenuate public uncertainty about vaccine safety in pregnancy. The available data may also improve uptake rates in pregnant women in future pandemics.
Disclosure of interests
None of the researchers have any conflict of interest to declare. No contractual constraints on publishing were imposed by the funding bodies.
Contribution to authorship
BC proposed the study initially and was responsible for study design along with UR, ME and FM; BC, UR and NM were responsible for acquisition and analysis of data; all authors were involved in drafting the article, revising it and final approval for publication.
Details of ethics approval
The study was approved by the Hospital’s Research Ethics Committee on 16th May 2012 (Study No. 3–2012).
BC was funded by the charity Friends of the Coombe and the School of Pharmacy, Royal College of Surgeons in Ireland.
We would like to gratefully acknowledge the funders: the Friends of the Coombe and the School of Pharmacy, Royal College of Surgeons in Ireland; Dr. Chris Fitzpatrick and Ann Fergus for facilitating data collection; the Midwives and other staff who collected the data and Emma McNamee from the IT Department for extracting the data.
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a Pharmacy Department, Rotunda Hospital, Dublin 1, Ireland
b School of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland
c Pharmacy Department, Coombe Women and Infants University Hospital, Dublin 8, Ireland
d Rotunda Hospital, Dublin 1, Ireland
e Discipline of Paediatrics, School of Medicine, Trinity College Dublin, Dublin 2, Ireland
f National Maternity Hospital, Dublin 2, Ireland
g Department of Obstetrics and Gynaecology, School of Medicine and Medical Science, University College Dublin, Dublin 4, Ireland
© 2014 Published by Elsevier B.V.