A class of scaled Bessel sampling theorems

Sampling theorems for a class of scaled Bessel unitary transforms are presented. The derivations are based on the properties of the generalized Laguerre functions. This class of scaled Bessel unitary transforms includes the classical sine and cosine transforms, but also novel chirp sine and modified Hankel transforms. The results for the sine and cosine transform can also be utilized to yield a sampling theorem, different from Shannon's, for the Fourier transform

Computer assisted ocular pathology search

Computer assisted ocular pathology searc

Guidelines for conducting birth defects surveillance

"In January of 1999, the National Birth Defects Prevention Network (NBDPN) established a Surveillance Guidelines and Standards Committee (SGSC) in order to develop and promote the use of standards and guidelines for birth defects surveillance programs in the United States. This set of guidelines is designed to serve as an important first step in the documentation of this process and as the vehicle for dissemination of the committee's findings. The Guidelines for Conducting Birth Defects Surveillance (henceforth referred to as The Surveillance Guidelines) were developed with three major long-term objectives in mind: To improve the quality of state birth defects surveillance data, including accuracy, comparability, completeness, and timeliness; To enhance the utility of state birth defects surveillance data for research on the distribution and etiology of birth defects; To encourage and promote the use of state birth defects surveillance data for the purposes of linking affected children with services and evaluation of those services. The technical guidelines that make up this document provide a way of improving the quality of birth defects surveillance data, which in turn enhances their use in support of the latter two objectives. Fundamental to quality is ensuring that procedures for all aspects of data definition, collection, management, and analysis are established and followed. Because state-based surveillance systems operate with different objectives and data needs, it is clear that, with respect to procedures and standards, 'one size does not fit all.' It is also clear, however, that common guidelines can provide a basis for the development of system-specific operating procedures and supporting manuals." - p. iIntroduction -- -- Chapter 1. The Whys and Hows of Birth Defects Surveillance - Using Data -- -- Chapter 2. Legislation -- Appendix 2.1. Sample State Legislation -- Appendix 2.2. Table of Birth Defects Legislation -- Appendix 2.3. Definitions Used to Determine Covered Entity Status Under the Privacy Rule -- Appendix 2.4. Office of Civil Rights (OCR) HIPAA Privacy Regulation Text -- -- Chapter 3.Case Definition -- Appendix 3.1. Birth Defects Included in the Case Definition of the National Birth Defects Prevention Network -- Appendix 3.2. NBDPN Abstractor's Instructions -- Appendix 3.3. Examples of Conditions Considered to Be Minor Anomalies -- Appendix 3.4. Conditions Related to Prematurity in Infants Born at Less Than 36 Weeks Gestation -- -- Chapter 4. Data Variables -- Appendix 4.1. Descriptions of Minimum (Core) Data Variables -- Appendix 4.2. Descriptions of Recommended Data Variables -- -- Chapter 5. Classification and Coding -- Appendix 5.1. Texas Disease Index -- Appendix 5.2. 6-Digit CDC Codes (updated 8/2007) -- -- Chapter 6. Case Ascertainment Methods -- Appendix 6.1. Data Source Described in Detail - Vital Records -- Appendix 6.2. Data Source Described in Detail - Hospital Data Sets -- Appendix 6.3. Data Source Described in Detail - Hospital and Patient Services Logs -- Appendix 6.4. Data Source Described in Detail - Genetic Services -- -- Chapter 7. Data Quality Management -- Appendix 7.1. Data Sources Descriptive Assessment Tool -- -- Chapter 8. Statistical Methods -- -- Chapter 9. Data Management and Security -- -- Chapter 10. Data Collaboration and Dissemination through the NBDPN -- -- Chapter 11. Data Presentation -- Appendix 11.1. Data Suppression -- Appendix 11.2. Use of Geographic Information Systems (GIS) to Map Data -- Appendix 11.3. Data Users Matrix -- Appendix 11.4. What Type of Chart or Graph Should I Use?edited by Lowell E. Sever."June 2004."Support for development, production, and distribution of these guidelines was provided by the Birth Defects State Research Partnerships Team, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention.Title from title caption (viewed on Jan. 6, 2012).Mode of access: Internet from the CDC web site as an Acrobat .pdf file ((7.6 MB, 627 p.).System requirements: Adobe Acrobat Reader.Includes bibliographical references.Text in PDF format.National Birth Defects Prevention Network (NBDPN). Guidelines for Conducting Birth Defects Surveillance. Sever, LE, ed. Atlanta, GA: National Birth Defects Prevention Network, Inc., June 2004

Using primary care data to assess population-level estimates of maternal smoking and nicotine replacement therapy during pregnancy

Background: Smoking in pregnancy is the most significant preventable cause of poor health outcomes for women and their babies and, therefore, is a major public health concern. In the UK there is a wide range of interventions and support for pregnant women who want to quit. One of these is nicotine replacement therapy (NRT) which has been widely available for retail purchase and prescribing to pregnant women since 2005. However, measures of NRT prescribing in pregnant women are scarce. These measures are vital to assess its usefulness in smoking cessation during pregnancy at a population level. Furthermore, evidence of NRT safety in pregnancy for the mother and child’s health so far is nebulous, with existing studies being small or using retrospectively reported exposures. Aims and Objectives: The main aim of this work was to assess population-level estimates of maternal smoking and NRT prescribing in pregnancy and the safety of NRT for both the mother and the child in the UK. Currently, the only population-level data on UK maternal smoking are from repeated cross-sectional surveys or routinely collected maternity data during pregnancy or at delivery. These obtain information at one point in time, and there are no population-level data on NRT use available. As a novel approach, therefore, this thesis used the routinely collected primary care data that are currently available for approximately 6% of the UK population and provide longitudinal/prospectively recorded information throughout pregnancy. The specific objectives for this thesis were: • To assess the quality of smoking data recorded during pregnancy in primary care • To quantify annual NRT prescribing trends in and around pregnancy and describe the characteristics of mothers prescribed NRT • To assess the association between NRT and smoking exposure during pregnancy and major congenital anomalies (MCAs), stillbirth, low birth weight and mode of delivery Methods: All women aged 15-49 years, with pregnancies ending in live or stillbirth, were identified from The Health Improvement Network (THIN) primary care database (2000-2009). Medical Read codes related to smoking status and Multilex smoking cessation drug prescription codes were used to extract data on women’s smoking status and NRT prescriptions. The proportion of pregnancies with a smoking status record was calculated and logistic regression was used to assess how this varied by women’s characteristics. Women were categorised as being smokers or non-smokers during pregnancy based on the recorded Read codes. Where smoking data were missing during pregnancy, smoking status recorded before pregnancy (up to 27 months before pregnancy, ever before pregnancy) was used as a proxy for smoking status during pregnancy. Annual smoking measures from THIN were then compared to other national datasets. Pregnancies ending in early fetal losses were not included for calculating smoking prevalence, as these outcomes can go unrecognised or can be the first recognised sign of pregnancy, making early ascertainment of all pregnancies uncomprehensive; this was also broadly in line with pregnancy ascertainment in the other national datasets. Prescribing prevalence of NRT and patterns of prescribing in terms of frequency, timing and different form of NRT were assessed. Logistic regression was used to assess women’s likelihood of receiving NRT prescriptions by maternal characteristics. Absolute and relative risks (99% Confidence Interval (CI)) for four birth outcomes (MCAs, stillbirth, low birth weight and mode of delivery) were calculated for women prescribed NRT (defined as the NRT group) and women who continued to smoke during pregnancy (defined as smokers) compared to women who did not smoke during pregnancy (defined as non-smokers) with appropriate adjustments for potential confounders. To assess MCAs and birth weight in relation to NRT and smoking a restricted cohort of children was used who had maternal-child linked records in THIN. Results: There were 277,552 pregnancies in 215,703 women, of which 28% had a gestational smoking status record. In 2000, smoking status was recorded in 9% of pregnancies; 43% in 2009. Smoking estimates from THIN data did not completely agree with estimates from other sources. For example, in 2009 smoking prevalence was 12.9% in THIN, compared to 19.5% in Child Health Systems Programme (CHSP) data. However, the use of smoking data recorded up to 27 months before conception increased the THIN prevalence to 22.9%, which was slightly higher, but compared better with the CHSP estimates. NRT was prescribed in 4,826 pregnancies for an average duration of 2 weeks (Interquartile range 1-2 weeks), which represented 2% of all pregnancies (11% in smokers). NRT prescribing prevalence before and after pregnancy was half the prevalence during pregnancy. NRT prescribing increased with socioeconomic deprivation (Odds Ratio (OR) =1.33, 95% CI 1.14-1.52) for the most compared to the least deprived group). Prescribing was higher in pregnant smokers with asthma (OR=1.34, 95% CI 1.21-1.50) and mental illness (OR=1.29, 95% CI 1.18-1.43) compared to smokers without these diagnoses. The absolute risk of MCA was 279/10,000 live births. Compared with non-smokers the adjusted OR for MCA in the NRT group was 1.34 (99% CI 0.94-1.91). No statistically significant increase in the risk of MCA for the NRT group was found when the reference group was changed to smokers (OR=1.35, 99% CI 0.94-1.93).The absolute risk of stillbirth was 4/1000 live and stillbirths. Compared with non-smokers the adjusted OR for stillbirth in the NRT group was 1.19 (99% CI 0.47-3.01). In smokers, the risk of stillbirth increased by 27% compared to non-smokers (OR 1.27, 99% CI 1.01-1.60). The mean birth weight was 3.41kg (standard deviation 0.59) and the absolute risk of low birth weight was 6.4%. Compared to non-smokers, the risk of women having low birth weight babies was 93% higher in the NRT group (OR 1.93, 99% CI 1.48-2.53). However, there was no statistically significant increase in the risk of low birth weight in the NRT group compared with smokers. There was no increased risk of assisted delivery or caesarean section in the NRT group compared to smokers. However the risk of assisted delivery decreased by 25% in the NRT group (Relative Risk Ratio 0.75, 99% CI 0.60-0.93) compared to non-smokers. Conclusion: The completeness of smoking status recording during pregnancy in primary care data is improving; however, under-recording of smoking status during pregnancy still results in unreliable estimates of the prevalence of smoking in pregnancy and needs improvement. Pre-conception smoking records are reasonably complete and it is possible that low recording in pregnancy is because a woman’s smoking status has not changed or that increased interaction with other health services, such as midwifery, during pregnancy means women are less likely to be asked about their smoking by their primary physician and information on their smoking does not get relayed back to their primary care record. Nevertheless records should be updated in pregnancy to ensure comprehensive health care. NRT was most commonly prescribed in pregnancy for about two weeks, which may not be adequate time for effective smoking cessation. Nevertheless, prescribing was higher during pregnancy compared to the nine months before and after pregnancy, which makes establishing its safety during pregnancy even more crucial. The safety studies in this thesis did not find NRT to be any more harmful than smoking during pregnancy if not beneficial. Considering that smoking in pregnancy remains one of the largest public health problems in the UK, improvements of antenatal and postnatal smoking in primary care may not only help identify women for preventive measures earlier but would be invaluable for safety studies considering the outcomes are rare yet severe

The prevalence and survival of children with congenital septal defects in the UK using CPRD

Background Congenital heart disease (CHD) is a major contributor to infant mortality worldwide, accounting for a third of total congenital defects and a fifth of total global early neonatal mortality. Congenital septal defects (SD) are the most common CHD. This study assesses the prevalence and survival of children diagnosed with congenital septal defects in the UK. Methods All children who survived to at least the first 30 days after birth and registered with a GP within their first year of birth diagnosed with any CHD at any time in England between January 1998 and June 2017 were extracted from Clinical Practice Research Datalink (CPRD). Similar records for children diagnosed with other congenital anomalies were also obtained as well as children without any congenital anomaly constituting as the control group. These records were matched with the Office for National Statistics (ONS) death registration data, and the Index of Multiple Deprivation (IMD) data to allow assessment of death records and deprivation records, respectively. Prevalence risk ratios were calculated according to specific sociodemographic factors such as gender, year of birth, ethnicity, socioeconomic status, and geographical location for SD and its variants. Mortality risk ratios were calculated by gender, ethnicity, and socioeconomic status for SD and its variants. Also, in the absence of Hospital Episode Statistics (HES) data, I assessed the recording of CHD-related procedures/interventions in children’s GP records as a measure of disease severity within the CPRD-based birth cohort used in this thesis. Results The prevalence of any CHD was 86.1 per 10,000 live GP-registered births (95% CI, 83.7 – 88.4). SD accounted for 53.4% of the total CHD within this population and the overall prevalence of SD was 48.64 per 10,000 live GP-registered births (95% CI 46.90-50.44). Of all SD diagnosis identified, 59.1% had a VSD diagnosis (35.50 per 10,000 live GP-registered births, 95% CI 34.02-37.04), 28.8% ASD (17.31 per 10,000 live GP-registered births, 95% CI 16.29-18.40), 6.5% for ToF (3.91 per 10,000 live GP-registered births, 95% CI 3.44-4.45), 0.3% for AoSD (0.17 per 10,000 live GP-registered births, 95% CI 0.09-0.31), 3.2% for AVSD (1.93 per 10.000 live GP-registered births, 95% CI 1.61-2.32), and 2.1% for unspecified SD (1.28 per 10.000 live GP-registered births, 95% CI 1.02-1.60). For any SD, gender was significantly associated with occurrence, with the prevalence in females being 15% more than males (PR (Male-Female) 1.15, 95% CI 1.07-1.24), however, there was considerable variation across specific SD variants. Whilst there was no evidence of an association with the year of birth, ethnicity, or socioeconomic status on the prevalence of overall SD, specific sub-analysis of the SD variants showed some associations. The prevalence of SD and its variants varied by geographical regions in England with the highest prevalence of any SD observed in the East Midlands. The total number of deaths due to CHD from 30 days after birth to 19 years between January 1998 and June 2017 was 166 and the mortality rate was 5.6 (95% CI, 4.8-6.5) per 1,000 person-years. By SD variants, children with Aortopulmonary septal defect (54.9; 95% CI 13.7-219.6), Atrioventricular septal defect (7.2; 95% CI, 3.0-17.3), and Tetralogy of Fallot (8.1; 95% 4.6-14.3) had the highest mortality rates compared to other defects, although small numbers of children resulted in large confidence limits for some of these estimations. The hazard of death for children with any septal defect was over 16-fold higher than for children without a CA (HR 16.2; 95% CI, 12.8-20.6); aHR 16.4, 95% CI, 13.0-20.9, p<0.001). Of this, children with Aortopulmonary septal defect had the highest hazard of death with a 160-fold increase compared to children without a CA (HR, 164.6, 95% CI, (41.1-659.5); aHR 159.3, 95% CI, 39.7-641.4, p<0.001) and was lowest for children with VSD (HR, 15.5, 95% CI, (11.7-20.5); aHR 14.9, 95% CI, 12.0-21.0, p<0.001). For overall septal defects, whilst there was no difference in the hazard of death or mortality rate by ethnicity, there was a significant association with socioeconomic status largely driven by ASD. Mortality rates by age groups between 0 and 9 years were also considered; whilst there was substantial variation within the various defects and age groups, there was a 12-fold increased risk of post neonatal death for all SD compared to children with no CA across age groups. Of the total SD cases in this dataset, 5% were recorded to have had an intervention within the first year of life. Of the SD sub variants, 4% of each of the total VSD and ASD had an intervention recorded in population. The proportion of interventions was higher for the other SD sub variants with ToF, AVSD and AoSD at 29%, 36% and 40% respectively. Of the 381 CHD patients who had a recording of at least one CHD-related intervention, only eight (8) patients died. The subsequent analysis of the severity of SD variants in relation to mortality was therefore precluded as for all variants the number of deaths recorded was less than 5. Conclusion Using a study population derived through data linkage between CPRD, ONS, and IMD in England, this study reinforces broadly that AoSD, ToF, AVSD whilst being the least prevalent SD, constitute the highest mortality variants of SD whilst VSD and ASD (the more prevalent forms) are not as lethal. Regardless, all SD variants considered had higher mortality than children without SD. Considerable effort is required to further improve the survival rates of children with these defects and ultimately improve the prognosis for children diagnosed with these defects. This study further raises the need for the consideration and development of region-specific and ethnicity-specific strategies to improving diagnosis and disease outcomes for children with a septal defect in England. As the dataset was not linked to HES, the ability to adequately assess the severity of septal defects in the study population was impaired. Using the limited codes for recording of CHD-related procedures within the GP-based dataset as a measure of severity unmasked the likely under-reporting of hospital events or procedures as children who should have received interventions based on their diagnosis did not always have this recorded in their GP record. Further studies incorporating the available information from HES are required to effectively determine the severity of septal defects and its variants especially with regards to how it affects mortality and mortalit

Using primary care data to assess population-level estimates of maternal smoking and nicotine replacement therapy during pregnancy

Background: Smoking in pregnancy is the most significant preventable cause of poor health outcomes for women and their babies and, therefore, is a major public health concern. In the UK there is a wide range of interventions and support for pregnant women who want to quit. One of these is nicotine replacement therapy (NRT) which has been widely available for retail purchase and prescribing to pregnant women since 2005. However, measures of NRT prescribing in pregnant women are scarce. These measures are vital to assess its usefulness in smoking cessation during pregnancy at a population level. Furthermore, evidence of NRT safety in pregnancy for the mother and child’s health so far is nebulous, with existing studies being small or using retrospectively reported exposures. Aims and Objectives: The main aim of this work was to assess population-level estimates of maternal smoking and NRT prescribing in pregnancy and the safety of NRT for both the mother and the child in the UK. Currently, the only population-level data on UK maternal smoking are from repeated cross-sectional surveys or routinely collected maternity data during pregnancy or at delivery. These obtain information at one point in time, and there are no population-level data on NRT use available. As a novel approach, therefore, this thesis used the routinely collected primary care data that are currently available for approximately 6% of the UK population and provide longitudinal/prospectively recorded information throughout pregnancy. The specific objectives for this thesis were: • To assess the quality of smoking data recorded during pregnancy in primary care • To quantify annual NRT prescribing trends in and around pregnancy and describe the characteristics of mothers prescribed NRT • To assess the association between NRT and smoking exposure during pregnancy and major congenital anomalies (MCAs), stillbirth, low birth weight and mode of delivery Methods: All women aged 15-49 years, with pregnancies ending in live or stillbirth, were identified from The Health Improvement Network (THIN) primary care database (2000-2009). Medical Read codes related to smoking status and Multilex smoking cessation drug prescription codes were used to extract data on women’s smoking status and NRT prescriptions. The proportion of pregnancies with a smoking status record was calculated and logistic regression was used to assess how this varied by women’s characteristics. Women were categorised as being smokers or non-smokers during pregnancy based on the recorded Read codes. Where smoking data were missing during pregnancy, smoking status recorded before pregnancy (up to 27 months before pregnancy, ever before pregnancy) was used as a proxy for smoking status during pregnancy. Annual smoking measures from THIN were then compared to other national datasets. Pregnancies ending in early fetal losses were not included for calculating smoking prevalence, as these outcomes can go unrecognised or can be the first recognised sign of pregnancy, making early ascertainment of all pregnancies uncomprehensive; this was also broadly in line with pregnancy ascertainment in the other national datasets. Prescribing prevalence of NRT and patterns of prescribing in terms of frequency, timing and different form of NRT were assessed. Logistic regression was used to assess women’s likelihood of receiving NRT prescriptions by maternal characteristics. Absolute and relative risks (99% Confidence Interval (CI)) for four birth outcomes (MCAs, stillbirth, low birth weight and mode of delivery) were calculated for women prescribed NRT (defined as the NRT group) and women who continued to smoke during pregnancy (defined as smokers) compared to women who did not smoke during pregnancy (defined as non-smokers) with appropriate adjustments for potential confounders. To assess MCAs and birth weight in relation to NRT and smoking a restricted cohort of children was used who had maternal-child linked records in THIN. Results: There were 277,552 pregnancies in 215,703 women, of which 28% had a gestational smoking status record. In 2000, smoking status was recorded in 9% of pregnancies; 43% in 2009. Smoking estimates from THIN data did not completely agree with estimates from other sources. For example, in 2009 smoking prevalence was 12.9% in THIN, compared to 19.5% in Child Health Systems Programme (CHSP) data. However, the use of smoking data recorded up to 27 months before conception increased the THIN prevalence to 22.9%, which was slightly higher, but compared better with the CHSP estimates. NRT was prescribed in 4,826 pregnancies for an average duration of 2 weeks (Interquartile range 1-2 weeks), which represented 2% of all pregnancies (11% in smokers). NRT prescribing prevalence before and after pregnancy was half the prevalence during pregnancy. NRT prescribing increased with socioeconomic deprivation (Odds Ratio (OR) =1.33, 95% CI 1.14-1.52) for the most compared to the least deprived group). Prescribing was higher in pregnant smokers with asthma (OR=1.34, 95% CI 1.21-1.50) and mental illness (OR=1.29, 95% CI 1.18-1.43) compared to smokers without these diagnoses. The absolute risk of MCA was 279/10,000 live births. Compared with non-smokers the adjusted OR for MCA in the NRT group was 1.34 (99% CI 0.94-1.91). No statistically significant increase in the risk of MCA for the NRT group was found when the reference group was changed to smokers (OR=1.35, 99% CI 0.94-1.93).The absolute risk of stillbirth was 4/1000 live and stillbirths. Compared with non-smokers the adjusted OR for stillbirth in the NRT group was 1.19 (99% CI 0.47-3.01). In smokers, the risk of stillbirth increased by 27% compared to non-smokers (OR 1.27, 99% CI 1.01-1.60). The mean birth weight was 3.41kg (standard deviation 0.59) and the absolute risk of low birth weight was 6.4%. Compared to non-smokers, the risk of women having low birth weight babies was 93% higher in the NRT group (OR 1.93, 99% CI 1.48-2.53). However, there was no statistically significant increase in the risk of low birth weight in the NRT group compared with smokers. There was no increased risk of assisted delivery or caesarean section in the NRT group compared to smokers. However the risk of assisted delivery decreased by 25% in the NRT group (Relative Risk Ratio 0.75, 99% CI 0.60-0.93) compared to non-smokers. Conclusion: The completeness of smoking status recording during pregnancy in primary care data is improving; however, under-recording of smoking status during pregnancy still results in unreliable estimates of the prevalence of smoking in pregnancy and needs improvement. Pre-conception smoking records are reasonably complete and it is possible that low recording in pregnancy is because a woman’s smoking status has not changed or that increased interaction with other health services, such as midwifery, during pregnancy means women are less likely to be asked about their smoking by their primary physician and information on their smoking does not get relayed back to their primary care record. Nevertheless records should be updated in pregnancy to ensure comprehensive health care. NRT was most commonly prescribed in pregnancy for about two weeks, which may not be adequate time for effective smoking cessation. Nevertheless, prescribing was higher during pregnancy compared to the nine months before and after pregnancy, which makes establishing its safety during pregnancy even more crucial. The safety studies in this thesis did not find NRT to be any more harmful than smoking during pregnancy if not beneficial. Considering that smoking in pregnancy remains one of the largest public health problems in the UK, improvements of antenatal and postnatal smoking in primary care may not only help identify women for preventive measures earlier but would be invaluable for safety studies considering the outcomes are rare yet severe

The safety of influenza vaccination in pregnancy: Examining major congenital malformations as potential adverse outcomes using UK electronic health records

The aim of this thesis was to examine the safety of maternal influenza vaccination with respect to major congenital malformations in live-born infants. UK electronic health records from the Clinical Practice Research Datalink were used and work was conducted using linked primary care, hospitalisation and mortality data. The first study systematically reviewed existing methods for identifying congenital malformations in UK electronic health records, and the results of any validation studies. Studies relied on stand-alone primary care or hospitalisation data to identify congenital malformations; none examined linkage between these. Overall, congenital malformations recorded in primary care data had a high positive predictive value (80-100%) but the validity in hospitalisation data was not explored. Methods from these studies informed the development of a comprehensive algorithm to identify major malformations in live-born infants. Using linked primary care, hospitalisation and mortality data, the second study in this thesis demonstrated that just 20% (95% CI, 19-21) of infants with a major malformation had evidence of their condition in both primary care and hospitalisation data. Almost 65% (95% CI, 64-66) only had evidence in hospitalisation data. The third study demonstrated that the overall prevalence of major malformations established in primary care data using this algorithm was slightly higher than published estimates from other studies using UK primary care records (Prevalence ratio, 1.2; 95% CI, 1.2-1.3). Comparisons of linked data with population-based registry data demonstrated a four-fold higher prevalence for major malformations overall in the linked electronic health records (Prevalence ratio, 4.3; 95% CI, 4.1-4.5). This was primarily driven by the high prevalence of some of these conditions in hospitalisation data, which could potentially be explained by nonspecific codes used to record certain malformations that could have related to either major or minor conditions. 5 The fourth study examined the association between the trivalent seasonal inactivated influenza vaccine and major malformations. Among 78,150 live-birth pregnancies, 6,872 (8.8%) were vaccinated in the first trimester whilst 46,669 (59.7%) were unvaccinated throughout pregnancy. There was no evidence to suggest an association between first-trimester vaccination and major malformations recorded in first year of infant life in models adjusted for confounding (HR, 1.06; 99% CI, 0.94-1.19; p=0.23). The fifth study, which examined the safety of the monovalent pandemic inactivated influenza vaccine, showed similar results (HR, 1.02; 99% CI, 0.72-1.46; p=0.86). However, although these vaccine safety studies did not find evidence for an association between vaccination and major malformations, terminations due to foetal anomaly were not included. Therefore, the possibility of an increased risk of the specific subtypes of major malformations typically detected during antenatal scans and subsequently terminated could not be discounted. These results provide additional evidence on the safety of maternal influenza vaccination but highlight the need for further explorations of major malformations among pregnancies that do not result in live-births. The component of this work relating to the methods used to identify major malformations highlights the potential to increase ascertainment through the use of linked data whilst underscoring the need for further studies, particularly in hospitalisation data, to establish the validity of codes used to record these conditions