Jennifer Campbell

Purpose: Maternal exposures before, during and after pregnancy can affect the infant. It is therefore important that researchers study mothers and their children.The CPRD GOLD Mother–Baby Link (MBL) algorithm was applied to the CPRD Aurum database, to extend the useful tool. Here, we present the algorithm and data resource profiles of the CPRD MBLs.Methods: Records of female patients registered with a CPRD practice between the 1st January 1987 and the 1st June 2023 were searched for evidence of delivery. Infants born and registered between 1st January 1987 and 1st June 2023 were matched to mothers on practice and household indicators. The resulting MBLs were characterised.Results: The CPRD MBL algorithm was applied to the CPRD databases resulting in nearly four‐million mother–baby pairs: 2.4‐million in CPRD Aurum. Mothers in the CPRD GOLD and CPRD Aurum MBL's were similar in terms of age; mean age 29.6 years (SD = 5.7) vs. 30.2 years (SD = 5.7), and length of GP registration; mean = 14.4 years (SD = 10.9) vs. mean = 13.7 (SD = 10.9). The median number of matches was slightly higher in the CPRD GOLD MBL; 2 (IQR = 1, 2) vs. 1 (IQR = 1, 2). The number of matches in both databases peaked in 2008–2011, followed by a steady decline to 2023.Conclusion: The CPRD MBL's offer a valuable tool for researchers to study the mother–infant relationship. Extending the CPRD MBL algorithm to CPRD Aurum has increased the capacity for researchers to investigate rarer exposures and outcomes.

Letter to the Editor Pharmacoepidemiology and Drug SafetyAuthors: Christopher Lee1, Silvia Rizzi 1, Ana Luiza Bierrenbach1, Luis Antunes1, Niina-Maria Nissinen1, Olga Rocha1, Jennifer Campbell2, Caroline Minassian3, Susan Hodgson2, Anne Broe1

Purpose: Real‐world data represents a valuable tool for pregnancy research. However, an algorithmic approach is needed to ascertain pregnancy timings from this complex data. The Clinical Practice Research Datalink (CPRD) GOLD Pregnancy Register, based on UK Primary care data, has therefore proven to be a valuable research tool. The same algorithmic approach was applied to the CPRD Aurum data to generate an equivalent register in the larger database.Methods: Records of female patients registered with a CPRD Aurum contributing practice between the 1st of January 1987 and the 30th of April 2021 were searched for evidence of pregnancy. The algorithm used to generate the CPRD GOLD Pregnancy Register was redeveloped and applied first to CPRD GOLD and then to CPRD Aurum. The resulting CPRD Aurum Pregnancy Register was validated against the CPRD GOLD register, linked Hospital Episode Statistics (HES) and the Office of National Statistics (ONS) live birth data.Results: There are 16 833 427 pregnancy episodes in the CPRD Aurum Pregnancy Register from 6 724 615 women, more than double the number in CPRD GOLD. The distribution of pregnancy outcome types was comparable between the registers. Across the whole register, there was good concordance between pregnancy episodes found in CPRD Aurum and linked HES. However, both CPRD registers saw a declining number of pregnancy episodes from 2007 onwards, steeper than in HES or the ONS birth data.Conclusions: A pregnancy register has been created in CPRD Aurum. Changes in antenatal care policies in the UK have led to declining numbers of pregnancies in EHR primary care data. However, the creation of this pregnancy register has tripled the number of patients in the CPRD Pregnancy Registers and will increase the capacity to study pregnancy in CPRD data, particularly rare or emerging exposures, and outcomes.

Introduction The COVID-19 pandemic has led to concerns about potential adverse pregnancy outcomes associated with infection, resulting in intensive research. Numerous studies have attempted to examine whether COVID-19 is associated with an increased risk of pregnancy loss. However, studies and reviews to date have drawn differing conclusions. The aim of this systematic review is to provide a summary of all quantitative research on the relationship between pregnancy loss and COVID-19 infection and, if appropriate, to synthesise the evidence into an overall effect estimate. Methods and analysis Three publication databases (Embase, PubMed and Cochrane) and four preprint databases (medRxiv, Lancet Preprint, Gates Open Research and Wellcome Open Research) will be searched. Boolean logic will be used to combine terms associated with pregnancy loss and COVID-19. The population of interest are pregnant women. Retrieved results will be assessed in two phases: (1) abstract screening and (2) full text evaluation. All studies which compare pregnancy loss outcomes in women who had COVID-19 versus those who did not quantitatively will be included. Narrative and non-English studies will be excluded. Two reviewers will screen independently, with results compared and discrepancies resolved by the study team. Study quality and risk of bias will be assessed using a quality appraisal tool. Results will be summarised descriptively and where possible synthesised in a meta-analysis. Ethics and dissemination This systematic review requires no ethical approval. This review will be published in a peer-reviewed journal and provide an important update in a rapidly evolving field of research. PROSPERO registration number CRD42022327437.

Objectives To investigate why episodes of pregnancy identified from electronic health records may be incomplete or conflicting (overlapping), and provide guidance on how to handle them. Setting Pregnancy Register generated from the Clinical Practice Research Datalink (CPRD) GOLD UK primary care database. Participants Female patients with at least one pregnancy episode in the Register (01 January 1937−31 December 2017) which had no recorded outcome or conflicted with another episode. Design We identified multiple scenarios potentially explaining why uncertain episodes occur. Criteria were established and systematically applied to determine whether episodes had evidence of each scenario. Linked Hospital Episode Statistics were used to identify pregnancy events not captured in primary care. Results Of 5.8 million pregnancy episodes in the Register, 932 604 (16%) had no recorded outcome, and 478 341 (8.5%) conflicted with another episode (251 026 distinct conflicting pairs of episodes among 210 593 women). 826 146 (89%) of the episodes without outcome recorded in primary care and 215 577 (86%) of the conflicting pairs were consistent with one or more of our proposed scenarios. For 689 737 (74%) episodes with recorded outcome missing and 215 544 (86%) of the conflicting pairs (at least one episode), supportive evidence (eg, antenatal records, linked hospital records) suggested they were true and current pregnancies. Furthermore, 516 818 (55 %) and 160 936 (64%), respectively, were during research quality follow-up time. For a sizeable proportion of uncertain episode, there is evidence to suggest that historical outcomes being recorded by the general practitioner during an ongoing pregnancy may offer explanation (73 208 (29.2%) and 349 874 (37.5%)). Conclusions This work provides insight to users of the CPRD Pregnancy Register on why uncertain pregnancy episodes exist and indicates that most of these episodes are likely to be real pregnancies. Guidance is given to help researchers consider whether to include/exclude uncertain pregnancies from their studies, and how to tailor approaches to minimise underestimation and bias.

Background Rare monogenic disorders in children and babies are difficult to diagnose, however establishing the diagnosis plays an important role in informing patient management and influencing clinical decision-making. On 1st October 2019, the National Rapid Exome Sequencing Service for acutely unwell children with a likely monogenic disorder (R14) was introduced across NHS England, via the National Genomic Test Directory. All Neonatal Intensive Care Units (NICUs) in England have access to the national R14 service. Informed consent for this test is essential, as the results may give uncertain or unexpected information, including about a child’s biological parents. Rapid trio Whole Exome Sequencing (WES) via R14 has enabled urgent diagnoses to be sought where this may affect the clinical management of the child. Objectives We undertook an audit and service evaluation of the R14 service in our region by reviewing all referrals to Yorkshire Regional Genetics Service (YRGS) over a one-year period since the commencement of the R14 service. Methods We reviewed all R14 referrals from YRGS to the nationally-commissioned Exeter Genomics Lab between 1st October 2019 and 30th September 2020. Our data collection tool enabled a standardised screening of patient notes, electronic patient records and genomic and other test results. Patient demographics, clinical and phenotypic information, and genomic outcome data were collected. Results 46 cases were identified; 18 male (39%), 28 female (61%). The median age of the proband at time of review was 20 days. A heat map demonstrated that most patients who had accessed the service were concentrated in West Yorkshire. At the time of request, 65% (n=30) of patients were on NICU. In 50% (n=23), the neonatal unit requested the test. In 43% (n=20), Clinical Genetics requested the test. In 4% (n=2), the test was requested by neurology, and 2% (n=1) by a High Dependency Unit. Request forms were fully complete in 74% (n=34) of cases. In 46% (n=21) of cases, consent for testing (via a record of discussion form) was not documented. The mean turnaround time from receipt of samples by the Exeter Genomics Lab to issuing of final reports was 12.7 days (range 7–25 days). In 52% (n=24) of cases, a genetic cause for the patient’s presentation was identified. Of these 24 cases, 96% (n=23) resulted in a change in management. The most common change in management was referral to a specialist (52%; n=12). Conclusions The R14 service for acutely unwell children heavily relies on effective collaboration between Neonatal and Clinical Genetics teams, as both teams are involved in the referral process. It is important that we improve our documentation – particularly around consent for testing - and ensure request forms are fully completed before submission. In over half of our cases, a genetic cause for the patient’s presentation was identified; in all but one of these cases, this affected some aspect of patient management. This audit has helped us to identify strategies to ensure equitable access to the R14 service across our region.