4-year PhD Studentship: In utero exposure to SARS-CoV-2 and adverse health outcomes amongst infants: enriching and utilizing a national, linked electronic health record resource

Since the onset of the COVID-19 pandemic, over 200 million infants have been born worldwide, of which a significant proportion will have been exposed to maternal SARS-CoV-2 infection in utero. Although vertical transmission of SARS-CoV-2 from mothers to babies is rare, and babies infected generally have positive health outcomes(1), little is known about the medium- to long-term effects of intrauterine exposure. A growing body of literature has shown exposure to SARS-CoV-2 infection in utero increases the risk of preterm delivery and stillbirth(2, 3), fetal growth restriction(4, 5) and placenta pathology(6). However, studies to date have been small, where rare outcomes cannot be examined. This project will use national, electronic health data to investigate the relationship between intrauterine SARS-CoV-2 exposure and infant outcomes, building on ongoing work led by the supervisors.

Key to investigating intrauterine effects (of maternal origin) on infant health using electronic health data is the ability to reliably link maternal to offspring records. This PhD will optimize probabilistic linkage methods currently used to establish family relationships in the English data, by developing models and comparing outputs with deterministic methods in the Welsh SAIL data resource, which benefits from gold-standard mother-infant identifiers.

Aims and Objectives

Aim: To investigate intrauterine exposure to maternal SARS-COV-2 infection and risk of adverse health events among infants in their first year of life.

Objectives:

1. Develop and evaluate methods for linking maternal and offspring electronic health records using data from two national electronic health resources
2. Describe health outcomes among infants exposed to maternal SARS-CoV-2 infection in utero, compared to those who were not
3. Investigate the effects of intrauterine exposure to SARS-CoV-2 infection on infant outcomes
4. Examine the mediating effect of preterm birth on the relationships in 3.

Methodology

The project will use linked electronic health records (EHR) of all English residents made available through the NHS Digital Trusted Research Environment (TRE).

1. A mother-baby linkage key is under development using probabilistic linkage methods in the English NHS Digital TRE, as a unique identifier is unavailable. SAIL, a Welsh linked EHR data resource, has a mother-baby unique key. A probabilistic linkage model will be developed, and compared to a gold standard, deterministic model, which will use the mother-baby identifier, in SAIL. Once developed, the probabilistic linkage model will be implemented in the English TRE.
2. In the English data, a hypothesis generating analysis will be conducted exploring health outcomes of infants born to mothers diagnosed with SARS-CoV-2 infection during pregnancy, compared to those who did not.
3. A causal analysis will be conducted investigating the effects between in utero exposure to SARS-CoV-2 and infant outcomes. Directed acyclic graphs will be used to identify confounders, and effect modifiers will be considered, and advanced statistical methods applied to test and estimate the hypothesized causal effects.
4. Mediation analysis will be performed to assess whether the association between intrauterine exposure to SARS-CoV-2 and infant outcomes is wholly or partially mediated by preterm birth.

Keywords

COVID-19, pregnancy, electronic health records, in utero exposure, infants, data linkage, methods development, health data science

How to apply for this project

This project will be based in Bristol Medical School - Population Health Sciences in the Faculty of Health Sciences at the University of Bristol.

Please visit the Faculty of Health Sciences website for details of how to apply