Pregnancy and children’s development (PRECEDE): how maternal inflammation in pregnancy affects child outcomes

Abstract

The main research question of this thesis is to examine how maternal inflammatory processes during pregnancy possibly affect a child’s development in domains of cognition, behaviour, and general school readiness. It starts with providing relevant background and basis of Barker’s hypothesis on the developmental origins of health and disease (DoHAD), which postulates effects on fetal and child development if the intrauterine environment is disrupted or compromised during pregnancy. It aims to narrow the gap between animal models and limited human studies through associating maternal inflammation in pregnancy with child outcomes. The predominant focus is using cohorts to examine how gestational biology processes such as infections or maternal metabolic markers are associated with child standardised developmental, cognitive, or socioemotional measures. This thesis also adopts different approaches towards how mother-child outcomes can possibly be affected by other factors, such as analysis of cord blood mediators to further understand mother-child associations during the perinatal period, or synthesis of high-quality evidence on how analgesic drug use during pregnancy affects child neurodevelopment. Overall conclusions will be drawn from quantitative models, seeking to provide careful evaluation and a translational review of previous and current empirical studies.

The first empirical chapter, Chapter 2 uses the Avon Longitudinal Study of Parents and Children (ALSPAC) United Kingdom cohort (N= 7,410 mother-child pairs with condition of infections present during pregnancy) to examine associations between maternal prenatal infections occurring in specific pregnancy trimesters and a child’s cognitive outcomes at three timepoints (18 months, 4 years, 8 years) using developmental and intelligence quotient scores. Regression analyses were run, adjusting for maternal and socioeconomic covariates. Results suggest associations between infections occurring at the third pregnancy trimester with verbal IQ at 4 years old, and verbal and performance IQ at 8 years old, however the magnitude of effect appears to be small.

Chapter 3 uses the Avon Longitudinal Study of Parents and Children (ALSPAC) United Kingdom cohort (N=15,133 mother-child pairs) to examine associations between maternal metabolic markers and child socio-emotional outcomes over time (4 to 16 years old; 7 timepoints). Growth curve models were fit, adjusting for maternal, child, and environmental covariates. Results showed specific maternal metabolic markers of fasting glucose, HDL, BMI, and triglycerides having differential effects on developmental trajectories of conduct and hyperactivity problems from 4 to 16 years old. Adjusted models also suggest maternal metabolic markers possibly having trimester-specific effects on child development.

Chapter 4 uses the Born in Bradford (BiB) United Kingdom cohort (N=10,600 mother-child pairs) to examine associations between maternal metabolic syndrome classification and child development outcomes at age 5, using child cord blood markers as potential mediators. Maternal markers in pregnancy were classified into metabolic syndrome risk, while child cord blood markers were individually measured. Child development outcomes were taken from a national development framework that assesses domains of school readiness. Mediation models were adjusted for maternal, child, and socioeconomic covariates. Mediation results showed no significant effects when looking at individual cord blood markers, however, they suggested significant combined effects of cord blood markers mediating the association between maternal cardiometabolic health and some child outcomes.

Chapter 5 consists of a protocol paper and an umbrella review to synthesise evidence on how maternal drug use during pregnancy is linked with child development outcomes. The review examined high-quality evidence on analgesic drug exposure and attention-deficit hyperactivity disorder (ADHD) risk in children. Findings showed significant associations between maternal prenatal acetaminophen (paracetamol) use and ADHD outcomes, with a potential dose-dependent relationship. This review method provides a different perspective on exploring how interventions that are applied to seek to improve a mother’s health may subsequently affect a child’s neurodevelopment.

Overall, this thesis uses several different methodologies to combine current literature with empirical data analyses to examine how maternal health affects child outcomes. The discussion chapter of this thesis expands on limitations and future directions, with emphasis on translating results into implications for clinical and educational providers.