Fetal Biometry and Early Behavioural Development
The overall aim of this thesis is to explore the use of standardised fetal biometric measurements and their relationship, if any, with later infant outcomes. In addition, the possible influence of fetal sex and several maternal conditions (polycystic ovary syndrome (PCOS), hirsutism and autism) on fetal growth measurements, are explored. The biometrics include anogenital distance (AGD), several brain measurements (transcerebellar diameter (TCD), ventricular atrium (VA)) and head circumference (HC). AGD was included as a proxy for prenatal sex steroid hormones, given the importance of the latter as an influence of brain development and for a number of autistic traits postnatally. The fetuses were assessed using ultrasound at 12-, 20- and between 26-30 weeks gestation and followed up at 18-20 months’ of age to see if these fetal biometric measurements are associated with later language and sensory development, as well as early autistic traits. Chapter 1 gives an overview of current research on fetal development, as well as the different methodologies used. This includes an introduction to the maternal conditions considered in this thesis and the fetal biometrics (HC, VA, TCD and AGD) that are measured. Chapter 2 explores potential sex differences and the influence that maternal conditions (PCOS, hirsutism and autism) may have on developing fetal brain structure. Results indicate no significant sex differences between fetal brain measurements, or growth velocity. In addition, there was no relationship between maternal conditions and the fetal growth measurements. Chapter 3 explores the feasibility of measuring AGD in utero (as a proxy for prenatal sex steroid hormones). Further, it examines the influence of maternal conditions such as PCOS (which is associated with increased testosterone) on AGD in utero. Significant sex differences in AGD were demonstrated, supporting previous findings. Results showed no relationship between fetal AGD and maternal testosterone related conditions (autism, PCOS and hirsutism). Chapter 4 examines population based differences in fetal biometry and the applicability of findings from Chapter 3 to an Israeli population. Results indicated that there were significant differences in AGD between Israeli and UK populations, potentially attributed to ethnicity. This supports the need for population-based or customisable growth charts if this measure is to be used clinically. Chapter 5 explores the relationship between fetal brain measures and early behavioural development at 18-20 months. The outcome measures include the Quantitative Checklist for Autism in Toddlers (Q-CHAT), the MacArthur-Bates Communicative Development Inventory (MB-CDI) short form and the Infant/Toddler Sensory Profile (ITSP). Results indicated a significant positive relationship between TCD and VA size at 20 weeks and Q-CHAT scores at 18-20 months’ of age, which remained significant for females only when examining sex differences. There were no significant associations between the other fetal brain measurements and the MB-CDI short form, Q-CHAT or the ITSP. Chapter 6 explores the relationship between fetal AGD and early behavioural development at 18-20 months. No significant relationships were found between fetal AGD length and infant development. The results from the thesis are summarised in Chapter 7 where broader theoretical and clinical implications of the findings are discussed. From the results presented in this thesis, it is apparent that one biometric measure (AGD) displays sex-based differences and will require sex-specific growth charts if it is to be used clinically. However further research is warranted to assess the clinical usefulness of AGD as a measurement. Additionally, for the first time a relationship between gross fetal brain structures (TCD and VA) and early autistic traits was measured. In conclusion, this thesis discussed the possible use of novel biometrics (AGD) for research and clinical use. Additionally, the potential for using fetal biometrics to help assess later infant outcomes, in particular autistic traits is presented.
fetal development, autism, fetal brain development, polycystic ovary syndrome, anogenital distance, ultrasound
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