Maternal fatty acid profiles in term and preterm pregnancies
File(s)
Author(s)
Sassine, Annie Belle
Type
Thesis
Abstract
Introduction: Preterm birth (PTB) is the leading cause of under-five mortality and a risk factor for neurodevelopmental disorders and lifelong morbidity. Maternal deficiency in omega-6 and omega-3 long-chain polyunsaturated fatty acids (LCPUFA) during pregnancy has been linked to PTB. The overall aims of this thesis were to assess the fatty acid (FA) profile during pregnancy in the maternal/cord bloods and placental tissues and, to explore the transport of FAs across the placentae of term and preterm pregnancies.
Methodology: Fatty acid analysis of erythrocyte, plasma, and placental tissues was carried out using the method of Folch et al and mRNA levels of fatty acid transporters were measured using qPCR.
Results: Study 1 results showed that preterm placentae had 15% lower omega-3 docosahexaenoic acid (DHA) proportions and 25% higher palmitoleic acid proportions but the remainder of FAs were similar. The preterm placentae exhibited 2 and 3-folds lower mRNA levels for major membrane FA transporters, particularly FAT/CD36 and FATP-4. Among the different causes of preterm birth, placenta from twin pregnancies exhibited the most variant fatty acid composition, in comparison to preterm and term non-labouring placenta. This stipulates the possibility that in twin pregnancies, maternal drain of essential FA may alter fatty acid composition of the placenta.
In the second study, results showed strong correlations between FAs in maternal blood, cord blood and matched placental tissue of non-labouring women. Data also demonstrated a clear biomagnification process, characterised by a preferential transfer of saturated FAs, arachidonic acid and DHA to the fetus. In contrast, oleic acid (OA) and eicosenoic acid were returned to the mother. Results demonstrated that red cell FA composition contained 23 times more adrenic acid, 14 times more lignoceric acid, and 7 times more nervonic acid to that of plasma, indicating that the body prepares in advance to meet the needs of myelination in the first 2 years of life.
Results from the third study showed that the FA profile of women presenting with threatened preterm labour who went into preterm delivery had slightly lower erythrocyte OA proportions (10.6%) in comparison to gestation-matched controls (11.4%). It is hypothesised that in these women, there is a larger placental transfer of OA and MUFAs to the fetus to compensate for the lack of available essential LCPUFAs, which are the prime substrates for fetal growth and development.
To confirm the above, I successfully gained regulatory approvals and launched an on-going longitudinal study of 1,000 pregnant women to study gestational changes in the FA profile in relation to inflammation and preterm birth from booking to delivery.
Conclusions: This thesis strengthens the evidence that maternal fatty acid profiles differ in preterm pregnancies and sheds light on an unknown directive physiology orchestrating the handling and transfer of specific fats to meet fetal demands for growth and brain development.
Methodology: Fatty acid analysis of erythrocyte, plasma, and placental tissues was carried out using the method of Folch et al and mRNA levels of fatty acid transporters were measured using qPCR.
Results: Study 1 results showed that preterm placentae had 15% lower omega-3 docosahexaenoic acid (DHA) proportions and 25% higher palmitoleic acid proportions but the remainder of FAs were similar. The preterm placentae exhibited 2 and 3-folds lower mRNA levels for major membrane FA transporters, particularly FAT/CD36 and FATP-4. Among the different causes of preterm birth, placenta from twin pregnancies exhibited the most variant fatty acid composition, in comparison to preterm and term non-labouring placenta. This stipulates the possibility that in twin pregnancies, maternal drain of essential FA may alter fatty acid composition of the placenta.
In the second study, results showed strong correlations between FAs in maternal blood, cord blood and matched placental tissue of non-labouring women. Data also demonstrated a clear biomagnification process, characterised by a preferential transfer of saturated FAs, arachidonic acid and DHA to the fetus. In contrast, oleic acid (OA) and eicosenoic acid were returned to the mother. Results demonstrated that red cell FA composition contained 23 times more adrenic acid, 14 times more lignoceric acid, and 7 times more nervonic acid to that of plasma, indicating that the body prepares in advance to meet the needs of myelination in the first 2 years of life.
Results from the third study showed that the FA profile of women presenting with threatened preterm labour who went into preterm delivery had slightly lower erythrocyte OA proportions (10.6%) in comparison to gestation-matched controls (11.4%). It is hypothesised that in these women, there is a larger placental transfer of OA and MUFAs to the fetus to compensate for the lack of available essential LCPUFAs, which are the prime substrates for fetal growth and development.
To confirm the above, I successfully gained regulatory approvals and launched an on-going longitudinal study of 1,000 pregnant women to study gestational changes in the FA profile in relation to inflammation and preterm birth from booking to delivery.
Conclusions: This thesis strengthens the evidence that maternal fatty acid profiles differ in preterm pregnancies and sheds light on an unknown directive physiology orchestrating the handling and transfer of specific fats to meet fetal demands for growth and brain development.
Version
Open Access
Date Issued
2019-09
Date Awarded
2020-03
Copyright Statement
Creative Commons Attribution NonCommercial Licence
Advisor
Johnson, Mark
Crawford, Michael
Sponsor
The Little Foundation
Publisher Department
Department of Surgery and Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)