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Title: Influence of maternal growth on placental growth, development and function in teenage pregancies
Author: Hayward, Christina Elizabeth
ISNI:       0000 0004 2685 0521
Awarding Body: The University of Manchester
Current Institution: University of Manchester
Date of Award: 2010
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The UK has the highest incidence of teenage pregnancy in Western Europe, accounting for -7% of all births in England and Wales. Teenagers are more susceptible than adults to delivering small for gestational age (SGA) and growth restricted infants. These infants are at an increased risk of perinatal morbidity and mortality, and chronic health problems in later life. The reasons for teenagers' susceptibility to reduced fetal growth are unknown. Previous studies implicate continued maternal growth as a potential risk factor. In support of this, growing adolescent sheep deliver growth restricted fetuses due to impaired placental growth and nutrient transfer to the fetus. However, a recent prospective observational study (the About Teenage Eating Study; ATE) of 500 pregnant teenagers in the UK demonstrated that maternal growth was not detrimental to fetal growth. One third of teenagers continued to grow during pregnancy and these teenagers delivered fewer SGA (13.1 % vs. 19.5%) and more large for gestational age (10.7% vs. 4.1 %) infants than nongrowing teenagers. The birthweight profile of infants delivered to growing teenagers resembles that in a normal adult population suggesting they can overcome the inherent susceptibility for SGA birth related to young maternal age. My PhD investigated potential placental mechanisms linking maternal and fetal growth, and tested the hypothesis that differences in pregnancy outcome between growing and non-growing teenagers were associated with alterations in placental growth, development and/or function. Placentas were collected from a subset of teenagers recruited to the ATE study. The impact of maternal growth was examined on placental villous morphometry and cell turnover; expression and activity of the amino acid transporter, system A; and maternal- and placental-derived growth factors. The aim was to explore the link between maternal growth factors and placental system A activity. Maternal growth had no major effects on placental weight, morphometry or cell turnover, and thus could not explain the difference in infant birthweight between growing and non-growing teenagers. However, growing teenagers, had higher birthweightplacental weight ratios than non-growing teenagers, suggesting that they have placentas which are more efficient. To determine whether this was due to increased nutrient transport, placental system A activity was assessed. Placental system A activity was lower in teenagers than adults, when comparing those who delivered infants that were appropriately grown for gestational age (AGA). This was consistent with reduced placental mRNA expression of system A transporters, slc38a 1, 2 and 4, in AGA infants delivered to teenagers compared with adults and indicated that placental system A transport, was inherently reduced in teenagers. In contrast, placental system A activity was higher in growing compared to non-growing teenagers, and was equivalent to the levels measured in adults. This could not be explained by changes in mRNA expression of the slc38a genes, indicating up-regulation of system A in growing teenagers at the level of activity. This suggests that growing teenagers were able to overcome inherently reduced placental system A activity. To explore the potential mechanisms, maternal plasma concentrations of insulin-like growth factor (IGF)-I, previously shown to stimulate of system A activity, were compared between growing and non-growing teenagers. Higher concentrations of IGF-I were detected in growing teenagers. However, short term application of IGF-I did not stimulate system A activity in placental villous fragments in vitro. Recent studies suggest that maternal growth is beneficial, rather than detrimental, to fetal growth, and that non-growing teenagers are more susceptible to SGA births. The current study provides evidence of inherently reduced placental nutrient transfer in teenagers, which may contribute to teenagers' susceptibility to SGA births. However, growing teenagers appear able to overcome this susceptibility with increased placental nutrient transport, which may be the result of a maternal hormonal milieu that is conducive to fetal growth. These studies indicate maternal growth primarily impacts placental nutrient transport rather than development. Further studies are required to delineate the underlying mechanisms and identify potential therapeutic strategies to improve pregnancy outcome in the teenage population.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available