Abstract
The aims of this thesis are firstly, to establish reference ranges of serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and free thryroxin (FT4) at 11-13 weeks’ gestation in singleton and twin pregnancies and to examine the effect of maternal characteristics and serum antithyroid antibodies and free ß-hCG on the levels of TSH, FT3 and FT4, and secondly to investigate the possible association between maternal thyroid dysfunction in pregnancies complicated by fetal death, preeclampsia (PE), delivery of small for gestational age (SGA) neonates, preterm delivery and fetal aneuploidies.The study population was derived from a prospective screening study for adverse obstetric outcomes in 4,852 women attending for their routine first hospital visit in pregnancy at 11+0-13+6 weeks’ gestation. In some of the pregnancy complication groups, we identified additional cases that were examined after screening period. Serum concentrations of FT3, FT4, TSH, anti-TPO and anti-Tg were measured by immunoassay using direct, chemiluminometric technology.
In normal pregnancy (n=4318), TSH increased whereas FT3 and FT4 decreased with gestation and all three were lower in Afro-Caribbean than in Caucasian women. Serum FT3 and FT4 decreased, but TSH did not change significantly with maternal age, TSH and FT3 increased whereas FT4 decreased with body mass index, TSH decreased whereas FT3 and FT4 increased with serum free ß-hCG. In the antibody positive group, compared to the negative group, median TSH was higher and median FT3 and FT4 were lower.
In 45% of women with known hypothyroidism (n=164) diagnosed before pregnancy and receiving levothyroxine at least one of the three biochemical tests was suggestive of persistent hypothyroidism. In pregnancies resulting in miscarriage or fetal death (n=202), the median serum TSH was increased and FT4 was decreased. In pregnancies that developed PE (n=102), there was evidence of hypothyroidism and increased serum TSH was observed in 5 times as many cases with PE compared with those who did not develop PE. In pregnancies delivering SGA neonates (n=212) and in those ending in spontaneous early preterm delivery (n=102) maternal thyroid function was not significantly different from pregnancies with normal outcome. In pregnancies with fetal trisomy 21 (n=30) free ß-hCG was increased and TSH was decreased and in cases with trisomy 18 (n=25) free ß-hCG was decreased and TSH was increased. In normal twin pregnancies (n=235), compared to singletons, serum FT4 was not significantly different but TSH was about 40% lower. The levels of serum TSH and FT4 were similar in dichorionic and monochorionic twins, with or without twin-to-twin transfusion syndrome (n=19) and there were no significant differences between the three groups in serum free ß-hCG.
The thesis established reference ranges of maternal thyroid function in early pregnancy and demonstrated altered function in association with certain pregnancy complications.
| Date of Award | 2013 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Kypros Nicolaides (Supervisor) & Anne Greenough (Supervisor) |