Maternal characteristics and outcomes affected by hypothyroidism during pregnancy (maternal hypothyroidism on pregnancy outcomes, MHPO-1).

BACKGROUND: Hypothyroidism in pregnancy is an arena of ongoing research, with international conflicts regarding screening, management, and outcomes. Various studies have described the outcomes depending on geographical and international diagnostic criteria. No study has been conducted in this regard from the region of Pakistan. Therefore, we aim to report the clinical features and maternal outcomes of hypothyroid pregnancies and compare the maternal outcomes between uncontrolled and controlled TSH levels in the preconception as well as the gestational period. METHODS: We conducted a cross-sectional retrospective study on 718 cases in the Aga Khan University Hospital after ethical approval. We collected information on pregnant females who have diagnosed hypothyroidism before conception or during their antenatal period. We noted the maternal characteristics and maternal comorbidities. Laboratory data were recorded for thyroid stimulating hormone levels before conception and during gestation. We recorded maternal outcomes as pregnancy loss (including miscarriage, stillbirth/intrauterine death, medical termination of pregnancy and ectopic pregnancy), gestational hypertension, pre-eclampsia, postpartum hemorrhage, placental abruption, and modalities of delivery. Data analysis was performed on Statistical Package for the Social Sciences version 20.0. RESULTS: Among 708 hypothyroid women 638 had live births. Postpartum hemorrhage was the most frequent maternal outcome (38.8%). The emergency cesarean section occurred in 23.4% of cases. We determined TSH levels in 53.2, 56.7, 61.7 and 66.6% of cases in preconception, 1st, 2nd, and 3rd trimester periods. A significant association existed between cesarean section and preconception thyrotropin levels > 2.5 mIU/L, whereas postpartum hemorrhage was significantly associated with thyrotropin levels > 2.5 mIU/L in the preconception and third trimester. CONCLUSION: Successful live births in our patients were complicated by maternal postpartum hemorrhage and a frequent number of emergency cesarean section.

Frequent hypomethylation of PTGS2 gene promoter in human term placenta.

BACKGROUND: Gene expression profiles of several tumor suppressor genes are regulated by the methylation and demethylation of their promoters. Here, we aim to identify and quantify the methylation status of four tumor suppressor genes from placentas at term and compare them with the maternal white-blood-cells. METHODS: In order to achieve this objective, DNA enriched from twenty placentas at term and maternal white blood cells was bisulfite-converted and amplified using quantitative real-time methyl-light polymerase chain reaction for the four-genes studied (RASSF1A, APC, RAR-beta, and PTGS2). RESULTS: Among the four genes examined, RASSF1A, APC and RAR-beta promoter regions were hypermethylated in all the placental samples compared with maternal WBCs. Strikingly, PTGS2 was found to be hypomethylated in the placentas compared to the maternal cells. CONCLUSION: Since placental DNA represents fetal methylation profile and it is an established fact that there is certain amount of cell free circulating DNA in human plasma/serum, these data strongly suggest that hypermethylation of RASSF1A, APC and RAR-beta can be used as gender independent biomarkers to distinctly identify placental DNA in maternal blood. In addition, this is the first report which demonstrates hypomethylation of PTGS2 locus which may have important clinical implications e.g. placental abnormalities.