Obstetric outcome and cytokine levels in threatened miscarriage

Abstract

Objectives. To evaluate the proportion of women with threatened miscarriage (TM) who proceed to miscarriage in a population of single ethnicity and to investigate prospectively their risk of adverse pregnancy outcome in relationship with the cytokines levels in their circulation.

Methods. We conducted a prospective observational study over a period of 1 year of 94 Maltese women presenting with TM at the same hospital and compared their clinical data with those of 564 age-matched controls from the National Obstetric Information System (NOIS) of Malta. Main outcome measures included gestational age and weight at delivery and incidence of adverse pregnancy outcomes. A pilot study was carried out, where in subgroups of 10 women with TM (n = 10), non-pregnant women (n = 12), normal pregnant controls (n = 9) and women presenting with missed-miscarriage (n = 11), the plasma levels of β-human chorionic gonadotrophin (β-hCG), tumour necrosis factor α (TNFα), interferon γ (IFNγ), interleukin-6 (IL-6), interleukin-10 (IL-10) and TNF-receptors 1 (R1) and 2 (R2) were measured.

Results. Of the women presenting with TM, 25 (26.6%) proceeded to complete miscarriage. The TM group had also a significantly higher incidence of antepartum haemorrhage (p < 0.005), pre-eclampsia (p < 0.05), foetal growth restriction (p < 0.05), premature labour (p < 0.001) and retained placenta (p < 0.005). In the pilot biochemical analysis, significantly (p < 0.05) higher levels of TNFα and lower levels of TNFR2 were found in the TM subgroup compared to non-pregnant controls. The ratio TNFα/IL-10 was significantly (p < 0.05) higher and the β-hCG levels was significantly lower (p < 0.01) in missed-miscarriage and non-pregnant subgroups than in TM and normal pregnant controls. The IFNγ/1L-10 and IFNγ/1L-6 ratio were significantly (<0.001) different between the four subgroups with the lowest level found in TM. No similar gradient was found for the TNFα/1L-6 ratio.

Conclusion. Women presenting with TM are at significantly increased risk of adverse pregnancy outcome and the pathophysiology of these conditions involves a change in the Th1/Th2 balance. Changes in levels of cytokines could help to predict and thus prevent the development of some of these complications.

Keywords:

• Threatened miscarriage
• pregnancy outcome
• tumour necrosis factor alpha
• TNF-receptor 1
• TNF-receptor 2

Acknowledgements

We thank Dr. Miriam Gatt, manager of the National Obstetric Information System at the Department of Health Information at St. Luke's Hospital, Malta, for granting us permission to use this data for publication. We also thank Dr. Christopher Barbara, Head of Pathology for his collaboration in sample processing.