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In Acta obstetricia et gynecologica Scandinavica ; h5-index 38.0

INTRODUCTION : Infection and inflammation have been implicated in the aetiology and subsequent morbidity associated with preterm birth. At present there are no tests to assess for fetal compartment infection. The thymus, a gland integral in the fetal immune system, has been shown to involute in animal models of antenatal infection, but its response in human fetuses has not been studied. This study aims to: 1) generate magnetic resonance imaging (MRI) derived fetal thymus volumes standardized for fetal weight. 2) To compare standardized thymus volumes from fetuses that delivered less than 32 weeks of gestation with fetuses that subsequently deliver at term 3) to assess thymus size as a predictor of preterm birth 4) to correlate the presence of chorioamnionitis and funisitis at delivery with thymic volumes in utero in fetuses that subsequently deliver preterm.

MATERIAL AND METHODS : Women at high-risk of preterm birth at 20-32 weeks of gestation were recruited. A control group was obtained from existing datasets acquired as part of three research studies. A fetal MRI was performed on a 1.5T or 3T MRI scanner: T2 weighted images were obtained of the entire uterine content and specifically the fetal thorax. A slice-to-volume registration method was used for reconstruction of 3D images of the thorax. Thymus segmentations were performed manually. Body volumes were calculated by manual segmentation and thymus:body volume ratios generated. Comparison of groups was performed using multiple regression analysis. Normal ranges were created for thymus volume and thymus:body volume ratios using the control data. Receiver operating curves (ROC) curves were generated for thymus:body volume ratio and gestation adjusted thymus volume centiles as predictors of PTB. Placental histology was analysed where available from pregnancies that delivered very preterm and the presence of chorioamnionitis/funisitis noted.

RESULTS : Normative ranges were created for thymus volume and thymus volume standardized for fetal size from fetuses that subsequently delivered at term, imaged 20-32 weeks gestation. Image datasets from sixteen women that delivered <32 weeks of gestation (ten with ruptured membranes and six with intact membranes) and 80 control women that delivered >37 weeks were included. Mean gestation at MRI of the study group was 28+4 weeks (SD 3.2) and the control group was 25+5 weeks (SD 2.4). Both absolute fetal thymus volumes and thymus:body volume ratios were smaller in fetuses that delivered preterm (p<0.001). Of the sixteen fetuses that delivered preterm thirteen had placental histology: eleven had chorioamnionitis and nine funisitis. The strongest predictors of prematurity were the thymus volume Z-score and thymus:body volume ratio Z-score (ROC areas 0.915 and 0.870 respectively).

CONCLUSIONS : We have produced MR derived normal ranges for fetal thymus and thymus:body volume ratios between 20 and 32 weeks of gestation. Fetuses that deliver very preterm had reduced thymus volumes when standardized for fetal size. A reduced thymus volume was also a predictor of spontaneous preterm delivery. Thymus volume may be a suitable marker of the fetal inflammatory response although further work is needed to assess this, increasing the sample size to correlate the extent of chorioamnionitis with thymus size.

Story Lisa, Zhang Tong, Uus Alena, Hutter Jana, Egloff Alexia, Gibbons Deena, Alison Ho, Al-Adnani Mudher, Knight Caroline L, Theodoulou Iakovos, Deprez Maria, Seed Paul T, Tribe Rachel M, Shennan Andrew H, Rutherford Mary


Preterm birth, Thymus, Volume, fetal thymus, infection, magnetic resonance imaging