OBJECTIVE:To compare the efficacy of two types of progestogen therapy for preventing preterm birth (PTB) and to review the relevant literature. DESIGN:A multicentre, randomised, open-label, equivalence trial and a meta-analysis. SETTING:Tertiary referral hospitals in South Korea. POPULATION:Pregnant women with a history of spontaneous PTB or short cervical length (<25 mm). METHODS:Eligible women were screened and randomised at 16-22 weeks of gestation to receive either 200 mg of vaginal micronised progesterone daily (vaginal group) or an intramuscular injection of 250 mg 17α-hydroxyprogesterone caproate weekly (IM group). Stratified randomisation was carried out according to participating centres and indications for progestogen therapy. This trial was registered at ClinicalTrials.gov (NCT02304237). MAIN OUTCOME MEASURE:Preterm birth (PTB) before 37 weeks of gestation. RESULTS:A total of 266 women were randomly assigned and a total of 247 women (119 and 128 women in the vaginal and IM groups, respectively) were available for the intention-to-treat analysis. Risks of PTB before 37 weeks of gestation did not significantly differ between the two groups (22.7 versus 25.8%, P = 0.571). The difference in PTB risk between the two groups was 3.1% (95% CI -7.6 to 13.8%), which was within the equivalence margin of 15%. The meta-analysis results showed no significant differences in the risk of PTB between the vaginal and IM progestogen treatments. CONCLUSION:Compared with vaginal progesterone, treatment with intramuscular progestin might increase the risk of PTB before 37 weeks of gestation by as much as 13.8%, or reduce the risk by as much as 7.6%, in women with a history of spontaneous PTB or with short cervical length. TWEETABLE ABSTRACT:Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation.

S.K. Lee1, J.Y. Kim1, S.E. Hur1, C.J. Kim1, B.J. Na2, M. Lee3, A. Gilman-Sachs4, and J. Kwak-Kim4,5,* Department of Obstetrics and Gynecology, College of Medicine, Konyang University, Gasoowon-dong, Seo-gu, Daejeon 302-718, Korea Department of Preventive Medicine, College of Medicine, Konyang University, Gasoowon-dong, Seo-gu, Daejeon 302-718, Korea Department of Microbiology and Immunology, School of Medicine, Cha University, Yatap-dong, Bundang-gu, Seongnam 463-836, Korea Department of Microbiology and Immunology, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA Department of Obstetrics and Gynecology, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, 830 West End Court, Suite 400, Vernon Hills, IL 60061, USA

BACKGROUNDT cells which produce interleukin (IL)-17 are involved in chronic inflammatory processes and regulatory T (Treg) cells are possibly the most important immune regulators. We aimed to investigate peripheral blood IL-17(+) T and Foxp3(+) Treg cells in women with idiopathic recurrent pregnancy loss (RPL).METHODSThe study design is a cross-sectional evaluation of Th1, Th2, IL-17(+) T and Treg cells in women with idiopathic RPL (n = 42) and age-matched parous controls (n = 24). Flow cytometric analysis was performed to measure IL-17(+) T and Foxp3(+) Treg cells, and ratios of Th1/Th2 cells using anti-IL-17A and anti-Foxp3 antibodies, and monoclonal antibodies to tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-10. Student's t-test and partial correlations were applied for statistical analysis.RESULTSTNF-α-/IL-10-producing CD3(+)CD4(+) T cell ratio was higher in women with RPL than controls (P = 0.048). Levels of IL-17(+) T cells (P = 0.021) and the IL-17(+) T/CD4(+)Foxp3(+) Treg cell ratio (P = 0.001) were increased, whereas Foxp3(+) (P = 0.035), Foxp3(low) (P = 0.032) and CD4(+)Foxp3(+) T cell (P = 0.037) levels were decreased in women with RPL, compared with controls. Levels of IL-17(+) T cells were correlated with TNF-α-producing CD3(+)CD4(+) T cells (r = 0.269, P = 0.033), and with ratios of TNF-α/IL-10 (r = 0.276, P = 0.027) and IFN-γ/IL-10 (r = 0.266, P = 0.035)-producing CD3(+)CD4(+) cells. Furthermore, the ratio of IL-17(+) T cells to CD4(+)Foxp3(+) Treg cells showed a positive correlation with TNF-α-producing CD3(+)CD4(+) T cells (P = 0.047) and IFN-γ-producing CD3(+)CD4(+) T cells (P = 0.048) as well as a ratio of IFN-γ/IL-10-producing CD3(+)CD4(+) T cells (P = 0.037).CONCLUSIONSEnhanced pro-inflammatory immune responses with suppressed immune regulation may be an important immune mechanism involved in RPL.

The purpose of this study was to evaluate whether prenatal ultrasonography predicts perinatal mortality of congenital diaphragmatic hernia (CDH). Medical records were retrospectively reviewed in 33 CDH cases who were prenatally diagnosed and delivered in Seoul National University Hospital in the period from January 1995 to March 2003. Several prenatal sonographic parameters were evaluated: side of visceral herniation, liver herniation, stomach herniation, polyhydramnios, hydrops, cardiac anomaly, extracardiac anomalies, mediastinal shift, abdominal circumference, estimated fetal weight, proportion of remaining contralateral lung area compared to the area of hemithorax. The predictive values of these parameters for perinatal mortality were analyzed. P value less than 0.05 was regarded as significant level. Of 33 cases, there were 18 cases (55%) of perinatal death including one case of stillbirth and 15 cases (45%) of survival. Among the parameters analyzed, proportion of contralateral lung area which was measured less than 25 percent of hemithorax on a four-chamber view (7/12 vs. 2/15), the fetal weight estimated less than 10th percentile at diagnosis (5/18 vs. 0/15) and the presence of cardiac anomalies (5/13 vs. 0/15) were significantly related to perinatal mortality. Excluding 4 cases associated with chromosomal abnormalities (2 Trisomy 13, 1 Trisomy 9, 1 46, XY/47, XY, + mar), proportion of contralateral lung area less than 25 percent of hemithorax (6/10 vs. 2/15) and the right-side herniation (5/14 vs. 1/15) were significantly related to perinatal mortality. The results of this study suggest that prenatal ultrasonographic findings are of value in predicting perinatal mortality of CDH. Remaining contralateral lung area was the most useful prognostic parameter.