Plasma progesterone, estradiol, and unconjugated estriol concentrations in twin pregnancies: Relation with cervical length and preterm delivery.

INTRODUCTION: The aim of this study was to examine the association between plasma hormone concentrations, cervical length, and preterm delivery in twin pregnancies, including the effect of progesterone treatment. MATERIAL AND METHODS: This study included 191 women pregnant with twins from a randomized placebo-controlled trial. A baseline blood sample was collected at 18-24 weeks before treatment with vaginal progesterone (n = 95) or placebo pessaries (n = 96), and 167 (87.4%) women had a second sample collected after 4-8 weeks of treatment. At baseline, 155 (81.2%) women had their cervical length measured. Progesterone, estradiol, and unconjugated estriol concentration was measured, and the association between hormone concentrations, cervical length, and gestational age at delivery was examined. Hormone concentrations were compared in the placebo and progesterone group. Statistical analysis included Spearman's rho, Mann-Whitney U test, Cuzick's test for trends, and linear regression analyses. RESULTS: A short cervical length was associated with preterm delivery. Cervical length and hormone concentrations were not associated (Spearman's rho; progesterone -.05, estradiol .04, estriol .08). Decreasing gestational age at delivery was associated with higher progesterone and estradiol concentrations at baseline (P trend; progesterone 0.04, estradiol 0.02) but not in the second sample or in the weekly change between samples. Progesterone treatment did not increase the progesterone concentration. CONCLUSIONS: Plasma concentrations of progesterone, estradiol, and unconjugated estriol at 18-24 weeks are not associated with cervical length or preterm delivery in twin pregnancies. Vaginal progesterone treatment does not increase the circulating progesterone concentration in twin pregnancies. Cervical length, but not hormone concentration, is predictive of preterm delivery in twin gestations.

Short- and long-term perinatal outcome in twin pregnancies affected by weight discordance.

INTRODUCTION: The objective was to investigate the association between chorionicity-specific intertwin birthweight discordance and adverse outcomes including long-term follow up at 6, 18, and 48-60 months after term via Ages and Stages Questionnaire. MATERIAL AND METHODS: In this secondary analysis of a cohort study (Oldenburg et al., n = 1688) and a randomized controlled trial (PREDICT study, n = 1045) twin pairs were divided into three groups according to chorionicity-specific birthweight discordance: <75th percentile, 75th-90th percentile and >90th percentile. Information on infant mortality, admittance to neonatal intensive care units, and gestational age at delivery was available for all pairs. Detailed neonatal outcomes were available for 656 pairs from PREDICT, of which 567 pairs had at least one Ages and Stages Questionnair follow-up. Logistic regression models were used for dichotomous outcomes. Ages and Stages Questionnair scores were compared using the method of generalized estimating equation to account for the correlation within twins. RESULTS: The 75th and 90th percentiles for birthweight discordance were 14.8 and 21.4% for monochorionic and 16.0 and 23.8% for dichorionic twins. After adjustment for small for gestational age and gender, birthweight discordance >75th and >90th percentile was associated with induced delivery <34 weeks [odds ratio 1.71 (95% confidence interval 1.11-2.65) and odds ratio 2.83 (95% confidence interval 1.73-4.64), respectively]. Discordance >75th-percentile was associated with an increased risk of infant mortality after 28 days [odds ratio 4.69 (95% confidence interval 1.07-20.45)] but not with major neonatal complications or with low mean Ages and Stages Questionnair scores at 6, 18, and 48-60 months after term. CONCLUSION: Chorionicity-specific intertwin birthweight discordance is a risk factor for induced preterm delivery and infant mortality, but not for lower scores for neurophysiological development at 6, 18, and 48-60 months.

Cytokines and the risk of preterm delivery in twin pregnancies.

OBJECTIVE: To estimate the association between cytokine levels in twin pregnancies and risk of spontaneous preterm delivery, including the effect of progesterone treatment. METHODS: This secondary analysis of a randomized placebo-controlled trial investigating the effect of progesterone treatment on preterm delivery in twin pregnancies included 523 women with available dried blood spot samples collected before treatment with progesterone (n=258) or placebo (n=265) and after 4-8 weeks of treatment. Samples were analyzed for cytokines using a sandwich immunoassay. Cytokine levels in spontaneous preterm delivery at 34-37 weeks of gestation and spontaneous preterm delivery before 34 weeks of gestation were compared with delivery at 37 weeks of gestation or more for placebo-treated women. The association between interleukin (IL)-8 and risk of spontaneous preterm delivery before 34 weeks of gestation was estimated further, including comparison according to treatment. Statistical analyses included Kruskal-Wallis test, Mann-Whitney U test, linear regression, and Cox regression analysis. RESULTS: We found a statistically significant association between IL-8 and spontaneous preterm delivery. At 23-33 weeks of gestation, the median IL-8 level was 52 pg/mL (interquartile range 39-71, range 19-1,061) for term deliveries compared with 65 pg/mL (interquartile range 43-88, range 14-584) for spontaneous preterm delivery at 34-37 weeks of gestation and 75 pg/mL (interquartile range 57-102, range 22-1,715) for spontaneous preterm delivery before 34 weeks of gestation (P<.001). Risk of spontaneous preterm delivery was associated with a large weekly increase in IL-8 (hazard ratio 2.0, 95% confidence interval [CI] 1.2-3.3). There was no effect of progesterone treatment on IL-8 levels. Levels of IL-8 at 18-24 weeks of gestation were associated with a cervix less than 30 mm (odds ratio 1.8, 95% CI 1.2-2.7). CONCLUSION: Risk of spontaneous preterm delivery before 34 weeks of gestation is increased in women with high IL-8 levels. Progesterone treatment does not affect IL-8 levels.

Influence of the time interval between hysteroscopy, dilation and curettage, and hysterectomy on survival in patients with endometrial cancer.

OBJECTIVE: To evaluate whether a prolonged time interval between dilation and curettage (D&C) and hysterectomy has an effect on survival in patients with surgically treated endometrial cancer. METHODS: In this multicenter study, time between D&C and hysterectomy was correlated to clinical data in 344 surgically staged patients with endometrioid endometrial cancer. RESULTS: The median (interquartile range) interval between D&C and hysterectomy in patients with endometrial cancer was 23 (13-34) days. In a univariable survival analysis, International Federation of Gynecology and Obstetrics (FIGO) tumor stage (P<.001, P<.001), tumor grade (P<.001, P<.001), and patients' age (P<.001, P<.001), but not time interval from D&C to hysterectomy (P=.06, P=.07) were associated with disease-free and overall survival, respectively. In a multivariable Cox regression model, FIGO tumor stage (P<.001, P<.001), and patients' age (P<.001, P<.001) but not tumor grade (P=.4, P=.2) or time interval between D&C and hysterectomy (P=.5, P=.8) were independent prognostic factors for disease-free and overall survival, respectively. CONCLUSION: We were not able to show that a prolonged time interval between D&C and hysterectomy has a significant effect on the prognosis of patients with endometrial cancer. LEVEL OF EVIDENCE: II.

Association of elevated C-reactive protein levels with an impaired prognosis in patients with surgically treated endometrial cancer.

OBJECTIVE: To evaluate whether C-reactive protein (CRP) serum levels are associated with prognosis in surgically treated endometrial cancer. METHODS: In the present multicenter study, CRP serum levels were measured preoperatively in 403 surgically staged patients with endometrioid endometrial cancer. Results were correlated to clinical data. RESULTS: The mean (standard deviation) serum CRP level in patients with endometrial cancer was 1.0 (1.8) mg/dL. Serum CRP levels were associated with tumor stage (P=.01), but not with tumor grade (P=.8), lymph node involvement (P=.8), and age at diagnosis (P=.9). In a univariable survival analysis, serum CRP levels, tumor stage, tumor grade, and age at diagnosis were associated with disease-free and overall survival (all P <.001). In a multivariable Cox regression model, serum CRP levels (P=.001, P=.004), tumor stage (P <.001, P <.001), tumor grade (P=.02, P=.009), and age at diagnosis (P=.002, P=.001) were independent prognostic factors for disease-free and overall survival. CONCLUSION: Our results suggest that elevated serum CRP levels are associated with a less favorable prognosis in patients with surgically treated endometrial cancer. LEVEL OF EVIDENCE: II.