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.

Fatal invasive cervical cancer secondary to untreated cervical dysplasia: a case report.

INTRODUCTION: Well-documented cases of untreated cervical intra-epithelial dysplasia resulting in fatal progression of invasive cervical cancer are scarce because of a long pre-invasive state, the availability of cervical cytology screening programs, and the efficacy of the treatment of both pre-invasive and early-stage invasive lesions. CASE PRESENTATION: We present a well-documented case of a 29-year-old Caucasian woman who was found, through routine conventional cervical cytology screening, to have pathologic Papanicolaou (Pap) grade III D lesions (squamous cell abnormalities). She subsequently died as a result of human papillomavirus type 18-associated cervical cancer after she refused all recommended curative therapeutic procedures over a period of 13 years. CONCLUSION: This case clearly demonstrates a caveat against the promotion and use of complementary alternative medicine as pseudo-immunologic approaches outside evidence-based medicine paths. It also demonstrates the impact of the individualized demands in diagnosis, treatment and palliative care of patients with advanced cancer express their will to refuse evidence-based treatment recommendations.

Maternal cardiac output between 11 and 13 weeks of gestation in the prediction of preeclampsia and small for gestational age.

OBJECTIVE: To investigate maternal cardiac output in the first trimester as a predictor of preeclampsia and delivery of small for gestational age (SGA) infants. METHODS: In women attending for routine care between 11(+0) and 13(+6) weeks of gestation, we recorded maternal variables and measured cardiac output by echocardiography. We compared cardiac output in those that developed preeclampsia (n=83), pregnancy-induced hypertension (PIH) (n=87), or SGA (n=532) with those unaffected by preeclampsia, PIH, or SGA (n=3,591). Regression analysis was used to first determine which of the factors among the maternal variables were significant predictors of cardiac output in the unaffected group and, secondly, to predict each complication by a combination of maternal variables and cardiac output. RESULTS: In the unaffected group, cardiac output increased with gestation and maternal weight and decreased with maternal age. Cardiac output was higher in parous women, in cigarette smokers, in those taking antihypertensive or beta-mimetic medications, and in those conceiving after in vitro fertilization, and lower in women of Afro-Caribbean origin. Compared with the unaffected group, cardiac output was significantly higher in the preeclampsia and PIH groups and lower in the SGA group. In screening by cardiac output and maternal variables, for a 10% false-positive rate, the detection rates were 43.4% for all preeclampsia, 52% for preeclampsia without SGA, 23.3% for PIH, and 23.9% for SGA. CONCLUSION: In pregnancies complicated by preeclampsia, PIH, and SGA, alterations in maternal cardiac output predate the clinical onset of the disorders by several months. Maternal cardiac output in the first trimester is increased in women who develop preeclampsia and decreased in women who deliver SGA infants. LEVEL OF EVIDENCE: II.