Risk of endometrial cancer in asymptomatic postmenopausal patients with thickened endometrium: data from the FAME-Endo study: an observational register study.

PURPOSE: To evaluate the risk for endometrial cancer (EC) in a large series of asymptomatic patients with thickened endometrium at ultrasound examination based on previously published data of a theoretical cohort. METHODS: In a prospective register study, a total of 1024 women with thickened endometrium in ultrasound examination undergoing histological diagnosis by dilation, hysteroscopy and curettage were evaluated. 124 patients were excluded due to current medication with tamoxifen and/or presence of HNPCC leaving 900 patients for further analysis. RESULTS: Mean [standard deviation (SD)] age of patients was 65.6 (8.6) years. Mean (SD) endometrial thickness was 11.9 (5.8) mm. 32 and 6 cases of EC and complex endometrial hyperplasia with atypia were found, respectively. In the univariate analysis, a statistically significant association between endometrial thickness, current use of antihypertensive medication, number of deliveries, and the presence of endometrial fluid in preoperative vaginal ultrasound (p < 0.05) with EC was found. A multivariate logistic regression model incorporating these parameters showed a statistically significant independent association of endometrial thickness, number of deliveries, and the presence of endometrial fluid in preoperative vaginal ultrasound (p < 0.05), but not current use of antihypertensive medication, with EC. Using a cut-off of the endometrial thickness of > 11 mm, the risk for "EC alone" and "EC and complex endometrial hyperplasia with atypia combined" was found to be 6.7% and 7.9%, respectively. CONCLUSIONS: Our data compare favorably to a theoretical cohort suggesting a clinically reasonable cut-off of > 11 mm endometrial thickness to discriminate between "normal" and "pathological". The data regarding "risk for endometrial cancer" can be used for counseling affected women.

Low placental weight and risk for fetal distress at birth.

UNLABELLED: Abstract Objective: The objective of this study was to assess whether low placental weight is associated with higher risk of emergency delivery (cesarean section and vacuum-assisted delivery). METHODS: This was a retrospective cohort study, including 657 normally developed term pregnancies. A strict methodology was used to provide reliable and reproducible placental weight measurement. Fetal heart rate patterns were analyzed according to the guidelines of the Royal College of Obstetricians and Gynecologists. Linear and logistic multiple regression analyses were used to assess risk factors for emergency delivery. RESULTS: Nulliparity, placental weight <10th percentile, and delivery after 40 weeks of gestation remain significantly associated with higher risk of emergency delivery for non-reassuring fetal status in the multivariable model [odds ratio (OR) 5.13, 95% confidence interval (CI) 2.85-9.22, P<0.001; OR 2.46, 95% CI 1.49-4.06, P<0.001; OR 2.23, 95% CI 1.26-4.51, P=0.01, respectively]. In the group of women who had an emergency delivery, 17.3% had a placental weight <10th percentile, which was significantly different to the group of women who delivered normally (9.4%, P≤0.04). If only emergency cesarean sections were analyzed, the percentage of women with placental weight <10th percentile was 37.5% in the cesarean section group compared to 9.8% in women who delivered normally (P≤0.001). CONCLUSION: This study suggests that, in clinically normally developed term pregnancies, placental weight <10th percentile is associated with an increased risk for emergency delivery during labor. These results warrant further prospective studies for potential use in clinical practice.

Influence of gestational diabetes mellitus on weight discrepancy in twin pregnancies.

OBJECTIVE: To evaluate the influence of gestational diabetes mellitus on weight discrepancy in twin pregnancies. METHODS: 200 twin pregnancies were included in the study. 157 nondiabetic pregnant women with twin gestations and 43 twin pregnancies with gestational diabetes mellitus (GDM) with viable fetuses born after 24 weeks of gestation were enrolled. Influence of maternal age, body-mass-index at the time of the oral glucose tolerance test, parity, smoking, chorionicity, gestational age at delivery and diagnosis of GDM on weight discrepancy of the twins was evaluated. RESULTS: Mean weight discrepancy of all analyzed twin pregnancies was 285 grams (+/- 231), relative weight discrepancy was 11.3% (+/- 8.6). Univariate regression analyses showed that GDM, chorionicity and gestational age at delivery were significantly associated with weight discrepancy. In the multivariate model only diagnosis of GDM was significantly associated with weight discrepancy. CONCLUSION: Twin pregnancies with insulin requiring gestational diabetes seem to have less birth weight discrepancy than twin pregnancies with normal glucose tolerance.

Notching and Pulsatility Index of the Uterine Arteries and Preeclampsia in Twin Pregnancies.

Increased uterine artery Doppler indices have been shown to be associated with preeclampsia and adverse pregnancy outcomes in singleton and twin pregnancies. At 20-22 weeks of gestation, we assessed the use of notching, the highest, lowest, and mean pulsatility index (PI), and the combination of notching and PI of the uterine arteries to screen for preeclampsia. This was done in a cohort of 380 twin pregnancies. The results showed that the combination of notching and the highest PI above the 95th centile of the uterine arteries gives the best screening characteristics for preeclampsia in twin pregnancies. We calculated sensitivities for preeclampsia for notching, highest PI, and the combination of notching and the highest PI of 50%, 45% and 91%, with specificities of 96%, 96% and 93%, respectively. The present findings demonstrate that notching, increased highest PI, and the combination of notching and the highest PI of the uterine arteries is associated with an increased risk of preeclampsia in twin pregnancies. We observed the highest sensitivity and specificity by using the combination of notching and the highest PI of the uterine arteries.

Plasma fibrinogen levels and prognosis in patients with ovarian cancer: a multicenter study.

INTRODUCTION: To evaluate pretherapeutic plasma fibrinogen levels as a prognostic parameter in patients with epithelial ovarian cancer (EOC). Materials and Methods. In the present multicenter study, pretherapeutic plasma fibrinogen levels were evaluated in 422 patients with EOC. Plasma fibrinogen levels were correlated with clinicopathological parameters and patient survival. RESULTS: The mean (standard deviation) pretherapeutic plasma fibrinogen level was 450.0 (150.1) mg/dl. Elevated plasma fibrinogen levels were associated with advanced tumor stage (p = .01) and the presence of a postoperative residual tumor mass (p < .001), but not with histological grade (p = .1) and histological type (p = .8). In a multivariate Cox regression model, tumor stage (p < .001 and p < .001), postoperative residual tumor mass (p = .001 and p = .008), and plasma fibrinogen level (p < .001 and p = .002), but not histological type (p = .8 and p = .2), patient age (p = .9 and p = .9), and serum cancer antigen 125 (p = 0.2 and p = 0.3) and C-reactive protein (p = .2 and p = .3) levels, were associated with disease-free and overall survival, respectively. Histological grade was associated with overall but not with disease-free survival (p = .01 and p = .8), respectively. CONCLUSIONS: Pretherapeutic plasma fibrinogen levels can be used as an independent prognostic parameter in patients with EOC.

The presence of postmenopausal bleeding as prognostic parameter in patients with endometrial cancer: a retrospective multi-center study.

BACKGROUND: To date, there is no consensus on the utility of screening procedures for the early detection of endometrial cancer. The value of transvaginal ultrasound for screening of asymptomatic endometrial cancer has been discussed controversially. This study was conducted to evaluate whether asymptomatic patients with endometrial cancer have a better prognosis than symptomatic patients with endometrial cancer diagnosed after postmenopausal bleeding. METHODS: In the present multi-center study, the effect of the presence of postmenopausal bleeding on prognosis was evaluated retrospectively in 605 patients with endometrial cancer using patients' files. 543 patients (133 patients were asymptomatic, 410 patients were symptomatic) with endometrioid endometrial cancer were enrolled in all further analysis. Student's t-test, Cox regression analysis and Kaplan-Meier analysis were used were appropriate. RESULTS: Presence/absence of a postmenopausal bleeding was not associated with tumor stage (p = 0.2) and age at diagnosis (p = 0.5). Asymptomatic patients with endometrial cancer had a significantly higher rate of well and moderate-differentiated tumors compared to symptomatic patients (p = 0.008). In univariable and multivariable survival analysis, tumor stage, tumor grade, and patients' age at diagnosis, but not presence/absence of a postmenopausal bleeding, were associated with disease free and overall survival. CONCLUSION: Asymptomatic patients with endometrial cancer have a higher rate of well differentiated tumors compared to patients with a postmenopausal bleeding prior to diagnosis. The prognosis of both groups of patients was similar.

Serum C-reactive protein as independent prognostic variable in patients with ovarian cancer.

PURPOSE: To evaluate serum C-reactive protein (CRP) as prognostic variable in patients with epithelial ovarian cancer (EOC). EXPERIMENTAL DESIGN: In a multicenter study, preoperative serum CRP was evaluated in 623 patients with EOC. Results were correlated with clinical data. RESULTS: Mean (SD) preoperative serum CRP was 3.6 (4.8) mg/dL. Serum CRP was significantly associated with International Federation of Gynecologists and Obstetricians stage (P < 0.001) and postoperative residual tumor mass (P < 0.001) but not with histologic grade (P = 0.1) and type (P = 0.7), patients' age (Pearson's correlation coefficient = 0.05; P = 0.2), and serum CA 125 (Pearson's correlation coefficient = 0.02; P = 0.6). Patients with platinum-resistant EOC had significantly higher CRP serum levels compared with patients with platinum-sensitive EOC [6.0 (6.6) mg/dL versus 2.8 (3.8) mg/dL; P < 0.001]. Higher International Federation of Gynecologists and Obstetricians stage (P < 0.001), presence of postoperative residual tumor mass (P < 0.001), tumor grade (P = 0.001), serum CA 125 (P = 0.03), and serum CRP (P = 0.001) were independently associated with overall survival. Patients with serum CRP < or =1 mg/dL versus >1 mg/dL had an overall 5-year survival of 82% versus 58.5% (P < 0.001). CONCLUSION: Serum CRP can be seen as a novel, widely available independent prognostic variable of ovarian cancer.

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.

Randomized controlled trial of induction at 38 weeks versus 40 weeks gestation on maternal and infant outcomes in women with insulin-controlled gestational diabetes.

OBJECTIVE: To compare the impact of induction of labor at 38 weeks of gestation with the induction of labor at 40 weeks of gestation in women with insulin-treated gestational diabetes on maternal and fetal outcome. STUDY DESIGN: In this study 100 pregnant women with insulin-treated gestational diabetes were randomized to either induction of labor at 38 (group I) or 40 weeks (group II) to evaluate the rate of large for gestational age newborns, neonatal hypoglycemia, success rate of deliveries within 48 h and cesarean section rate after induction in both groups. RESULTS: The difference of large for gestational age newborns was not significant between the two groups (6.8% vs. 12.8%, p = 0.49), 16 (36.4%) newborns in group I and 8 (17.0%) newborns in group II developed hypoglycemia <35 mg/dl (p = 0.04). The success rate for deliveries within 48 h after induction of labor for groups I and II was 77.3% and 92.3%, respectively (p = 0.25). The cesarean section rate after induction of labor was not significantly different between the two groups (24.1% vs. 18.7%, p = 0.49). CONCLUSION: In a cohort of women with insulin-treated gestational diabetes, induction of labor at 38 weeks did not significantly reduce the rate of large for gestational age newborns compared to induction at 40 weeks but seems to increase the rate of neonatal hypoglycemia.

Large-for-gestational-age newborns in women with insulin-treated gestational diabetes under strict metabolic control.

OBJECTIVE: To assess the influence of strict metabolic control in women with insulin-treated gestational diabetes on the risk of large-for-gestational-age (LGA) newborns, the frequency of obstetrical complications and fetal outcome. METHODS: In this prospective cohort study, 875 women were screened for gestational diabetes mellitus with a 75 g oral glucose tolerance test (OGTT) between weeks 24 and 28 of gestation. The study group (n = 162) consisted of women with insulin-treated gestational diabetes mellitus (GDM) and the control group (n = 713) of women with normal glucose tolerance (NGT). In the women with diabetes, strict adjustments of fasting glucose levels to 90 mg/dl and 130 mg/dl postprandially were achieved with insulin administration. RESULTS: No increased risk for LGA newborns was observed in women with GDM and good metabolic control (16.7% vs. 12.3%; p = 0.1). In women with NGT, maternal prepregnancy BMI was significantly higher in those who delivered LGA newborns than in those who gave birth to newborns below the 90th percentile [27.2 kg/m(2) (5.0) vs. 24.4 kg/m(2) (5.6); p = 0.006], whereas there was no influence of maternal BMI on birth weight of newborns in women with GDM. There was no difference between the two groups with respect to maternal birth traumata and fetal outcome, except for plexus palsy which occurred in three GDM women with macrosomic newborns. CONCLUSION: Strict metabolic control and surveillance in women with insulin-treated GDM seems to attenuate the risk for LGA newborns, diabetic fetopathia, and the influence of maternal BMI on fetal growth.

Severe diabetic fetopathy despite strict metabolic control.

In pregnant women, diabetes mellitus (DM) can cause severe complications for both mother and child during pregnancy and delivery; for example, hypertension, pre-eclampsia, macrosomia or intrauterine fetal death. It is therefore essential to achieve good metabolic control in the mother from before conception to the postpartum period. A 35-year-old primipara with type 2 DM presented herself at our outpatient department at 21 weeks of gestation. Until this time her DM had been treated with oral antidiabetic drugs; these were withdrawn and conventional insulin therapy was initiated. Except for the first two weeks after insulin adjustment, blood glucose values were within the required range. Biometric tests performed until week 30 of gestation showed discreet fetal growth. In the week 31, fetal abdominal girth near the 95% limit was observed for the first time; this was soon followed by an explosion-like enlargement of the abdomen along with glycemic values at the lower limit. A cesarean section was performed in week 35 of gestation because of the excessive macrosomia. The female newborn had a birth weight of 4920 g and, one hour after delivery, a blood glucose of 10 mg/dl requiring an intravenous glucose bolus. In addition, the child needed oxygen and also needed both an enteral and a parenteral supply of glucose until day 7 after delivery. Mother and child were discharged from the clinic 19 days postpartum in good general condition. This case illustrates the complexity of treatment of glucose-tolerance disturbances during pregnancy and underlines the importance of fetal monitoring by ultrasound, given that measurement of maternal blood glucose does not always provide sufficient information on the metabolic situation of the fetus.

Fetal hyperinsulinism and maternal one-hour postload plasma glucose level.

OBJECTIVE: Fetal insulin concentrations reflect the intrauterine glucose load given the fetus by the mother. In this study, we assessed the association between maternal glucose levels during oral glucose tolerance testing and fetal cord insulin. METHODS: Pregnant women with an oral glucose tolerance test (OGTT) result were included in this prospective study. The patients were divided into 3 groups according to their 1-hour OGTT glucose concentration: up to 160 mg/dL (control, group I), 160-179 mg/dL (intermediate, group II), and gestational diabetes mellitus (GDM, group III). Patients with GDM were assigned to insulin therapy if blood glucose levels were not in the preferable range. RESULTS: Of the 930 patients who entered the study, 570 (61.3%) were assigned to group I, 76 (8.2%) to group II, and 284 (30.5%) to group III. The cord blood insulin value was significantly (P < .001, Mann-Whitney test) higher in group II (median, 12.8 microU/mL; range, 3-130 microU/mL) than in group I (median, 7.25 microU/mL; range, < 3-98 microU/mL). Cord blood insulin values were higher, albeit not significantly (P = .100, Mann-Whitney test), in group II than in group III (median, 9.9 microU/mL; range, < 3-61 microU/mL). CONCLUSION: Children whose mothers had a 1-hour value between 160 and 179 mg/dL had significantly higher cord blood insulin values than offspring of women with a 1-hour value below 160 mg/dL.

Calpain-10 haplotype combination and association with gestational diabetes mellitus.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a frequent complication of pregnancy. Epidemiologic and pathophysiologic data suggest a close link of this disease to non-insulin-dependent diabetes mellitus. Within the calpain-10 gene various single-nucleotide polymorphisms have been identified that increased the risk for non-insulin-dependent diabetes mellitus. Therefore, we examined single-nucleotide exchanges of this gene in women with GDM. METHODS: A total of 875 unselected women were prospectively screened for GDM. Eighty women of this population, 40 patients with an abnormal oral glucose tolerance test and 40 normal controls, were randomly selected. DNA samples isolated from sera of the control and study groups were analyzed with respect to single-nucleotide polymorphisms of the calpain-10 gene at positions 43, 19, and 63 using polymerase chain reaction amplification and restriction analysis. RESULTS: Women with GDM were more likely to be homozygous for the allele 1 of single-nucleotide polymorphism 63 (P =.02 by chi(2) test). With respect to single-nucleotide polymorphisms 19 and 43, no significant differences in allele distribution were detected between controls and women with GDM. When comparing the different haplotypes for calpain-10 (single-nucleotide polymorphisms 43, 19, and 63), all women with the haplotype combination 121/221 (n = 8) had gestational diabetes (P =.005 by Fisher exact test). CONCLUSION: Our results indicate that the haplotype 121/221 of the calpain-10 gene may be associated with disturbances of glucose metabolism during pregnancy. LEVEL OF EVIDENCE: II-1

Genetic factors in assisted reproduction.

It is still unclear whether the procedures of assisted reproduction increase the risk of congenital malformations. Thus, it remains to be clarified whether an increased risk, if any, of congenital malformations in these children is caused by the procedure of assisted reproduction itself or by the underlying maternal and paternal background. From the genetic point of view, infertility patients seeking assisted reproduction have to be classified as a high-risk group. The prevalence of numerical chromosomal abnormalities is around 10% in these patients, compared with 0.85% in the general population. The prevalence of structural chromosomal abnormalities is around 0.1% in the general population and is increased up to 1% in patients seeking assisted reproduction. In addition, patients with microdeletions of the Y-chromosome or mutations in the cystic fibrosis transmembrane-conductance regulator gene are likely to be encountered at the fertility clinic. Therefore, genetic screening and counselling should be routinely offered to infertility patients. They also need to understand that parental factors can be transferred to offspring that would most likely not have been conceived by natural means.

Suture Closure versus Non-Closure of Subcutaneous Fat and Cosmetic Outcome after Cesarean Section: A Randomized Controlled Trial.

INTRODUCTION: To investigate the effect of subcutaneous fat suture closure versus non-closure at cesarean section (CS) on long-term cosmetic outcome. MATERIAL AND METHODS: Women undergoing planned or unplanned CS were randomized to either subcutaneous fat suture closure or non-closure using a 1∶1 allocation algorithm. Participants and outcome assessors were blinded to group allocation. Scar evaluation was performed after two and six months. Primary outcome measures were Patient and Observer Scar Assessment Scale (POSAS) summary scores six months after surgery. Secondary outcome measures were Vancouver Scar Scale (VSS) summary scores, retraction of the scar below the level of the surrounding skin, duration of surgery, and development of hematoma, seroma, surgical site infection (SSI) or wound disruption. Data were analyzed according to the intention to treat principle. RESULTS: A total of 116 women were randomized and 91 participants, 47 in the closure and 44 in the non-closure group, completed the trial and were analyzed. There were no differences in patient morphometrics or surgery indications between groups. At two and six months no significant differences were found with respect to POSAS or VSS scores between groups. After two months significantly more women in the non-closure group described their scar as being retracted below the level of the skin (36% vs. 15%, p = 0.02) whereas no difference was observed at six months. There were significantly more hematomas in the non-closure (25%) compared to the closure group (4%) (p = 0.005). There was no difference in duration of surgery, SSI, seroma formation or wound disruption between groups. CONCLUSIONS: Suture closure of the subcutaneous fat at CS does not affect long-term cosmetic outcome. (Level I evidence). TRIAL REGISTRATION: ClinicalTrials.gov NCT01542346.

Postoperative gum chewing after gynecologic laparoscopic surgery: a randomized controlled trial.

OBJECTIVE: To investigate the effect of postoperative gum chewing on bowel motility after laparoscopic gynecologic surgery. METHODS: In this randomized controlled trial, patients were allocated to either postoperative gum chewing every 2 hours for 15 minutes or standard postoperative care without gum chewing. The study's primary end points were time to first regular bowel sounds and time to first passage of flatus after surgery. Secondary end points were time of operation to first defecation, patient satisfaction concerning postoperative gum chewing, potential side effects of postoperative gum chewing, and potential effect of gum chewing on postoperative pain therapy. RESULTS: One hundred seventy-nine patients were included in this trial. We found a significantly shorter interval between surgery and passage of first flatus in the intervention group compared with the control group (median 6.2 hours compared with 8.1 hours; P=.002) and a significantly higher rate of regular bowel sounds 3 hours (76% compared with 47%; P<.001) and 5 hours (91% compared with 78%; P=.01) after surgery. Fewer opioid analgetics were administered to patients allocated to the intervention group (P=.02). There was no significant difference in time to first defecation between groups (median 26.3 hours compared with 29.0 hours, P=.165). Gum chewing was well tolerated and well accepted by patients, and no intervention-related side effects were observed. CONCLUSION: Gum chewing seems to have beneficial effects on bowel motility when used as an adjunct treatment in postoperative care after minimally invasive surgery. Gum chewing should be recommended to patients after gynecologic laparoscopic surgery. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, NCT 01549353. LEVEL OF EVIDENCE: I.

Common oxytocin receptor gene polymorphisms and the risk for preterm birth.

Oxytocin is crucially involved in the onset and maintenance of labor. We investigated the association between oxytocin receptor gene polymorphisms and preterm birth. The presence of four common oxytocin receptor gene polymorphisms (rs2254298, rs53576, rs2228485 and rs237911) was evaluated in one hundred women with preterm birth and one hundred healthy women using restriction fragment length polymorphism genotyping. No association was found between the presence of any individual oxytocin receptor gene polymorphism and preterm birth. In haplotype analysis, the haplotype combination of rs2254298 A allele, rs2228485 C allele and rs237911 G allele was found to be significantly associated with an increased risk of preterm birth (OR=3.2 [CI 1.04-9.8], p=0.043). In conclusion our findings suggest that a combination of three oxytocin receptor gene polymorphisms is associated with an increased risk for preterm birth. We propose further studies investigating the role of oxytocin receptor gene polymorphisms and preterm birth.

Association between pregnancy-associated plasma protein-A and gestational diabetes requiring insulin treatment at 11-14 weeks of gestation.

OBJECTIVE: To evaluate whether gestational diabetes mellitus (GDM) requiring insulin treatment (White's classification A2) is associated with an alteration of pregnancy-associated plasma protein-A (PAPP-A) serum levels at first-trimester screening between 11 and 14 weeks of gestation. METHODS: We collected data (2007-2010) of all women who developed GDM requiring insulin treatment and completed first-trimester combined screening program including the determination of serum PAPP-A and free ß-human chorionic gonadotropin (ß-hCG). A total of 288 women were included in this study. Each of the 72 women who developed GDM was matched with three unaffected controls. RESULTS: Women with GDM were significantly older (34.2 ± 5.9 vs. 32.3 ± 5.5 years, P = 0.007) and delivered significantly earlier (38.40 ± 2.25 vs. 39.1 ± 2.2 gestational weeks, P = 0.01). Multiple regression analysis revealed, that PAPP-A and ß-hCG were independently associated with each other (P = 0.04) but there was no association between GDM/no GDM and the first-trimester serum markers (P = 0.77). CONCLUSION: Our data suggest that women who are developing GDM needing insulin treatment do not have altered PAPP-A levels at 11-14 weeks.

Interleukin-1 beta gene polymorphisms and preterm birth.

OBJECTIVE: To investigate the association between two genetic variations in the Interleukin-1 beta (IL1B) gene and preterm birth. STUDY DESIGN: In this case-control study we tested the allelic distribution of two of its common polymorphisms (IL1B +3953C>T [rs1143634], IL1B -511C>T [rs16944]) in one hundred women with preterm birth and one hundred healthy women with at least one uncomplicated full term pregnancy and no history of preterm birth. RESULTS: A significant association was found between the presence of the IL1B +3953C>T polymorphism and preterm birth (p=0.049, OR 0.6 [0.3-1.0]). No significant association was found between the IL1B -511C>T polymorphism and preterm birth (p=0.471, OR 1.3 [0.7-2.3]). CONCLUSION: Our findings suggest that the IL1B +3953C>T polymorphism is associated with a risk reduction for preterm birth in Caucasian women, possibly by altering the inflammatory response during pregnancy.

Transcription factor 7-like 2 gene polymorphisms and gestational diabetes mellitus.

OBJECTIVE: Transcription factor 7-like 2 (TCF7L2) gene polymorphisms were shown to be associated with insulin resistance. We examined two single nucleotide exchanges in this gene in women with gestational diabetes mellitus (GDM) and in women with normal glucose tolerance. METHODS: A total of 1800 unselected women were prospectively screened for GDM by oral glucose tolerance test (OGTT) between 24 and 28 weeks of gestation. Two hundred and fifty Caucasian women of this collective, 125 patients with pathological OGTT and 125 patients with normal glucose tolerance were randomly selected. DNA samples were isolated and TCF7L2 gene polymorphisms (TCF7L2rs12255372 and TCF7L2rs7903146) were analyzed. RESULTS: Women with GDM were significantly older (30.1 ± 3.4 years vs. 28.2 ± 4.8 years, p = 0.01), had a significantly higher body mass index (26.4 kg/m(2); interquartile range: 23.33-31.19 vs. 24.6 kg/m(2); interquartile range: 21.05-27.28, p = 0.02) and were significantly more often homozygous for the T allele of TCF7L2rs12255372 (17.2% vs. 2.6%, p = 0.002) than patients with normal glucose tolerance. Binary logistic regression analysis showed that the homozygous variant of TCF7L2rs12255372 (T/T) is an independent risk factor for GDM (OR 7.7, 95% CI: 1.71-34.60), but not the homozygous variant of TCF7L2rs7903146 (T/T). CONCLUSIONS: TCF7L2rs12255372 variant (T/T) is associated with increased risk of GDM in Caucasian women.