Impact of general anaesthesia on breast cancer survival: a 5-year follow up of a pragmatic, randomised, controlled trial, the CAN-study, comparing propofol and sevoflurane.

Background: Anaesthesia may impact long-term cancer survival. In the Cancer and Anaesthesia study, we hypothesised that the hypnotic drug propofol will have an advantage of at least five percentage points in five-year survival over the inhalational anaesthetic sevoflurane for breast cancer surgery. Methods: From 2118 eligible breast cancer patients scheduled for primary curable, invasive breast cancer surgery, 1764 were recruited after ethical approval and individual informed consent to this open label, single-blind, randomised trial at four county- and three university hospitals in Sweden and one Chinese university hospital. Of surveyed patients, 354 were excluded, mainly due to refusal to participate. Patients were randomised by computer at the monitoring organisation to general anaesthesia maintenance with either intravenous propofol or inhaled sevoflurane in a 1:1 ratio in permuted blocks. Data related to anaesthesia, surgery, oncology, and demographics were registered. The primary endpoint was five-year overall survival. Data are presented as Kaplan-Meier survival curves and Hazard Ratios based on Cox univariable regression analyses by both intention-to-treat and per-protocol. EudraCT, 2013-002380-25 and ClinicalTrials.gov, NCT01975064. Findings: Of 1764 patients, included from December 3, 2013, to September 29, 2017, 1670 remained for analysis. The numbers who survived at least five years were 773/841 (91.9% (95% CI 90.1-93.8)) in the propofol group and 764/829 (92.2% (90.3-94.0)) in the sevoflurane group, (HR 1.03 (0.73-1.44); P = 0.875); the corresponding results in the per-protocol-analysis were: 733/798 (91.9% (90.0-93.8)) and 653/710 (92.0% (90.0-94.0)) (HR = 1.01 (0.71-1.44); P = 0.955). Survival after a median follow-up of 76.7 months did not indicate any difference between the groups (HR 0.97, 0.72-1.29; P = 0.829, log rank test). Interpretation: No difference in overall survival was found between general anaesthesia with propofol or sevoflurane for breast cancer surgery. Funding: Swedish Research Council; Uppsala-Örebro Regional Research Council; Västmanland Regional Research Fund; Västmanland Cancer Foundation; Stig and Ragna Gohrton Foundation; Birgit and Henry Knutsson Foundation.

Effects on postpartum weight retention after antenatal lifestyle intervention - a secondary analysis of a randomized controlled trial.

INTRODUCTION: High weight retention after pregnancy is related to an increased risk of future obesity. The objective was to evaluate whether an antenatal intervention, compared with standard care, could reduce postpartum weight retention (PPWR). MATERIAL AND METHODS: Women with body mass index >19, age ≥18 years, knowledge of Swedish, and pregnancy ≤16 weeks' gestation were randomized. Standard care was compared with a composite intervention including a personalized weight graph, education on recommended weight gain, prescription of exercise, and monitoring of weight until 1 year after delivery. Mean (kg) PPWR was compared between the groups and risk estimates (odds ratio) for excessive weight retention were calculated. RESULTS: Of 445 women randomized, 267 remained for analysis at ≤16 weeks postpartum and 168 at 1 year postpartum. The intervention group had a significantly lower mean PPWR at ≤16 weeks [1.81 kg (standard deviation, SD, 4.52) vs. 3.19 kg (SD 4.77), p = 0.016]. At one year postpartum, mean retention was still 0.7 kg lower in the intervention group [0.30 kg (SD 5.52) vs. 1.00 kg (SD 5.46)]; the difference was not statistically significant (p = 0.414). Gestational weight gain above Institute of Medicine recommendations was a significant risk factor for excessive weight retention (>5 kg) one year after delivery (OR 2.44; 95% CI 1.08-5.52, p = 0.029). CONCLUSIONS: A composite lifestyle intervention during pregnancy reduced short-term weight retention, but the effect of the intervention did not remain at 1 year postpartum. A gestational weight gain above Institute of Medicine recommendations increases the risk of excessive long-term weight retention.

Randomized controlled study in pregnancy on treatment of marked hyperglycemia that is short of overt diabetes.

INTRODUCTION: A randomized multicenter study was conducted in the Stockholm-Örebro areas in Sweden to evaluate how treatment aiming at normoglycemia affects fetal growth, pregnancy and neonatal outcome in pregnant women with severe hyperglycemia. MATERIAL AND METHODS: Pregnant women with hyperglycemia defined as fasting capillary plasma glucose <7.0 mmol/L and a two-hour plasma glucose value ≥10.0 and <12.2 mmol/L following a 75-g oral glucose tolerance test (OGTT) diagnosed before 34 weeks of gestation were randomized to treatment (n = 33) or controls (n = 36). Women assigned to the control group were blinded for the OGTT results and received routine care. The therapeutic goal was fasting plasma glucose 4-5 mmol/L, and <6.5 mmol/L after a meal. Primary outcomes were size at birth and number of large-for-gestational age (>90th percentile) neonates. Secondary outcomes were pregnancy complications, neonatal morbidity and glycemic control. RESULTS: The planned number of participating women was not reached. There was a significantly reduced rate of large-for-gestational age neonates, 21 vs. 47%, P < 0.05. Group differences in pregnancy complications and neonatal morbidity were not detected because of limited statistical power. In total, 66.7% of the women in the intervention group received insulin. Of all measured plasma glucose values, 64.1% were in the target range, 7.2% in the hypoglycemic range and 28.7% above target values. There were no cases of severe hypoglycemia. CONCLUSIONS: Aiming for normalized glycemia in a pregnancy complicated by severe hyperglycemia reduces fetal growth but is associated with an increased rate of mild hypoglycemia.

Placental gene expression of inflammatory markers and growth factors--a case control study of obese and normal weight women.

OBJECTIVE: To survey the placental gene expression of inflammatory markers and growth factors in non-smoking obese women with an uncomplicated pregnancy without associated morbidity and delivery at term compared with normal weight women. METHODS: Placental tissue samples from 32 obese women (body mass index, BMI≥35.0 kg/m2) were compared with samples from 94 normal weight women (BMI 18.5-25.0 kg/m2) matched for age (±1 year), gestational age (±3 days), parity and mode of delivery. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to analyse toll receptor-2 and -4, interleukin-6 and -8, tumour necrosis factor-α, leptin, adiponectin, insulin-like growth factor-1 and -2, hepatocyte growth factor, hepatocyte growth factor receptor and insulin receptor. RESULTS: There was no significant difference in gene expression in placental tissue samples from obese and normal weight women. CONCLUSION: We found no difference in the occurrence of inflammatory marker and growth factor mRNA levels in placental tissue samples from a large group of obese women without associated morbidity and with healthy infants compared to a closely matched control group of healthy normal weight women. Compared with the previous studies, this anomalous finding may be explained by the absence of associated morbidity in the obese women in our study.

Posttraumatic stress among women after induced abortion: a Swedish multi-centre cohort study.

BACKGROUND: Induced abortion is a common medical intervention. Whether psychological sequelae might follow induced abortion has long been a subject of concern among researchers and little is known about the relationship between posttraumatic stress disorder (PTSD) and induced abortion. Thus, the aim of the study was to assess the prevalence of PTSD and posttraumatic stress symptoms (PTSS) before and at three and six months after induced abortion, and to describe the characteristics of the women who developed PTSD or PTSS after the abortion. METHODS: This multi-centre cohort study included six departments of Obstetrics and Gynaecology in Sweden. The study included 1457 women who requested an induced abortion, among whom 742 women responded at the three-month follow-up and 641 women at the six-month follow-up. The Screen Questionnaire-Posttraumatic Stress Disorder (SQ-PTSD) was used for research diagnoses of PTSD and PTSS, and anxiety and depressive symptoms were evaluated by the Hospital Anxiety and Depression Scale (HADS). Measurements were made at the first visit and at three and six months after the abortion. The 95% confidence intervals for the prevalence of lifetime or ongoing PTSD and PTSS were calculated using the normal approximation. The chi-square test and the Student's t-test were used to compare data between groups. RESULTS: The prevalence of ongoing PTSD and PTSS before the abortion was 4.3% and 23.5%, respectively, concomitant with high levels of anxiety and depression. At three months the corresponding rates were 2.0% and 4.6%, at six months 1.9% and 6.1%, respectively. Dropouts had higher rates of PTSD and PTSS. Fifty-one women developed PTSD or PTSS during the observation period. They were young, less well educated, needed counselling, and had high levels of anxiety and depressive symptoms. During the observation period 57 women had trauma experiences, among whom 11 developed PTSD or PTSS and reported a traumatic experience in relation to the abortion. CONCLUSION: Few women developed PTSD or PTSS after the abortion. The majority did so because of trauma experiences unrelated to the induced abortion. Concomitant symptoms of depression and anxiety call for clinical alertness and support.

The prevalence of posttraumatic stress among women requesting induced abortion.

OBJECTIVES: To describe the prevalence and pattern of traumatic experiences, to assess the prevalence of posttraumatic stress disorder (PTSD) and posttraumatic stress symptoms (PTSS), to identify risk factors for PTSD and PTSS, and to analyse the association of PTSD and PTSS with concomitant anxiety and depressive symptoms in women requesting induced abortion. METHODS: A Swedish multi-centre study of women requesting an induced abortion. The Screen Questionnaire - Posttraumatic Stress Disorder was used for research diagnoses of PTSD and PTSS. Anxiety and depressive symptoms were evaluated by the Hospital Anxiety and Depression Scale (HADS). RESULTS: Of the 1514 respondents, almost half reported traumatic experiences. Lifetime- and point prevalence of PTSD were 7% (95% confidence interval [CI]: 5.8-8.5) and 4% (95% CI: 3.1-5.2), respectively. The prevalence of PTSS was 23% (95% CI: 21.1-25.4). Women who reported symptoms of anxiety or depression when requesting abortion were more likely to have ongoing PTSD or PTSS. Also single-living women and smokers displayed higher rates of ongoing PTSD. CONCLUSIONS: Although PTSD is rare among women who request an induced abortion, a relatively high proportion suffers from PTSS. Abortion seeking women with trauma experiences and existing or preexisting mental disorders need more consideration and alertness when counselled for termination.

Acidemia at birth in the vigorous infant as a trigger incident to assess intrapartum care with regard to CTG patterns.

OBJECTIVE: To evaluate if acidemia in vigorous infants is a useful variable in the assessment of intrapartum care with regard to cardiotocographic (CTG) patterns during the second stage. METHODS: Cases (n = 241) were infants with an umbilical artery pH < 7.05, controls (n = 482) were infants with pH ≥ 7.05. Apgar score was ≥ 7 at 5 min in both groups. CTGs during the last two hours of labor were assessed and neonatal outcomes compared. A sub-analysis of cases with metabolic acidemia: pH < 7.00 and base deficit ≥ 12 mmol/L and acidemia: 7.00 < pH < 7.05 was performed. RESULTS: 63% of cases had a pathological CTG versus 26% of controls (p < 0.001). Patterns with severe variable decelerations had a significantly longer duration in cases. Metabolic acidemia was significantly associated with severe variable decelerations and decreased variability. Infants to cases were admitted to neonatal care in 19% versus 2% of controls (p < 0.001). With metabolic acidemia, 32% were admitted. CONCLUSION: An umbilical artery pH < 7.05 at birth of vigorous infants may be a useful variable for quality control of intrapartum management with regard to the assessment of second-stage CTGs. Differences in duration of pathological patterns indicate passiveness in academic cases.

Outcomes of gestational diabetes in Sweden depending on country of birth.

OBJECTIVE: To analyze maternal and neonatal outcomes for women with gestational diabetes mellitus (GDM) in Sweden, depending on country of birth (Nordic vs. non-Nordic women). DESIGN: Population-based cohort study using the Swedish Medical Birth register. SETTING: Data on pregnant women in Sweden with diagnosed GDM. POPULATION: All singleton births to women with GDM between 1998 and 2007 (n = 8560). METHODS: Logistic regression in an adjusted model to assess the risk of adverse maternal and neonatal outcomes. Chi-squared tests or Student's unpaired t-tests were used to analyze differences between maternal and fetal characteristics. MAIN OUTCOME MEASURES: Maternal and neonatal complications. RESULTS: GDM incidence was higher at 2.0% among non-Nordic women, compared with 0.7% in the Nordic group. The non-Nordic women were older, had less chronic hypertensive disease, smoked less, and had lower BMI and shorter height. Preeclampsia was significantly lower in the non-Nordic group. The mean birthweight (3561 vs. 3698 g, p < 0.001) and the large-for-gestational age rate (11.7 vs. 17.5%, p < 0.001) were significantly lower in the non-Nordic group. Large-for-gestational age was dependent on maternal height [crude odds ratio 0.6 (0.5-0.7) and adjusted odds ratio 0.8 (0.6-0.9)]. CONCLUSIONS: Non-Nordic women with GDM in Sweden have better obstetrical and neonatal outcomes than Nordic women. These results do not support the idea of inequality of health care. Large-for-gestational age as a diagnosis is highly dependent on maternal height, which raises the question of the need for individualized growth curves.

Acidemia at birth, related to obstetric characteristics and to oxytocin use, during the last two hours of labor.

OBJECTIVE: Evaluate obstetric characteristics during the last two hours of labor in neonates born with acidemia. DESIGN: Case-control study. SETTING: Delivery units at two university hospitals in Sweden. STUDY POPULATION: Out of 28,486 deliveries during 1994-2004, 305 neonates had an umbilical artery pH value <7.05 at birth. CASES: neonates with an umbilical artery pH < 7.05. Controls were neonates with pH > or = 7.05 and an Apgar score > or =7 at 5 minutes. Obstetric characteristics, cardiotocographic patterns and oxytocin treatment during the last two hours of labor were recorded. RESULTS: In the univariate analysis, > or =6 contractions/10 minutes (odds ratio (OR) 4.94, 95% confidence interval (CI) 3.25-7.49), oxytocin use (OR 2.20, 95% CI 1.66-2.92), bearing down > or =45 minutes (OR 1.77, 95% CI 1.31-2.38) and occipito-posterior position (OR 2.18, 95% CI 1.19-3.98) were associated with acidemia at birth. In the multivariate analysis, only > or =6 contractions/10 minutes (OR 5.36, 95% CI 3.32-8.65) and oxytocin use (OR 1.89, 95% CI 1.21-2.97) were associated with acidemia at birth. Among cases with > or =6 contractions/10 minutes, 75% had been treated with oxytocin. Pathological cardiotocographic patterns occurred in 68.8% of cases and in 26.1% of controls (p<0.001). CONCLUSION: A hyperactive uterine contraction pattern and oxytocin use are the most important risk factors for acidemia at birth. The increased uterine activity was related to overstimulation in the majority of cases. The duration of bearing down is less important when uterine contraction frequency has been considered.

Teenage mothers -- a high-risk group for new unintended pregnancies.

INTRODUCTION: One of the targets of national health programs is to prevent unintended pregnancies, especially among teenagers. It is well established that these often lead to abortion. Preventive programs aimed at decreasing abortion rates should identify target groups at risk for unintended pregnancies. PURPOSE: This study was conducted to determine whether young mothers under 20 years of age constitute a group at risk for new unintended pregnancies. METHODS: A retrospective cohort study comprising teenagers giving birth to their first child from 1996 to 2000 was performed at Orebro University Hospital, Sweden. Data were collected from antenatal and medical records with particular regard to compliance with the postpartum visit and to whether a contraceptive method was prescribed. Information concerning repeat pregnancies during the 12 months after delivery was obtained. RESULTS: A total of 250 deliveries were recorded; 70% of the mothers attended the postpartum visit, and 71% received contraceptive prescriptions. At the 12-month follow-up, 56 (25%) had a new pregnancy, and of those, 20 (36%) had a legal abortion, making the abortion rate fivefold higher than expected in this age group. CONCLUSION: This study shows that teenagers giving birth constitute a high-risk group for future unintended pregnancies and legal abortion.

Gestational diabetes and preeclampsia.

OBJECTIVE: To determine whether gestational diabetes mellitus (GDM) increases the risk for preeclampsia independent of other risk factors. STUDY DESIGN: The association between GDM and preeclampsia was analyzed in a population of women who had given birth to singletons registered in Swedish Medical Birth Register from 1992 through 1996 (n=430,852). RESULTS: GDM occurred in 0.8% and preeclampsia in 2.9% of all pregnancies. The rate of preeclampsia was higher in the GDM than in the non-GDM group (6.1% versus 2.8%). High age, nullipara, chronic hypertension, kidney disease, and high body mass index (BMI) were all independently associated with increased risk for preeclampsia. Smoking was associated with decreased risk. Adjusted odds ratio for GDM as a risk factor for preeclampsia was 1.61 (95% confidence interval (CI) 1.39-1.86) when prepregnancy BMI, which was a true confounder, was included in the last step of the multiple logistic regression analysis. CONCLUSIONS: There is an independent and significant association between GDM and preeclampsia. Obesity is a major confounding factor but could not explain the total excess risk.

Repeated random blood glucose measurements as universal screening test for gestational diabetes mellitus.

BACKGROUND: To determine the value of repeated random blood glucose (R-B-glucose) measurements alone or in combination with traditional risk factors [family history of diabetes, obesity, prior large-for-gestational-age (LGA) infant or prior gestational diabetes mellitus (GDM)] to predict the outcome of the oral glucose tolerance test (OGTT). METHODS: A prospective population-based study was undertaken in a Swedish county. All pregnant nondiabetic women (n = 4918) visiting the maternal health care clinics over a 2-year period were offered a 75-g OGTT in gestational weeks 28-32. Traditional risk factors and values of repeated R-B-glucose measurements were registered, as well as the results of the OGTT, in terms of fasting B-glucose and 2-h B-glucose. RESULTS: A total of 3616 women (73.5%) had an OGTT. Of these, 1.7% had GDM, 1.3% impaired glucose tolerance (IGT) and 0.4% diabetes mellitus (DM). An R-B-glucose cut-off level > or =8.0 mmol/L as the only indicator for an OGTT was optimal for detecting GDM with regard to sensitivity (47.5%) and specificity (97.0%). It has the same sensitivity for detecting GDM as using traditional risk factors, but reduces the need to carry out the OGTT from 15.8% to 3.8% of the population. Combined with prior LGA infant or prior GDM as indications for the OGTT in the present study, all women with DM and 44.7% of those with IGT will be identified. Only 7.3% of the population will have to take the OGTT. CONCLUSION: A random B-glucose level > or = 8.0 mmol/L prior LGA infant or prior GDM as an indicator for taking the OGTT is a simple and effective first step in a two-step screening model for GDM.

Maternal and fetal outcomes if gestational impaired glucose tolerance is not treated.

OBJECTIVE: To evaluate whether there is increased maternal or neonatal morbidity in connection with impaired glucose tolerance (IGT) during pregnancy when the condition is not treated. RESEARCH DESIGN AND METHODS: During the study period of 1997-2001, in a defined geographical area in Sweden, the diagnostic criteria for gestational diabetes mellitus (GDM) were limited to the criteria for diabetes. Prospectively, 213 women who were identified with IGT during pregnancy were undiagnosed and untreated. Data on maternal and fetal outcome was collected from records. For each case subject, four control subjects were taken from the same delivery department. RESULTS: The proportion of women who underwent cesarean section was significantly higher in the case subjects than in the control subjects and was independently associated with IGT. The adjusted odds ratio (OR) was 1.9 (95% CI 1.2-2.9). The proportion of infants who were large for gestational age (LGA), defined as birth weight >2 SDs greater than the mean for gestation and sex, was independently significantly associated with untreated IGT during pregnancy (OR 7.3, 95% CI 4.1-12.7). Admission to a neonatal intensive care unit (NICU) for 2 days or longer was more common (adjusted OR 2.0, 95% CI 1.1-3.8). However, 71.3% of the children in the IGT group and 87.3% of the control subjects had no neonatal complications. CONCLUSIONS: There is increased independent association between cesarean section rate, prematurity, LGA, and macrosomic infants born to mothers with untreated IGT. Most of the children were healthy, but there is still increased morbidity. Therefore, to evaluate the effects of treatment, there is a need for a randomized study.

Occurrence of gestational diabetes mellitus and the value of different screening indicators for the oral glucose tolerance test.

BACKGROUND: The objective of the present study was to determine prevalence of gestational diabetes mellitus (GDM) in terms of impaired glucose tolerance (IGT) and diabetes mellitus (DM), and the value of traditional anamnestic risk factors for predicting outcome of the oral glucose tolerance test (OGTT). METHODS: A prospective population-based study in a defined geographic area in Sweden. All pregnant nondiabetic women (n = 4918) attending maternal health care from July 1994 to June 1996 were offered a 75g OGTT in gestational weeks 28-32. Traditional anamnestic risk factors, as well as results of the OGTT in terms of fasting-B-glucose and 2h-B-glucose, were registered. RESULTS: 3616 (73.5%) women agreed to perform the OGTT. Sixty-one (1.7%) of those had GDM [47 (1.3%) had impaired glucose tolerance and 14 (0.4%) had diabetes mellitus]. 15.8% fulfilled traditional risk factor criteria. Traditional anamnestic risk factors as an indicator to perform an OGTT identified 29/61 GDM women and 9/14 women with DM. Among primiparas, 4/21 with gestational diabetes mellitus were detected. CONCLUSION: Using traditional risk factors as an indicator to perform an OGTT gives a low sensitivity to detect GDM and even DM especially among primiparas.