BJOG An International Journal of Obstetrics & Gynaecology

To determine fetal haemodynamic responses to hyperoxaemia and hypoxaemia in early pregnancy. Repeated measurements in acute experiments. Experimental physiology laboratory. Non-invasive Doppler ultrasound of the umbilical vein, ductus venosus, umbilical and common carotid arteries of 12 fetal lambs (0.27-0.56 gestation) during maternal hyperoxaemia and hypoxaemia under ketamine anaesthesia. The effect of gestational age, hyperoxaemia, and hypoxaemia were assessed based on analysis of variance for dependent measurements and P < or = 0.05 was considered significant. Differences between groups were considered significant if the 95% confidence interval did not include zero. Gestational age had a significant effect on the blood velocity in the umbilical vein and ductus venosus. There were no circulatory changes during hyperoxaemia, but a simultaneous increase of pCO2 was an important confounder. However, hypoxaemia caused significantly reduced heart rate, reduced maximum and weighted mean blood velocity, and augmented pulsation in the umbilical vein. Hypoxaemia also caused reduced velocities in the ductus venosus (peak velocity during systole and minimum during diastole, and time-averaged velocity) and augmented pulsation of the flow velocity. Additionally, the pulsatility of blood flow increased in the umbilical artery and was reduced in the common carotid artery. Maternal hypoxaemia in early pregnancy causes similar fetal circulatory responses to those in late pregnancy: bradycardia, reduced venous flow velocities, augmented pulsatility in veins and a redistributional flow velocity pattern of the umbilical and common carotid arteries.

Sir,We read with interest the meta-analysis confirming that elec-tive caesarean section and avoidance of breastfeeding does notreduce the risks of transmission of chronic hepatitis C. Theauthors conclude that ‘‘these results do not support routineantenatal screening for hepatitis C virus infection’’, but they failto address the other benefits of antenatal testing for hepatitis C. Insome areas of Europe, the prevalence of chronic hepatitis Cinfection in pregnant women is high, typically around 1%

To investigate incidence trends and demographic, social and health factors associated with the rate of hysterectomy and morbidity outcomes in Western Australia and compare these with international studies. Population-based retrospective cohort study. All hospitals in Western Australia where hysterectomies were performed from 1981 to 2003. All women aged 20 years or older who underwent a hysterectomy. Statistical analysis of record-linked administrative health data. Rates, rate ratios and odds ratios for incidence measures and length of stay in hospital and odds ratios for morbidity measures. The age-standardised rate of hysterectomy adjusted for the underlying prevalence of hysterectomy decreased 23% from 6.6 per 1000 woman-years (95% CI 6.4-6.9) in 1981 to 4.8 per 1000 woman-years (95% CI 4.6-4.9) in 2003. Lifetime risk of hysterectomy was estimated as 35%. In 2003, 40% of hysterectomies were abdominal. The rate of hysterectomy to treat menstrual disorders fell from 4 per 1000 woman-years in 1981 to 1 per 1000 woman-years in 1993 and has since stabilised. Low socio-economic status, having only public health insurance, nonindigenous status and living in rural or remote areas were associated with increased risk of having a hysterectomy for menstrual disorders. Indigenous women had higher rates of hysterectomy to treat gynaecological cancers compared with nonindigenous women, particularly in rural areas. The odds of a serious complication were 20% lower for vaginal hysterectomies compared with abdominal procedures. Western Australia has one of the highest hysterectomy rates in the world, although proportionally, significantly fewer abdominal hysterectomies are performed than in most countries.

To study whether pregnancy week at delivery is an independent risk factor for shoulder dystocia. Population study. Medical Birth Registry of Norway. All vaginal deliveries of singleton offspring in cephalic presentation in Norway during 1967 through 2009 (n = 2 014 956). The incidence of shoulder dystocia was calculated according to pregnancy week at delivery. The associations of pregnancy week at delivery with shoulder dystocia were estimated as crude and adjusted odds ratios using logistic regression analyses. We repeated the analyses in pregnancies with and without maternal diabetes. Shoulder dystocia at delivery. The overall incidence of shoulder dystocia was 0.73% (n = 14 820), and the incidence increased by increasing pregnancy week at delivery. Birthweight was strongly associated with shoulder dystocia. After adjustment for birthweight, induction of labour, use of epidural analgesia at delivery, prolonged labour, forceps-assisted and vacuum-assisted delivery, parity, period of delivery and maternal age in multivariable analyses, the adjusted odds ratios for shoulder dystocia were 1.77 (1.42-2.20) for deliveries at 32-35 weeks of gestation, and 0.84 (0.79-0.88) at 42-43 weeks of gestation, using weeks 40-41 as the reference. In pregnancies affected by diabetes (n = 11 188), the incidence of shoulder dystocia was 3.95%, and after adjustment for birthweight the adjusted odds ratio for shoulder dystocia was 2.92 (95% CI 1.54-5.52) for deliveries at weeks 32-35 of gestation, and 0.91 (95% CI 0.50-1.66) at 42-43 weeks of gestation. The risk of shoulder dystocia was associated with increased birthweight, diabetes, induction of labour, use of epidural analgesia at delivery, prolonged labour, forceps-assisted and vacuum-assisted delivery, parity and period of delivery but not with post-term delivery.

Women are increasing soy intake to prevent uterine cancer. The amount that would do this is unknown. What is known is that over 0.07 g of soy isoflavones per day results in endometrial profusion and bleeding. In the recent article by Myung et al.,1 showing a usefulness of soy intake in decreasing the risk of endocrine‐related gynaecological cancer, the optimal amount of soy food intake for the prevention of endocrine‐related gynaecological cancers remained undetermined. Of interest, dose‐related effects of isoflavones on endometrial bleeding in perimenopausal and postmenopausal women have been evaluated. • 0.20 g/day or 2 liters of soy milk for 3 years was associated in a single case study with abnormal uterine bleeding with endometrial pathology.2, 3 0.15 g/day for 5 years was associated with significantly higher endometrial hyperplasia.4 0.092 g/day of isoflavones for 6 months was associated with one of 19 (5%) cases of endometrial proliferation in women aged over 40 years with no period for the past year.5 0.080 g/day of total isoflavones was associated with three of 32 (9%) postmenopausal women aged 40–60 years presenting with endometrial activity.6 0.070 g/day of isoflavones for 12 months was associated with bleeding in eight of 395 (2%) postmenopausal women aged 45–65 years with no normal periods for at least 2 years.7 0.054 g/day of isoflavones for 2 years in 389 postmenopausal women yielded no endometrial hyperplasia or bleeding.8 0.050 g/day of isoflavones for 12 weeks in 177 postmenopausal women with an average age of 55 years yielded no endometrial hyperplasia.9 An intake of isoflavones of more than 0.070 g/day was associated with endometrial bleeding in postmenopausal women. Unfortunately, few products are currently labelled with their isoflavone content. https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/j.1471-0528.2009.02490.x

Objective To compare rates of adverse perinatal outcomes between planned home births versus planned hospital births. DesignA nationwide cohort study. SettingThe Netherlands. PopulationLow-risk women in midwife-led care at the onset of labour. Methods Analysis of national registration data. Main outcome measuresIntrapartum and neonatal death, Apgar scores, and admission to a neonatal intensive care unit (NICU) within 28days of birth. ResultsOf the total of 814979 women, 466112 had a planned home birth and 276958 had a planned hospital birth. For 71909 women, their planned place of birth was unknown. The combined intrapartum and neonatal death rates up to 28days after birth, including cases with discrepancies in the registration of the moment of death, were: for nulliparous women, 1.02 for planned home births versus 1.09 parts per thousand for planned hospital births, adjusted odds ratio (aOR) 0.99, 95% confidence interval (95% CI) 0.79-1.24; and for parous women, 0.59 parts per thousand versus 0.58 parts per thousand, aOR 1.16, 95% CI 0.87-1.55. The rates of NICU admissions and low Apgar scores did not significantly differ among nulliparous women (NICU admissions up to 28days, 3.41 parts per thousand versus 3.61 parts per thousand, aOR 1.05, 95% CI 0.92-1.18). Among parous women the rates of Apgar scores below seven and NICU admissions were significantly lower among planned home births (NICU admissions up to 28days, 1.36 versus 1.95 parts per thousand, aOR 0.79, 95% CI 0.66-0.93). Conclusions We found no increased risk of adverse perinatal outcomes for planned home births among low-risk women. Our results may only apply to regions where home births are well integrated into the maternity care system.

The objective of the study was to determine the efficacy of 1,5-anhydro-D-glucitol (1,5 AG) for the prediction of gestational diabetes and gestational impaired glucose tolerance (GIGT). One hundred and eighty-five pregnant women with epidemiological risk factors of gestational diabetes or GIGT underwent 75 g oral glucose tolerance test and plasma 1,5 AG assay at 26 to 28 weeks of gestation. There was no significant difference in plasma 1,5 AG either before or after an oral glucose load. The area under the receiver operator characteristic curve for 1,5 AG was only 0.485 which implies that 1,5 AG is a poor predictor of GIGT or gestational diabetes.

The role of cytokines in protecting against human papillomavirus (HPV) and HPV-associated disease is not fully understood. We compared the frequency of the interleukin (IL)-10 polymorphism (G allele) at position --1082 and the distribution of GG/GA/AA genotypes among 116 HPV-positive women, grouped according to their cervical cytological profiles, with 119 HPV-negative controls with normal smears. No difference was observed in genotype frequency between the groups. Among women in the HPV-positive, smear-normal group, who were re-tested for HPV after 12 months, there was a significant inverse association between presence of at least one variant G allele (high activity) and HPV persistence (OR per G allele = 0.082 [95% CI 0.009-0.73], P= 0.001; after controlling for ethnicity). This association remained significant after controlling for age, smoking and hormonal contraception (OR = 0.028 [95% CI 0.001-0.66], P= 0.001). This preliminary study suggests that higher levels of IL-10 may prevent cervical neoplasia through their role in eliminating HPV.

The clinical and endometrial efficacy and lipid response of two different doses of intrauterine levonorgestrel were assessed in comparison with sequential oral medroxyprogesterone acetate in postmenopausal women receiving continuous oral E2-valerate. One-year prospective multicentre randomised control trial. Four outpatient clinics in Oulu, Helsinki and Jyväskylä, Finland. A total of 163 healthy volunteer postmenopausal women with climacteric complaints or already using hormone replacement therapy (HRT). Subjects were randomly allocated to receive a new intrauterine system releasing 10 microg of levonorgestrel daily or an established intrauterine system (Mirena) releasing 20 microg of levonorgestrel daily or sequential oral medroxyprogesterone acetate (5mg/day, 14/30 days). All three regimens were combined with an oral daily dose of 2mg of E2-valerate. Bleeding patterns were assessed by diaries kept by the subjects. Endometrial effects were evaluated by histologic biopsies taken at the baseline and after six and 12 months of therapy. Serum concentrations of total, HDL and LDL cholesterol, triglycerides and lipoprotein(a) were determined at the baseline and after six and 12 months of therapy. Insertion of the smaller 10 microg levonorgestrel system was easy in 70% and difficult in 4% and that of Mirena was easy in 46% and difficult in 21% of the subjects. After six months of therapy, 43 (95.6%) of the 47 subjects receiving 10 microg levonorgestrel and 54 (98.2%) of the 55 subjects receiving 20 microg levonorgestrel had no bleeding, while the sequential medroxyprogesterone acetate regimen produced typical cyclic withdrawal bleedings. Endometrial hyperplasia was not observed in any of the treatment groups during the 12-month study. After 12 months of therapy, strong endometrial suppression was found in 46/47 and 55/55 of the subjects receiving 10 microg and 20 microg of levonorgestrel, respectively, while the endometrium was proliferative in 18/47 of the subjects in the medroxyprogesterone acetate group. Serum total cholesterol decreased in all treatment groups. HDL cholesterol increased in women receiving medroxyprogesterone acetate or the smaller intrauterine dose of levonorgestrel. Both intrauterine doses of levonorgestrel provided good endometrial protection in postmenopausal women on oestrogen replacement therapy. The advantage of the 10 microg system with a smaller size is the easier insertion of the system and a minimal attenuation of the favourable effects of oral oestrogen on the serum lipid profile.

To evaluate two algorithms for prediction of preeclampsia in a population of nulliparous women in Norway. Prospective screening study. National Centre for Fetal Medicine in Trondheim, Norway. Five hundred and forty-one nulliparous women. The women were examined between 11(+0) and 13(+6) weeks with interviews for maternal characteristics and measurements of mean arterial pressure, uterine artery pulsatility index, pregnancy-associated plasma protein A and placental growth factor. The First Trimester Screening Program version 2.8 by The Fetal Medicine Foundation (FMF) was compared with the Preeclampsia Predictor TM version 1 revision 2 by Perkin Elmer (PREDICTOR). Prediction of preeclampsia requiring delivery before 37 weeks, before 42 weeks and late preeclampsia (delivery after 34 weeks). The performance of the two algorithms was similar, but quite poor, for prediction of preeclampsia requiring delivery before 42 weeks with an area under the curve of 0.77 (0.67-0.87) and sensitivity 40% (95% CI 19.1-63.9) at a fixed 10% false positive rate for FMF and 0.74 (0.63-0.84) and sensitivity 30% (95% CI 11.9-54.3) at a fixed 10% false positive rate for PREDICTOR. The FMF algorithm for preeclampsia requiring delivery <37 weeks had an area under the curve of 0.94 (0.86-1.0) and sensitivity of 80% (95% CI 28.4-99.5) at a 10% fixed false positive rate. Fetal Medicine Foundation and PREDICTOR algorithms had similar and only modest performance in predicting preeclampsia. The results indicate that the FMF algorithm is suitable for prediction of preterm preeclampsia. © 2014 Royal College of Obstetricians and Gynaecologists.

To investigate whether maternal serum levels of 25-hydroxyvitamin D [25(OH)D] in the first trimester are altered in pregnant women with pre-existing type 2 diabetes, women who subsequently develop gestational diabetes mellitus (GDM) and women who deliver large for gestational age (LGA) neonates compared with normoglycaemic pregnant women who deliver an appropriate for gestational age (AGA) neonate. Case-control study. Antenatal clinic. Singleton pregnancies at 11(+0) -13(+6) weeks, including 50 women with type 2 diabetes, 100 women who subsequently developed GDM, 50 nondiabetic women who subsequently delivered LGA neonates and 1000 nondiabetic controls who delivered AGA neonates. Maternal serum total 25(OH)D levels were measured in the four groups of pregnancies. Multiple regression analysis in the controls was used to identify factors among maternal characteristics with a significant contribution to the levels of serum 25(OH)D, so that the values in all cases were expressed as a multiple of the median (MoM) in the controls. Comparison of MoM 25(OH)D in the four groups. In controls, significant independent contributions to the serum level of 25(OH)D were provided by maternal age, body mass index, smoking status, racial origin and season of sampling. The median and interquartile range (IQR) of serum 25(OH)D in the type 2 diabetes group (1.01; IQR, 0.68-1.47 MoM), GDM group (0.93; IQR, 0.67-1.23 MoM) and LGA group (0.97; IQR, 0.67-1.25 MoM) were not significantly different from those in the controls (0.99; IQR, 0.71-1.33 MoM) (overall P = 0.643). The first-trimester maternal serum level of 25(OH)D is not altered in women with type 2 diabetes, those who develop GDM or those who deliver LGA neonates.

To determine the occurrence of high venous velocities at the umbilical ring in the normal early second trimester, based on the assumption that a narrow umbilical ring may cause obstruction and increased venous blood velocity at the abdominal wall. Cross-sectional study. Hospital antenatal clinic. One hundred and one low risk singleton pregnancies specifically recruited for the study. Ultrasound was used at 11-19 weeks to determine the diameter and velocity in the umbilical vein at the fetal end of the cord and at the inlet through the abdominal wall. Outcome measures 10th, 50th and 90th centiles were estimated for the time-averaged maximum velocity in the cord and at the abdominal inlet. The increase of velocity as the blood entered the abdominal wall was calculated in percent of the velocity in the cord. During weeks 11-12 there was hardly any difference between blood velocity in the umbilical vein at the umbilical ring and that in the cord. From week 13 onwards it was increasingly common to find blood acceleration at the umbilical ring of 50-500%. Velocity increment >50% was found in 0/12 fetuses (0%) at 11-12 weeks, 5/20 (25%) at 13-14 weeks, and in 21/28 (75%) at 17-19 weeks. Blood velocity is higher in the umbilical vein at the abdominal wall than the cord, particularly after 13 weeks of gestation. If acceleration of blood velocity at the umbilical ring is a sign of a narrow inlet, it seems that a progressive tightening occurs during the second trimester.

In a number of pregnant women ovarian cysts are found incidentally during the routine first trimester scan. These cysts may pose diagnostic difficulties, and the measurement of serum CA125 levels can be used to aid management. In this study we measured maternal serum CA125 levels in 188 women with uncomplicated pregnancies between 11-14 weeks of gestation. All women had morphologically normal ovaries observed on ultrasound examination. The median serum CA125 levels were 23.4 U/mL (range 2.2-166.3 U/mL, 95% reference interval 5.28-70.15) and did not change significantly with gestation. We conclude that CA125 levels are increased at 11-14 weeks of gestation and cut off values which are used to assess the nature of ovarian cysts in nonpregnant women cannot be applied to pregnant women at this gestation.

To determine the performance of screening for pre-eclampsia by maternal characteristics, urine albumin concentration and albumin-to-creatinine ratio (ACR) at 11(+0) to 13(+6) weeks. Prospective cross-sectional observational study. Routine antenatal visit. A total of 2679 pregnant women at 11(+0) to 13(+6) weeks of gestation. Maternal variables, urine albumin concentrations and ACR of 51 women who developed pre-eclampsia were compared with 2364 women who were unaffected by hypertensive disorders. Regression analysis was used first to determine which of the factors among the maternal characteristics were significant predictors of urine albumin concentration and ACR in the unaffected group and second to determine the contribution of urine albumin concentration and ACR in the prediction of pre-eclampsia. Development of pre-eclampsia. In the unaffected group, log urine albumin concentration and log ACR were influenced by ethnic origin, age, body mass index (BMI), parity and smoking. In the prediction of pre-eclampsia, significant contributions were provided by log urine albumin concentration, log ACR, ethnic origin, BMI, age, family and history of pre-eclampsia. The median urine albumin concentration and the median ACR in the pre-eclampsia group were significantly higher than those in the unaffected group. However, in screening for pre-eclampsia, the area under the receiver operating characteristic curve was not significantly improved by the combined models than with maternal variables alone. The value of urine albumin concentration was not improved by correcting for the creatinine concentration. In the prediction of pre-eclampsia, urine albumin concentration at 11(+0) to 13(+6) weeks does not provide additional value to maternal variables.

Failure to visualise the fetal nasal bones at 11-14 weeks of gestation is associated with a significant increase in the risk for trisomy 21. However, it is not known whether the ethnic origin of the mother has any effect on the fetal profile and the prevalence of this marker. Prospective study. London Teaching Hospital. Four thousand and four hundred and ninety-two consecutive fetuses undergoing routine first trimester ultrasound scanning at 11-14 weeks of gestation in a multiethnic population. Examination of the nasal bones was attempted in the fetuses. Rate of visualisation of the fetal nasal bones. Five hundred fetuses were excluded from the analysis because of chromosomal abnormalities or a technically unsatisfactory examination. In the remaining 3992 fetuses, the maternal ethnic origin was African in 13.0%, Asian in 15.3% and Caucasian in 66.0%. Compared with Caucasians, the failure to visualise the fetal nasal bones was significantly higher in women of African (P= 0.0001) but not Asian origin (P= 0.24). A multivariable logistic regression model showed that having a mother of African origin is still significantly associated with an increased likelihood of absent fetal nasal bones compared with Caucasians (odds ratio 2.33), even after correcting for maternal age, parity and crown-rump length. There is a significant difference in the rate of visualisation of the fetal nasal bones in the first trimester in mothers of different ethnic origin. This suggest that corrections for maternal ethnicity will be required to ensure equity of fetal nasal bone screening in multiracial populations. Whether corrections are required for the father's ethnic origin remains to be determined.

To assess the potential epidemiological and economic impact of a prophylactic quadrivalent human papillomavirus (HPV) (6/11/16/18) vaccine for preventing cervical cancer, cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3), CIN1 and genital warts. Cost-utility analysis. UK. Female and male UK population 12 years or older. We adapted a previously developed multi-HPV type dynamic transmission to compare four female vaccination strategies, routine vaccination at age 12 years, and routine vaccination at age 12 years combined with temporary catch-up vaccination at ages 12-14, 12-17 and 12-24 years. Costs, cases avoided, incremental cost per quality-adjusted life year (QALY). The model projected that at year 100, each vaccination strategy could reduce the number of HPV 6/11/16/18-related cervical cancer, CIN2/3, CIN1 and genital wart cases among women by 86, 85, 79 and 89% respectively. Over 25 years, routine vaccination at age 12 years combined with a 12- to 24-year-old catch-up programme was the most effective strategy, reducing the cumulative number of cases of cervical cancer, CIN2/3, CIN1 and genital warts by 5800, 146 000, 28 000, and 1.1 million respectively. Over 100 years, the incremental cost-effectiveness ratios across all strategies ranged from pound5882 to pound11,412 per QALY gained. In the UK, a quadrivalent HPV vaccination programme that includes a catch-up strategy can reduce the incidence of cervical cancer, CIN and genital warts at a cost per QALY ratio within the range typically regarded as cost-effective.

To compare women's experiences of either see and treat (ST) or defer and treat (DT) at first visit to colposcopy following abnormal cytology. A prospective postal questionnaire survey. Colposcopy clinics of a University Hospital. A total of 272 women with high-grade cervical intraepithelial neoplasia (CIN) referred to colposcopy. A total of 136 women receiving ST and a matched sample of women receiving DT (N = 136) were sent a postal questionnaire 7 days after first appointment at colposcopy to assess evaluations of their experience, psychological distress and relief. Subsequent appointment keeping was extracted from medical records. Anxiety and subsequent behaviour. Women undergoing ST were significantly less anxious and more relieved than those undergoing DT. They also evaluated their first appointment as more motivationally congruent. While women undergoing ST were less likely than DTs to keep their second appointment, there was no overall difference in did not attend (DNA) rates at 15-month follow up. ST is psychologically beneficial and may be preferred by women with CIN2/3.

To assess the reduction in size of fibroids following uterine artery embolisation and to analyse women's views of the success of treatment. An uncontrolled case series of 114 consecutive women who underwent uterine artery embolisation for the treatment of fibroids over two years. The Diagnostic and Interventional Radiology Department at The Royal Surrey County Hospital, Guildford, UK. Bilateral uterine artery embolisation was performed for the treatment of symptomatic fibroids. Magnetic resonance imaging was carried out before and six months following embolisation. Women completed outcome questionnaires following their treatment. The sites. imaging signal characteristics and percentage reduction in the volume of three dominant fibroids were determined from the magnetic resonance scans. Outcome was measured by questionnaire. Women were asked whether their symptoms resolved completely, improved, remained unchanged or deteriorated. One hundred and sixty-five fibroids of 114 women (mean age 42) were analysed. Forty-five percent of women had complex fibroid masses and 50% had fibroids > or =8.5cm in diameter. The median reduction in the fibroid volume was 58%. The median reduction of the volume of complex fibroid masses, submucous fibroids, fibroids > or =8.5cm and fibroids with high and low signal on T2 weighted sequences were 58%, 63%, 50%, 62% and 51%, respectively. Ninety-one percent of the women's symptoms had resolved or improved following embolisation. The majority of women were satisfied with their outcome. We have shown that uterine artery embolisation is a successful treatment for symptomatic fibroids of all types, sizes and signal characteristics.

To study the relationship between lymphovascular space involvement (LVSI) in stage 1a or 1b well-differentiated endometrial cancer and survival. Retrospective study consisting of a search of an oncology database to identify women with endometrial cancer between January 1990 and December 2004. Tertiary referral centre, Dublin, Ireland. Women who had well-differentiated stage 1a or 1b endometrial cancer. During the period 1990-2004, 226 patients with endometrial cancer were treated in the National Maternity Hospital, Dublin. We looked at all patients who had well-differentiated endometrioid adenocarcinoma of the endometrium with invasion of <50% thickness of the myometrium. Forty-one patients fulfilled these inclusion criteria. The presence or absence of LSVI was determined by review of haematoxylin and eosin sections. Patients were followed for 5 years or till death if earlier. Mortality was calculated. Statistical analysis was performed using Fisher's exact test. An odds ratio and 95% confidence interval was calculated using fixed effect Mantel-Haenszel model. Death from recurrence of endometrial cancer. Of the 41 patients, five (12%) were found to have (LVSI). Of the five patients with LVSI, three (60%) patients died of recurrence. All patients with recurrence died of disease and none of the patients without LVSI died (0 of 36). Overall, the survival rate was 92.7%. The presence of LVSI was a highly significant predictor of recurrence (P < 0.001). In patients with early stage well-differentiated adenocarcinoma of the endometrium, the presence of LVSI is associated with a high risk of death.

To analyse the fertility rates, complications and recurrences in a group of women who have undergone radical vaginal trachelectomy and pelvic lymphadenectomy for early-stage cervical cancer. An observational series. A Gynaecological Oncology Centre. One hundred and twenty-three consecutive women who underwent radical vaginal trachelectomy and pelvic lymphadenectomy for early-stage cervical cancer. Data were collected prospectively. MAIN OUTCOME MEASURES Complications, recurrences, pregnancies and live births are presented as percentages of the total population. Fertility is presented as a 5-year cumulative rate, with women attempting to conceive as the denominator. A total of 123 women were followed up for an average of 45 months. Eleven (8.9%) had completion treatment (two radical hysterectomies and nine chemoradiotherapy) at the time of initial treatment. There were three recurrences (2.7%) among the women who did not have completion treatment and two (18.2%) in those who did. There were 6 perioperative and 26 postoperative complications. Sixty-three women attempted pregnancy. There were 55 pregnancies in 26 women and 28 live births in 19. Three women had continuing pregnancies. The 5-year cumulative pregnancy rate among women trying to conceive was 52.8%. All but two women were delivered by classical caesarean section and seven (25.0%) babies were born at 31+6 weeks or less. For selected women with early-stage cervical cancer, radical vaginal trachelectomy and pelvic lymphadenectomy are fertility-sparing options, with a low incidence of recurrence and acceptable cumulative conception rates. Complications are few, although there is a high premature labour and miscarriage rate among pregnant women.

To evaluate the safety of KUR-1246 as a tocolytic agent, we examined the effects of its long term infusion on respiratory and cardiovascular systems and general metabolism in pregnant sheep and their fetuses. Animal experiment with chronically instrumented ewes and their fetuses. Center for animal experiments, Hokkaido University School of Medicine, Japan. Eight Suffolk ewes at 117 to 120 days of gestation. At 120-124 days of gestation, ewes (n= 4) were infused intravenously for 24 hours with KUR-1246 at 0.03 microg/kg/minute, a dose that completely inhibits oxytocin-induced uterine contractions in pregnant sheep. The controls received saline instead (n= 4). Statistical comparisons were carried out by repeated-measures ANOVA followed by Dunnett's test. Maternal and fetal values of heart rate, blood pressure, plasma electrolytes, glucose, insulin and non-esterified fatty acid levels, and blood gases and lactate level. The maternal plasma levels of KUR-1246 increased and reached a plateau at 15 hours or later from the start of the infusion, whereas the fetal levels of it were below the lower limit of quantification (0.1 ng/mL) throughout the experiment. Significant differences over time between the ewes that had received with KUR-1246 and the controls were found for the following parameters: maternal heart rate, blood lactate, plasma glucose, and plasma insulin levels, and fetal plasma glucose and plasma insulin levels (P < 0.05). In the KUR-1246 treated ewes, significant changes from the pre-infusion value were detected in maternal blood lactate and fetal plasma glucose levels within 6 hours from the start of the infusion (P < 0.05). No significant differences were observed in other parameters in either ewes or fetuses. The physiologic changes induced by a 24-hour infusion of KUR-1246 were transient and considered to be within the compensatory capacity in both pregnant ewes and their fetuses, suggesting that KUR-1246 is a potentially safe tocolytic agent for use by long term infusion.

To investigate persistent faecal incontinence (FI) 12 years after birth and association with delivery mode history and quality of life. Twelve-year longitudinal study. Maternity units in Aberdeen, Birmingham and Dunedin. Women who returned questionnaires 3 months and 12 years after index birth. Data on all births over 12 months were obtained from units and women were contacted 3 months, 6 years and 12 years post birth. Persistent FI, defined as reported at 12 years and one or more previous contacts. SF12 assessed quality of life. Of 7879 women recruited at 3 months, 3763 responded at 12 years, 2944 of whom also responded at 6 years: nonresponders were similar in obstetric factors. Prevalence of persistent FI was 6.0% (227/3763); 43% of 12-year responders who reported FI at 3 months also reported it at 12 years. Women with persistent FI had significantly lower SF12 scores. Compared with only spontaneous vaginal deliveries, women who had one or more forceps delivery were more likely to have persistent FI (odds ratio [OR] 2.08, 95% confidence interval [95% CI] 1.53–2.85) but it was no less likely with exclusively caesarean births (OR 0.93, 95% CI 0.54–1.58). More obese women than normal weight women reported persistent FI (OR 1.52, 95% CI 1.06–2.17). This longitudinal study has demonstrated persistence of FI many years after birth and shown that one forceps birth increased the likelihood, whereas exclusive caesarean birth showed no association. Obesity, which increased symptom likelihood, is a modifiable risk factor.

To assess the value of placental protein 13 (PP13) as an early marker of pre-eclampsia. Sequential blood samples were obtained from women with singleton viable pregnancies at 6-10, 16-20 and 24-28 weeks of gestation. Samples were tested for PP13 using a solid-phase sandwich enzyme-linked immunosorbent assay. Levels were expressed as multiples of the medians (MoM) of the unaffected population. The slope or rate of change in PP13 concentration per week of gestation was also calculated. Thirty-five prenatal care community clinics. In total, 1,366 women were recruited, and subsequently, 20 were diagnosed with pre-eclampsia, 41 with gestational hypertension and 1,178 were unaffected. Sensitivity and specificity of screening with PP13 at each gestational period and of PP13 level combined with the slope of PP13 between two testing periods. At 6-10 gestational weeks, PP13 levels were significantly lower among the pre-eclampsia group with a median 0.28 MoM (95% CI 0.15-0.39, P < 0.004). Using a cutoff of 0.40 MoM, the sensitivity was 80%, false-positive rate (FPR) was 20% and odds ratio was 16.0 (95% CI 5.3-48.4). Combining MoM of 6-10 weeks and slope between 6-10 and 16-20 weeks, the sensitivity was 78%, the FPR was 6% and odds ratio was 55.5 (95% CI 18.2-169.2). The gestational hypertension group was not different from the normal group. PP13 in the first trimester alone or in combination with the slope between the first and the second trimesters may be a promising marker for assessing the risk of pre-eclampsia.

To compare the psychological impact, acceptability and clinical effectiveness of medical versus surgical termination of pregnancy (TOP) at 13-20 weeks of gestation. Randomised trial. Large UK tertiary centre. Women accepted for TOP at 13-20 weeks of gestation. Medical TOP (MTOP) using mifepristone and misoprostol or surgical TOP (STOP) by vacuum aspiration at <15 weeks of gestation, and by dilatation and evacuation at 15 or more weeks of gestation. Distress 2 weeks after TOP, measured by the impact of events scale (IES), and acceptability, measured by the proportion of women who would opt for the same procedure again. One hundred and twenty two women were randomised: 60 to the MTOP group and 62 to the STOP group. Twelve women opted to continue their pregnancy. Follow-up rates were low (n=66/110; 60%). At 2 weeks post-procedure there was no difference in total IES score between groups. However, compared with women undergoing STOP, women undergoing MTOP had a higher score on the IES intrusion subscale (mean difference 6.6; 95% CI 1.4-11.8), and a higher score on the general health questionnaire (GHQ) (P=0.033). Women found STOP more acceptable: compared with MTOP, more women would opt for the same procedure again (100% versus 53%, P≤0.001), and fewer women found the experience to be worse than expected (0% versus 53%, P=0.001). Women who had MTOP experienced more bleeding (P=0.003), more pain on the day of the procedure (P=0.008), and more days of pain (P=0.020). Of the 107 women who declined to participate, 58 (67%) preferred a STOP. Randomised trials of women requesting midtrimester TOP are challenging. Women found STOP less painful and more acceptable than MTOP.

To compare the impact of 1000 micrograms of self-administered vaginal misoprostol versus self-administered vaginal placebo on preoperative cervical ripening after pre-treatment with estradiol vaginal tablets at home in postmenopausal women prior to day-care operative hysteroscopy. Randomised double-blind placebo-controlled sequential trial. The boundaries for the sequential trial were calculated on the primary outcomes of a difference of cervical dilatation > or = 1 millimetre, with the assumption of a type 1 error of 0.05 and a power of 0.95. Norwegian university teaching hospital. Postmenopausal women referred for day-care operative hysteroscopy. The women were randomised to either 1000 micrograms of self-administered vaginal misoprostol or self-administered vaginal placebo the evening before day-care operative hysteroscopy. All women had administered a 25-microgram vaginal estradiol tablet daily for 14 days prior to the operation. Preoperative cervical dilatation (difference between misoprostol and placebo group, primary outcome), difference in dilatation before and after administration of misoprostol or placebo, number of women who achieve a preoperative cervical dilatation > or = 5 millimetres, acceptability, complications and side effects (secondary outcomes). Intra-operative findings and distribution of cervical dilatation in the two treatment groups: values are given as median (range) or n (%). Difference in dilatation before and after administration of misoprostol and placebo: values are given as median (range) of intraindividual differences. Percentage of women who achieve a cervical dilatation of > or = 5 mm, percentage of women who were difficult to dilate. Acceptability in the two treatment groups: values are given as completely acceptable n (%), fairly acceptable n (%), fairly unacceptable n (%), completely unacceptable n (%). Pain in the two treatment groups: pain was measured with a visual analogue scale ranging from 0 (no pain) to 10 (unbearable pain): values are given as median (range). Occurrence of side effects in the two treatment groups. Values are given as n (%). Complications given as n (%). No pharmaceutical company was involved in this study. A research grant from the regional research board of Northern Norway has been awarded to finance Dr K.S.O.'s leave from Hammerfest hospital as well as travel expenses between Hammerfest and Oslo, and research courses. The research grant from Prof B.I.N. (Helse Øst) funded the purchase of estradiol tablets, the manufacturing costs of misoprostol and placebo capsules from the hospital pharmacy, as well as the costs incurred for preparing the randomisation schedule and distribution of containers containing capsules to hospital. Prof B.I.N.'s research grant also funded insurance for the study participants. Estimated completion date 31 December 2008.

Documented routine antenatal anti-D prophylaxis was given to 90% and 81-87% of eligible women at 28 and 34 weeks of gestation, respectively, during the early 1990s and early 2000s. With increasing experience and education, a significant improvement in the timing of the first (OR 0.26, 95% CI 0.16-0.41: P < 0.0001) and second injections (OR 0.40, 95% CI 0.26-0.61: P < 0.0001) occurred during the latter period. Despite these improvements, there was no reduction in the sensitisation rate at 0.4%. However, this low rate occurred despite significant proportions of women delivering more than 42 days after the second injection. Fifteen of the 16 sensitised women had received routine antenatal prophylaxis.

To examine the accuracy of sonographic determination of chorionicity in twin pregnancies at 10-14 weeks of gestation. Prospective study on the sonographic prediction of chorionicity at 10-14 weeks of gestation. During a 30 month period, from October 1997 to May 2000, 165 women attending the departments of fetal medicine or ultrasound. Sonographic criteria used in the diagnosis of chorionicity were the number of placental sites, the lambda (lambda) and T signs and the thickness of the inter-twin membrane. The diagnosis of chorionicity was made at the time of the ultrasound examination using all these features and subsequently compared with the postnatal diagnosis, confirmed either by placental histology or discordancy in infant sex. In 150 cases with confirmation of chorionicity following delivery, 116 were postnatally classified as dichorionic and 34 monochorionic. Prenatal ultrasound examination correctly identified chorionicity in 149 (99.3%) cases. The most reliable indicator for dichorionicity was a combination using the lambda sign or two separate placentae with a sensitivity and specificity of 97.4% and 100%, respectively. The most useful test in predicting monochorionicity was the T sign with a sensitivity of 100% and specificity of 98.2%. Measurement of the inter-twin membrane thickness was a less reliable indicator where the sensitivity for dichorionicity and specificity for monochorionicity was only 92.6%. Ultrasound examination of twin pregnancies at 10-14 weeks of gestation predicts chorionicity with a high degree of accuracy using a combination of the number of placentae, lambda and T signs and inter-twin membrane thickness. All hospitals should encourage departments providing ultrasound services to undertake chorionicity determination when examining women with twin pregnancies at this gestation.

To assess the impact of introduction of the STAN monitoring system. Prospective observational study. Tertiary referral labour ward, St George's Hospital, London. High-risk term pregnancies. We report all consecutive cases of intrapartum monitoring using the STAN S 21 fetal heart monitor. Cases with adverse neonatal outcome were evaluated in relation to the ST waveform analysis and cardiotocography (CTG). Cord artery metabolic acidosis, neonatal encephalopathy (NNE) and reasons behind cases with poor outcome. Between 2002 and 2005, there were 1502 women monitored by STAN. Based on combined STAN analysis in the 1502 women, action was indicated in 358 women (23.8%), while in 1108 women (73.8%) no action was indicated. Traces were not interpretable in 36 women (2.4%). Of the 836 cases (55.7%) where cord blood gases were available, there were 23 cases (2.8%) of metabolic acidosis and 16 of these (70%) were identified by STAN. Overall, there were 14 cases of NNE monitored by STAN. Retrospective analysis of these highlights human errors, such as poor CTG interpretation, delay in taking appropriate action and not following the guidelines. Our experience suggests the need for more intense training on interpretation of CTG and strict adherence to guidelines.

Functional single nucleotide polymorphisms (SNPs) of interleukin (IL)-4 -590 (C>T), toll-like receptor (TLR)-2 +2258 (G>A) and matrix metalloproteinase (MMP)-9 -1562 (C>T) were examined by polymerase chain reaction-restriction fragment length polymorphism to identify their merit as genetic markers for pre-eclampsia. One hundred and seventeen pre-eclamptic women and 146 control subjects with uncomplicated singleton pregnancies participated in this study, conducted at Leeds General Infirmary and St James's University Hospital. While the TLR-2 +2258 (G>A) and MMP-9 -1562 (C>T) SNPs failed to present any significant association with pre-eclampsia, there was a marked trend for an association between the IL-4 -590 (C>T) SNP and pre-eclampsia (chi(2)= 5.87, P = 0.055), with a prevalence of TT homozygous women in this group (OR 4.455, 95% CI 1.286-15.350).

To investigate the agreement between conventional colposcopic impression, dynamic spectral imaging (DSI) colposcopy and histology, for human papillomavirus type 16-positive (HPV16(+)) and non-16 high-risk (hr) HPV(+) women. Prospective, comparative, multicentre clinical trial. Three colposcopy clinics in the Netherlands. Women (n = 177) aged 18 years or over with an intact cervix, referred for colposcopy. The colposcopist graded the lesion by using the DSI colposcope as a regular video colposcope. Subsequently the DSI impression was displayed and biopsies were taken from all abnormal areas as well as from a random (normal) site. A cervical smear was taken for HPV typing. Histologically confirmed high-grade cervical intraepithelial neoplasia or cancer (CIN2(+)), positive for HPV16 or for any other hrHPV type. The DSI colposcope identified more CIN2(+) cervical lesions among HPV16(+) women than in non-16 hrHPV(+) women (P = 0.032 regardless of final histology and P = 0.009 among women with CIN2(+)). Consequently, the sensitivity of the DSI colposcope for detecting CIN2(+) lesions was higher in HPV16(+) women than in non-16 hrHPV(+) women (97% versus 74%, P = 0.009). No such differences were seen for the colposcopist impression. In addition, mainly smaller cervical lesions are missed by the colposcopist. The sensitivity of DSI colposcopy for CIN2(+) is higher in HPV16(+) than in non-16 hrHPV(+) women. Furthermore, regardless of HPV16 status, the sensitivity of DSI for CIN2(+) is higher than that of the colposcopist, probably because colposcopists tend to miss smaller cervical lesions.

To evaluate the prevalence of anal incontinence at 16 weeks of gestation and to identify possible maternal and obstetrical risk factors. Cross sectional study and cohort study. Department of Obstetrics and Gynaecology, Aarhus University Hospital, Denmark. Cross sectional study: 7,557 women attending antenatal care. Cohort study: a subgroup of 1,726 pregnant women with one previous delivery at our department. The prevalence of anal incontinence within the preceding year was 8.6%. Incontinence of liquid and solid stools was reported in 2.3% and 0.6%, respectively. Isolated flatus incontinence at least once a week was reported in 4.2%. The risk of flatus incontinence at least once a week was increased with age > 35 years (OR 1.6; 95% CI 1.1-2.4) and with previous lower abdominal or urological surgery (OR 1.5, 95% CI 1-1-2.1) in a logistic regression model controlling for maternal factors. Increasing parity did not increase the risk. The risk of flatus incontinence was increased after anal sphincter tear and birthweight > 4,000 g in a logistic regression model controlling for maternal and obstetric variables. Episiotomy was insignificantly associated, while spontaneous perineal tear > 3 cm and a number of other intrapartum factors were not associated. CONCLUSION True faecal incontinence is rare among younger women. However, an age > 35 years and previous lower abdominal or urological surgery increased the risk of flatus incontinence in contrast to increasing parity. This suggests that childbirth plays a minor role compared with age. However, when analysing obstetric variables separately, a birthweight > 4,000 g, and anal sphincter tears were significant risk factors for flatus incontinence.

Prognostic evaluation of HPV-16 genome status of the pelvic lymph nodes, the integration status of HPV-16 and p53 codon 72 polymorphism in cervical cancer. Prospective cohort study. Department of Gynaecological Oncology, University of Debrecen, Hungary. Thirty-nine patients with HPV-16 positive cervical cancer. Primary tumour specimens of 39 cervical cancer patients with HPV-16 positive primary tumour were subjected to multiplex polymerase chain reaction using HPV-16 E1/E2, E7 and p53 codon 72 allele-specific primers. Pelvic lymph nodes of the same patients were also tested for the presence of HPV-16 DNA and for its integration status using HPV-16 E7 and E1/E2 ORF specific primers, respectively. Progression-free survival. Metastatic lymph nodes carried HPV-16 DNA more frequently than nodes with no evidence of disease (100.0% vs 35.7%, P = 0.001). Cases with HPV-16 positive nodes had higher recurrence rate than those with HPV-16 negative nodes (42.9% vs 11.1%, P = 0.009). There was no difference between cases with and without histologically proven nodal disease with regard to integration status of HPV-16 DNA in the primary tumour (integrated 90.9% vs 71.4%, episomal 9.1% vs 21.4%, mixed 0% vs 7.1%) and p53 codon 72 polymorphism (Arg/Arg 54.5% vs 67.9%, Pro/Pro 0 vs 7.1%, Arg/Pro 45.5% vs 21.4%). Regardless of the presence of nodal metastasis, HPV-16 status of the nodes is a significant predictor of recurrent disease. HPV-16 integration status and p53 codon 72 genotype do not seem to have a bearing on disease outcome in cervical cancer with HPV-16 positive primary.

To assess the association between maternal gestational weight gain (GWG) during the first 20 weeks of gestation and overweight/obesity and abdominal obesity of offspring at the age of 16 years. A prospective cohort study. The two northernmost provinces of Finland. Mothers and their adolescent offspring born from singleton pregnancies (3265 boys; 3372 girls) in the Northern Finland Birth Cohort 1986. Maternal weight at 20 weeks of gestation was measured in municipal maternity clinics. Maternal GWG was based on the difference between the measured weight and self-reported pre-pregnancy weight, and was classified into quartiles. Offspring weight, height and waist circumference were measured by study nurses during a clinical examination. Logistic regression analyses [with and without adjustment for maternal pre-pregnancy body mass index (BMI), glucose metabolism, education level, haemoglobin, smoking status, parity, and gender of offspring] were performed. Offspring overweight/obesity, based on BMI and abdominal obesity at 16 years. The highest quartile of maternal weight gain (>7.0 kg during the first 20 weeks of gestation) was independently associated with BMI-based overweight/obesity and abdominal obesity in the 16-year-old offspring (OR 1.46, 95% CI 1.16-1.83, and OR 1.37, 95% CI 1.10-1.72, respectively). Among all covariates, maternal pregravid obesity showed the highest odds for both overweight/obesity and abdominal obesity (OR 4.57, 95% CI 3.18-6.57, and OR 4.43, 95% CI 3.10-6.34, respectively). Maternal overnutrition during the first half of gestation predicts offspring overweight/obesity and abdominal obesity in adolescence, yet a high pregravid BMI appears to be a more important determinant of both outcomes.

Pre-eclampsia is diagnosed by hypertension and proteinuria, probably caused by endothelial dysfunction, resulting in symptoms including oedema, inflammation and altered metabolism. Vascular endothelial growth factor A (VEGF-A) is detected at higher concentrations in plasma from patients with pre-eclampsia than in plasma from normotensive pregnant patients when determined by radioimmunoassay. This study tested the hypothesis that circulating VEGF-A in pre-eclamptic plasma is biologically active in vivo, and aimed to identify specific isoforms responsible for this activity. Plasma from pre-eclamptic (n = 17) and normotensive (n = 10) pregnant women was perfused into Rana mesenteric microvessels, and the subsequent change in microvascular permeability was measured using a single-vessel perfusion micro-occlusion technique. Pre-eclamptic but not normotensive plasma resulted in a 5.25 ± 0.8-fold acute increase in vascular permeability (P = 0.0003). This increase could be blocked by the incubation of plasma with bevacizumab, an antibody to VEGF-A (n = 7; P = 0012), and by VEGF-A receptor inhibition by SU5416 at doses specific to VEGF-A receptor-1 (VEGFR1), but not by the VEGF-A receptor-2 inhibitor, ZM323881. Although VEGF(165) b levels were not significantly altered in the PET samples, the increase in permeability was also inhibited by incubation of pre-eclamptic plasma with an inhibitory monoclonal antibody specific for VEGF₁₆₅b (n=6; P<0.01), or by the addition of placental growth factor 1 (PlGF-1; n = 3; P < 0.001). PlGF-1 was detected at lower concentrations in pre-eclamptic plasma than in normotensive plasma. These findings suggest that circulating VEGF-A levels in pre-eclampsia are biologically active because of a loss of repression of VEGFR1 signalling by PlGF-1, and VEGF₁₆₅b may be involved in the increased vascular permeability of pre-eclampsia.

To define the contribution of prenatal investigation and evaluate the prognosis of isolated mild ventriculomegaly (IMV). Retrospective study. University hospital between January 1992 and December 2002. One hundred and sixty-seven cases of prenatal unilateral or bilateral IMV without any associated anomaly at the time of initial diagnosis. Complementary investigations were performed: amniocentesis with karyotyping, screening for viruses and acetylcholinesterase electrophoresis, magnetic resonance imaging (MRI), and ultrasonography every 3-4 weeks. Results of prenatal investigations, pregnancy outcome, and postnatal psychomotor development. IMV was diagnosed around 26.5 weeks. Amniocentesis revealed four chromosomal anomalies and two cytomegalovirus infections. MRI diagnosed brain-associated anomalies in 15 cases and ultrasonographic monitoring highlighted malformations not initially diagnosed in 28 cases. Termination of pregnancy (TOP) was considered in 21 pregnancies (12.6%). Indications were aneuploidy, fetal infectious disease or associated malformations. In women for whom a TOP was considered, consanguinity, fetus of female sex and frontal horn enlargement were statistically more frequent, ventriculomegaly was more often bilateral and asymmetrical, atrial width, and the rate of progressive ventricular enlargement were significantly higher. One hundred and one children with prenatal IMV were assessed between 19 and 127 months (mean age 54.68 +/- 2.87 months). Twelve children had neurological disease or psychomotor delay and 89 children had a normal psychomotor development. Poor neurological outcome was more often associated with atrial width greater than or equal to 12 mm, asymmetrical bilateral enlargement, and progression of the ventriculomegaly. The detection of IMV raises the question of the child's psychomotor development and justifies meticulous prenatal investigation. In addition to associated anomalies, three criteria are often associated with an unfavourable outcome: atrial width greater than 12 mm, progression of the enlargement, and asymmetrical and bilateral ventriculomegaly.

We investigated the application of high-resolution microarray-based comparative genomic hybridisation (array CGH) on a fetus showing increased nuchal translucency (NT). Case study. Tertiary referral obstetrics unit. Pregnant woman attended the antenatal clinic. Conventional karyotyping and genetic test was carried out for the alpha-globin gene. High-resolution array CGH using the high-density 244K Agilent microarray was performed on fetal blood sample by cordocentesis to investigate the possibility of any genomic imbalance. Detection of chromosomal abnormality. Karyotyping analysis showed 46,XY. Molecular genetic diagnosis confirms the fetus has Hb-H constant spring disease but cannot explain the increased NT to 3.2 mm. Array CGH analysis discovered a 1.32-Mb microdeletion on chromosome 16p13.11. Deletion at 16p13.11 has been implicated to predispose to autism and/or mental retardation. Baby was delivered at 40 weeks of gestation, and follow up was carried out at 3 months of age without sign of mental retardation/developmental delay. This case study demonstrated that array CGH can accurately calibrate the size and identify de novo interstitial chromosome imbalances. However, the presence of chromosome copy variants with unknown clinical significance currently limits its wider scale application in prenatal diagnosis and needs further investigations.

Objective: To assess the association between maternal cytomegalovirus (CMV) antibodies in mid-pregnancy and pre-eclampsia. Design: Nested case-control study. Setting: Pregnancies registered in the Norwegian Mother and Child Cohort Study (MoBa): a large population-based pregnancy cohort (1999-2006). Sample: A cohort of 1500 women with pre-eclampsia and 1000 healthy pregnant women. Methods: Plasma samples and pregnancy-related information were provided by the MoBa. Antibody status (CMV IgG and CMV IgM) and levels (CMV IgG) at 17-18 weeks of gestation were determined by enzyme-linked immunosorbent assay (ELISA). Main outcome measure: A diagnosis of pre-eclampsia, as defined in the Medical Birth Registry of Norway. Results: There was no evidence of an effect of CMV IgG seropositivity on the likelihood of developing pre-eclampsia, and CMV IgG antibody levels among women who were seropositive did not differ between groups. Adjusted for maternal age, parity and smoking, the odds ratio for pre-eclampsia in women seropositive for CMV IgG was 0.89 (95% CI 0.74-1.05; P = 0.17). The proportions of women who were seropositive for IgM did not differ between women with pre-eclampsia and women who were healthy (P = 0.98). Among nulliparous women, the proportion of women who were seropositive for CMV IgG was slightly lower among women with pre-eclampsia (53.5%) than among healthy women (59.8%) (P = 0.03). Subgroup analyses were performed for women with early or late onset pre-eclampsia, with preterm delivery and/or with neonates that were small for gestational age, but antibody status did not differ between pre-eclampsia subtypes and controls. Conclusions: The presence of maternal antibodies to CMV was not associated with pre-eclampsia in our study. The results suggest that CMV infection is unlikely to be a major cause of pre-eclampsia.

To study the influence of gestational age on lactate concentration in arterial and venous umbilical cord blood at birth and to define gestational age-specific reference values for lactate in vigorous newborns. Population-based comparative. University hospitals. Vigorous newborns with validated umbilical cord blood samples. From 2000 to 2004, routine cord blood gases, lactate and obstetric data from two university hospitals were available for 17 867 newborns from gestational week 24 to 43. After validation of blood samples and inclusion only of singleton pregnancies aimed for vaginal delivery, 10 700 women remained. Among those, reference values were defined in 10 169 vigorous newborns, that is in newborns with a 5-minute Apgar score corresponding to the gestational age-specific median value minus 1 point score, or better. Cord lactate concentration relative to gestational age. The arterial and venous lactate concentrations increased monotonously with gestational age from 34 weeks. Considerable differences were found between mean and median values, but after logarithmic transformation the log-lactate values were normally distributed. Simple linear regression analysis showed a significant association between the log-lactate values and gestational age (P < 10(-6), R(2)= 0.024). Reference curves were constructed after anti-logarithmic transformation. Both the gestational age and the time of the second stage of labour influenced, independently of each other, the lactate concentrations. Lactate concentrations in arterial and venous umbilical cord blood are increasing significantly with advancing gestational age.

To evaluate the relationship between interleukin (IL)-18 in cervical mucus and amniotic fluid and microbial invasion of amniotic fluid, preterm delivery and intra-amniotic inflammation in women in preterm labour, with preterm prelabour rupture of membranes and at term. A prospective follow up study. Sahlgrenska University Hospital, Göteborg, Sweden. Women with singleton pregnancies (<34 weeks) presenting with preterm labour (n = 87) or preterm prelabour rupture of membranes (n = 47) and women, not in labour, at term (n = 28). Amniotic fluid was retrieved transabdominally. Cervical mucus was taken from the uterine cervix of women in preterm labour and at term. IL-18 was analysed with enzyme-linked immunosorbent assay. IL-18 in relation to microbial invasion of the amniotic fluid, delivery within seven days or <34 weeks of gestation and intra-amniotic inflammation. The levels of IL-18 in cervical mucus and amniotic fluid were higher in women with preterm labour than in those not in labour at term. In the preterm labour group, significant associations were found between elevated IL-18 in amniotic fluid and microbial invasion of the amniotic fluid, as well as between delivery within seven days or <34 weeks of gestation and intra-amniotic inflammation. Delivery was delayed longer in the preterm prelabour rupture of membranes subgroup with IL-18 >or=1.0 ng/mL than in that with IL-18 <1.0 ng/mL. In the preterm labour group, high IL-18 in amniotic fluid (but not in the cervix) was associated with microbial invasion of the amniotic fluid, intra-amniotic inflammation and prompt delivery. On the other hand, elevated IL-18 in preterm prelabour rupture of the membranes group correlated with a longer interval to delivery.

To investigate the prognostic value of metabolic tumour volume (MTV) and total lesion glycolysis (TLG), measured by preoperative positron emission tomography and computerised tomography (PET/CT), in women with endometrial cancer. Retrospective cohort study. A tertiary referral centre. Women with endometrial cancer who underwent preoperative (18) F-FDG PET/CT in the period 2004-2009. Clinicopathological data for 84 women with endometrial cancer were reviewed from medical records. Cox proportional hazards modelling identified recurrence predictors. The receiver operating characteristic (ROC) curve was used to determine the cut-off value for predicting recurrence. Disease-free survival (DFS). The number of patients with International Federation of Gynecology and Obstetrics (FIGO) stages were: I (58); II (11); III (13); and IV (2). The median DFS was 48 (1-85) months. By univariate analysis, DFS was significantly associated with FIGO stage, histology, peritoneal cytology, myometrial invasion, nodal metastasis, serum CA-125, MTV, and TLG. Using multivariate analysis, the MTV (P = 0.010; hazard ratio, HR = 1.010; 95% confidence interval, 95% CI = 1.002-1.018) and TLG (P = 0.024; HR = 1.001; 95% CI = 1.000-1.002) were associated with DFS. The area under the ROC curve was 0.679 (95% CI = 0.505-0.836) after discriminating for recurrence using an MTV cut-off value of 17.15 ml. Regarding TLG, the cut-off value was 56.43 g and the area under the ROC plot was 0.661 (95% CI = 0.501-0.827). Kaplan-Meier survival graphs demonstrated a significant difference in DFS between groups categorised using the cut-off values for MTV and TLG (P < 0.022 for MTV and P < 0.047 for TLG, by log-rank test). Preoperative MTV and TLG could be independent prognostic factors predicting the recurrence of endometrial cancer.

The safety of use of the calcium channel blocker nifedipine in pregnancy as it affects child development has not been well evaluated. We report the results, with regard to the safety for children of use of nifedipine in pregnancy, on children followed up at 18 months of age born from women recruited in a study comparing routine treatment with nifedipine compared with no treatment.

Please cite this paper as: Gartland D, Donath S, MacArthur C, Brown S. The onset, recurrence and associated obstetric risk factors for urinary incontinence in the first 18 months after a first birth: an Australian nulliparous cohort study. BJOG 2012;119:1361–1369. Objective To investigate the contribution of obstetric risk factors to persistent urinary incontinence (UI) between 4 and 18 months postpartum. Design Prospective pregnancy cohort. Setting Six metropolitan public hospitals in Victoria, Australia. Sample A total of 1507 nulliparous women recruited to the Maternal Health Study in early pregnancy (≤24 weeks of gestation). Methods Data from hospital records and self-administered questionnaires/telephone interviews at ≤24 and 30–32 weeks of gestation and at 3, 6, 9, 12 and 18 months postpartum analysed using logistic regression. Main outcome measures Persistent UI 4–18 months postpartum in women continent before pregnancy. Results Of the women who were continent before pregnancy, 44% reported UI 4–18 months postpartum, and 25% reported persistent UI (symptoms at multiple follow ups). Compared with spontaneous vaginal birth, women who had a caesarean before labour (adjusted odds ratio [aOR] 0.4, 95% confidence interval [95% CI] 0.2–0.9), in first-stage labour (aOR 0.4, 95% CI 0.2–0.6) or in second-stage labour (aOR 0.4, 95% CI 0.2–1.0) were less likely to report persistent UI 4–18 months postpartum. Prolonged second-stage labour in women who had an operative vaginal birth was associated with increased likelihood of UI (aOR 2.5, 95% CI 1.3–4.6). Compared with women who were continent in pregnancy, women reporting UI in pregnancy had a seven-fold increase in odds of persistent UI (aOR 7.4, 95% CI 5.1–10.7). Conclusions Persistent UI is common after childbirth and is more likely following prolonged labour in combination with operative vaginal birth. The majority of women reporting persistent UI at 4–18 months postpartum also experienced symptoms in pregnancy.

To compare indicators of systemic inflammatory response in the second trimester in women who developed pre-eclampsia with normal pregnancies. Prospective nested case control study derived from a cohort of 2190 pregnant women. Blood samples were obtained at 18 weeks of gestation. The following inflammatory parameters were measured: tumour necrosis factor-alpha (TNF-alpha), plasminogen activator inhibitor-1 (PAI-1), interleukin-1beta (IL-1beta), IL-6, IL-10, microCRP and tissue factor (TF). Institute of Medical Genetics, University of Oslo, and Department of Medical Genetics, Ullevål University Hospital and Departments of Obstetrics and Gynecology, Aker University Hospital, Oslo, Norway. The cases were 71 women who subsequently developed pre-eclampsia. The controls were 71 healthy, pregnant women matched for age, parity and first trimester body mass index (BMI). Venous blood was drawn from fasting subjects into 5 mL test tubes containing EDTA. Samples were analysed for inflammatory parameters: IL-1-beta, IL-6, IL-10, TNF-alpha, PAI-1, TF (ELISA-technique) and CRP (latex-enhanced immunonephelometric assay), strictly according to the manufacturer's recommendation. The matched case and control subjects were compared by the paired two-tailed Wilcoxon signed rank test. All P values were two-tailed and P < 0.05 was deemed statistically significant. We found no differences in plasma concentrations of PAI-1, IL-1beta, IL-6,IL-10, microCRP, TNF-alpha or TF at 18 weeks of gestation between women who subsequently developed pre-eclampsia and matched control women. In contrast to findings from women with overt pre-eclampsia, the present study indicates that there are no indications of intensified systemic inflammatory response at 18 weeks of gestation in women who later develop pre-eclampsia.

To determine the value of amniotic fluid interleukin-18 (AF IL-18) in the diagnosis of microbial invasion of the amniotic cavity and prediction of preterm delivery (PTD). Analysis of the results of AF collected prospectively following genetic amniocentesis between February 2006 and September 2007. A tertiary referral centre for fetal medicine. Following amniocentesis, a sample of amniotic fluid was transferred to the laboratory for aerobic and anaerobic bacterial cultures, Ureaplasma urealyticum culture and IL-18 assays. All women who delivered preterm (<37 weeks of gestation) formed the study group. The control group consisted of the two subsequent women who also underwent amniocentesis during the same time period and delivered a normal neonate at term, matched for maternal age, parity and indication for amniocentesis. The relationship between AF IL-18 levels and the risk of both microbial invasion of the amniotic cavity and PTD. Forty-eight women who delivered preterm (<37 weeks) were matched with 96 controls. The preterm delivery group had significantly higher concentrations of IL-18 (median=609 pg/ml, interquartile range: 445.7-782.7) compared to controls (median=322.1 pg/ml, interquartile range: 277.7-414.4), (P<0.001). IL-18 level was also significantly higher (P<0.001) in cases with positive amniotic fluid cultures (median=697.7, interquartile range: 609.0-847.2) compared to those with negative ones (median=330.9 pg/ml, interquartile range: 235.2-440.8). Elevated mid-trimester concentrations of AF IL-18 can identify women at risk for intraamniotic infection and spontaneous PTD.

To investigate if advanced maternal age at first birth increases the risk of psychological distress during pregnancy at 17 and 30 weeks of gestation and at 6 and 18 months after birth. National cohort study. Norway. A total of 19 291 nulliparous women recruited between 1999 and 2008 from hospitals and maternity units. Questionnaire data were obtained from the longitudinal Norwegian Mother and Child Cohort Study, and register data from the national Medical Birth Register. Advanced maternal age was defined as ≥ 32 years and a reference group of women aged 25-31 years was used for comparisons. The distribution of psychological distress from 20 to ≥ 40 years was investigated, and the prevalence of psychological distress at the four time-points was estimated. Logistic regression analyses based on generalised estimation equations were used to investigate associations between advanced maternal age and psychological distress. Psychological distress measured by SCL-5. Women of advanced age had slightly higher scores of psychological distress over the period than the reference group, also after controlling for obstetric and infant variables. The youngest women had the highest scores. A history of depression increased the risk of distress in all women. With no history of depression, women of advanced age were not at higher risk. Changes over time were similar between groups and lowest at 6 months. Women of 32 years and beyond had slightly increased risk of psychological distress during pregnancy and the first 18 months of motherhood compared with women aged 25-31 years.