PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.     

妊娠早期糖化血红蛋白联合PAPP-A对妊娠期糖尿病的预测意义

目的:探讨妊娠早期血清学指标糖化血红蛋白(glycohemoglobin,HbA1c)联合妊娠相关血浆蛋白A(pregnancy-associated plasma protein A,PAPP-A)对妊娠期糖尿病(gestational diabetes mellitus,GDM)的预测意义。方法:随机选取2018年12月1日-2019年7月30日孕11~13+6周于我院门诊产检的妊娠妇女,进行临床资料采集并记录妊娠早期(11~13+6周)空腹血糖(fasting plasma glucose,FPG)、HbA1c、PAPP-A中位数倍数(multiple of the median,MoM)水平,根据孕24~28周进行的75 g口服葡萄糖耐量试验(oral glucose tolerance test,OGTT)结果将研究对象分为研究组和对照组,统计分析妊娠早期血清学指标预测GDM的最佳截断值并得出最适宜的联合预测方案。结果:多因素Logistic回归分析显示,高水平FPG和HbA1c、低水平PAPP-A、受孕方式采用辅助生殖技术、有家族糖尿病史以及妊娠早期体质量指数(BMI)为超重或肥胖均是GDM发生的独立危险因素。有糖尿病家族史和使用辅助生殖技术受孕发生GDM的风险显著增高(OR分别为7.206和47.512,均P<0.001)。分析不同预测指标的受试者工作特征(receiver operating characteristic,ROC)曲线及曲线下面积(area under the curve,AUC)显示,PAPP-A MoM联合HbA1c及FPG诊断时AUC最大(0.728),其后依次为PAPPA MoM联合HbA1c(0.721)、HbA1c联合FPG(0.717),均大于HbA1c(0.707)和FPG(0.647),而PAPP-A MoM的AUC为0.380,对GDM没有诊断意义。结论:具有高风险因素的孕妇,推荐在妊娠早期联合检测HbA1c与PAPPA MoM,以早期预测GDM。     

胎儿生长迟缓与新生儿胰岛素敏感性变化的相关性

目的探讨胎儿生长迟缓(FGR)与新生儿胰岛素敏感性变化的关系。 方法昆明医学院第一附属医院于2004年4~12月，对72例小于胎龄儿(SGA)和48例适于胎龄儿(AGA)空腹血糖(FPG)、空腹胰岛素(FINS)、C 肽、HDL C、LDL C、TG、非酯化脂肪酸(NEFA)等指标，计算葡萄糖/胰岛素比值(G/I)、胰岛素敏感性指数(ISI)、胰岛素抵抗指数(HOMA IR)、胰岛β细胞功能(HBCI)等，探讨FGR与新生儿胰岛素敏感性变化的关系。 结果(1)SGA组FPG、HDL C低于AGA组，而FINS、LDL C、TG、NEFA高于AGA组(P<001)；(2)SGA组G/I比值、ISI低于AGA组，HOMA IR高于AGA组(P<001)，而HBCI两组相比差异无显著性(P>005)。 结论FGR儿在生命早期存在胰岛素敏感性降低和不同程度的胰岛素抵抗(IR)，而胰岛β细胞功能无明显变化。     

Is neighbourhood deprivation a risk factor for gestational diabetes mellitus?

AIMS: To assess the relationship between neighbourhood deprivation and the rate of gestational diabetes mellitus (GDM) using routinely collected data from a clinical information system, in Plymouth, UK. METHODS: Between 1 January 1996 and 31 December 1997, 3933 women residing within the Plymouth Primary Care Trust (PCT) were screened for GDM using indices of neighbourhood deprivation and prevalence of GDM. Areas (n = 43) were classified according to the Townsend index, measuring material deprivation. Pregnant women with and without GDM were compared. RESULTS: The prevalence of GDM was 1.7%[95%, confidence interval (CI) 1.20, 2.11]. The prevalence of GDM ranged from 1.05% (95% CI 0.60, 1.70) in the most deprived to 2.10% (95%, CI 1.34, 3.13), in the least deprived neighbourhood. Crude rates decreased by 50%[relative prevalence (RP) (95% CI) 0.50 (0.27, 0.94); P = 0.06] amongst those living in the most-deprived compared with those living in the least-deprived areas. Using a stepwise binary logistic regression model, older age at delivery significantly increased the risk of developing GDM. [RP (95%, CI) 1.09, (1.04, 1.13)]. Townsend deprivation score had no significant independent association with GDM when other covariates were considered. CONCLUSION: These data suggest that the neighbourhood context in which women live has no impact on the risk of GDM. Diabet.     

Maternal glycated haemoglobin, pre-gestational weight, pregnancy weight gain and risk of large-for-gestational-age babies: a Danish cohort study of 209 singleton Type 1 diabetic pregnancies.

AIMS: To examine the association between maternal glycated haemoglobin in the second half of diabetic pregnancies and the relative risk of delivering large-for-gestational-age (LGA) babies, controlling for maternal body mass index (BMI) before pregnancy, weight gain, age, White class and smoking habits. METHODS: We identified all pregnant diabetic women in North Jutland County, Denmark from 1985 to 2003. Data on HbA(1c) values from the 20th gestational week to term were collected from medical records and the babies were classified as large, normal or small for gestational age. The association between glycated haemoglobin (HbA(1c)) and relative risk of delivering an LGA baby was quantified based on logistic regression models and stratified analysis controlling for the five covariates. RESULTS: We included 209 singleton pregnancies with assessable HbA(1c) values of which 59%[95% confidence interval (CI) 52-65%] terminated with an LGA baby. Increasing levels of HbA(1c), BMI and weight gain were all associated with increasing risk of delivering an LGA baby. Analyses stratified according to maternal BMI showed that the association between HbA(1c) and risk of delivering an LGA baby was restricted to pregnancies with pre-pregnancy BMI > 23 kg/m(2). We found no association between HbA(1c) and risk of delivering an LGA baby in pregnancies with lower BMI. CONCLUSION: The positive association between glycated haemoglobin and birth of an LGA baby seems to be restricted to women with BMI > 23 kg/m(2).     

Proposed diagnostic thresholds for gestational diabetes mellitus according to a 75-g oral glucose tolerance test. Maternal and perinatal outcomes in 3260 Danish women.

AIMS: To study if established diagnostic threshold values for gestational diabetes based on a 75-g, 2-h oral glucose tolerance test can be supported by maternal and perinatal outcomes. METHODS: Historical cohort study of 3260 pregnant women examined for gestational diabetes on the basis of risk indicators. Information on oral glucose tolerance test results and clinical outcomes were collected from medical records. RESULTS: There was an increased risk of delivering a macrosomic infant in women with 2-h capillary blood glucose of 7.8-8.9 mmol/l compared with women with 2-h glucose < 7.8 mmol/l. Despite treatment, 2-h glucose of 9.0-11.0 mmol/l and > or = 11.1 mmol/l were both associated with increased rates of macrosomia, spontaneous preterm delivery, hypertensive complications, and neonatal hypoglycaemia. Adverse outcomes tended to be more frequent in women with 2-h glucose > or = 11.1 mmol/l than in women with 2-h glucose of 9.0-11.0 mmol/l. CONCLUSIONS: The risk for several maternal and perinatal complications increased with the diagnostic threshold for 2-h glucose. Large-scale blinded studies are needed to clarify the question of a clinically meaningful diagnosis of gestational diabetes mellitus. Until these results are available, a 2-h threshold level of 9.0 mmol/l after a 75-g oral glucose tolerance test seems acceptable.     

Non-genetic surrogacy: no cure but problems for infertility?

Non-genetic surrogacy characterizes a situation where the gestational mother is not the genetic mother. It further widens a circle that started with the introduction of in-vitro fertilization (IVF) and creates problems in defining motherhood and identifying at birth the mother who will have the rights and responsibilities of rearing the child.     

Terminal transverse limb defects and early chorionic villus sampling: Evaluation of 4,300 cases with completed follow-up

Data from 4,300 consecutive cases following prenatal diagnosis by transcervical (TC) CVS (n = (1,570) and transabdominal (TA) CVS (n = 2,370) were evaluated. In the follow-up study only infants examined by a physician were included. Gestational age varied between 8.5 and 11.6 weeks (mean 10.3 weeks) for TC-CVS and between 9.3 and 20 weeks (mean 12.3 weeks) for TA-CVS 98% of TC-CVS was performed at 9–10 weeks, 80.7% of TA-CVS procedures were carried out at 12–15 weeks. Selective termination took place in 97 cases of TC-CVS (6.1%) and in 72 cases of TA-CVS (2.6%). Another 8 Women had a termination for psychosocial reasons, resulting in 4,123 (1,469 TC, 2,645 TA) continuing pregnancies. The overall fetal loss rare <28 weeks was 5.4% (n = 80) for TC-CVS and 2.6% (n = 70) for TA-CVS. The overall incidence of congenital abnormalities after birth was 0.9%. Two terminal transversal limb defects were detected in the TC-CVS group (0.14%) against one (0.04%) in the TA-CVS group. © 1993 Wiley-Liss, Inc.     

再论妊娠期糖尿病与胎儿生长发育

目的 研究妊娠期糖尿病与胎儿生长发育中糖代谢特点的关系。方法 选择妊娠期糖尿病25例（GDM组），正常孕妇20例（对照组），分别测孕妇空腹血糖、糖耐量、C肽、IGF－I、新生儿出生2h内空腹血糖，并依据新生儿出生体重分为大于胎龄儿组（LGA组，≥4000g），适于胎龄儿组（AGA组，2500－3999g)。结果 C肽及新生儿出生2h内空腹血糖GDM组与对照组差异有显著性；糖耐量各时点血糖值餐后2h血糖值LGA和AGA组差异有显著性。结论 血糖始终是影响胎儿生长发育的重要因素，孕妇餐后2h血糖水平与巨大儿的发生呈正相关。