Establishment of MOM Correction Models in NTD Prenatal Screening on IMMULITE 2000

目的 探讨和构建北京人群神经管缺陷(neural tube defect,NTD)产前筛查的血清标志物甲胎蛋白(α-fetoprotein,AFP)浓度中位数倍数(multiple of the median,MOM)的校正模型.方法 选取5668例孕中期孕妇,通过分析其AFP浓度与孕周和体重之间的相关性,分别进行回归分析,根据统计量和校正决定系数选取最优模型,校正AFP.结果 35岁以下(<35y)组,分别用指数和幂回归模型进行孕周和孕妇体重的校正；35岁及以上(≥35y)组,分别用S和二次回归模型进行孕周和孕妇体重的校正.校正前,孕周与AFP MOM值呈显著正相关(＜35y:r =0.412,P=0.000；≥35y:r =0.435,P=0.000),体重与AFP MOM值呈显著负相关(＜35y:r=-0.232,P =0.000;≥35y:r=-0.228,P=0.000)；校正后,AFPMOM值与孕周(＜35y:r =0.446,P=0.911；≥35y；r=0.001,P=0.985)和体重(＜35y:r =0.010,P =0.483；≥35y:r=0.008,P=0.887)均无相关性.结论 基于北京人群孕中期妇女血清标志物AFP水平建立的MOM校正模型可以有效地消除孕周和体重的影响.     

孕中期应用血清甲胎蛋白和游离β绒毛膜促性腺激素筛查Down综合征的研究

目的探讨完善孕中期血清学筛查胎儿Down综合征的方法,增加检出率,有效减少假阴性及假阳性。方法应用酶联免疫吸附方法(ELISA)测定16636名孕中期(14-20w)孕妇血清甲胎蛋白(AFP)及游离β绒毛膜促性腺激素(freeβ-hCG)浓度;应用专用软件综合评价妊娠Down综合征胎儿的风险度。结果孕14-20w孕妇血清AFP浓度随孕周的增加而迅速增加,β-hCG浓度随孕周的增加而迅速降低。1005例(6.0%)为Down's综合征高危妊娠,诊断妊娠染色体异常胎儿15例,漏检3例。妊娠染色体异常胎儿检出率83.3%。筛查假阳性率5.9%。结论孕中期应用ELISA法筛查Down综合征筛查效果满意。应注意孕周的核对以及筛查截断值的确定,制定良好的筛查策略。     

甘肃地区干血斑法孕中期产前筛查指标中位数系统建立

目的建立甘肃地区干血斑法孕中期产前筛查指标甲胎蛋白(alpha fetoprotein,AFP)和游离绒毛膜促性腺激素(free-beta human chorionic gonadotropin,Freeβ-HCG)中位数系统,为干血斑法在该地区人群孕中期的产前筛查风险评估提供实验室数据依支持。方法采用时间分辨荧光分析法检测11 257例妊娠15~20+6w妊娠女性干血斑样本中AFP和Freeβ-HCG的浓度,利用产筛风险评估软件(Life Cycle 3.2,LC3.0)的Medians Tool统计不同孕周AFP和Freeβ-HCG的人群中位数,并计算出MOM值。结果甘肃地区人群干血斑法孕中期产前筛查指标:AFP和Freeβ-HCG在各孕周的中位数均较Life Cycle 3.2内嵌值高。结论不同地区干血斑法孕中期产前筛查的中位数切割值可能存在差异,有必要建立本地区人群中位数系统。     

孕中期母血清学对出生缺陷的产前筛查及影响因素的研究

目的通过分析孕中期母血清标志物甲胎蛋白、绒毛膜促性腺激素和游离雌三醇,研究孕中期母血清学对胎儿出生缺陷筛查的意义以及相关影响因素。方法对10 115例孕中期孕妇采用时间分辨免疫荧光法检测血清中的AFP、β-HCG和u E3浓度,通过评估软件计算21三体、18三体和开放性神经管缺陷风险值,高风险者进一步产前诊断确诊;分析AFP、β-HCG和u E3的浓度在21三体低风险与高风险的变化;分析孕周和年龄对产前筛查的影响。结果筛出21三体高风险329例,确诊6例,其中假阴性1例,其他出生缺陷8例;18三体5例,确诊0例,其他出生缺陷1例;开放性神经管缺陷36例,确诊2例,其他出生缺陷4例。AFP和u E3浓度随孕周增加而逐渐增加,β-HCG浓度随孕周增加而逐渐降低,AFP和u E3在21三体高风险比低风险浓度降低(P0.05),而β-HCG浓度升高(P0.01),具有统计学意义;不同孕周对21三体高风险的筛查无明显影响;高龄使21三体阳性率增加。结论 AFP和u E3在21三体高风险比低风险浓度降低,β-HCG浓度升高,孕中期母血清学对21三体及某些严重胎儿缺陷筛查的具有重要意义。     

怀化市孕中期唐氏综合征的血清筛查和产前诊断分析

目的探讨孕中期采用甲胎蛋白(AFP)、游离β-绒毛膜促性腺激素(Free-β-HCG)、游离E3(uE3)联合筛查法在孕中期筛查唐氏综合征(DS)、神经管缺陷(NTD)及其他胎儿异常的可行性。方法应用时间分辨免疫荧光法检测孕妇血清中AFP、Free-β-HCG、uE3浓度,结合母龄、体重、孕周等个体参数,经过软件计算风险率;对高风险孕妇在知情的情况下,自愿选择进行染色体核型分析。结果 12 559例样本共筛查出高危孕妇862例,其中457例进行羊水染色体核型诊断;检出唐氏综合征儿16例,染色体结构异常27例,染色体多态11例。结论孕中期应用母血清三联法筛查,结合产前诊断是减少出生缺陷发生的有效手段之一。     

江苏地区孕中期唐氏综合征筛查母血清标志物中位倍数标化方法的探讨

目的 探讨我国唐氏综合征产前筛查时应用国外软件MultiCalc作内嵌参数估计的适用性.方法 通过构建血清指标中位浓度与孕龄间的回归关系,选取最优模型得到指标中位浓度.并对中位倍数(multiple of the median,MoM)与体重的关系进行探讨,选取最优模型得到体重调整后的MoM值.结果 在未经体重校正的条件下,江苏地区孕中期孕妇的甲胎蛋白(alpha fetal protein,AFP)平均水平比MultiCalc软件内嵌参数源人群(欧洲白人)AFP平均水平要高出16%,而游离β-人绒毛膜促性腺激素(β-human chorionic gonadotrophin,β-hCG)要高出14%.经过体重校正后,MultiCalc软件计算的表达成MoM值的AFP平均水平为0.99,游离β-hCG平均水平为1.02,而模型标化的血清标志物的MoM中位数均为1.00.结论 江苏地区孕中期妇女的血清指标平均水平与MultiCalc软件内嵌参数源人群没有差别,MultiCalc软件适合于江苏省孕妇的唐氏综合征筛查.     

抑制素A在孕中期唐氏综合征产前筛查中的参考价值分析

目的探讨抑制素A在孕中期唐氏综合征的产前筛查中的参考价值。方法选取2016年6月至2018年6月于我院行孕中期(13-28w)产前筛查的孕妇为研究对象,以确诊的48例唐氏综合征为试验组,另外同期选取了50例正常妊娠结局的孕妇为正常组,检测孕妇的血清中的抑制素A、甲胎蛋白(AFP),人绒毛膜促性腺激素(hCG)以及游离雌三醇(uE3)的水平,分析对比各种筛查方法的敏感性和特异性。结果两组患者的年龄、孕周、B超计算的孕周比例和体重均无显著差异性(P均0.05);试验组的血清的抑制素A的浓度显著高于正常组(P0.05);联合AFP+hCG+uE3+抑制素A的筛查方法的检测率、假阳性率和ROC曲线下面积均优于AFP+hCG、AFP+hCG+uE3方法(P均0.05)。结论抑制素A是一种相对敏感而有效的孕中期的产前筛查的血清标志物,临床上联合使用抑制素A对唐氏综合征的诊断具有较好的参考价值。     

6746例孕妇血清生化二联标记物筛查唐氏综合征分析

目的探讨孕妇血清标志物甲胎蛋白(AFP)和游离绒毛膜促性腺激素(Free-βhCG)对孕中期妇女进行胎儿唐氏综合征(Down's syndrome,DS)为主的先天缺陷筛查的作用.方法对孕15w～19w妇女进行上述二项血清标志物检测,结合孕妇年龄、孕周、体重等因素,经过软件计算风险率,对高风险孕妇进行羊水细胞染色体检查及三维彩超进行确诊.结果6746例孕妇中,发现DS 2例,18-三体综合征2例,其它胎儿异常24例.结论孕中期血清AFP、Free-βhCG二项血清标志物联合检测,可作为孕中期唐氏综合征筛查优选项目;在孕中期用AFP、Free-βhCG检测还可以筛查神经管缺陷(NTD),18-三体综合征等其它胎儿异常.     

孕中期母血清学产前筛查对预测妊娠结局的价值研究

目的探讨孕中期血清标志物甲胎蛋白(AFP)和人绒毛膜促性腺激素β亚单位(β-HCG)在妊娠结局预测中的临床意义。方法利用时间分辨免疫荧光法测定6515例孕中期孕妇血清AFP和β-HCG,追踪受检孕妇妊娠结局。按AFP和β-HCG结果分成:不升高组、一项升高组(AFP组和β-HCG)和两项升高组(定义为大于2Mo M为升高),分析每个组流产、早产、胎死宫内、妊娠期高血压子痫前期、胎盘异常,和低出生体重等的不良妊娠结局的比例。结果 1项升高组比不升高组不良妊娠结局比例都有少量增加,而两项升高组不良妊娠结局比例则有明显增加,差异有统计学意义(P0.05)。结论孕妇孕中期血清AFP和a-HCG的异常预示不良妊娠结局的几率增加。     

ADAM12在孕早期筛查唐氏综合征的价值探讨

目的探讨去整合素金属蛋白酶12(ADAM12)在孕早期唐氏综合征(DS)中的筛查价值。方法选取2018年2月至2019年2月于我院行DS筛查的孕早期孕妇为研究对象,分析其血清中的人绒毛膜促性腺激素(β-hCG)、甲胎蛋白(AFP)和ADAM12水平,探讨其在不同孕周中的水平变化,以及各检验方法的检验灵敏度和特异度。结果不同孕周的孕妇的年龄和体重分布均无显著差异(P均0.05);随着孕周增加,孕妇的AFP和ADAM12水平逐渐增加,而β-hCG水平逐渐下降,其在各孕周差异具有显著的统计学意义(P均0.05);唐氏综合征阳性组和正常组的β-hCG、AFP和ADAM12水平均存在显著的统计学差异(P均0.05);联合β-hCG、AFP和ADAM12检测的AOC曲线下面积显著大于联合β-hCG和AFP检测、以及单独的ADAM12检测(P0.05)。结论 ADAM12在孕早期筛查唐氏综合征中具有较高的应用价值,有待进一步验证后推广使用。     

金华地区产前筛查孕中期中位数倍数的应用

目的对金华地区孕中期孕妇的血清标志物中位数倍数进行统计分析,了解本地区正常与缺陷儿孕妇的血清标志物中位数倍数,以防缺陷儿的出生。方法利用美国Perkin Elmer公司Auto DELFIA全自动时间分辨荧光免疫分析仪对20232例孕中期单胎孕妇血清（孕周在15～20^＋6w）各标志物浓度进行检测分析,用Lifecycle3.2软件计算唐氏综合征风险,拟合出的符合本地中位数方程计算唐氏综合征风险。结果显示随孕周增加,血清AFP和u E3值有明显增加趋势,分析呈正相关（P〈0.01）;而freeβ-h CG值水平明显降低,呈负相关（P〈0.01）,孕妇体重随着孕周的增加而增加,各血清标志物与体重呈负相关（P〈0.01）;在确诊的唐氏综合征、开放性神经管畸形、18-三体综合征的病例中相关孕妇血清指标Mo M值表现为异常。结论当有血清标志物Mo M值明显大于或小于正常时应召回孕妇做进一步的产前咨询与诊断,以防缺陷儿的出生。     

抑制素A水平与中孕期筛查标志物及影响因素的相关性分析

目的评估中孕期母亲血清中抑制素A水平与其它血清标志物和影响因素的相关性。方法选择2008年3月-2010年12月在广州市妇女儿童医疗中心接受中孕期＂三联＂唐氏筛查的单胎妊娠孕妇共2802例。采用全自动酶联免疫化学发光分析法检测血清中抑制素A水平。结果 （1）在正常妊娠孕妇血清样本,抑制素A与中孕期血清标志物freeβ-hCG、AFP相关且有统计学意义（P〈0.01）,尤其与freeβ-hCG的相关性最高（r=0.502）,而与uE3相关性没有统计学意义（P〉0.05）;在胎儿唐氏综合征孕妇血清样本,抑制素A与freeβ-hCG、AFP和uE3的相关性均没有统计学意义（P〉0.05）。（2）135例阴道流血和40例糖尿病孕妇血清中抑制素A水平与无合并症的孕妇没有差异（P均〉0.05）。孕期母亲体重与血清中抑制素A水平呈负相关（r=-0.101）,并有统计学意义（P〈0.01）。男性胎儿孕妇血清中抑制素A水平低于女性胎儿孕妇并有统计学意义（P〈0.01）。结论血清中抑制素A水平与中孕期标志物freeβ-hCG的相关性最高,与母亲体重呈负相关性,且与胎儿性别相关,但不受孕期母亲阴道流血或糖尿病的影响。     

Omphalocele, advanced maternal age, and fetal morbidity outcomes

In this study we wanted to determine if the risk for adverse neonatal outcome among omphalocele-affected fetuses is increased among older gravidas. This was a retrospective cohort study on live-born infants with omphalocele delivered in New York State from 1983 through 1999. We compared infants of older (>or=35 years) with those of younger (<35 years) mothers with respect to the following fetal morbidity indices: low birth weight and very low birth weight, preterm and very preterm, and small for gestational age. We used adjusted odds ratios to approximate relative risks. Data on a total of 1,010 infants with omphalocele were analyzed. Mean gestational age and birth weight were similar in both maternal age categories: mean+/-standard deviation (SD) for infants with omphalocele born to older mothers=37.4 weeks+/-3.9 versus 38.0 weeks+/-5.1 for those of younger mothers (P=0.2); mean birth weights+/-SD for infants with omphalocele born to older mothers=2,813+/-871.1 versus 2,958+/-809.9 for those of younger mothers (P=0.08). Also, the two maternal age sub-groups did not differ with respect to the fetal morbidity outcome: low birth weight (OR=0.95; 95% CI=0.60-1.51), very low birth weight (OR=0.78; 95% CI=0.36-1.69), preterm (OR=0.95; 95% CI=0.58-1.57), very preterm (OR=0.73; 95% CI=0.34-1.58), and SGA (OR=1.00; 95% CI=0.44-2.27). Thus, advanced maternal age does not appear to be a risk factor for fetal morbidity outcomes among omphalocele-affected fetuses. This information is potentially useful in counseling affected parents.     

Vanishing twins: a predictor of small-for-gestational age in IVF singletons

BACKGROUND: The purpose of this study was to assess the effect of a vanishing twin on the risk of being small-for-gestational age (SGA) in in vitro fertilization (IVF) singletons. METHODS: The study included 642 survivors of a vanished co-twin, 5237 primary singletons and 3678 primary twins. The survivor cohort was subdivided according to gestational age at the time of vanishing to give groups of early (<8 weeks), intermediate (8-22 weeks) and late (>22 weeks) survivors. RESULTS: The rate of SGA infants was significantly higher in survivors than in singletons (OR: 1.50, 95%CI: 1.03-2.20) and a significant inverse correlation was observed between SGA and the gestational age at the time of vanishing (r = -0.10, P < 0.02). Also in term infants, the risk of birthweight <2500 g was higher in survivors than in singletons (OR: 1.71, 95%CI: 1.06-2.74). A similar increase in the rate of low birthweight in term survivors was seen with increasing gestational age at the time of vanishing (r = -0.12; P < 0.01). In multiple logistic regression analysis adjusting for maternal age, parity, child gender and pre-eclampsia, the vanishing of a co-twin (OR: 1.56, 95%CI: 1.06-2.27) and gestational age at the time of vanishing (OR: 2.08, 95%CI: 1.00-4.35) were the only significant predictors of being SGA. CONCLUSIONS: IVF singletons with a vanished co-twin had a higher rate of SGA than singletons from a single gestation and the risk of SGA is increased with increasing gestational age at the time of vanishing.     

Genes or placenta as modulator of fetal growth: evidence from the insulin-like growth factor axis in twins with discordant growth

To determine whether fetal growth is regulated by placental and/or fetal factors, we measured maternal and fetal concentrations of insulin-like growth factor-I (IGF-I), IGF-II and insulin-like growth factor binding protein-1 (IGFBP-1) (total and non-phosphorylated) in dichorionic (DC) and monochorionic (MC) twins with (DC, n = 13; MC, n = 12) or without (DC, n = 13; MC, n = 12) discordant birth weight. In the discordant MC pregnancy, growth-restricted (IUGR) twins had lower IGF-II concentrations (P < 0.001) but similar IGF-I concentrations compared to the appropriate for gestational age(AGA) co-twin. The differences in IGF-II concentrations showed a positive association with percentage birth weight discordance (r = 0.60; P < 0.05) in MC twins. In contrast, IUGR DC twins had lower IGF-I concentrations (P < 0.05) but similar IGF-II concentrations compared to the AGA co-twins. There was a positive correlation between IGF-I concentrations and birth weight (r = 0.47; P < 0.05) in DC twins. Total IGFBP-1 concentrations were higher in both MC and DC IUGR twins (P < 0.05) compared to AGA twins. A negative association was found between total IGFBP-1 concentrations and birthweight of both MC (r = 0.47; P < 0.05) and DC (r = 0.58; P < 0.01) twins. No such differences in IGF concentrations were found between concordant MC and DC twin pairs. The maternal IGF concentrations were comparable between the MC and DC groups. These data suggest that growth discordances of twins exposed to the same maternal environment may be due to variations in either IGF-I or IGF-II/IGFBP-1, depending upon the functioning of the placenta.     

Risk factors and long-term health consequences of macrosomia: a prospective study in Jiangsu Province,China

We sought to determine risk factors associated with fetal macrosomia and to explore the long-term consequence of infant macrosomia at the age of 7 years.A prospective population based cohort study was designed to examine the associations between maternal and perinatal characteristics and the risk of macrosomia.A nested case-control study was conducted to explore the long-term health consequence of infant macrosomia.The mean maternal age of the macrosomia group was 24.74±3.32 years,which is slightly older than that in the control group(24.35±3.14 years,P = 0.000).The mean maternal body mass index(BMI) at early pregnancy was 22.75±2.81 kg/m 2,which was also higher than that in the control group(21.76±2.59 kg/m 2,P = 0.000).About 64.6% of macrosomic neonates were males,compared with 51.0% in the control group(P = 0.000).Compared with women with normal weight(BMI:18.5-23.9 kg/m 2),women who were overweight(BMI:24-27.9 kg/m 2) or obese(BMI ≥ 28 kg/m 2),respectively,had a 1.69-fold(P = 0.000) and a 1.49-fold(P = 0.000) increased risks of having a neonate with macrosomia,while light weight(BMI18.5 kg/m 2) women had an approximately 50% reduction of the risk.Furthermore,macrosomia infant had a 1.52-fold and 1.50-fold risk,respectively,of developing overweight or obesity at the age of 7 years(P = 0.001 and P = 0.000).Older maternal age,higher maternal BMI at early pregnancy and male gender were independent risk factors of macrosomia.Macrosomic infant was associated with an increased predisposition to develop overweight or obesity at the beginning of their childhood.     

Early life and current determinants of bone in South African children of mixed ancestral origin

BACKGROUND: The influence of early life factors on the bone mineral density of children has been identified, however the contribution of these determinants may vary. AIM: The study investigated determinants of bone mineral content (BMC) in South African children of mixed ancestral origin. SUBJECTS AND METHODS: Early life data including birth weight, maternal alcohol consumption and smoking during pregnancy were collected on 9-year-old children of mixed ancestral origin (n = 64). Grip strength was measured, and physical activity, housing density and dietary data were collected. Whole body BMC (WB BMC), fat-free soft tissue and fat tissue were measured using dual energy X-ray absorptiometry. RESULTS: Maternal alcohol consumption during pregnancy was associated with WB BMC, however after adjusting for possible confounders, this was no longer significant. When combined with gender, gestational age and maternal BMC in a multiple regression, maternal alcohol consumption during pregnancy could explain 20% of the variance in the WB BMC, however when current height was included in the model, the contribution of the other factors was insignificant. There was however a significant correlation between current height and birth weight (r = 0.34; p < 0.01) and alcohol consumption during pregnancy (r = 0.34; p < 0.05). A model consisting of current factors such as age, weight, gender, grip strength and calcium intake was able to explain 81.5% of the variance. Housing density was negatively correlated with WB BMC (r =-0.11; p = 0.05). CONCLUSION: These data suggest that although early life factors may contribute indirectly to the bone mass of children of mixed ancestral origin, the contribution of current factors is greater. In addition, environmental factors such as housing density have a direct effect on bone mass, independent of body size.     

An in-vivo study on placental transfer of naproxen in early human pregnancy

BACKGROUND: Naproxen is one of the most common non-steroidal anti-inflammatory drugs used by women of reproductive age. Naproxen is known to be teratogenic in animals. The aim of this study was to investigate the placental transfer of naproxen in the first trimester of human pregnancy, and to determine the amount of the drug in different embryonic compartments. METHODS: Twenty-eight patients who requested surgical termination of pregnancy in the first trimester were given two oral 500 mg doses of naproxen before the surgical procedure. Four biological samples, maternal venous blood, coelomic fluid, amniotic fluid and fetal tissue, were collected from each patient for drug analyses by high performance liquid chromatography. RESULTS: Naproxen was detected in all samples. The mean (+/- SD) concentrations were 69.5 +/- 12.2 microg/ml, 6.4 +/- 2.4 microg/g, 1.85 +/- 1.03 microg/ml and 0.14 +/- 0.11 microg/ml in maternal serum, fetal tissue, coelomic fluid and amniotic fluid respectively. The mean amniotic fluid/maternal drug ratio and fetal/maternal drug ratio were 0.002 (range 0.0005-0.0064) and 0.092 (range 0.022-0.155) respectively. There was a positive correlation between the fetal drug concentration (r = 0.59, P = 0.001), amniotic fluid drug concentration (r = 0.47, P = 0.013), amniotic fluid/maternal ratio (r = 0.536, P = 0.003) and fetal/maternal ratio (r = 0.72, P < 0.001) with advancing gestational age. CONCLUSIONS: Although naproxen can cross the placenta readily in the first trimester of human pregnancy, only a small amount was present in fetal tissues. Since there is no information on whether this small amount of naproxen would be teratogenic or not, women of reproductive age who are taking naproxen regularly should be warned of the possible fetal side-effects.     

Development of the fetal uterus between 19 and 38 weeks of gestation: in-utero ultrasonographic measurements.

In-utero assessment of the internal female genitalia is important for determination of fetal gender in fetuses with suspected genital tract anomalies. We therefore measured fetal uterine transverse width and circumference from 19 weeks of gestation until term, using transvaginal and transabdominal high-resolution ultrasound techniques in order to establish nomograms. A prospective, cross-sectional study on 180 normal singleton pregnancies was performed. Data were obtained for 140 normal fetuses. The mean +/- SD uterine width and circumference were 12.9 +/- 4.1 mm (95% confidence interval 12.1-13.7), and 40.2 +/- 12.5 mm (95% confidence interval 37.9-42.5) respectively. Uterine size as a function of gestational age was expressed by the regression equations: uterine width (mm) = 12.9 + 0.7 x gestational age (weeks), and uterine circumference (mm) = 40.2 + 2.1 x gestational age. The correlation coefficients, r = 0.885 and r = 0.888, for uterine width and circumference, by gestational age respectively, were highly statistically significant (P < 0.001). A nomogram of uterine width and circumference per gestational week, and the 95% prediction limits were defined. The present data offer baseline measurements of the fetal uterus that may allow intrauterine assessment of the female genital tract and associated fetal gender.