Evaluation of a commercial immunoenzymometric assay for alpha-fetoprotein

A two-site immunoenzymometric assay (Abbott Diagnostics) for alpha-fetoprotein (AFP) in maternal serum and amniotic fluid has been evaluated for its suitability as a screening test for open neural tube defects. In a retrospective study based on 190 pregnancies of known outcome, performance of the kit in measuring both serum and amniotic fluid AFP correlated well with that of an in-house radioimmunoassay. Of 39 pregnancies associated with open neural tube defects, only four would not have been detected by the use of sequential measurement of serum and amniotic fluid AFP (also essentially in agreement with results obtained by the RIA). We conclude that this immunoassay could form the basis for a screening program for antenatal detection of open neural tube defects.     

产前筛查先天性缺陷与胎儿染色体异常的研究

目的 探讨孕中期血清标志物在产前筛查胎儿染色体异常的作用和价值.方法 对2555例孕中期(14～22周)孕妇血清甲胎蛋白、β-HCG和uE3 3项指标进行检测,并结合孕妇年龄、孕周、体质量、是否双胎、有无糖尿病等,采用仪器配套软件计算风险概率,对南风险孕妇进行染色体检查确认.结果 2555例孕妇中筛查出唐氏综合征高风险210例,占筛查总数的8.2％;18-三体综合征高风险26例,占筛查总数的1.0％;神经管缺陷高风险29例,占筛查总数的1.1％.高风险孕妇中有207例自愿进行了羊水细胞染色体检查或胎儿脐血染色体检查,检测出染色体异常核型12例,异常率为5.8％.结论 孕中期孕妇血清唐氏综合征、18-三体综合征、神经管缺陷联合筛查胎儿先天缺陷是行之有效的方法,可以作为产前筛查的常规项目.     

Prenatal detection of anencephaly

Summary Fetal anomalies were suspected clinically in 3 patients, during the second trimester of pregnancy, due to advanced maternal age, hydramnios and abnormal vaginal bleeding respectively. Sonography revealed anencephaly in all of them, confirmed by roentgenograms and also by high amniotic fluid level alpha-fetoprotein in 1 of them. The antenatal diagnosis was confirmed in the 3 abortuses. Early screening of all pregnancies at risk for neural tube malformations is strongly recommended.     

HBsAg carrier status and the association between gestational diabetes with increased serum ferritin concentration in Chinese women

OBJECTIVE: To determine whether the high prevalence of hepatitis B surface antigen (HBsAg) carriage in our population can explain the previous observation of an association between increased maternal serum ferritin concentration and gestational diabetes in Hong Kong Chinese women. RESEARCH DESIGN AND METHODS: A retrospective study was performed on 767 nonanemic women with singleton pregnancy who had iron status assessed at 28-30 weeks. The result of the routine antenatal HBsAg screening was retrieved from patient records. The HBsAg-positive and -negative groups were compared for maternal characteristics, prevalence of gestational diabetes in the third trimester, prevalence of high serum ferritin and iron concentrations, and transferrin saturation, which is defined as a value in the highest quartile established by the measurements obtained from the HBsAg-negative group. RESULTS: The incidences of oral glucose tolerance test and gestational diabetes were significantly increased in the HBsAg-positive group. The HBsAg-positive women with gestational diabetes had significantly increased prevalence of high serum ferritin compared with the HBsAg-negative women, irrespective of the latter's gestational diabetes status. Multiple logistic regression analysis confirmed the independent association between HBsAg carrier status with gestational diabetes (relative risk 3.51, 95% CI 1.83-6.73) but excluded high ferritin as an independent factor. CONCLUSIONS: Our results indicate that maternal HBsAg carriage could explain in part the association between increased serum ferritin concentration with gestational diabetes in Hong Kong Chinese women, and that HBsAg carrier status is an independent risk factor for gestational diabetes.     

Maternal serum screening for Down's syndrome, open neural tube defects and trisomy 18.

Maternal serum screening identifies women at an increased risk of a pregnancy with Down's syndrome or trisomy 18 or an open neural tube defect. The triple test, consisting of maternal serum alpha-fetoprotein, unconjugated estriol and human chorionic gonadotropin was carried out by a chemiluminescence immunoassay method in our laboratory. The study consisted of 373 pregnant women. The gestational range for the study group was 14-22 weeks. The mean maternal age for the study group was 28.53 +/- 5.46 years (range 17.4 to 43.5 years); 9.1% of the women were considered at high risk for Down's syndrome based on the test results. In our study the detection rate for Down's syndrome by prenatal karyotyping was 66.6%. Maternal serum screening allows reduction of the number of women requiring amniocentesis without a significant decrease in the detection rate.     

Maternal vitamin B12 and the risk of fetal neural tube defects in Egyptian patients

OBJECTIVE: Folic acid insufficiency is a known risk factor for neural tube defects (NTDs), while the role of vitamin B12 is questionable. Thus, our purpose was to investigate whether low maternal serum vitamin B12 is associated with an increased risk of NTDs. SETTING: Prenatal Diagnosis and Clinical Genetics Clinics, National Research Centre, in collaboration with the Radioisotope Department, Nuclear Research Centre, Cairo. MATERIALS AND METHODS: The study groups included 36 women who were, or had been, pregnant with a NTD-affected fetus. The control groups comprised 35 healthy women with normal prior or current pregnancy and uncomplicated obstetric histories. Fasting plasma homocysteine, serum folate and cobalamin (vitamin B12) were determined. Odds ratio (OR) and 95% confidence intervals were calculated. RESULTS: The fasting homocysteine was significantly higher in the study groups as compared to the controls. The median serum folate concentrations were similar in cases and controls, while the median vitamin B12 concentrations were significantly lower in the study groups compared to the controls. Low vitamin B12 concentration was associated with an approximately 2- to 3-fold increased risk for NTDs. CONCLUSION: Low maternal serum values of vitamin B12 can be considered an important etiologic factor for the development of neural tube defects in our population. This may help in both genetic counseling for families with a history of NTD malformation, and as a pre-conceptional prophylactic measure by maternal supplementation of vitamin B12 and folic acid.     

Prenatal screening for open neural tube defects

The era of prenatal screening for serious birth defects began in the 1970s with the discovery that amniotic fluid and maternal serum levels of alpha-fetoprotein (AFP) were increased in pregnancies affected by fetal open neural tube defects. Since then, prenatal screening has become a part of routine obstetric care. In this article, the use of AFP in prenatal screening for open neural tube defects is discussed in the context of the laboratory and the laboratory's interactions with the practicing obstetrician.     

Preconception care and the risk of congenital anomalies in the offspring of women with diabetes mellitus: a meta-analysis

Offspring of women with pregestational diabetes mellitus are at increased risk for congenital malformations, largely attributable to poor periconceptional glycaemic control. We assessed the effect of preconception care in reducing congenital malformations, in a meta-analysis of published studies of preconception care in women with diabetes mellitus. Articles were retrieved from Medline (1970 to June 2000) and Embase (1980 to June 2000), and data abstracted by two independent reviewers. The rates and relative risks (RR) for major and minor congenital malformations were pooled from all eligible studies using a random effects model, as were early first-trimester glycosylated haemoglobin values. In 14 cohort studies, major congenital malformations were assessed among 1192 offspring of mothers who had received preconception care, and 1459 offspring of women who had not. The pooled rate of major anomalies was lower among preconception care recipients (2.1%) than non-recipients (6.5%) (RR 0.36, 95%CI 0.22-0.59). In nine studies, the risk for major and minor anomalies was also lower among women who received preconception care (RR 0.32, 95%CI 0.17-0.59), as were the early first-trimester mean glycosylated haemoglobin values (pooled mean difference: 2.3%, 95%CI 2.1-2.4). Women who received preconception care were, on average, 1.8 years older than non-recipients, and fewer smoked (19.6% vs. 30.2%). Only one study described the routine use of periconception folic acid. Out-patient preconception care probably reduces the risk of major congenital anomalies among the offspring of women with pregestational diabetes mellitus. Because many women with diabetes neither plan their pregnancy nor achieve adequate glycaemic control before conception, strategies are needed to improve access to these programs, and to maximize those interventions associated with improved pregnancy outcome, such as smoking cessation and folic acid use.     

Prenatal testing for maternal serum alpha-fetoprotein

The maternal serum alpha-fetoprotein level should be measured in all pregnant women at 16 to 20 weeks of gestation. Elevated alpha-fetoprotein levels require evaluation by ultrasonography and, sometimes, amniocentesis to detect neural tube defects. Low alpha-fetoprotein levels may be associated with chromosomal anomalies and should be evaluated with amniocentesis. Alpha-fetoprotein testing is cost-effective, and medicolegal liability makes it imperative to offer this screening test to all pregnant women.     

Urinary tract infections in pregnancy

QUESTION: My pregnant patients often present with urinary tract infections. Are the medications commonly used for the management of urinary tract infections safe to use during pregnancy? ANSWER: Existing data indicate that exposure to penicillins, cephalosporins, fluoroquinolones, nitrofurantoin, or phenazopyridine during pregnancy is not associated with increased risk of fetal malformations. Trimethoprim-sulfamethoxazole should be avoided, if possible, during the first trimester of pregnancy because of the antifolate effect associated with neural tube defects.     

孕中期产前筛查在优生优育中的重要性

目的对孕妇血清甲胎蛋白AFP、游离绒毛膜促性腺激素β—HCG用于唐氏综合征、18-三体和神经管畸形筛查进行回顾性分析,探讨产前筛查在优生优育中的重要意义。方法对2009年11月至2010年12月我院国产保健门诊单胎孕妇2969例妊娠中期（15周-20^＋6周）,采用时间分辨法检测AFP、Free—β-HCG,对筛查高风险者转诊,诊断机构作产前诊断确诊。结果2969例中筛出3例异常,经确诊其中1例为腹璧裂,1例为神经管缺陷,1例为染色体异常。结论孕妇清标记物筛查能有效降低需要进行创伤性产前诊断的孕妇比例,降低染色体痰病患儿出生几率,提高出生人口素质。     

2616例孕中期孕妇的血清特异性标志物筛查结果分析

目的探讨孕中期产前筛查的临床应用价值,并探讨影响其风险值的主要因素。方法检测2616例孕中期（14～24周）孕妇血清中的甲胎蛋白（AFP）、人绒毛膜促性腺激素β亚单位（[3-HCG）和游离雌三醇（uE3）的浓度,其中AFP、β-HCG使用电化学发光法,uE3使用酶联免疫法检测;使用T21$SOFTw筛查软件评估风险。建议唐氏综合征或18-三体综合征高风险孕妇行胎儿羊水染色体核型分析,神经管缺陷高风险者接受高分辨超声检查。结果唐氏综合征、18-三体综合征、神经管缺陷高风险发生率分别为5．73％、0．34％、1．11％;高风险孕妇经产前诊断确诊唐氏综合征1例,神经管缺陷2例,其它染色体异常疾病3例。结论对孕中期孕妇进行产前筛查,是减少患染色体疾病和神经管缺陷患儿出生的有效方法;在筛查软件中应对诸多影响因素予以校正,而孕周的准确与否对筛查结果影响较大。     

Epidemiology, natural history, and management of urinary tract infections in pregnancy

The urinary tract undergoes profound physiologic and anatomic changes during pregnancy that facilitate the development of symptomatic UTIs in women with bacteriuria. Although the adverse effects of asymptomatic bacteriuria on maternal and fetal health continue to be debated, it is clear that asymptomatic bacteriuria is the major risk factor for developing symptomatic UTI and that symptomatic infections are associated with significant maternal and fetal risks. Because the majority of symptomatic UTIs develop in women with bacteriuria earlier in pregnancy, treatment of bacteriuria is undertaken to prevent symptomatic infections. All women should be screened at the first antenatal visit, which is reliably and inexpensively done with a dipstick culture. Short-course therapy is as effective as prolonged therapy and should be followed with a repeat culture to document clearing of the bacteriuria. Failure to eliminate bacteriuria with repeated therapy or recurrence with the same organism is indicative of renal parenchymal infection or a structural abnormality. All women with persistent bacteriuria or recurrent infection should have follow-up cultures and a complete urologic evaluation after delivery.     

Life without amniocentesis: elevated maternal serum alpha-fetoprotein in the Manitoba program 1986-91.

Pregnant women demonstrating an elevated maternal serum alpha-fetoprotein level are at increased risk for fetal neural tube defect or other anomaly. Diagnostic procedures to evaluate these pregnancies include high-resolution ultrasound and amniocentesis to measure amniotic fluid levels of alpha-fetoprotein and N-acetylcholinesterase. We wished to examine the efficacy of detailed ultrasound examination alone, in evaluation of women with 'unexplained' elevation of maternal serum alpha-fetoprotein. The results showed that no neural tube defects were missed in the assessment of 1325 pregnancies with a raised level of maternal serum alpha-fetoprotein over 6 years, despite complete reliance on ultrasound in 98%. Detailed fetal ultrasound evaluation by experienced personnel is adequate to identify all cases of neural tube defects in a selected high-risk population.     

孕中期检测孕妇血清标志物筛查唐氏综合征及神经管缺陷

目的检测孕中期（14～20周）妇女血清中甲胎蛋白（AFP）和游离绒毛膜促性腺激素（F-β-hCG）的含量,探讨其在唐氏综合征（DS）筛查中的价值。方法采用化学发光免疫分析法分别对孕中期妇女进行上述2项血清标志物检测,结合孕妇临床资料用分析软件计算风险率,以1：250作为高风险的切割值,并对高风险孕妇进行羊水细胞染色体核型分析给予确诊。结果筛查的1659例孕妇中,DS高危孕妇98例,阳性率5．9％,神经管缺陷高危孕妇12例,阳性率0．7％。35岁或35岁以上的孕妇组胎儿异常发生率高于35岁以下孕妇组（P〈0.01）,且两组异常胎儿染色体检出率差异有统计学意义（P〈0.01）。DS查高风险组胎儿异常发生率高于低风险组（P〈0．01）。结论利用DS筛查结合B超产前诊断能提高胎儿先天缺陷的早期发现和诊断。     

Routine ultrasound screening in diabetic pregnancies.

OBJECTIVES: To assess the detection rate of congenital fetal malformations and specific problems related to routine ultrasound screening in women with pre-existing diabetes. METHODS: A retrospective study was carried out to assess the performance of routine ultrasound screening in women with pre-existing diabetes (Types 1 and 2) within a tertiary institution. The incidence, type and risk factors for congenital fetal malformations were determined. The detection rate of fetal anomalies for diabetic women was compared with that for the low-risk population. Factors affecting these detection rates were evaluated. RESULTS: During the study period, 12 169 low-risk pregnant women and 130 women with pre-existing diabetes had routine ultrasound screening performed within the institution. A total of 10 major anomalies (7.7%) and three minor anomalies (2.3%) were present in the fetuses of the diabetic women. Central nervous system and cardiovascular system anomalies accounted for 60% of the major anomalies. Periconceptional hemoglobin A1c of more than 9% was associated with a high prevalence of major anomalies (143/1000). Women who had fetuses with major anomalies had a significantly higher incidence of obesity (78% vs. 37%; P < 0.05). Ultrasound examination of these diabetic pregnancies showed high incidences of suboptimal image quality (37%), incomplete examinations, and repeat examinations (17%). Compared to the 'low-risk' non-diabetic population from the same institution, the relative risk for a major congenital anomaly among the diabetic women was 5.9-fold higher (95% confidence interval, 2.9-11.9). The detection rate for major fetal anomalies was significantly lower for diabetic women (30% vs. 73%; P < 0.01), and the mean body mass index for the diabetic group was significantly higher (29 vs. 23 kg/m2; P < 0.001). CONCLUSION: The incidence of congenital anomalies is higher in diabetic pregnancies. Unfortunately, the detection rate for fetal anomalies by antenatal ultrasound scan was significantly worse than that for the low-risk population. This is likely to be related to the maternal body habitus and unsatisfactory examinations. Methods to overcome these difficulties are discussed.     

Maternal and perinatal outcomes amongst haemoglobinopathy carriers: a systematic review

With the introduction of screening programmes for haemoglobinopathies (HbP), more women will be aware of their HbP status. The genetic risk for women who are carriers of HbP is well known. However, midwives and obstetricians need to know whether there are other risks involved in the pregnancies of women who are carriers of HbP. The objective of this study was to investigate the hypothesis that being a carrier of HbP has no consequences for the health of pregnant women and the outcome of their pregnancies. A systematic search was carried out until August 2008 in the Cochrane Library, Medline, EMBASE and CINAHL databases. All references were inspected to identify further studies. The authors of key publications were contacted for any unpublished research. Selection of studies was made on the basis of the following criteria: Cohort and case-control studies, pregnant women with a singleton pregnancy, exposure: HbAS or thalassaemia minor and the following outcomes: urinary tract infection (UTI), anaemia, (pre-)eclampsia, gestational diabetes, premature labour, low birth weight, intrauterine growth retardation, miscarriage, neonatal death, low Apgar score, neural tube defects. Quality assessment and data extraction were carried out by two researchers. A total of 780 subjects were identified of which nine were included in the study. A protective effect of sickle cell trait was found for premature birth, low Apgar score and perinatal mortality rate. No significant effect was found for low birth weight, growth retardation, UTI or high blood pressure. The risk of anaemia and bacteriuria was increased. In conclusion, the risks amongst pregnant HbP carriers are low. Midwives and obstetricians need to be aware of the risk of anaemia and UTI.     

Women with impaired glucose tolerance during pregnancy have significantly poor pregnancy outcomes

OBJECTIVE: This article tests the hypothesis that women with impaired glucose tolerance (IGT) have the same pregnancy outcomes as those of their counterparts with normal glucose tolerance. RESEARCH DESIGN AND METHODS: From December 1998 to December 1999, 84 of 90 antenatal care base units (ACBUs) under the Tianjin Antenatal Care Network in China participated in the first screening program for gestational diabetes mellitus (GDM). A total of 9,471 pregnant women under the care of participating ACBUs were screened. Of the women screened, 154 were positive for IGT. Of the 154 women, 102 opted for conventional obstetric care. The comparison group was 302 women of normal glucose tolerance (NGT). The initial screening consisted of a 50-g 1-h glucose test, and was carried out at 26-30 gestational weeks. Women with a serum glucose > or =7.8 mmol/l were followed up with a 75-g 2-h oral glucose tolerance test. The World Health Organization's diagnostic criteria for GDM were used. RESULTS: Women with IGT were at increased risk for premature rupture of membranes (P-ROM) (odds ratio [OR] 10.07; 95% CI 2.90-34.93); preterm birth (6.42; 1.46-28.34); breech presentation (3.47; 1.11-10.84); and high birth weight (90th percentile or 4,000 g) (2.42; 1.07-5.46); adjusting for maternal age, pregravid BMI, hospital levels, and other confounding factors. CONCLUSIONS: The presence of IGT in pregnancy is predictive of poor pregnancy outcomes.     

Prenatal genetic screening

This article presents a discussion of screening principles and techniques available to screen for common birth defects during pregnancy. Sixty-five to 70% of women have serum screening and /or ultrasound during pregnancy to evaluate the health and well-being of the developing fetus. The most common birth defects identified by screening include neural tube defects and chromosome abnormalities. Nurses employed in prenatal care settings need to have accurate information they can provide to women so they understand the benefits and limitations of screening. Timely presentation of information and identification of available resources will help nurses minimize confusion and provide support for women as they proceed with pregnancy screening.     

3320例孕中期妇女唐氏综合征产前筛查结果分析

目的探讨孕中期妇女(14~20周)血清标志物甲胎蛋白(AFP)、游离绒毛膜促性腺激素(f-βhCG)及游离雌三醇(uE3)在胎儿唐氏综合征(DS)、18三体综合征和神经管畸形(NTD)筛查中的应用。方法采用化学发光技术检测孕妇血清中AFP、f-βhCG及uE3的浓度,结合孕妇年龄、孕周,利用上海腾臣唐氏软件计算胎儿患DS、18三体综合征和NTD的风险概率。结果对3 320例孕妇筛查结果进行分析,DS高危孕妇155例,阳性率4.67%;18三体综合征高危孕妇27例,阳性率0.81%;NTD高危孕妇57例,阳性率1.72%。经羊水穿刺确诊DS25例,经B超确诊NTD 9例。结论产前筛查对于严重先天性缺陷儿的宫内诊断具有重要的临床价值,对孕妇血清中AFP、f-βhCG及uE3标志物检测可有效地筛查出DS高危孕妇,能显著降低需要进行创伤性产前诊断的孕妇比例,降低唐氏儿出生率。