Placental thickness at mid-pregnancy as a predictor of Hb Bart's disease

The measurement of placental thickness can effectively differentiate normal pregnancies from affected pregnancies requiring invasive work-up. The objective was to evaluate the efficacy of placental thickness at mid-pregnancy in predicting fetal Hb Bart's disease in pregnancies at risk. Among 17 254 pregnant women screened for severe thalassaemia between June 1994 and December 1998, 345 pregnancies at risk for having a fetus with Hb Bart's disease underwent ultrasound examinations and cordocentesis at 18-21 gestational weeks. Before cordocentesis, the placental thickness was measured and recorded.The definite fetal diagnosis was performed with high performance liquid chromatography. The efficacy of placental thickness in predicting Hb Bart's disease was evaluated by sensitivity and specificity. Various cut-off values of the placental thickness were used for calculation and the best cut-off value was determined by a receiver-operating characteristic (ROC) curve. Of 345 pregnancies at risk, 70 fetuses with Hb Bart's disease were finally diagnosed. The mean placental thickness (+/-SD) of the normal pregnancies and pregnancies with Hb Bart's fetuses were significantly different, 24.6+/-5.2 mm and 34. 5+/-6.7 mm, respectively (Student's t-test, p<0.001). The sensitivity and specificity of placental thickness in prediction were calculated for various cut-off values. Based on the ROC curve, the best cut-off value was 30 mm (>30 mm considered abnormal), giving a sensitivity of 88.57 per cent, specificity of 90.18 per cent, positive-predictive value of 78.48 per cent and negative-predictive value of 96.87 per cent. For couples at risk, when sonographic placental thickness is normal, the risk of having an Hb Bart's fetus is markedly decreased. The measurement of placental thickness can effectively, though not absolutely, differentiate the normal pregnancies from affected ones requiring invasive work-up.     

胎儿大脑中动脉收缩峰期血流速度与二维超声预测重型α地中海贫血的对比研究

目的:探讨和比较应用超声多普勒技术测量胎儿大脑中动脉收缩峰期血流速度(MCA-PSV)与二维超声预测胎儿重型α地中海贫血(地贫)的价值。方法:为129例具有重型α地贫风险的胎儿行二维及多普勒超声检查,测量胎儿MCA-PSV并行羊膜腔穿刺或脐血穿刺术进行α地贫基因诊断。MCA-PSV用中位数的倍数(MOM)表示。结果:重型α地贫胎儿MCA-PSV明显高于非重型α地贫胎儿,差异有显著的统计学意义(P0.001)。MCA-PSV1.29MOM预测胎儿重型α地贫的检出率为81.25%,高于二维超声(P0.05);MCA-PSV联合二维超声对胎儿重型α地贫的检出率为90.63%。MCA-PSV最早可在孕16周预测胎儿重型α地贫,MCA-PSV预测胎儿重型α地贫的平均孕龄小于二维超声(P0.05)。结论:MCA-PSV预测胎儿重型α地贫优于二维超声。MCA-PSV联合二维超声可提高胎儿重型α地贫的检出率。超声多普勒测量胎儿MCA-PSV对早期预测胎儿重型α地贫,早期处理以减少产科并发症的发生具有临床价值。     

Sonographic diagnosis of limb reduction defects in a fetus with haemoglobin Bart's disease at 12 weeks of gestation.

Limb reduction defect is a rare event but is found in eight per cent of fetuses affected by haemoglobin Bart's disease. We present a case of haemoglobin Bart's disease with terminal transverse limb reduction defects of all four limbs diagnosed by abdominal ultrasound examination at 12 weeks of gestation. The pregnancy was terminated by suction curettage. Just prior to the procedure, transabdominal needle embryoscopy was performed and this confirmed the sonographic diagnosis. The present case demonstrates the need and feasibility of a detailed anatomic survey of a fetus affected by haemoglobin Bart's disease at 12 weeks. This is particularly relevant if the patient is considering the option of intra-uterine therapy.     

中晚孕期18-三体综合征胎儿的超声特征

目的:研究中晚孕期18-三体综合征胎儿超声影像的变化。方法:回顾分析经羊膜腔穿刺、脐血管穿刺胎儿染色体分析确诊为18-三体的胎儿24例的临床资料和超声影像特征。结果:24例18-三体胎儿中,22例超声影像有变化,占全部病例的91.7%;最常见的超声变化是心脏畸形,共15例,占62.5%;其它常见的异常有脉络膜囊肿、脐带异常、肢体异常、宫内生长迟缓、脑室扩大、小脑延髓池扩大等;还可见颅骨变形、颜面裂、颈项皮肤增厚、消化道闭锁、腹壁缺损、膈疝、肾盂轻度积水、羊水过多等。结论:超过90%的18-三体胎儿中晚孕期可发现超声影像改变,中晚孕期胎儿超声检查是产前筛查18-三体胎儿的有效手段。     

Simple non-invasive prenatal detection of Hb Bart's disease by analysis of fetal erythrocytes in maternal blood

OBJECTIVE: To investigate a simple non-invasive technique for early detection of Hemoglobin (Hb) Bart's disease. METHOD: Maternal blood smears from 8 known Hb Bart's pregnancies and 40 at-risk pregnancies were investigated. Maternal peripheral blood smears were stained with fluorescence-labeled monoclonal antibodies against alpha- and embryonic zeta-globin chains. RESULTS: Fetal nonnucleated red blood cells, stained with anti-zeta but not with anti-alpha globin antibodies were found in 15 out of 16 affected pregnancies but were not detected in 23 out of 24 unaffected pregnancies. CONCLUSION: Results showed that non-invasive immunofluorescence staining of maternal blood is a feasible approach for screening Hb Bart's disease before ultrasound manifestation in affected pregnancies.     

Second trimester maternal serum markers and a predictive model for predicting fetal hemoglobin Bart’s disease

Objective: To compare the levels of maternal serum α-fetoprotein (AFP), unconjugated estriol (uE3) and free β-human chorionic gonadotropin (free β-hCG) between pregnancies with fetal Hb Bart’s disease and unaffected pregnancies. Methods: 148 pregnancies at risk of fetal Hb Bart’s disease scheduled for cordocentesis at 18 to 22 weeks were prospectively recruited into the study. AFP, uE3 and free β-hCG concentrations were measured before cordocentesis and the final fetal diagnosis of Hb Bart’s disease was based on fetal Hb typing using high-performance liquid chromatography. Results: AFP and free β-hCG were significantly higher whereas uE3 was lower in women with fetal Hb Bart’s disease than those with unaffected fetuses (1.94 MoM, 1.38 MoM and 0.81 MoM respectively). Hb Bart’s predictive model; probability = 1/1+e^{?[2.876 + 1.333(AFP) ? 6.310(uE3)]}, effectively predicted fetal Hb Bart’s disease (AUC ROC 0.91, 95% CI 0.84–0.97) with 61.5% sensitivity and 98.1% specificity using a cut-off probability at greater than 0.5. Conclusions: In triple test, serum AFP and hCG levels are significantly higher while serum uE3 is significantly lower in pregnancies with fetal Hb Bart’s disease. Hb Bart’s predictive model included AFP and uE3 is relatively effective and may be helpful in Hb Bart’s prenatal screening.     

Prenatal diagnosis of fetal primary cytomegalovirus infection

Objective To determine the reliability of prenatal diagnosis for congenital cytomegalovirus in women with primary infection.
Design Retrospective analysis of case records between 1992 and 1997.
Setting Fetal medicine unit of a large teaching hospital.
Population Forty-two pregnant women with primary cytomegalovirus infection.
Methods Fetal diagnosis was made by amniocentesis for viral culture and amplification of cytomegalovirus DNA by polymerase chain reaction (   n = 37  ), or by cordocentesis for the detection of cytomegalovirus -specific IgM antibodies (   n = 13  ). All patients had serial ultrasonographic scans in order to detect those fetuses with abnormalities that could be associated with cytomegalovirus infection.
Results Fourteen pregnancies (33.3%) had evidence of vertical transmission. Nine out of 14 (64.3%) had positive amniotic fluid culture, while 11 (78.6%) had positive polymerase chain reaction results. The combination of both tests allowed antenatal diagnosis in 12 of the 14 infected fetuses (sensitivity 85.7%). All women who underwent cordocentesis for the detection of cytomegalovirus-specific IgM antibodies had negative results, but in two cases cytomegalovirus infection was detected by amniotic fluid studies. In five of the infected fetuses there were abnormal ultrasonographic findings. All pregnancies with evidence of vertical transmission were terminated and the remainder proceeded normally to term.
Conclusions Our data showed that amniotic fluid studies, preferably polymerase chain reaction amplification of viral DNA, are the best diagnostic tools for the detection of vertical transmission in pregnancies with primary cytomegalovirus infection. For women with positive amniotic fluid studies who elect to continue their pregnancies, cordocentesis and serial ultrasound scans may be useful for assessment of fetal status.     

Diagnostic cordocentesis: two years of experience

The first diagnostic cordocentesis was performed in our unit in October 1985, our 2-year experience is reported. 144 samplings were performed in 137 patients (139 fetuses - 2 patients had twin pregnancies) during gestational weeks 14 to 42. The first attempt was successful in 80% of the procedures, 4 samplings failed. There were no fetal deaths within 3 days after diagnostic cordocentesis, a transient fetal bradycardia was observed in 12.2% of the cases, bleeding occurred in 13.6% of the cases. The indications for cordocentesis were: risk of fetal infection, karyotyping, hemophilia A, alloimmunisation, search for paternity, assessment of fetal acid-base status. Our data confirm that cordocentesis is a safe and reliable diagnostic procedure providing guidelines for management of the pregnancy.     

Doppler measurements of blood flow in the middle cerebral artery for the diagnosis of fetal anemia

OBJECTIVES: This paper presents a possibility of non-invasive diagnosis of fetal anemia based on the Doppler assessing of peak systolic velocity (PSV) in the fetal middle cerebral artery. The results of Doppler measurements were compared with fetal peripheral blood count estimated after cordocentesis. MATERIALS AND METHODS: Doppler measurements of blood flow velocity in the fetal middle cerebral artery were performed in years 2000 and 2001 in 22 pregnancies complicated by maternal blood group alloimmunisation. Gestation age varied from 27 to 36 weeks, the mean gestation age was 32 weeks. Depending on hemoglobin concentration in the fetal blood sample the severity of anemia was divided into three groups: severe anemia (Hb = < 7 g%), middle (Hb = = 8-10 g%) and light (Hb = = 10-12 g%). The fourth group consisted of fetuses without anemia (Hb > 12 g%). The results were statistically analyzed to estimate correlation between the Doppler blood flow indexes (PI, RI, SD and PSV) in the middle cerebral artery and the peripheral blood count (Hb, Ht, erythrocyte count) of fetal blood received by cordocentesis. Using T-Student-test the differences of average maximal blood flow velocities and mean Doppler indexes in the group of fetuses with severe anemia (Hb < 7 g%) and fetuses without anemia (Hb > 12 g%) were compared. RESULTS: Highest (negative) correlation was found between the peak systolic velocity and the fetal hemoglobin concentration. The correlation index was -0, 85, which means the higher the peak systolic velocity the lower the hemoglobin concentration. The difference between the mean peak systolic velocity in the group of fetuses with severe anemia and the group without anemia was statistically significant (p < 0.001). However, there was no statistical significant difference in the mean peak systolic velocity between the group with middle anemia (Hb = 10-12 g%) and the group without anemia (Hb > 12 g%). CONCLUSIONS: Doppler ultrasonography with the measurement of peak systolic velocity in the middle cerebral artery is a good method in evaluating of fetal peripheral blood count. Non-invasive peak systolic velocity measurements in the middle cerebral artery allow to assess the fetal hemoglobin concentration and also to reduce the count of diagnostic cordocentesis.     

A characteristic cluster of fetal sonographic markers that are predictive of fetal Turner syndrome in early pregnancy

OBJECTIVE: The purpose of this study was to describe a characteristic cluster of sonographic features of fetuses with Turner syndrome in early pregnancy. STUDY DESIGN: A targeted transvaginal ultrasound examination of all fetal organs was performed for 40123 consecutive pregnant women at 14 to 16 weeks of gestation. Both low- and high-risk pregnancies were included. Fetal karyotyping was performed in 9348 cases. The main indications were major fetal anomalies, advanced maternal age, abnormal biochemical markers, maternal anxiety, and request. RESULTS: Turner syndrome was detected in 13 fetuses (0.03%, 1/3086 early pregnancies). Huge septated cystic hygroma, severe subcutaneous edema, and hydrops were observed in all cases. A short femur was detected in 12 of 13 fetuses. A narrow aortic arch was visualized in all 8 fetuses who were scanned after 1995, when scanning of the aortic arch became mandatory in our institution. Four other fetuses had three or four of the five markers, 2 of the fetuses had trisomy 21, 1 fetus was normal, and one case of missed abortion occurred without a karyotype. CONCLUSION: A reliable diagnosis of Turner syndrome by sonographic means is possible in early pregnancy.     

Second trimester maternal serum inhibin-A in fetal anemia secondary to hemoglobin Bart’s disease

Abstract

Objective: To compare the levels of inhibin-A between pregnancies with fetal anemia secondary to Hb Bart’s disease and pregnancies with normal non-anemic fetuses.

Methods: Sixty-five pregnancies at risk of fetal Hb Bart’s disease scheduled for cordocentesis at 18–22 weeks were prospectively recruited into the study. Inhibin-A levels were measured from maternal blood drawn before cordocentesis. Fetal blood samples were collected for fetal Hb typing and hemoglobin (Hb) levels.

Results: Maternal serum inhibin-A was significantly higher in women with fetal Hb Bart’s disease than those with unaffected fetuses (1.03?MoM (multiple of median) and 0.75 MoM, respectively, p?=?0.001). The relationship between maternal serum inhibin-A and fetal Hb level was a quadratic equation; inhibin-A?=?5.248?–?9.415(Hb)?+?4.919(Hb)² (r²?=?0.274, p?<?0.001). Maternal serum inhibin-A did not correlate with cardiomegaly but was significantly associated with placental thickness; inhibin-A?=?1.372?–?0.751(Pl)?+?0.214(Pl)² (r²?=?0.237, p?=?0.007).

Conclusions: Maternal serum inhibin-A levels were significantly higher in pregnancies with fetal Hb Bart’s disease. The elevation of inhibin-A was likely to be a consequence of fetal anemia and placentomegaly. Since inhibin-A is commonly used as a component of quadruple test; the calculated risk of Down’s syndrome may be unreliable in pregnancies with fetal Hb Bart’s disease or possible fetal anemia.     

Umbilical cord diameter at 11-14 weeks of gestation: relationship to nuchal translucency, ductus venous blood flow and chromosomal defects

OBJECTIVE: To compare the umbilical cord diameter (UCD) in euploid and aneuploid fetuses at 11-14 weeks of gestation. METHODS: In 299 fetuses at 11-14 weeks of gestation the UCD, the nuchal translucency and the a-wave of the ductus venosus were measured. Reference ranges for the UCD according to the gestational age and to the crown-rump-length (CRL) were obtained by measuring the UCD by outer-to-outer border of 244 singleton pregnancies with normal karyotype. The fetal karyotype was established by chorionic villus sampling, amniocentesis or in case of suspected chromosomal abnormalities in the newborn. Linear regression was used to determine the significance of the association between the UCD and CRL or gestational age. RESULTS: Two hundred and ninety-nine fetuses were examined. The median fetal CRL was 64.5 mm (range 45-84) and the median gestational age was 13 (range 11-14) weeks. In the chromosomally normal group the UCD significantly increased with the CRL (r=0.620; p<0.001) and the gestational age (r=0.555; p<0.001). The regression equation for the mean UCD (y) according to the gestational days (x) was: y=-0.604+0.051*x. The regression equation for the mean UCD (y) according to the CRL (x) was: y=1.962+0.029*x. There were no significant differences in the mean UCD in fetuses without and with chromosomal abnormalities. The proportion of fetuses with an UCD above the 95th centile for CRL was higher in aneuploid compared to euploid fetuses (5/14 vs. 13/285, p<0.005). In 5/14 (35.7%) fetuses with chromosomal defects the NT and the UCD were above the 95th centile, whereas none of the fetuses with normal karyotype showed this combination. The proportion of fetuses with increased UCD and abnormal DV blood flow was increased in the cases with chromosomal abnormalities (33.3 vs. 1.8%, p<0.005). CONCLUSION: Umbilical cord diameter at 11-14 weeks increases with fetal CRL. Fetuses with chromosomal abnormalities are more likely to have an UCD above the 95th centile. Therefore, sonographic evaluation of the umbilical cord during first trimester ultrasound might be of additional value in the assessment of fetuses at risk for aneuploidies.     

Ultrasound diagnosis of fetal abnormalities and cytogenetic evaluation.

Over a 6 1/2 year period, in 288 pregnancies a variety of fetal malformations were detected by ultrasound. Two hundred and ten fetuses (73 per cent) were karyotyped. Gestational age at detection ranged from 11 to 38 weeks. The incidence of an abnormal karyotype in the total series was 14 per cent and 14.7 per cent in the 210 pregnancies in which a karyotype was performed. Single structural anomalies were found in 149 cytogenetically investigated fetuses, of which 25 had a chromosomal abnormality (17 per cent). Multiple structural malformations were present in 61 fetuses, of which 16 had an abnormal karyotype (26 per cent). Trisomy 18 was the most frequent finding. The most constant ultrasound finding in cases of an abnormal karyotype was polyhydramnios and severe IUGR in combination with structural defects. There is a need for extensive detailed ultrasound examination in high-risk pregnancies.     

Fetal breathing movements and prostaglandin levels in pregnancies complicated by premature rupture of the membranes.

We have previously demonstrated that maternal and fetal prostaglandin levels may be elevated in patients with pregnancies complicated by premature and prolonged rupture of the membranes (PPROM) compared to patients with intact membranes. In the fetal lamb, infusion of prostaglandin abolishes fetal breathing movements and in human pregnancies with PPROM and with poor outcome, fetal breathing movements are absent. The aim of this study was to determine fetal breathing activity in pregnancies complicated by PPROM which had elevated prostaglandin levels. One-hour ultrasound examinations were performed on nine fetuses whose mothers had had premature rupture of the membranes at 28 weeks gestation and a median of 4 days prior to the ultrasound examination. The number of fetal breathing movements (FBM) and percentage of time that each fetus spent breathing was documented and this was then related to control values. Following the completion of the ultrasound examination, cordocentesis was performed and blood sent for estimation of bicyclo PGEM levels. All of the fetuses made some breathing activity during the one-hour period, but the number of FBM varied from 1 to 181 (median 21). The percentage time that the fetuses spent breathing was much lower than that which would be expected for their gestational age, being a median of 1.3% (range less than 0.1 to 50.8%) of control values. As bicyclo PGEM levels were elevated in these nine fetuses, these data suggest that reduction in breathing activity in fetuses of pregnancies complicated by PPROM may be due to elevated prostaglandin levels.     

Platelet count in normal, small, and anemic fetuses

A reference range for fetal platelet count with gestation was established from the study of samples obtained by cordocentesis from 229 pregnancies that had prenatal diagnosis. The mean platelet count increased from 187 +/- 47 x 10(9)/L at 15 weeks to 274 +/- 47 x 10(9)/L at 40 weeks' gestation. In 113 red cell-isoimmunized pregnancies, the moderately anemic fetuses were significantly thrombocythenic, whereas the severely anemic fetuses were thrombocytopenic. In 136 small-for-gestational-age fetuses the platelet count was reduced and there were significant correlations between the magnitude of the thrombocytopenia and the degree of fetal smallness, hypoxemia, and acidemia.     

Association between first trimester absence of fetal nasal bone on ultrasound and Down syndrome

OBJECTIVES: To evaluate the association between absence of nasal bone on ultrasound and Down syndrome in fetuses at 11-14 weeks of pregnancy. METHODS: One hundred and ninety-four consecutive fetuses from singleton pregnancies undergoing chorionic villi sampling (CVS) were evaluated by transabdominal ultrasound. A sagittal view of the fetal face was obtained and the absence or presence of nasal bone was recorded and correlated with the fetal karyotype. RESULTS: A successful view of the fetal profile was possible in 183 of 194 (94%) fetuses. The nasal bone was absent in three of five fetuses with Down syndrome, and in one of 175 (0.6%) chromosomally normal fetuses. CONCLUSION: Absence of nasal bone by first trimester ultrasound was significantly associated with Down syndrome. When a proper view of the fetal face was obtained, the nasal bone was visible in more than 99% of karyotypically normal fetuses.     

Early genetic sonogram for Down syndrome detection

OBJECTIVE: The purpose of this study was to determine the Down syndrome sensitivity of early genetic sonography (14-<16 weeks of gestation) and to compare its diagnostic accuracy with that later in the mid trimester (16-24 weeks of gestation). STUDY DESIGN: Nuchal thickness, humerus and femur lengths, hyperechoic bowel, hypoplastic fifth digit (clinodactyly), and any gross anatomic defects were measured or ascertained in singleton pregnancies that were undergoing genetic amniocentesis. Multiple stepwise logistic regression analysis was used to determine the significant sonographic markers for Down syndrome detection in each group. Multivariate gaussian algorithms that included maternal age were used to estimate patient-specific Down syndrome risk. Sensitivity and false- positive rates, receiver-operating characteristic curves, and area under the curves were calculated and compared for both groups. RESULTS: There were 1,727 pregnancies with 22 Down syndrome fetuses (1.27%) in the early group versus 3,914 pregnancies with 86 Down syndrome fetuses (2.2%) in the later group. The mean +/- SD ages were 15.5 +/- 0.4 weeks versus 17.6 +/- 1.4 weeks, respectively. Early genetic sonography (14-<16 weeks) had a 100% detection rate, with a 21.2% false-positive rate. The early versus later genetic sonography had an 81.8% versus 61.6% detection rate, respectively, at a fixed 4.8% false-positive rate. Early sonography had significantly higher diagnostic accuracy (area under the curve, 0.962 vs 0.871, respectively; P =.005). In fetuses at 14 to 15 weeks, the genetic sonography was also highly accurate, with 100% detection with a 21.9% false-positive rate. CONCLUSION: Early genetic sonography is highly sensitive and statistically superior to later ultrasonography for Down syndrome detection. Early midtrimester sonography achieved a diagnostic accuracy similar to that currently reported for first-trimester nuchal translucency.     

Treatment of fetal anemia in Rh isoimmunized pregnancies with intrauterine fetal blood transfusion

Introduction

Despite the availability of prophylactic rhesus immune globulin, hemolytic disease of the newborn and fetal death (hydrops fetalis) due to rhesus alloimmunization, is still a major contributor to perinatal morbidity and mortality in India. Pregnancy outcome after fetal therapy with ultrasound guided intrauterine transfusion (IUT) for fetal anemia was studied.

Methods

A prospective cohort study of 99 Rh isoimmunized pregnancies, Indirect Coomb’s test Positive (ICT > 1:16) was conducted from July 2002 to June 2007. Intensive fetal monitoring by sériai ultrasound and middle cerebral artery peak systolic velocity using Color Doppler was performed to detect fetal anemia. When necessary, invasive testing with cordocentesis for Hb, PCV was per-formed if pregnancy was less than 32–34 weeks gestation. If PCV was <30, or there was fetal hydrops, Ultrasound guided intrauterine transfusion was carried out by the intravascular (IVT) or the intraperitoneal (IPT) routes. Primary outcome variables were fetal survival in relation to gestational age and procedure related factors.

Result

Of 99 pregnancies, 43 cases (25 — hydropic, 18-nonhydropic fetuses) required 135 intrauterine blood transfusions. The rest 56 pregnancies were managed conservatively and did not need IUT. IUTs were performed when indicated starting from 16 weeks (IPT) and 21 weeks (IVT) of gestation by the intraperitoneal / intravascular routes respectively. Pre-transfusion Hb ranged from 3g% to 8g%. The amount of blood transfused varied from 10 ml to > 110 ml depending on the period of gestation and degree of fetal anemia. The number of transfusions per pregnancy was 1–7, at intervals of 1–4 weeks, till delivery at 28 to 36 weeks of gestation. Survival of hydropic babies (88%) was almost similar to those without hydrops (83.3%) Prognosis was slightly better in Rh isoimmunized pregnancies not requiring IUT (94%) compared to fetuses receiving transfusions (85.6%)

Conclusion

Intrauterine fetal blood transfusion was found to be the only life saving therapy, and very effective in the management of preterm Rh isoimmunized pregnancies. Results are comparable with the best centers in the world, hence early referral to specialized centers with expertise of specialized intensive fetal monitoring for early diagnosis of fetal anemia, and of intrauterine fetal blood transfusion are important for optimal perinatal outcome.