First trimester maternal serum AFP and total hCG in aneuploidies other than trisomy 21

Total human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) were measured in maternal serum at 10-14 weeks of gestation from 53 pregnancies affected by trisomy 18, 42 cases with trisomy 13, 46 with Turner's syndrome and 13 with other sex aneuploides. The only significant association was the finding of reduced levels of total hCG in cases of trisomy 18 and 13. The association of increased levels of AFP in cases of trisomy 18 with ventral wall defects and the slight increase in AFP in cases of sex chromosomal anomalies other than Turner's syndrome was found. AFP and total hCG are not likely to replace the markers free beta-hCG and PAPP-A in first trimester screening for chromosomal anomalies.     

Second trimester maternal serum screening using alpha fetoprotein, free beta human chorionic gonadotropin and maternal age specific risk: result of chromosomal abnormalities detected in screen positive for Down syndrome in an Asian population.

BACKGROUND: This study was to determine the incidence of chromosome abnormalities in Taiwanese women undergoing prenatal chromosome analysis after a second trimester Down syndrome screening by using maternal age and serum dual-marker testing (alpha-fetoprotein and free-beta unit human chorionic gonadotropin). METHODS: A total of 10,098 Taiwanese women with pregnancy between 15 and 23 weeks' gestation received second-trimester Down syndrome risk evaluation by dual-marker and maternal age specific risk testing in a single medical center. The study took 22 months. Ninety-seven percent of this study population was less than 34 years old. Ninety-six percent of our cases were screened between 15-20 weeks of gestation. This population was included only after a routine ultrasonography scan for correction of gestational age and exclusion of major structural anomalies. By using an algorithm to detect Down's syndrome, with a risk of 1:270 as a cut-off value, 816 patients were screen-positive for Down syndrome (screen-positive rate 8.0%). Karyotypes were reviewed for 670 (82.1%) mothers who received prenatal karyotype analysis. RESULTS: Twelve cases of Down syndrome were identified in the screen positive group with an estimated detection rate of 67% (false positive rate 8%). Three cases of Down syndrome were detected in late trimester among the screen-negative group. Seven other fetal chromosome abnormalities were also found among the screen-positive pregnancy. In addition, seven cases were screen-positive for trisomy 18; all of these patients received amniocentesis and only one case was confirmed. CONCLUSION: These findings indicate that this screening program combining alpha-fetoprotein (AFP), free beta human chorionic gonadotropin (free-hCG) and maternal age-specific would achieve a screening efficiency in Taiwanese populations as comparable to those obtained in Caucasian populations. Our results also suggest that approximately 3% of pregnancies with a positive dual marker and maternal age-specific screen results will have a chromosome abnormality despite having a normal routine ultrasound scan. Mothers with positive screening results should be made aware of the implications of a positive result.     

Compromise ultrasound dating policy in maternal serum screening for Down syndrome

Routine ultrasound biometry is the method of choice for gestational dating when screening for Down syndrome. However, it is costly and an alternative policy is to restrict ultrasound to women most likely to have menstrual dating errors. This was evaluated by statistical modelling with parameters from 14,274 women screened between January 1997 and July 2001 using free beta-human chorionic gonadotrophin (free beta-hCG), alpha-fetoprotein (AFP) and unconjugated estriol (uE(3)). A total of 12,711 (89%) women had both ultrasound and menstrual gestations, but in 4101 (29%) women either the last menstrual period (LMP) was uncertain or a pill-withdrawal period, or there were irregular or abnormal length cycles. The LMP was not entered in the test request form for a further 1404 (9.8%) women. Routine ultrasound dating yielded a predicted detection rate higher than for menstrual dating by 3.9-7.1%, depending on the marker combination and cut-off. The false-positive rate was reduced by 0.2-1.1%. Selectively scanning the 39% with unreliable dates increased detection by 2.6-4.6%, and reduced the false-positive rate by 0.04-0.6%. Some centres only use the ultrasound estimate of gestation when it differs from the menstrual estimate by more than 7 days. Such a rule reduces the gain in detection rate to 2.5-4.6% for routine ultrasound and 1.7-3.1% with the compromise policy; the false-positive rate reductions are 0.06-0.6% and 0.0-0.3%, respectively. We conclude that if routine ultrasound is not financially and practically feasible, the compromise policy yields a clinically important improvement in screening performance compared to menstrual dating.     

Villous trophoblast abnormalities in extremely preterm deliveries with elevated second trimester maternal serum hCG or inhibin-A

Elevated levels of the maternal prenatal screening markers hCG and inhibin-A, measured at 15-20 weeks gestation, increase the subsequent risk of severe pre-eclampsia and intra-uterine growth restriction (IUGR). Since both markers are produced by syncytiotrophoblast, we tested the hypothesis that these elevations were due to accelerated differentiation of the villous trophoblast compartment. We performed a retrospective study of 12 cases from our Placenta Clinic with total hCG and/or inhibin-A levels of ≥3.0 multiples of the median that subsequently delivered by 28 weeks gestation and compared their placental pathology findings with 24 gestational age-matched controls. Morphometric analysis demonstrated a 41% reduction in the volume ratio of Ki67 positive cytotrophoblast nuclei to total trophoblast in cases vs controls (Student’s T-test; p = 0.028). Distal villous hypoplasia (DVH) was significantly more common in cases (10/12) than controls (4/24); Fisher’s exact test, p = 0.002. Wave-like syncytial knot (WLSK) formation was significantly more common in cases (9/12) than controls (1/24); Fisher’s exact test, p < 0.0001. WLSK formation was associated with DVH and resulted from accumulation of senescent/apoptotic syncytiotrophoblast nuclei along inherent lines of syncytial nuclear organization. Our data support the hypothesis that elevated second trimester maternal serum levels of total hCG and/or inhibin-A may result from premature accelerated differentiation of the villous cytotrophoblasts. The subsequent pathologic findings in the syncytiotrophoblast could render the pregnancy at risk of severe pre-eclampsia and IUGR.     

Second trimester amniotic fluid adiponectin level is affected by maternal tobacco exposure,insulin, and PAPP-A level

Objectives

Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and antiatherosclerotic properties. The objectives of the present study were to determine the amniotic fluid (AF) concentration of adiponectin during the second trimester of pregnancy and to demonstrate its association with maternal and fetal variables and AF concentrations of insulin, leptin, and pregnancy-associated-plasma-protein A (PAPP-A).

Study design

We performed a cross-sectional study of 222 pregnant women who underwent amniocentesis at 15–18 weeks for genetic reasons. No malformation or chromosomal disorder was found in the newborn after birth. AF adiponectin, leptin, PAPP-A, and insulin concentrations were measured using commercially available assays. All maternal, fetal, and biochemical variables were studied using univariate and multivariate linear regression analysis to determine their association with the AF concentration of adiponectin.

Results

Adiponectin concentration was negatively correlated with maternal smoking status (β = −5.208; p < 0.001) and positively correlated with levels of insulin (β = 0.621; p = 0.002) and PAPP-A (β = 40.150; p < 0.001). Non-significant correlations were found between adiponectin concentration and maternal age, maternal body mass index, gestational age at amniocentesis, fetal gender, and AF level of leptin.

Conclusion

These findings suggest that the fetus and its membrane adipocytokines, in relationship with maternal and other fetal variables, play a dynamic role in the regulation of energy and oxidative stress homeostasis due to its insulin-sensitizing and antiatherosclerotic effects. The association of these molecules with maternal tobacco consumption during pregnancy could have perinatal implications.     

Second trimester levels of maternal serum inhibin A in pregnancies affected by fetal neural tube defects

Inhibin A is effective as a second trimester maternal serum marker for Down syndrome screening. In the present study, inhibin A levels were measured in second trimester maternal serum samples from 28 pregnancies affected with open neural tube defects; 12 associated with open spina bifida and 16 associated with anencephaly. Each measurement was expressed as a multiple of the median (MoM) for control singleton pregnancies (n=1464) of the same completed week of gestation. Inhibin A levels were not significantly altered in cases of open neural tube defects; the median value was 0.96 MoM in cases of open spina bifida and 1.19 MoM in cases of anencephaly. Therefore, second trimester maternal serum inhibin A levels will not have an impact on prenatal detection of open neural tube defects.     

对高龄孕妇于孕中期行血清学二联指标筛查胎儿唐氏综合征的多中心前瞻性研究

目的 探讨高龄孕妇(至预产期时的年龄≥35岁)于孕中期行血清学二联指标筛查胎儿唐氏综合征的可行性.方法 收集2004年5月至2006年9月期间在北京协和医院等11家医疗单位就诊的、孕周为14～20周+6并同意接受产前筛查的单活胎孕妇行血清甲胎蛋白(AFP)和游离人绒毛膜促性腺激素β亚单位(β-hCG)二联指标检测,将二联指标测定值输入唐氏综合征风险计算软件,以1/270为高危切割值,≥1/270确定为唐氏综合征筛查阳性孕妇,对阳性孕妇进行遗传咨询,并记录所有孕妇的妊娠结局.11家医疗单位共有66 132例孕妇纳入本研究.按预产期年龄不同分为高龄组(≥35岁)3610例(5.46%,3610/66 132)和低龄组(<35岁)62 522例(94.54%,62 522/66 132).分别计算两组孕妇的筛查检出率、假阳性率和阳性预测值.结果 (1)两组孕妇的胎儿唐氏综合征筛查结果 比较:高龄组孕妇中诊断胎儿唐氏综合征22例,低龄组孕妇中诊断胎儿唐氏综合征75例.以1/270为高危切割值进行筛查,共筛查出阳性孕妇5470例,从中诊断胎儿唐氏综合征91例.其中高龄组中阳性孕妇727例(13.3%,727/5470),胎儿唐氏综合征22例(24.2%,22/91).低龄组中阳性孕妇4743例(86.7%,4743/5470),胎儿唐氏综合征69例(75.8%,69/91).筛查阴性孕妇共60 662例,从中诊断胎儿唐氏综合征6例.其中高龄组阴性孕妇2883例,未发现胎儿唐氏综合征;低龄组筛查阴性孕妇57 779例,诊断胎儿唐氏综合征6例.在66 132例孕妇中共发现胎儿唐氏综合征97例,在本研究人群中的胎儿唐氏综合征发生率为0.15%(9q/66 132);高龄组中胎儿唐氏综合征发生率为0.61%(22/3610);低龄组中胎儿唐氏综合征发生率为0.12%(75/62 522).(2)两组孕妇筛查检出率、假阳性率和阳性预测值比较:以1/270为高危切割值,采用孕中期行血清学二联指标对高龄组孕妇筛查胎儿唐氏综合征的检出率为100%,假阳性率为19.7%,阳性预测值为3.0%;低龄组孕妇筛查检出率为92.0%,假阳性率为7.5%,阳性预测值为1.5%,两组上述各指标间分别比较,差异均有统计学意义(P<0.01).结论 对高龄孕妇行孕中期血清学二联指标筛查胎儿唐氏综合征,其筛查效率高于低龄孕妇,以1/270为高危切割值,可以有效地检出妊娠胎儿唐氏综合征的高危、高龄孕妇,降低羊膜腔穿刺率.建议对高龄孕妇在知情同意的基础上采用个体化的胎儿唐氏综合征产前筛查和诊断策略.     

Second trimester maternal serum analytes in triploid pregnancies: correlation with phenotype and sex chromosome complement

Second trimester maternal serum alpha-fetoprotein (MS-AFP), human chorionic gonadotrophin (hCG), unconjugated estiol (uE3), and inhibin-A (INH-A) levels were evaluated in pregnancies complicated by triploidy. In addition to seven new triploid pregnancies, the results for 67 published cases were reviewed. All cases appear to fall into two major groups. First, those identifiable as screen-positive for both Down syndrome and an open neural tube defect (ONTD) with elevated MS-AFP, grossly elevated hCG, low/normal uE3, and probably elevated INH-A. Pregnancies in the second group are identifiable as screen-positive for trisomy 18 with low/normal MS-AFP, and very low hCG, uE3 and INH-A. Triploid pregnancies with high maternal serum hCG nearly always show a placenta with partial mole (25/27 or 93%), a high frequency of ONTDs or ventral wall defects (VWDs) (8/28 or 29%) and have either an XXX or XXY karyotype (observed ratio 6:10, respectively). Low hCG is infrequently associated with a molar placenta (1/11 or 9%), does not appear to be associated with ONTDs or VWDs (0/29 or 0%), and shows an excess of XXX over XXY karyotypes (observed ratio 17:2). There were 16 cases with either a molar placenta, an ONTD or a VWD that received the MS-AFP and hCG tests. All 16 were screen-positive for an ONTD (MS-AFP> or =2 multiples of the median). In addition, all 31 cases that received MS-AFP, hCG, uE3 (and where available INH-A) were screen-positive for either Down syndrome or trisomy 18. The findings are discussed in the context of expected differences between digynic and diandric triploidy. It is suggested that the sex chromosome complement in triploidy is an important factor in determining risk for partial mole development and in utero survival.     

对孕中期妇女行血清学二联指标筛查胎儿唐氏综合征的多中心前瞻性研究

目的 建立中国孕妇孕中期血清学二联指标筛查胎儿唐氏综合征的数据库,探讨适合中国大陆孕妇筛查胎儿唐氏综合征的策略.方法 应用有区域代表性的多中心前瞻性研究方法,收集2004年5月至2006年9月期间在北京协和医院等11家医疗单位就诊的、孕周为14～20周+6并同意接受产前筛查的66 132例妊娠单活胎孕妇(平均年龄27岁)行血清甲胎蛋白(AFP)和游离人绒毛膜促性腺激素B亚单位(freeβ-Hcg)二联指标检测,将二联指标测定值输入以高加索人群数据库为基础的唐氏综合征风险计算软件.根据本研究中孕妇的数据重新计算血清AFP和游离B-Hcg的中位数倍数值及胎儿罹患唐氏综合征的风险.设定1/270为高危切割值,≥1/270确定为唐氏综合征筛查高危.并与高加索人群数据库筛查结果进行比较.结果 经染色体核型分析,66 132例孕妇中共诊断唐氏综合征97例.(1)以高加索人群筛查参数计算的结果:66 132例中筛查出高危孕妇5470例,其中诊断唐氏综合征91例,高危孕妇的唐氏综合征检出率为94%(91/97),假阳性率为8.15%,阳性预测值为1.66%(91/5470);筛查低危的60 662例孕妇中有6例产后诊断为唐氏综合征.调整假阳性率为5%时,有70例患唐氏综合征的孕妇筛查为唐氏综合征高危,其检出率为72%(70/97);当校正检出率为60%时,筛查高危孕妇为2785例,其中唐氏综合征孕妇为58例,假阳性率为4.1%.假设所有筛查高危的孕妇都接受羊膜腔穿刺,每检出l例唐氏综合征患儿需要进行60例的羊膜腔穿刺术.(2)以中国孕妇人群筛查参数计算的结果:66 132例中筛查高危孕妇4332例,高危率为6.551%(4332/66 132),其中诊断唐氏综合征88例,唐氏综合征的检出率为90%(88/97),假阳性率为6.43%;在筛查低危的61800例孕妇中,有9例经产后诊断为唐氏综合征.调整假阳性率为5%时,有74例孕妇筛查为唐氏综合征高危,其检出率为76%(74/97);校正检出率为60%时,筛查高危孕妇为2541例,其中唐氏综合征孕妇58例,则假阳性率可降至3.8%.假设所有筛查高危孕妇均接受羊膜腔穿刺,每检出1例唐氏综合征患儿需要进行50例羊膜腔穿刺术,低于高加索人群筛查参数计算的结果.结论 中国大陆孕妇人群和高加索孕妇人群之间存在血清学指标的差异,以中国孕妇人群的数据库为基础,采用孕中期血清学二联指标筛查胎儿唐氏综合征,可以明显提高筛查的产前诊断效率,获得较令人满意的筛查结果.     

The behavior of serum hCG level in normal and disordered pregnancy--a prognostic factor

The increase of serum hCG was determined in 305 pregnant women at least twice in the first 10 to 12 weeks of pregnancy. In a large number of cases this was done to rule out a disturbance of pregnancy. The results were evaluated by means of a comparison to the time-dependent changes of the normal range. They were classified in the following manner: 1 = Normally increasing values, 2 = Values lower than normal, but normal increase, 3 = values to low and increasing too slowly, 4 = Serum hCG too low or declining, 5 = initially normal values failing to rise. A type 4 secretion pattern was invariably followed by a demise of pregnancy. In about one half of the cases showing a type 2 pattern, the pregnancy either miscarried or was found to be in an ectopic location. In normal pregnancies, type 2 pattern was found in 29% and type 1 in 71%. A comparison of the results of the first and second hCG determination revealed close agreement in more than 90% of the cases, and in 84% when the comparison was extended to a third sample.     

Detection of maternal serum hCG glycoform variants in the second trimester of pregnancies affected by Down syndrome using a lectin immunoassay

AIM: To assess whether glycoform variants of human chorionic gonadotrophin (hCG) are present in altered concentrations in the maternal serum in pregnancies affected by Down syndrome. METHODS: In a series of 50 cases of pregnancies complicated by Down syndrome and 278 unaffected pregnancies, we have examined maternal serum levels of hCG glycoforms (GlyhCG) in samples collected in the second trimester (14 to 21 weeks) using a sialic acid binding lectin immunoassay. We have compared these levels with those of other second trimester serum markers (Free beta-hCG, alpha fetaprotein (AFP) and Total hCG) and modelled detection rates and false positive rates of various biochemical markers in conjunction with maternal age using a maternal age standardized population. RESULTS: Maternal serum GlyhCG in cases of Down syndrome was significantly elevated (Median MoM 1.81) with 15 of 50 (30%) cases above the 95th centile for unaffected pregnancies. Free beta-hCG was also elevated (Median MoM 2.16) with 18 of 50 (36%) cases above the 95th centile. AFP levels were reduced (Median MoM 0.75) with 9 of 50 (18%) cases below the 5th centile. Total hCG levels whilst elevated (Median MoM 1.88) had only 15 of 50 (30%) cases above the 95th centile. Maternal serum GlyhCG levels showed significant correlation with total hCG and free beta-hCG (r = 0.6880 and 0.6922) in the Down group but not with AFP (r = 0.1237). When GlyhCG was combined together with AFP and maternal age, at a 5% false positive rate, the modelled detection rate was 53%, some 13% lower than when free beta-hCG was used and some 7% lower than when total hCG was used. CONCLUSION: Maternal serum GlyhCG, as measured by the sialic acid-binding lectin immunoassay is unlikely to be of additional value when screening for Down syndrome in the second trimester.     

Community-based screening for Down's Syndrome in the first trimester using ultrasound and maternal serum biochemistry

Two years of community-based first trimester screening (FTS) were audited. All women with singleton pregnancy in a defined health region who completed FTS (ultrasound and biochemistry) were included (n= 10,436) and outcomes obtained for 98.4%. All scans were performed or supervised by experienced sonologists with Fetal Medicine Foundation (FMF) accreditation. FMF software generated all risk assessments based on nuchal translucency (NT), maternal serum-free beta human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein A (PAPP-A). The detection rate for Trisomy 21 was 90.6% with a screen-positive rate of 3.9%. These findings indicate that where FTS is accessible within routine antenatal care, a detection rate of 90% and low screen-positive rate can be achieved using the FMF programme.     

The influence of smoking on maternal serum PAPP-A and free beta hCG levels in the first trimester of pregnancy

In an analysis of 3111 singleton pregnancies routinely screened in the first trimester with nuchal translucency, free beta hCG and pregnancy associated plasma protein A (PAPP-A) smoking has been found to occur in 20.8 per cent of pregnant women. When the individual marker levels were assessed in smokers and non-smokers, levels of PAPP-A were reduced in smokers by some 15 per cent. Despite free beta hCG levels being reduced by 10-14 per cent in the second trimester of smoking women, in the first trimester period this is not evident. Simulation studies would suggest that in smokers the detection of trisomy 21 using free beta hCG, PAPP-A and maternal age will be reduced by some 5 to 6 per cent compared with that of the general population.     

Second trimester maternal serum biochemical screening for Down's syndrome: experience of a single obstetric unit.

The objective of this study was to assess the effects of mid-trimester biochemical screening on the prenatal diagnosis of Down's syndrome. All patients booked for antenatal care at the Royal Free Hospital are offered a double marker biochemical screening test (alpha-fetoprotein and free beta human chorionic gonadotrophin). The results of double marker screening tests and the notes of all cases of trisomy 21 from 1 April 1993 to 31 March 1995 were reviewed. Of the 6170 women booked in the antenatal clinic during this 2-year period 4427 (71.8%) took up the offer of biochemical screening. Four hundred and twenty-nine (9.7% of those screened) were reported positive and 293 karyotypes were performed in this group (68.3% uptake) and 253 karyotypes were also performed for other indications. Thirteen of 21 affected pregnancies had biochemical screening. The detection rate of biochemical screening in women aged <37 years was 0% (0/2) with a 8.4% false positive rate. In women aged 37 years the detection rate was 100% (11/11) with a false positive rate of 23%. The overall detection rate for Down's syndrome was 84.6% and the false positive rate was 9.5%. In conclusion, biochemical screening successfully targeted affected pregnancies in women aged 37 years and was useful in reducing the fetal karyotyping rate. However, it was disappointing in the prenatal diagnosis of trisomy 21 in women <37 years old.     

Advanced maternal age and adverse perinatal outcomes in an Asian population

Objective

To investigate (1) whether there is an increasing trend in the mean maternal age at the birth of the first child and in the group of women giving birth at age 35 or older, and (2) the association between advanced maternal age and adverse perinatal outcomes in an Asian population.

Study design

We conducted a retrospective cohort study involving 39,763 Taiwanese women who delivered after 24 weeks of gestation between July 1990 and December 2003. Multivariable logistic regression was used to adjust for potential confounding variables.

Results

During the study period, the mean maternal age at the birth of the first child increased from 28.0 to 29.7 years, and the proportion of women giving birth at age 35 or older increased from 11.4% to 19.1%. Compared to women aged 20–34 years, women giving birth at age 35 or older carried a nearly 1.5-fold increased risk for pregnancy complications and a 1.6–2.6-fold increased risk for adverse perinatal outcomes. After adjusting for the confounding effects of maternal characteristics and coexisting pregnancy complications, women aged 35–39 years were at increased risk for operative vaginal delivery (adjusted odds ratio [OR] 1.5, 95% confidence interval [CI] 1.2–1.7) and cesarean delivery (adjusted OR 1.6, 95% CI 1.5–1.7), while women aged 40 years and older were at increased risk for preterm delivery (before 37 weeks of gestation) (adjusted OR 1.7, 95% CI 1.3–2.2), operative vaginal delivery (adjusted OR 3.1, 95% CI 2.0–4.6), and cesarean delivery (adjusted OR 2.6, 95% CI 2.2–3.1). In those women who had a completely uncomplicated pregnancy and a normal vaginal delivery, advanced maternal age was still significantly associated with early preterm delivery (before 34 weeks of gestation), a birth weight <1500 g, low Apgar scores, fetal demise, and neonatal death.

Conclusion

In this population of Taiwanese women, there is an increasing trend in the mean maternal age at the birth of the first child. Furthermore, advanced maternal age is independently associated with specific adverse perinatal outcomes.     

Plasma oestriol in normal pregnancy in an Asian population.

Serial plasma oestriol levels were measured by a radioimmunoassay in 49 normal pregnancies, Plasma oestriol rose from 43 ng/ml (149-1 nmol/l) at 22 weeks to 357 ng/ml (1237-91 nmol/l) at 40 weeks. The rise was gradual between 22 and 32 weeks and steep between 32 and 40 weeks. No significant relationship could be found between plasma oestriol and parity, maternal age, maternal height, maternal weight or fetal sex. However, a significant but low correlation was found between birth weight and plasma oestriol prior to labour and also oestriol increments from 30 weeks to delivery. The average day to day coefficient of variation of plasma oestriol in 11 patients was found to be 16-2 per cent.     

Increased level of second trimester maternal serum chorionic gonadotropin in pregnancy with a fetus affected by homozygous alpha-thalassemia 1

With enzyme immunoassay, maternal serum chorionic gonadotropin (MShCG) level was determined in 58 pregnancies affected with fetal homozygous alpha-thalassemia 1. In 40 pregnancies with a gestational age of 10 to 14 weeks, 8 (20%) had an MShCG level above 2.5 multiples of the median (MoM); while in the other 18 pregnancies with a gestational age of 15 to 23 weeks, 14 (78%) had a level above 2.5 MoMs and none had a level below the median. Homozygous alpha-thalassemia 1 of the fetus was associated with an elevated MShCG. Therefore in second-trimester screening for Down's syndrome by measurement of MShCG, homozygous alpha-thalassemia 1 should also be considered if elevated MShCG levels are found. Received: 15 December 1993 / Accepted: 6 April 1994