Outcome of Multifetal Pregnancy Reduction in Women with a Dichorionic Triamniotic Triplet Pregnancy to a Singleton Pregnancy: A Retrospective Nationwide Cohort Study.

OBJECTIVE: To study the pregnancy outcomes of women with a dichorionic triamniotic triplet pregnancy that was reduced to a singleton pregnancy and to review the literature. METHODS: We performed a nationwide retrospective cohort study. We compared time to delivery and perinatal mortality in dichorionic triplet pregnancies reduced to singletons with ongoing dichorionic triplet pregnancies and primary singleton pregnancies. Additionally, we reviewed the literature on the subject. RESULTS: We studied 46 women with a reduced dichorionic triplet pregnancy and 42 women with an ongoing dichorionic triplet pregnancy. Median gestational age at delivery was 38.7 vs. 32.8 weeks, respectively (p < 0.001). Delivery <24 weeks occurred in 9 (19.6%) women with a reduced triplet pregnancy and 4 (9.5%) with an ongoing triplet pregnancy (p = 0.19). Perinatal survival rates between the reduced group and the ongoing triplet group were not significantly different. CONCLUSION: Multifetal pregnancy reduction in women with a dichorionic triplet pregnancy to a singleton pregnancy prolongs median gestational age at birth. No statistically significant association was found with miscarriage and perinatal survival rates.

Pregnancy outcome after fetal reduction in women with a dichorionic twin pregnancy.

STUDY QUESTION: What are the pregnancy outcomes for women with a twin pregnancy that is reduced to a singleton pregnancy? SUMMARY ANSWER: Fetal reduction of a twin pregnancy significantly improves gestational age at birth and neonatal birthweight, however at an increased risk of pregnancy loss and preterm delivery. WHAT IS KNOWN ALREADY: Women with a multiple pregnancy are at increased risk for preterm delivery. Fetal reduction can be considered in these women. STUDY DESIGN, SIZE, AND DURATION: Retrospective cohort study of 118 women with a twin pregnancy reduced to a singleton pregnancy between 2000 and 2010. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: We compared the outcome of pregnancy in consecutive women with a dichorionic twin pregnancy that was reduced to a singleton pregnancy to that of women with a dichorionic twin pregnancy that was managed expectantly and women with a primary singleton pregnancy. Reductions were performed between 10-23(6/7) weeks' gestation by intracardiac or intrathoracic injection of potassium chloride, mostly for congenital anomalies. We compared median gestational age, pregnancy loss <24 weeks, preterm delivery <32 weeks, neonatal birthweight and perinatal deaths. MAIN RESULTS AND THE ROLE OF CHANCE: We studied 118 women with a twin pregnancy that was reduced to a singleton, 818 women with an ongoing dichorionic twin pregnancy and 611 women with a primary singleton pregnancy. Loss of the entire pregnancy <24 weeks and preterm delivery occurred significantly more in the reduction group compared with the ongoing twin group (11.9 versus 3.1% <24 weeks, P< 0.001 and 18.6 versus 11.5% <32 weeks, respectively, P < 0.001). In the reduction group, the percentage of women without any surviving child was significantly higher compared with the ongoing twin and primary singleton group (14.4, 3.4 and 0.7%, respectively, P < 0.001). Median gestational age was 38.9 weeks (interquartile range (IQR) 34.7-40.3) for reduced pregnancies, 37.1 weeks (IQR 35.3-38.1) for ongoing twin pregnancies and 40.1 (IQR 39.1-40.9) for primary singletons (P < 0.001 for all comparisons). LIMITATIONS, REASONS FOR CAUTION: The main limitations of the study were its retrospective character, and the fact that indications for reduction were heterogeneous. WIDER IMPLICATIONS OF THE FINDINGS: In women with a dichorionic twin pregnancy fetal reduction increases median gestational age only at considerable risk of complete early pregnancy loss. STUDY FUNDING/COMPETING INTERESTS: The study was not funded. None of the authors has conflicts of interest.

[Alpha-foetoprotein assessment in amniotic fluid for the detection of neural tube defects: limited added value beyond week 20 ultrasound; retrospective study]. / Alfafoetoproteïnebepaling in vruchtwater voor de detectie van neuralebuisdefecten: beperkte meerwaarde boven de 20-wekenecho; retrospectiefonderzoek.

OBJECTIVE: To evaluate the diagnostic additional value of routine alpha-foetoprotein (AFP) assessment in amniotic fluid for the detection of neural tube defects (NTDs), compared with week 20 ultrasonographic examination. DESIGN: Retrospective. METHOD: We retrospectively determined AFP concentrations in amniotic fluid obtained from 7981 women who had undergone amniocentesis for karyotyping and AFP assessment. An AFP concentration greater than 2.5 times the median was considered abnormal. Women were categorised into 4 groups based on the indication for invasive prenatal diagnostic assessment: advanced maternal age (group I; n = 6179), increased risk of foetal NTDs (group II; n = 258), ultrasonographically confirmed foetal NTDs (group III; n = 55) or other indications (group IV; n = 1489). RESULTS: In group I, 18 of 6179 samples had increased AFP levels (0.3%), 2 of which were associated with NTDs. In group II, 2 of 258 samples had increased AFP levels (0.8%); both were associated with NTDs. Increased AFP levels were found in 44 of 55 samples from group III (80%), and 223 of 1489 samples from group IV (15.0%). CONCLUSION: Routine assessment of AFP in amniotic fluid based on advanced maternal age provides little additional value in the detection of NTDs beyond that of week 20 ultrasound.

Maternal health, antenatal and at 8 weeks after delivery, in home versus in-hospital fetal monitoring in high-risk pregnancies.

OBJECTIVE: To assess maternal health outcome, comparing high-risk pregnant women to either domiciliary monitoring or in-hospital monitoring, and a low risk pregnant group. DESIGN: Paper and pencil questionnaire, distributed antenatal and 8 weeks after the delivery. SETTING: A university hospital. SUBJECTS: Three groups: 130 high-risk pregnant women, who entered a randomized clinical trial and were allocated to either home (n=69) or in-hospital monitoring (n=61), and a reference cohort of low risk pregnant women (n=55). MAIN OUTCOME MEASURES: Antenatal physical and mental health (RAND36) and social experiences; mode of delivery; complications postpartum; physical health, mental health, and social experiences at 8 weeks postpartum. RESULTS: In all groups, antenatal physical health was considerably lower compared to the physical health of US women aged 18--44 years. Antenatal mental health was lower in high-risk women than in low-risk women (P<0.05). Antenatal maternal health, the mode of delivery, and maternal complications postpartum did not differ significantly between in-hospital and domiciliary monitored women. Eight weeks after delivery, physical health improved considerably in all groups; mental health was significantly lower in high-risks as compared to low-risk women (P<0.01). The allocated monitoring strategy showed a significant effect on mental health at 8 weeks after delivery; the mental health score being lower in the domiciliary monitored group (P<0.05). CONCLUSIONS: At 8 weeks after the delivery, physical health improves substantially in all groups. Mental health is higher in low-risks than in high-risks. Within the high-risk group domiciliary and in-hospital monitored women have the same physical maternal outcome at 8 weeks after delivery. However, mental maternal health in in-hospital monitored women at 8 weeks was probably biased by a medicalization effect.

Comparing treatment valuations between and within subjects in clinical trials: does it make a difference?

Valuations may be sensitive to biases, especially if elicited alongside randomized clinical trials. We investigated the construction of valuations assigned by women who entered a randomized clinical trial and were allocated to in-hospital or domiciliary monitoring. Women assigned valuations (0-10 visual analogue scale) to the strategy they had been allocated to and to the alternative strategy. Valuations were expressed as a between-subject difference (assigned by the women allocated to the respective strategies) and as within-subject differences (assigned by all women). Domiciliary monitoring was valued higher by the women allocated to that strategy (P = 0.10). In-hospital monitoring was valued higher by the women allocated to that strategy (P = 0.02). The average within-subject differences differed by allocated strategy (P<0.01). The within-subject valuation differences showed large variability between and within groups. An overrepresentation of women favoring domiciliary monitoring and asymmetric treatment experience inflated the average within-subject difference in the domiciliary group but deflated that difference in the in-hospital group. Neither the average between-subject difference nor the average within-subject differences are free of bias. Other study designs probably cannot prevent bias. Comparing within-subject and between-subject differences is instructive.

Classification of discordant fetal growth may contribute to risk stratification in monochorionic twin pregnancies.

OBJECTIVES: To determine whether classification of discordant growth between fetal twins allows risk stratification in monochorionic twin pregnancies. METHODS: In 12 twin-to-twin transfusion syndrome (TTTS) pregnancies and 12 cases that were suspected of developing the syndrome, fetal growth was determined by serial standard sonography. Fetal growth was expressed as the difference-average-ratio (DAR), defined as the difference in estimated fetal weight between both twins divided by their average weight. In each case, we determined the maximum value of DAR and the rate of change of DAR using a least squares linear fit of the estimated fetal weights. RESULTS: For the TTTS cases the maximum value of DAR was 0.44 +/- 0.21 versus 0.52 +/- 0.13 for the suspected TTTS cases (P = 0.25). The rate of change of DAR was 0.052 +/- 0.034 per week for the TTTS versus 0.0055 +/- 0.0092 for the suspected TTTS cases (P = 0.0004). After laser therapy, DAR decreased in four successful cases, with a rate of change of -0.0146 +/- 0.0093 per week, but increased further in one unsuccessful case, due to patent anastomoses. In the seven TTTS cases treated with amnioreduction, DAR did not decrease; in one of two suspected TTTS cases the DAR decreased slightly. In the nine amnioreduction cases, the average rate of change of DAR was 0.067 +/- 0.083 per week. This was significantly different from the four successful laser cases (P = 0.01). CONCLUSIONS: The rate of change of DAR, but not DAR itself, has prognostic value for the development of suspected TTTS pregnancies, for the onset and severity of TTTS and for the efficacy of therapy. This parameter is derived from routine sonography examination and may contribute to risk stratification in monochorionic twin pregnancies.

Interobserver variability of the neurological optimality score.

OBJECTIVE: To assess the interobserver reliability of the neurological optimality score. STUDY DESIGN: The neurological optimality score of 21 full term healthy, neurologically normal newborn infants was determined by two well trained observers. RESULTS: The interclass correlation coefficient was 0.31. Kappa for optimality (score of 58 or higher) was 0.19. A systematic difference of 1.3 points between the two observers was present. CONCLUSIONS: The interobserver variability of the neurological optimality score of the newborn infant is substantial. The subtle judgement of elicited responses as optimal or non-optimal proved to be especially critical in this concordance study. A difference of at least two points in the score is considered as a valid endpoint for comparative studies. If two or more observers are involved in the neurological examination of the newborn infant in a study to assess influences on perinatal morbidity, frequent re-instruction sessions are recommended.

[Third circulation: twin transfusion syndrome]. / Derde circulatie: tweelingtransfusiesyndroom.

The estimated incidence in the Netherlands of serious previable twin-to-twin transfusion syndrome is 50-100 cases per year. The polyhydramnion-oligohydramnion sequence is the most prominent feature. Prognosis without treatment is dismal: previable preterm birth. Risk of serious morbidity in the surviving twin in case of foetal demise of the other is impressive. Once the diagnosis of monochorionicity has been made in the first trimester, detailed ultrasound examination is mandatory for early recognition of the development of the syndrome, as therapeutic options exist. Therapeutic options include piercing of the intertwin membrane, repeated amniocenteses or laser occlusion of the chorionic vasculature. In seven Dutch centres over three years time 61 cases were identified: 36 needed intervention; 63 (of the 122) children survived, 10 with longterm morbidity.

First-trimester non-invasive prenatal diagnosis of triploidy.

We report a case of fetal triploidy in which fetal nucleated red blood cells were isolated from the maternal peripheral circulation at 12 weeks' gestation. FISH analysis with X and Y specific probes revealed three hybridization signals for the X chromosomes in 14 cells. The karyotype as established after CVS was shown to be 69,XXX. Two other non-invasive first-trimester screening methods were also evaluated. The serum markers pregnancy-associated plasma protein A (PAPP-A) and the free beta-chain of chorionic gonadotrophin (free beta-hCG) were both shown to be decreased in the same blood sample. An enlarged nuchal translucency (5 mm > or =95th centile) was seen at 13+2 weeks of gestation.

Clinical outcome and follow-up of sonographically suspected in utero urinary tract anomalies.

PURPOSE: We determined the outcome of pregnancy and long-term renal function in cases of sonographically detected fetal urinary tract anomalies (UTAs). METHODS: This was a retrospective cohort study done at an academic hospital (tertiary referral center). All records of prenatal sonographic examinations done between January 1985 and October 1994 that indicated a suspicion for UTA were examined for perinatal mortality, postnatal confirmation of sonographic diagnosis, postnatal management, and calculated creatinine clearance to determine the ultimate renal function. RESULTS: Of 99 cases with suspected UTAs, 28 pregnancies were terminated because the UTA was considered fatal, and 32 fetuses died perinatally. Twenty-one children are alive with good renal function, 4 with moderate renal function, and 2 with poor renal function. The prenatal diagnosis was not confirmed after birth in 12 children, all of whom are alive with good renal function. The prognosis for prenatally suspected UTA was worse in cases of bilateral involvement and in cases with associated multiple malformations. CONCLUSIONS: The prognosis of prenatally diagnosed UTAs depends on the specific anomaly suspected. Abnormal karyotype, other associated malformations, and bilateral involvement are unfavorable determinants of the prognosis in individual cases.

Twin-to-twin transfusion syndrome: a case report. Antepartum prediction of underlying placental vascular pattern in monochorionic twin pregnancies may be possible.

A case of twin-to-twin transfusion syndrome is described. Comparing data of serial antepartum ultrasonography with a haemodynamic model suggests the possibility of predicting the underlying placental vascular anatomy. It is suggested that serial ultrasonography, including full biometry, pulsatility indices of the umbilical arteries, foetal echocardiography, assessment of amniotic fluid indices and foetal bladder filling could serve as ultrasound parameters for pattern recognition of the underlying placental vascular anomaly. Biometry should be plotted serially in a difference/average plot. Future application of such intensive ultrasound monitoring in monochorionic twins, as soon as monochorionicity is established, may distinguish those monochorionic twins who may benefit from treatment from those whom it would be better only to observe.

Low-level mosaicism for both trisomy 15 and monosomy-X in amniotic fluid cells confirmed in fetal tissues.

We report here a case of true fetal mosaicism for both trisomy 15 and monosomy-X; the aberrant cell lines were initially detected at amniocentesis as low-level mosaicism (trisomy 15) and multiple-cell pseudo-mosaicism (monosomy-X). In the fetal lymphocytes, only metaphases with a normal chromosome complement were observed. After termination of the pregnancy, various fetal biopsies revealed both trisomy 15 and monosomy-X mosaicism, whereas, at autopsy, no external or internal abnormalities could be detected in the fetus. The karyotype can be described as 45,X[15]/47,XY,+15[3]/46,XY[27]. Our results implicate that an additional amniocentesis could be more helpful than fetal blood sampling in predicting the fetal karyotype after diagnosis of chromosome mosaicism at amniocentesis.

Neurodevelopmental outcome at three years of age after fetal 'brain-sparing'.

Intrauterine growth restriction (IUGR), occurring preterm, may be related to impaired neurodevelopmental outcome. We measured neurodevelopmental outcome (Hempel examination) at the age of three years in a cohort of infants born between 26 and 33 weeks in 1989. Fetuses were studied haemodynamically, using Doppler ultrasound. The ratio between the umbilical and the cerebral artery Pulsatility Index (U/C ratio) was calculated. This is a measure of redistribution of fetal blood preferentially to the brain and this may be a marker of fetal adaptation to placental insufficiency. Impaired fetal growth was also measured by the fetal growth ratio. Neonatal cranial ultrasound was performed to document intracranial haemorrhages and/or ischaemia. From the original cohort of 106 infants, 96 (91%) infants were examined at three years. After adjustment for obstetric variables, adverse Hempel outcome was related to neonatal cranial ultrasound abnormality and low head circumference at three years. Neither the U/C ratio nor fetal growth were independently associated with Hempel outcome. Fetal 'brain-sparing' in IUGR appears to be a benign adaptive mechanism preventing severe brain damage.

The VS and V blood group polymorphisms in Africans: a serologic and molecular analysis.

BACKGROUND: VS and V are common red cell antigens in persons of African origin. The molecular background of these Rh system antigens is poorly understood. STUDY DESIGN AND METHODS: Red cells from 100 black South Africans and 43 black persons from Amsterdam, the Netherlands, were typed serologically for various Rh system antigens. Allele-specific polymerase chain reaction and sequencing of polymerase chain reaction products were used to analyze C733G (Leu245Val) and G1006T (Gly336Cys) polymorphisms in exons 5 and 7 of RHCE and the presence of a D-CE hybrid exon 3. RESULTS: The respective frequencies of all VS+ and of VS+ V-(r's) phenotypes were 43 percent and 9 percent in the South Africans and 49 percent and 12 percent in the Dutch donors. All VS+ donors had G733 (Val245), but six with G733 were VS- (4 V+w, 2 V-). The four VS- V+w donors with G733 appeared to have a CE-D hybrid exon 5. T1006 (Cys336) was present in 12 percent and 16 percent of donors from the two populations. With only a few exceptions, T1006, a D-CE hybrid exon 3, and a C410T (Ala137Val) substitution were associated with a VS+ V-phenotype ((C)ces or r's haplotype). Two VS+ V-individuals, with the probable genotype, (C)ces/(C)ces), were homozygous for G733 and for T1006. CONCLUSIONS: It is likely that anti-VS and anti-V recognize the conformational changes created by Val245, but that anti-V is sensitive to additional conformational changes created by Cys336.

Risk factors for preeclampsia in nulliparous women in distinct ethnic groups: a prospective cohort study.

OBJECTIVE: To determine whether baseline characteristics during early pregnancy, proposed as potential risk factors for preeclampsia, show differences in prevalence and effects within distinct ethnic groups. METHODS: In a prospective cohort study of 2413 healthy nulliparous women from eight midwives' practices, we analyzed risk factors for preeclampsia (maternal age, body mass index, blood pressure at booking, smoking habit, and abortion history) in white, Mediterranean, Asian, and black women. In a univariate analysis, we estimated the relative risk of preeclampsia for the baseline variables and for ethnicity. In a multivariate analysis, we evaluated the simultaneous effect of the baseline variables in white (n = 1641) and black (n = 317) women. RESULTS: Significant differences were found in the prevalence of the risk factors in different ethnic groups. In the univariate analysis, the relative risk (RR) of preeclampsia in black women was 2.4 (95% confidence interval [CI] 1.1, 5.6) compared with white women. In the multivariate analysis in white women, the adjusted RR of preeclampsia for a diastolic blood pressure at booking above 70 mmHg was 4.4 (CI 0.9, 20.8). Among black women, the adjusted RR of preeclampsia was increased for high maternal age (RR 1.2; CI 1.0, 1.4), but not for a diastolic blood pressure at booking above 70 mmHg (RR 0.8; CI 0.2, 3.9). CONCLUSION: In studies of risk factors for preeclampsia, black women should be analyzed separately from white women.

Intensification of fetal and maternal surveillance in pregnant women with hypertensive disorders.

OBJECTIVE: To examine the need to intensify fetal and maternal surveillance in pregnant women with mild pregnancy hypertension. METHODS: The multi-center cohort study in 2413 healthy nulliparae analyzed differences in hypertension-related adverse events (small-for-gestational age, perinatal mortality, eclampsia, abruptio placentae and HELLP syndrome) according to maximum diastolic blood pressure and proteinuria. RESULTS: Compared to the reference group (diastolic blood pressure 70-85 mmHg) (n = 1882) the relative risks of adverse fetal and maternal outcome in 34 proteinuric hypertensive women were 8.9 (95% CI 3.3-24.1) and 41.5 (95% CI 9.7-178.4), respectively. In 203 non-proteinuric women with a maximum diastolic blood pressure of > or = 95 mmHg only the relative risk of adverse maternal outcome was increased (11.6, 95% CI 3.1-42.8), but it was not increased in 230 non-proteinuric women with a maximum diastolic of 90 mmHg. CONCLUSIONS: Intensified surveillance in women with mild pregnancy hypertension is not indicated and should be reserved for groups with increased fetal and maternal risk.

Low sodium diet and pregnancy-induced hypertension: a multi-centre randomised controlled trial.

OBJECTIVE: To examine the effectiveness of the standard policy in the Netherlands to prescribe a sodium restricted diet to prevent or to treat mild pregnancy-induced hypertension. DESIGN: Multi-centre randomised controlled trial between April 1992 and April 1994. SETTING: Seven practices of independent midwives and one university hospital. PARTICIPANTS: The experimental group comprised 184 women given a low sodium diet (< or = 50 mmol sodium/day) and a control group of 177 women given a normal diet. Eligible women for inclusion had had a rise of blood pressure, or excessive weight gain or oedema during the antenatal period. The 361 women in the trial were recruited from 2020 nulliparae, of whom 1512 (75%) gave informed consent at the beginning of their pregnancy to participate in the study. MAIN OUTCOME MEASURES: The difference between highest diastolic blood pressure after randomisation and diastolic blood pressure at the moment of randomisation; referral and admission to hospital for hypertension. RESULTS: There was no difference in increase of diastolic blood pressure after randomisation, the percentage of referral and admission to hospital for hypertension, or in obstetric outcome between the two groups. Urinary sodium excretion after randomisation in the normal diet group was significantly higher than in the low sodium group. CONCLUSION: Prescribing a sodium-restricted diet to prevent or to treat mild pregnancy-induced hypertension is not effective. Therefore there is no need to introduce a salt restricted diet in prenatal care, although increasing evidence shows that a low sodium diet prevents hypertension in non-pregnant individuals.

Cost-minimization analysis of domiciliary antenatal fetal monitoring in high-risk pregnancies.

OBJECTIVE: To compare safety and cost-effectiveness of domiciliary antenatal fetal monitoring (cardiotocography and obstetric surveillance) with in-hospital monitoring in high-risk pregnancies. METHODS: From September 1992 to June 1994, 150 consecutive women with high-risk pregnancies, who would otherwise be monitored in the hospital, entered a randomized controlled trial of in-hospital (n = 74) or domiciliary (n = 76) monitoring. The main outcome measures were neonatal safety (Prechtl neurologic optimality score, the proportion of non-optimals) and cost-effectiveness. To test a two-point difference in mean Prechtl scores (two-tailed o = .05. 1-beta = .80), 150 women were needed. Safety and cost-effectiveness were analyzed according to intention to treat. Conditional on the safety outcomes, a cost-minimization analysis based on actual resource use was performed. Uncertainty of results was explored by sensitivity analyses. RESULTS: Neonatal outcomes were equal. No cost-shifting between the antenatal and postpartum period occurred. Substituting domiciliary for in-hospital monitoring reduced mean (standard deviation) antenatal costs from $3558 ($2841) to $1521 ($1459) per woman (P < .001). If costs were varied by the addition of 50%, costs were still reduced. The magnitude of the reduction was sensitive to the costs of hospital care and less sensitive to the costs of domiciliary monitoring. CONCLUSION: Domiciliary monitoring is safe and reduces costs by one-half. The technique seems transferable to other settings but local circumstances may sometimes hamper its dissemination.

Molecular background of VS and weak C expression in blacks.

BACKGROUND: The Rh system is complex and consists of as many as 45 different antigens. Red cells of about 25 percent of the black population carry VS an Rh-system antigen (Rh20), but this antigen is very rare in whites. VS positivity is always associated with a weak expression of e, and usually also of C. STUDY DESIGN AND METHODS: The RH genes of 11 black VS-positive donors were studied. Transcripts were sequenced for four VS-positive donors, three of whom had red cells with a weak expression of C. In the other donors, only analysis of genomic DNA was carried out. RESULTS: The occurrence of VS was shown to be related to a single-point mutation in exon 5 of the RHCE gene (cytosine 733 guanine, leading to the Leu245Val substitution). The presence of this polymorphism in exon 5 may explain the simultaneously occurring weak e, because the E/e polymorphism is located in the same exon. Study of VS-positive donors with different Rh phenotypes showed that the polymorphism can occur in different alleles of the RHCE gene. In all three donors whose red cells showed a weak expression of C, a hybrid D-CE-D transcript was found, containing exon 4, 5, 6, 7, and (probably) 8 from the RHCE gene. No transcripts were encountered carrying DNA markers normally associated with C expression. CONCLUSION: It is therefore postulated that the hybrid gene is responsible for the weak expression of C in these individuals. The hybrid gene carried a Leu62Phe substitution, as well as the Leu245Val substitution responsible for VS. The gene most probably cosegregates with a C allele encoding Cys 16 (normally encoded only by the C allele) and Val245 (responsible for VS antigenicity when encoded by the RHCE gene). This explains the combination of weak expression of C and VS positivity that is frequently found in blacks.