Decision-making for non-invasive prenatal testing for Down syndrome: Hong Kong Chinese women's preferences for individual vs relational autonomy.

Individual autonomy in antenatal screening is internationally recognized and supported. Policy and practice guidelines in various countries place emphasis on the woman's right to make her own decision and are related to concepts such as self-determination, independence, and self-sufficiency. In contrast, the dominant perspective in Chinese medical ethics suggests that the family is pivotal in making medical decisions, hence providing support for relational autonomy. This study explored Hong Kong Chinese pregnant women's preferences for individual vs relational autonomy for non-invasive prenatal testing (NIPT) for Down syndrome. A qualitative study was carried out using semi-structured interviews with 36 women who had undertaken NIPT in Hong Kong. The findings show that most Hong Kong Chinese women valued aspects of both relational and individual autonomy in decision-making for NIPT. Women expected support from doctors as experts on the topic and wanted to involve their husband in decision-making while retaining control over the outcome. Somewhat surprisingly, the findings do not provide support for the involvement of family members in decision-making for NIPT. The adequacy of current interpretations of autonomy in prenatal testing policies as an individual approach needs discussion, where policy developers need to find a balance between individual and relational approaches.

Maternal reporting of prenatal ultrasounds among women in the National Birth Defects Prevention Study.

BACKGROUND: Increased availability and usage of ultrasound screening have led to improved identification of fetal structural abnormalities prenatally. Few population-based studies have been published on prenatal detection for structural birth defects in the United States. The aim of this study is to determine the frequency of maternal reporting of abnormal prenatal ultrasounds for selected birth defects and to investigate associated maternal characteristics. METHODS: Participants included 4013 mothers enrolled in the National Birth Defects Prevention Study who carried a fetus with at least one of 14 structural birth defects between 1997 and 2004. Frequencies of abnormal prenatal ultrasounds were based on maternal report and computed for isolated and multiple defects. Associations between maternal characteristics and abnormal prenatal ultrasounds were assessed using logistic regression. RESULTS: Overall, 46% of participants reported an abnormal ultrasound. Infants with omphalocele, anencephaly, gastroschisis, and renal agenesis were more likely to have abnormal prenatal ultrasounds than those with cleft and limb abnormalities. Hispanic women were less likely to report abnormal prenatal ultrasounds of birth defects than Caucasians, as were women who had a body mass index ≥ 30 kg/m(2) compared with those with a normal body mass index. CONCLUSION: Of the 14 selected birth defects in this study, less than half were reported by mothers of affected infants to have had an abnormal ultrasound during pregnancy. The frequency of reporting abnormal prenatal ultrasounds varies by type of defect, maternal race/ethnicity, and maternal body mass index status.

[Results of prenatal screening for fetal chromosome abnormality during the first trimester pregnancy in Guangzhou].

OBJECTIVE: To evaluate the efficiency of first trimester prenatal screening for fetal chromosome abnormality using maternal serum marker test and(or) plus nuchal translucency (NT) in Guangzhou region. METHODS: The results of prenatal screening were retrospectively analyzed among 43 703 women with singleton pregnancies from January 2007 to September 2012. A total of 43 703 pregnancies between 9 and 13(+6) weeks of pregnancy were collected and analyzed for maternal serum pregnancy-associated plasma protein A (PAPPA), free ß -human chorionic gonadotropin (free ß -hCG) with or without crown-rump length (CRL). Nuchal translucency was measured by ultrasonographic scan between 11 and 13(+6) weeks of pregnancy. Gestational age was estimated by ultrasonographic scan. The risk values of Down syndrome (DS) and trisomy 18 were calculated using the software Lifcycle. Comparing the difference between the combined screening (PAPPA, free ß -hCG and NT) and serum marker screening (PAPPA and free ß -hCG). RESULTS: Among the 43 703 pregnant women, screening showed that 1385 (3.17%) were Down syndrome positive and 55 (0.13%) were trisomy 18 positive. The final outcomes of pregnancy showed that 142 cases presented chromosomal abnormalities, of which 54 cases suffered from Down syndrome, 13 had trisomy 18, and 75 had other chromosome abnormalities. The total detection rate of Down syndrome and trisomy 18 were 83.33% and 76.92%, respectively.The positive rate is lower, and the detection rate is higher in combined screening group than serum marker screening group. The median PAPPA MoM was lower and the median free ß -hCG MoM and NT measured value was higher in Down syndrome pregnancies than control group. The median PAPPA and free ß -hCG MoM were lower and the median NT measured value was higher in trisomy 18 pregnancies than control group. CONCLUSION: The first trimester prenatal screening can effectively detect Down syndrome and trisomy 18 pregnancy. The combined screening method is superior to the serum marker screening and is the preferred strategy in the first trimester prenatal screening.

Maternal and fetal factors associated with mortality and morbidity in a multi-racial/ethnic registry of anti-SSA/Ro-associated cardiac neonatal lupus.

BACKGROUND: Cardiac manifestations of neonatal lupus include conduction disease and, rarely, an isolated cardiomyopathy. This study was initiated to determine the mortality and morbidity of cardiac neonatal lupus and associated risk factors in a multi-racial/ethnic US-based registry to provide insights into the pathogenesis of antibody-mediated injury and data for counseling. METHODS AND RESULTS: Three hundred twenty-five offspring exposed to maternal anti-SSA/Ro antibodies with cardiac neonatal lupus met entry criteria. Maternal, fetal echocardiographic, and neonatal risk factors were assessed for association with mortality. Fifty-seven (17.5%) died, 30% in utero. The probability of in utero death was 6%. The cumulative probability of survival at 10 years for a child born alive was 86%. Fetal echocardiographic risk factors associated with increased mortality in a multivariable analysis of all cases included hydrops and endocardial fibroelastosis. Significant predictors of in utero death were hydrops and earlier diagnosis, and of postnatal death were hydrops, endocardial fibroelastosis, and lower ventricular rate. Isolated heart block was associated with a 7.8% case fatality rate, whereas the concomitant presence of dilated cardiomyopathy or endocardial fibroelastosis quadrupled the case fatality rate. There was a significantly higher case fatality rate in minorities compared with whites, who were at a lower risk of hydrops and endocardial fibroelastosis. Pacing was required in 70%; cardiac transplantation was required in 4 children. CONCLUSION: Nearly one fifth of fetuses who develop cardiac neonatal lupus die of complications predicted by echocardiographic abnormalities consistent with antibody-associated disease beyond the atrioventricular node. The disparity in outcomes observed between minorities and whites warrants further investigation.

Fetal heart disease and interruption of pregnancy: factors influencing the parental decision-making process.

OBJECTIVE: To identify factors influencing parental decision when a fetal cardiac disease is diagnosed. METHOD: All pregnancies with fetal cardiac abnormalities diagnosed at three academic hospitals of Marseille, France, between 2004 and 2008, were retrospectively studied. The association between maternal and fetal variables (maternal age, parity, ethnicity, gestational age at diagnosis, nuchal translucency, fetal gender, chromosomal and extra cardiac abnormalities, and severity of the cardiopathy) and parental decision was tested using univariate and multivariate statistical methods RESULTS: One hundred eighty-eight cases of fetal cardiac disease were analysed, of which 63 were interrupted pregnancies (IP) and 125 continued pregnancies (CP). Four factors were important in the parental decision-making process: the severity of cardiac malformation, the ethnic origin of the parents, the gestational age at diagnosis and the chromosomal abnormalities. CONCLUSION: Counselling of parents following the diagnosis of a congenital heart disease should take into account that, in addition of the severity of the congenital heart disease (CHD), ethnicity, gestational age at diagnosis and chromosomal abnormalities influence parental decision regarding pregnancy continuation or interruption.

Profile of maternal and foetal complications during labour and delivery among women giving birth in hospitals in Matlab and Chandpur, Bangladesh.

Worldwide, for an estimated 358,000 women, pregnancy and childbirth end in death and mourning, and beyond these maternal deaths, 9-10% of pregnant women or about 14 million women per year suffer from acute maternal complications. This paper documents the types and severity of maternal and foetal complications among women who gave birth in hospitals in Matlab and Chandpur, Bangladesh, during 2007-2008. The Community Health Research Workers (CHRWs) of the icddr,b service area in Matlab prospectively collected data for the study from 4,817 women on their places of delivery and pregnancy outcomes. Of them, 3,010 (62.5%) gave birth in different hospitals in Matlab and/or Chandpur and beyond. Review of hospital-records was attempted for 2,102 women who gave birth only in the Matlab Hospital of icddr,b and in other public and private hospitals in the Matlab and Chandpur area. Among those, 1,927 (91.7%) records were found and reviewed by a physician. By reviewing the hospital-records, 7.3% of the women (n=1,927) who gave birth in the local hospitals were diagnosed with a severe maternal complication, and 16.1% with a less-severe maternal complication. Abortion cases--either spontaneous or induced--were excluded from the analysis. Over 12% of all births were delivered by caesarean section (CS). For a substantial proportion (12.5%) of CS, no clear medical indication was recorded in the hospital-register. Twelve maternal deaths occurred during the study period; most (83%) of them had been in contact with a hospital before death. Recommendations include standardization of the hospital record-keeping system, proper monitoring of indications of CS, and introduction of maternal death audit for further improvement of the quality of care in public and private hospitals in rural Bangladesh.

Early prenatal diagnosis of thalassemia: the first report of experience in mainland China.

In this study, we report our experience with chorionic villus sampling (CVS) for prenatal diagnosis of thalassemia in mainland China. During a 4-year period, 308 pregnant women chose to have CVS for prenatal diagnosis. Chorionic villus sampling was successful in all cases, and post-CVS abortion was seen in only two cases (0.6%). DNA diagnosis was correctly done in 307 (99.7%) prenatal samples but maternal contamination was found in one (0.3%) subject. In total, 77 pregnancies were found with an affected fetus, and all of the affected pregnancies were terminated within 1 week after the CVS procedure. Our experience indicates that CVS is a feasible and effective technique for prenatal diagnosis of thalassemia.

Emergence of pregnancy-related listeriosis amongst ethnic minorities in England and Wales.

Listeriosis is a rare but severe food-borne disease that predominantly affects pregnant women, the unborn, newborns, the elderly and immunocompromised people. Following a large outbreak in the 1980s, specific food safety advice was provided to pregnant women and the immunocompromised in the United Kingdom. Following two coincident yet unconnected cases of pregnancy-related listeriosis in eastern European women in 2008, a review of the role of ethnicity in pregnancy-related listeriosis in England and Wales was undertaken in 2009. Cases reported to the national listeriosis surveillance scheme were classified as 'ethnic', belonging to an ethnic minority, or 'non-ethnic' based on their name, and trends were examined. Between 2001 and 2008, 1,510 cases of listeriosis were reported in England and Wales and, of these, 12% were pregnancy-related cases. The proportion of pregnancy-related cases classified as ethnic increased significantly from 16.7% to 57.9% (chi-square test for trend p=0.002). The reported incidence among the ethnic population was higher than that among the non-ethnic population in 2006, 2007 and 2008 (Relative Risk: 2.38, 95% confidence interval: 1.07 to 5.29; 3.82, 1.82 to 8.03; 4.33, 1.74 to 10.77, respectively). This effect was also shown when analysing data from January to September 2009, using extrapolated live births as denominator. Increased immigration and/or economic migration in recent years appear to have altered the population at risk of pregnancy-related listeriosis in England and Wales. These changes need to be taken into account in order to target risk communication strategies appropriately.

Medians and correction factors for biochemical and ultrasound markers in Chinese women undergoing first-trimester screening for trisomy 21.

OBJECTIVE: To establish normative values and distribution parameters of first-trimester maternal serum free beta-human chorionic gonadotropin (beta-hCG), pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency (NT) thickness in Chinese women and to examine the effects of covariates on their levels. METHODS: Maternal serum free beta-hCG, PAPP-A and fetal NT were measured in 9762 women presenting for first-trimester combined screening for Down syndrome at 11 to 14 weeks of gestation. Individuals' markers were converted to multiples of the median (MoM) using expected medians estimated by performing a weighted regression analysis. Multivariate regression analysis was performed to assess the influence of maternal weight, parity, ethnicity, chorionicity in twin pregnancies, smoking, insulin-dependent diabetes and mode of conception on individual marker MoM levels. RESULTS: Both free beta-hCG and PAPP-A median values demonstrated an exponential relationship with gestational age in days. Multivariate regression analysis indicated that free beta-hCG MoM was statistically significantly dependent on maternal weight (P < 0.0001) and chorionicity in twin pregnancy (both monochorionic and dichorionic P < 0.0001), that PAPP-A MoM was dependent on maternal weight (P < 0.0001), parity (P < 0.0001), chorionicity in twin pregnancy (both monochorionic and dichorionic P < 0.0001) and mode of conception (P = 0.002), and that fetal NT-MoM was dependent on maternal weight (P = 0.0006) and mode of conception (P = 0.012). CONCLUSION: Normative values have been generated to allow conversion of NT, free beta-hCG and PAPP-A to their MoM equivalents and correction factors have been determined to adjust for maternal and pregnancy characteristics for use in ethnic Chinese women undergoing first-trimester screening for aneuploidy.

First-trimester screening for trisomy 21 by free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A: impact of maternal and pregnancy characteristics.

OBJECTIVES: To use multiple regression analysis to define the contribution of maternal variables that influence the measured concentration of free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A), and the interaction between these covariates, in first-trimester biochemical screening for trisomy 21. METHODS: This was a multicenter study of prospective screening for trisomy 21 by a combination of fetal nuchal translucency thickness, and maternal serum free beta-hCG and PAPP-A at 11 + 0 to 13 + 6 weeks of gestation. In the pregnancies subsequently found to have trisomy 21 and in those with no obvious chromosomal abnormality, we used multiple regression analysis to account for pregnancy characteristics that influence the measured concentrations of free beta-hCG and PAPP-A. We fitted Gaussian distributions to the distribution of log multiples of the median (MoM) values in trisomy 21 and in unaffected pregnancies. RESULTS: There were 491 cases of trisomy 21 and 96 803 chromosomally normal pregnancies. Compared with values in Caucasian women, those who were parous, non-smokers and those who conceived spontaneously, PAPP-A was 57% higher in women of Afro-Caribbean origin, 3% higher in South Asians, 9% higher in East Asians, 2% higher in nulliparous women, 17% lower in smokers and 10% lower in those conceiving by in-vitro fertilization (IVF). Free beta-hCG was 12% higher in women of Afro-Caribbean origin, 9% lower in South Asians, 8% higher in East Asians, 2% higher in nulliparous women, 4% lower in smokers and 9% higher in those conceiving by IVF. In screening for trisomy 21 by maternal age and serum free beta-hCG and PAPP-A the estimated detection rate was 65% for a false-positive rate of 5%. CONCLUSIONS: In first-trimester biochemical screening for trisomy 21 it is essential to adjust the measured values of free beta-hCG and PAPP-A for maternal and pregnancy characteristics.

Medians for second-trimester maternal serum markers: geographical differences and variation caused by median multiples-of-median equations.

OBJECTIVES: To establish gestational age-specific mid-trimester normal medians for the prenatal serum markers alpha fetoprotein (AFP), human chorionic gonadotropin (HCG) and unconjugated oestriol (uE3) for a Belgian population by using the Beckman Coulter Access chemiluminiscent immunoassays; to compare these data with data obtained from other geographical regions; to propose regression coefficients for regressed medians and analyse variation induced by different regression equations; to evaluate the effect of formulas used for gestation correction on estimating risk in Down's syndrome. DESIGN: Data derived from 862 fresh serum samples from women being screened for Down's syndrome pregnancy, composed of selected pregnancies deemed to be normal, were examined in a retrospective study. Regressed medians were calculated by using a first-degree logarithmic-linear fit of the raw data. Multiples-of-median (MoM) values estimated by using a simple logarithmic-linear equation were compared with those calculated with higher-degree polynomials chosen with a goodness-of-fit analysis. Model-specific variation was estimated and the effect on risk for Down's syndrome was evaluated. RESULTS: Regressed medians (Y) for Access serum markers AFP (IU/ml), HCG (IU/ml) and uE3 (nmol/l) for a Belgian population can be estimated with the equation Y = 10((A+BX)) with X = decimal weeks. The best fit was obtained with a third-degree and a second-degree polynomial for AFP and uE3, respectively. Differences between the medians and among the slopes of the geographical populations were found to be significant (analysis of covariance, p<0.001). CONCLUSIONS: Belgian marker medians versus gestational time are found to show a pattern that is similar to that in the literature. The log-linear equation is observed to give a good fit and can be suggested as a tool for calculating median MoM values for Belgian laboratories that use Access biochemical prenatal markers.

[Mutation screening and prenatal diagnosis of hidrotic ectodermal dysplasia in a Chinese family].

OBJECTIVE: To analyze the mutations in Cx30 gene in a Chinese family with hidrotic ectodermal dysplasia (HED) and to make prenatal diagnosis on the embryo which has been pregnant for 5 months. METHODS: A family including 2 affected and 4 unaffected individuals was collected, and their informed consents were obtained. The affected woman had a five-month pregnancy. An 884 bp fragment containing the whole GJB6 coding sequence was amplified by PCR and the products were bi-direction sequenced directly. The mutation was further confirmed with restriction endoenzyme digesting. On the base of successful gene diagnosis, the following detection procedure on the pregnant baby was performed. First the whole coding region of Cx30 was amplified using primers Cx30-F and Cx30-R and the PCR products were digested by Hae II. Then the PCR products were cloned into pUCm-T vector. Blue-white blot screening method and PCR-restriction endoenzyme digesting technique were used to identify the correct clones. The mutant allele clone was sequenced to confirmed the mutation. RESULTS: A heterozygous missense mutation 263C --> T in the Cx30 gene was detected in the affected little girl and her affected mother, which led to an amino acid substitution (A88V) in the second transmembrane domain of GJB6. The mutation was confirmed by Hae II digestion. A88V mutant allele cannot be cut while the wild normal allele can be cut into two fragments, 520 and 278 bp. The result of analyse on the five-month pregnancy show the embryo carried the A88V mutation too. So the embryo will be a patient. CONCLUSION: An A88V missense mutation in the Cx30 gene can also cause HED in Chinese Han population. Based on the gene diagnosis, prenatal diagnosis can be played using bi-direction sequencing and confirmed with restriction endoenzyme digesting.

[Relationship of phenotype with type of deletion of dystrophin gene].

OBJECTIVE: To detect the distribution characteristics of dystrophin gene deletions in the northeastern of China and the relationship of severity with type of deletion. METHODS: To screen deletion distribution of 124 DMD/BMD patients via multiplex PCR, male high-risk fetuses were detected deletion by the same method. RESULTS: The deletion frequency was 49%. Deletions located in the regions of exons 45 - 53 and exons 8 - 19 were 41 (67%) and 13 (21%) cases respectively, and in 5 (8%) cases deletions were scattered over both regions, still 2 cases (3%) were checked up deletions lying in exons 34 and 43; there were 9 cases of in-frame deletions and 49 frameshift mutations in all deletions; of 30 high-risk fetuses 10 male ones were screened deletions, who had the same deletion-segments as their probands. CONCLUSIONS: The distribution of dystrophin gene deletions in the northeastern of China cluster mainly in two hot-spots, neighboring regions of exon 8 might be a real deletion "hot spot" in this region; the phenotype is associated with the type of gene deletion, the phenotype is BMD when in-frame deletions occur; severe DMD when frameshift mutations occur. Multiplex PCR method provides the short-cuts for detecting patients and making prenatal gene diagnosis.

Frequency of echogenic intracardiac focus by race/ethnicity in euploid fetuses.

OBJECTIVE: To determine the frequency of echogenic intracardiac focus (EIF) by race/ethnicity. METHODS: We performed a retrospective analysis from January 1996 through June 2003. We reviewed all initial sonograms from 14 to 23 weeks gestation in singleton pregnancies. Mothers on admission for delivery provided race/ethnicity. RESULTS: There were 8207 ultrasounds and deliveries that met study criteria. There were 4636 (56.5%) Caucasian, 2087 (25.4%) African-American, 1261 (15.4%) Hispanic and 223 (2.7 %) Asian subjects. There were 347 (4.2%) EIF detected. The frequency by race/ethnicity varied significantly (p < 0.0001). CONCLUSIONS: This large, population-based study showed that fetuses born to Asian mothers were significantly more likely to have an EIF. This racial difference should be taken into account when counseling patients about the potential for Down syndrome.

Neonatal lupus erythematosus: a review of the racial differences and similarities in clinical, serological and immunogenetic features of Japanese versus Caucasian patients.

There has been tremendous interest in neonatal lupus erythematosus (NLE) since the reports of anti-Ro/SSA antibodies as a diagnostic marker. Recent studies, including ours, have revealed racial differences as well as similarities in the clinical features and immunogenetic backgrounds of Japanese and Caucasian patients with NLE. The frequency of photosensitivity and subacute cutaneous LE lesions is not high in Japanese infants with NLE, which is in sharp contrast to their Caucasian American counterparts. The majority of Japanese infants with NLE develop annular, erythematous or edematous lesions which have also been reported in association with Sjögren's syndrome. The frequency of isolated congenital heart block (CHB) is about 50% in Japanese anti-Ro/SSA positive neonatal lupus infants; this is similar to the frequency among Caucasians. The HLA-DR3 phenotype, which is found in the great majority of Caucasian mothers of NLE infants, is absent in Japanese mothers. Finally, both Japanese and Caucasian children with CHB are often identical to their mothers in their alleles of HLA-DRB1, DQA1 and DQB1 loci.

Population differences affect nonstress test reactivity.

The nonstress test (NST) is the most widely used test of fetal well-being. Recently it has been suggested that race may play a role in NST reactivity. The objective of this research was to explore population variables in addition to race that may influence NST reactivity. Study subjects were 1263 black and 658 white women who underwent NST in the week preceding delivery at a tertiary facility. Retrospective analysis of data from a comprehensive database was conducted. It was found that the percentage of black women with a nonreactive NST was more than three times the percentage of white women, and that from 35 weeks' to 42 weeks' gestation there were significantly fewer reactive NSTs for blacks than for whites (P less than .05). Racial differences in NST results persisted in a logistic regression analysis controlling for several population variables including pregnancy complications and demographic and behavioral factors (odds ratio 3.81; 95% CI 3.03 to 4.78). Regression analysis also confirmed that gestational age, maternal education, epilepsy, and smoking significantly influenced NST reactivity. These results indicate that population differences in NST reactivity exist at our facility. Further prospective study of population determinants of NST reactivity is needed to determine how race, test indication, and other clinical, demographic, and behavioral variables should be used in interpretation of tests of fetal well-being. Standard criteria for NST testing may not be useful in all obstetrical populations.

The association of maternal BMI with fetal echogenic intracardiac foci and echogenic bowel.

OBJECTIVES: To evaluate the impact of maternal body mass index (BMI) as well as maternal ethnicity on the detection of either echogenic intra-cardiac focus (EIF) or echogenic bowel (EB). METHODS: This prospective study identified 74 uncomplicated singleton fetuses in which EIF and/or EB were detected between 18 and 21 weeks of gestation (i.e. study group). Seventy four consecutively scanned fetuses without EIF or EB, at the same gestational age, were selected as controls. The differences in maternal BMI and maternal ethnicity were compared between the two groups using the chi(2) test, Fisher's exact test, and the Student t-test. A multivariable logistic regression model was constructed to control for confounders. Odds ratios (OR) and their 95% confidence interval (CI) were computed. RESULTS: The mean maternal BMI was significantly lower in the study group as compared to controls (22.9 +/- 3.1 vs. 28.0 +/- 7.5 kg/m(2), respectively; p < 0.0001). Patients with fetal EIF and/or EB were significantly more likely to be Asians (20.3% vs. 5.4%, OR = 4.5; 95% CI 1.3-16.9). Using a multivariable analysis, controlling for ethnicity, the association between maternal BMI and fetal EIF or EB remained significant (OR = 0.83; 95% CI 0.76-0.91). However, based on this model Asian ethnicity was not an independent risk factor for the detection of EIF and/or EB (OR = 2.6; 95% CI 0.8-8.9). CONCLUSIONS: Our data suggests an inverse relationship between the maternal BMI and the detection of fetal EIF and/or EB. Moreover, it appears that low maternal BMI, and not Asian ethnicity, is an independent risk factor for the detection of these echogenic fetal findings.

New mutations on platelet GPIIb in Sub-Saharan African populations revealed by genotyping discrepancies.

BACKGROUND: Previous studies of platelet allele frequencies in Sub-Saharan African populations enabled us to identify discrepancies in HPA-3 typing, suggesting the presence of new mutations and of a greater polymorphism than so far described in other populations. OBJECTIVES: To analyze these discrepancies and to assess the factors leading to potential alloimmunization in these populations. SAMPLES: Maternal samples from a Beninese woman following in utero death and panels of blood donors from Benin, Cameroon, Congo, and Pygmies from Central Africa. TECHNIQUES: Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), PCR-sequence specific primers (PCR-SSP) and sequencing techniques. RESULTS: Three new mutations were found on GPIIb gene: exon 26 a) 2614C>A situated between HPA-3 and HPA-9w, b) 2645C>T downstream of HPA-3, c) intron 26 IVS26+89G>A. These mutations may lead to discrepant DNA typing results, due either to a localization in the complementary sequence recognized by the primer or to the appearance of a new enzyme restriction site. Furthermore, a bilateral linkage << deletion (Delta9 bp) intron 21 and the HPA-3b allele (exon 26) >> found in Caucasian, Asian, and Oceanian populations is not found in African populations, suggesting that its appearance was prior to HPA-3. CONCLUSION: Three new mutations have been identified, two of them potentially immunogenic through their position. Furthermore, the polymorphism found on intron 26, localized in the complementary sequence of the PCR primer, may lead to a false typing assignation. It is therefore important to diversify techniques, both genomic (PCR-RFLP and PCR-SSP), and proteomic monoclonal antibody-specific immobilization of platelets antigen (MAIPA) to ensure accurate HPA antigenic system typing.