Routine Prenatal Testing Research Articles

Second-Trimester Maternal Serum Markers in Twin Pregnancy with Complete Mole: Report of 2 Cases

We present second-trimester serum marker levels in cases of twin pregnancy with complete hydatidiform mole and a coexistent fetus (CHMCF). Second-trimester inhibin A (InhA) levels have not been previously reported in such cases. Second-trimester maternal serum screening, alpha-fetoprotein (AFP), unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and InhA measurements combined with maternal age to estimate a patient's risk of Down syndrome during pregnancy was performed as a routine prenatal test in 2 cases of CHMCF. Hospital records containing serum marker data, patient history, pathology reports, and pregnancy outcome were reviewed. In cases of CHMCF, maternal serum AFP and uE3 levels were similar to those of a normal singleton pregnancy, whereas hCG and InhA levels were markedly increased. Second-trimester maternal serum marker profiles in cases of CHMCF are a composite of normal singleton and molar tissue secretions. We have found, for the first time, that second-trimester InhA levels are markedly increased in these cases. Serum marker levels may be useful in diagnosis of CHMCF, prenatal counseling, and evaluation of risk for persistent trophoblastic disease.

Introduction of Routine HIV Testing in Prenatal Care—Botswana, 2004

In 2003, approximately 37% of pregnant women in Botswana (2001 population: 1.7 million; approximately 40,000 births per year) were infected with human immunodeficiency virus (HIV). Since 2001, all prenatal clinics in Botswana have offered HIV screening and interventions for prevention of mother-to-child transmission of HIV (PMTCT), which can decrease vertical transmission of HIV from 35%-40% to 5%-10%. Historically, HIV testing in Botswana has been performed after individual pretest counseling, with patients actively choosing whether to be tested (i.e., an "opt-in" approach). In 2003, 52% of pregnant women receiving prenatal care nationwide learned their HIV status. In 2004, to increase use of free national PMTCT and antiretroviral treatment (ARV) programs, Botswana began routine, noncompulsory (i.e., "opt-out") HIV screening in prenatal and other health-care settings. Concerns have been raised that routine testing in Africa might deter women from seeking prenatal care and might result in fewer women returning for their test results and HIV care after testing. To assess the early impact of routine testing on HIV-test acceptance and rates of return for care, the CDC Global AIDS Program and the PMTCT program in Botswana evaluated routine prenatal HIV testing at four clinics in Francistown, the second largest city in Botswana, where HIV prevalence has been > or =40% since 1995. This report describes the results of that assessment, which indicated that, during February-April 2004, the first 3 months of routine testing, 314 (90.5%) of 347 pregnant women were tested for HIV, compared with 381 (75.3%) of 506 women during October 2003-January 2004, the last 4 months of the opt-in testing period (p<0.001). However, many women who were tested never learned their HIV status because of logistical problems or not returning to the clinic. Substantial increases in HIV testing of pregnant women were also observed at the Francistown referral hospital and at prenatal clinics nationwide. These findings highlight the potential public health impact of routine HIV testing with rapid, same-day results for programs seeking to increase the number of persons with access to HIV-prevention and treatment services.

Potential Factors That May Affect Acceptance of Routine Prenatal HIV Testing

Despite increasing advocacy for an "opt-out" strategy in routine prenatal HIV screening programs in Canada, no published studies have examined factors that may affect acceptance of prenatal HIV testing. We included all pregnant women in Alberta who received prenatal care (N = 38,712) and their caregivers (N = 2,007) between January 1 and November 30, 2000. Factors associated with non-acceptance of HIV testing in both pregnant women and their caregivers were assessed using multivariate logistic regression. Overall, 1.5% of women declined HIV testing. First Nations women were about twice as likely to decline the test (adjusted odds ratio [OR(adj)] 1.91, 95% CI [1.42-2.58]) compared to non-First Nations women (p < 0.001). The proportion also increased with age (chi2 trend p < 0.001) in the general population. In First Nations women, however, most (3.2%) declined in the 20-24 year age group. No significant effect was seen for a socio-economic status marker or for the place of residence. The caregivers of women who declined HIV testing were more likely to be female (OR(adj) 1.56 [1.28-1.89]), midwives (OR(adj) 140.65 [58.61-337.49]), other non-obstetrical medical specialties (OR(adj) 4.92 [1.94-12.47]), and general practitioners (OR(adj) 3.44 [1.87-6.33]). In an "opt-out" routine prenatal HIV screening program, the characteristics of both the pregnant women and their caregivers may contribute to the non-acceptance of HIV testing. A higher likelihood of declining HIV testing among First Nations pregnant women and other pregnant women under the care of midwives and female physicians warrants further study.

Routine Prenatal HIV Testing as a Standard of Care

There are various clinical and ethical arguments against the concept of implied consent for prenatal HIV testing. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.

Prolonged Activated Partial Thromboplastin Time In Pregnancy: A Brief Report

Limited data are available regarding causes of prolonged activated partial thromboplastin time (aPTT) in otherwise normal pregnancies. We retrospectively evaluated clinical data of pregnant women in whom an elevated aPTT was noted on routine prenatal testing. Our intent was to identify various causes of prolonged aPTT and to evaluate whether the pregnancies were adversely affected. A retrospective review of medical records of 36 pregnant patients with a prolonged aPTT as the sole abnormal coagulation test seen in the outpatient department of a tertiary care hospital over a period of 4 years. Patients' median age was 26 (range, 19-41) years and median duration of gestation period was 19 (range, 8-38) weeks. Fifteen patients were primigravida. Of 36 patients, repeated aPTT values were normal in 24 (67%) patients, whereas 12 (33%) patients had persistently elevated aPTT values. Factor XI deficiency was found in 5 patients, lupus anticoagulant in 3 patients, elevated anticardiolipin antibody in 2 patients, and low von Willebrand Factor level in 1 patient. Overall, 23 patients delivered. No patients experienced excessive bleeding or thromboembolism. Factor XI deficiency and antiphospholipid antibody were 2 major abnormalities identified in patients with prolonged aPTT. These coagulopathies were not associated with excessive bleeding or thromboembolism. Repeat normal aPTT in approximately 2 thirds of patients suggests that proper sample collection and processing are important for coagulation assays to avoid erroneous clotting times.

Integrating prevention of mother-to-child HIV transmission into antenatal care: learning from the experiences of women in South Africa

In 1999, for the first time in South Africa, a Mother-to-Child HIV Transmission (MTCT) prevention programme was implemented at the routine primary care level and not as part of a research protocol. A total of 264 women attending prenatal care in these clinics were interviewed in Xhosa using a standardized questionnaire. All had been offered HIV testing, and 95% had accepted. Women who had not been tested were four times more likely to believe that in the community families reject HIV-positive women (p<0.005). Of women who tested, 19% were HIV positive and 83% had told their partner that they had taken the test. HIV-positive women who had not disclosed testing to their partners were three times more likely to believe that, in the community, partners are violent towards HIV-positive women (p<0.005); 86% stated that they would have taken AZT if found to be HIV positive. Only 11% considered that the use of formula feeding indicated that a woman was HIV positive. In conclusion, routine prenatal HIV testing and interventions to reduce perinatal HIV transmission are acceptable to the majority of women in a South African urban township, despite an awareness of discrimination in the community towards HIV-positive women.

Legal Barriers to Implementing Recommendations for Universal, Routine Prenatal HIV Testing

Administraation of antiretroviral therapy to women during pregnancy, labor and delivery, and to infants postnatally can dramatidy reduce mother-to- child HIV transmission (MTCT). However, pregnant women need to know that they are HIV-infected to take advantage of antiretroviral therapy, and many women do not know their HIV status. One-half of HIV-infected infants in the United States were bornto women who had not been tested for HIV or for whom the time of testing was not known. Although fewer than 400infants are infected perinatally in the United States each year, that number could be reduced even further through policies aimed at HIV testing during pregnancy.The reasons toadopt such a policy are strong: the pathophysiology of perinatal transmission is clear, prophylaxis is effective and safe, and the intended beneficiaries of the intervention - babies - cannot protect themselves.

First report of prenatal diagnosis of genetic congenital deafness in a routine prenatal genetic test

We aimed to screen for connexin26 gene (GJB2) mutations associated with autosomal recessive non-syndromic neurosensory deafness (NSRD) in a general risk population. Screening for the most common connexin26 gene mutations was offered to all women undergoing a second-trimester amniocentesis for fetal karyotype analysis in our Center. After rapid DNA extraction from amniotic fluid, PCR amplification was performed and products analysed to detect mutations of GJB2 gene by a sequencing technique. In particular, we searched for the 20 most frequently reported mutations (out of the approximately 90 so far described) and for which there are commercially available tests. From a total of 4819 consecutive amniotic fluids examined, the following five different heterozygous mutations were detected: 35delG in 80 cases, 167delT in 3 cases and 1 occurrence of each of the following mutations: M34T, 35insG and W77R. From these data, a prevalence of 1 : 56 (1.78%) for the heterozygous condition can be estimated in the Mediterranean general risk population. The striking predominance of 35delG mutation is confirmed. In addition, we detected a homozygous 35delG mutation condition in a foetus of no risk parents. In this case, the early diagnosis permitted prompt application of an acoustic prosthesis allowing for cochlear implantation in due time, with significant improvement of the prognosis. In a general risk population, a carrier status for congenital deafness can be observed in 1 : 56 (1.78%) amniotic fluids; this is mostly due to the presence of a 35delG mutation of the connexin26 gene. Occasional identification of homozygous states, although rare, allows the best therapeutic approach.

Reasons for trisomy 13 or 18 births despite the availability of prenatal diagnosis and pregnancy termination

Background: Few studies have evaluated the reasons why lethal chromosomal anomalies continue to occur despite the importance of this question for maximizing perinatal care. Aims: To determine why trisomy 13 or 18 births continue to occur in Alaska. Study design: Case series involving review of maternal and infant medical records. Subjects: All 28 known infants and fetuses that died with trisomy 13 or 18 during 1992–2001 and their mothers. Outcome measures: The proportion of mothers that declined or received a variety of routine prenatal tests, the results of prenatal testing, and the impact of testing on decisions related to pregnancy. Results: Seventeen women declined pregnancy termination or amniocentesis, 10 had no prenatal risk factors and were not offered these procedures, and one woman had an amniocentesis but was not offered pregnancy termination. Twenty-six women had ≥1 prenatal ultrasounds; for 17 women, these were interpreted as normal throughout pregnancy ( n=11) or until after 30 weeks gestation ( n=6) despite substantial fetal malformations. Fourteen of 15 women with an abnormal ultrasound had an amniocentesis compared to one of eight women whose only risk factor was advanced maternal age. Conclusions: Most trisomy 13 or 18 deliveries occurred to women who declined amniocentesis or pregnancy termination. Failure to identify abnormalities on prenatal ultrasound may have contributed to the decision not to have these procedures.

Technical report: perinatal human immunodeficiency virus testing and prevention of transmission. Committee on Pediatric Aids.

In 1994, the US Public Health Service published guidelines for the use of zidovudine to decrease the risk of perinatal transmission of human immunodeficiency virus (HIV). In 1995, the American Academy of Pediatrics and the US Public Health Service recommended documented, routine HIV education and testing with consent for all pregnant women in the United States. Widespread incorporation of these guidelines into clinical practice has resulted in a dramatic decrease in the rate of perinatal HIV transmission and has contributed to more than a 75% decrease in reported cases of pediatric acquired immunodeficiency syndrome (AIDS) since 1992. Substantial advances have been made in the treatment and monitoring of HIV infection; combination antiretroviral regimens that maximally suppress virus replication are now available. These regimens are recommended for pregnant and nonpregnant individuals who require treatment. Risk factors associated with perinatal HIV transmission are now better understood, and recent results from trials to decrease the rate of mother-to-child HIV transmission have contributed new strategies with established efficacy. However, perinatal HIV transmission still occurs; the Centers for Disease Control and Prevention estimates that 300 to 400 infected infants are born annually. Full implementation of recommendations for universal, routine prenatal HIV testing and evaluation of missed prevention opportunities will be critical to further decrease the incidence of pediatric HIV infection in the United States. This technical report summarizes recent advances in the prevention of perinatal transmission of HIV relevant to screening of pregnant women and their infants.

Hepatitis C: screening in pregnancy

Hepatitis C virus infection, which is far more prevalent than human immunodeficiency virus (HIV)-1, can lead to cirrhosis, hepatocellular carcinoma, hepatic failure, and death. Like HIV-1, hepatitis C is transmitted parenterally, sexually, and from mother to infant. The American Academy of Pediatrics and the Centers for Disease Control and Prevention (CDC) recently recommended that all children born to women who are infected with hepatitis C virus or have risk factors for infection be screened for hepatitis C. Most infected women are asymptomatic and unaware of their infection, so routine prenatal testing is needed to fully meet that goal. We do not believe that current data justify universal testing, but we believe it is time for all obstetricians to test selectively based on risk factors.

Another undectectable viral load: HIV-2.

AIDS: A case study is presented of a pregnant woman from Ghana whose prenatal screening indicated that she was HIV-positive. She was given AZT and 3TC to prevent transmitting the virus to her newborn, but declined to take the drugs, thinking they were unnecessary. The baby tested positive, and further testing of the mother revealed that they were infected with HIV-2, not HIV-1 for which they had been tested. HIV-2 is a lentivirus capable of causing the same clinical syndrome as HIV-1 with regard to CD4-cell depletions and opportunistic infections in some people. HIV-2 is not transmitted as easily via sexual intercourse or childbirth as is HIV-1. Common in West Africa, HIV-2 may be more widely spread than HIV-1. Treatment options for the patient are described.

Economic evaluation of prenatal carrier screening for fragile X syndrome.

The objective of this study was to conduct an economic evaluation of routine prenatal carrier testing for fragile X syndrome. This economic analysis was conducted from the societal perspective. A cost-benefit equation was developed based on the premise that the cost of routinely offering prenatal carrier testing for fragile X syndrome should be at least equal to, or less than, the cost of the current practice of not offering such testing. Sensitivity analyses included key assumptions regarding therapeutic abortion rates (50-100%) and patient screening acceptance rates (50-80%). A policy of routinely offering prenatal carrier testing for fragile X syndrome may be beneficial only if the cost per screening test is less than $120 during the first year of the screening program, or less than $240 when the program reaches its full maturity. Given the current cost per screening test of $250, prenatal screening for carrier status for fragile X syndrome carries the potential for annual losses of approximately $10 to $195 million in the United States. In addition, approximately 46-115 fetal lives may be lost due to invasive genetic procedures. Prenatal screening for fragile X syndrome may be economically beneficial only if the cost of the prenatal screening test for carrier identification is considerably less than the current cost.

Economic Evaluation of Prenatal Carrier Screening for Fragile X Syndrome

Objective: The objective of this study was to conduct an economic evaluation of routine prenatal carrier testing for fragile X syndrome.Methods: This economic analysis was conducted from the societal perspective. A cost-benefit equation was developed based on the premise that the cost of routinely offering prenatal carrier testing for fragile X syndrome should be at least equal to, or less than, the cost of the current practice of not offering such testing. Sensitivity analyses included key assumptions regarding therapeutic abortion rates (50–100%) and patient screening acceptance rates (50–80%).Results: A policy of routinely offering prenatal carrier testing for fragile X syndrome may be beneficial only if the cost per screening test is less than $120 during the first year of the screening program, or less than $240 when the program reaches its full maturity. Given the current cost per screening test of $250, prenatal screening for carrier status for fragile X syndrome carries the potential for annual losses of approximately $10 to $195 million in the United States. In addition, approximately 46–115 fetal lives may be lost due to invasive genetic procedures.Conclusions: Prenatal screening for fragile X syndrome may be economically beneficial only if the cost of the prenatal screening test for carrier identification is considerably less than the current cost.

Human Immunodeficiency Virus Test Refusal in Pregnancy

In Brief Objective To determine if awareness of methods to reduce vertical transmission of human immunodeficiency virus (HIV) is associated with HIV test acceptance and to clarify patients' attitudes toward routine versus elective prenatal HIV testing. Methods In a cross-sectional study, 247 antenatal patients were surveyed regarding HIV knowledge, self-perceived HIV risk, and willingness to learn a positive test result. This information, along with demographic and risk factor data, was related to HIV test acceptance. Patients also indicated their attitudes toward routine versus elective prenatal testing for HIV and other common prenatal screening tests. Results Seventy-two percent of antenatal patients accepted HIV testing. Test acceptance was not associated with the presence of risk factors, self-perceived HIV risk, or demographic factors, including race and ethnicity. Test acceptance was associated positively with patients' knowledge of a medical intervention to reduce vertical transmission and their willingness to learn a positive HIV test result. Only 24% of patients knew that the risk of vertical transmission could be reduced using medication. Sixty-nine percent of patients said that prenatal HIV testing should be routine, whereas 27% said that it should be done only after specific written consent. As a group, our patients viewed HIV screening no differently from screening for other infections in pregnancy. Conclusion Interventions aimed at increasing HIV testing rates among pregnant women should focus on educating patients about vertical transmission reduction and promising new therapies for HIV infection. Proponents of elective testing should re-evaluate the assumption that patients view HIV testing differently from other prenatal tests for which separate written consent is not required. Most pregnant women will accept testing for human immunodeficiency virus if they know that a medication exists to reduce transmission to their infants, but few are aware of this intervention.

Human Immunodeficiency Virus Test Refusal in Pregnancy: A Challenge to Voluntary Testing

Objective: To determine if awareness of methods to reduce vertical transmission of human immunodeficiency virus (HIV) is associated with HIV test acceptance and to clarify patients’ attitudes toward routine versus elective prenatal HIV testing.Methods: In a cross-sectional study, 247 antenatal patients were surveyed regarding HIV knowledge, self-perceived HIV risk, and willingness to learn a positive test result. This information, along with demographic and risk factor data, was related to HIV test acceptance. Patients also indicated their attitudes toward routine versus elective prenatal testing for HIV and other common prenatal screening tests.Results: Seventy-two percent of antenatal patients accepted HIV testing. Test acceptance was not associated with the presence of risk factors, self-perceived HIV risk, or demographic factors, including race and ethnicity. Test acceptance was associated positively with patients’ knowledge of a medical intervention to reduce vertical transmission and their willingness to learn a positive HIV test result. Only 24% of patients knew that the risk of vertical transmission could be reduced using medication. Sixty-nine percent of patients said that prenatal HIV testing should be routine, whereas 27% said that it should be done only after specific written consent. As a group, our patients viewed HIV screening no differently from screening for other infections in pregnancy.Conclusion: Interventions aimed at increasing HIV testing rates among pregnant women should focus on educating patients about vertical transmission reduction and promising new therapies for HIV infection. Proponents of elective testing should re-evaluate the assumption that patients view HIV testing differently from other prenatal tests for which separate written consent is not required.

Proposal for routine antenatal screening at 14 weeks for hepatitis B surface antigen. Dutch Study Group on Prevention of Neonatal Hepatitis.

To develop a low cost, high compliance screening programme for identification of carriers of hepatitis B surface antigen in the obstetric population of the Netherlands. A seven year open, descriptive study of screening for hepatitis B surface antigen as part of routine prenatal laboratory testing at 14 weeks of gestation. Compliance with programme evaluated by checking delivery records (hospitals) or registration of births in the 30 participating municipalities (rural area). Three large city hospitals (two tertiary referral centres) and one rural area with a large number of home deliveries. 99,706 pregnant women applying for prenatal care for the first time. Proportion of pregnant women routinely screened; prevalence of hepatitis B surface antigen in large cities and rural area. Uptake of screening reached 97% in the hospitals after inclusion of 10% screened at delivery; the estimated uptake in the rural area was > 95%. Prevalence of hepatitis B surface antigen was 1.6% in the large cities and 0.3% in the rural area. For screening at delivery the prevalence was 2.5 times higher (4%, P < 0.01) than for screening at week 14 of gestation. Incorporation of universal testing for hepatitis B surface antigen into routine prenatal laboratory testing is practical; high compliance is achieved when screening is supplemented with rapid screening at delivery for those who escaped routine prenatal care.

Confessions of a blood donor

My friend Jilly is a blood donor and, as in all areas of her life, she undertakes her duties with boundless enthusiasm. Greece is a country with a high demand for blood, mainly owing to the numbers of children with thalassaemia major who, throughout their tragically short lives, regularly attend the local hospitals for monthly transfusions; fortunately, these numbers are decreasing thanks to routine prenatal testing and the offer of early abortion. Many systems have been devised to cover these additional needs, including the inducement of days off to army recruits and civil servants who become donors, but it is still common practice, for those undergoing operations where transfusion is likely to be …

Ranitidine-associated autoimmune hemolytic anemia in a health maintenance organization population

Reversible hematologic abnormalities including hemolytic anemia [l] with a positive direct Coombs' test have been associated with ranitidine. In addition to the case report cited above, the U.S. Food and Drug Administration had received five other cases of hemolysis associated with recent intake of ranitidine as of February 1991. To investigate the possible association of ranitidine with autoimmune hemolytic anemia, a study was conducted to determine how often diagnoses of hemolytic anemia or abnormal Coombs' test results followed dispensing of ranitidine using the automated medical and pharmacy records of a large health maintenance organization. No occurrences of hemolytic anemia were identified among 12,054 individuals following 38,686 prescriptions for this medication. The 95% upper confidence bound was 3.1 cases/ 10,000 exposed persons. One abnormal direct Coombs' test with mild anemia was discovered during routine prenatal testing of an asymptomatic patient who was dispensed ranitidine two and a half months previously. Hemolysis, however, was not demonstrated and an association with prior ranitidine use could not be confirmed. Additional analyses indicate that in only 30% of ranitidine courses was a blood count obtained. In those courses with hematocrits below 40%, less than 1 % had a Coombs' test performed. Chart review suggests that the majority of individuals with severe anemia have alternative explanations other than autoimmune hemolysis for their anemia. This analysis indicates that ranitidine is unlikely to be a common cause of clinically recognized autoimmune hemolytic anemia and demonstrates the utility of large automated medical and pharmacy data bases to conduct post-marketing studies of spontaneously reported adverse drug effects.

Lack of knowledge in health professionals: a barrier to providing information to patients?

To assess obstetricians' and midwives' knowledge of routine prenatal screening tests for fetal abnormality and factors associated with such knowledge. Questionnaire assessment of antenatal clinic staff. Six hospitals within the United Kingdom (four district general hospitals in London, one district general hospital in Wales, and one teaching hospital in Wales), offering routine prenatal screening tests. 29 obstetricians and 97 midwives were invited to participate, of whom 21 and 70 respectively responded to the questionnaire. Knowledge of prenatal tests, according to 19 item multiple choice questionnaire, reluctance to disclose uncertainty, and clinical experience. The overall response rate was 72% (91/126). In all, 43% of midwives and 14% of obstetricians obtained correct responses on fewer than half the items. Reluctance to disclose uncertainty to patients was associated in obstetricians with having less knowledge about prenatal testing (r = -0.50; p < 0.025, Pearson product moment correlation) and in midwives with more clinical experience (r = 0.43; p < 0.001). Lack of knowledge and greater clinical experience seem to be important barriers to providing patients with information about prenatal screening tests.