Twenty-year outcome analysis of genetic screening programs for Tay-Sachs and beta-thalassemia disease carriers in high schools.

Programs for education, screening, and counseling of senior-high-school students, in populations at high risk for Tay-Sachs and beta-thalassemia diseases, have existed for >20 years in Montreal. Four process and outcome variables are reported here: (i) voluntary participation rates in the high-school cohort; (ii) uptake rates for the screening test; (iii) origin of carrier couples seeking the prenatal diagnosis option in the programs; and (iv) change in incidence of the two diseases. Between 1972 and 1992, we screened 14,844 Ashkenazi-Jewish students, identified 521 HexA-deficient carriers (frequency 1:28), reached 89% of the demographic cohort in the educational component of the program, and achieved 67% voluntary participation in the subsequent screening phase. The corresponding data for the beta-thalassemia program are 25,274 students (mainly of Mediterranean origin) representing 67% of the cohort with 61% voluntary participation in the screening phase (693 carriers; frequency 1:36). From demographic data, we deduce that virtually all the carriers identified in the high-school screening program remembered their status, had their partner tested if they did not already know they were a carrier couple, and took up the options for reproductive counseling/prenatal diagnosis. In Montreal, the current origin of all couples using prenatal diagnosis for Tay-Sachs and beta-thalassemia diseases is the corresponding genetic screening/testing program, whereas, at the beginning of the programs, it was always because there was a history of an affected person in the family. Incidence of the two diseases has fallen by 90%-95% over 20 years; the rare new cases are born (with two exceptions) outside the target communities or to nonscreened couples.     

Antenatal screening for cystic fibrosis: a trial of the couple model.

OBJECTIVE--To assess the delivery and acceptability of antenatal couple screening for cystic fibrosis. Carrier status was notified only when both members of a partnership had cystic fibrosis alleles and therefore a one in four risk of having an affected child. DESIGN--Mouthwash samples were tested when both partners participated. Results were returned only to positive couples. SETTING--Two large maternity hospitals in Edinburgh. SUBJECTS--Screening was offered to all couples who booked at one of the two hospitals. MAIN OUTCOME MEASURES--(a) The take up of screening, carriers and carrier couples identified, take up of prenatal diagnosis, and numbers of affected fetuses detected; (b) questionnaire measures of patient satisfaction and stress. RESULTS--Screening was offered to 8536 couples. 714 (8.4%) were regarded as ineligible, usually because of late booking or absence of a partner. 1900 (24.3%) of the remainder declined screening. Among the 5922 screened couples, four tested positive--that is, both partners were cystic fibrosis heterozygotes. All four elected to have prenatal diagnosis. There were three terminations of pregnancy because of an affected fetus, one couple having two successive pregnancies with affected fetuses. The participation rate was 76% for eligible couples (5922/7822) and 69% for all couples (5922/8536). Only 89 screened couples (1.5%) requested information on individual carrier status. No anxiety was detected among a cohort of the screened population, and 99% of questioned participants expressed satisfaction with the concept of couple screening. CONCLUSIONS--Antenatal couple screening is a satisfactory and acceptable way of screening for cystic fibrosis and has been adopted as routine in the two trial hospitals.     

Prenatal screening for hemoglobinopathies. I. A prospective regional trial.

Prenatal hemoglobinopathy screening was chosen as a model system for the study of patient receptivity to unsolicited genetic information. Providers of prenatal care in Rochester, NY, were offered free testing of all their prenatal patients and genetic counseling of women found positive. The 18,907 prenatal samples tested in a 5-year period represented 35.1% of the pregnancies in the Rochester metropolitan region. A hemoglobinopathy was found in 810 pregnancies (4.3%). Of the 21 different types of hemoglobinopathies detected, the most common were sickle cell trait (59%), hemoglobin C trait (19%), beta-thalassemia trait (11%), and hemoglobin E trait (5%). At the time of phlebotomy, 75% of the pregnancies were of less than 18 wk duration. Sixty-six percent of the pregnancies occurred in patients unaware of their diagnosis, and 80% occurred in patients unaware that they might be at risk for a child with a serious blood disorder. Of the 810 positive pregnancies, 551 (68%) occurred in patients who came for counseling. Of 453 women counseled during their first screened pregnancy, 390 (86%) said they wanted their partners tested and 254 (55%) had their partner tested. In the 77 pregnancies thus found to be at risk, the couple was too late for prenatal diagnosis in 12 cases, and the condition for which the fetus was at risk was too mild in 12 cases. Prenatal diagnosis was offered in the remaining 53 pregnancies and was accepted by 25 couples (47%). These results indicate that unselected patients in the primary care setting in this region, even though pregnant, are receptive to and utilize genetic information.     

Prevention of homozygous beta-thalassemia by carrier screening and prenatal diagnosis in Sardinia.

We report here results of a 3-year pilot voluntary screening program coupled with prenatal diagnosis directed to the prospective prevention of homozygous beta-thalassemia (beta-thal) in Sardinia. The screening program took two approaches: outreach community testing and hospital testing on request after a period of sensibilization. The outreach testing was very effective as, taking into account the already known number of couples at risk with an affected proband (20), 74% of the couple at risk expected (61) on the basis of the carrier rate were identified. Less effective was the hospital testing in which half of the couples at risk expected were detected (502 with the 199 without an affected proband). After nondirective genetic counseling, approximately 85% of the couples at risk, which had a pregnancy, with no statistically significant difference between those with and those without a proband, requested prenatal testing. This figure showed a steadily increase from the beginning in 1977 to 1980. All the pregnancies (42), but two carrying homozygous fetuses, were terminated on parental request. A continuous hospital survey of thal-major admissions in the different hospitals of the counties showed a steady decline in the incidence figure at birth from 1976 (1:213) to 1978 (1:290). These results showed that even in a medium-developed, rural, Catholic population screening coupled with prenatal diagnosis can be successful in the control of a fatal, recessively inherited disorder.     

Cystic fibrosis carrier population screening in the primary care setting.

To determine the receptivity of prenatal care providers and their patients to carrier testing for cystic fibrosis (CF), we offered free carrier screening, followed by genetic counseling of carriers, to all prenatal care providers in Rochester, NY, for all their female patients of reproductive age, pregnant or not. Of 124 prenatal care providers, only 37 elected to participate, but many of these offered screening only to pregnant women. The acceptance rate among pregnant women was approximately 57%. The most common reasons for accepting screening were to obtain reassurance (50.7%) and to avoid having a child with CF (27.8 %). The most common reasons for declining screening were not intending to terminate a pregnancy for CF (32.4%) and believing that the chance of having a CF child was very low (32.2%). Compared with decliners, acceptors were more likely to have no children, regarded having a child with CF as more serious, believed themselves more susceptible to having such a child, knew more about CF, would be more likely to terminate a pregnancy if the fetus were shown to have CF, and more strongly supported offering CF screening to women of reproductive age. Of 4,879 women on whom results were obtained, 124 were found to be carriers. Of these 124 carriers, the partners of 106 were tested. Of the five at-risk couples, four requested prenatal diagnosis and one requested neonatal diagnosis. No woman found to be a carrier whose partner tested negative requested prenatal diagnosis. Except for the imperfect knowledge of those testing negative, none of the adverse outcomes predicted for CF carrier testing in the general population were observed in this study.     

Prenatal hemoglobinopathy screening. IV. Follow-up of women at risk for a child with a clinically significant hemoglobinopathy.

To determine the benefits and burdens of prenatal hemoglobinopathy carrier identification and genetic counseling and its impact on subsequent reproductive behavior, we recontacted women whom we had previously identified as at risk for having a child with a clinically significant hemoglobinopathy, regardless of whether they had accepted the offer of prenatal diagnosis. Of the 46 such women, 31 were available for interview. These 31 women had received offers of prenatal diagnosis in 47 pregnancies. Seventeen had been accepted, and 30 had been declined. The proportion of patients accepting the offer of prenatal diagnosis was higher for the index pregnancy (50%) than for subsequent pregnancies (22%). The mean interval between the initial counseling of the patient and the follow-up interview was 43 mo (standard error +/- 2.7 mo). Ninety-four percent of those interviewed recalled having received information from the screening program; 74% recalled the name of their condition; 90% knew that trait did not affect their health; 84% recalled the name of the condition for which their fetus had been at risk; and 77% could state at least one symptom of the disease. Of the 29 women asked whether they intended to use prenatal diagnosis in future pregnancies, 13 said yes and 16 said no. Of the 26 patients asked about satisfaction with their previous decision about prenatal diagnosis, all were satisfied with their decision. Eighteen said they would make the same decision in their next pregnancy, but seven patients said they would not, and one was undecided.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cystic fibrosis heterozygote screening in 5,161 pregnant women.

A screening program for cystic fibrosis (CF) heterozygotes was conducted in a large HMO prenatal population, to evaluate the level of interest among eligible patients, the effectiveness of prescreening education, attitudes toward the screening process, psychological effects, and utilization of prenatal diagnosis and its outcomes. The heterozygote identification rate and frequency of specific CFTR mutations were also assessed. Identified carriers were offered genetic counseling and testing of male partners. Prenatal diagnosis was offered if both parents were identified as carriers. A total of 5,161 women underwent carrier testing; 947 others completed survey instruments only. The acceptance rate of screening was high (78%), and pretest education by videotape was generally effective. Adverse psychological effects were not reported. Participants generally found screening to be desirable and useful. Screening identified 142 female heterozygotes, 109 couples in which the male partner was not a carrier, and 7 high-risk couples. The incidence of R117H mutations was much higher than expected. The number of identified carriers was much lower in Hispanics than in Caucasians. We conclude that large-scale prenatal screening for CF heterozygotes in the absence of a family history of CF is an acceptable method for identifying couples at risk for affected fetuses. Sufficient pretest education can be accomplished efficiently, test insensitivity is well accepted, adverse psychological events are not observed, and general patient satisfaction is high.     

Carrier screening for Gaucher disease in couples of mixed ethnicity

With the advent of mutational analysis for Gaucher disease, carrier screening has been incorporated into many Jewish genetic disease screening programs. Frequencies and mutations for Gaucher disease in non-Jewish populations are less well established and the detection rate of carriers are lower. Testing is problematic for resolving residual risk in a couple of mixed ethnicity. We report the testing choices made by 20 consecutive couples of mixed ethnicity where the Ashkenazi Jewish partner was identified to be a Gaucher disease gene carrier. Carrier studies of the non-Jewish partner were elected as follows: DNA studies alone, 5 (25%); enzymatic assay, 2 (10%); both, 6 (30%); no carrier studies, 7 (35%). Of the 7 couples not electing carrier studies, one was not in a pregnancy and 6 elected prenatal diagnosis in lieu of parental testing by enzymatic analysis of amniocytes. One couple elected parental carrier studies as well as prenatal diagnosis. All couples electing prenatal Gaucher determination had amniocentesis for other indications as well (4, advanced maternal age; 4, parental anxiety). We conclude that Gaucher screening is feasible for couples of mixed ethnicity if appropriate counseling and testing are offered.     

Antenatal screening for carriers of cystic fibrosis: randomised trial of stepwise v couple screening.

OBJECTIVE--To perform a rigorous comparative evaluation of stepwise and couple approaches to antenatal carrier screening for cystic fibrosis. DESIGN--Pragmatic randomised trial. SETTING--Hospital antenatal clinic serving a regional population. SUBJECTS--2002 women (couples) attending for booking antenatal visit at less than 17 weeks'' gestation with no family history of cystic fibrosis. INTERVENTIONS--Offering counselling and carrier testing for cystic fibrosis, either to women in the first instance (stepwise) or to couples (couple screening). MAIN OUTCOME MEASURES--Uptake rates; anxiety; knowledge of cystic fibrosis and carrier status (both partners); attitudes to health, pregnancy, the baby, and screening (both partners); and uptake of carrier testing by relatives. RESULTS--Uptake of screening was the same for both approaches (90%). After delivery most women remembered test results and their meaning, but 53/253 (21%) of those with negative results of couple testing had forgotten that repeat testing would be advisable if they had a pregnancy with a new partner. With stepwise screening women identified as carriers had high levels of anxiety when results were received (mean anxiety score 52.3). This dissipated with a reassuring partner''s result (carriers'' mean anxiety score 36.1) to levels similar to those receiving negative results from couple screening. Of those receiving negative results, women who had stepwise screening were significantly less anxious than those who had couple screening (mean score with result 32.1 v 35.4, 95% confidence interval for difference -4.7 to -2.1). CONCLUSIONS--Couple screening allows carriers to avoid transient high levels of anxiety, but is associated with more anxiety and false reassurance among most screenees who will test negative. Stepwise screening gives carriers and their relatives genetic information and is, in our opinion, the better method.     

Prenatal genetic counseling for hemoglobinopathy carriers: a comparison of primary providers of prenatal care and professional genetic counselors.

Health personnel trained in medical genetics are insufficient to meet the demand for genetic services. Methods must be found to enable primary care providers to offer commonly needed genetic services themselves. In our recently reported community-wide prenatal screening program for hemoglobinopathies, 36% of women detected to have a hemoglobinopathy did not come to a tertiary center for counseling and thus may have not benefited from testing. To determine whether the efficiency of the program could be increased if counseling were provided by the prenatal care provider (obstetrician or family practitioner), we developed a pilot training program on the basis of our experience in offering such services and enlisted 68% of regional prenatal care providers to participate. The proportion of patients detected to have a hemoglobinopathy who received counseling was similar in the primary and tertiary provider groups: 59% versus 50%, respectively, for sickle trait, and 69% versus 66%, respectively, for beta-thalassemia trait. Knowledge after counseling was also similar for the primary and tertiary provider groups: 64% versus 66% (mean % correct), respectively, for sickle trait, and 79% versus 78%, respectively, for beta-thalassemia trait. However, the two provider groups significantly differed with regard to whether or not the patient had her partner tested. For sickle trait, it was 25% for the primary providers but 49% for the tertiary providers (P < .001). For beta-thalassemia trait, it was 47% for the primary providers but 78% for the tertiary providers (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Beta-thalassemia disease prevention: genetic medicine applied

We report here an evaluation of a program for thalassemia-disease prevention, comprising education, population screening for heterozygotes, and reproductive counseling; the evaluation includes cost analysis. A preprogram survey in 1978 of 3,247 citizens in the high-risk communities (85% were high-school students) showed that 88% favored a program but that only 31% considered fetal diagnosis as an acceptable option. Screening in high school or before marriage was preferred by 56%. In a 25-month period (December 1979-December 1982), we screened 6,748 persons, including 5,117 senior high-school students, using MCV/HbA2 indices. The participation rate was 80% in the high-school group. The frequency for beta-thalassemia heterozygosity was 4.7% with 10-fold variation among ethnic groups at risk; the overall frequency for all variants found was 5.4%. We surveyed 60 carriers and 120 noncarriers after screening high-school students (response rate 77%): most carriers told parents (95%) and friends (67%) the test result; and 38% of the carriers' parents (vs. 18% of the noncarriers' parents) were also screened. Carriers would ascertain their spouses' genotype (91%) and approved uniformly (95%) the high-school screening experience and its goal. We performed 11 fetal diagnoses in a 25-month interval (greater than 75% participation in target population) either by fetoscopy and globin-chain analysis or by amniocentesis and genomic DNA analysis; two of three affected fetuses were aborted at parental request, there was one spontaneous abortion (after fetoscopy), and seven live births. The at-risk couples claimed pregnancy would not be contemplated without the fetal-diagnosis option. We analyzed economic costs of the program: cost per case prevented is approximately equal to $ 6,700, slightly less than cost-per-patient-treatment-year or about 4% of undiscounted treatment cost incurred in the first 25 years of life for an affected individual. These findings indicate: collective acceptance of the program, appropriate attitudes among carriers, general acceptance and efficacy of fetal diagnosis, and global cost-effectiveness.     

Male Perspectives on Incorporating Men into Antenatal HIV Counseling and Testing

Background

Male partner involvement in antenatal voluntary HIV counseling and testing (VCT) has been shown to increase uptake of interventions to reduce the risk of HIV transmission in resource-limited settings. We aimed to identify methods for increasing male involvement in antenatal VCT and determine male correlates of accepting couple counseling in these settings.

Methodology/Principal Findings

We invited women presenting to a Nairobi antenatal clinic to return with their male partners for individual or couples VCT. Male attitudes towards VCT and correlates of accompanying female partners to antenatal clinic and receiving couple counseling were determined. Of 1,993 women who invited their partner, 313 (16%) returned with their partners to ANC. Men attending antenatal clinic were married (>99%), employed (98%), and unlikely to report prior HIV testing (14%). Wanting an HIV test (87%) or health information (11%) were the most commonly cited reasons for attending. Most (95%) men who came to antenatal clinic accepted HIV testing and 39% elected to receive counseling as a couple. Men who received counseling with partners were younger, had fewer children, and were less knowledgeable about prevention of mother-to-child HIV transmission (PMTCT) than those who received counseling individually (p<0.05). Only 27% of men stated they would prefer HIV testing at a site other than the ANC. There was agreement between male and female reports for sociodemographic characteristics; however, men were more likely to report HIV preventive behaviors and health communication within the partnership than their partners (p<0.05).

Conclusions/Significance

Offering VCT services to men at antenatal clinic with options for couple and individual counseling is an important opportunity and acceptable strategy for increasing male involvement in PMTCT and promoting male HIV testing.     

Audit of prenatal diagnosis for haemoglobin disorders in the United Kingdom: the first 20 years.

OBJECTIVES: To audit services for prenatal diagnosis for haemoglobin disorders in the United Kingdom. DESIGN: Comparison of the annual number of cases recorded in a United Kingdom register of prenatal diagnoses for haemoglobin disorders, with the annual number of pregnancies at risk of these disorders, by ethnic group and regional health authority. The number of pregnancies at risk was estimated using data on ethnic group from the 1991 census and data from the United Kingdom thalassaemia register, which records the number of babies born with thalassaemia. SETTING: The three national prenatal diagnosis centres for haemoglobin disorders. SUBJECTS: 2068 cases of prenatal diagnosis for haemoglobin disorders in the United Kingdom from 1974 to 1994. MAIN OUTCOME MEASURES: Utilisation of prenatal diagnosis by risk, ethnic group, and regional health authority. Proportion of referrals in the first trimester and before the birth of any affected child. RESULTS: National utilisation of prenatal diagnosis for haemoglobin disorders was around 20%. During the past 10 years it has remained steady at about 50% for thalassaemias and risen from 7% to 13% for sickle cell disorders. Utilisation for sickle cell disorders varies regionally from 2% to 20%. Utilisation for thalassaemias varies by ethnic group. It is almost 90% for Cypriots and ranges regionally for British Pakistanis from 0% to over 60%. About 60% of first prenatal diagnoses are done for couples without an affected child. Less than 50% of first referrals are in the first trimester. CONCLUSIONS: National utilisation of prenatal diagnosis for haemoglobin disorders is far lower than expected, and there are wide regional variations. A high proportion of referrals are still in the second trimester and after the birth of an affected child. The findings point to serious shortcomings in present antenatal screening practice and in local screening policies and to inadequate counselling resources, especially for British Pakistanis.     

Prenatal diagnosis of inherited hemoglobinopathies

In this paper we reviewed the different methods presently available for prenatal diagnosis of hemoglobin disorders and the impact of this technology in the control of beta-thalassemia in several Mediterranean populations. The vast majority of the inherited hemoglobinopathies can now be detected in the fetus by amniocyte or trophoblast DNA analysis. alpha-thalassemias, delta beta-thalassemias and gamma delta beta-thalassemias, which are usually caused by a gross structural rearrangement of the DNA, may be directly detected by Southern blot analysis. Only a few beta-thalassemia lesions are caused by gene deletion or affect a restriction recognition site and thus may be directly identified by this method. The major part of beta-thalassemia are due to single nucleotide substitution, small deletion or addition which do not alter a restriction recognition site. These mutations may be directly detected by complementary oligonucleotide probes. Alternatively, when normal or affected children are available, fetal diagnosis may be accomplished by linkage analysis with polymorphic restriction sites. Fetal blood analysis is used at present time for those cases presenting too late in the pregnancy for characterization of the molecular defect and in prospective parents in whom the defect is not known. Introduction of prenatal diagnosis in combination with carrier screening in several mediterranean populations led to a consistent reduction in the incidence of homozygous beta-thalassemia.     

Carrier screening for cystic fibrosis in a prenatal setting

Maternal prenatal cystic fibrosis (CF) screening was offered from September, 1997, to April, 1999, at the Ghent University Hospital, to couples undergoing prenatal diagnosis (amniocentesis) for reasons not related to CF. Fifteen minutes were devoted to explaining CF, CF screening, and the study protocol. The purpose was to assess the short- and long-term knowledge of CF, the attitude towards carrier screening, and carriership. A total of 314 couples entered the pilot study; 13 female CF carriers were identified. None of their partners carried an identifiable mutation. Our survey results show that information about CF and CF screening can be given effectively as part of antenatal care because most couples recalled important medical and genetic issues, valued the genetic test for CF, and seemed to cope well with the results. Risk estimates and actual numbers were more difficult to process and recall. From the small number of couples in which the woman alone was found to be a carrier, there was little or no evidence of marked distress.     

Consequences of Missed Opportunities for HIV Testing during Pregnancy and Delayed Diagnosis for Mexican Women,Children and Male Partners

Introduction

HIV testing during pregnancy permits prevention of vertical (mother-to-child) transmission and provides an opportunity for women living with HIV to access treatment for their own health. In 2001, Mexico’s National HIV Action Plan committed to universal offer of HIV testing to pregnant women, but in 2011, only 45.6% of women who attended antenatal care (ANC) were tested for HIV. The study objective was to document the consequences of missed opportunities for HIV testing and counseling during pregnancy and late HIV diagnosis for Mexican women living with HIV and their families.

Methods

Semi-structured-interviews with 55 women living with HIV who had had a pregnancy since 2001 were completed between 2009 and 2011. Interviews were analyzed thematically using a priori and inductive codes.

Results

Consistent with national statistics, less than half of the women living with HIV (42%) were offered HIV testing and counseling during ANC. When not diagnosed during ANC, women had multiple contacts with the health-care system due to their own and other family members’ AIDS-related complications before being diagnosed. Missed opportunities for HIV testing and counseling during antenatal care and health-care providers failure to recognize AIDS-related complications resulted in pediatric HIV infections, AIDS-related deaths of children and male partners, and HIV disease progression among women and other family members. In contrast, HIV diagnosis permitted timely access to interventions to prevent vertical HIV transmission and long-term care and treatment for women living with HIV.

Conclusions

Omissions of the offer of HIV testing and counseling in ANC and health-care providers’ failure to recognize AIDS-related complications had negative health, economic and emotional consequences. Scaling-up provider-initiated HIV testing and counseling within and beyond antenatal care and pre-service and in-service trainings on HIV and AIDS for health-care providers can hasten timely HIV diagnosis and contribute to improved individual and public health in Mexico.     

Cost effectiveness of antenatal screening for cystic fibrosis.

OBJECTIVE--To estimate the cost effectiveness of different antenatal screening programmes for cystic fibrosis. SETTING--Antenatal clinics and general practices in the United Kingdom. DESIGN--Four components of the screening process were identified: information giving, DNA testing, genetic counselling, and prenatal diagnosis. The component costs were derived from the literature and from a pilot screening study in Yorkshire. The cost of a given screening programme was then obtained by summing the components according to the specific screening strategy adopted (sequential and couple), the proportion of carriers detected by the DNA test, and the uptake of screening. Baseline assumptions were made about the proportion with missing information on carrier status from previous pregnancies (20%), the proportion changing partners between pregnancies (20%), and the uptake of prenatal diagnosis (100%). Sensitivity analysis was performed by varying these assumptions. MAIN OUTCOME MEASURE--Cost per affected pregnancy detected. RESULTS--Under the baseline assumptions sequential screening costs between pounds 40,000 and pounds 90,000 per affected pregnancy detected, depending on the carrier detection rate and uptake. Couple screening was more expensive, ranging from pounds 46,000 to pounds 104,000. From the sensitivity analysis a 10% change in the assumed proportion with missing information from a previous pregnancy alters the cost by pounds 4000; a 10% change in the proportion with new partners has a similar effect but only for couple screening; and cost will change directly in proportion to the uptake of prenatal diagnosis. CONCLUSIONS--While economic analysis cannot determine screening policy, the paper provides the NHS with the information on cost effectiveness needed to inform decisions on the introduction of a screening service for cystic fibrosis.     

Effects of Maternal Pregnancy Intention,Depressive Symptoms and Social Support on Risk of Low Birth Weight: A Prospective Study from Southwestern Ethiopia

Background

Low birth weight (LBW) is the principal risk factor for neonatal and infant mortality in developing countries. This study examines the effects of unwanted pregnancy, prenatal depression and social support on the risk of low birth weight in rural southwestern Ethiopia. We hypothesized that unwanted pregnancy and prenatal depression increase the risk of low birth weight, while social support mediates this association.

Methods

Data for the study comes from a prospective study in which women were followed from pregnancy through to delivery. Six hundred twenty two women were followed and 537 birth weights were measured within 72 hours. Multivariable log binomial regression was used to model the risk of low birth weight.

Results

The mean birth weight was 2989 grams (SD±504 grams), and the incidence of LBW was 17.88%. The mean birth weight of babies after unwanted pregnancy was 114 g lower compared to births from intended pregnancy. Similarly, mean birth weight for babies among women with symptoms of antenatal depression was 116 grams lower. Results of unadjusted log-binomial regression showed that unwanted pregnancy, prenatal depression and social support were associated with LBW. The relationship between antenatal depressive symptoms and LBW was mediated by the presence of social support, while the association between LBW and unwanted pregnancy remained after multivariable adjustment.

Conclusion

The incidence of low birth weight is high in the study area. Poverty, nonuse of antenatal care, low social support and unwanted pregnancy contribute to this high incidence of low birth weight. Hence, identifying women’s pregnancy intention during antenatal care visits, and providing appropriate counseling and social support will help improve birth outcomes.     

Evaluation of routine prenatal ultrasound examination in detecting fetal chromosomal abnormalities in a low risk population

Prenatal diagnosis performed by fetal ultrasound scan is now a routine part of antenatal care in many countries. We have used our registry of congenital malformations to determine how many fetal anomalies and consequently how many chromosomal abnormalities are detected by this procedure. In our region, evaluation of prenatal diagnosis of chromosomal abnormalities in women of 38 years and younger (chromosomal prenatal diagnosis is offered to women 38 years) with no personal or familial history of chromosomal anomaly was performed in 119 099 consecutive pregnancies of known outcome from 1980 to 1987. At least one ultrasonographic examination seeking congenital malformations was performed in more than 95% of the pregnant women studied. The total number of chromosomal anomalies during the study period was 199, 123 of these being Down syndrome. Only 41 (34.5%) of the 119 fetuses with chromosomal abnormalities and congenital malformation examined had been found to have a malformation at ultrasound examination. This low sensitivity was different for the diverse chromosomal abnormalities. Only 10 out of the 54 fetuses with Down syndrome and malformations (18.5%) were detected and only 3 out of 24 (12.5%) atrioventricular canal defects in those trisomie 21 patients were detected. Only 5 out of 11 (45.4%) fetuses with trisomy 13, 13 out of 26 (50.0%) fetuses with trisomy 18, 7 out of 12 patients with monosomy X (58.3%) and 6 out of 27 (22.2%) fetuses with other chromosomal abnormalities were diagnosed. Moreover, the time of detection of these anomalies was early enough to allow amniocentesis and termination of pregnancy in the case of a chromosomal abnormality in only 15 out of these 41 patients, including 7 cases of cystic hygroma in fetuses with monosomy X. This low sensitivity is not the result of the quality of the ultrasound equipment. It may be explained by the inadequate qualification of some operators and by the insufficient duration of the routine examination. In conclusion, our study has shown that the sensitivity of the detection of chromosomal abnormalities by routine prenatal ultrasound screening is low. Other screening methods are needed.     

胎盘特异性基因4 mRNA基因在孕妇外周血中的检测及临床价值

目的:应用实时荧光定量PCR(RT-PCR)技术对不同孕周孕妇外周血浆胎盘特异性基因4(PLAC4)m RNA基因进行检测,寻找唐氏综合征产前诊断的可靠生物学标志物,为无创性产前诊断提供新的突破口。方法:按入组标准随机选取健康育龄未妊娠女性5例,正常健康妊娠孕妇60例(早期妊娠20例、中期妊娠20例、晚期妊娠20例),唐氏筛查高危孕妇8例,正常分娩24 h女性5例。共收集外周血浆样本78例。应用RT-PCR技术,检测样本中的PLAC4 m RNA基因含量,并进行相对定量分析。结果:健康育龄未妊娠女性及正常分娩后24 h女性外周血浆中均无游离胎儿PLAC4 m RNA基因的存在;正常健康妊娠孕妇不同孕周标本均检测到PLAC4 m RNA基因,以早期妊娠作为对照,中期妊娠是早期妊娠的1.99倍,晚期妊娠是早期妊娠的3.73倍;唐氏筛查高危孕妇均检出PLAC4 m RNA基因,含量是早期妊娠的6.36倍。结论:PLAC4 m RNA基因有望成为唐氏综合征产前诊断的可靠性生物学标志物。