Factors influencing genetic counseling attendance rate: A geographically based study

Abstract

A study of factors influencing genetic counseling attendance rate has been conducted in the Bouches‐du‐Rhône area, in the south of France. In this area, a birth defects monitoring system (Eurocat n°22) annually covers 23,000 births. All the genetic services are delivered by only one genetic center located in Marseilles, and the data collected are computerized. The comparison of these two data bases gives an opportunity to estimate the rate of genetic counseling attendance after the occurrence of an affected stillbirth or live birth. Among the parents of 358 infants born in 1983–84 in this area with a pathology requiring genetic counseling, 226 (63 per cent) attended the Genetic Center within the first year after birth. The rate of attendance is statistically higher (p < 0.01) for the parents who had a stillbirth (78 per cent) than for those who had a live birth (57 per cent). It is also higher (p < 0.01) for the Marseilles maternities group (68 per cent) than for the group outside Marseilles (50 per cent). The referral delays are also analyzed according to malformation etiology and to viability of the child by the eighth day of lue. Besides evaluating a particular genetic center's effectiveness in diffusing information to the public concerned, this work shows that couples’ request is strongly dependent on a psychological need.     

Preimplantation Genetic Diagnosis and Natural Conception: A Comparison of Live Birth Rates in Patients with Recurrent Pregnancy Loss Associated with Translocation

Background

Established causes of recurrent pregnancy loss (RPL) include antiphospholipid syndrome, uterine anomalies, parental chromosomal abnormalities, particularly translocations, and abnormal embryonic karyotypes. The number of centers performing preimplantation genetic diagnosis (PGD) for patients with translocations has steadily increased worldwide. The live birth rate with PGD was reported to be 27-54%. The live birth rate with natural conception was reported to be 37-63% on the first trial and 65-83% cumulatively. To date, however, there has been no cohort study comparing age and the number of previous miscarriages in matched patients undergoing or not undergoing PGD. Thus, we compared the live birth rate of patients with RPL associated with a translocation undergoing PGD with that of patients who chose natural conception.

Methods and Findings

After genetic counseling, 52 patients who desired natural conception and 37 patients who chose PGD were matched for age and number of previous miscarriages and these comprised the subjects of our study. PGD was performed by means of fluorescence in situ hybridization analysis. The live birth rates on the first PGD trial and the first natural pregnancy after ascertainment of the carrier status were 37.8% and 53.8%, respectively (odds ratio 0.52, 95% confidence interval 0.22-1.23). Cumulative live birth rates were 67.6% and 65.4%, respectively, in the groups undergoing and not undergoing PGD. The time required to become pregnancy was similar in both groups. PGD was found to reduce the miscarriage rate significantly. The prevalence of twin pregnancies was significantly higher in the PGD group. The cost of PGD was $7,956 U.S. per patient.

Conclusions

While PGD significantly prevented further miscarriages, there was no difference in the live birth rate. Couples should be fully informed of the similarity in the live birth rate, the similarity in time to become pregnancy, the advantages of PGD, such as the reduction in the miscarriage rate, as well as its disadvantages, such as the higher cost, and the advantages of a natural pregnancy, such as the avoidance of IVF failure. The findings presented here should be incorporated into the genetic counseling of patients with RPL and carrying a translocation.     

Contraceptive use and efficacy in a genetically counseled population

Abstract

This paper reports contraceptive use and efficacy rates among 648 married women aged 15 to 44 who had received genetic counseling six months previously. Over half (53.5 per cent) of the counseled population were using non‐surgical contraception; 20 per cent were pregnant or postpartum; 10 per cent were seeking to become pregnant; 11 per cent were sterilized. Only 4.5 per cent were neither using contraceptives nor seeking to become pregnant. Women who were certain about their reproductive intentions after counseling utilized contraceptives effectively, with only two pregnancies at six months among those seeking to delay wanted pregnancies and only one pregnancy among those seeking to prevent pregnancy. This represents six‐month contraceptive failure rates of 4.3 and 2.1 per cent respectively for the two groups, rates similar to those with comparable intentions in the U. S. population at large. A distinguishing characteristic of the genetically counseled group was that 32 per cent of contraceptive users reported that their reproductive intentions were uncertain after counseling. The six‐month pregnancy rate in this uncertain group was 10 per cent.     

Mourning response and intervention in stillbirth: An alternative genetic counseling approach

Abstract

Stillbirth is a frequently occurring tragedy that causes intense problems for parents experiencing it. A review of the literature suggests that the grief response of parents to stillbirth or neonatal death may present more problems than do other types of bereavement. An assessment of these problems suggests that a successful plan for management requires intervention as soon as possible after the death occurs. A protocol for such intervention is presented. It is suggested that such intervention is the proper domain of genetic counselors and represents an expanded approach to genetic counseling, particularly in the light of the recent movement toward a more psychologically oriented paradigm of genetic counseling.     

A TEN-YEAR STUDY OF ANENCEPHALY

The incidence of anencephaly at the Los Angeles County General Hospital during the period of July, 1948 through June, 1958 was 0.049 per cent. Worldwide the range of reported incidence is 0.012 per cent to 0.671 per cent.In this study 65 per cent of the total number of anencephalics delivered were females, a predominance agreeing with reports by other investigators.Polyhydramnios appeared in 38 per cent of the anencephalic pregnancies of this study, while 15 per cent of the deliveries were complicated by placenta praevia.A significant number (48 per cent) of the multiparae gave a history of previous stillbirths or abortions.The present study does not support observations by other investigators which indicated an increase in anencephalic births during the winter months.Evidence from stillbirth statistics would seem to indicate that anencephaly is primarily a genetically induced phenomenon. Further evaluation and analysis of the predominance of females in anencephalic stillbirths and abortions is suggested, in order to study whether the observed secondary or birth sex ratio (in which males predominate) is, in fact, due to genetic effect.     

Natural selection and reproductive behavior in Italy, 1930-1993

We studied the relaxation of natural selection affecting the newborn population in Italy between 1930 and 1993 due to the decrease in the stillbirth (mortality) rate and the simultaneous changes in women's reproductive behavior (strategies). Results show that, apart from a drastic overall reduction, the stillbirth rate has varied among different groups of neonates. The present stillbirth rate of less than 5 per thousand, observed in 8 of the 20 phenotypic classes defined on the basis of maternal age at delivery and neonate birth order, most likely represents an unavoidable biological or genetic cost. A 9 per thousand stillbirth rate, about twice the potential minimum, exists among neonates born to women delivering at advanced age (> or = 35): the risk they face at the first or, in adverse living conditions, the fourth pregnancy could, however, be decreased by a policy aimed at countering the tendency to delay maternity and improving antenatal care in economically disadvantaged areas of the country.     

Impact of BRCA1 testing on women with cancer: a pilot study

We sought to understand better the impact of genetic testing and counseling in a group of women who had early breast cancer (age <50) or ovarian cancer and a family history of cancer. Thirty-five women underwent genetic counseling and genetic testing for BRCA1/2 at the University of Colorado Cancer Center, Hereditary Cancer Clinic. Psychological assessment (IES and Hopkins Symptom Checklist) was made before counseling, and 1 month after genetic test results were reported to women. A statistically significant decrease in anxiety was evidenced 1 month after results were given (p = 0.024). Decreased intrusive thoughts related to genetic testing were seen only for those testing negative (p = 0.0003). Women diagnosed with cancer less than 1 year prior to genetic testing experienced the greatest cancer-specific distress (p = 0.01) and distress related to genetic testing (p = not significant). Satisfaction with the counseling and testing process was high. In conclusion, genetic testing and counseling can occur with little anxiety and stress. However, women less than 1 year from a cancer diagnosis will experience the greatest distress associated with genetic testing and counseling. Women who are considering genetic testing and counseling close to a diagnosis of cancer may require greater psychological support.     

A retrospective study of infant mortality of cotton-top tamarins (Saguinus oedipus) in captive breeding

Fifty of 156 (32%) colony bred cotton-top tamarins were stillborn, and 31 (20%) died within the first week after birth. The stillbirth rate was related to litter size and parity in captivity. A higher percent of single births were stillborn (69%) compared to those of twin births (26%) (p less than 0.005). A higher percent of infants born of the first litter in captivity (42%) were stillborn than those of subsequent litters (23%) (p less than 0.025). Stillbirths were not related to season of birth or sex of infant. Survival of live infants was unrelated to season of birth, sex, litter size, or number of litters.     

Cystic fibrosis newborn screening: a pilot study to maximize carrier screening

Newborn screening for cystic fibrosis (CF) is expanding because early diagnosis has been shown to result in improved nutrition and growth. Most newborns identified by a mutation panel have a single detected mutation and require sweat testing to exclude an additional undetected mutation. The resulting identification of CF carrier newborns, although not the primary purpose of screening, has three potential benefits, (1) the detection of trait-trait couples, (2) presymptomatic testing of these couples' previously born children who may have undetected CF, and (3) a carrier parent alerting his/her extended family members to the chance of also being a CF carrier. Reaping each benefit requires genetic counseling of parents and their accepting carrier testing. The purpose of this study was to utilize the sweat testing visit to educate parents about the value of carrier testing for themselves and their blood relatives. We compared special care (genetic counseling after explaining the sweat test result and offering of parental DNA testing, all on the sweat test visit) versus standard care (sweat test result reported by phone to the parents the next day by the newborn's physician, ideally with the recommendation to arrange genetic counseling and parental carrier testing). In the first year of New York State CF screening, 64 newborns with one detected mutation were reported in the nine-county region that includes Rochester. Of these, parents of 39 agreed to participate in the study and to be randomized to special or standard care. Sixty-one parents completed both the initial and 1-year follow-up questionnaires (30 couples and one mother). Of the 61 parents, 23 had carrier testing after the birth of the baby. The frequency of such parental testing was significantly higher in the special care group (17/34 or 50%) than in the standard care group (6/27 or 22%) (p < 0.05). This is the first evidence from a randomized trial that genetic counseling and offering carrier testing to parents on the sweat test visit increases identification of carrier parents. Such identification detects trait-trait parents and facilitates carrier testing among relatives.     

Genetic screening and genetic counseling: knowledge, attitudes, and practices in two groups of family planning professionals.

67 obstetrical and gynecological physicians and 102 professional staff members of family planning clinics (FPCs) in the Pittsburgh, Pennsylvania, area returned questionnaires relating to knowledge of basic genetic principles and attitudes towards genetic screening and genetic counseling. The best understood genetic risk was Down's syndrome in children born to mothers over 40 years of age. Nearly 90% of physicians and 85% of FPC staff knew this but only 12% of physicians and 30% of FPC staff knew it is caused by chromosomal aberration. Next best understood defect is sickle cell anemia. In overall knowledge the physicians had a mean score of 4.45 of 7 genetic questions, FPC staff, 3.32. However, FPC workers who had received in-service genetic training scored 4.42 (p less than .001). Knowledge of the 2 genetic clinics in the area and acceptance of the principles of genetic screening were associated with the individual's acceptance of sterilization as a method of birth control and acceptance of abortion if the fetus had significant risk of being born deformed. Both of these associations were at the significant level for both physicians and FPC workers. Both physicians and FPC workers who have themselves had genetic counseling or who have family members who have had such counseling show higher acceptance levels. An association was also found between acceptance and genetic educational background. About 92% of respondents who had read articles or textbooks pertaining to genetics during the preceding year approved of including genetic information as part of maternal and child health projects compared with 82% of those who had not (p less than .02). Among the physicians 36% felt it should be required, 34% voluntary, and 30% did not know; for FPC workers, 59, 27, and 14%, respectively. Protestants and Jews tended to favor required premarital screening while Catholics tended to oppose it (p less than .007). It is disconcerting that over 50% of the physicians did not know the recurrence risk of PKU and over 20% did not know the gene is the basic unit of inheritance. While it is true that over 1/2 completed basic professional education more than 20 years ago when genetics was not part of the medical school curriculums this basic knowledge needs to have been acquired during continuing medical education. In this study more than 1/3 of the FPC staff indicated they had been asked to provide genetic counseling or had referred clients. This points up the importance of such workers in a comprehensive genetic counseling service.     

Causes of low utilization of amniocentesis by women of advanced maternal age

Abstract

The objectives of this study were to determine current usage of amniocentesis by women of advanced maternal age in a southwestern Ohio county and to determine potential usage levels by surveying women not utilizing the procedure to understand their reasons. For women age 35 and older giving birth in Hamilton County, Ohio, the estimated percentage using amniocentesis was 3.9 in 1978, 7.6 in 1979, and 13.3 in 1980. Approximately comparable statewide utilization rates were 7.0, 11.5, and 17.2 respectively. A telephone survey during the summer of 1980 of 81 Hamilton County women age 35 and older recently giving birth to a normal baby found four main reasons why they did not utilize amniocentesis: (1) they did not feel at an increased risk (29.6 per cent); (2) they had never heard of the test (24.7 per cent); (3) they were opposed to abortion (21.0 per cent); and (4) no one suggested they have the test done (19.8 per cent). Their physicians reported that 81 per cent of these women had received prenatal counseling. Thus, of those counseled, over two‐thirds apparently missed at least one essential message of the counseling they were presumably provided. These findings, coupled with 47.7 per cent of women who knew about amniocentesis saying they would most likely use it if they became pregnant again and their physician recommended it, indicate that utilization of prenatal diagnosis by at least 50 per cent of women age 35 and older is likely with greater public education and greater support of the procedure by obstetricians.     

The management and outcome of higher order multifetal pregnancies: obstetric, neonatal and follow-up data.

The objective of this study was to describe current obstetric, neonatal, and long-term neurodevelopmental outcomes of higher order multifetal gestations (> or = 3 fetuses) in the 1990s. We also intended to identify a target gestational age at which neonatal and neurodevelopmental morbidities are low. Records from all multifetal pregnancies (> or = 3 viable fetuses > or = 20 weeks gestation) delivered at the two perinatal centers in Toronto, Ontario, Canada during the study period (January 1, 1990-December 31, 1996) were reviewed. Data were collected on obstetric, neonatal, and long-term neurodevelopmental outcomes. Follow up data were gathered regarding the presence of a severe deficit in four categories (vision, hearing, cognition, and motor skills). Statistical analysis was performed to determine a gestational age at which a significant decrease in deficit occurred. During the study period 165 multifetal pregnancies were delivered. This resulted in 511 fetuses, of which 496 were live births. Of these 496 infants, 453 survived to discharge. Follow up data were obtained on 332 (73.3 per cent) infants. Infant survival increased with gestational age, and was approximately 90 per cent or greater at 26 weeks or more. Of all infants followed, the proportion of those without deficit increased with increasing gestational age, such that the percent without deficit was 96.9 at 31 weeks or greater. Of all infants followed, 301 (90.7 per cent) had no deficit. Statistical analysis revealed a significant difference in long-term neurodevelopmental outcome between infants born before and after 28 weeks gestation. The incidence of a major deficit was 44.1 per cent for those born earlier than and 5.4 per cent for those born later than this gestational age (p = 0.001). In our cohort, survival figures were high. Even in lower gestational groupings, survival was high, but not without serious concerns about severe morbidity. This information is useful when counseling parents of higher order multifetal pregnancies.     

Performance and financial consequences of stillbirth in Holstein dairy cattle

Stillbirth is an economically important trait on dairy farms. Knowledge of the consequences of, and the economic losses associated with stillbirth can help the producer when making management decisions. The objectives of this study were to determine the effects of stillbirth on productive and reproductive performance as well as financial losses due to stillbirth incidence in Iranian Holstein dairy farms. Economic and performance data were collected from nine Holstein dairy farms in Isfahan and Khorasan provinces of Iran from March 2008 to December 2013. The final data set included 160 410 calving records from 53 265 cows. A linear mixed model was developed to evaluate the effects of stillbirth on performance of primiparous and multiparous cows separately and overall. An economic model was used to estimate the economic losses due to stillbirth. The incidence of stillbirth cases per cow per year was 4.2% on average (3.4% to 6.8% at herd level). The least square means results showed that a case of stillbirth significantly (P<0.05) reduced 305-day milk production in multiparous cows and overall, but had no significant effects on primiparous cows production performance (P>0.05). Overall, a case of stillbirth reduced 305-day milk yield by 544.0±76.5 kg/cow per lactation. Stillbirth had no significant effects on 305-day fat and protein percentages in either primiparous or multiparous cows. Overall, cows that gave birth to stillborn calves had significantly increased days open by 14.6±2.6 days and the number of inseminations per conception by 0.2 compared with cows that gave birth to live calves (P<0.01). In general, the negative productive and reproductive effects associated with stillbirth were smaller and non-significant for primiparous cows compared with multiparous cows. The financial losses associated with stillbirth incidence averaged US$ 938 per case (range from $US 767 to $US 1189 in the nine investigated farms). The loss of a calf was not the only cost associated with stillbirth, as it accounted for 71.0% of the total cost. The costs of dystocia (7.6%) and culling and replacement expenses (6.3%) were the next most important costs associated with stillbirth. These results can be used to assess the potential return from management strategies to reduce the occurrence of stillbirths.     

Live Birth and Cumulative Live Birth Rates in Expected Poor Ovarian Responders Defined by the Bologna Criteria Following IVF/ICSI Treatment

ObjectiveTo determine the live birth and cumulative live birth rates of expected poor ovarian responders according to the Bologna criteria and to compare their outcomes with those of expected normal respondersDesignRetrospective analysisSettingUniversity infertility clinicPatientsA total of 1,152 subfertile women undergoing their first in vitro fertilization (IVF) cycleInterventionsWomen were classified into 4 groups according to the Bologna criteria for comparisonResultsWomen with expected poor response (POR) had the lowest live birth rate than the other 3 groups (23.8%, p = 0.031). Cumulative live birth rates were significantly lower in those with expected POR than those with expected normal ovarian response (NOR) (35.8% vs 62.8%, p<0.0001). In the subgroup analysis, the cumulative live birth rates in expected PORs were significantly lower in those who had ≤3 oocytes retrieved (18.6% for ≤3 oocytes vs 44.0% for >3 oocytes, p = 0.006) whereas the live birth rates in fresh cycle did not differ (17.8% vs 30.9%, p = 0.108).ConclusionWomen who were expected POR according to the Bologna criteria had lower live birth and cumulative live birth than expected NOR but they still can achieve reasonable treatment outcomes and IVF treatment should not be precluded.     

A multiple pregnancy register in the north of England.

A regional population-based Multiple Pregnancy Register was established in 1998, with the aim of collecting detailed information on multiple pregnancies to enable research into mortality and morbidity in multiples. Multiple pregnancies are notified to the Register as soon as they are detected, irrespective of whether they resulted in a spontaneous abortion, termination of pregnancy or registered birth. Nine hundred and twenty-six twin pregnancies were recorded during 1998-99, giving a twinning rate of 14.8 per 1000 maternities (rate at birth 13.0 per 1000 maternities). Sixty one per cent of twin pregnancies were detected before 13 weeks of gestation. Chorionicity was determined in 82.6% of 849 twin maternities with at least one stillbirth or livebirth. The fetal loss rate before 24 weeks of gestation was 10.5% (194/1852). The perinatal and infant mortality rates were 40.6 per 1000 births and 32.6 per 1000 livebirths respectively. A prospective Multiple Pregnancy Register not only allows monitoring of trends in multiple birth rates and mortality, but also etiological research and long-term follow-up studies.     

Stillbirth pattern in an isolated mediterranean population: La Alpujarra, Spain

This study attempted to analyze the effect of several factors on the stillbirth pattern in a relatively isolated rural population, La Alpujarra (Spain), during the first half of the 20th century. The study was a retrospective analysis from a total sample of 2199 births to 525 mothers, allowing for birth year of mother, maternal age, parental inbreeding, family size, birth order, sex, single/twin delivery, and birth interval. Binomial probability distribution of stillbirths provided no evidence for any significantly increased risk in relation to family size. Analysis of covariance (ANCOVA) of stillbirth risk in affected families indicated a significant effect for sex of the child, parental consanguinity, and birth year of mother. Logistic regression showed increased risk in twin delivery and pregnancy order one, but not for birth order other than one. Multivariate analysis of variance (MANOVA) testing for differences between affected and unaffected families supported a temporal decrease of stillbirths during the period studied. Although the birth interval average was significantly shorter in affected families (p < 0.0001), this association did not hold, in a more detailed analysis, for individual intervals in these families (p = 0.20). There was no significant effect of maternal age on stillbirths in the whole sample or limited to first pregnancies. These results suggest that birth order one and twin delivery were the main determinants of the stillbirth pattern in La Alpujarra. Furthermore, our data indicate that the decline in stillbirth rate began before medical facilities for perinatal care became available, which was not until after 1950. The temporal decrease in stillbirth rates may therefore be related to an increasing social attention to deliveries rather than to prenatal care medical facilities.     

Impact of highly purified versus recombinant follicle stimulating hormone on oocyte quality and embryo development in intracytoplasmic sperm injection cycles

The quality of oocytes and developing embryos are the most relevant factors determining the success of an in vitro fertilization (IVF) treatment. However, there are very few studies analyzing the effects of different gonadotrophin preparations on oocyte and embryo quality. A retrospective secondary analysis of data collected from a prospective randomized study was performed to compare highly purified versus recombinant follicle stimulating hormone (HP-FSH vs. rFSH). The main outcome measures were quantity and quality of oocytes and embryos, dynamics of embryo development, cryopreservation, clinical pregnancy and live birth rate. The number of retrieved and of mature (MII) oocytes showed no significant differences. Fertilization rate was significantly higher in the HP-FSH group (68.9% vs. 59.9%, p = 0.01). We also found significantly higher rate of cryopreserved embryos per all retrieved oocytes (23.4% vs. 14.5%, p = 0.002) in the HP-FSH group. There were no significant differences in clinical pregnancy and in live birth rates. Oocytes obtained with HP-FSH stimulation showed higher fertilisability, whereas pregnancy and live birth rates did not differ between the groups. However, patients treated with HP-FSH may benefit from the higher rate of embryos capable for cryopreservation, suggesting that cumulative pregnancy rates might be higher in this group.     

Perinatal mortality in eastern Uganda: a community based prospective cohort study

Background

To achieve a child mortality reduction according to millennium development goal 4, it is necessary to considerably reduce neonatal mortality. We report stillbirth and early neonatal mortality risks as well as determinants of perinatal mortality in Eastern Uganda.

Methods

A community-based prospective cohort study was conducted between 2006 and 2008. A total of 835 pregnant women were followed up for pregnancy outcome and survival of their children until 7 days after delivery. Mother''s residence, age, parity, bed net use and whether delivery took place at home were included in multivariable regression analyses to identify risk factors for perinatal death.

Results

The stillbirth risk was 19 per 1,000 pregnancies and the early neonatal death risk 22 per 1,000 live births. Overall, the perinatal mortality risk was 41 [95%CI: 27, 54] per 1,000 pregnancies. Of the deaths, 47% followed complicated deliveries and 24% preterm births. Perinatal mortality was 63/1,000 pregnancies among teenage mothers, 76/1,000 pregnancies among nulliparous women and 61/1,000 pregnancies among women delivering at home who, after controlling for potential confounders, had a 3.7 (95%CI: 1.8, 7.4) times higher perinatal mortality than women who gave birth in a health facility. This association was considerably stronger among nulliparous women [RR 8.0 (95%CI: 2.9, 21.6)] than among women with a previous live birth [RR 1.8 (95%CI: 0.7, 4.5)]. All perinatal deaths occurred among women who did not sleep under a mosquito net. Women living in urban slums had a higher risk of losing their babies than those in rural areas [RR: 2.7 (95%CI: 1.4, 5.3)].

Conclusion

Our findings strengthen arguments for ensuring that pregnant women have access to and use adequate delivery facilities and bed nets.     

Factors determining dissemination of results and uptake of genetic testing in families with known BRCA1/2 mutations

BACKGROUND: Uptake of genetic testing remains low, even in families with known BRCA1 and BRCA2 (BRCA1/2) mutations, despite effective interventions to reduce risk. We report disclosure and uptake patterns by BRCA1/2-positive individuals to at-risk relatives, in the setting of no-cost genetic counseling and testing. METHODS: Relatives of BRCA1/2-positive individuals were offered cost-free and confidential genetic counseling and testing. If positive for a BRCA1/2 mutation, participants were eligible to complete a survey about their disclosure of mutation status and the subsequent uptake of genetic testing by at-risk family members. RESULTS: One hundred and fifteen of 142 eligible individuals responded to the survey (81%). Eighty-eight (77%) of those surveyed disclosed results to all at-risk relatives. Disclosure to first-degree relatives (FDRs) was higher than to second-degree relatives (SDRs) and third-degree relatives (TDR) (95% vs. 78%; p < 0.01). Disclosure rates to male versus female relatives were similar, but reported completion of genetic testing was higher among female versus male FDRs (73% vs. 49%; p < 0.01) and SDRs (68% vs. 43%; p < 0.01), and among members of maternal versus paternal lineages (63% vs. 0%; p < 0.01). Men were more likely than women to express general difficulty discussing positive BCRA1/2 results with at-risk family members (90% vs. 70%; p = 0.03), while women reported more emotional distress associated with disclosure than men (48% vs. 13%; p < 0.01). DISCUSSION: We report a very high rate of disclosure of genetic testing information to at-risk relatives. However, uptake of genetic testing among at-risk individuals was low despite cost-free testing services, particularly in men, SDRs, and members of paternal lineages. The complete lack of testing among paternally related at-risk individuals and the lower testing uptake among men signify a significant barrier to testing and a challenge for genetic counselors and physicians working with high-risk groups. Further research is necessary to ensure that family members understand their risk and the potential benefits of genetic counseling.     

Outcomes of pregnancy in insulin dependent diabetic women: results of a five year population cohort study.

OBJECTIVE: To monitor pregnancies in women with pre-existent insulin dependent diabetes for pregnancy loss, congenital malformations, and fetal growth in a geographically defined area of north west England. DESIGN: Population cohort study. SETTING: 10 maternity units in Cheshire, Lancashire, and Merseyside which had no regional guidelines for the management of pregnancy in diabetic women. SUBJECTS: 462 pregnancies in 355 women with insulin dependent diabetes from the 10 centres over five years (1990-4 inclusive). MAIN OUTCOME MEASURES: Numbers and rates of miscarriages, stillbirths, and neonatal and postneonatal deaths; prevalence of congenital malformations; birth weight in relation to gestational age. RESULTS: Among 462 pregnancies, 351 (76%) resulted in a liveborn infant, 78 (17%) aborted spontaneously, nine (2%) resulted in stillbirth, and 24 (5%) were terminated. Of the terminations, nine were for congenital malformation. The stillbirth rate was 25.0/1000 total births (95% confidence interval 8.9 to 41.1) compared with a population rate of 5.0/1000, and infant mortality was 19.9/1000 live births (5.3 to 34.6) compared with 6.8/1000. The prevalence of congenital malformations was 94.0/1000 live births (63.5 to 124.5) compared with 9.7/1000 in the general population. When corrected for gestational age, mean birth weight in the sample was 1.3 standard deviations greater than that of infants of non-diabetic mothers. Infants with congenital malformations weighed less than those without. CONCLUSION: In an unselected population the infants of women with pre-existent insulin dependent diabetes mellitus have a 10-fold greater risk of a congenital malformation and a fivefold greater risk of being stillborn than infants in the general population. Further improvements in the management of pregnancy in diabetic women are needed if target of the St Vincent declaration of 1989 is to be met.