RESUMEN
OBJECTIVE: The proportion of circulating cell free DNA derived from the feto-placental unit (fetal fraction or FF) correlates with test success and interpretation reliability. Some fetal disorders are associated with systematically lower FF, sometimes resulting in noninformative results. METHODS: We analyzed results from pregnancies tested in a nested case/control study derived from a cohort of 4664 high-risk pregnancies. Low FF was defined before and after adjusting for maternal weight and gestational age. RESULTS: Compared with euploid pregnancies, the median FF was significantly higher in Down syndrome pregnancies (ratio 1.17) and significantly lower in trisomy 18 and triploid pregnancies (ratios 0.71 and 0.19, respectively). Among 2157 pregnancies tested, 13 (0.6%) had FF <3.0% (all noninformative), including three trisomy 18 and three triploidy fetuses. After adjustment, 16 pregnancies (0.7%) had FF <0.3 multiples of the median (six informative), including one trisomy 18 and three triploidy fetuses. Modeled positive predictive values for low and high-risk populations were 7% and 30%, respectively. CONCLUSION: Among women with noninformative results attributable to low FF, trisomy 18 and/or triploidy risk are sufficiently high to warrant offering additional assessments (e.g. ultrasound). If the testing indication is ultrasound abnormality, amniocentesis and karyotype/microarray should be considered. © 2014 John Wiley & Sons, Ltd.
Asunto(s)
ADN/metabolismo , Síndrome de Down/metabolismo , Feto/metabolismo , Síndrome de Turner/metabolismo , Adulto , Amniocentesis , Estudios de Casos y Controles , Cromosomas Humanos Par 18/genética , Cromosomas Humanos Par 18/metabolismo , Estudios de Cohortes , ADN/genética , Síndrome de Down/genética , Femenino , Humanos , Cariotipificación , Masculino , Embarazo , Embarazo de Alto Riesgo , Diagnóstico Prenatal , Trisomía/genética , Síndrome de la Trisomía 18 , Síndrome de Turner/genéticaRESUMEN
PURPOSE: To summarize a conference convened to examine how cystic fibrosis screening might appropriately be introduced into routine prenatal practice. METHODS: Participants included experts from various relevant disciplines. Systematic reviews and data from individual trials were presented; issues were identified and discussed. RESULTS: Judged by published criteria, prenatal cystic fibrosis screening is suitable for introduction. Screening can be performed cost-effectively by identifying racial/ethnic groups at sufficient risk and then using either of two models for delivering laboratory services. Validated educational materials exist. Ethical issues are not unique. CONCLUSIONS: Once adequate facilities for patient and provider education, testing, counseling, quality control, and monitoring are in place, individual programs can begin prenatal screening for cystic fibrosis.
Asunto(s)
Fibrosis Quística/diagnóstico , Fibrosis Quística/genética , Asesoramiento Genético , Pruebas Genéticas , Diagnóstico Prenatal , Ensayos Clínicos como Asunto , Revelación , Ética Médica , Femenino , Asesoramiento Genético/economía , Asesoramiento Genético/tendencias , Pruebas Genéticas/economía , Pruebas Genéticas/tendencias , Humanos , Masculino , Mutación , Diagnóstico Prenatal/economía , Diagnóstico Prenatal/tendencias , Relaciones Profesional-Paciente , Factores de RiesgoRESUMEN
This study examines a couple-based screening protocol for cystic fibrosis (CF) during pregnancy. The screening test is positive only when both partners carry an identifiable mutation. The risk for the fetus to be homozygous is 1 in 4, and definitive prenatal diagnostic testing can be offered. Between six and seven of every ten CF cases can be identified by testing for seven CF mutations. Couple screening for CF has not been evaluated in a decentralized health-care system. Office guides, informational materials, and consent forms were provided to 69 physicians in Maine. Women sent buccal samples to the study centre and brought sampling materials to their partners. Samples from both individuals were required. When a mutation was identified in the woman's sample, the partner's sample was tested. Screening results were reported to the physician. Standardized follow-up surveys were carried out in selected women, key office staff, and physicians. 1770 women and 1682 partners submitted samples. Testing was successfully completed for 1645 couples. Screening results were positive in one couple; the fetus was homozygous for CF. Physicians, office staff, and nearly all women were satisfied with the screening process. Couple screening for CF is feasible and acceptable in decentralized primary care settings.
Asunto(s)
Fibrosis Quística/prevención & control , Atención Prenatal/normas , Diagnóstico Prenatal/normas , Atención Primaria de Salud/normas , Adulto , Alelos , Mejilla , Fibrosis Quística/epidemiología , Fibrosis Quística/genética , ADN/análisis , ADN/aislamiento & purificación , Análisis Mutacional de ADN , Recolección de Datos/métodos , Recolección de Datos/estadística & datos numéricos , Femenino , Frecuencia de los Genes , Asesoramiento Genético , Pruebas Genéticas , Humanos , Maine/epidemiología , Masculino , Mucosa Bucal/citología , Satisfacción del Paciente , Proyectos Piloto , Embarazo , Atención Prenatal/estadística & datos numéricos , Diagnóstico Prenatal/estadística & datos numéricos , Atención Primaria de Salud/estadística & datos numéricos , Juego de Reactivos para DiagnósticoRESUMEN
OBJECTIVE: To investigate the feasibility and impact of integrating a cotinine-assisted smoking intervention programme with an existing antenatal maternal serum alpha-fetoprotein (AFP) screening service for open neural tube defects. DESIGN: A multisite randomized controlled trial. SETTING: 139 physician offices and clinic sites in Maine providing antenatal care. SUBJECTS: 2848 pregnant women who smoked 10 or more cigarettes daily, enrolled at between 15 and 20 weeks gestation, from a population base of approximately 18,000 pregnancies. INTERVENTIONS: The women were individually allocated at random to intervention or control groups within each centre at the time the serum sample was received for AFP measurement. The intervention group received an interpreted measurement of the serum cotinine, reported through the physician to the woman, along with a self-help smoking cessation booklet and a repeat serum cotinine measurement one month later, again interpreted and reported through the physician to the woman. Women in the control group received the usual anti-smoking advice provided by the antenatal care site and were not told of the study. MAIN OUTCOME MEASURES: Birthweight, physician cooperation with study protocol (as measured by effectiveness in obtaining repeat serum samples for cotinine measurements). RESULTS: Pregnancy outcome data were available for 97% of the study population, including birthweight for 2700 singleton viable pregnancies. The smoking intervention programme led to a significant 66 g increase in mean birthweight (P = 0.03; 95% CI+9 to +123 g) and to a 30% reduction in the rate of low birthweight in pregnancies managed by the 70 physicians who secured the highest rate of obtaining repeat serum samples for cotinine measurements in their intervention group. Among the remaining 69 physicians, intervention had no detectable effect on birthweight. CONCLUSION: A cotinine-assisted smoking intervention programme managed from a central location as an adjunct to a maternal serum AFP screening service can, with the cooperation of physicians responsible for antenatal care, lead to a significant and cost-effective reduction in the number of low birthweight babies. This programme is inexpensive, requires little extra effort, and does not need specially trained personnel.
Asunto(s)
Cotinina/sangre , Recién Nacido de Bajo Peso , Cooperación del Paciente , Prevención del Hábito de Fumar , alfa-Fetoproteínas/análisis , Adulto , Análisis Costo-Beneficio , Femenino , Edad Gestacional , Humanos , Recién Nacido , Embarazo , Autocuidado/métodosAsunto(s)
Biomarcadores/sangre , Síndrome de Down/diagnóstico , Asesoramiento Genético/métodos , Pruebas Genéticas/métodos , Embarazo/sangre , Diagnóstico Prenatal/métodos , alfa-Fetoproteínas/química , Síndrome de Down/epidemiología , Síndrome de Down/genética , Femenino , Pruebas Genéticas/normas , Pruebas Genéticas/tendencias , Política de Salud , Humanos , Edad Materna , Diagnóstico Prenatal/normas , Diagnóstico Prenatal/tendencias , Relaciones Profesional-Paciente , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
The concentration of serum cotinine (the major metabolite of nicotine) was measured in sera from 4211 women at between 15 and 21 weeks gestation to determine whether a serum cotinine level was a better predictor of low birthweight than the self-reported number of cigarettes smoked per day. Both cotinine levels and smoking history were significantly associated with reduced birthweight, but cotinine correlated significantly better. Smokers of greater than or equal to 25 cigarettes per day, representing the 2.7% of women with the greatest cigarette consumption, had infants 289 g lighter than the 68% of women who were nonsmokers. Women with serum cotinine levels in the top 2.7% (greater than or equal to 284 ng/ml) had infants 441 g lighter than the 68% of women with the lowest cotinine levels (less than or equal to 24 ng/ml). Our results strengthen the evidence linking smoking with low birthweight and also demonstrate that cotinine can be satisfactorily used to assess and monitor cigarette smoking in pregnancy.
Asunto(s)
Peso al Nacer , Cotinina/sangre , Pirrolidinonas/sangre , Fumar , Femenino , Humanos , Recién Nacido , Embarazo , Segundo Trimestre del EmbarazoAsunto(s)
Defectos del Tubo Neural/etiología , Complicaciones Posoperatorias , Estómago/cirugía , Adulto , Dieta , Femenino , Humanos , Recién Nacido , Yeyuno/cirugía , Métodos , Obesidad/terapia , EmbarazoRESUMEN
To assess the interrelation between maternal serum alpha-fetoprotein (MSAFP) levels and vaginal bleeding as a combined pregnancy risk factor, we studied 6829 singleton pregnancies without fetal malformations during the second trimester. The predictive powers of the two risk factors, analysed separately, are consistent with published reports in relation to fetal death and low birthweight. Until now, however, these two risk factors have not been analysed together. The present study demonstrates that MSAFP and vaginal bleeding are largely independent of each other as predictors of fetal death, relative risks being 0.7 (MSAFP less than 0.7 multiples of the median (MoM), vaginal bleeding absent), 3.5 (MSAFP less than 2.0 MoM vaginal bleeding present), 5.8 (MSAFP greater than or equal to 2.0 MoM, vaginal bleeding absent), and 12.6 (MSAFP greater than or equal to 2.0 MoM, vaginal bleeding present). Corresponding risks for low birthweight are: 0.7, 1.8, 2.5 and 1.6 (mean birthweights in the four categories are 3516 g, 3407 g, 3238 g, and 3176 g).
Asunto(s)
Complicaciones Cardiovasculares del Embarazo , Hemorragia Uterina/complicaciones , alfa-Fetoproteínas/análisis , Femenino , Muerte Fetal/etiología , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Embarazo , Complicaciones Cardiovasculares del Embarazo/sangre , Riesgo , Hemorragia Uterina/sangreRESUMEN
The effect of cigarette smoking during pregnancy on serum alpha-fetoprotein (AFP) levels was studied in 1925 consecutive women at 16-18 weeks gestation who subsequently had liveborn singleton infants. Cotinine and AFP were measured in sera in all the women and answers to a smoking questionnaire were analysed in 894. Cotinine, a metabolic derivative of nicotine, serves as an objective measure of the average daily absorption of smoking products because of its relatively long half-life. Infants born to women who smoked were, on average, 198 g lighter than those born to non-smokers, even though maternal weights were comparable. Whether analysed by self-reporting or by serum cotinine, cigarette smoking had no measurable effect on serum AFP levels.
PIP: The effects of cigarette smoking during pregnancy on serum alpha-fetoprotein (AFP) levels was assessed in 1925 consecutive women at 16-18 weeks, gestation who subsequently delivered a liveborn singleton infant. Cotinine and AFP were measured in sera in all study subjects and answers to a smoking questionnaire were analyzed in 894 subjects. Mean serum AFP levels for the 308 self-reported smokers and the 586 nonsmokers were similar at all 3 gestational weeks. When analyzed by cotinine levels, cigarette smoking again had no measurable effect on serum AFP levels. However, infants born to women who smoked were an average of 198 gm lighter than those born to nonsmokers. The finding that cigarette smoking during pregnancy does not influence serum AFP levels differs from that reported in an earlier study, despite the fact that women in both studies had similar median body weights. It is concluded that, unless data to the contrary appear, meternal smoking habits should not be part of the interpretive process for maternal serum AFP levels.
Asunto(s)
Embarazo , Fumar , alfa-Fetoproteínas/análisis , Peso al Nacer , Peso Corporal , Cotinina/sangre , Femenino , Humanos , Segundo Trimestre del EmbarazoRESUMEN
In Maine, maternal serum alpha-fetoprotein (AFP) values equaled 2 or more multiples of the median in 4.8% of screened women. Between 2.0 and 2.9 multiples of the median repeat maternal serum AFP testing and sonography were comparable as the next diagnostic step; at 3 multiples of the median or higher sonography was superior. Sonography moved dates back in only ten singleton viable pregnancies with maternal serum AFP elevations; three of these had open fetal defects. Among singletons, all five anencephaly cases, one of two open spina bifida lesions, and all three open ventral wall defects were identified. Three closed singleton neural tube defects and two open spina bifida defects in twins were not detected. Nineteen of 36 multiple gestations had maternal serum AFP 2 or higher multiples of the median. In singletons, maternal serum AFP of 3 or higher multiples of the median indicated a thirtyfold increased risk for fetal death and a sevenfold increased risk for birth weight under 2500 g.
Asunto(s)
Anomalías Congénitas/diagnóstico , Diagnóstico Prenatal , alfa-Fetoproteínas/análisis , Femenino , Estudios de Seguimiento , Humanos , Maine , Médicos de Familia , Proyectos Piloto , Embarazo , Embarazo Múltiple , UltrasonografíaRESUMEN
Maternal serum alpha-fetoprotein concentrations are influenced by maternal weight during the second trimester. Heavier pregnant women have lower median values, apparently as a result of a diluting effect of larger blood volume. This phenomenon is of clinical interest because alpha-fetoprotein concentration in a pregnant woman's serum is one of the factors considered in assessing risk of poor outcome. A revision of the reference interval for alpha-fetoprotein to take body weight into account might improve its use as a diagnostic aid, especially in heavier women.