Objective We sought to evaluate performance of a noninvasive prenatal test for fetal trisomy 21 (T21) and trisomy 18 (T18). Study Design A multicenter cohort study was performed whereby cell-free DNA ...from maternal plasma was analyzed. Chromosome-selective sequencing on chromosomes 21 and 18 was performed with reporting of an aneuploidy risk (High Risk or Low Risk) for each subject. Results Of the 81 T21 cases, all were classified as High Risk for T21 and there was 1 false-positive result among the 2888 normal cases, for a sensitivity of 100% (95% confidence interval CI, 95.5–100%) and a false-positive rate of 0.03% (95% CI, 0.002–0.20%). Of the 38 T18 cases, 37 were classified as High Risk and there were 2 false-positive results among the 2888 normal cases, for a sensitivity of 97.4% (95% CI, 86.5–99.9%) and a false-positive rate of 0.07% (95% CI, 0.02–0.25%). Conclusion Chromosome-selective sequencing of cell-free DNA and application of an individualized risk algorithm is effective in the detection of fetal T21 and T18.
Background In both the biomedical and public health literature, the risk for preterm birth has been linked to maternal racial/ethnic background, in particular African-American heritage. Despite this ...well-documented health disparity, the relationship of comorbid conditions, such as chronic hypertension, to maternal race/ethnicity and preterm birth has received relatively limited attention in the literature. Objective The objective of the study was to evaluate the interaction between chronic hypertension and maternal racial/ethnic background on preterm birth. Study Design This is a retrospective cohort study of singleton pregnancies among women who delivered between 2002 and 2015 at the University of California, San Francisco. The associations of chronic hypertension with both spontaneous and medically indicated preterm birth were examined by univariate and multivariate logistical regression, adjusting for confounders including for maternal age, history of preterm birth, maternal body mass index, insurance type (public vs private), smoking, substance abuse, history of pregestational diabetes mellitus, and use of assisted reproductive technologies. The interaction effect of chronic hypertension and racial/ethnicity was also evaluated. All values are reported as odds ratios, with 95% confidence intervals and significance set at P = .05. Results In this cohort of 23,425 singleton pregnancies, 8.8% had preterm deliveries (3% were medically indicated preterm birth, whereas 5.5% were spontaneous preterm births), and 3.8% of women carried the diagnosis of chronic hypertension. Chronic hypertension was significantly associated with preterm birth in general (adjusted odds ratio, 2.74, P < .001) and medically indicated preterm birth specifically (adjusted odds ratio, 5.25, P < .001). When evaluating the effect of chronic hypertension within racial/ethnic groups, there was an increased odds of a preterm birth among hypertensive, African-American women (adjusted odds ratio, 3.91, P < .001) and hypertensive, Asian-American/Pacific Islander women (adjusted odds ratio, 3.51, P < .001) when compared with their nonhypertensive counterparts within the same racial/ethnic group. These significant effects were also noted with regard to medically indicated preterm birth for hypertensive African-American women (adjusted odds ratio, 6.85, P < .001) and Asian-American/Pacific Islander women (adjusted odds ratio, 9.87, P < .001). There was no significant association of chronic hypertension with spontaneous preterm birth (adjusted odds ratio, 0.87, P = .4). Conclusion The effect of chronic hypertension on overall preterm birth and medically indicated preterm birth differs by racial/ethnic group. The larger effect of chronic hypertension among African-American and Asian/Pacific Islander women on medically indicated and total preterm birth rates raises the possibility of an independent variable that is not captured in the data analysis, although data regarding the indication for medically indicated preterm delivery was limited in this data set. Further investigation into both social-structural and biological predispositions to preterm birth should accompany research focusing on the effect of chronic hypertension on birth outcomes.
Chromosomal microarray analysis is a high-resolution, whole-genome technique used to identify chromosomal abnormalities, including those detected by conventional cytogenetic techniques, as well as ...small submicroscopic deletions and duplications referred to as copy number variants. Because chromosomal microarray analysis has a greater resolution than conventional karyotyping, it can detect deletions and duplications down to a 50- to 100-kb level. The purpose of this document is to discuss the technique, advantages, and disadvantages of chromosomal microarray analysis and its indications and limitations. We recommend the following: (1) that chromosomal microarray analysis be offered when genetic analysis is performed in cases with fetal structural anomalies and/or stillbirth and replaces the need for fetal karyotype in these cases (grade 1A); (2) that providers discuss the benefits and limitations of chromosomal microarray analysis and conventional karyotype with patients who are considering amniocentesis and CVS, and that both options should be available to women who choose to undergo diagnostic testing (grade 1B); (3) that pre- and posttest counseling should be performed by trained genetic counselors, geneticists, or other providers with expertise in the complexities of interpreting chromosomal microarray analysis results (Best Practice); (4) that patients be informed that chromosomal microarray analysis does not detect every genetic disease or syndrome and specifically does not detect autosomal-recessive disorders associated with single gene point mutations, as well as that chromosomal microarray analysis can detect consanguinity and nonpaternity in some cases (Best Practice); (5) that patients in whom a fetal variant of uncertain significance is detected by prenatal diagnosis receive counseling from experts who have access to databases that provide updated information concerning genotype-phenotype correlations (Best Practice); and (6) that chromosomal microarray analysis not be used as a first-line test to evaluate first and second trimester pregnancy losses due to limited data (grade 1C).
Objective Nonimmune hydrops is the presence of ≥2 abnormal fetal fluid collections in the absence of red cell alloimmunization. The most common etiologies include cardiovascular, chromosomal, and ...hematologic abnormalities, followed by structural fetal anomalies, complications of monochorionic twinning, infection, and placental abnormalities. We sought to provide evidence-based guidelines for the evaluation and management of nonimmune hydrops fetalis. Methods A systematic literature review was performed using MEDLINE, PubMed, EMBASE, and Cochrane Library. The search was restricted to English-language articles published from 1966 through June 2014. Priority was given to articles reporting original research, although review articles and commentaries also were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion in this document. Evidence reports and guidelines published by organizations or institutions such as the National Institutes of Health, Agency for Health Research and Quality, American Congress of Obstetricians and Gynecologists, and Society for Maternal-Fetal Medicine were also reviewed, and additional studies were located by reviewing bibliographies of identified articles. Grading of Recommendations Assessment, Development, and Evaluation methodology was employed for defining strength of recommendations and rating quality of evidence. Consistent with US Preventive Task Force guidelines, references were evaluated for quality based on the highest level of evidence. Results and Recommendations Evaluation of hydrops begins with an antibody screen (indirect Coombs test) to determine if it is nonimmune, detailed sonography of the fetus(es) and placenta, including echocardiography and assessment for fetal arrhythmia, and middle cerebral artery Doppler evaluation for anemia, as well as fetal karyotype and/or chromosomal microarray analysis, regardless of whether a structural fetal anomaly is identified. Recommended treatment depends on the underlying etiology and gestational age; preterm delivery is recommended only for obstetric indications including development of mirror syndrome. Candidates for corticosteroids and antepartum surveillance include those with an idiopathic etiology, an etiology amenable to prenatal or postnatal treatment, and those in whom intervention is planned if fetal deterioration occurs. Such pregnancies should be delivered at a facility with the capability to stabilize and treat critically ill newborns. The prognosis depends on etiology, response to therapy if treatable, and the gestational age at detection and delivery. Aneuploidy confers a poor prognosis, and even in the absence of aneuploidy, neonatal survival is often <50%. Mirror syndrome is a form of severe preeclampsia that may develop in association with fetal hydrops and in most cases necessitates delivery.
Objective We sought to provide evidence-based guidelines for the diagnosis and management of fetal anemia. Methods A systematic literature review was performed using MEDLINE, PubMed, EMBASE, and the ...Cochrane Library. The search was restricted to English-language articles published from 1966 through May 2014. Priority was given to articles reporting original research, in particular randomized controlled trials, although review articles and commentaries were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion. Evidence reports and published guidelines were also reviewed, and additional studies were located by reviewing bibliographies of identified articles. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology was used for defining the strength of recommendations and rating the quality of evidence. Consistent with US Preventive Task Force guidelines, references were evaluated for quality based on the highest level of evidence. Results and Recommendations We recommend the following: (1) middle cerebral artery peak systolic velocity (MCA-PSV) measured by ultrasound Doppler interrogation be used as the primary technique to detect fetal anemia; (2) amniotic fluid delta OD450 not be used to diagnosis fetal anemia; (3) MCA-PSV assessment be reserved for those patients who are at risk of having an anemic fetus (proper technique for MCA-PSV evaluation includes assessment of the middle cerebral artery close to its origin, ideally at a zero degree angle without angle correction); (4) if a fetus is deemed at significant risk for severe fetal anemia (MCA greater than 1.5 multiples of the median or hydropic), fetal blood sampling be performed with preparation for an intrauterine transfusion, unless the pregnancy is at a gestational age when the risks associated with delivery are considered to be less than those associated with the procedure; (5) if a fetus is deemed at significant risk for severe fetal anemia, the patient be referred to a center with expertise in invasive fetal therapy; (6) MCA-PSV be considered to determine the timing of a second transfusion in fetuses with anemia, and, alternatively, a predicted decline in fetal hemoglobin may be used for timing the second procedure; and (7) pregnancies with a fetus at significant risk for fetal anemia be delivered at 37-38 weeks of gestation unless indications develop prior to this time.
Objective The objective of the study was to examine the effect of selective fetoscopic laser photocoagulation (SFLP) vs serial amnioreduction (AR) on perinatal mortality in severe twin-twin ...transfusion syndrome (TTTS). Study Design This was a 5 year multicenter, prospective, randomized controlled trial. The primary outcome variable was 30 day postnatal survival of donors and recipients. Results There was no statistically significant difference in 30-day postnatal survival between SFLP or AR treatment for donors at 55% (11 of 20) vs 55% (11 of 20) ( P = 1.0, odds ratio OR 1, 95% confidence interval CI 0.242 to 4.14) or recipients at 30% (6 of 20) vs 45% (9 of 20) ( P = .51, OR 1.88, 95% CI 0.44 to 8.64). There was no difference in 30 day survival of 1 or both twins on a per-pregnancy basis between AR at 75% (15 of 20) and SFLP at 65% (13 of 20) ( P = .73, OR 1.62, 95% CI 0.34 to 8.09). Overall survival (newborns divided by the number of fetuses treated) was not statistically significant for AR at 60% (24 of 40) vs SFLP 45% (18 of 40) ( P = .18, OR 2.01, 95% CI 0.76 to 5.44). There was a statistically significant increase in fetal recipient mortality in the SFLP arm at 70% (14 of 20) vs the AR arm at 35% (7 of 20) ( P = .25, OR 5.31, 95% CI 1.19 to 27.6). This was offset by increased recipient neonatal mortality of 30% (6 of 20) in the AR arm. Echocardiographic abnormality in recipient twin Cardiovascular Profile Score is the most significant predictor of recipient mortality ( P = .055, OR 3.025/point) by logistic regression analysis. Conclusion The outcome of the trial did not conclusively determine whether AR or SFLP is a superior treatment modality. TTTS cardiomyopathy appears to be an important factor in recipient survival in TTTS.
Objective To evaluate the incidence, etiology, and 1-year mortality of nonimmune hydrops fetalis (NIHF) and to identify risk factors for mortality in a contemporary population-based dataset. Study ...design The California Office of Statewide Health Planning and Development maintains a database linking maternal and infant hospital discharge, readmissions, and birth and death certificate date from 1 year before to 1 year after birth. We searched the database (2005-2012) for infants with NIHF (identified by the International Classification of Diseases, 9th Revision, Clinical Modification code). Hazard models were used to identify risk factors for mortality in infants with NIHF; results are presented as hazard ratios (HRs, 95% CI). Results The incidence of NIHF was 2.5 out of 10 000 among live born infants. Neonatal mortality was 35.1% (364 out of 1037) and overall mortality was 43.2% (448 out of 1037) at 1 year of age. Gestational age (GA) was predictive of mortality with a HR of 2.4 (95% CI 1.9-3.2) for preterm compared with term infants. The GA-adjusted HR for mortality was 1.3 (95% CI 1.1-1.6) for polyhydramnios and 1.5 (95% CI 1.2-2.0) for large for gestational age infants compared with appropriate for GA infants. Aneuploid infants with critical congenital heart disease had an adjusted HR of 2.3 (95% CI 1.5-3.6) compared with euploid infants without a structural birth defect. Conclusions In this large, population-based study, prematurity, polyhydramnios, and large for gestational age were predictors of increased mortality. Mortality is highly variable among euploid and aneuploid infants with and without structural birth defects and critical congenital heart disease.
Fetal blood sampling Berry, Stanley M., MD; Stone, Joanne, MD; Norton, Mary E., MD ...
American journal of obstetrics and gynecology,
09/2013, Letnik:
209, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Objective We sought to review indications, technical aspects, risks, and recommendations for fetal blood sampling (FBS). Methods A systematic review was performed using MEDLINE, PubMed, EMBASE, and ...Cochrane Library using the terms “fetal blood sampling,” “percutaneous umbilical blood sampling,” and “cordocentesis.” The search was restricted to English-language articles published from 1966 through July 2012. Priority was given to articles reporting original research, in particular randomized controlled trials, although review articles and commentaries also were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion in this document. Evidence reports and guidelines published by organizations or institutions such as the National Institutes of Health, Agency for Health Research and Quality, American Congress of Obstetricians and Gynecologists, and Society for Maternal-Fetal Medicine were also reviewed, and additional studies were located by reviewing bibliographies of identified articles. Grade (Grading of Recommendations Assessment, Development, and Evaluation) methodology was employed for defining strength of recommendations and rating quality of evidence. Consistent with US Preventive Task Force guidelines, references were evaluated for quality based on the highest level of evidence. Results and Recommendations Ultrasound-guided FBS is the only procedure that provides direct access to the fetal circulation. When invasive testing is planned for suspected severe fetal anemia or thrombocytopenia, we recommend FBS as the procedure of choice, with availability of immediate transfusion if confirmed. We recommend against the use of FBS for indications in which other less invasive, and therefore lower risk, alternatives are available. The overall success rate of FBS is high, and blood samples can be obtained in >98% of patients. We suggest that counseling for FBS include discussion about the potential risk of FBS that may include, but may not be limited to: bleeding from puncture site (20-30%); fetal bradycardia (5-10%); pregnancy loss (≥1.3%, depending on indication, gestational age, and placental penetration); and vertical transmission of hepatitis or human immunodeficiency virus. We recommend that FBS be performed by experienced operators at centers with expertise in invasive fetal procedures when feasible.
Background Accurate gestational dating is a critical component of obstetric and newborn care. In the absence of early ultrasound, many clinicians rely on less accurate measures, such as last ...menstrual period or symphysis-fundal height during pregnancy, or Dubowitz scoring or the Ballard (or New Ballard) method at birth. These measures often underestimate or overestimate gestational age and can lead to misclassification of babies as born preterm, which has both short- and long-term clinical care and public health implications. Objective We sought to evaluate whether metabolic markers in newborns measured as part of routine screening for treatable inborn errors of metabolism can be used to develop a population-level metabolic gestational dating algorithm that is robust despite intrauterine growth restriction and can be used when fetal ultrasound dating is not available. We focused specifically on the ability of these markers to differentiate preterm births (PTBs) (<37 weeks) from term births and to assign a specific gestational age in the PTB group. Study Design We evaluated a cohort of 729,503 singleton newborns with a California birth in 2005 through 2011 who had routine newborn metabolic screening and fetal ultrasound dating at 11–20 weeks’ gestation. Using training and testing subsets (divided in a ratio of 3:1) we evaluated the association among PTB, target newborn characteristics, acylcarnitines, amino acids, thyroid-stimulating hormone, 17-hydroxyprogesterone, and galactose-1-phosphate-uridyl-transferase. We used multivariate backward stepwise regression to test for associations and linear discriminate analyses to create a linear function for PTB and to assign a specific week of gestation. We used sensitivity, specificity, and positive predictive value to evaluate the performance of linear functions. Results Along with birthweight and infant age at test, we included 35 of the 51 metabolic markers measured in the final multivariate model comparing PTBs and term births. Using a linear discriminate analyses-derived linear function, we were able to sort PTBs and term births accurately with sensitivities and specificities of ≥95% in both the training and testing subsets. Assignment of a specific week of gestation in those identified as PTBs resulted in the correct assignment of week ±2 weeks in 89.8% of all newborns in the training and 91.7% of those in the testing subset. When PTB rates were modeled using the metabolic dating algorithm compared to fetal ultrasound, PTB rates were 7.15% vs 6.11% in the training subset and 7.31% vs 6.25% in the testing subset. Conclusion When considered in combination with birthweight and hours of age at test, metabolic profile evaluated within 8 days of birth appears to be a useful measure of PTB and, among those born preterm, of specific week of gestation ±2 weeks. Dating by metabolic profile may be useful in instances where there is no fetal ultrasound due to lack of availability or late entry into care.
Objective We sought to examine the association between increased first-trimester fetal nuchal translucency (NT) measurement and major noncardiac structural birth defects in euploid infants. Study ...Design Included were 75,899 singleton infants without aneuploidy or critical congenital heart defects born in California in 2009 through 2010 with NT measured between 11-14 weeks of gestation. Logistic binomial regression was employed to estimate relative risks (RRs) and 95% confidence intervals (CIs) for occurrence of birth defects in infants with an increased NT measurement (by percentile at crown-rump length CRL and by ≥3.5 mm compared to those with measurements <90th percentile for CRL). Results When considered by CRL adjusted percentile and by measurement ≥3.5 mm, infants with a NT ≥95th percentile were at risk of having ≥1 major structural birth defects (any defect, RR, 1.6; 95% CI, 1.3–1.9; multiple defects, RR, 2.1; 95% CI, 1.3–3.4). Infants with a NT measurement ≥95th percentile were at particularly high risk for pulmonary, gastrointestinal, genitourinary, and musculoskeletal anomalies (RR, 1.6-2.7; 95% CI, 1.1–5.4). Conclusion Our findings demonstrate that risks of major pulmonary, gastrointestinal, genitourinary, and musculoskeletal structural birth defects exist for NT measurements ≥95th percentile. The ≥3-fold risks were observed for congenital hydrocephalus; agenesis, hypoplasia, and dysplasia of the lung; atresia and stenosis of the small intestine; osteodystrophies; and diaphragm anomalies.
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