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Archives of Gynecology and Obstetrics Apr 2022Screening for chromosomal disorders, especially for trisomy 21, has undergone a number of changes in the last 50 years. Today, cell-free DNA analysis (cfDNA) is the... (Review)
Review
Screening for chromosomal disorders, especially for trisomy 21, has undergone a number of changes in the last 50 years. Today, cell-free DNA analysis (cfDNA) is the gold standard in screening for trisomy 21. Despite the advantages that cfDNA offers in screening for common trisomies, it must be recognized that it does not address many other chromosomal disorders and any of the structural fetal anomalies. In the first trimester, the optimal approach is to combine an ultrasound assessment of the fetus, which includes an NT measurement, with cfDNA testing. If fetal structural defects are detected or if the NT thickness is increased, an amniocentesis or a CVS with at least chromosomal microarray should be offered.
Topics: Chromosome Aberrations; Female; Humans; Nuchal Translucency Measurement; Pregnancy; Pregnancy Trimester, First; Prenatal Diagnosis; Trisomy
PubMed: 35279726
DOI: 10.1007/s00404-022-06477-5 -
Journal of Medicine and Life 2019The last decade has seen incredible advances in the genetic era, in next-generation sequencing of cell-free DNA in the maternal plasma, detecting abnormal fetal... (Review)
Review
The last decade has seen incredible advances in the genetic era, in next-generation sequencing of cell-free DNA in the maternal plasma, detecting abnormal fetal chromosomes. Non-invasive prenatal testing (NIPT) has showed increased sensitivity and specificity for Down syndrome superior to any other screening test. Technical advances have made possible the detection of other conditions which does not necessarily mean clinical benefit for the patient. Private laboratories have added multiple conditions in the panel of NIPT, but some of these abnormalities are so rare, that their prevalence is not even clear. Data regarding clinical performance of extended NIPT is lacking. Implementation of such a test has to be carefully weighed, and not only the benefits but also the harm should be taken into account.
Topics: Counseling; Down Syndrome; Female; Fetus; Humans; Pregnancy; Prenatal Diagnosis; Trisomy; World Health Organization
PubMed: 31666820
DOI: 10.25122/jml-2019-0053 -
European Journal of Haematology Aug 2019Given the wide heterogeneity of phenotypes and of the underlying pathophysiological mechanisms associated with the disorder, pregnancy and delivery in von Willebrand... (Review)
Review
Given the wide heterogeneity of phenotypes and of the underlying pathophysiological mechanisms associated with the disorder, pregnancy and delivery in von Willebrand disease (VWD) represent a significant clinical challenge. The variable pattern of changes observed during pregnancy of von Willebrand factor (VWF) and factor VIII (FVIII), the protein carried by VWF, prompts a careful evaluation of pregnant women with VWD to plan the most appropriate treatment at the time of parturition. However, there are also instances during pregnancy (amniocentesis, vaginal bleeding associated with placental detachment, sudden abortion) that may require urgent hemostatic treatment to prevent bleeding. Thus, women with VWD should start pregnancy after being well characterised as to their type, subtype and treatments. Women with VWD who have VWF and FVIII basal levels >30 U/dL typically normalise these levels at the end of pregnancy and specific anti-haemorrhagic prophylaxis is seldom required. On the contrary, those with basal levels <20 U/dL usually show a lesser increase and specific treatment is required. Some women with DNA variants associated with increased clearance can be treated with desmopressin, while those unresponsive or with contra-indications to this agent need replacement therapy. For these latter women, the risk of vaginal bleeding during pregnancy may be increased and prophylaxis with VWF concentrates required. Similarly, women with type 2 VWD who maintain reduced VWF activity throughout pregnancy require replacement therapy with FVIII/VWF concentrates. Delayed postpartum bleeding may occur when replacement therapy is not continued for some days. Tranexamic acid is useful at discharge to avoid excessive lochia.
Topics: Amniocentesis; Biopsy; Delivery, Obstetric; Disease Management; Factor VIII; Female; Hemorrhage; Humans; Parturition; Postpartum Period; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Hematologic; Risk; von Willebrand Diseases; von Willebrand Factor
PubMed: 31107984
DOI: 10.1111/ejh.13250 -
American Journal of Obstetrics and... Aug 2019Cervical insufficiency is a risk factor for spontaneous midtrimester abortion or early preterm birth. Intra-amniotic infection has been reported in 8-52% of such...
Evidence that antibiotic administration is effective in the treatment of a subset of patients with intra-amniotic infection/inflammation presenting with cervical insufficiency.
BACKGROUND
Cervical insufficiency is a risk factor for spontaneous midtrimester abortion or early preterm birth. Intra-amniotic infection has been reported in 8-52% of such patients and intra-amniotic inflammation in 81%. Some professional organizations have recommended perioperative antibiotic treatment when emergency cervical cerclage is performed. The use of prophylactic antibiotics is predicated largely on the basis that they reduce the rate of complications during the course of vaginal surgery. However, it is possible that antibiotic administration can also eradicate intra-amniotic infection/inflammation and improve pregnancy outcome.
OBJECTIVE
To describe the outcome of antibiotic treatment in patients with cervical insufficiency and intra-amniotic infection/inflammation.
STUDY DESIGN
The study population consisted of 22 women who met the following criteria: (1) singleton pregnancy; (2) painless cervical dilatation of >1 cm between 16.0 and 27.9 weeks of gestation; (3) intact membranes and absence of uterine contractions; (4) transabdominal amniocentesis performed for the evaluation of the microbiologic and inflammatory status of the amniotic cavity; (5) presence of intra-amniotic infection/inflammation; and (6) antibiotic treatment (regimen consisted of ceftriaxone, clarithromycin, and metronidazole). Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and polymerase chain reaction for Ureaplasma spp. was performed. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms or a positive polymerase chain reaction for Ureaplasma spp., and intra-amniotic inflammation was suspected when there was an elevated amniotic fluid white blood cell count (≥19 cells/mm) or a positive rapid test for metalloproteinase-8 (sensitivity 10 ng/mL). For the purpose of this study, the "gold standard" for diagnosis of intra-amniotic inflammation was an elevated interleukin-6 concentration (>2.6 ng/mL) using an enzyme-linked immunosorbent assay. The results of amniotic fluid interleukin-6 were not available to managing clinicians. Follow-up amniocentesis was routinely offered to monitor the microbiologic and inflammatory status of the amniotic cavity and fetal lung maturity. Treatment success was defined as resolution of intra-amniotic infection/inflammation or delivery ≥34 weeks of gestation.
RESULTS
Of 22 patients with cervical insufficiency and intra-amniotic infection/inflammation, 3 (14%) had microorganisms in the amniotic fluid. Of the 22 patients, 6 (27%) delivered within 1 week of amniocentesis and the remaining 16 (73%) delivered more than 1 week after the diagnostic procedure. Among these, 12 had a repeat amniocentesis to assess the microbial and inflammatory status of the amniotic cavity; in 75% (9/12), there was objective evidence of resolution of intra-amniotic inflammation or intra-amniotic infection demonstrated by analysis of amniotic fluid at the time of the repeat amniocentesis. Of the 4 patients who did not have a follow-up amniocentesis, all delivered ≥34 weeks, 2 of them at term; thus, treatment success occurred in 59% (13/22) of cases.
CONCLUSION
In patients with cervical insufficiency and intra-amniotic infection/inflammation, administration of antibiotics (ceftriaxone, clarithromycin, and metronidazole) was followed by resolution of the intra-amniotic inflammatory process or intra-amniotic infection in 75% of patients and was associated with treatment success in about 60% of cases.
Topics: Adult; Amniocentesis; Amniotic Fluid; Anti-Bacterial Agents; Biomarkers; Candida albicans; Ceftriaxone; Cerclage, Cervical; Chorioamnionitis; Clarithromycin; Delivery, Obstetric; Female; Humans; Interleukin-6; Leukocytes; Matrix Metalloproteinase 8; Metronidazole; Pregnancy; Retrospective Studies; Streptococcus anginosus; Ureaplasma; Uterine Cervical Incompetence
PubMed: 30928565
DOI: 10.1016/j.ajog.2019.03.017 -
Ultrasound in Obstetrics & Gynecology :... Oct 2019To estimate the procedure-related risk of miscarriage after amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and an... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
To estimate the procedure-related risk of miscarriage after amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and an updated meta-analysis.
METHODS
A search of MEDLINE, EMBASE and The Cochrane Library was carried out to identify studies reporting complications following CVS or amniocentesis. Eligible for inclusion were large controlled studies reporting data for pregnancy loss prior to 24 weeks' gestation. Study authors were contacted when required to identify additional necessary data. Data for cases that had an invasive procedure and controls were inputted into contingency tables and the risk of miscarriage was estimated for each study. Summary statistics based on a random-effects model were calculated after taking into account the weighting for each study included in the systematic review. Procedure-related risk of miscarriage was estimated as a weighted risk difference from the summary statistics for cases and controls. Subgroup analyses were performed according to the similarity in risk levels for chromosomal abnormality between the invasive-testing and control groups. Heterogeneity was assessed using the I statistic. Egger's bias was estimated to assess reporting bias in published studies.
RESULTS
The electronic search yielded 2943 potential citations, from which 12 controlled studies for amniocentesis and seven for CVS were selected for inclusion in the systematic review. A total of 580 miscarriages occurred following 63 723 amniocentesis procedures, resulting in a weighted risk of pregnancy loss of 0.91% (95% CI, 0.73-1.09%). In the control group, there were 1726 miscarriages in 330 469 pregnancies with a loss rate of 0.58% (95% CI, 0.47-0.70%). The weighted procedure-related risk of miscarriage following amniocentesis was 0.30% (95% CI, 0.11-0.49%; I = 70.1%). A total of 163 miscarriages occurred following 13 011 CVS procedures, resulting in a risk of pregnancy loss of 1.39% (95% CI, 0.76-2.02%). In the control group, there were 1946 miscarriages in 232 680 pregnancies with a loss rate of 1.23% (95% CI, 0.86-1.59%). The weighted procedure-related risk of miscarriage following CVS was 0.20% (95% CI, -0.13 to 0.52%; I = 52.7%). However, when studies including only women with similar risk profiles for chromosomal abnormality in the intervention and control groups were considered, the procedure-related risk for amniocentesis was 0.12% (95% CI, -0.05 to 0.30%; I = 44.1%) and for CVS it was -0.11% (95% CI, -0.29 to 0.08%; I = 0%).
CONCLUSIONS
The procedure-related risks of miscarriage following amniocentesis and CVS are lower than currently quoted to women. The risk appears to be negligible when these interventions were compared to control groups of the same risk profile. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Abortion, Spontaneous; Adult; Amniocentesis; Chorionic Villi Sampling; Chromosome Aberrations; Embryo Loss; Female; Gestational Age; Humans; Pregnancy; Pregnancy Trimester, Second; Prenatal Diagnosis; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 31124209
DOI: 10.1002/uog.20353 -
Ultrasound in Obstetrics & Gynecology :... Oct 2021Cytomegalovirus (CMV) maternal primary infection (MPI) in early pregnancy is the main risk factor for congenital CMV (cCMV) infection with long-term sequelae. Our aim...
OBJECTIVE
Cytomegalovirus (CMV) maternal primary infection (MPI) in early pregnancy is the main risk factor for congenital CMV (cCMV) infection with long-term sequelae. Our aim was to evaluate, in a single center offering CMV serology screening at 11-14 gestational weeks, secondary prevention of cCMV by administration of high-dosage maternal oral valacyclovir (VACV) in the first trimester of pregnancy.
METHODS
This was a case-control study in a longitudinal cohort of pregnancies with CMV-MPI diagnosed prior to 14 weeks of gestation by serology screening (immunoglobulin (Ig) M and IgG measurement and IgG avidity) between 2009 and 2020. From October 2019 onwards, all women presenting at our center with MPI before 14 weeks' gestation were offered treatment with high-dosage oral VACV (8 g/day, 4 g twice/day). We used propensity score matching to compare fetal infection rates in cases treated with maternal oral VACV (8 g/day) with those in untreated controls. Fetal infection was assessed following amniocentesis at 17-22 weeks of gestation, by polymerase chain reaction (PCR) analysis of amniotic fluid for viral DNA.
RESULTS
Of 310 cases of CMV-MPI identified, 269 underwent amniocentesis for PCR. Of these, 66 were offered, and 65 accepted, treatment with VACV. From the remaining untreated cases, we selected 65 controls, matched for proportion of periconceptional infections and gestational age at amniocentesis. VACV was initiated at a median gestational age of 12.71 (interquartile range (IQR), 10.00-13.86) weeks and the median duration of treatment was 35 (IQR, 26-54) days. On multivariate logistic regression, fetal infection was lower in the treated group (odds ratio, 0.318 (95% CI, 0.120-0.841); P = 0.021). One treated patient developed acute renal failure 4 weeks after initiation of VACV therapy, but this resolved within 5 days after treatment was stopped.
CONCLUSION
This study confirms the acceptability, tolerance and benefit of secondary prevention by VACV of cCMV infection in a clinical setting with a well-established routine maternal serum screening policy in the first trimester of pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Adult; Amniocentesis; Antiviral Agents; Case-Control Studies; Cytomegalovirus; Cytomegalovirus Infections; Female; Fetal Diseases; Gestational Age; Humans; Infectious Disease Transmission, Vertical; Logistic Models; Longitudinal Studies; Maternal Serum Screening Tests; Odds Ratio; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, First; Propensity Score; Secondary Prevention; Treatment Outcome; Valacyclovir
PubMed: 33998084
DOI: 10.1002/uog.23685 -
Journal of Perinatology : Official... Jul 2020Many genetic disorders are detectable in the prenatal period, and the capacity to identify them has increased remarkably as molecular genetic testing techniques continue... (Review)
Review
Many genetic disorders are detectable in the prenatal period, and the capacity to identify them has increased remarkably as molecular genetic testing techniques continue to improve and become incorporated into clinical practice. The indications for prenatal genetic testing vary widely, including follow-up of an anomaly found by routine ultrasound or maternal aneuploidy screening, a family history of genetic disease, advanced maternal or paternal age, or evaluation of a low-risk pregnancy due to parental concern. The interpretation of genetic variants identified in the prenatal period poses unique challenges due to the lack of ability for deep phenotyping as well as the option to make critical decisions regarding pregnancy continuation and perinatal management. In this review, we address the various modalities currently available and commonly used for genetic testing, including preimplantation genetic testing of embryos, cell-free DNA testing, and diagnostic procedures such as chorionic villous sampling, amniocentesis, or percutaneous umbilical blood sampling, from which samples may be sent for a wide variety of genetic tests. We discuss the difference between these modalities for the genetic diagnosis of a fetus, their strengths and weaknesses, and strategies for their optimal use in order to direct perinatal care.
Topics: Amniocentesis; Aneuploidy; Female; Fetus; Genetic Testing; Humans; Pregnancy; Prenatal Diagnosis
PubMed: 32094481
DOI: 10.1038/s41372-020-0627-z -
American Journal of Perinatology May 2024Approximately, 2% of women who undergo chorionic villi sampling (CVS) will subsequently undergo amniocentesis due to placental mosaicism or sampling/laboratory...
OBJECTIVE
Approximately, 2% of women who undergo chorionic villi sampling (CVS) will subsequently undergo amniocentesis due to placental mosaicism or sampling/laboratory issues. Our objective was to compare obstetric outcomes in women who underwent both procedures with those who had CVS alone.
STUDY DESIGN
Retrospective case-control study of patients with singleton pregnancies undergoing invasive testing from 2010 to 2020 was performed. All women who underwent CVS followed by amniocentesis were compared with a control group who underwent CVS alone matched (2:1) for age and year of pregnancy. Women with pregnancy loss at <16 weeks were excluded from the control group. Pregnancies terminated for genetic abnormalities were excluded. Obstetric outcomes were compared between cases and controls. Student -test and Fisher's exact test were used for statistical comparison.
RESULTS
During the study period 2,539 women underwent CVS, and 66 (2.6%) subsequently underwent amniocentesis. The 66 cases were compared with 132 age-matched controls who underwent CVS alone. Mean maternal age was 36.8 ± 3.4 years, and 43% of women were nulliparous. Amniocentesis was performed due to sampling or laboratory issues in 33% of cases, placental mosaicism in 44%, and further diagnostic testing in 23%. There were no pregnancy losses or stillbirths in either group. Those who had two invasive procedures delivered at similar gestational ages and birthweights and did not have higher rates of adverse outcomes compared with those who underwent CVS alone.
CONCLUSION
Patients considering CVS who are concerned about the possibility that a second invasive procedure could be required should be reassured that this does not appear to be associated with higher rates of adverse outcomes. Due to study size, we cannot exclude the possibility of small differences in uncommon outcomes, such as pregnancy loss or stillbirth.
KEY POINTS
· Amniocentesis may be recommended after CVS due to mosaicism, sampling issues, or further testing.. · Amniocentesis after CVS is not associated with pregnancy loss or other adverse outcomes compared.. · Patients who have both CVS and amniocentesis deliver at similar gestational ages and birthweights..
Topics: Humans; Amniocentesis; Female; Pregnancy; Retrospective Studies; Adult; Chorionic Villi Sampling; Case-Control Studies; Mosaicism; Pregnancy Outcome
PubMed: 35240697
DOI: 10.1055/a-1787-6785