Fetal loss rates after mid-trimester amniocentesis

Objective: Amniocentesis is an invasive cytogenic test traditionally associated with a 1/200 procedure–related pregnancy loss rate. Recent studies have questioned the validity of the traditionally stated rate. The purpose of this study was to document the results of second-trimes- ter genetic amniocentesis performed at our pe- rinatalogy clinic. Study Design: A retrospective review of all the amniocentesis procedures per- formed between 15 and 22 weeks of gestation on singleton pregnancies between May 2004 and December 2008 was performed. Spontaneous loss was defined as any unintentional preg- nancy loss at < 24 weeks of gestation. Setting: Zonguldak Karaelmas University, Faculty of Me- dicine, Department of Obstetrics and Gynecology. Population: Pregnant women followed at the Obstetrics Department. Methods: A retrospective review of all the amniocentesis procedures performed between May 2004 and December 2008 was performed. Main outcome measure: Pregnancy loss due to amniocentesis. Results: A total of 447 amniocentesis procedures were performed during the study period. The major indication for amniocentesis was positive maternal triple screening (44%). The mean gestational age at amniocentesis was 18.80 ± 2.70 weeks. The results of cytogenetic analyses revealed an abnormal karyotype in 19 pregnancies (4.3%), nine of which were trisomy 21. The overall spontaneous loss rate was 0.89% (n = 4). Conclusion: It would be useful for each center to investigate its own pregnancy loss rate and thereby provide a firmer basis for its policy for counseling women requesting amniocentesis. If enough such investigations were reported, a true benchmark figure could also emerge.

Amniocentesis: A contemporary review

Amniocentesis is an essential tool in obstetrics. Invasive testing remains the only modality for diagnostic genetic testing and the only way to provide comprehensive test-ing for chromosomal abnormalities. Despite increasing use of cell free fetal deoxyribonucleic acid （DNA） testing, amniocentesis should still be offered to all women who desire more complete and accurate genetic testing. Counseling patients on the limitations of screening tests is of the upmost importance and amniocentesis should continue to be recommended to confrm positive results from cell free fetal DNA testing or in the case of failed cell free fetal DNA test. As cell free fetal DNA screening has not adequately been studied in multiple gestations, its use is not recommended in this population and invasive testing should be offered. Amniocentesis is also very useful in providing additional information in settings other than genetic testing the second and third trimester. If intraamniotic infection is suspected, but the clinical fndings are not enough to guide manage-ment, amniocentesis can provide testing that can both immediately clarify the picture （interleukin-6, gram stain, glucose levels） and finally confirm the presence of infection （culture）. It can also be used to detect the presence of intrauterine viral infections. Additionally, amniocentesis may be used to test for markers of fetal lung maturity. The American Congress of Obstetricians and Gynecologists recommends that amniocentesis for this indication not be used in cases where late preterm delivery is indicated. It may be useful in guiding decision-making, however , when late preterm delivery is indicated, but when exact timing is unclear. Regardless of the indication, amniocentesis appears to be a relatively low risk procedure with minimal risk to the patient. Additional randomized controlled trials are not likely, as they are not feasible to due extremely high number of participants that would be needed to detect a difference in loss rates. Based on current literature, however, the risk of pregnancy loss from second trime-ster amniocentesis is low in both singleton and twin gestations. We counsel patients that technique has changed since the original studies in the 1970s and feel comfortable quoting a loss rate of 1/500-1/1000 based on contemporary data.

Instrument-Dependent or Instrument-Independent Indications and Prevalence of Chromosomal Abnormalities by Amniocentesis in China:An Analysis of 4146 Cases of Amniocentesis

Objective:There is a high incidence of birth defects in China,and prenatal diagnosis is an important method of intervention.This study aims to describe the clinical indications and cytogenetic results of amniocentesis cases in central China.Methods:We retrospectively reviewed cases at the Maternal and Child Care Service Centre in Henan Province from January 2012 to December 2014.A total of 4497 at-risk mothers(risk factors:advanced maternal age,history of intrauterine fetal death or aborted fetuses,chromosomal abnormality in one of the parents,high-risk maternal serum screening results,and abnormal ultrasonographic findings in the first or second trimester)were recruited for amniocentesis(AS).The subjects included were between 11–14 and 18–22 weeks of gestation.All cases were divided into two groups based on instrument-independent or instrument-dependent indications.Results:A total of 4146 cases were analyzed.Of these,chromosomal abnormalities were detected in 232 cases(5.6%),and autosomal aneuploidy,including trisomy 21 and trisomy 18,was found to be the most common(55.7%)chromosomal abnormality.The mean age of 29.94 years was not expected as all mothers older than 35 years old were routinely offered amniocentesis at the time of the study.Amniocentesis was carried out in 1711 cases because of instrument-independent indications,and 285 of these cases were diagnosed with chromosomal abnormality.In 2376 cases,amniocentesis was conducted because of instrumentdependent indications,and 176 of these were diagnosed with chromosomal abnormality.Thus,5.6%of the cases were diagnosed with chromosomal abnormalities,and autosomal aneuploidy,including trisomy 21 and trisomy 18,were the most common chromosomal abnormalities detected in the present study Conclusion:Our result indicated the significance of instrument-independent indications in the screening of chromosomal abnormalities,especially in developing areas.Birth defects may be reduced by paying more attention to the patients’history of medication.

Prenatal ultrasonic characteristics and diagnosis of fetal Currarino syndrome:Report of 2 cases and review of literature

Objective To explore prenatal ultrasonic characteristics of fetal Currarino syndrome(CS)and methods for prenatal diagnosis of CS.Methods Two fetuses with CS confirmed by genetic examination were retrospectively analyzed,while 6 CS fetuses with complete prenatal ultrasonic data in literature were reviewed.Prenatal ultrasonic characteristics of CS fetuses and the method for prenatal diagnosis of CS were discussed.Results Among 8 CS fetuses diagnosed with prenatal ultrasound,4 were female singletons with a clear family history of CS,and MNX 1 gene mutation was found in 1 fetus.The other 4 fetuses were 2 pairs of male monochorionic twins,all with MNX 1 gene mutation.Among 8 CS fetuses,complete triad(sacral agenesis abnormalities,anorectal malformation and presacral mass)were displayed only in 2 fetuses,while all 8 had sacral agenesis abnormalities and 6(6/8,75.00%)were detected with prenatal ultrasound,6 had low location of conus medullaris and 2(2/6,33.33%)detected with prenatal ultrasound.Conclusion Prenatal ultrasound was the first choice for non-invasive diagnosis of fetal CS.When one of sacral agenesis abnormalities,anorectal malformation and presacral mass was found with prenatal ultrasound,the possibility of CS should be considered,and fetal MRI,genetic examination and prenatal genetic counselling should be recommended if necessary.

Invasive Procedures for Prenatal Diagnosis in Salmaniya Medical Complex in Bahrain: A Retrospective Cross-Sectional Descriptive Study

Background: Prenatal diagnosis is the process of evaluating the presence of disease or potential disease in the fetus, this enables families to be better prepared before the birth of the baby. There are non-invasive prenatal diagnosis procedures and invasive prenatal diagnosis procedures. The invasive prenatal diagnosis procedures are CVS (chorionic villus sampling) and amniocentesis. The American College of Obstetricians and Gynecologists states that invasive diagnostic testing should be available to all women, regardless of age or risk. Objective: To determine the indications, outcome and results of diagnostic invasive prenatal procedures. Study setting: The obstetrics and Gynecology Department in Salmaniya Medical Complex in Kingdom of Bahrain. Study design: Retrospective descriptive study. Study subjects and Methods: This retrospective descriptive study was conducted on 175 pregnant women who underwent invasive prenatal procedures (CVS and amniocentesis) between January 2013 and December 2018 at SMC in Kingdom of Bahrain. All medical records of the participants were reviewed and entered the study. According to the implemented procedures, medical records were categorized into two chorionic villus sampling (CVS) and amniocentesis groups. The study subject will include indications of the procedures which are advanced maternal age, hematological disorders, genetic disorders, metabolic disorders, abnormal structural findings in fetal ultrasound and previous child with aneuploidy. In addition, the study will address the complications, outcome and results of procedures. Results: About half of our indications of the procedures were due to hematological disorders (47.6%) followed by abnormal structural findings in fetal ultrasound (30.1%) then genetic disorders (15.7%), metabolic disorders (4.8%) and advanced maternal age (1.8%). Regarding complications of the procedure;threatened miscarriage or loss of pregnancy within 3 weeks was (2.3%), amniotic fluid leakage (0.7%), abdominal cramps (0.7%) and Insufficient or contaminated sample (6.2%). Regarding outcome of the pregnancy, our results showed that the loss of pregnancy was (4.8%), intrauterine fetal death or still birth was (13.9%), live birth was (63.9%), preterm delivery was (7.8%), preterm premature rupture of membrane (PPROM) was (1.8%), limbs reduction was (0.0%). Termination of pregnancy outside the country was (7.8%) of chorionic villus sampling and amniocentesis. Conclusion: CVS and amniocentesis are useful outpatient procedures to detect diagnosis or to assess whether a patient is at increased risk of having an affected fetus and that will minimize the psychological impact on the patient and to provide a proper antenatal care to the pregnant women by her obstetrician and follow up to the baby by pediatrician. In this study it was observed that most of the patients who underwent the procedure were couples either carrier or affected to sickle cell disease or Beta thalassemia.

Cytogenetic Analysis for Fetal Chromosomal Abnormalities by Amniocentesis:Review of Over 40,000 Consecutive Cases in a Single Center

Background:The aim of this study was to retrospectively investigate the 18-year experience of prenatal diagnosis of fetal karyotype analysis by amniocentesis.Methods:In this study,the authors reviewed the cytogenetic results of 40,208 fetuses with indications for amniocentesis enrolled from December 1998 to December 2015.Cytogenetic analysis of amniotic fluid was performed in all these pregnancies.Eight indications for amniocentesis were included.The detection rate and distribution of abnormal karyotypes were observed in each indication.Results:Among all these samples,abnormal maternal serum screening test was the most common indication for amniocentesis(17,536,43.67%),followed by advanced maternal age(11,734,29.18%),abnormal ultrasound findings(5,328,13.25%),and required by pregnant women(2,557,6.36%).Chromosomal abnormality was detected in 1,349(3.36%)samples,63.01%of the abnormalities were numerical,and 36.99%were structural.The detection rates of abnormal karyotype were 55.60%in one of the couple with chromosomal abnormality,4.43%in the pregnant women with pathological ultrasound finding,2.83%in the pregnant women with advanced age,and 2.73%in women with abnormal maternal serum screening tests.Of the fetuses with chromosome aberrations,680(50.41%)had trisomy 13,trisomy 18,or trisomy 21,and 138(10.23%)had sex chromosome disorder.The other 531 abnormal samples included translocation,mosaicism,inversion,deletion,addition,and marker chromosome.Conclusions:Cytogenetic analysis,therefore,remained an effective approach to decrease the birth defects of fetuses with indications for amniocentesis.These results could provide meaningful suggestions for clinical genetic consulting and prenatal diagnosis.

An Early Pregnant Chinese Woman with Cerebral Venous Sinus Thrombosis Succeeding in Induction of Labor in the Second Trimester

Cerebral venous sinus thrombosis(CVST)is a rare condition in early pregnancy.A22-year-old Chinese woman at10weeks of pregnancy requested induced abortion and was diagnosed as CVST for a severe headache accompanying with nausea and vomiting.The patient was treated successfully with anticoagulation,followed by amniocentesis,and finally succeeded in induction of labor safely.The diagnosis,treatment and prognosis for this rare condition are discussed in this paper.

The AL-SENSE Test is Reliable for Detection of Second Trimester Amniotic Fluid

Objective: To validate the reliability and stability of the AL-SENSE panty-liner for detection of amniotic fluid in the second trimester. Study design: Amniotic fluid drawn during amniocentesis between 16 to 23 weeks of gestation was used for the study.100 μl and 400 μl of amniotic fluid, were dripped onto two panty liners, respectively. After 5 minutes the indicator strip was removed from the AL-SENSE, dried and examined. The color was recorded at time 0 and 5 minutes, and then every 10 minutes for the first 30 minutes, then at 1, 2, 6 and 12 hours. Results: 50 women were enrolled and 49 completed the study. 100% of both volume samples changed color from yellow to blue during the first 5 minutes and remained stable after twelve hours of follow-up. In the 100 μl subgroup, seven of the 49 samples (14.3%) had a delayed color change and in the 400 μl subgroup one of 49 (2.04%) had a delay in change of color. Conclusion: Amniotic fluid drawn during amniocentesis at weeks 16 - 23 of gestation have a positive, stable staining effect on the AL-SENSE panty liner. Hence, AL-SENSE may be reliable for detection of amniotic fluid leakage during the second trimester.

Prenatal Diagnosis and Management of Fetal Goiter Treated Successfully with Intra-Amniotic Levothyroxine

Goiter is an enlargement of the thyroid gland which can be associated with a number of complications both for the mother and the fetus. A 34-year-old pregnant woman with normal thyroid function was referred to our Department of Obstetrics and Gynecology at Microcitemico Pediatric Hospital, Cagliari, for suspected fetal goiter at 32 gestational weeks. The case was monitored regularly by ultrasound and treated successfully with intra-amniotic levothyroxine (L-T4) administration. Fetal goiter was observed to decrease after this treatment and the thyroid ultrasound findings were also normal both at birth and in subsequent follow-ups. Our case report confirms the feasibility of conservative treatment with L-T4, which can effectively prevent complications related to fetal goiter.

Preimplantation gender diagnosis by fluorescence in situ hybridization

Objective To describe the clinical application of fluorescence in situ hybridization (FISH) in preimplantation gender diagnosis.Methods Preimplantation gender diagnosis was performed in 2 female hemophilia A carriers, 1 male patient with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and 2 male patients with Y chromosome abnormality. Embryo sex was identified by FISH in total of 6 treatment cycles.Results A total of 123 cumulus-oocytes were retrieved in 6 treatment cycles. Sixty-one embryos were available for embryo biopsy. The success rate of biopsy was 86.9% (53/61), with a further cleavage rate of 62.3% (33/53). In the FISH procedure, one cell was lost during fixation, leading to a 98.1% (52/53) fixation rate. Totally, 16 female embryos and 3 male embryos were transferred to 5 patients in 6 cycles. Three healthy babies were born. The diagnosis was confirmed by subsequent analysis of amniocytes and embryonic buds after embryo reduction.Conclusions FISH is an efficient and reliable technique for determining the sex of human preimplantation embryos. Selective abortion and births of affected children can be avoided by preimplantation gender diagnosis.

Prenatal cytogenetic diagnosis study of 2782 cases of high-risk pregnant women

Background Prenatal diagnoses are extremely advantageous for pregnant women with high-risk indicators and can help prevent the birth of malformed infants. However, no large-scale statistical study analyzing the correlation between fetal chromosome disorders and abnormal indicators during pregnancy has been done in China. The objectives of this study were to diagnose and analyze fetal chromosome abnormalities, determine the feasibility of the various prenatal test methods and establish diagnostic guidelines for the early, middle, and late trimesters. Methods From January 2004 to May 2009, 2782 pregnant women at high-risk underwent prenatal diagnoses. Categorized data expressed as either actual counts or percentages were analyzed by the chi-square or Fisher＇s exact test. Chorionic villus sampling was performed in the early-trimester （10-12 weeks of gestation）, amniocentesis in mid-trimester （16-28 weeks of gestation）, and umbilical cord blood collection in mid- or late-trimester （16-37 weeks of gestation）. In 51 cases either autopsy samples from intrauterine fetal deaths or placental tissues from aborted fetuses were tested. Results Chromosomal abnormalities were observed in 3.99% （111/2782） of the samples. Overall, the success rate of cytogenetic analysis for high-risk pregnancy groups was 98.17% （2731/2782）. It was significantly less successful when used to analyze data from the chorionic villus sampling compared with that from amniocentesis and umbilical cord blood （P=-0.000）. Abnormal chromosome carriers had the highest percentage of abnormal chromosomes （67.86%） when compared with chromosomal abnormalities in patients with ultra-sonographic ＂soft markers＂ （11.81%）, advanced maternal age （4.51%） and those who had positive serum screening results （P=-0.000）. Conclusions Invasive prenatal diagnostic techniques are feasible tools for confirming fetal chromosomal abnormalities. Abnormal chromosomes detected in one of the parents carrying abnormal chromosome, ultrasound soft markers, advanced maternal age or positive serum screening results were associated with a higher frequency of fetal genetic diseases.

Genetic counseling, prenatal screening and diagnosis of Down syndrome in the second trimester in women of advanced maternal age： a prospective study

Background The incidence of autosomal trisomy in livebirths is strongly dependent on maternal age. Special consideration is given to the provision of prenatal screening and cytogenetic testing to women of advanced maternal age （AMA）. The aim of this study was to evaluate the effectiveness of second trimester prenatal screening and amniocentesis for Down syndrome （DS） and compare the trends of choice of screening and amniocentesis among AMA women. Methods A total of 5404 AMA patients with natural singleton pregnancy were recruited for this prospective study from January 2008 to December 2010. The gestational weeks were from 15 weeks to 20~6 weeks. The patients referred were grouped into a screening group （2107 cases） and an amniocentesis group （3297 cases） by their own decision. The prevalence of DS was compared between the two groups by chi-square test. Choice rates for each maternal age with trends were compared by regression analysis. Results There were 18 cases of fetal DS detected in the screening group with a prevalence of 8.54%o （18/2107）. Twenty- five cases of fetal DS were diagnosed in the amniocentesis group with a prevalence of 7,58%0 （25/3297）. No statistical difference was observed in the prevalence of DS between the screening and amniocentesis group （P=0.928）. The invasive testing rate for DS in the amniocentesis group was 5.54 times higher than that of the screening group （1/131.88 vs. 1/23.78）. With the increase of the maternal age, the choice of amniocentesis increased while the choice of the screening showed an opposite trend. The choice of the AMA women between the screening and amniocentesis was significantly age relevant （P=0.012）. Conclusions The second trimester serum screening age alone to screen for DS. We suggest educating screening and amniocentesis options. in combination with maternal age was more effective than maternal the patients by recommending AMA women be informed of both

Prenatal Testing or Screening?

Over the past 50 years,the scope and extent of prenatal diagnosis and screening for genetic disorders have improved geometrically.There has been a pendulum like swing from testing to screening back and forth as new technologies emerge.The concurrent developments of cell free fetal DNA analysis of maternal blood has dramatically changed patient’s choices towards screening.However,with the use of array comparative genomic hybridization of fetal DNA that requires diagnostic procedures(Chorionic villus sampling and amniocentesis),much more extensive diagnosis can be obtained.Until noninvasive methods can replicate what can be done with diagnostic procedures there still will be a"price to be paid"for opting for the non-invasive methods.