Diagnostic mid trimester amniocentesis: how safe?

OBJECTIVE: Genetic mid-trimester amniocentesis is a common invasive procedure. The origin of the commonly quoted 0.5% rate of procedure-related pregnancy loss after amniocentesis is obscure and is in conflict with the only randomized prospective study that reported a procedure-related rate of loss of 1.0%. This review was performed to establish an estimate of procedure-related pregnancy loss after mid-trimester amniocentesis. The impact of placental puncture on the rate of loss and the risk of direct needle injury to the fetus were also examined. STUDY DESIGN: The National Library of Medicine database was used to identify English language reports of >1000 amniocenteses with sufficient detail and follow up data to allow the calculation of the rate of spontaneous pregnancy loss after amniocentesis but before 28 completed weeks. These reports were divided into 2 groups to assess the impact of the ultrasound technique. Group I described only preamniocentesis ultrasound evaluation; group II described primarily concurrent ultrasound needle guidance. Pregnancy loss between the 2 groups was compared. The impact of placental puncture and reported direct fetal trauma were examined. The significance of differences was tested using chi-square analysis, with significance at a probability value of < or =.05. RESULTS: Twenty-nine reports that totaled 68,119 amniocenteses were examined. In a comparison of all studies in group I with all studies in group II, there was a lower rate of loss after amniocenteses with the use of concurrent guidance (1.4%) compared with the use of preamniocentesis ultrasound evaluation (2.1%) that was significant ( P <.001). Among only the 5 controlled studies that used preamniocentesis ultrasound evaluation, the difference in rate of loss between amniocentesis patients and control subjects was 0.6% ( P =.0042; 95% CI, 0.19, 1.03), which was identical to the difference in the rate of loss of 0.6% between amniocentesis patients and control subjects from the 5 controlled studies that used concurrent ultrasound needle guidance ( P <.0001; 95% CI, 0.31, 0.90). Multiple case reports and small series of presumed fetal needle trauma were reviewed, but most of these attributed causation to the amniocentesis needle based only on circumstantial association. Two cases with direct evidence of fetal needle trauma are discussed. Finally, the rate of loss after placental puncture from among 9 reports that provided this detail was 1.4% and not different from the overall rate of loss that was noted in group II. CONCLUSION: This examination of experience with 68,119 amniocenteses from both controlled and uncontrolled studies provides a substantive basis for several conclusions: (1) Contemporary amniocentesis with concurrent ultrasound guidance in controlled studies appears to be associated with a procedure-related rate of excess pregnancy loss of 0.6% (95% CI, 0.31, 0.90). To determine the total rate of loss, this must be added to the reported natural rate of loss without amniocentesis among control patients of 1.08%. (2) The use of concurrent ultrasound guidance appears to reduce the number of punctures and the incidence of bloody fluid. Concurrent ultrasound guidance was associated with a reduced rate of loss when all studies were compared, but not among controlled studies. (3) Direct fetal needle trauma is rare, and rarely proved, but may occur more frequently than is reported because of a failure to diagnose and a failure of the consistent production of sequelae. (4) This experience does not substantiate an increased rate of pregnancy loss if placental puncture is required.     

Nasal bone measurement during the 1st trimester: is it useful?

The aim of this study was to present our preliminary data about nasal bone measurements at 11-14 weeks of pregnancy. This study was conducted in our prenatal unit between 2000 and 2003. A total of 642 pregnant women (single pregnancies) were enrolled into the study. During the first trimester of pregnancy, crown-rump length, nuchal translucency thickness, and fetal nasal bone length measurements and ductus venosus Doppler images were evaluated. The distribution of absent or small nasal bones in both normal fetuses and in those having some pathological conditions was compared by statistical analysis. p < 0.05 was considered significant. Nasal bone evaluation was successful in 600 of 642 (93.4%) ultrasound examinations. The linear regression line showed a significant positive slope with increasing crown-rump length (r=0.54, p < 0.001). Absent or small nasal bones were more common in abnormal than in normal fetuses (p=0.007). It is clear that the fetal nasal bone is becoming a powerful tool in prenatal screening for aneuploidy. Larger studies to be performed in a low-risk population are needed to assess whether the measurement of the nasal bone length provides additional benefits beyond the assessment of the presence or absence of the nasal bone.     

Isolated polyhydramnios in the third trimester: is a gestational diabetes evaluation of value?*

We evaluated implications of testing for gestational diabetes mellitus (GDM) in pregnancies complicated by third trimester isolated polyhydramnios with previous negative diabetes screening test. In this retrospective cohort study of 104 pregnant women with polyhydramnios between 2005 and 2013, all had normal first trimester fasting glucose and normal glucose challenge test (GCT?p?=?0.38) or fasting glucose values (82 vs. 86?mg/dL, p?=?0.29) between women in the polyhydramnios group with and without late GDM diagnosis. Moreover, no significant difference was found in relation to the mode of delivery or birth weight between the studied groups (3437?±?611 vs. 3331?±?515?g, p?=?0.63). Diagnosis of third trimester polyhydramnios was not associated with increased risk for GDM or neonatal complications.     

Fetal loss following second trimester amniocentesis. Who is at greater risk? How to counsel pregnant women?

Objective: The purpose of this retrospective observational cohort study was to determine the impact of certain risk factors on fetal loss, after mid-trimester amniocentesis.

Material and methods: Six thousand seven-hundred and fifty-two (6752) consecutive amniocenteses with known pregnancy outcome performed during a 7-year period (2004–2010) were included in this study. Different maternal-, fetal- and procedure-related factors were evaluated in this study.

Results: During this 7-year period, 6752 cases who underwent amniocentesis, with complete data available were evaluated for the outcome and risk factors mentioned. Total fetal loss rate (FLR) up to the 24th week was 1.19%. Risk factors associated with increased risk of fetal loss after amniocentesis were maternal age (OR:2.0), vaginal spotting (OR:2.2) and serious bleeding (OR:3.5) during pregnancy, history of 2nd trimester termination of pregnancy (OR:4.0), history of more than three spontaneous (OR:3.0) or surgical first trimester abortions (OR:2.1), fibromas (OR:3.0) and stained amniotic fluid (OR:6.1).

Conclusions: Amniocentesis is a safe-invasive procedure for prenatal diagnosis with total FLR of 1.19% in our institution during the study period. The present study has emphasized the significance of certain risk factors for adverse outcome and therefore the need to individualize the risk.     

Genetic amniocentesis complications: is the incidence overrated?

AIMS: To estimate the complication rate of 2nd-trimester amniocentesis and to determine the associated risk factors. METHODS: A retrospective chart review of genetic amniocenteses performed at a single tertiary care institution, from 1996 to 1998, was done. The variables studied included gestational age, indication for amniocentesis, number and site of needle punctures, and amniotic fluid color. Complications included fetal loss, rupture of membranes, and bleeding. RESULTS: Out of the 1,347 procedures analyzed, the most common indications were advanced maternal age (72.3%) and abnormal triple screen (20.3%). Transplacental genetic amniocenteses totaled 234 (17.4%). Clear fluid was observed in 98.2% of the patients. Twenty-two complications (1.6%) were observed: fetal loss (0.22%), bleeding (0.59%), and rupture of membranes (0.82%). An abnormal karyotype was detected in 34 (2.5%) fetuses. In separate univariate logistic regression analyses, complications were significantly associated with gestational age [odds ratio OR = 1.19; 95% confidence interval CI = (1.08, 1.32); p = 0.001], number of punctures [OR = 8.2; 95% CI = (1.76, 37.97); p = 0.007], and ultrasound anomalies [OR = 5.82; 95% CI = (1.65, 20.58); p = 0.006]. Gestational age and number of punctures remained significant in multivariate logistic regression analysis. CONCLUSIONS: Genetic amniocentesis performed at a tertiary care institution is rather safe, and the fetal loss rate of 0.22% is significantly lower (p < 0.001) than the previously published incidence of 1/200. The risk of complications is significantly and independently associated with advanced gestational age and number of punctures.     

Antibiotic prophylaxis in diagnostic hysteroscopy: is it necessary or not?

Objective

Surgical site infection remains the most common complication of surgery. Up to 5% of patients undergoing operative procedures will develop an infection leading to a prolonged hospital stay with increased cost. On the other hand the indiscriminate use of antibiotics has been associated with the development of antibiotic-resistant bacteria. The aim of this study was to examine the effect of antibiotic prophylaxis in cases of diagnostic hysteroscopy.

Study design

This was an eight-year randomized controlled clinical trial. The study group consisted of 364 women who underwent diagnostic hysteroscopy because of menometrorrhagia, post-menopausal vaginal bleeding, ultrasound findings of increased thickness of the endometrium, or as a routine examination prior to a first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment.

Results

Of the 364 women who underwent diagnostic hysteroscopy during this eight-year study period, 176 received antibiotic prophylaxis whereas 188 did not. There were no significant differences in the prevalence of postoperative infections observed between women who received antibiotic prophylaxis (0.57%) and those who underwent the procedure without prophylaxis (0.53%).

Conclusion

Given the very low risk of infection after diagnostic hysteroscopy and lack of evidence of efficacy, routine antibiotic prophylaxis is not recommended.     

Low-risk corpus cancer: is lymphadenectomy or radiotherapy necessary?

OBJECTIVE: The objective of this study was to find readily ascertainable intraoperative pathologic indicators that would discriminate a subgroup of early corpus cancers that would not require lymphadenectomy or adjuvant radiotherapy. STUDY DESIGN: Between 1984 and 1993, a total of 328 patients with endometrioid corpus cancer, grade 1 or 2 tumor, myometrial invasion < or =50%, and no intraoperative evidence of macroscopic extrauterine spread were treated surgically. Pelvic lymphadenectomy was performed in 187 cases (57%), and nodes were positive in nine cases (5%). Adjuvant radiotherapy was administered to 65 patients (20%). Median follow-up was 88 months. RESULTS: The 5-year overall cancer-related and recurrence-free survivals were 97% and 96%, respectively. Primary tumor diameter and lymphatic or vascular invasion significantly affected longevity. No patient with tumor diameter < or =2 cm had positive lymph nodes or died of disease. CONCLUSION: Patients who have International Federation of Gynecology and Obstetrics grade 1 or 2 endometrioid corpus cancer with greatest surface dimension < or =2 cm, myometrial invasion < or =50%, and no intraoperative evidence of macroscopic disease can be treated optimally with hysterectomy only.     

Gene therapy for the fetus: is there a future?

Gene therapy uses the intracellular delivery of genetic material for the treatment of disease. A wide range of diseases - including cancer, vascular and neurodegenerative disorders and inherited genetic diseases - are being considered as targets for this therapy in adults. There are particular reasons why fetal application might prove better than application in the adult for treatment, or even prevention of early-onset genetic disorders such as cystic fibrosis and Duchenne muscular dystrophy. Research shows that gene transfer to the developing fetus targets rapidly expanding populations of stem cells, which are inaccessible after birth, and indicates that the use of integrating vector systems results in permanent gene transfer. In animal models of congenital disease such as haemophilia, studies show that the functionally immature fetal immune system does not respond to the product of the introduced gene, and therefore immune tolerance can be induced. This means that treatment could be repeated after birth, if that was necessary to continue to correct the disease. For clinicians and parents, fetal gene therapy would give a third choice following prenatal diagnosis of inherited disease, where termination of pregnancy or acceptance of an affected child are currently the only options. Application of this therapy in the fetus must be safe, reliable and cost-effective. Recent developments in the understanding of genetic disease, vector design, and minimally invasive delivery techniques have brought fetal gene therapy closer to clinical practice. However more research needs to be done in before it can be introduced as a therapy.     

Does amniotic fluid alpha-fetoprotein have diagnostic or prognostic value at the time of second midtrimester genetic amniocentesis?

In order to assess the usefulness of amniotic fluid alpha-fetoprotein (AFP) levels at the time of midtrimester genetic amniocentesis, 4,430 cases were retrospectively studied to compare the high, normal or low AFP values with the karyotype characteristics and fetal anatomy using ultrasound (US) scanning and confirmed by postnatal evaluation or necroscopy in the case of termination of pregnancy. All the cases presenting malformations were correctly diagnosed by US examinations. AFP levels over the 2nd standard deviation (SD) were found in 112 cases (2.52%) and below the 2nd SD in 11 cases (0.24%). The characteristics of these cases are presented and discussed. According to our results, it is concluded that routine assessment of AFP at the time of midtrimester genetic amniocentesis, if coupled with optimal US scanning, is no longer justified.     

Ultrasound evaluation of the fetal nasal bone: what is the most appropriate first-trimester cut-off point for aneuploidy screening?

Purpose  

To establish fetal nasal bone length cut-off points for first trimester aneuploidy screening based on a normal curve of a Brazilian population.     

Third trimester abortion: is compassion enough?

One comprehensive ethical framework that can be applied to cases of third trimester abortion is based on the following notion: patient trust depends upon physicians developing specific virtues and basing their professional actions on these virtues. One such virtue, as described by Dr. John Gregory in 1772, is sympathy for the distress of others that overcomes self-interest. This application of sympathy and desire to relieve suffering can justify late term abortion in some cases. The compassionate response to sympathy forwarded by Gregory, however, must be properly regulated by reason, as Gregory himself recognized. Thomas Percival (1740-1803), author of the classic text "Medical Ethics," charged physicians with uniting "tenderness" (Gregory's "sympathy") with "steadiness." This combination of virtues reoccurs in the contemporary work of bioethicists Edmund Pellegrino and David Thomasma. The intellectual component of compassion requires physicians to exhibit compassion towards their patients, and this includes fetal patients. Thus, third trimester abortion is only justified in cases where fetal abnormalities are associated with the certainty or near certainty of early death or of a complete absence of cognitive developmental capacity. Most anomalies fail to meet these criteria, and physicians must exhibit the virtues of self-effacement and integrity to make rigorous, clinical, ethical judgements and properly balance the interests of the pregnant woman and the fetus.