Prenatal diagnosis on fetal cells from maternal blood: practical comparative evaluation of the first and second trimesters

Objectives- Several attempts have been made to determine the gestational period in which the maximum number of fetal cells can be found in maternal blood and consequently which is the best week in which to perform a reliable non-invasive prenatal diagnosis. Most studies conclude that the number of nucleated red blood cells (NRBC) increases in line with gestation, but the number of cells that are fetal in origin (FNRBC) decreases in the third trimester. The aim of the present study was to make a practical comparative evaluation of the first and second trimesters to ascertain the period in which a greater number of FNRBC can be found of the total number of NRBC identified. Methods- Double density gradient and a posterior positive selection (CD71) by magnetic activated cell sorting (MACS) were employed. In the final fraction, erythroblasts were identified using Kleihauer staining and were studied using the fluorescence in situ hybridization (FISH) interphasic technique. Results- There was a significant difference (p<0.05) between the mean number of FNRBC found in the first and second trimesters. Conclusions- The number of FNRBC increases from the first to the second trimester. It appears that the optimum week in which to perform a reliable non-invasive prenatal diagnosis is around the 15th week.     

Prenatal diagnosis by transabdominal chorionic villus sampling in the second and third trimesters

From October 1989 through December 1993, 124 pregnant women (114 in the second trimester and 10 in the third trimester) underwent transabdominal chorionic villus sampling (CVS) for prenatal molecular or cytogenetic diagnosis. The mean gestational age was 18.2 weeks. Indications for CVS comprised single gene disease (72%), fetal anomalies detected by ultrasound (17%), advanced maternal age (6%), and previous siblings with chromosomal aberration (5%). Among the 89 fetuses at risk for single gene disease, 20 were diagnosed as affected by DNA analysis. Among the 35 fetuses at risk for chromosomal anomaly, 4 had trisomy, 3 had a 45, XO karyotype and 2 had a structural chromosomal abnormality. The miscarriage rate was 1.8% (2/114) and the spontaneous preterm birth rate was 2.4% (3/124). No maternal or other fetal complications occurred. This study suggested that second- and third trimester CVS is a safe and useful method for prenatal diagnosis.     

Pharmacological modulation of cervical compliance in the first and second trimesters of pregnancy

Health practitioners use many methods and agents to bring on cervical ripening in early pregnancy, such as intracervical tents and pharmacological techniques, to induce a therapeutic abortion. Prostaglandins alter myometrial and cervical tissue and are the most often used pharmacological technique. Reduced collagen concentration, an increase in water volume, an increase in prostaglandins (PGE2, PGI2, and PGF2 alpha), and a change in the glycosaminoglycan (GAG) content coincide with cervical ripening, yet the mechanism responsible for these changes is obscure. Prostaglandins appear to cause the breakdown of collagen or change the GAG/proteoglycan content. Research shows that prostaglandins can initiate cervical ripening at any stage of pregnancy. Estradiol stimulates prostaglandin production thereby al so inducing cervical dilation. Relaxin also demonstrates an ability to ripen the cervix. In addition, mifepristone (RU-486) is gaining acceptance as a cervical ripening agent. In fact, RU-486 and gemeprost have at least 95% success rate compared to 92% for gemeprost alone or 85% with RU-486 alone. The only effective and acceptable prostaglandins to use at gestation of 0-8 weeks are sulprostone, gemeprost, and 9-methylene-PGE2. At t his gestational age, pharmacological modulation is all that is needed. Even though they are effective (abortion rate 90%), side effects are expected to occur (pain, nausea, and vomiting). Similarly, prostaglandin analogues are preferable for cervical ripening in women at 8-12 weeks gestation. Suction curettage or other surgical techniques then are used to remove the conceptus. At 12-16 weeks gestation, many physicians prefer the same protocol as that of 8-12 weeks gestation. Other choose to infuse PGE2 and saline into the amniotic fluid to stimulate uterine contractions. Another procedure at 12-16 weeks involves 1mg vaginal pessaries of gemeprost every 3 hours to ripen the cervix and stimulate contractions. After 16 weeks, the methods for 12-16 weeks still apply.     

Rapid karyotyping for prenatal diagnosis in the second and third trimesters of pregnancy

Direct chromosome preparations were performed on placental villi obtained by ultrasound-guided needle aspiration between 18 and 37 weeks of pregnancy in 53 patients. The sampling yielded a sufficient amount of tissue with a maximum of two, and in most cases one, insertions. Placental biopsy is easily performed in cases of severe oligohydrammnios, where fetal blood sampling is usually more difficult. Direct karyotyping of placental villi is faster than chromosome analysis from fetal blood or application of the pipette method on amniotic fluid cells, and currently represents the most rapid approach to prenatal diagnosis of chromosomal abnormalities from the first to the third trimester of pregnancy.     

Prenatal diagnosis in the first trimester of pregnancy

In the past 2 decades, the second trimester of pregnancy has been the most common time for prenatal diagnosis of fetal anomalies and chromosomal aneuploidies. More recently, screening for and diagnosis of chromosomal abnormalities are increasingly being performed in the first trimester. With improvements and technological advances in ultrasound, it is now possible to identify many fetal structural anomalies at 11 to 13 6/7 weeks' gestation. At 10 to 11 weeks' gestation, biochemical markers in serum-PAPP-A, free beta-hCG, AFP, and uE3-combined with sonographic measurement of nuchal translucency and the presence/absence of the nasal bone can achieve a Down syndrome detection rate of 97.5% at a false-positive rate of 5%. Structural anomalies of the central nervous system, and the cardiac, renal, and gastrointestinal tracts can now be diagnosed by either transabdominal or transvaginal scanning, achieving detection of up to 80% of CNS anomalies by 13 weeks' gestation. In future, the emphasis in prenatal diagnosis will likely be in the first trimester. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to explain the rationale for first trimester combined ultrasound and serum analyte screening for fetal Down syndrome, describe the fetal anatomic structures that can be seen and evaluated in the first trimester, provide patient counseling about the relative benefits of genetic amniocentesis versus chorionic villous sampling, and discuss the application of Doppler technology to the evaluation of a first trimester fetus.     

Maternal serum prostate-specific antigen and Down syndrome in the first and second trimesters of pregnancy. International Prenatal Screening Research Group.

It has been suggested that high levels of maternal serum prostate-specific (PSA) may be associated with fetal Down syndrome. We retrieved stored blood samples from 102 singleton Down syndrome pregnancies at 8-14 weeks' gestation and 99 at 15-22 weeks' gestation, together with samples from five unaffected singleton control pregnancies matched for gestational age. PSA was measured using an ultrasensitive assay. Contrary to earlier reports, PSA levels were similar in affected and unaffected pregnancies in both the first and second trimester of pregnancy; 1.1 and 0.9 multiple of the normal median, respectively, in affected pregnancies. There was no indication that PSA would be a useful screening marker.     

Combination of screening tests for fetal abnormalities in the first and second pregnancy trimesters

OBJECTIVE: Screening for fetal abnormalities in the second trimester of pregnancy, based on the concentrations of various markers in serum and maternal age, has become widely used in the past decade. In the first trimester fetal malformations are associated with high values for fetal NT. DESIGN: We propose a new screening method in which measurements obtained during both trimesters are integrated to provide a single estimate of a woman's risk of having a pregnancy affected by genetic syndrome. MATERIAL AND METHODS: Study groups comprised 775 pregnant women where examinations were done between 11th-14th and 15th-19th pregnancy weeks. Nuchal translucency thickness was measured by ultrasound examination in both trimesters of pregnancy. AFP, -HCG and oestriol were measured by ELISA assays. Derived risks were then calculated. RESULTS: Eight fetal aneuploidies were diagnosed. When we used a risk of 1:250 as the cutoff to define a positive result on the integrated test, the rate of detection of fetal abnormalities was 100%, with a false positive rate of 0.6%. CONCLUSION: Integrated test, which is a combination of the ultrasound examination and the triple test allows to achieve high sensitivity and the decrease in the percentage of false positive results, which leads to the reduction in the number of amniocentesis to be performed.     

Hyperglycosylated-hCG (h-hCG) and Down syndrome screening in the first and second trimesters of pregnancy

OBJECTIVE: To validate Down syndrome screening protocols that include hyperglycosylated-hCG (h-hCG) measurements. METHODS: Measuring h-hCG in 21 641 fresh first- and second-trimester maternal serum samples, but not for clinical interpretation. Nuchal translucency (NT) and pregnancy associated plasma protein-A (PAPP-A) measurements were available in the first trimester; alpha-fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotropin (hCG) measurements in the second trimester. RESULTS: Of the 23 first- and 26 second-trimester Down syndrome pregnancies identified, 52 and 65% of h-hCG measurements were above the 95th centile, respectively. At a 3% false positive rate, maternal age, NT, PAPP-A and h-hCG detected 78% of cases (95% CI, 56-93%). Other combinations were consistent with previous modeling utilizing stored samples. A literature summary indicates h-hCG is as strong a marker as free-beta between 10 and 13 weeks' gestation. CONCLUSIONS: Down syndrome screening performance of h-hCG using fresh samples meets published expectations based on stored samples. h-hCG could replace free beta measurements, at gestational ages as early as 10 weeks.     

Plasma HCG levels in patients with bleeding in the first and second trimesters of pregnancy.

The prognostic value of maternal plasma human chorionic gonadotrophin (hCG) determinations, measured by a specific beta-subunit radioimmunoassay, was studied in 188 patients with bleeding between 6 and 20 weeks gestation. The patients were arranged into different subgroups according to ultrasound findings as well as clinical and histopathological evidence. In threatened abortion with successful outcome (50 per cent of all patients studied), the weekly mean hCG values were normal or even slightly elevated. In patients with a blighted ovum, the first hCG level measured was in the normal range in 34 per cent of the patients. In patients who aborted embryo with former life signs hCG values were generally normal before the abortion. The hCG levels were usually low in patients with incomplete abortion and ectopic pregnancy. An initially subnormal level of hCG was associated with a poor outcome of pregnancy in 92 per cent of patients. If the first hCG level was within the normal range the outcome of pregnancy was favourable in 79 per cent of patients.     

Anthropometric characteristics and success rates of oral or vaginal misoprostol for pregnancy termination in the first and second trimesters

Objective

To assess the effect of anthropometric characteristics related to weight on medical pregnancy termination with misoprostol.

Methods

In this prospective cohort study, 454 women admitted for medical pregnancy termination in the first or second trimester took 400 µg of misoprostol sublingually plus 800 µg of misoprostol vaginally or orally. The regimen was readministered after 24 hours if there was no response or the abortion was incomplete, and surgical evacuation was done when needed. Linear regression was performed for possible correlations between the studied characteristics and treatment process and outcome.

Results

There was no correlation between the number of misoprostol administrations and any of the studied anthropometric characteristics. The numbers of both misoprostol administrations and surgical interventions were associated with oral administration.

Conclusion

The route of misoprostol administration, but not anthropometric characteristics related to weight, were found to be associated with the success of pregnancy termination with misoprostol.     

Prenatal diagnosis of body stalk anomaly in the first trimester of pregnancy

Objective: To compare outcomes from uterine ruptures (UR) among women without versus with a prior cesarean. Method: This case–control study matched on gestational age +/– 1 week and birth year +/– 2 years using a variable numbers of controls (maximum = 4) for each case. All URs in Massachusetts between 1990 and 1998 were identified using ICD-9 codes from linked hospital discharge and birth/fetal death certificate files and confirmed by medical record review. Complete hospitalization records were abstracted. Maternal outcomes were hysterectomy, transfusion, ICU admission, shock, assisted ventilation, and hospital length of stay. Infant outcomes were 5?min Apgar less than 3 or need for ventilation at birth, death, or poor prognosis at discharge. Results: The UR incidence in women without a prior cesarean was 7 per 100,000 births. Of the 49 women without a prior cesarean and a UR, 36 women met study criteria and were matched to 140 controls. Women without a prior cesarean had more severe maternal morbidity (50% vs. 16%) (adj OR 3.28, 95% CI: 1.70, 6.32) with 47% of cases requiring transfusion and 33% requiring ICU admission. Their hospital stays were nearly two days longer. Among their infants, 14% died or had a poor prognosis at discharge compared to 7% of control infants (OR = 2.42, 95% CI 0.94, 6.28). Conclusion: Although UR in a woman without a prior cesarean is uncommon, providers should be prepared for more severe maternal morbidity which may be mitigated by prompt surgical intervention and heightened hemodynamic surveillance.     

Sonographic detection of placenta accreta in the second and third trimesters of pregnancy

OBJECTIVE: The purpose of this study was to determine whether ultrasonography can detect placenta accreta reliably in at-risk patients. STUDY DESIGN: All patients with a previous cesarean delivery and an anterior placenta or placenta previa were evaluated prospectively at each visit for sonographic signs of placenta accreta (interruption of the posterior bladder wall-uterine interface, absence of the retroplacental clear zone, and placental lacunae). RESULTS: This evaluation involved 2002 patients over a 12-year period. Of the 14 patients with a confirmed diagnosis of placenta accreta who had ultrasound examinations between 15 and 20 weeks of gestation, the diagnosis was suspected strongly in 86% of the patients (12/14 patients). There were 18 false-positive cases (54.5%; 18/33 patients), most of which were due to a lack of visualization of the echolucent area between the placenta and the myometrium (obliteration of the 'clear space') during the third trimester. The presence of multiple linear irregular vascular spaces within the placenta (placental lacunae) was the diagnostic sign with the highest positive predictive value for placenta accreta. CONCLUSION: Placenta accreta can be detected as early as 15 to 20 weeks of gestation in most at-risk patients by visualization of irregular vascular spaces within the placenta (placental lacunae). Obliteration of the retroplacental 'clear space' is not a reliable diagnostic sign for placenta accreta.     

Doppler study of uterine artery blood flow: comparison of findings in the first and second trimesters of pregnancy.

In 55 women with singleton pregnancies, colour flow mapping and pulsed wave velocimetry were used to measure impedance to flow in the uterine arteries at 10-13 weeks gestation and again at 19-22 weeks. In the first trimester, examinations were performed both transabdominally and transvaginally and in the second trimester transabdominally only. There were significant associations between the first- and second-trimester measurements obtained with both Doppler techniques. These associations were higher when transvaginal than transabdominal Doppler was used and when the measurement of impedance was the pulsatility index (PI) rather than the resistance index. These data suggest that impedance to flow in the uteroplacental circulation in the second trimester is dependent on impedance in the first trimester. In any prospective, first-trimester, uterine artery Doppler screening study for pregnancy complications, it may be preferable to use transvaginal Doppler and measure PI.     

Association between first trimester vaginal bleeding and uterine artery Doppler measured at second and third trimesters of pregnancy

Abstract

Objective: To evaluate the prevalence of first trimester vaginal bleeding among patients with abnormal second and third trimester uterine artery Doppler.

Methods: A prospective study of patients with a uterine artery Doppler measurement between 27 and 42 weeks’ gestation was undertaken. A comparison was made between two groups: patients with and without first trimester vaginal bleeding. Abnormal uterine artery Doppler was defined as PI >95th% or the presence of a diastolic notch.

Results: Of the 277 patients that were included in the study, 65 (23%) had first trimester vaginal bleeding. No differences were noted in uterine artery Doppler waveforms among patients with and without first trimester vaginal bleeding.

Among patients with first trimester vaginal bleeding, 9 (14%) had a bilateral uterine artery notch and 56 (86%) did not, compared with 51 (24%) and 161 (76%), in the control group, respectively. Patients with first trimester vaginal bleeding, and a bilateral uterine artery notch had significantly higher rates of small for gestational age neonates, low-Apgar scores (<7) at one minute and cesarean deliveries compared to patients with first trimester vaginal bleeding who did not have bilateral uterine artery notch.

Conclusion: First trimester vaginal bleeding was not associated with a higher incidence of abnormal uterine artery waveforms or with placental related conditions. However, adverse perinatal outcomes were found when first trimester vaginal bleeding was associated with second and third trimester bilateral uterine artery notchs.