Pathological pregnancies. Results of amniotic fluid studies and fetal outcome

Late amniocenteses (greater than 20 weeks' gestation) were performed in 114 pregnancies with no a priori genetic risk, but referred because of abnormal clinical and/or ultrasound findings suggesting fetal malformations. Reasons for referral included polyhydramnios (51 cases), oligohydramnios (15 cases), fetal growth retardation (FGR) (16 cases) and abnormal fetal ultrasound findings excluding anencephaly (32 cases). In 42 of these cases, referral was motivated by a combination of the above abnormal findings. When polyhydramnios was the sole anomaly (25 cases), 5 fetuses were malformed (20%), abnormal fetal karyotype and/or elevated amniotic fluid alphafetoprotein (AFP) were demonstrated in 2 cases. Oligohydramnios was the sole anomaly in one case; the infant died of prematurity. Fetal growth retardation was the sole anomaly in 14 cases, 11 otherwise normal newborns were small for date, 2 died at birth and 1 was malformed (1/14, 7%). In this group all fetal karyotypes were normal and in 2 cases amniotic fluid AFP were increased. In the 32 pregnancies without abnormal amniotic fluid volume and/or FGR and with fetal malformation(s) suggested by ultrasound, all malformations except one (ovarian cyst possibly ruptured during birth) were confirmed at birth, amniotic fluid AFP was elevated, and/or karyotype was abnormal in 6 cases. In 42 pregnancies where more than one alarm sign was present, abnormal karyotype and/or elevated amniotic fluid AFP level were recorded in 21 of the 39 cases where amniocentesis was performed, 33 fetuses were malformed (79%) and 13 died in the perinatal period (31%). The high incidence of abnormal results of amniocentesis found in this survey of pathological pregnancies, particularly in those with multiple alarm signs, emphasizes the need for amniocentesis in these situations.     

Risk of fetal loss in twin pregnancies undergoing second trimester amniocentesis(1)

OBJECTIVE: To assess the rate of fetal loss among bichorionic twin gestations undergoing genetic amniocentesis compared with singletons undergoing the procedure and untested twins. METHODS: In a retrospective cohort study, three groups were compared: 476 women with twins undergoing amniocentesis, 489 women with singleton gestations undergoing amniocentesis, and 477 women with twins presenting at a similar gestational age for ultrasound studies only. All subjects were scanned at 17-18 weeks' gestation and again approximately 4 weeks after the procedure or first ultrasound scan. Excluded were twin pregnancies after fetal reduction or chorionic villus sampling, fetuses with structural anomalies, and cases in which one fetus had died at the time of examination or after fetal reduction. RESULTS: Thirteen twin gestations in the tested group (2.73%) aborted spontaneously up to 4 weeks after the procedure compared with three twin controls (0.63%, P =.01) and three post-procedure singleton controls (0.6%, P =.01). An abnormal karyotype was discovered in 15 tested twin pregnancies (3%) and in six tested singletons (1.23%). All affected twin pairs were discordant for the chromosomal anomaly. CONCLUSION: The risk of early fetal loss in twins undergoing amniocentesis appears to be higher than that of exposed singletons or unexposed twins.     

Antenatal detection of congenital malformations by routine ultrasonography

Routine ultrasound examination was performed in 9012 fetuses of a general pregnant population to detect fetal malformations. The examination was done on 3098 fetuses at 18 weeks, and on 5914 fetuses it was repeated at 34 weeks. Ninety-three infants (1.03%) showed 123 major malformations, of which 65 (52.8%) in 54 children were visualized in utero. The sensitivity of detection of malformed fetuses was 58.1% (54 of 93), specificity 99.9%, positive predictive value 91.5%, and negative predictive value 99.6%. Five fetal hydronephroses were the only false-positive cases (0.06%), with apparent spontaneous resolution after birth. Fetal growth retardation, polyhydramnios, or oligohydramnios was observed in 43% of the malformed cases, suggesting the importance of these conditions in ultrasound screening. Abnormality of pregnancy was suspected clinically in only 25.8% of the cases at the time of diagnosis of fetal malformation, emphasizing the necessity for ultrasound examination of all pregnancies.     

Ultrasound diagnosis of fetal abnormalities and cytogenetic evaluation.

Over a 6 1/2 year period, in 288 pregnancies a variety of fetal malformations were detected by ultrasound. Two hundred and ten fetuses (73 per cent) were karyotyped. Gestational age at detection ranged from 11 to 38 weeks. The incidence of an abnormal karyotype in the total series was 14 per cent and 14.7 per cent in the 210 pregnancies in which a karyotype was performed. Single structural anomalies were found in 149 cytogenetically investigated fetuses, of which 25 had a chromosomal abnormality (17 per cent). Multiple structural malformations were present in 61 fetuses, of which 16 had an abnormal karyotype (26 per cent). Trisomy 18 was the most frequent finding. The most constant ultrasound finding in cases of an abnormal karyotype was polyhydramnios and severe IUGR in combination with structural defects. There is a need for extensive detailed ultrasound examination in high-risk pregnancies.     

A normal ultrasound does not obviate the need for amniocentesis in patients with elevated serum alpha-fetoprotein

Elevated levels of maternal serum alpha-fetoprotein (MSAFP) will identify a population at increased risk for specific congenital malformations, which are accurately diagnosed by amniotic fluid AFP and acetylcholinesterase. The risk for spontaneous abortion related to amniocentesis, combined with increasing confidence in the accuracy of ultrasound diagnosis, has caused us to question the need for amniocentesis in the diagnostic workup of pregnancies complicated by elevated levels of AFP in maternal serum. A retrospective study of 257 pregnancies evaluated for elevated serum AFP levels revealed 16 fetal malformations diagnosed by amniotic fluid AFP and acetylcholinesterase. Only 12 of these malformations were diagnosed on the initial ultrasound study. All malformations were diagnosed when ultrasound examination was repeated for increased acetylcholinesterase activity. Earlier gestational age at scanning, smaller defects, and pure technical failure were implicated as causes of misdiagnosis. The rate of fetal malformations identified in this high-risk population (6.23%) and the rate of ultrasound misdiagnosis (1.5% of the population with elevated levels of MSAFP) imply that amniocentesis should still be considered an essential part of the diagnostic workup in these situations.     

Long-term experience of general ultrasound screening in pregnancy

Since January 1, 1974, 43,000 routine ultrasound examinations have been performed on 22,400 pregnant women in the Department of Obstetrics and Gynecology, MalmöGeneral Hospital. At the present time, one examination is performed in the seventeenth week of pregnancy and one in thirty-third week. At the first examination, the number of fetuses, fetal anatomy, cardiac activity, and placental site are indicated. Fetometry is performed. Gestational age is adjusted according to the value of the biparietal diameter. The second ultrasound examination is aimed at detecting fetal growth deviations and malformations. In 15% of all pregnancies, ultrasound corrected gestational age by more than 14 days. Ultrasound appeared to be superior to the clinical assessment in 88% of these discrepant pregnancies in predicting date of delivery. The early examination detected 98% of the twin pregnancies, with no false positive results. If an ultrasound examination had been performed within 3 weeks of delivery, 92% of the fetuses with growth retardation were detected. Altogether, the program detected 60% of the growth-retarded fetuses. In 0.4% of the examinations, malformations were detected (0.6% during the last 2 years). A cost-benefit analysis suggested that large economical gains are to be realized by screening. However, organizational and educational problems must be properly solved before general screening is offered to a healthy pregnant population.     

Ontogeny of isolated ultrasound markers for fetal aneuploidy.

OBJECTIVE: To evaluate the natural history of isolated ultrasound markers for fetal aneuploidy observed at 14-16 weeks of affected gestations. STUDY DESIGN: 76 aneuploid gestations were diagnosed among a predominantly low-risk population undergoing targeted ultrasonography in the early second trimester. Indications for evaluation of fetal karyotype included fetal malformations or sonographic markers for aneuploidy, maternal age over 35 years and abnormal serum screening results. Markers were re-evaluated at the time of amniocentesis or at pregnancy termination for fetal anomalies. RESULTS: Sonographic markers for aneuploidy (SMA) were observed in 68 of 76 aneuploid gestations diagnosed in the study group. In 46 cases, SMA were associated with major fetal malformations and in 22 cases, markers were isolated. Only 2 of 22 isolated markers for aneuploidy were documented at the time of amniocentesis. CONCLUSION: Isolated ultrasound markers for aneuploidy are transient and may disappear later on in gestation. Transvaginal sonography at 14-16 weeks of gestation appears to provide the best time window for detection of markers for fetal abnormal karyotype.     

Evaluation of prenatal diagnosis by a registry of congenital anomalies.

Prenatal diagnosis performed by fetal karyotype and ultrasound scan is now a routine part of antenatal care in many countries. How many fetal anomalies are actually detected by these procedures? We have used our registry of congenital malformations to answer this question. In our region, prenatal diagnosis was performed in 23.1 per cent of fetuses with a chromosomal aberration and in 20.1 per cent of fetuses with non-chromosomal anomalies. Only 6.9 per cent of the pregnancies with fetuses with non-chromosomal anomalies were terminated. The sensitivity of prenatal diagnosis by ultrasonographic examination was much lower for isolated malformations (fetuses with only one anomaly) than for multiple malformed children, 15.3 and 48.3 per cent respectively, chromosomal anomalies excluded.     

Transvaginal sonography-detection of findings suggestive of fetal chromosomal anomalies in the first and early second trimesters.

Over a 4-year period, 14 dyskaryotic fetuses were diagnosed by amniocentesis, performed after early detection of malformations using transvaginal sonography (TVS). These 14 dyskaryotic fetuses were detected out of 4878 sonographic screenings performed by TVS between 9 and 16 weeks' gestation. Twenty-eight per cent of the referrals were at high risk and 72 per cent were at low risk for fetal malformations. Two hundred and twenty-nine fetuses (4.7 per cent) of the screened population had 265 anomalies, 39 per cent of them being transient. In 7 of the 14 dyskaryotic fetuses (50 per cent), the sonographically detected anomalies were transient, being undetected by follow-up sonographic screenings at later gestational ages (greater than or equal to 18 weeks). Postponing the first sonographic scan aimed at malformation detection to a later gestational age may lead to transient anomalies and their associated dyskaryosis being missed.     

Evaluation of fetal heart rate variation during amniocentesis: correlation with fetal karyotype

Objective.?We monitored the fetal heart rate (FHR) during amniocentesis in fetuses at 16–18 weeks of gestation and investigated whether an abnormal FHR is associated with chromosomal abnormalities.

Methods.?This prospective study involves 807 women at 16–18 weeks of gestation who underwent genetic amniocentesis. The FHR, expressed as beats for minute, is recorded before (FHR1), immediately after (FHR2) and 60?min after (FHR3) the invasive procedure. Structural malformations detected by ultrasound and multiple pregnancy are excluded from the study.

Results.?Chromosomal abnormalities have been diagnosed in 27 fetuses. A mean FHR decrease after amniocentesis has been observed in normal and in abnormal fetuses. The mean variation during amniocentesis is significant in both groups (P?<?0.01). The comparison between the mean FHR of the two groups shows no differences in FHR1 and FHR2 (P?>?0.05) but a significant difference in FHR3 (P?<?0.05).

Conclusion.?The FHR decreases after amniocentesis; the decrease is larger in chromosomally abnormal fetuses than in normal fetuses. This difference in heart rate reaction to amniocentesis might be due to cardiac defects or developmental delay associated with the abnormal karyotype.     

Risk factors associated with true knots of the umbilical cord

OBJECTIVE: To determine obstetrical risk factors and pregnancy outcome of fetuses with true knot of the umbilical cord. METHODS: Study population included 69,139 singleton deliveries occurring between the years 1990-1997. Data were retrieved from the database of the Soroka University Medical Center. Fetuses with malformations were excluded. RESULTS: The incidence of true knots was 1.2% (841/69,139). In a multivariate analysis the following factors were found to be significantly associated with true knot of cord: grandmultiparity, chronic hypertension, hydramnios, patients who undergone genetic amniocentesis, male gender and cord problems (prolapse of cord and cord around the neck). The incidence of fetal distress and meconium stained amniotic fluid was significantly higher among patients with true knots of cord (7% versus 3.6%, P<0.001 and 22% versus 16%, respectively, P<0.0001). Moreover, there was a four-fold higher rate of antepartum fetal death among those fetuses (1.9% versus 0.5%, P<0.0001). In addition, fetuses with true knots of the umbilical cord were more often delivered by a cesarean section (130/841 versus 711/68,298, P<0.0001). The following obstetrical factors were found to be significantly correlated to true knots of the umbilical cord in a multiple logistic regression model: gestational diabetes, hydramnios, patients undergoing genetic amniocentesis, male fetuses. CONCLUSIONS: Patients with hydramnios, who underwent genetic amniocentesis and those carrying male fetuses are at an increased risk for having true knots of the umbilical cord. Thus, careful sonographic and Doppler examinations should be seriously performed in these patients for detection of the complication of the umbilical cord.     

Prenatal diagnosis of trisomy 2 mosaicism: a case report

We report a case of trisomy 2 mosaicism detected upon amniocentesis in a woman with advanced maternal age. A mos 47,XY,+2(4)/46,XY(21) karyotype was revealed using standard GTG banding. There were no pathological sonographic findings and the fetal size was normal for gestational age at 16th week. The use of serial high-resolution ultrasound examination of the fetus to detect major abnormalities was offered as an option to the parents who, however, decided for termination of the pregnancy. Fetal autopsy did not reveal any malformations. Trisomy 2 mosaicism is associated with variable phenotypic abnormalities without a specific pattern, intrauterine growth restriction, fetal demise or stillbirth. The rarity of trisomy-2 mosaicism in prenatal diagnosis, as well as the increased risk of an abnormal outcome makes the diagnostic approach and genetic counseling difficult.     

Clinical utility of fetal autopsy and comparison with prenatal ultrasound findings.

OBJECTIVES: To present a comprehensive analysis of autopsy findings in 206 fetuses referred to our genetic center and to assess the clinical utility of fetal autopsy in reaching a final diagnosis, which is essential for counseling regarding the risk of recurrence. We also compared the autopsy findings with prenatal ultrasound findings to evaluate the potential benefit of fetal autopsy in fetuses terminated after prenatal diagnosis of malformations. STUDY DESIGN: Retrospective review of patient records in a tertiary referral genetic center in North India during 5-year period (April 2000-March 2005). This includes 206 fetuses, 138 terminated after detecting an anomaly in ultrasonogram and 68 spontaneous fetal losses. In all cases, fetal autopsy was carried out and complimented by radiography, karyotype wherever possible and histopathological examination wherever necessary. In fetuses with prenatally diagnosed malformations, ultrasound findings were compared with autopsy findings. RESULTS: Fetal autopsy was able to provide a definite final diagnosis in 59% (122/206) cases. Fetal autopsy confirmed the ultrasound findings in all cases but two. Moreover, autopsy provided additional findings in 77 cases and of these, 24 cases had a significant change of recurrence risk. CONCLUSION: This study confirms the utility of fetal autopsy in identifying the cause of fetal loss, which will help in the genetic counseling of the couple. In cases with prenatally diagnosed anomalies, the new information from fetal autopsy changes the predicted probability of recurrence in 18% cases. Even though the prenatal ultrasonogram reasonably predicts the malformations, fetal autopsy gives significant additional malformations in one-third of the cases and is essential for genetic counseling.     

Umbilical artery Doppler flow velocity waveforms after transplacental amniocentesis

OBJECTIVE: To assess the influence of transplacental versus nontransplacental needle passage during genetic amniocentesis on umbilical artery (UA) pulsatility index (PI) and fetal heart rate (FHR). METHODS: Genetic amniocentesis was performed in 205 women with no major fetal malformations detected by prenatal ultrasound at a median gestational age of 14 weeks and 3 days (range 13 weeks and 1 day to 18 weeks and 6 days). Chromosomal abnormalities were observed in five fetuses. These pregnancies were excluded from further analyses. The study group consisted of 56 of the remaining 200 women in whom amniocentesis had been performed transplacentally. As controls two patients with nontransplacental needle passage were chosen for each woman in the study group, matched for gestational age (+/- 3 days) and as far as possible for the indication for amniocentesis. The UA PI and the FHR were measured immediately before and after the amniocentesis. RESULTS: Amniocentesis did not cause significant changes in UA PI and FHR within or between the two groups. Division of the study population into three subgroups dependent on gestational age did not alter the results. Pregnancy outcome was similar in the two groups. CONCLUSION: Transplacental needle passage during amniocentesis did not induce any changes in UA PI or FHR relative to a group with nontransplacental amniocentesis.     

The role of ultrasound in evaluation of patients with elevated maternal serum alpha-fetoprotein: a review.

Accumulated experience with the sonographic detection of spina bifida and its associated fetal cranial changes indicates that nearly all these fetuses may be identified by ultrasound examination alone. A review of data from multiple centers shows that a complete and detailed, normal ultrasound is an appropriate basis for a reduction of at least 95% in the maternal serum alpha-fetoprotein (MSAFP)-based risk for neural tube defects. The use of this adjusted risk in patient counseling before amniocentesis may lower the rate of the procedure with no significant loss of diagnostic sensitivity. Among patients with elevated MSAFP, the rate of abnormal cytogenetic findings in fetuses with no abnormalities detected at ultrasound appears to be near 0.61%. Furthermore, the spectrum of abnormal cytogenetic results appears to differ from that associated with increased maternal age, in that the incidence of sex chromosome abnormalities is higher and that of Down syndrome is lower.     

Ultrasound screening of fetal structural abnormalities at 12 to 14 weeks in Hong Kong

OBJECTIVE: Ultrasound screening for fetal abnormalities is conventionally performed at 18 to 20 weeks of gestation. Recent data suggested that many fetal structural abnormalities could be detected by ultrasound examination at 12 to 14 weeks of pregnancy. In this study, we investigated the effectiveness of early ultrasound examination in the detection of fetal abnormalities in women aged 35 years or older. METHODS: From February 1998 to March 2001, pregnant women aged 35 or above were examined by transabdominal and transvaginal sonography between 12 and 14 weeks of gestation. If the anatomical survey was normal, the women underwent routine 16- to 20-week ultrasound examination. Pregnancy outcome was obtained from the hospital records or by contacting the subjects. RESULTS: Twenty-six of the 1609 fetuses had structural abnormalities. Fourteen were detected at the ultrasound examination at 12 to 14 weeks. Detection rate was 53.8% (14/26; 95% CI 44, 64) with a false-positive rate of 0.3% (5/1583; 95% CI 0.16, 0.44). Six additional abnormalities (23.1%, 6/26) were detected at 16- to 20-week ultrasound examination. The overall detection rate of structural abnormalities was 76.9% (20/26; 95% CI 68.6, 85.2). CONCLUSIONS: The effectiveness of ultrasound examination at 12 to 14 weeks to screen for fetal abnormalities approached that achieved at 20 weeks and can be a good adjunct to the conventional examination.     

The utility of detailed first trimester ultrasound examination in abnormal fetal nuchal translucency

OBJECTIVE: To determine the value of a first trimester fetal ultrasound examination in cases of an increased nuchal translucency (NT). METHOD: A detailed fetal ultrasound examination was performed within 4 days of a detection of a first trimester increased NT. RESULTS: As many as 23 fetuses were evaluated. Severe anomalies were detected in eight and mild anomalies were detected in six fetuses. Two fetuses had trisomy 13, one had trisomy 21, and 16 fetuses had a normal karyotype. A chromosomal analysis was not available in four fetuses with major anomalies due to parental decision. In one fetus, craniosynostosis was detected only at 24 weeks' gestation. CONCLUSIONS: The current study shows that a first trimester targeted scan of fetuses with an increased NT in an experienced center can shorten the parental decision-making process and spare parents a prolonged period of diagnostic uncertainty and anxiety, particularly when a structural anomaly is clearly diagnosed in the first trimester.     

Cytogenetic evaluation of fetal death: the role of amniocentesis

Fetal death can be associated with chromosomal abnormalities. Because of the degree of tissue maceration and autolysis seen in stillborn fetuses, it is often impossible to successfully culture these tissues for cytogenetic studies. We performed genetic amniocentesis in four cases of fetal death and were successful in obtaining cytogenetic results in all four, whereas the culture of fetal tissues for cytogenetics was successful in only one case. Chromosomal abnormalities were found in three of the four cases, including two fetuses with Down's syndrome and one fetus with Turner's syndrome. Because of the importance of cytogenetic studies in most cases of fetal death, we recommend amniocentesis at the time of diagnosis rather than waiting for delivery of fetal tissues, when postmortem changes may make it impossible to successfully culture fetal cells.     

Pathologic ultrasound findings and risk for congenital anomalies in teenage pregnancies

Objective: To detect the number and diagnosis of fetal malformations in teenage pregnancies and to evaluate whether low maternal age or epigenetic factors have an influence on this issue. Materials and methods: We performed a retrospective analysis in a single center for prenatal diagnostics in Northern Germany. We searched our electronic databank for all pregnancies with maternal age under 20 years. Pregnancy outcome and fetal malformations are described. Results: The incidence of teenage pregnancies in our study was 638 patients (4.4%). The total of fetal malformations in teenage pregnancies was 51(8.3%). Chromosomal aberrations were found in 5 cases (0.9%). 9 cases of fetal gastroschisis as one of the most frequent malformations were followed up and neonatal outcome was uneventful. Furthermore we found 16 cases with different heart defects and 30 cases with other malformations. Patients’ body mass indices showed an increase over the years and nicotine consumption was testified in more than 50% of the patients. Conclusions: Teenage pregnancies are at risk for fetal non-chromosomal and chromosomal abnormalities. As these might be detected by first-trimester-screening prenatal care in teenage pregnancies should include at least early ultrasound examination. Epigenetic factors may play a key role in certain fetal malformations.