Abnormal pregnancy sonogram: selective indication for fetal karyotype

The inability to make a definitive diagnosis in the fetus with a sonographically identified abnormality often results in parental and physician uncertainty. An antenatal chromosome evaluation could resolve this uncertainty. Forty-one fetuses with an abnormal ultrasound examination were tested for karyotypic abnormality using a variety of specimens. Nearly one-third (13 of 41) of these fetuses had various chromosome abnormalities. There were only seven survivors in this series, underscoring the often poor prognosis when a significant ultrasound defect is detected antenatally. Knowledge of the fetal chromosome constitution in the setting of an abnormal ultrasound has important epidemiologic, cost-benefit, counseling, and pregnancy management implications.     

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.     

Comparison of pregnancy outcome after amniocentesis for previous neural tube defect or raised maternal serum alphafetoprotein

Amniocentesis was performed in 219 pregnancies because a previous pregnancy produced a fetus with neural tube defect (NTD) and in 212 pregnancies in which the indication for amniocentesis was a high maternal serum alphafetoprotein (AFP) level. The proportion of abnormal fetuses, the frequency of low birth weight infants, and the frequency of undesired fetal loss were significantly greater in the group with high maternal serum AFP, in which there was also a significant excess of male births. It is concluded that maternal serum AFP screening defines a group of high risk pregnancies. The greater fetal loss and low birth weight associated with high maternal serum AFP levels were not the result of amniocentesis but were an inherent feature of these pregnancies.     

Pre-existing diabetics: Relationship between glycemic control and emotional status in pregnancy

The purpose of this retrospective study was to determine if maternal serum (MSAFP) or amniotic fluid (AF-AFP) α-fetoprotein analysis might he useful in detecting fetal structural defects in the first trimester. During a 5-year period, 20 fetal anomalies were diagnosed at 11–13 weeks by transvaginal ultrasound scanning. A MSAFP sample was obtained in all 20 patients and 17 patients had AF-AFP results obtained by an early amniocentesis. Ten of 20 patients (50%) had elevated MSAFP levels, and 6 or 17 patients had elevated AF-AFP samples (35%). MSAFP was elevated in 4 of 5 cases of anencephaly (80%), in one fetus with the combined malformations of anencephaly and omphalocele, in one fetus with a large encephalocele, in 2 of 3 fetuses (67%) with an omphalocele, and in two cases of cystic hygroma with an abnormal karyotype. AF-AFP was elevated in 3 of 3 cases of anencephaly, in one fetus with the combined defects of anencephaly and omphalocele, in 1 of 3 cases (33%) of omphalocele, and in one fetus with an encephalocele.

Our study suggests that MSAFP and AF-AFP analysis may prove useful in detecting fetal malformations in the first trimester. Larger prospective studies are needed to evaluate further the association of fetal anomalies and first-trimester AFP analysis.     

The association of echogenic fetal lungs with trisomy 21

OBJECTIVE: To evaluate the association between echogenic appearing lungs on ultrasonographic examination of the fetus and aneuploidy. METHODS: Cases in which echogenic lungs were prospectively identified on ultrasonographic examination were collected. Other abnormal ultrasonographic findings were documented, as were patient data pertinent to the risk of aneuploidy, such as maternal age and results of serum screening. The chromosomal complement of each identified case is reported. RESULTS: Five fetuses were identified with diffusely echogenic lungs on ultrasound examination over a two-year period. In three of the five cases, there were other ultrasound abnormalities, although in only one of these was a major congenital abnormality detected. In all three of these cases, the fetal chromosomal complement showed trisomy 21. In 1 of the 2 cases in which the echogenic lungs were an isolated finding, the fetus also was found to have trisomy 21. CONCLUSIONS: Bilateral and diffusely echogenic lungs appear to have an association with fetal trisomy 21.     

Maternal serum alpha-fetoprotein screening in a provincial Health District.

Maternal serum alpha-fetoprotein (AFP) estimation as a routine screening test for neural tube defect (NTD) was introduced into the West Berkshire Health District, where 17 per cent of all deliveries and most of the antenatal care is undertaken by the general practitioners. In the first year, 4458 patients were screened and 43 of those (0.96 per cent) had raised serum AFP levels. Amniocentesis was performed on 31 patients (0.69 per cent). Ten fetuses with severe NTDs and one with exomphalos were detected and the pregnancies terminated. In six patients, raised serum AFP levels were due to fetal death. No normal pregnancy was terminated. Acceptability by patients was high. Provided that a good diagnostic ultrasound facility is available locally, maternal serum AFP estimation seemed to be a valuable screening test.     

A role for maternal serum screening in detecting chromosomal abnormalities in fetuses with isolated choroid plexus cysts: a prospective multicentre study.

A prospective multicentre study was performed to identify patients with fetal choroid plexus cysts and examine the association between choroid plexus cysts and chromosome abnormalities in the context of variables such as maternal age, serum triple-screen results, race, other prenatally-identified fetal anomalies and cyst characteristics. A total of 18 437 scans were performed in 5 centres and 257 fetuses were identified with choroid plexus cysts. Outcome was available on 250 patients, and of these, chromosomal abnormalities were detected in a total of 13 (5.2 per cent) fetuses. 26 patients in the group had additional ultrasound abnormalities, and 8 of these had fetal chromosome abnormalities. Among the 224 patients with isolated choroid plexus cysts, 5 (2.2 per cent) were found to have chromosomal abnormalities. All cases with identified chromosomal abnormalities were associated with an additional risk factor, such as other ultrasound findings, advanced maternal age or abnormal maternal serum triple-screen results.     

alpha-Fetoprotein levels in pregnancies complicated by gastrointestinal abnormalities of the fetus.

alpha-Fetoprotein (AFP) levels have been measured in maternal serum and amniotic fluid in a variety of gastrointestinal abnormalities of the fetus. Maternal serum AFP levels were consistently elevated in abdominal wall defects of the fetus after 15 weeks gestation and the amniotic fluid levels were raised in 3 of the 4 patients measured. In atresia of the gastrointestinal tract and diaphragmatic hernia, serum AFP levels were usually normal unless there was an associated neural tube defect or multiple pregnancy, although the majority were not measured between 15 and 26 weeks gestation. If elevated amniotic fluid levels of AFP are used in the decision to terminate pregnancy on the assumption of a probable neural tube defect of the fetus, a proportion of terminations will be performed because of abdominal wall defects of the fetus.     

Screening for fetal neural tube defects by maternal plasma alpha-fetoprotein determination.

A total of 5539 consecutive pregnant patients at three maternity units in the City and Hackney District of London were screened for fetal neural tube defect by measurement of maternal plasma alpha-fetoprotein (AFP) levels. Only 25-7% of women booked at 16 to 22 weeks, the optimum time for this screening test; 54-1% booked before 16 weeks and 20-2% after 22 weeks. Of the women tested before 23 weeks, 300 had elevated levels of AFP in plasma and 14 of them had fetuses with abnormalities known to cause a rise in AFP levels (12 fetuses had a neural tube defect and 2 had alimentary tract abnormalities). Of women examined before 23 weeks, half of those with twin pregnancies had elevated levels of plasma AFP as did 16-7% of those who ultimately had a spontaneous abortion.     

Detection of neural tube defects with alpha-fetoprotein measurement in amniotic fluid. A protocol for managing elevated values

The clinical efficacy of rocket immunoelectrophoresis (RIE) and radioimmunoassay (RIA) methods for the measurement of amniotic fluid alpha-fetoprotein (AFP) were compared in separate series of over 1,000 pregnancies each. Using a mean +3 SD limit, 21 of 1,414 pregnancies monitored with RIE and 21 of 1,006 monitored with RIA were interpreted as having borderline elevated values. Five of the elevated AFP values in each series represented abnormal fetuses. No neural tube defects went undetected, although one was recognized only with ultrasound. Only two of seven abnormal fetuses had a family history of neural tube defects, indicating that maternal serum AFP measurement is an important preventive measure in pregnancies that are not recognized as at high risk. The data support the use of commercially available RIA kits for amniotic fluid AFP measurement and suggest a protocol for management of elevated values.     

Screening for chromosomal anomalies with maternal serum alpha-fetoprotein

Between July 1, 1986 and January 31, 1988, genetic amniocentesis was performed on 205 patients. The maternal serum alpha-fetoprotein (AFP) and amniotic fluid AFP levels were measured by enzyme immunoassay. Gestational dates were confirmed by sonography, and AFP results were expressed as multiples of the median (MOM). The median of maternal serum AFP from 15 to 17 weeks of gestation was 43.4, 62.6 and 72.5 ng/ml. Three fetuses with chromosomal anomalies were diagnosed; trisomy 21, 4p trisomy, and trisomy 18 (trisomy 18 was in one fetus of a twin pregnancy; the other fetus was normal). Maternal serum AFP levels were, 0.41, 0.49 and 1.30 MOM. Maternal serum AFP less than 0.5 MOM in normal pregnancies was 1/205 (0.5%) and less than 0.6 MOM was 9/205 (4.4%). There was no relationship between maternal serum AFP and amniotic fluid AFP levels. Our results are in agreement with the majority of the results in the literature, showing that maternal serum AFP levels are lower in association with autosomal trisomy fetuses.     

Antenatal evaluation of an encephalocele in a dizygotic twin pregnancy using fast magnetic resonance imaging

We report a case of an encephalocele in a dizygotic twin pregnancy, following ovulatory induction. In the involved fetus, an abnormal shadow like an encapsulated-solid tumor located on the occiput was found by routine maternal transabdominal ultrasonography at 17 weeks of gestation. The parents did not accept induced abortion because of the presence of another fetus with no abnormality on ultrasonography. At 35 weeks of gestation, transabdominal ultrasound examination showed a large occipital cyst, composed of protrusive fetal brain and cerebrospinal fluid. Fast-scanning magnetic resonance imaging delineated more clearly the inside of the abnormal lesion and thus allowed confirmation of the putative diagnosis of fetal encephalocele during pregnancy. Surgical report was possible in this case, and the patient had no severe physical or neurological abnormalities 10 months after birth. Since the prognosis appears to depend primarily on how prominent the brain tissue is inside the herniated sac, this approach had benefit for clinical decision making.     

双胎妊娠中结构异常胎儿染色体核型异常的临床特征

目的：探讨双胎妊娠中结构异常胎儿的染色体核型异常的临床特征。方法2000年1月-2010年9月,中山大学附属第一医院就诊的双胎妊娠孕妇181例（共362个胎儿）,对其中介入性产前诊断的308个胎儿按不同因素分组如下。(1)按孕妇年龄分组：≥35岁孕妇（105个胎儿）为高龄孕妇组;＜35岁孕妇（203个胎儿）为适龄孕妇组。(2)按受孕方式分组：辅助生育孕妇（81个胎儿）为辅助生育组,自然受孕（227个胎儿）为自然受孕组。(3)按绒毛膜性质分组：单绒毛膜双胎（MCT,123个胎儿）为MCT组,双绒毛膜双胎（DCT,185个胎儿）为DCT组。(4)按结构异常分组：205个结构异常胎儿为异常胎儿组,103个正常胎儿为正常胎儿组。对362个胎儿进行超声检查并对其中的308个双胎胎儿行染色体核型分析。结果(1)胎儿染色体核型分析结果：181例双胎孕妇中检出胎儿核型异常23例(12.7％,23/181),核型异常的23例双胎孕妇中,20例检查了两个胎儿的核型。308个胎儿中检出异常核型的胎儿26个(8.4％,26/308),以非整倍体最多见,占异常核型的53.8％ (14/26)。205个异常胎儿中21个有染色体核型异常(10.2％,21/205);103个正常胎儿中5个有染色体异常(4.9％,5/103),两者比较,差异无统计学意义(P＞0.05)。(2)MCT组和DCT组胎儿染色体核型异常发生率比较：MCT组123个胎儿中7个有染色体异常,发生率为5.7％ (7/123);DCT组185个胎儿中19个有染色体异常,发生率为10.3％( 19/185),两组胎儿的染色体异常发生率比较,差异无统计学意义(P＞0.05)。在染色体异常类别中,DCT组有14个胎儿为非整倍体异常,非整倍体率为7.6％(14/185),而MCT组无一例发生,两组比较,差异有统计学意义(P＜0.05)。DCT组中,两例双胎中因l胎死亡仅检查有结构异常的另一个活胎,分别为21三体和18三体;其余17例均分别检查了两个胎儿,两个胎儿的染色体核型不相同。DCT组19个核型异常的胎儿中,15个胎儿超声检查提示为结构异常(15/19)。MCT组中,4例双胎中有7个胎儿检出染色体异常。(3)高龄孕妇组和适龄孕妇组胎儿染色体异常发生率比较：高龄孕妇组胎儿的染色体异常发生率为7.6％(8/105),适龄孕妇组为8.9％( 18/203),两组比较,差异无统计学意义(P＞0.05);在染色体异常类别中,高龄孕妇组6个胎儿为非整倍体异常(5.7％,6/105),适龄孕妇组仅8个胎儿(3.9％,8/203),高龄孕妇组胎儿的非整倍体率显著高于适龄孕妇组,差异有统计学意义(P＜0.05)。(4)辅助生育组和自然受孕组胎儿染色体异常发生率比较：辅助生育组81个胎儿中有l1个染色体异常(13.6％,11/81),自然受孕组227个胎儿中有15个染色体异常(6.6％,15/227),差异有统计学意义(P＜0.05)。在染色体异常类别中,辅助生育组7个胎儿为非整倍体异常(8.6％,7/81),自然受孕组也为7个胎儿(3.1％,7/227),差异无统计学意义(P＞0.05)。(5)异常胎儿组和正常胎儿组染色体异常发生率比较：异常胎儿组205个胎儿中有21个染色体异常(l0.2％,21/205),正常胎儿组103个胎儿中有5个染色体异常(4.9％,5/103),两组比较,差异无统计学意义(P＞0.05);在染色体异常类别中,异常胎儿组13个胎儿为非整倍体异常(6.3％,13/205),正常胎儿组仅1个胎儿(1.0％,1/103),两组比较,差异有统计学意义(P＜0.05)。结论非整倍体是双胎合并胎儿结构异常时最常出现的染色体异常,以21三体最为常见。双胎之间的核型不一致和双胎之一出现非整倍体的情况常见于DCT,而MCT时两个胎儿核型往往一致,但两个胎儿发生相同的染色体异常可能出现不同的表型;双胎之一合并胎儿结构异常时,建议分别对两个胎儿同时行染色体核型分析。     

2nd-trimester maternal serum human chorionic gonadotropin and alpha-fetoprotein levels in male and female fetuses with Down syndrome

BACKGROUND/OBJECTIVE: Several studies have shown that the 2nd-trimester maternal serum alpha-fetoprotein (AFP) level is significantly lower and that the maternal serum human chorionic gonadotropin (hCG) level is significantly higher in the presence of a female fetus. This may potentially affect Down syndrome (DS) screening such that a higher false-positive rate may occur in women carrying a female fetus, whereas a lower detection rate may result in those carrying males. The purpose of this study was to evaluate the gender impact on marker levels in DS pregnancies and its effect on DS screening. METHODS: The study included 62 DS pregnancies with a single fetus of known gender (31 male and 31 female). Only pregnancies with chromosomal analysis showing trisomy 21 were included. The maternal serum levels of hCG, AFP, and unconjugated estriol were measured at 16-20 weeks of pregnancy. These levels were expressed as gestational-age-corrected multiples of the median. RESULTS: No statistically significant differences were noted in maternal serum levels of hCG or AFP in DS pregnancies between women carrying a female and those carrying a male DS fetus. No statistically significant differences in 'screen-negative' rates were noted among male and female fetuses. CONCLUSIONS: In normal pregnancies, the maternal serum hCG level is higher, and the AFP level is lower in the presence of a female fetus. However, this gender-related difference is not apparent in DS pregnancies. Therefore, the gender-related differences in serum marker levels would not result in a lower detection rate of DS in male fetuses.     

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.     

Comparison between ultrasound and magnetic resonance imaging in assessment of fetal cytomegalovirus infection

OBJECTIVE: To evaluate whether fetal brain magnetic resonance imaging (MRI) adds useful information to the one obtained by ultrasound in fetuses with cytomegalovirus (CMV) infection. METHODS: MRI and ultrasonographic findings were analyzed retrospectively in 38 fetuses with proven congenital CMV infection. Both techniques were performed on the same week at a mean gestational age of 33 weeks (24-37). The referral indications were maternal seroconversion (n = 19), and ultrasound findings (n = 19). The results were compared with the fetopathologic examination in cases with fetal death or termination of pregnancy (TOP) or the infant's neurological examination. RESULTS: The 38 cases were classified into three groups, depending on ultrasound findings at referral. Group 1: no ultrasound features (n = 11); group 2: extracerebral features without cerebral abnormalities at ultrasound (n = 13); group 3: presence of cerebral features at ultrasound (n = 14). In group 1, MRI was always normal. In group 2, MRI revealed cerebral features in six cases (46%). In group 3, MRI always confirmed the lesions seen at ultrasound and highlighted other cerebral features. CONCLUSIONS: MRI can provide important additional information with regard to abnormal gyration, cerebellar hypoplasia, or abnormal signal in white matter. It is certainly useful in the assessment of fetuses with extracerebral features without brain abnormalities detected with ultrasounds. If the fetal ultrasound is strictly normal in an infected fetus, MRI may not detect brain anomalies; however, it seems difficult to not perform this noninvasive procedure.     

Evaluation of elevations in maternal serum alpha-fetoprotein: a review.

Maternal serum AFP screening has had significant clinical impact on reducing unrecognized anencephaly and open neural tube defects at delivery. In addition, a growing number of other associations with maternal serum AFP elevations have become apparent since antepartum screening has become commonplace. We present in this review a clinically oriented approach to understanding the physiologic basis of maternal serum AFP elevations, both true- and false-positives. Compartmentalization of etiology, fetal and maternal, and routes of communication, amniotic fluid and placenta, allows a more logical approach to developing a differential diagnosis in this group of patients. In evaluating an elevation in maternal serum AFP, it is first necessary to consider the amount of fetal production by confirming the gestational age of the fetus and the number of fetuses present. Adjustments for maternal factors (weight, race, diabetes) must also be made. Fetal developmental defects which may lead primarily to leakage of the fetal proteins into the surrounding amniotic fluid with secondary elevations of maternal serum AFP enter into the differential diagnosis. The placenta itself is probably not a production source of AFP, but when the placenta is abnormal, a greater amount of AFP may be transported to the maternal circulation. Although our thoughts frequently do turn first to an increased maternal serum AFP reflecting an increased AFP concentration in the amniotic cavity with greater transference "across the membranes," in fact a far more common etiology is an increased transfer from the fetal circulation to the maternal via the fetal-maternal interface within the placenta. This is supported by the simple fact that the vast majority of maternal serum AFP elevations are not associated with amniotic fluid AFP elevations; the amniotic fluid AFP concentrations are usually normal. Thus, in circumstances where the fetal anatomy is grossly normal and there is not another explanation for elevations in maternal serum AFP, the placenta, either secondary to providing increased areas of transport or in providing an abnormal endothelial barrier, allows for greater transfer of fetal serum, and thus AFP, into the maternal compartment. An abnormal placenta is also a likely explanation for the increased risk of adverse pregnancy outcome that is associated with increased maternal serum AFP elevations for which no obvious etiology is found. The case herein reported suggests that an abnormal placenta which provides an altered interface for AFP flow between the fetal and maternal circulations may in fact be the etiology of the significant elevations of maternal serum AFP seen in cases of triploidy.(ABSTRACT TRUNCATED AT 400 WORDS)     

Elevated maternal serum alpha-fetoprotein, second-trimester oligohydramnios, and pregnancy outcome

Although the primary purpose of maternal serum alpha-fetoprotein (AFP) screening is to detect open neural tube defects, the technique is of value in the diagnosis of other fetal abnormalities. Six patients from the Alpha-Fetoprotein Screening Program, Perinatal Region IV, were found to have twice elevated maternal serum AFP levels associated with severe early second-trimester oligohydramnios. Five of the fetuses were found to have urinary tract abnormalities. The source of the elevated maternal serum AFP is not clear. Pregnancy prognosis appears poor. These cases should be thoroughly studied so that patients may be accurately informed of the recurrence risk.     

Second trimester ultrasound screening for chromosomal abnormalities

The use of prenatal ultrasound has proven efficacious for the prenatal diagnosis of chromosomal abnormalities. The first sonographic sign of Down syndrome, the thickened nuchal fold, was first described in 1985. Since that time, multiple sonographically-identified markers have been described as associated with Down syndrome. The genetic sonogram, involving a detailed search for sonographic signs of aneuploidy, can be used to both identify fetuses at high risk for aneuploidy and, when normal, can be used to decrease the risk for aneuploidy for a pregnancy when no sonographic markers are identified. Combining the genetic sonogram with maternal serum screening may be the best method of assessing aneuploidy risk for women who desire such an assessment in the second trimester. Trisomy 18, Trisomy 13, and triploidy are typically associated with sonographically identified abnormalities and have a high prenatal detection rate. The use of the described sonographic signs in low-risk women requires further investigation, however, patients at increased risk for aneuploidy due to advanced maternal age or abnormal serum screening can benefit from a genetic sonogram screening for sonographic signs of aneuploidy to adjust their baseline risk of an affected fetus.     

Concordant occipital encephalocele in monoamniotic twins

Anomalies occur with a greater frequency in twin gestations. Due to its multifactorial inheritance, twins are usually discordant for encephalocele. We present a case of monoamniotic twins concordant for occipital encephalocele and discordant for lung and cord anomalies.Ultrasonographic examination at 17 weeks' gestation revealed occipital encephalocele in both fetuses. The maternal serum level of alpha-fetoprotein was increased. Fetal autopsy revealed occipital encepaholocele in both twins and right pulmonary hypoplasia and one umbilical artery in one sibling. Monoamniotic twins concordant for encephalocele occur with extreme rarity. To the best of our knowledge, monoamniotic twins concordant for this neural tube defect have not been previously reported.