Second-trimester cystic hygroma: prognosis of septated and nonseptated lesions.

OBJECTIVE: To compare karyotypic, ultrasonographic, and prognostic features of septated cystic hygromas and nonseptated cystic hygromas in second-trimester fetuses. METHODS: A computerized ultrasound data base was used to identify fetuses diagnosed with cystic hygromas at 14-22 weeks' gestation. Photographs from the initial ultrasound were reviewed retrospectively for hygroma type (septated or nonseptated) and any abnormal structural findings. Fetal karyotypes were obtained from amniotic fluid, aspiration of hygroma pouches, or fetal tissue culture. Pregnancy outcome information was obtained from hospital charts and physician office records. Ultrasound findings were then compared with fetal karyotype results and pregnancy outcome data. RESULTS: From 1990 to 1995, 61 fetuses with cystic hygromas were identified. Karyotypes were obtained in 55 fetuses, and pregnancy outcome was available for 59. Abnormal karyotype was present in 42 of 55 fetuses (76%). The most common chromosomal abnormality in septated hygromas was the 45,X karyotype. Trisomy 21 was the most common chromosomal abnormality in nonseptated hygromas. Compared with fetuses with nonseptated cystic hygromas, those with septated cystic hygromas were more likely to be aneuploid (33 of 39 [85%] versus nine of 16 [56%]; P = .03), more likely to develop hydrops (27 of 45 [60%] versus three of 16 [19%]; P = .005), and less likely to be live-born (one of 44 [2%] versus four of 15 [27%]; P = .01). CONCLUSIONS: Fetuses with septated cystic hygromas are more likely to be aneuploid and to develop hydrops, and thus are less likely to be survive than fetuses with nonseptated hygromas.

Pregnancy outcome following genetic amniocentesis at 11-14 versus 16-19 weeks' gestation.

OBJECTIVE: To compare pregnancy complications in women having genetic amniocentesis at 11-14 weeks versus those undergoing amniocentesis at 16-19 weeks' gestation. METHODS: A genetics data base was used to identify patients retrospectively, those who had genetic amniocenteses by three experienced operators during a 4-year period. The study group consisted of women who had amniocenteses at 11-14 weeks' gestation. For each study patient (early amniocentesis), two controls (amniocentesis at 16-19 weeks) were identified and matched for maternal age, race, and the number of prior spontaneous abortions. An immediate post-procedure complication was defined as any vaginal bleeding, rupture of membranes, or fetal loss occurring up to 30 days after the amniocentesis. A later complication was defined as any fetal death longer than 30 days after the amniocentesis, any preterm delivery, any infant weighing less than the tenth percentile for gestational age, and any neonatal death. Immediate and later complications were compared between the study and control groups. RESULTS. The study group consisted of 314 patients who were matched to 628 controls. Women who had a genetic amniocentesis performed at 11-14 weeks were significantly more likely to have post-procedure amniotic fluid leakage (2.9 versus 0.2%), post-procedure vaginal bleeding (1.9 versus 0.2%), and a fetal loss within 30 days of the amniocentesis (2.2 versus 0.2%) than women undergoing genetic amniocentesis at 16-19 weeks' gestation. Four of the seven patients (57%) with a fetal loss within 30 days of an early amniocentesis had procedure-related complications, such as amniotic fluid leakage, bleeding, and infection, that caused the pregnancy to be lost. No differences were noted between the two groups in the number of preterm deliveries, later fetal deaths, neonatal deaths, or newborns weighing less than the tenth percentile for gestational age. CONCLUSION: Genetic amniocentesis at 11-14 weeks is associated with more post-procedure complications and a higher fetal loss rate within 30 days of the procedure than a genetic amniocentesis performed at 16-19 weeks' gestation.

Multiple marker screening test: identification of fetal cystic hygroma, hydrops, and sex chromosome aneuploidy.

The goal of this study was to determine if the multiple marker screening test (maternal serum alpha-fetoprotein, unconjugated estriol, human chorionic gonadotrophin, and maternal age) detects fetal Turner syndrome or just cystic hygroma/hydrops. Multiple marker screening tests from 4 groups were compared: 1) Turner syndrome with hydrops/ hygroma group (n = 10) = fetuses with cystic hygroma/hydrops and a 45X karyotype, 2) Turner syndrome without hydrops/hygroma (n = 9) = sonographically unremarkable fetal Turner syndrome or Turner mosaic, 3) hydrops group (n = 8) = all cases of fetal cystic hygroma/hydrops excluding Turner syndrome, 4) sex chromosome aneuploidy group (n = 16) = other sonographically normal fetal sex chromosome aneuploidies. Positive screening tests (Down syndrome risk > or = 1:190 or MSAFP > or = 2.5 MOM) were found in 60% (6/10) of the Turner syndrome with hydrops/hygroma group, but only 11% (1/9) of the Turner syndrome without hydrops/hygroma group (P = .04). The incidence of positive screening tests in the Hydrops group was 75% (6/8), while it was only 12.5% (2/16) in the other sex chromosome aneuploidy group. We conclude that the multiple marker screening test identifies fetuses with cystic hygroma/hydrops, and may do so independently of the etiology of the hydrops.

Paracentric inversions in humans: a review of 446 paracentric inversions with presentation of 120 new cases.

We present a large review of 446 cases of paracentric inversions (PAI), including 120 new cases, to assess their incidence, distribution, inheritance, modes of ascertainment, interchromosomal effects, viable recombinant offspring, and clinical relevance. All 23 autosomes and sex chromosomes had inversions. However, none were identified in chromosome arms 18p, 19q, 20q, and Yp. PAI were most commonly reported in chromosomes 1, 3, 5, 6, 7, 11, and 14 and less frequently in chromosomes 4, 16, 17, 18, 19, 20, 21, 22, and Y. Inversions were most common in chromosome arms 6p, 7q, 11q, and 14q and observed least in chromosome arms 2p, 2q, 3q, 4q, and 6q. Frequently encountered breakpoints included 3(p13p25), 6(p12p23), 6(p12p25), 7(q11q22), and 11(q21q23). Ascertainment was primarily incidental (54.5%), mental retardation and/or congenital anomalies (22.2%), spontaneous abortions (11.4%), associations with syndromes (3.0%), and infertility (2.0%) accounted for the remainder. Ascertainment was neither related to the length of the inverted segment nor to specific inversions except for PAI of Xq which often presented with manifestations of Ullrich-Turner syndrome. Sixty-six percent of PAI were inherited while 8.5% were de novo. Recombination was observed in 17 cases, 15 of which resulted in a monocentric chromosomal deletion or duplication. No common factors were identified that suggested a tendency towards recombination. The incidence of viable recombinants was estimated to be 3.8%. This review documents that PAI are perhaps more commonly identified than suggested in previous reviews. Despite the possible bias of ascertainment in some cases, there may be associated risks with PAI that require further examination. Our data suggest that PAI carriers do not appear to be free of risks of abnormalities or abnormal progeny and caution is recommended when counseling.

The utility of fetal biometry as an adjunct to the multiple-marker screening test for Down syndrome.

OBJECTIVE: Our purpose was to investigate fetal biometry as an adjunct to the multiple-marker screen (maternal age, serum alpha-fetoprotein, estriol, and human chorionic gonadotropin) for Down syndrome. STUDY DESIGN: Fifty-two cases of Down syndrome were compared with 7514 normal fetuses. The measured/predicted femur length ratio had the best discriminant value (1.0 +/- 0.11 vs 0.93 +/- 0.13, p < 0.0001). Multivariate gaussian algorithms were developed and each computed a likelihood ratio for Down syndrome. The trivariate algorithm incorporated the three maternal analytes, whereas the quadrivariate version also included the femur length ratio. The study population included 38 cases of Down syndrome and 1098 euploid controls. The midtrimester risk was the product of the age-related risk and the likelihood ratio. RESULTS: The relative difference in the femur length ratio between normal and affected fetuses was small in comparison to that of the maternal serum analytes. At a risk cutoff of > or = 1:190 the detection rates were similar and actually favored the trivariate algorithm but differed only by one case of Down syndrome. CONCLUSION: The addition of the measured/predicted femur length ratio had a negligible effect on the performance of the multiple-marker screening test.

Relationship between amniotic fluid and maternal blood nutrient levels.

To study the relationships between amniotic fluid and maternal blood nutrient concentrations, we obtained amniotic fluid and blood samples simultaneously from 76 pregnant women at around 17 weeks gestation. Folate and vitamin B-12 levels were measured by microbiological assay and radioassay, respectively, and zinc, copper and iron levels by atomic absorption spectrophotometry. Mean concentrations of plasma and red blood cell (RBC) folate and plasma copper of the pregnant women were 38 (+/- 1, SD), 1,501 (+/- 374) nmol/L, and 32.7 (+/- 4.8) mumol/L, respectively, all of which were higher than those of healthy non-pregnant controls (p < 0.001). Mean concentrations of plasma vitamin B-12, zinc and iron levels and RBC zinc were 320 (+/- 130) pmol/L, 12.2 (+/- 2.3), 21.7 (+/- 6.1) and 177 (+/- 30) mumol/L and these were similar to those of non-pregnant controls. Amniotic fluid folate, zinc, copper and iron concentrations were 21 (+/- 13) nmol/L, 1.4 (+/- 0.6), 1.7 (+/- 0.6) and 6.8 (+/- 2.1) mumol/L, respectively, which were significantly lower than plasma levels (p < 0.001). However, this relationship was reversed for vitamin B-12 (650 +/- 420 pmol/L). Significant correlations were found between amniotic fluid and maternal plasma and RBC for folate, and between amniotic fluid and maternal plasma for vitamin B-12 (p < 0.001). No such correlations were observed for zinc, copper and iron. There was no correlation between amniotic fluid and/or blood nutrient concentrations and pregnancy outcome including birth weight of infants.

Nutrient levels in amniotic fluid from women with normal and neural tube defect pregnancies.

We analyzed nutrient levels in amniotic fluid obtained during the second trimester of normal, uncomplicated pregnancies from 221 women who delivered apparently healthy infants and from 8 with neural tube defect (NTD) pregnancies. Folate was measured by microbiological assay, vitamin B12 by a radiobinding method, and zinc, copper and iron by atomic absorption spectrophotometry. We found that the mean amniotic fluid nutrient levels of normal pregnancies were 24.7 nmol/l for folate, 600 pmol/l for vitamin B12, and 1.7, 1.9, and 9.0 mumol/l for zinc, copper and iron, respectively. Amniotic fluid folate, zinc, copper and iron levels of NTD pregnancies were similar to those found during normal pregnancy, however, vitamin B12 levels were markedly lower than those of normal pregnancies.

Fetal obstructive uropathies. Importance of chromosomal abnormalities and associated anomalies to perinatal outcome.

The ultrasound records of 30 fetuses suspected of having an obstructive uropathy were reviewed retrospectively. A prenatal karyotype was obtained with amniocentesis on each patient. After delivery, neonatal urologic records, renal ultrasound reports and autopsy information were reviewed and compared to the ultrasound records and fetal karyotype results. Chromosomal defects were found in 23% of fetuses with a suspected obstructive fetal uropathy. In five patients the chromosomal abnormality was lethal and caused 45% of the perinatal deaths in this series. If a fetus with an obstructive uropathy was female, there was a significant likelihood of an extrarenal anomaly or a complex genitourinary tract malformation. Seventeen percent of patients with an obstructive uropathy had a coexistent extrarenal defect. A prenatal karyotype should be obtained if a fetal obstructive uropathy is suspected antenatally since lethal chromosomal defects are an important cause of perinatal death. A female karyotype may indicate a fetus at higher risk of extrarenal anomalies or complex genitourinary malformations.

Management of prenatally detected nonlethal fetal anomalies: is a karyotype of benefit?

The pregnancy outcomes of 155 women who underwent an amniocentesis for a prenatal karyotype after being diagnosed by ultrasound as having one or more nonlethal structural anomalies are presented. Thirty-three (21%) patients were found to have an abnormal karyotype. Knowledge of the prenatal karyotype was useful in the subsequent management of these pregnancies. A pregnancy with a fetal anomaly diagnosed prior to 24 weeks was more likely to be terminated if an abnormal karyotype was also present. In women who were diagnosed as having a fetal anomaly with an abnormal karyotype at 24 weeks or later, only 3 of 13 (23%) infants survived the neonatal period. Knowledge of the karyotype results influenced decisions regarding the place, timing, and route of delivery in these fetuses. In 32 women, (21%) a karyotype was beneficial by avoiding maternal transport, cesarean delivery, and neonatal expenses at a Level III perinatal center.

Second case report of del(4) (q25q27) and review of the literature.

We report a malformed infant with a de novo interstitial deletion of 4q. This is the second patient reported with del(4) (q25q27). Although there are several common features such as marked hypotonia, cardiac abnormalities, cleft palate, and micrognathia noted in our case and that of Chudley et al. (1988), we conclude from our comparison of the seven previously reported cases involving deletions of bands 4(q25q27) that a specific phenotype cannot yet be described for this deletion.

45,X/47,XYY mosaicism: clinical discrepancy between prenatally and postnatally diagnosed cases.

45,X/47,XYY mosaicism is a rare chromosomal disorder with clinical information limited to 11 postnatal cases in the literature and with uncertainty regarding prenatal prediction of phenotype and prognosis. We report on 7 new cases of 45,X/47,XYY mosaicism, three detected prenatally and 4 diagnosed postnatally. A clinical comparison of the cases of 45,X/47,XYY mosaicism is presented together with a literature review.

Sonographic measurements and ratios in fetuses with Down syndrome.

Ultrasound measurements of 15 fetuses with trisomy 21 detected during the 17th week of gestation were matched retrospectively to those of 45 normal controls. We compared nine standard ultrasound measurements of the fetal head, abdomen, and femur in these two groups. The fetuses with trisomy 21 had significantly shorter mean femur lengths, narrower occipitofrontal diameters, and increased biparietal diameter (BPD)/femur length and abdominal circumference/femur length ratios. An increased BPD/femur length ratio was the ultrasound finding that best predicted a fetus with Down syndrome. A BPD/femur length ratio of 1.80 or higher was 40% sensitive and 97.8% specific in predicting Down syndrome, and had a false-positive rate of only 2.2%. An increased second-trimester BPD/femur length ratio measured by ultrasound may prove beneficial as an additional screening test for Down syndrome.

Amniotic fluid alpha-fetoprotein levels and pregnancy outcome.

Elevated and low levels of maternal serum alpha-fetoprotein in the midtrimester of pregnancy have been linked with adverse events in later gestation, such as fetal and neonatal deaths, chromosomal abnormalities, and low birth weight infants. It is not known if this same association with poor pregnancy outcome is also true of amniotic fluid alpha-fetoprotein. In this study, alpha-fetoprotein was obtained from the fluid of 1060 women undergoing genetic amniocentesis for advanced maternal age. Poor pregnancy outcome was defined as (1) a fetal or neonatal death, (2) preterm delivery, or (3) low birth weight infants. Amniotic fluid alpha-fetoprotein was compared to each type of adverse outcome. No significant association with a poor pregnancy outcome in later gestation was noted. Although serum alpha-fetoprotein in the midtrimester of pregnancy may relate to certain poor outcomes in later gestation, midtrimester amniotic fluid alpha-fetoprotein offers no predictive value for the course of events in later gestation.

Decreased levels of amniotic fluid alpha-fetoprotein associated with Down syndrome.

Low maternal serum alpha-fetoprotein levels have been associated with fetal aneuploidies. Amniotic fluid alpha-fetoprotein levels have been reported to be low with Down syndrome (trisomy 21) but not with other fetal trisomies. We compared the amniotic fluid alpha-fetoprotein levels from 25 cases of autosomal trisomy (18 of trisomy 21, four of trisomy 13, three of trisomy 18) diagnosed by midtrimester fetal cytogenetic studies with those from matched, cytogenetically normal pregnancies. With these normal pregnancies used as controls, statistical analyses were performed on the data for all the trisomic fetuses, on the data for trisomy 21 only, and on the data for trisomies 13 and 18 combined. Amniotic fluid alpha-fetoprotein levels were significantly lower in the 25 trisomic cases compared with controls, 0.77 +/- 0.34 versus 1.03 +/- 0.34 mg/dl (p less than 0.001). However, further analysis revealed that the difference was due to the trisomy 21 data alone. In the trisomy 21 cases there was a significant difference for alpha-fetoprotein levels between cases and controls (p less than 0.001), whereas there was no difference for the combined trisomy 13 and 18 cases compared to controls (p greater than 0.40). These findings suggest that the low maternal serum levels of alpha-fetoprotein reported in cases of Down syndrome may be related to reduced amniotic fluid concentrations. However, the reduced maternal serum alpha-fetoprotein levels reportedly associated with trisomies 13 and 18 do not seem to be explained by low amniotic fluid concentrations.