Prenatal diagnosis of Freeman–Sheldon syndrome (whistling face)

The diagnosis of Freeman–Sheldon syndrome was made by ultrasonographic evaluation of a 20-week fetus with a positive family history. The ultrasonographic features were abnormalities of the extremities and mouth.     

Second-trimester cancer antigen 125 and Down's syndrome

This study explores if assay of cancer antigen 125 (CA 125) in maternal serum might aid the detection of Down's syndrome in the second trimester of pregnancy. CA 125 levels were determined retrospectively in stored maternal serum samples from ten Down's syndrome pregnancies and 78 controls matched for gestational and maternal age. In addition, second-trimester amniotic fluid samples from nine Down's syndrome and 109 unaffected pregnancies were analysed for CA 125. Maternal serum CA 125 values for Down's syndrome pregnancies were lower, with the median being 0.72 multiples of the unaffected population median. The medians for affected and unaffected pregnancies did not differ significantly and there was a considerable overlap in the range of values of cases and controls. The distribution of amniotic fluid CA 125 levels for Down's syndrome pregnancies resembled that for controls. From our present results, we could not find an association between Down's syndrome and second-trimester maternal serum or amniotic fluid CA 125 levels.     

Early prenatal diagnosis of an infratentorial arachnoid cyst: Association with an unbalanced translocation

Arachnoid cysts are an uncommon central nervous system malformation, representing only 1 per cent of all intracranial masses. We report the second-trimester prenatal diagnosis of a posterior fossa arachnoid cyst, associated with an unbalanced X;9 translocation.     

Attitudes to prenatal screening,diagnosis and research among pregnant women who accept or decline an alpha-fetoprotein test

The aim of the study was to describe the opinion of pregnant women who had accepted or declined an alpha-fetoprotein (AFP) test, not only on AFP screening in general, but also on whether every pregnant woman should be offered amniocentesis (AC)/chorionic villus sampling (CVS) and an ultrasound scan for fetal malformations. An additional aim was to describe pregnant women's attitudes concerning continued research in the prenatal field. The study was performed as a questionnaire study in two regions over a 1-year period from 1 October 1988 to 30 September 1989. Results are based on answers from 3331 women who had taken an AFP test and 336 women who had declined the offer of a test. A total of 79 per cent of the women thought that an AFP test, 70 per cent that an ultrasound scan for fetal malformations, and 26 per cent that AC or CVS should be offered to all pregnant women. Fifty-nine per cent of the women were positive towards continued research in the prenatal field. Women who had had an AFP test were generally much more positive towards screening and research than women who had declined, who were generally against. Women who had left school without a high school degree were on average more positive towards the screening issues than women who had this degree. In conclusion, the results obtained in this study strongly suggest that women's attitudes are very dependent on how the prenatal screening programme is already organized in their local area.     

Flow sorting of fetal erythroblasts using intracytoplasmic anti-fetal haemoglobin: Preliminary observations on maternal samples

Monoclonal antibody to fetal haemoglobin (a₂γy₂) has been proposed as a fetal-specific reagent. We developed an intracellular staining protocol that combines fluorescein isothiocyanate or phycoerythrin conjugated anti-γ with the DNA binding dye Hoechst 33342 to identify and flow sort fetal erythroblasts from maternal blood. Our preliminary observations on anti-γ-positive cells sorted from four different pregnant women are described here, using fluorescence in situ hybridization (FISH) with chromosome-specific probes to identify fetal cells. Our data demonstrate that far fewer candidate fetal cells are sorted with this protocol than by current cell surface staining methods that employ the monoclonal antibody CD71. This results in increased fetal cell sorting purities. With this protocol, standard FISH techniques require modification due to the rigorous fixation with 4 per cent paraformaldehyde. Our initial data indicate the promise of this approach.     

Enhanced twin pregnancy detection within an open neural tube defect and down syndrome screening protocol using free-beta hCG and AFP

We have applied our multimarker approach of maternal serum alpha-fetoprotein (AFP) and free-beta human chorionic gonadotropin (hCG) for Down syndrome screening to multiple gestations to assess its efficacy for improved detection of twin and triplet pregnancies. This study matched 225 cases of twin pregnancy and 39 cases of triplet pregnancy each with ten singleton pregnancies based on gestational week, race, time to receive sample, time of year of sample, and geographical area. The ratios of the MOM for each group at the tenth, 50th, and 90th percentiles were compared by the Wilcoxon test. Risks for twins were calculated using Bayes' rule, the age-related incidence of twins, and the levels of AFP and free-beta hCG. The tenth, 50th, and 90th percentiles of free-beta hCG MOMs in twin and triplet cases were 0.85, 1.99, and 4.51, and 1.38, 2.78, and 4.07, respectively. For AFP, the MOMs at these percentiles were 1.26, 1.91, and 2.99, and 2.02, 2.68, and 5.30, respectively. The twin and triplet distributions for each marker were statistically significantly different from the singleton distributions (P<0.0001) and from each other (P=0.0012). At a twin risk cut-off of 1 in 50, 77.4 per cent of all twin gestations can be detected in a second-trimester AFP and free-beta hCG screening protocol with 5.1 per cent of singleton pregnancies falsely identified as at risk for twins. Our dual marker protocol for mid-trimester pregnancy screening combining AFP and free-beta hCG can identify over 77 per cent of twin pregnancies in women less than 35 years of age. This benefit may contribute to an improved outcome of pregnancy by early detection of multiple gestation.     

Origin of raised maternal serum alpha-fetoprotein levels in second-trimester oligohydramnios

Concanavalin A (Con A) subtyping of alpha-fetoprotein (AFP) revealed higher concentrations of AFP non-reactive with Con A in sera of 12 pregnant women with second-trimester oligohydramnios and raised total serum AFP levels than in sera of 42 pregnant women with raised total serum AFP levels and a normal amniotic fluid volume. This suggests that in oligohydramnios the origin of excess AFP in the maternal compartment is amniotic fluid. It is proposed that oligohydramnios and the associated raised maternal serum AFP levels are caused by damage of the fetal membranes prior to 16 weeks of gestation resulting in leakage of amniotic fluid to the decidual tissue and resorption in the maternal circulation.     

Superovulation fails to increase human blastocyst yield after uterine lavage

Uterine lavage affords the potential for non-invasive human blastocyst recovery, with obvious potential for preimplantation genetic diagnosis. In an effort to duplicate in women the multiple blastocyst recovery per cycle that can be achieved in several other species, we initiated a programme in which fertile women underwent superovulation, followed by lavage and embryo collection. We superovulated 15 fertile women, aged 21–40, in 29 cycles using one of four regimens. Insemination was by either intercourse or artificial intracervical donor insemination with cryopreserved sperm from men of proven fertility. In 28 of 29 cycles, the uterus was lavaged daily for 1, 2, or 3 days between 5 and 10 days after human chorionic gonadotropin (hCG) administration or luteinizing hormone (LH) surge. Almost total fluid volume was recovered in every lavage. There were no retained pregnancies and no complications. Surprisingly, only two morulae, one blastocyst, and four unfertilized ova were recovered. Thus, alterations in ovulation induction, insemination timing, or lavage techniques must be contemplated in order to increase the blastocyst yield and thus fulfil the potential of uterine lavage for preimplantation diagnosis.     

Association of generalized dystrophic epidermolysis bullosa with positive acetylcholinesterase and markedly elevated maternal serum and amniotic fluid alpha-fetoprotein

A case of fatal generalized dystrophic epidermolysis bullosa is described in a prematurely born female whose mother had strikingly elevated mid-trimester serum and amniotic fluid alpha-fetoprotein concentrations, a positive amniotic fluid acetylcholinesterase band, and negative serial ultrasound studies. This case lends further support to an association between autosomal recessive generalized dystrophic epidermolysis bullosa and increased levels of alpha-fetoprotein, positive amniotic fluid acetylcholines'terase, and normal ultrasound findings.     

First and early second-trimester diagnosis of fetal urinary tract anomalies using transvaginal sonography

Urinary tract anomalies are common. Prenatal diagnosis is important and enables either special obstetric management or termination of pregnancy and probably in the future, intrauterine intervention. Transvaginal sonography (TVS) allows visualization of the normal and anomalous fetal urinary tract at an early stage. One thousand nine hundred and forty women were examined via TVS at an early stage of pregnancy between 10 and 16 weeks from the last menstrual period (LMP) and 35 anomalies (1·8 per cent) were clearly identified: 29 cases of low urinary tract obstruction, 2 cases of multicystic dysplastic kidney, 2 cases of polycystic kidney (infantile type), 1 case of double collecting system, and 1 case of horseshoe kidney. Potter syndrome could be ruled out in three patients who had delivered fetuses suffering from this anomaly in previous pregnancies. The concise and early identification of anomalies makes TVS an important aid in the hands of the obstetrician, ultrasonographer, and neonatologist.