Grief and mid-trimester fetal loss

Fetal loss through miscarriage or termination of pregnancy for genetic reasons often provokes the grief of bereavement. This is not fully understood, and the extent of the distress is often underestimated by professionals and family alike. We have examined elements of the normal bereavement process and have found that they may occur in specific and accentuated forms in mid-trimester fetal loss. We discuss our findings in the light of the attachment theory—a psychodynamic model for understanding grief reactions.     

Fetal tissue involvement in the late infantile type of neuronal ceroid lipofuscinosis

Prenatal diagnosis in a pregnancy at risk for late infantile neuronal ceroid lipofuscinosis (Batten's disease) was undertaken at 17 weeks' gestation by ultrastructural examination of amniotic fluid cells. The presence of curvilinear profiles indicated an affected fetus and the diagnosis was confirmed, after the pregnancy was terminated, by the finding of many typical curvilinear profiles in multiple tissues which included skin, amnion, umbilical vessels, blood, liver, and brain. Comparison between the involved cells in the amniotic fluid and fetal tissues suggests that these cells are probably derived from the periderm, and possibly also from the amnion. The prominent presence of cytosomes in the periderm and intermediate cells of the fetal epidermis and occasionally also in the endothelial cells of the dermis suggests that fetal skin may be a useful alternative site for assessing fetal involvement. Control specimens of the amniotic fluid, fetal skin, amnion, and liver showed no similar cytosomes. However, some control amniotic fluid samples did contain cells with large collections of irregular trilaminar membranes, and these could be open to misinterpretation. It is important that only typical curvilinear profiles are considered as an indication of an affected pregnancy.     

Prenatal diagnosis of a fetus with partial monosomy 7(q34→qter) and partial trisomy 18(q21→qter)

Ultrasound examination of a 31-year-old woman at 27 weeks' gestation revealed fetal growth retardation, a bilateral cleft lip and palate, and the absence of median cerebral structures. Chromosome analysis after cordocentesis showed an abnormal karyotype with a structural abnormality of the long arm of chromosome 7: 46,XX,—7,+der(7), t(7;18) (q34;q21.3)mat. The pregnancy was terminated at week 29. The ultrasound findings were confirmed by post-mortem examination, which also revealed a semilobar holoprosencephaly.     

Can gestational dates routinely derived from very early ultrasound be used to interpret maternal serum alpha-fetoprotein measurements?

This study assesses the reliability of estimating gestational age via crown-rump or gestational sac measurements obtained at 8 weeks' gestation or earlier as part of routine physician office practice. To accomplish this, we studied 88 pregnancies managed at 45 different sites in which both an early first-trimester ultrasonically-derived gestational age estimate and a second-trimester biparietal diameter (BPD) estimate were available. The first-and second-trimester determinations were highly correlated, but the first-trimester determinations were, on average, 0.43 weeks earlier than the second. The first-trimester estimates were satisfactory for use in interpreting maternal serum alpha-fetoprotein (MSAFP) screening measurements, but second-trimester BPD measurements obtained prior to MSAFP screening should be the method of choice for interpreting MSAFP values, due to the increased sensitivity for detecting open spina bifida.     

Chorionic villus sampling for fetal karyotyping in missed abortions

Chorionic villus sampling (CVS) was performed in 12 pregnant women (9–25 gestational weeks) with ultrasonographic evidence of missed abortion. An ultrasonographically guided transabdominal (eight cases) or transcervical (four cases) approach was used. Fetal karyo-typing was successful in all cases; in five, chromosomal aberrations were found and in seven, chromosome analyses revealed normal karyotypes. Tissue culture for fetal karyotyping was successful in only 72.5 per cent of 40 live pregnancies which were electively interrupted because of abnormal ultrasonographic findings or an abnormal fetal karyotype, and in 57 per cent of seven missed abortions. CVS is suggested as a feasible and effective method for fetal karyotyping in missed abortions and it seems to be superior to post-abortion tissue culture.     

A normal 46,XX infant with a 46,XX/ 69.XXY placenta: A major contribution to the placenta is from a resorbed twin

A predominantly triploid 69,XXY placenta was found associated with a normal 46,XX infant. Therefore, a triploid placenta is apparently capable of supporting normal fetal development. The chromosome and pathological results support the conclusion that the triploid placenta originates from a ‘vanishing twin’ pregnancy. This case is unusual in that persistence of the placenta from the vanished twin has virtually replaced most of the normal placenta.     

Mosaicism of autosomes and sex chromosomes in morphologically normal,monospermic preimplantation human embryos

We have previously detected chromosome abnormalities in human embryos whilst identifying the sex for preimplantation diagnosis of X-linked disease. In this study we assess the incidence of these abnormalities, both for sex chromosomes and autosomes 1 and 17, using dual fluorescent in situ hybridization (FISH). Sixty-nine normally fertilized embryos of good morphology at the 6–10 cell stage (day 3 post-insemination) were examined. The embryos were spread whole using HCl and Tween 20 to dissolve the cytoplasm. Thirty-four embryos were analysed for the sex chromosomes and 35 for autosomes 1 and 17. All probes were directly labelled with fluorochromes allowing analysis in 2 h. Control lymphocytes demonstrated that the probes were of high specificity. For the sex chromosomes, five embryos were mosaic (15 per cent) with the remaining 29 being uniformly XX or XY. In no case was an XX nucleus found in an otherwise XY embryo, indicating that even though mosaicism for the sex chromosomes is present, such abnormalities would not lead to a misdiagnosis of sex. For the autosomes, 16 embryos were abnormal (46 per cent); one embryo was triploid, one was monosomic for chromosome 1, and ten others were diploid mosaics (three diploid/aneuploid, three diploid/polyploid, and four diploid/haploid). A further four embryos had variable chromosome numbers in the majority of nuclei which appeared to be the result of uncontrolled mitotic division. The presence of haploidy or double monosomy, which occurred in 15 per cent of nuclei, has important implications for the diagnosis of trisomies and dominant disorders.     

Isolation of fetal cells from transcervical samples by micromanipulation: Molecular confirmation of their fetal origin and diagnosis of fetal aneuploidy

Transcervical cell (TCC) samples have been shown to contain fetal cells amenable to molecular analysis. However, the presence of ‘contaminating’ maternal cells limits their use for prenatal diagnoses. In this report we show that clumps of fetal cells can be isolated from transcervical samples by micromanipulation and tested by fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR). Out of 129 clumps, isolated from mucus aspirates and transcervical lavages from 29 patients, 29 clumps from 11 patients were found to be exclusively of fetal origin as judged by the detection of chromosome 21-specific polymorphic DNA markers and Y-derived DNA sequences by PCR and FISH. One case of a male triploid fetus, diagnosed by the analysis of TCC samples obtained by mucus aspiration and lavage, was confirmed by testing clumps of cells isolated by micromanipulation.     

Evaluation of a prenatal screening procedure for β-thalassaemia carriers in a chinese populationbased on the mean corpuscular volume (MCV)

Haemoglobin A₂ (HbA₂) levels were determined on 25 β-thalassaemia carriers by the microcolumn method and were found to range from 4.5–7.2 per cent (mean 5.2±0.82 S.D.). The haemoglobin level (Hb), mean corpuscular volume (MCV), plasma ferritin and HbA₂ levels were measured on a further 299 cconsecutive Chinese pregnant women at a gestation of less than 24 weeks. 18 patients (6 per cent) had HbA₂ level greater than 4.5 per cent and were diagnosed to be β-thalassaemic carriers. It was observed that all these patients had a MCV below 75 fl. If this level is selected in a screening procedure based on measurement of MCV alone all β-thalassaemia carriers could be detected and 11 per cent of the population screened would require HbA₂ estimation. At a lower cut-off level of 70 fl, 8 per cent of the population screened wouid require HbA₂ measurement (a decrease of 27 per cent) but the detection rate will be lowered considerably (83 per cent). The high false positive rate at all cut-off levels of MCV was largely due to the prevalence of iron deficiency anaemia in the population. Estimation of plasma ferritin level in patients with low MCV will reduce this false positive rate, but there will be a considerable delay in diagnosis in patients with concomitant iron deficiency and β-thalassaemia. The presence of iron deficiency in β-thalassaemia carriers did not reduce their HbA₂ level below the diagnostic range in this study. Measurement of Hb level did not appear to be useful as a screening method since one third of the β-thalassaemia carriers had a Hb level over 11 g/dl. The validity of the MCV cut-off levels derived from the first part of the study was assessed in screening a larger population. 61 β-thalassaemia carriers (6 per cent) were detected out of 1166 patients screened. This incidence was not significantly different from the first part of the study. All these 61 patients had a MCV less than 75 ml. It was concluded that a two-step screening policy, based on MCV measurement followed by HbA₂ estimation when the MCV value is less than 75 fl, is suitable for our population. It is efficient, straight forward with excellent sensitivity and required less time and effort for both laboratory staff and clinicians.