Transabdominal chorionic villus biopsy in second and third trimesters of pregnancy to determine fetal karyotype.

Transabdominal chorionic villus biopsy is an established method of obtaining material for analysing fetal chromosomes in the first trimester of pregnancy but has not been widely used for karyotyping in the second and third trimesters, when rapid results are required. The technique was evaluated in two groups of patients, comprising 106 at risk of having a fetus with chromosomal anomalies (105) or X linked disease (one) studied between 13 and 22 weeks (median 15 weeks) of gestation (group 1) and 21 with abnormal fetal findings on ultrasonography studied between 13 and 38 weeks (median 27 weeks) (group 2). Chorionic tissue was collected at the first attempt in 109 patients and at the second attempt in a further 17 independent of the position of the placenta. In one case from group 1 sufficient material for analysis could not be obtained. Seven abnormal karyotypes (six in group 1 and one in group 2) were diagnosed. Karyotyping was unsuccessful in two cases in group 1 (at 17 and 18 weeks'' gestation) and in two in group 2 (at 29 and 38 weeks'' gestation). Follow up of group 1 four weeks after sampling showed no signs of adverse fetal development apart from one unexplained intrauterine fetal death. The findings suggest that chorionic sampling is a safe and valuable additional technique for the late detection of chromosomal defects.     

Fetal haematology in rhesus isoimmunisation.

Haematological studies were carried out in pure fetal blood samples obtained fetoscopically in 29 rhesus isoimmunised pregnancies at 18-24 weeks'' gestation, and the values were compared with those obtained in 62 normal control pregnancies. Fetal reticulocytosis or erythroblastaemia was seen only in association with a haemoglobin concentration of 4 g/dl or less. Ten of the 14 fetuses with a haemoglobin concentration below 4 g/dl showed ultrasonographic evidence of hydrops.     

Continuous-flow plasmapheresis in management of severe rhesus disease.

Eight patients with severe rhesus disease and expected fetal loss were treated by intensive plasmapheresis using a continuous-flow cell separator. Plasmapheresis was started at 16-27 weeks'' gestation, and continued until planned intrauterine transfusion or until the infant was delivered or the rhesus disease became uncontrolled again. Altogether 24 to 2371 of plasma was exchanged over periods ranging from seven to 16 weeks. In seven of the eight patients the anti-D concentration fell during the period of plasmapheresis. Amniotic fluid spectrophotometry values remained below those recorded in the preceding pregnancy in six out of seven women. In five patients an attempt was made to control the rhesus disease by plasmapheresis alone, and two of these women delivered infants who survived. In the other three cases the infants died, one from the idiopathic respiratory distress syndrome and the other two in utero. These preliminary findings suggest that intensive plasmapheresis with a cell separator may reduce fetal haemolysis is delivered. Nevertheless, plasmapheresis may best be used to reduce haemolysis until intrauterine transfusions may be given more safely after 30 weeks'' gestation.     

Changing prognosis for babies of less than 28 weeks' gestation in the north of England between 1983 and 1994. Northern Neonatal Network.

OBJECTIVE: To investigate the changing prognosis for babies of less than 28 weeks'' gestation. DESIGN: A prospective, collaborative, population based survey. SETTING: The former Northern Regional Health Authority. SUBJECTS: All the births between 1983 and 1994 at 22 to 27 completed weeks'' gestation to women normally resident in the region. MAIN OUTCOME MEASURES: Miscarriage, stillbirth, death in the first year of life, and disability in survivors. RESULTS: There were 479070 registered births in the study period. No baby of 22 weeks'' gestation survived; only eight (4%) of the 197 babies of 23 weeks who were alive at the onset of labour survived for a year-a proportion that did not change during the study period. Survival among other babies of less than 28 weeks improved progressively between 1983-6 and 1991-4, but administration of artificial surfactant to babies requiring ventilation from mid-1990 was associated with further improvement in survival only in those over 25 weeks'' gestation. Babies of 24 weeks required three times as much high dependency care per survivor as babies of 27 weeks (76 v 26 days). The rate of severe disability in the one year survivors of less than 26 weeks'' gestation (30/123; 24%) was similar to that seen in the sampled survivors of 26 and 27 weeks (29/108; 27%); the proportion disabled did not change significantly during the study period. All the children born in 1983, 1987, and 1991 were later reassessed in greater detail: 10% (13/136) seemed destined for a continuing life of total dependency. CONCLUSIONS: Gestation, if accurately assessed, can give a woman facing very preterm delivery a clear indication of the prognosis for her baby and help her judge the appropriateness of accepting obstetric intervention and sustained perinatal support.     

Antenatal diagnosis of thalassaemia major.

Haemoglobin synthesis was studied in fetal blood samples obtained at 17 to 20 weeks'' gestation in 22 women at risk of carrying a fetus with homozygous beta-thalassaemia. A presumptive diagnosis of homozygous beta-thalassaemia was made in four cases, and the pregnancy was terminated. An inconclusive answer was obtained in one case, and the patient also chose to have her pregnancy terminated. Two fetuses were lost as a result of the procedure. Of the remaining 15 pregnancies, 13 proceeded to term and two to 36 weeks; in each case a normal infant or one heterozygous for beta-thalassaemia was delivered. Current efforts should be directed towards improving the blood sampling technology so that fetal blood sampling can be used widely in those countries where thalassaemia is a major problem.     

Randomised controlled comparative study of methyldopa and oxprenolol in treatment of hypertension in pregnancy.

One hundred pregnant women with hypertension (defined as diastolic blood pressure at or above 95 mm Hg) were allocated at random to treatment with methyldopa or oxprenolol and were compared with nonhypertensive controls matched according to parity and gestation at delivery. The patients were also stratified into those entering the study early (before 32 weeks'' gestation) and those entering late (after 32 weeks'' gestation). Although there were no differences in diastolic blood pressure between the hypertensive groups before or during treatment, in the early entry group the systolic blood pressure at entry of those allocated to oxprenolol was significantly higher than that of those receiving methyldopa; this difference remained throughout the treatment period. Also in the early entry group further increments of drug treatment were required to control blood pressure of patients receiving oxprenolol than in those receiving methyldopa. The eventual fetal outcome for all patients treated with methyldopa was the same as that for those treated with oxprenolol; birth weight, placental weight, head circumference, and Apgar score were not significantly different and there were no stillbirths in either group.     

Five Years' Experience with Intrauterine Transfusion

Five years'' experience with intrauterine transfusion involving 94 transfusions on 50 fetuses forms the basis of the paper. Twenty-three fetuses survived, which represents an overall salvage of 46%. Of 22 fetuses who received intrauterine transfusions before 28 weeks'' gestation, seven (31.9%) survived, which justifies the attempt. Of 28 fetuses who received intrauterine transfusions after 28 weeks'' gestation, 16 (57.1%) survived, which compares favourably with other series. A comparison of two different procedural techniques shows no statistically significant difference in ultimate results. Indications for amniocentesis are outlined and intrauterine transfusion was advised if the optical density difference fell in Liley''s zone III (or a very high zone II) and rose at a rate which anticipated a zone III reading prior to 32 weeks'' gestation. A pediatric assessment and therapeutic management of the 33 live births are presented. Twenty-eight babies received exchange transfusions. Five were excluded for reasons outlined in the text. Ten of the live-born died neonatally. The 23 survivors continue to thrive mentally and physically and follow-up continues.     

High incidence of preterm births and early losses in pregnancy after in vitro fertilisation. Australian in vitro fertilisation collaborative group.

A fertilisation cohort of 244 pregnancies resulting from in vitro fertilisation was reported to a national register by eight units specialising in in vitro fertilisation. Early pregnancy losses were high, with 5% tubal ectopic pregnancies, 18% biochemical pregnancies, and an incidence of spontaneous abortion of 27%. Among pregnancies of at least 20 weeks'' gestation 22% were multiple, with 26 pairs of twins and four sets of triplets. The incidence of preterm births was more than three times higher than in the general population. Low birthweight rates were also higher, owing both to preterm births and to multiple pregnancies. The sex ratio and the incidence of major congenital malformations were similar to those in naturally conceived pregnancies. In this series the high fetal losses at all stages of pregnancy suggested maternal reproductive causes and should not be interpreted as being due to factors peculiar to in vitro fertilisation. Further analysis will be necessary when larger numbers are available.     

Antenatal diagnosis of sphingolipid and mucopolysaccharide storage diseases.

In 4 years of 24 fetuses at risk for various sphingolipid and mucopolysaccharide storage diseases were examined. Amniocentesis at 16 weeks'' gestation was followed in most cases by culture of amniotic fluid cells and measurement in the cells of the activity of the enzyme suspected to be deficient. Six fetuses were affected; five were examined morphologically and biochemically after abortion. Two fetuses had Tay-Sachs disease, two had GM1 gangliosidosis and one had Hurler''s syndrome. Although in each affected detus the specific enzyme activity was absent, we found in the placenta 5 to 50% of the normal activity.     

Endpiece: The noble profession

ObjectivesTo assess whether bacterial vaginosis or chlamydial infection before 10 weeks'' gestation is associated with miscarriage before 16 weeks.DesignProspective cohort study.Setting32 general practices and five family planning clinics in south London.Participants1216 pregnant women, mean age 31, presenting before 10 weeks'' gestation.Results121 of 1214 women (10.0%, 95% confidence interval 8.3% to 11.7%) miscarried before 16 weeks. 174 of 1201 women (14.5%, 12.5% to 16.5%) had bacterial vaginosis. Compared with women who were negative for bacterial vaginosis those who were positive had a relative risk of miscarriage before 16 weeks'' gestation of 1.2 (0.7 to 1.9). Bacterial vaginosis was, however, associated with miscarriage in the second trimester at 13-15 weeks (3.5, 1.2 to 10.3). Only 29 women (2.4%, 1.5% to 3.3%) had chlamydial infection, of whom one miscarried (0.32, 0.04 to 2.30).ConclusionBacterial vaginosis is not strongly predictive of early miscarriage but may be a predictor after 13 weeks'' gestation. The prevalence of Chlamydia was too low to assess the risk, but it is unlikely to be a major risk factor in pregnant women.

What is already known on this topic

Miscarriages are common and associated with considerable morbidity and costsBacterial vaginosis is associated with miscarriage after 16 weeks'' gestation and preterm birth but the role of chlamydial infection is uncertain

What this study adds

Bacterial vaginosis is not a strong predictor of miscarriage before 16 weeks'' gestation but may be associated with miscarriage at 13-15 weeks'' gestationThe prevalence of chlamydial infection was too low for it to be a major risk factor for miscarriage in this population of healthy pregnant womenNon-invasive screening for bacterial vaginosis and chlamydial infection by using self administered vaginal swabs is feasible in pregnant women in the community     

Attitudes to viability of preterm infants and their effect on figures for perinatal mortality.

OBJECTIVE--To examine how local attitudes to management of extreme preterm labour can influence data on perinatal mortality. DESIGN--One year prospective study in a geographically defined population. SETTING--The 17 perinatal units of Trent region. PATIENTS--All preterm infants of less than or equal to 32 weeks'' gestation in the Trent region. INTERVENTIONS--Infants who had been considered viable at birth were referred for intensive care; those who had been considered non-viable received terminal care. MAIN OUTCOME MEASURES--Whether each infant was born alive, dead, or alive but considered non-viable. RESULTS--Large differences were observed among units in the rates of delivery of infants of less than or equal to 27 weeks'' gestation (rates varied from 7.2 to 0 per 1000 births). These differences were not present in the data relating to infants of between 28 and 32 weeks'' gestation. The variation seemed to result from different approaches to the management of extreme preterm labour--that is, whether management took place in a labour ward or a gynaecology ward. CONCLUSIONS--Place of delivery of premature babies (less than or equal to 27 weeks'' gestation) may influence classification and hence figures for perinatal mortality. In addition, the fact that the onus of judgment regarding viability and classification is often placed on relatively junior staff might also affect the figures for perinatal mortality. The introduction of a standard recording system for all infants greater than 500 g would be advantageous.     

Fetal nuchal translucency: ultrasound screening for chromosomal defects in first trimester of pregnancy.

OBJECTIVE--To examine the significance of fetal nuchal translucency at 10-14 weeks'' gestation in the prediction of abnormal fetal karyotype. DESIGN--Prospective screening study. SETTING--The Harris Birthright Research Centre for Fetal Medicine, King''s College Hospital, London. SUBJECTS--827 fetuses undergoing first trimester karyotyping by amniocentesis or chorionic villus sampling. MAIN OUTCOME MEASURE--Incidence of chromosomal defects. RESULTS--The incidence of chromosomal defects was 3% (28 of 827 cases). In the 51 (6%) fetuses with nuchal translucency 3-8 mm thick the incidence of chromosomal defects was 35% (18 cases). In contrast, only 10 of the remaining 776 (1%) fetuses were chromosomally abnormal. CONCLUSION--Fetal nuchal translucency > or = 3 mm is a useful first trimester marker for fetal chromosomal abnormalities.     

Extended fetal echocardiographic examination for detecting cardiac malformations in low risk pregnancies.

OBJECTIVE--To improve the rate of prenatal detection of cardiac malformations in a low risk population. DESIGN--Comparison of extended fetal echocardiography with the standard four chamber view in detecting abnormalities. Extended echocardiography comprised the four chamber view and visualisation of the left ventricular outflow tract, the right ventricular outflow tract, and the main pulmonary artery and its branches. In cases with abnormal results complete echocardiographic studies were performed by a paediatric cardiologist using M mode, Doppler, and colour flow mapping techniques. SETTING--Obstetric ultrasonographic unit at Shaare-Zedek Medical Centre, Jerusalem. SUBJECTS--5400 fetuses in low risk pregnancies between 18 and 24 weeks'' gestation (mean 21 weeks); 53 were lost to follow up. MAIN OUTCOME MEASURES--Detection of abnormality before and after birth. RESULTS--During the study 23 infants (0.4%) were born with cardiac abnormalities, 21 of whom had major structural and functional heart disease. 18 fetuses had heart disease diagnosed prenatally, 11 by the four chamber view alone (sensitivity 48%) and a further seven by extended echocardiography (sensitivity 78%). Five fetal cardiac defects were missed prenatally (false negative rate 22%). These included coarctation of aorta, persistent truncus arteriosus, tetralogy of Fallot, ventricular septal defect, and pulmonic stenosis. Only one false positive diagnosis (coarctation of aorta) was made (specificity 99.9%, false positive rate 0.1%). The abnormality was correctly identified in 17 out of 18 cases. CONCLUSIONS--The extended fetal heart examination detected 86% (18/21) of major abnormalities in a low risk population. The examination should be incorporated into routine prenatal ultrasonographic investigations.     

Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies)

OBJECTIVE: To determine whether treatment with low dose aspirin and heparin leads to a higher rate of live births than that achieved with low dose aspirin alone in women with a history of recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies), lupus anticoagulant, and cardiolipin antibodies (or anticardiolipin antibodies). DESIGN: Randomised controlled trial. SETTING: Specialist clinic for recurrent miscarriages. SUBJECTS: 90 women (median age 33 (range 22-43)) with a history of recurrent miscarriage (median number 4 (range 3-15)) and persistently positive results for phospholipid antibodies. INTERVENTION: Either low dose aspirin (75 mg daily) or low dose aspirin and 5000 U of unfractionated heparin subcutaneously 12 hourly. All women started treatment with low dose aspirin when they had a positive urine pregnancy test. Women were randomly allocated an intervention when fetal heart activity was seen on ultrasonography. Treatment was stopped at the time of miscarriage or at 34 weeks'' gestation. MAIN OUTCOME MEASURES: Rate of live births with the two treatments. RESULTS: There was no significant difference in the two groups in age or the number and gestation of previous miscarriages. The rate of live births with low dose aspirin and heparin was 71% (32/45 pregnancies) and 42% (19/45 pregnancies) with low dose aspirin alone (odds ratio 3.37 (95% confidence interval 1.40 to 8.10)). More than 90% of miscarriages occurred in the first trimester. There was no difference in outcome between the two treatments in pregnancies that advanced beyond 13 weeks'' gestation. Twelve of the 51 successful pregnancies (24%) were delivered before 37 weeks'' gestation. Women randomly allocated aspirin and heparin had a median decrease in lumbar spine bone density of 5.4% (range -8.6% to 1.7%). CONCLUSION: Treatment with aspirin and heparin leads to a significantly higher rate of live births in women with a history of recurrent miscarriage associated with phospholipid antibodies than that achieved with aspirin alone.     

Cardiac ultrasonography in structural abnormalities and arrhythmias. Recognition and treatment.

Fetal cardiac ultrasonography has become an important tool in the evaluation of fetuses at risk for cardiac anomalies. It can both guide prenatal treatment and assist the management and timing of delivery. We recommend that a fetal echocardiogram be done when there is a family history of congenital heart disease; maternal disease that may affect the fetus; a history of maternal drug use, either therapeutic or illegal; evidence of other fetal abnormalities; or evidence of fetal hydrops. The optimal timing of evaluation is 18 to 22 weeks'' gestation. An entire range of structural cardiac defects can be visualized prenatally, including atrioventricular septal defect, ventricular septal defect, cardiomyopathy, ventricular outlet obstruction, and complex cardiac defects. The outcome for a fetus with a recognized abnormality is unfavourable, with less than 50% surviving the neonatal period. Fetal cardiac arrhythmias are also a common occurrence, 15% in the series described here. Premature atrial or ventricular contractions are most commonly seen and usually require no treatment. Supraventricular tachycardia can result in hydrops and require in utero treatment to prevent fetal demise. Complete heart block, particularly in association with structural heart disease, has a poor prognosis for fetal survival.     

Cadmium exposure on day 12 of gestation in the Wistar rat: distribution, uteroplacental blood flow, and fetal viability

The effects of cadmium exposure (40 mumole CdCl2/kg, s.c.) on day 12 of gestation were evaluated in the Wistar rat. At 16-18 hours following such cadmium exposure, blood flow (as determined by radiolabeled microspheres) to the chorioallantoic placenta (CAP) was significantly reduced by 35%; at 24-26 hours, blood flow to the CAP had returned to control levels and was still unaffected at 38-43 hours. Uterine blood flow was not significantly altered at any of these timepoints. Between 16-18 and 24-26 hours after cadmium exposure, the concentration of cadmium in the placenta decreased significantly, while total cadmium content did not change. By 38-43 hours after cadmium exposure, total cadmium content of the placenta had increased significantly, although cadmium concentration was unchanged. There were no adverse effects on fetal viability or growth, as determined on day 20 of gestation. In sharp contrast, near-term (day 18) exposure to 40 or 50 mumole CdCl2/kg (s.c.) resulted in 53% and 82% mean incidences of fetolethality, respectively, within 24 hours. Administration of 50 mumole CdCl2/kg (sc) on day 12 also had no effect on fetal growth but resulted in increased fetolethality (12%). Thus midgestational cadmium exposure and its accompanying alterations in placental blood flow do not compromise fetal viability or growth. The differential response to cadmium at mid- and late gestation, in terms of fetolethality, is not due to maternal cadmium dose.     

Free Amino-acid Concentrations in Fetal Fluids

The pattern of free amino-acid concentrations in maternal venous plasma, fetal umbilical arterial plasma, fetal urine, and amniotic fluid at 15 to 20 weeks'' gestation has been determined. Free amino-acid concentrations were greater in fetal plasma than in maternal plasma, amniotic fluid, or fetal urine.The ratios of amino-acid concentrations in fetal umbilical arterial plasma and urine indicate that the fetal kidney can effectively conserve amino-acids, possibly reaching an adult level of competence in this respect.There was little correlation between amino-acid concentrations in the fluids analysed with the exception of that between amniotic fluid and fetal urine.     

Elective delivery and the neonatal respiratory distress syndrome.

A prospective study was carried out to determine how often moderate or severe respiratory distress syndrome in infants delivered electively after 32 weeks'' gestation or more is avoidable. During a 9-month period 64 such newborns were evaluated. The disease was considered avoidable in 14 (22%) since the indication for elective delivery was questionable. The mean birth weight and gestational age of these 14 infants were 2550 +/- 430 g and 36.3 +/- 1.7 weeks, and the mortality was 14%. This study demonstrated that elective delivery can produce severe neonatal complications, that despite their availability diagnostic tests of fetal age and maturity of the fetal lungs are not being used universally, and that the indications for elective delivery in cases of premature rupture of the membranes must be re-evaluated.     

The fetal phenotype of the 18p-syndrome. Report of a male fetus at twenty-one weeks

Morphological and cytogenetic findings in a male fetus at 21 weeks gestation after prenatally detected monosomy 18p are reported. The fetus displayed dysmorphic features resembling the 18p-syndrome, such as decreased head circumference, slightly receding forehead, hypertelorism, epicanthus, horizontal palpebral fissures, depressed nasal bridge, long philtrum, carp mouth, irregular crenated maxillar alveolar ridge, retrognathia, lowset dysplastic ears with posterior rotation, edema of neck, hands and feet respectively, fingers with drop-shaped tips, short first toes with dysplastic nails, hypoplastic male external genitalia. After termination of the pregnancy, biopsies from different fetal organs as well as from the placenta were taken and set up for long term cell cultures. The metaphases of fetal organs all showed the karyotype 46,XY,18p-. A fetal blood culture failed to grow. Unexpectedly, the metaphases of the placenta showed the mosaic karyotype 46,XY/46,XY,18p-/46,XY,18p+.