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Objective: To determine whether a policy of offering cffDNA testing to all RhD-negative women at about 16 weeks' gestation to avoid anti-D administration when the fetus is RhD-negative could be implemented successfully in the NHS without additional funding., Design: Prospectively planned observational service implementation pilot and notes audit., Setting: Three maternity services in the South West of England., Population: All RhD-negative women in a 6-month period., Methods: Prospective, intervention, cross-sectional observational study, using pre-intervention data as controls., Main Outcome Measures: Proportion of suitable women who offered and accepted the test. Accuracy of the cffDNA result as assessed by cord blood group result. Fall in anti-D doses administered., Results: 529 samples were received; three were unsuitable. The results were reported as RhD-positive (n = 278), RhD-negative (n = 185) or inconclusive, treat as positive (n = 63). Cord blood results were available in 502 (95%) and the only incorrect result was one case of a false positive (cffDNA reported as positive, cord blood negative - and so given anti-D unnecessarily). The notes audit showed that women who declined this service were correctly managed and that anti-D was not given when the fetus was predicted to be RhD-negative. The total use of anti-D doses fell by about 29% which equated to about 35% of RhD-negative women not receiving anti-D in their pregnancy unnecessarily., Conclusions: We recommend this service is extended to all UK NHS services., (© 2014 Royal College of Obstetricians and Gynaecologists.)

Red cell alloimmunisation involves the transplacental movement of maternally derived red cell antibodies into the fetal circulation, causing red cell haemolysis, fetal anaemia and ultimately fetal death. Current standard UK practice is to prevent sensitisation to the D antigen by administering anti-D at about 28 weeks' gestation to all RhD negative pregnancies. The determination of fetal blood group by non-invasive cell free fetal DNA testing offers an improved and more efficient service to RhD negative pregnant women and avoids the potential iatrogenic harm associated with standard practice. It also has significantly improved the management of women with red cell alloimunisation to D and other antigens. This review summarises the past and future management of red cell alloimmunisation during pregnancy and the impact of ffDNA tests., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

There has been a huge effort in the last 2-3 decades to develop non-invasive prenatal diagnosis to avoid the risks to the fetus caused by invasive procedures. Obtaining fetal nucleic material for molecular analysis without the need of invasive procedures has been a goal of prenatal diagnosis for many years; this is now been made possible by the use of non-cellular fetal nucleic acids circulating in maternal blood. The placenta is the primary source of these nucleic acids, raising the possibility that they could be a marker for pregnancy complications resulting from placental disease/dysfunction such as pre-eclampsia and fetal growth restriction. If so, these markers might be able to identify cases at risk, predict disease and/or its severity or allow early diagnosis. This has the potential to allow improvements in the management of complicated pregnancies.

Objectives: We aimed to establish the earliest gestational age at which fetal DNA in maternal plasma could be detected and whether this was reliable at 12-13 weeks' gestation., Study Design: A prospective observational cohort study of 32 pregnancies either after IVF or before prenatal diagnosis by CVS. Maternal blood was taken and RT-PCR was carried out to detect the multi-copy Y chromosome associated DSY14 gene. The end point was gender as assessed at delivery or on karyotype., Results: Y signal was obtained as early as 14 days post conception (4 weeks' gestation) and has a good prediction rate by 12 weeks' gestation., Conclusion: Free fetal DNA allows very early prediction of fetal sex in some cases and could be useful for clinical use for X-linked conditions by the end of the first trimester.

Background: Fetomaternal alloimmune thrombocytopenia occurs when the mother produces antibodies against a platelet alloantigen that the fetus has inherited from the father. A consequence of this can be a reduced number of platelets (thrombocytopenia) in the fetus, which can result in bleeding whilst in the womb or shortly after birth. In severe cases this bleeding may lead to long-lasting disability or death. Antenatal management of fetomaternal alloimmune thrombocytopenia centres on preventing severe thrombocytopenia in the fetus. Available management options include administration of intravenous immunoglobulins or corticosteroids to the mother or intrauterine transfusion of antigen compatible platelets to the fetus. All options are costly and need to be assessed in terms of potential risk and benefit to both the mother and an individual fetus., Objectives: To determine the optimal antenatal treatment of fetomaternal alloimmune thrombocytopenia to prevent fetal and neonatal haemorrhage and death., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group trials register (February 2004), EMBASE (1980 to February 2004) and bibliographies of relevant publications and review articles., Selection Criteria: Randomised controlled studies comparing any intervention, including corticosteroids with no treatment, or comparing any two interventions., Data Collection and Analysis: Two reviewers independently assessed eligibility, trial quality and extracted data., Main Results: One study met the inclusion criteria (54 pregnant women). This trial compared intravenous immunoglobulins plus corticosteroid (dexamethasone) with intravenous immunoglobulins alone. No significant differences were reported between the treatment and control groups, in any outcome measured: mean platelet count at birth (weighted mean difference (WMD) 14.10 x 10 9/l, 95% confidence interval (CI) -30.26 to 58.46), mean gestational age at birth (WMD -0.50 weeks, 95% CI -2.69 to 1.69), mean rise in platelet count from first to second fetal blood screen (WMD -3.50 x 10 9/l, 95% CI -24.62 to 17.62) and mean rise in platelet count from birth to first fetal blood screen (WMD 24.40 x 10 9/l (95% CI -14.17 to 62.97)). This trial had adequate methodological quality; however the method used to calculate sample size was inappropriate: therefore the power calculation was not sufficient to determine any significance in differences between the treatment groups., Authors' Conclusions: There are insufficient data from randomised controlled trials to determine the optimal antenatal management of fetomaternal alloimmune thrombocytopenia. Future trials should consider the dose of intravenous immunoglobulins, the timing of initial treatment, monitoring of response to treatment by fetal blood sampling, laboratory measures to define pregnancies with a high risk of intercranial haemorrhage, management of non-responders and long-term follow up of children.

Two infants found to have ileal atresia after birth and who had intrauterine laser treatment to interupt twin to twin transfusion are presented. The donor twin in each pregnancy died in utero.

Objectives: To investigate the relationship between intestinal atresia and fetal growth, intrapartum cardiotocograph abnormalities and staining of the amniotic fluid in gastroschisis pregnancies., Design: Observational study of 115 gastroschisis pregnancies conceived between 1980 and 1996., Setting: South West Region of England., Main Outcome Measures: Birthweight, intrapartum cardiotocograph abnormality, staining of amniotic fluid and Apgar score., Results: There was no statistically significant difference between the Apgar scores or the frequency of amniotic fluid staining of gastroschisis cases with or without atresia. Patent bowel gastroschisis was associated significantly with more cardiotocograph abnormalities (61% vs 26%, P = 0.026) and reduced growth (P = 0.02), when compared with cases with intestinal atresia., Conclusions: Bile vomiting may be an important cause of amniotic fluid staining. Bowel atresia protects against the increased incidence of cardiotocograph and growth abnormality found in cases of gastroschisis which may reflect their aetiology.

Objective: To evaluate chorionic villus sampling (CVS) as a technique for karyotyping after the first trimester by examining the incidence of result failure, confined placental mosaicism, and false positive or negative results at different gestational ages., Methods: During a nine year period between 1989 and 1997, all results of CVS between 8 and 37 weeks of gestation provided by the Regional Cytogenetics Centre were analysed retrospectively by examining indications for CVS, weights of tissue received, gestational age at sampling and karyotype results., Results: There were 2424 chorionic villus samples analysed by the direct method and/or cell culture. In 1548 cases CVS was performed before 14 weeks (Group 1), in 685 between 15 and 20 weeks (Group 2), in 160 between 21 and 28 weeks (Group 3) and in 31 cases after 29 weeks (Group 4). Although there was a trend for an increasing rate of failed direct preparation results from Groups 1 to 4 which were 3.8%, 4.7%, 5.6% and 6.6%, respectively; these results were not significantly different. There were 19 cases of confined placental mosaicism and the incidence was significantly greater in Group 3 compared with Group 1 (P < 0.05), and in Groups 3 and 4 combined compared with Group 1. There were six false positive and one false negative result following direct analysis with no significant differences between gestationar ages., Conclusions: CVS is a useful test after the first trimester, especially when a fast result is clinically required. However, after 20 weeks, when cordocentesis is available, the higher rate of cytogenetic discordancy between the placenta and the fetus means that cordocentesis may be preferable.

Objective: To determine whether there is a relationship between maternal serum insulin-like growth factor-I and fetal growth, consistent with the hypothesis that insulin-like growth factor-I influences maternal constraint upon fetal growth by controlling placental transfer., Design: A prospective, observational study., Setting: Fetal medicine unit and antenatal clinic of a large teaching hospital., Population: One hundred and forty-one pregnant women identified as having small or normally grown fetuses., Methods: Fetuses were scanned every two weeks with maternal venesection at each visit. Cases (birthweight < 5th centile) were assigned to two groups: fetal growth restriction due to placental dysfunction (umbilical artery Doppler, growth velocity pulsatility index > +2 SD; n = 25) and normal small-for-gestational-age (normal Doppler, growth velocity and amniotic fluid; n = 27). Eighty-nine controls had birthweights between the 5th and the 95th centiles, normal Doppler, growth velocity and amniotic fluid. Insulin-like growth factor-I was measured by radioimmunoassay, and its relationship to gestational age and birthweight was assessed by regression analysis. Comparisons between case groups were made by Student's t test or analysis of covariance to allow for the effect of birthweight., Outcome Measure: The last insulin-like growth factor-I level before delivery within the different subgroups., Results: In controls, maternal insulin-like growth factor-I increased with gestational age (r = 0.40; P = 0.0001) but did not correlate with birthweight. Insulin-like growth factor-I was low in the mothers of growth restricted fetuses (-1.56 SD; P = 0.0001), but not in those with small-for-gestational age fetuses., Conclusions: The control and small-for-gestational-age data suggest that maternal insulin-like growth factor-I is not associated with endocrine control of normal placental function. Low insulin-like growth factor-I relates to poor placental transfer, as indicated by Doppler, rather than to low birthweight. Whether this is a regulatory mechanism, a cause or a consequence of placental dysfunction needs further study.

Objective: To describe the incidence of gastroschisis and to identify possible aetiological factors., Design: A retrospective case review study., Setting: The South West Region of England., Population: All known cases of gastroschisis were identified from the regional fetal medicine, ultrasound, pathology and neonatal surgery, databases. Datasets to be collected were agreed prospectively and included demographic, past medical, family and obstetric information for all pregnancies conceived between January 1987 and December 1995., Results: In the first eight years the incidence was 1.6/10,000 but in 1995 a highly statistically significant rise to 4.4/10,000 was found (P = 0.0009). The increased incidence was not associated with changes in maternal age, proportion of primigravidae, use of tobacco or illicit drugs, conception while taking the oral contraceptive pill, or an increase in the number of teenage pregnancies. The median maternal age at last menstrual period for pregnancies with gastroschisis was 20.4 years which was much younger than the national average of 28 years. Thirty-seven percent of these conceptions occurred during the first quarter of the year compared with the expected 25%., Conclusions: The incidence of gastroschisis has risen to a higher level than previously reported which, despite a marked association with young maternal age at conception, is not due to an increase in the teenage pregnancy rate. As the average length of inpatient stay in the neonatal intensive care unit for cases with this malformation is approximately four weeks, the rise has considerable cost implications. The increasing incidence may also offer opportunities to determine the cause of gastroschisis.

Placental lesions are difficult to assess because there is often a discrepancy between the ultrasound findings, clinical diagnosis and pathology. Large placental lesions especially when solid and echogenic on ultrasound may be associated with a high maternal serum alpha-fetoprotein, intrauterine growth retardation or uteroplacental insufficiency. We report three cases in which mainly solid placental lesions were noted to increase in size during the second trimester and the placental weights at birth were relatively heavy when compared to the fetal weight. In all cases there were serious pregnancy complications. Pathological examination showed infarction, haematoma or both. We suggest that the growth of placental lesions during pregnancy may be an important sign related to the severity of the disease and therefore poor outcome.

Small-for-gestational-age fetuses are frequently detected in general obstetric practice. Despite remarkable improvements in our understanding and management of this group of conditions over the past 20 years, much more research is required. During the year reviewed in this article, advances were reported in identification, association/causation, relationship to maternal smoking, fetal endocrinology, clinical investigation and management, and these are discussed in turn.

Objective: To assess the relationship between subsequent neuro-development and measurements in small for gestational age (SGA) fetuses, including oxygenation at cordocentesis., Design: A longitudinal study of a cohort of SGA fetuses using those with normal oxygenation as controls., Subjects: 65 chromosomally normal children aged 12-66 months who, as fetuses, had been small for gestational age, had undergone cordocentesis and had been delivered after 32 weeks' gestation., Results: Griffiths' developmental quotient (DQ) was significantly associated with fetal blood pH (r = 0.41, P = 0.0008), PO2 (r = 0.25, P = 0.047) and PCO2 (r = -0.28, P = 0.027) at cordocentesis but not with the severity of growth retardation (r = 0.18, P = 0.17). However, the significant correlations between DQ and both PO2 and PCO2 were explained by their co-correlations with pH and neither remained significant after removing the effect of pH by analysis of variance. The association between DQ and pH was still significant after removing the effect of confounding variables. Maternal smoking during pregnancy was significantly associated with DQ (F to remove = 6.89, P = 0.011) even after allowing for the effects of possible confounding variables including fetal blood pH., Conclusions: Both fetal pH at cordocentesis and maternal smoking correlate significantly with subsequent neuro-development. Further investigation into the causes of these associations is required.

The aim of the study was to determine the outcome of fetuses with non-immune hydrops (NIH) following modern invasive investigation and therapy. This prospectively planned observational study involved 23 women with singleton fetuses in whom a diagnosis of NIH was made in our fetal medicine unit in 1 year. After investigation and counselling 15 of the 23 women opted for termination of pregnancy (10 chromosomal and 5 structural abnormalities) and there was 1 intrauterine fetal death before therapy was attempted. One case with diaphragmatic hernia was treated with shunting which successfully reversed the hydrops, the pregnancy continued to term, the malformation was surgically corrected but the neonate died from pulmonary hypoplasia. In the remaining 6 cases structural and chromosomal abnormalities were excluded. One had amniotic fluid drainage for polyhydramnios but despite this delivered at 30 weeks' gestation and the neonate died on day 5. The remaining 5 cases had fetal therapy between 22 and 32 weeks' gestation (4 shunt insertions, 1 blood transfusion) and in all the hydrops reversed and the pregnancy continued to at least 35 weeks' gestation. All 5 neonates were discharged from hospital alive and well. Fetal therapy in cases of NIH with normal structure and karyotype was associated with a very good outcome. Giving a uniform poor prognosis is no longer justified because if other fetal abnormalities are excluded, in utero treatment, reversal of the hydrops and survival are often possible. We recommend urgent referral of these cases to a fetal medicine unit.

Objective: To assess the ability of noninvasive tests of fetal wellbeing to predict hypoxic morbidity independent of fetal size., Design: A prospectively planned, longitudinal, observational study., Setting: Fetal Surveillance Unit, King's College Hospital, London., Subjects: One hundred and ninety-one pregnant women with singleton pregnancies who were delivered after 32 weeks' gestation who were seen in the Fetal Surveillance Unit within seven days of delivery., Interventions: Fetal surveillance by fetal abdominal circumference, heart rate variability (mean range), biophysical profile score and umbilical artery pulsatility index measurements., Main Outcome Measures: Birthweight was classified as > or < or = 2.5th centile (AGA or SGA) for gestational age and sex. Morbidity was defined as at least one of the following at birth: delivery by emergency caesarean section for fetal distress, umbilical venous blood pH less than 7.15, 5 min Apgar score less than 7 or admission to the Special Care Baby Unit (SCBU)., Results: Fetal abdominal circumference was the best indicator of which fetuses (n = 30) would be SGA. Fourteen of the 30 (47%) SGA fetuses had morbidity at birth and abnormal umbilical Doppler studies significantly predicted this (chi 2 = 2.93, P = 0.003). By contrast, fetal heart rate variability and the biophysical profile score did not. Twenty-seven of the 161 (17%) AGA fetuses had morbidity at birth, but this was not significantly predicted by heart rate variability, biophysical profile score or umbilical Doppler studies., Conclusions: None of the antenatal testing techniques studied predicted morbidity in normally grown fetuses but Doppler studies indicated whether a small fetus was 'sick small' or 'normal small'.

Objective: To compare computer cardiotocographic (CTG) analysis with clinical visual analysis., Design: A retrospective blind comparison of the two techniques of CTG assessment., Setting: Fetal Assessment Unit, King's College Hospital, London., Subjects: One hundred CTG traces of women referred to the unit were studied; the traces were taken after 32 weeks' gestation, within 10 days of delivery and where outcome was known., Interventions: The CTG traces were assessed both by the computer (System 8000 computerised CTG analyser, Oxford Sonicaid Ltd) and visually, by one of us., Main Outcome: Computer mean range from 0 to 80 in ms clinical visual CTG score from 0 to 80 (arbitrary units). A score < 20 is ominous; suspicious when between 20 and 30; and normal when > 30., Results: There was close correlation between the computer mean range and clinical visual assessment (r = 0.78, n = 100, P = 0.001). However, there were 13 occasions where the computer classified the trace as abnormal when clinical visual assessment was normal, indicating computer false positives. All these pregnancies had normal outcomes. There were no traces where computer analysis was normal and clinical visual assessment abnormal., Conclusions: Computerised CTG analysis gives an objective assessment which agrees closely with experienced visual assessment. It also provides a number which can be used to assess the value of fetal heart rate analysis.

A substantial proportion of fetuses with severe early onset growth retardation are chromosomally abnormal and in these cases detailed ultrasound scanning will often demonstrate the presence of fetal anatomical defects. Chromosomally normal SGA fetuses with no biochemical abnormalities are likely to be normal small fetuses and seem to develop normally. SGA fetuses with evidence of impaired placental perfusion such as altered fetal cardiovascular dynamics and disturbances in biochemical, haematological, metabolic and endocrine status are at increased of neurodevelopmental delay. Although incomplete, the data collected so far suggest the biochemical changes may be caused by reduced placental transfer of nutrients (e.g. oxygen, glucose and essential amino-acids) and subsequent reduced fetal metabolism leading to high levels of substrates (e.g. triglycerides and non-essential amino-acids) and low levels of tissue products (e.g. thyroid hormone, insulin, platelets and white cells).

Objective: To investigate whether Doppler studies of placental perfusion and antenatal tests for fetal hypoxia can identify reduced placental functional reserve in women with unexplained antepartum haemorrhage (APH)., Design: A prospective, longitudinal study., Setting: Fetal Surveillance Unit, King's College Hospital, London., Subjects: 48 women with bleeding from the genital tract after 26 weeks gestation without a clinical diagnosis of abruption or ultrasound evidence of placenta praevia., Interventions: Fetal surveillance by Doppler measurements of the umbilical and uterine arteries, biophysical profile scoring and computerized measurement of the mean minute range of FHR variation., Main Outcome Measures: A poor outcome was defined by one or more of the following: (i) birthweight greater than 2SD below the normal mean for gestational age and sex, (ii) abnormal FHR pattern in labour resulting in operative delivery, (iii) umbilical vein blood pH at delivery less than 7.15, (iv) a 5-min Apgar score less than 7., Results: Fifteen of the 48 pregnancies had a poor outcome; seven occurred in the 10 women delivered preterm (less than 37 weeks) and eight in the 36 women delivered between 37 and 42 weeks. Two women were delivered after 42 weeks and both infants had a good outcome. The results of Doppler studies of uterine and umbilical arteries, fetal biophysical profile or FHR variation were not significantly different between the two outcome groups. The 36 pregnancies delivered between 37 and 42 weeks were matched retrospectively for maternal age, parity and race with 36 pregnancies without APH; there was no significant difference in outcome between the women with unexplained APH and the matched comparison group., Conclusion: Morbidity related to unexplained APH is associated with preterm delivery rather than with damage to utero-placental function.

Objective: To analyse the effect of a fetal surveillance unit, which undertakes a wide range of maternal and fetal tests on an outpatient or inpatient basis, on the number and length of antenatal hospital admissions., Design: A comparison of the number and length of antenatal admissions six months before and five months after the opening of the unit on 1 July 1990., Main Outcome Measures: Admission rate, antenatal bed occupancy, and interval from admission to discharge or delivery., Results: The antenatal bed occupancy rate fell by 22% from 174/100 deliveries during the six months before the unit was opened to 136/100 deliveries in the five months after it was opened. The difference in distribution of lengths of admission after the unit was opened from before was highly significant (Mann-Whitney test = 5.14, n = 752 and 679; p less than 0.0001), and this was due to shorter intervals from admission to discharge and from admission to delivery. In contrast, the antenatal admission rate did not change significantly (50/100 deliveries v 49/100 deliveries). There was no significant change in the stillbirth rate (6/1294 births v 8/1372 births; difference between rates = 0.0012, 95% confidence interval-0.0043 to 0.0067)., Conclusion: Obstetricians are more prepared to discharge antenatal patients from hospital and, similarly, admit patients for delivery rather than for assessment if the patients are reliably monitored on an outpatient basis. If this change in practice is sustained substantial financial and social benefits will result as well as improvements in organisation, audit, teaching, and research.

Umbilical venous blood pO2, pCO2, pH, erythroblast count, and plasma lactate were measured in twenty-nine fetuses with growth retardation. There were significant negative correlations between the severity of fetal hypoxia, hypercapnoea, acidosis, and hyperlactaemia and the mean velocity of blood in the fetal aorta measured by doppler ultrasound.

Cordocentesis for prenatal diagnosis has allowed extensive progress in our knowledge of human fetal physiology. It is now being used to guide obstetric management of acquired fetal diseases (e.g., timing of delivery and intrauterine therapy). The most established indications are blood disorders (e.g., fetal anemia and thrombocytopenia) and further investigation of potentially correctable fetal malformation, but it is being used increasingly in placental insufficiency (e.g., fetal hypoxia and hypoglycemia).

Aldolase and phosphoglycerate kinase activity were markedly reduced in muscle from two mouse mutants, 129 J-dy and A2G-adr, with abnormal muscle development. The pentose-phosphate shunt enzymes, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, were both greatly increased in the gastrocnemius of 129 J-dy mice, but only the former was slightly increased in A2G-adr muscle. Alanine and aspartate aminotransferase activities were normal or low in 129 J-dy muscle but increased to approximately 200% in A2G-adr muscle. Liver from 129 J-dy mice showed increased activity of glucose-6-phosphate dehydrogenase. These findings are compatible with the well-recognised lipid involvement in the 129 J-dy mutant but indicate that an abnormality of amino acid metabolism in relation to energy supply is probably more important in the A2G-adr mutant.

Intervillous, umbilical venous and umbilical arterial blood samples were obtained by cordocentesis or fetoscopically from 200 pregnancies at 16-38 weeks gestation. The fetuses were either not affected by the condition under investigation or it was one which would not affect blood gas and acid-base status. Blood pH, pO2, pCO2, bicarbonate, base excess and plasma lactate concentration were determined and ranges for each parameter are presented. Samples obtained fetoscopically were more acidotic, hypercapnic and had a greater base deficit than those obtained by cordocentesis. In the umbilical venous samples, the pO2 decreased, while the bicarbonate, base excess and lactate increased with gestation. In the umbilical arterial samples the pO2 decreased and pCO2 increased; there were no other significant changes with gestation. Similarly, in the intervillous samples the only significant change with gestation was that of a decrease in pO2.

Amniotic fluid temperature in first trimester pregnancies and fetal subcutaneous tissue and amniotic fluid temperature in second trimester pregnancies, measured by a thermocouple probe, did not increase during sector, linear-array or Doppler ultrasound scanning. The mean fetal muscle temperature was higher (36.9 degrees C) than mean amniotic fluid temperature (36.6 degrees C) during the second trimester.

Humidified oxygen (55%) was administered continuously through a face mask to 5 patients whose pregnancies (4 singleton and 1 twin) were all complicated by severe intrauterine growth retardation, oligohydramnios, high blood-flow impedance in the fetal aorta and umbilical artery, and low mean blood-velocity in the fetal thoracic aorta. All the fetuses were hypoxic and 2 were acidotic. After maternal hyperoxygenation, the fetal pO2 increased to within or near the normal range, and resulted in a sustained increase in the mean blood-velocity in the fetal thoracic aorta. 5 fetuses survived with minimum neonatal morbidity. The effect of maternal hyperoxygenation on the fetal pO2 in such cases may prove to be a useful method of assessing placental function and guiding management.

In order to determine whether the differences between fetal and adult hemoglobins are important to fetal oxygenation, pH, PO2, PCO2, bicarbonate, and base excess were measured in umbilical venous and arterial blood samples obtained from fetuses with erythroblastosis fetalis. The values from fetuses that had previously been transfused and had predominantly adult hemoglobins were compared with those that had not been transfused and had predominantly fetal hemoglobin. Umbilical arterial blood was more acidotic and had a greater base deficit, while the umbilical venous PO2 was 4.8 mm Hg higher in the samples with adult hemoglobins than in those with fetal hemoglobin. The results suggest that oxygenation of fetal tissue is better with fetal hemoglobin but that adult hemoglobin can be compensated by an increase in oxygen transfer.

A total of 130 cordocenteses, including 96 intravascular fetal blood transfusions, were performed in 21 pregnancies complicated by red cell isoimmunization. Transfusions were commended at 18-34 weeks' gestation and repeated up to 7 times, at 1- to 4-week intervals. The volumes of transfused blood were 5-150 ml, the haematocrits 62-88% and the rate of transfusions 1-15 ml/min. The pretransfusion fetal haematocrits were 5-34% and the posttransfusion ones 28-60%. Final transfusions were given at 32-36 weeks' gestation. Of the 21 pregnancies, 18 delivered at 31-39 weeks and 3 are continuing; 1 baby was stillborn and 17 are alive and well.

In 79 pregnancies with erythroblastosis fetalis, fetal blood was sampled to assess the level of anaemia. Significant correlations were found between the haemoglobin concentration and umbilical artery pH, bicarbonate concentration and base excess. Compensatory mechanisms help to maintain oxygen supply in anaemia but their failure is associated with hydrops fetalis.

The pH, PO2, PCO2, and lactate concentration were measured in umbilical blood samples obtained by cordocentesis from 208 appropriate-for-gestational-age and 196 small-for-gestational-age fetuses at 18 to 38 weeks' gestation. In the appropriate-to-gestational-age fetuses umbilical venous (n = 173) and arterial (n = 35) PO2 and pH decreased, and umbilical venous and arterial PCO2 increased with advancing gestation. Blood lactate concentration did not change. Compared with the appropriate-for-gestational-age fetuses, the small-for-gestational-age fetuses were hypoxemic, hypercapnic, hyperlacticemic, and acidotic. There was mixed respiratory and metabolic acidosis, and the decrease in pH was significantly correlated with both hypercapnia and hyperlacticemia. In the umbilical artery (n = 53) there was a significant linear correlation between the degree of hypoxemia and the degrees of hypercapnia or acidosis. In the umbilical vein (n = 143), the correlations between the degree of hypoxemia and the degrees of hypercapnia, hyperlacticemia, or acidosis were exponential.

Fetal and maternal placental (intervillous) blood samples were obtained by means of an outpatient ultrasound-guided technique from a 33-week pregnancy with symmetrical intrauterine growth retardation. The baby was delivered by emergency caesarean section because blood gas, pH, and lactate measurements showed severe hypoxic acidosis, due to inadequate placental transfer.

A reference range of fetal haemoglobin concentration (g/dl) was established from umbilical cord blood samples obtained by cordocentesis (n = 200) or at delivery (n = 10). In normal pregnancy the mean fetal haemoglobin increases linearly from 11 g/dl at 17 weeks' gestation to 15 g/dl at 40 weeks' gestation and one standard deviation is approximately 1 g/dl. The haemoglobin was also measured in fetal blood from 154 red cell isoimmunised pregnancies from 17 to 36 weeks' gestation. In 48 fetuses with ultrasound features of hydrops the haemoglobin was 7-10 g/dl below the normal mean for gestation. It is proposed that in pregnancies complicated by red cell isoimmunisation the severity of the disease should be assessed and treated on the basis of the deviation of the fetal haemoglobin from the normal mean for gestation into mild (haemoglobin deficit less than 2 g/dl), moderate (deficit 2-7 g/dl), and severe (deficit greater than 7 g/dl).

In 32 pregnancies complicated by intra-uterine growth retardation, umbilical venous blood was sampled by cordocentesis and the utero-placental blood velocity resistance index (RI) was recorded using Doppler ultrasound. Significant correlations were found between the utero-placental RI and fetal hypoxia, hypercapnea, acidosis, hyperlactaemia and erythroblastosis.

Histology reports of endometrial curettage and hysterectomy specimens were compared in patients with stage 1 uterine malignancy. In 63 of 117 (54%) the tumour grade or type reported in the curettage specimen differed from that described in the hysterectomy specimen; the grading was as likely to be more as less well differentiated at hysterectomy. The differences were not related to endometrial sampling technique or pre-operative intracavity radiotherapy. The results suggest that if decisions about patient management continue to be based on histological grading of tumours in endometrial curettage samples, unnecessary morbidity will be caused to some patients and inadequate treatment will be given to others.