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.     

Functional abilities at age 4 years of children born before 29 weeks of gestation.

OBJECTIVES--To assess the rate of impairment and disability among babies born very preterm and to investigate the association between such impairment and gestational age at birth. DESIGN--Cohort study of a geographically defined population of babies. SETTING--Oxford Regional Health Authority. SUBJECTS--All babies born alive before 29 weeks of gestation to mothers resident in the region during 1984-6. MAIN OUTCOME MEASURES--Survival rates and rates of impairment and disability among survivors at the age of 4 years. RESULTS--Of the 342 babies, half (170) survived to be discharged home. Of the 164 survivors to age 4 years, 153 (93%) were assessed. A total of 35 (23%; 95% confidence interval 16% to 30%) were severely disabled and only 54 (35%; 28% to 43%) were unimpaired. The risk of impairment and disability increased with decreasing gestational age at birth (p < 0.003). CONCLUSIONS--With the increasing survival rate among babies born before 29 weeks of gestation, we need urgently to establish reliable ways of monitoring the proportion of survivors who have a disability.     

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.     

Protective effect of vitamin E (DL-alpha-tocopherol) against intraventricular haemorrhage in premature babies.

Forty four babies, of less than 32 weeks'' gestation, were either randomly given 25 mg/kg vitamin E (DL-alpha-tocopherol acetate) intramuscularly after birth (day 0) and on days 1, 2, and 3 or served as controls. Frequent real time ultrasound examinations of the brain were made in each baby during the first week and less frequently thereafter. In babies under 32 weeks'' gestation the incidence of intraventricular haemorrhage was lower in supplemented babies (18.8%) compared with the controls (56.3%). On days 0, 1, 2, and 3 median plasma vitamin E concentrations in babies without haemorrhage and in those with subependymal haemorrhage only were similar. Babies with intraventricular haemorrhage had lower median concentrations on day 1 (p less than 0.002) and day 2 (p less than 0.05) compared with those with subependymal haemorrhage and lower concentrations on day 0 (p less than 0.02) and day 1 (p less than 0.05) compared with those without haemorrhage. These findings suggest that in premature babies vitamin E, an antioxidant, protects endothelial cell membranes from oxidative damage and disruption and limits the magnitude of haemorrhage and its spread from the subependyma into the ventricles.     

Morbidity and survival in neonates ventilated for the respiratory distress syndrome.

In a retrospective analysis the records of all (210) infants ventilated to treat the respiratory distress syndrome over three years were reviewed. A mortality of 19% was found. Intraventricular haemorrhage was associated than a significant increase in mortality in infants of less with 30 weeks'' gestation (p less than 0.001) and was the commonest cause of death. Pneumothoraces developed in one third of babies regardless of gestational age but were significantly associated with an increase in mortality only in infants of 27-29 weeks'' gestation. Patent ductus arteriosus was present in 31 infants and was commoner in babies of very low birth weight. The presence of a patent ductus arteriosus was not associated with decreased survival but was significantly related to an increased need for prolonged respiratory support (p less than 0.001). Thirty six infants developed chronic lung disease, three of whom died. Comparison with data from earlier studies indicated a steady improvement over the past decade in outcome for infants ventilated for the respiratory distress syndrome.     

Babies with spina bifida treated without surgery: parents' views on home versus hospital care.

From 1971 to 1981, 98 babies born with meningomyelocoele at the North Staffordshire Hospital Centre''s district maternity hospital, were thought not suitable for surgery. Sixty three survived for more than one week. Over the period the hospital''s policy changed: initially all such babies were kept in hospital, but later parents were given the choice of taking their baby home for palliative and terminal care. In an attempt to determine parents'' views on the care of their baby the parents of 44 of the babies who survived to one week were traced in 1985-6, five to 14 years later; 80 of them were asked how they felt about the lives and deaths of their babies. Eighteen babies had been taken home, and they had lived longer than the 26 who had been cared for in hospital. Parents whose baby had remained in hospital were sadder than those who had taken their baby home when they looked back at their experiences, and they also considered that their baby''s life had been of poor quality. Most of those who had taken their baby home had a more positive view of their child''s life. The figures suggest that the bereavement process after a baby''s death is longer than has been thought, but despite residual sadness just over half of the parents interviewed thought that something positive had come out of their experience.     

Prognosis for infants born at 23 to 28 weeks' gestation.

The survival and neurodevelopmental outcome of 356 extremely preterm infants born at 23 to 28 weeks'' gestation were reported by week of gestation. Their corrected 1 year survival improved from 7% at 23 weeks to 75% at 28 weeks. The overall incidence of impairment was 19% and of major disability 12%. Boys had a significantly lower normal survival than girls. Multiple births had a significantly lower survival and higher incidence of impairment than singleton births. Predictions of outcome were made before delivery, after resuscitation, and at 1 week to aid the development of guidelines on when perinatal intensive care is justified, whether obstetric intervention for fetal reasons is warranted, and what initial and ongoing prognoses to give to parents. Intensive care for progressively smaller and more immature infants, many of whom were previously considered non-viable, needs to be carefully monitored by every perinatal centre.     

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.     

The experience and effectiveness of the Nova Scotia Rh program, 1964-84.

A program to reduce the incidence of erythroblastosis fetalis was started in Nova Scotia in 1964. Up to the end of 1984, 120 fetuses received 247 intrauterine transfusions. The survival rate was 45.6% in the first 10 years of the program and 66.7% in the next 11 years. For fetuses at or over 26 weeks'' gestation the figures were 51.5% and 73.7% respectively. Postpartum prevention was started in 1968, with administration of Rh immune globulin (RhIG) to Rh-negative unimmunized women within 72 hours after the birth of an Rh-positive infant. Antepartum prevention, started in 1979, consisted of administration of RhIG at 28 weeks'' gestation to Rh-negative unimmunized women. The effectiveness of the prevention program was evaluated by enumerating the known cases of Rh(D) alloimmunization in the province from 1982 to 1984: 55 cases were identified, a rate of 1.5 per 1000 births instead of the expected rate of about 10 per 1000.     

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.     

Twin pregnancy with complete hydatidiform mole and coexisting fetus following ovulation induction with a non-prescribed clomiphene citrate regimen: a case report

Introduction

Until now, studies on paracetamol given intravenously have mainly been performed with the pro-drug propacetamol or with paracetamol in preterm babies above 32 weeks of gestation. Studies in these babies indicate that intravenous paracetamol is tolerated well, however studies on the efficacy of intravenous paracetamol are lacking. There are no pharmacokinetic data on the administration of multiple doses of paracetamol in preterm babies with a gestational age below 32 weeks.

Case presentation

We present a case series of nine Caucasian preterm babies, six boys and three girls, with a mean gestational age of 28.6 weeks (range 25.9 to 31.6 weeks). Case one, a girl with a gestational age of 25 weeks and six days, presented with necrotizing enterocolitis. In the second case, a female baby with a gestational age of 26 weeks and two days presented with hematoma. In case three, a female baby with a gestation of 26 weeks and one day developed intraventricular hemorrhage. In case four, a male baby with a gestational age of 31 weeks and four days presented with pain after vacuum delivery. Case five, a female baby born after a gestation of 29 weeks and six days presented with hematoma. In case six, a male baby with a gestation of 30 weeks and six days presented with hematoma. In case seven, a male baby, born with a gestational age of 30 weeks and six days, presented with caput succedaneum and hematoma. In case eight, a male baby, born after a gestation of 28 weeks and four days, developed abdominal distention. Case nine, a female baby, born with a gestational age of 27 weeks and three days presented with hematoma. These babies were treated with intravenous paracetamol 15 mg/kg every six hours. Serum concentrations and aspartate transaminase were determined after prolonged administration. Pain scores were assessed using the Premature Infant Pain Profile.

Conclusion

Paracetamol serum concentrations ranged from 8 to 64 mg/L after eight to 12 doses of intravenous paracetamol. Adequate analgesia was obtained in seven babies. During paracetamol therapy the median serum level of aspartate transaminase was 20 U/L (range 12 to 186 U/L). This case series indicates that prolonged intravenous administration of paracetamol in preterm babies with a gestational age of less than 32 weeks is tolerated well in the first days after birth. However, in the absence of proper pharmacokinetic data in this age group we cannot advocate the use of paracetamol intravenously.     

Maternal and fetal nutrition in south India.

The relation between the nutrition of the mother and that of her baby was assessed in a south Indian community where malnutrition is common and women do not smoke. Unselected mothers and their infants of over 37 weeks'' gestation were studied in two groups: those who paid for their care (150) and a poorer group who did not (172). There were significnat differences between the paying and non-paying groups in maternal triceps skinfold thickness, infant weight, and infant length. Overall there was a significant positive correlation between maternal triceps thickness and infant weight, length, and triceps and subscapular skinfold thickness. The correlation with the infant head circumference was less significant. These findings are further evidence that the nutrition of the mother has an important effect on the nutrition of her baby and that malnutrition is an important reason why Indian babies are lighter than European ones.     

Changing overall workload in neonatal units.

An epidemiological study was carried out in the current Nottingham health district to determine changes in both neonatal unit workload and in the infants requiring neonatal care during two study periods. All admissions for 1977 and again for the 12 months 1 April 1983 to 31 March 1984 were reviewed. Total numbers of admissions have shown roughly a 50% reduction because of a more rigorous admission policy locally. The admissions of infants of 33 weeks'' gestation or less have shown a significant increase, while the overall survival of infants less than 33 weeks'' gestation has improved.     

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.     

Rh isoimmunization during pregnancy: antenatal prophylaxis.

Of 3533 Rh-negative women who began a pregnancy without detectable Rh antibodies, 62 (1.8%) demonstrated evidence of Rh isoimmunization during pregnancy or within 3 days after delivery. All denied transfusions as well as abortions or previous pregnancies not followed by the administration of Rh immune globulin. Rh isoimmunization during pregnancy or within 3 days after delivery, which will not be prevented by the administration of Rh immune globulin after delivery, is the most important cause of residual Rh isoimmunization. A clinical trial of antenatal administration of Rh immune globulin, initially at 34 weeks''s and subsequently at 28 and 34 weeks'' gestation, in 1357 Rh-negative pregnant women who were delivered of Rh-positive babies, was effective in preventing the development of Rh isoimmunization during pregnancy or within 3 days after delivery. Antenatal prophylaxis with Rh immune globulin will be necessary if the incidence of Rh isoimmunization is to be reduced to its lowest possible level. Antenatal prophylaxis at 28 weeks'' gestation is now an insured service in Manitoba.     

Value of routine ultrasound scanning at 19 weeks: a four year study of 8849 deliveries.

OBJECTIVE--To evaluate the effectiveness of routine ultrasound scanning at 19 weeks'' gestation in an unselected population in terms of accuracy of detection of fetal structural abnormality and the effect on obstetric and neonatal care. DESIGN--Prospective study over four years. Scans performed by radiographers with overall supervision by a radiologist. SETTING--Ultrasound department of district general hospital. SUBJECTS--All pregnant women were offered scans; 8523 of 8849 (96%) accepted. MAIN OUTCOME MEASURES--Information obtained from hospital records, genetic analysis, and post-mortem findings. RESULTS--166 fetal anomalies occurred; 140 were detected at 19 weeks (sensitivity 85%; specificity 99.9%). In 27 cases fetuses were shown to have severely crippling or lethal abnormalities; termination of pregnancy was requested in 25. Early diagnosis influenced timing and place of delivery in babies with severe cardiac or gastrointestinal anomalies. CONCLUSION--Scanning at 19 weeks with availability of termination can reduce perinatal morbidity and mortality. Scanning can be performed in a general ultrasound department with adequate counselling facilities and close cooperation between radiographers, midwives, obstetricians, paediatricians, and the radiologist.     

Mothers' birth weight and survival of their offspring: population based study.

OBJECTIVE: To test the hypothesis that a baby''s survival is related to the mother''s birth weight. DESIGN: Population based dataset for two generations. SETTING: Population registry in Norway. SUBJECTS: All birth records for women born in Norway since 1967 were linked to births during 1981-94, thereby forming 105104 mother-offspring units. MAIN OUTCOME MEASURES: Perinatal mortality specific for weight for offspring in groups of maternal birth weight (with 500 g categories in both). RESULTS: A mother''s birth weight was strongly associated with the weight of her baby. Maternal birth weight was associated with perinatal survival of her baby only for mothers with birth weights under 2000 g. These mothers were more likely to lose a baby in the perinatal period (odds ratio 2.3, 95% confidence interval 1.4 to 3.7). Among mothers with a birth weight over 2000 g there was no overall association between mother''s weight and infant survival. There was, however, a strong interaction between mother''s birth weight, infant birth weight, and infant survival. Mortality among small babies was much higher for those whose mothers had been large at birth. For example, babies weighing 2500-2999 g had a threefold higher mortality if their mother''s birth weight had been high (> or = 4000 g) than if the mother had been small (2500-2999 g). CONCLUSION: Mothers who weighed less than 2000 g at birth have a higher risk of losing their own babies. For mothers who weighed > or = 2000 g their birth weight provides a benchmark for judging the growth of their offspring. Babies who are small relative to their mother''s birth weight are at increased risk of mortality.     

Proctalgia fugax: a cause of marital dysharmony.

A survey of the records of all hospitals with obstetric services in Nova Scotia revealed that during 1980-84 there were 122 pregnancies involving a neural tube defect. The mean rate was 2/1000 births. Of the affected fetuses or infants 54% had spina bifida, 35% had anencephaly and 11% had encephalocele. The records showed that in the early part of the period studied at least one prenatal ultrasonographic examination had been performed in 60% of the pregnancies; in 1984 the rate was 74%. When examinations done before 16 weeks'' gestation were excluded, the overall detection rates at the first ultrasonographic examination were 100% for anencephaly and 73% for spina bifida and encephalocele; the rates improved toward the end of the study period.     

Neonatal risk factors for cerebral palsy in very preterm babies: case-control study.

OBJECTIVE: To identify neonatal risk factors for cerebral palsy among very preterm babies and in particular the associations independent of the coexistence of antenatal and intrapartum factors. DESIGN: Case-control study. SETTING: Oxford health region. SUBJECTS: Singleton babies born between 1984 and 1990 at less than 32 weeks'' gestation who survived to discharge from hospital: 59 with cerebral palsy and 234 randomly selected controls without cerebral palsy. MAIN OUTCOME MEASURES: Adverse neonatal factors expressed as odds ratios and 95% confidence intervals. RESULTS: Factors associated with an increased risk of cerebral palsy after adjustment for gestational age and the presence of previously identified antenatal and intrapartum risk factors were patent ductus arteriosus (odds ratio 2.3; 95% confidence interval 1.2 to 4.5), hypotension (2.3; 1.3 to 4.7), blood transfusion (4.8; 2.5 to 9.3), prolonged ventilation (4.8; 2.5 to 9.0), pneumothorax (3.5; 1.6 to 7.6), sepsis (3.6; 1.8 to 7.4), hyponatraemia (7.9; 2.1 to 29.6) and total parenteral nutrition (5.5; 2.8 to 10.5). Seizures were associated with an increased risk of cerebral palsy (10.0; 4.1 to 24.7), as were parenchymal damage (32; 12.4 to 84.4) and appreciable ventricular dilatation (5.4; 3.0 to 9.8) detected by cerebral ultrasound. CONCLUSION: A reduction in the rate of cerebral palsy in very preterm babies requires an integrated approach to management throughout the antenatal, intrapartum, and neonatal periods.     

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.