Anaesthesia, 1976, Volume 3 1, pages 398-402 CASE REPORT
Neonatal flaccidity Survival after neonatal respiratory failure with extreme flaccidity
B . M. MORGAN
Case history A healthy 27-year-old primiparous patient, who had been taking contraceptive tablets until 4 months beforehand, presented at the antenatal clinic 13 weeks pregnant by dates. Her blood pressure was 120/80 mmHg, haemoglobin 12-6 g/dl and she weighed 65 kg. A small vaginal haemorrhage occurred during the 13th week and she was admitted to hospital for 2 weeks but there was no further bleeding. The patient remained well until 38 weeks by size and dates, when she was admitted because of pre-eclampsia when the blood pressure was I15/80 mmHg. There was ankle oedema and mild proteinuria and she now weighed 84 kg. Some improvement took place as a result of bed rest and labour was induced at 39 weeks by rupturing the membranes after 10mg diazepam had been given intravenously. Foetal scalp electrodes were applied and an intrauterine pressure catheter inserted so that the foetal heart rate and intrauterine contractions could be monitored at the same time. Oxytocin 2 units in 500 ml of 5% dextrose was given by intravenous infusion. An extradural catheter was inserted and 4 ml bupivacaine (0.5%) without adrenaline injected; the foetal heart rate was 130 beats per minute. The rate of the intravenous infusion was governed by the Cardiff pump, which delivers the oxytocin in milli-units per ml according to the strength of the uterine contractions, for this purpose 10 U oxytocin were added to 500 ml 5% dextrose in water. Three further doses of 7 ml bupivacaine were given during the first stage of labour which lasted for 7 hours. Labour was conducted with the patient supine but there was no evidence of aorto-caval compression : the maternal blood pressure, which was taken intermittently throughout labour by mercury manometer, never fell below 110/80 mmHg. The foetal heart rate was constant, the cardio-tachograph tracing showed no late deceleration patterns in relation to the intrauterine pressure graph. The second stage lasted for 1 hour and ended with the normal delivery of a female infant. The third stage of labour was completed in a further 8 minutes. The placenta (weight 700 g) was complete, healthy and had no retroplacental clots. B. M. Morgan, MB, BCh, FFARCS, Senior Lecturer, Department of Anaesthesia, Queen Charlotte’s Hospital for Women, London W6.
398
Neonatal flaccidity
399
The baby had an Apgar score of 2 at 1 minute with a heart rate of 80 beats per minute and blue extremities. There was no response to a nasal suction catheter and the muscle tone was very poor. No attempt was made to breathe. Endotracheal intubation was performed at 2 minutes and intermittent positive pressure ventilation commenced. The lungs were easy to inflate and had good air entry: the baby rapidly became pink on 100% oxygen with a heart rate of 120 beats per minute. The baby remained completely flaccid and was kept warm by a radiant heater. The pupils were equal and reacted to light. Intermittent positive pressure ventilation was required for I + hours. Extubation was performed when the infant attempted to breathe and she was now assessed by a paediatrician as mature with normal cardiovascular and respiratory systems and a normal abdomen but with very poor muscle tone for which no cause could be found. A presumptive diagnosis of intracranial haemorrhage was made. Blood-gases and pH were not measured. The infant was placed in an incubator in an atmosphere of 30”/, oxygen. Breathing was adequate but muscle tone was still poor and the child now made occasional attempts to cry. Improvement was steady and by 3+ hours the muscle tone was normal and the baby cried and sucked well. The birthweight was 3.310 kg. Discharge from the hospital took place at 13 days. Assessment at the paediatric out-patient clinic at 3 weeks of age and again at 15 weeks of age, showed a normal baby.
Discussion Foetal maturity The condition of the baby before the start of labour in a healthy mother depends entirely upon the function of the placenta. This can be assessed by tests which are designed to reveal the hormonal state of the mother. The most important of these tests is the 24 hour urinary oestriol levels (normal values at term are 2 M O mg/24 hours of urine). In this mother, these levels were normal, the last value being 39.3 mg/24 hour at 38 weeks. The measurement of human placental lactogen is another diagnostic test of the foeto-placental state after 28 weeks. The normal range at term is 5-10 mg/ml and was normal in this patient with the last value at 38 weeks being 8.1 mg/ml. In addition, the maternal weight gain pattern is important and failure to gain weight is an ominous sign. This mother gained 16 kg throughout pregnancy. It is well-known that dates are an unreliable indication of foetal maturity because the date of the last menstrual period may be inaccurately remembered or because ovulation may occur at unusual times within the cycle especially if contraceptive pills have been taken. Foetal maturity can be assessed by serial ultrasonic measurements of biparietal diameter. Tests on amniotic fluid may be useful. The ‘orange’ cell test counts the degenerated squames present: after staining these cells are orangecoloured and their number gives an indication of foetal maturity. Amniotic fluid creatinine levels of 1-5-2 mg/100 ml are associated with a baby of more than 36 weeks. The phospholipids in amniotic fluid can be measured, especially the lecithin and sphingomyelin, and the ‘L-S ratio’ is an indication of the amount of surfactant formed in the foetal lungs and, therefore, also of foetal maturity in a normal pregnancy. At term this ratio is 2: 1. Amniocentesis was not done in this patient as the baby war clinically a good size for dates.’
400
B. M . Morgan
Certain maternal conditions give rise to infants who are at greater risk than normal, for example, diabetes mellitus, Rhesus incompatibility and pre-eclamptic toxaemia. The patient reported here was admitted for bedrest with a very mild degree of pre-eclamptic toxaemia. This condition is associated with placental dysfunction with reduction of intervillous blood flow due to spasm of the uterine wall spiral arterioles; this may reduce exchange across the placenta but the hormonal tests of placental function were normal and it is unlikely that this condition had developed. The conclusion is that no abnormality in the infant was to be expected from evaluation of tests of placental function. Knowledge of the intrauterine environment can be increased during labour by monitoring intrauterine pressure changes during contractions and by some foetal measurements. The continuous combined recording of the foetal heart rate and intrauterine pressure has a value in predicting the condition of the neonate.’ Foetal cardiotachometry is the technique of monitoring of the foetal heart rate with simultaneous monitoring of uterine contractions. Uterine contractions represent repetitive stresses to the foetus and it is the responses to these repeated episodes of stress which indicate the state of the foetus. In the established terminology, acceleration and deceleration refer to periodic changes in the foetal heart rate associated with uterine contractions. Bradycardia and tachycardia refer to ‘base-line’ changes sustained for more than 10 minutes. Variations in heart rate and amplitude are observable on a beat basis. In the healthy foetus the cardiotachograph shows a heart rate of 120-160 beats per minute with average beat to beat variability and possibly some periodic tachycardia but no periodic deceleration^.^ Periodic deceleration patterns, however, do occur and indicate a limitation of foetal reserve in that the momentary decrease in foetal oxygenation, associated with uterine contractions is not tolerated by the foetus. There are three types of periodic deceleration depending on the wave form and time in relation to uterine contractions. Early decelerations begin with the onset of a contraction and return to the baseline with the uterine pressure curve. This pattern of deceleration is not ominous and is related to foetal head compression. It is mediated via the vagus. Neither changes in maternal posture nor increasing maternal oxygenation affect this pattern. Late decelerations are identical in form but begin later in the contraction and return to the base-line long after the uterine pressure curve. This deceleration pattern is related to foetal hypoxia caused by placental insufficiency. It is found in association with decreased placental function, with maternal hypotension and with excessive uterine activity. Variable decelerations bear no time-relationship to contractions, are inconstant in shape, the most common of decelerations and are believed to indicate cord compression. They can often be abolished by changing the mother’s position. Periodic accelerations are invariably benign. Persistent tachycardia not associated with late decelerations may represent the normal heart rate for that foetus, infection, or compensation for a previous hypoxic episode. Base-line tachycardia occurring with late or variable decelerations is important. Variability of frequency and amplitude occurs during labour and may be increased in the healthy foetus but decreased variability with late or variable deceleration indicates a poor foetal outcome. Decreased variability without periodic decelerations is seen in a premature foetus and following the administration of some drugs to the mother. In this foetus the cardiotachograph showed some increased variability and some periodic accelerations only.
Neonatal flaccidity
401
The cardiotachograph recording showed no evidence of uteroplacental insufficiency: the base-line rate was 140 beats per minute with average variability and no periodic decelerations. There was no meconium in the amniotic fluid. Neonatal flaccidity
The differential diagnosis of neonatal flaccidity includes cerebral depression caused by drugs which have crossed the placental barrier. This mother received only 10 mg diazepam intravenously 7 hours before delivery. Diazepam quickly crosses the placental barrier and then accumulates in the foetal circulation, because binding of the drug to foetal plasma proteins is presumed to occur: 6 hours after intravenous administration to the mother, the concentration of the drug in foetal brain and liver is still high.4 There are reports of foetal hypoactivity and hypotonicity in infants whose mothers received diazepam in labour, even in doses as small as that received by this patient.’ Cerebral damage from birth injury may cause a neonate to fail to breathe. This child presented a picture very similar to that of classical pallid asphyxia, in which the infant is pale instead of blue, flaccid instead of rigid. It is either impossible to induce spontaneous ventilation at all or if the infant does breathe it does so in a feeble, shallow fashion. The pulse is rapid and the fontanelles are soft. This is regarded as shock resulting from haemorrhage into the posterior fossa or injury to the medulla. These babies, however, seldom survive more than a few hours. The baby reported here had none of the other stigmata of cerebral injury but it is possible that she had a small degree of cerebral injury which resulted in cerebral oedema from which recovery was complete. Congenitally defective nervous systems may react excessively to mild birth trauma. Other symptoms of defective development might not become evident until several months after birth. Peripheral disorders may result in failure to breathe and cause flaccidity. Diseases like amyotonia congenita or Werdnig-Hoffmann’s disease can cause a ‘floppy baby syndrome’ in the newborn. Drugs affecting the neuromuscular junction must also be considered. The fact that all local anaesthetics cross the placental barrier is well-established. Bupivacaine has a low umbilical vein/maternal venous blood ratio of 0.2-0.4 because it is 90-95% bound to plasma protein in the maternal blood.6 The amount of the drug that does cross the placental barrier is itself bound to foetal plasma protein, which lowers the amount of active drug in the foetal circulation by 45-70%.’ Metabolites of bupivacaine, whose effects have not been fully investigated, are also present in the foetal circulation. The time taken to metabolise these drugs by the relatively inefficient foetal liver is much greater than in the adult. Local anaesthetics are known to effect impulse transmission at the neuromuscular junction in adults in doses higher than those found in the infant but the available studies in animals indicate a significant difference between adult and infant neuromuscular transmission.* The mechanism of this action of local anaesthetics is unknown but it appears to involve both pre- and post-junctional transmission. The total amount of bupivacaine injected into the extradural space was 125 mg (25 ml of 0.5%) bupivacaine without adrenaline over a period of 7 hours. The mother showed no untoward effects due to bupivacaine, was not excessively drowsy and had only moderate motor paralysis of her legs.
402
B. M. Morgan
It is not possible to exclude the action of bupivacaine on the neuromuscular junction as the cause for flaccidity in this infant. Prediction about the outcome of extreme flaccidity and respiratory failure is difficult and decision about the fate of any neonate should not be precipitate. summary
The birth of a flaccid neonate is described. Oxytocin, diazepam and extradural bupivacaine were used during labour, The baby survived 13 hours of artificial ventilation and was subsequently healthy. An account is given of the assessment of foetal maturity and the diagnosis of neonatal flaccidity is discussed. Acknowledgments Thanks are due to Mr A. Amias, Consultant Obstetrician, St George’s Hospital, London, for permission to describe the patient admitted under his care, and to Dr D. M. Davies, Consultant Anaesthetist, St George’s Hospital, London, for his help with the preparation of this paper. References 1. GLUCK,L. & KULOVICH, M.V. (1973) Lecithin/sphingomyelin ratios in amniotic fluid in normal and abnormal pregnancy. American Journal of Obstetrics and Gynecology, 115, 539. B.S. &DAME,L. (1972) Foetal heart rate patterns. Prediction of Apgar score. Journal of 2. SCHIFRIN, the American Medical Association, 219, 1322. B.S. & SMITH,T.S. (1 973) Foetal surveillance during labour. International Anesthesiology 3. SCHIFRIN, Clinics, 11, 17. 4. INDANPAAN-HEIKKILA, J.E., JOUPPILA, P.I., POULAKKA, J.O. & VORNE,M.S. (1971) Placental
transfer and fetal metabolism of diazepam in early human pregnancy. AmericanJournalofObstetrics & Gynecology, 109, 1011. 5. FLoweRs, C.E., RUDOLPH, A.J. & DESMOND, M.M. (1969) Diazepam (Valium) as an adjunct in obstetric analgesia. Obstetrics & Gynecology, 34, 68. F. & TAYLQR, G. (1970) Maternal and neonatal blood concentrations of bupivacaine. 6. REYNOLDS, A comparison with lignocaine during continuous extradural analgesia. Anaesthesia, 25, 14. B.R. (1974) Obstetric analgesia and the newborn baby. Lancet, i, 1283. 7. BLOGG,C.E.& SIMPSON, P.A. (1970) Neuromuscular transmission in newborn rats. Journal of Physiology, 209, 8. REDFERN, 701.
Neonatal flaccidity Survival after neonatal respiratory failure with extreme flaccidity
B . M. MORGAN
Case history A healthy 27-year-old primiparous patient, who had been taking contraceptive tablets until 4 months beforehand, presented at the antenatal clinic 13 weeks pregnant by dates. Her blood pressure was 120/80 mmHg, haemoglobin 12-6 g/dl and she weighed 65 kg. A small vaginal haemorrhage occurred during the 13th week and she was admitted to hospital for 2 weeks but there was no further bleeding. The patient remained well until 38 weeks by size and dates, when she was admitted because of pre-eclampsia when the blood pressure was I15/80 mmHg. There was ankle oedema and mild proteinuria and she now weighed 84 kg. Some improvement took place as a result of bed rest and labour was induced at 39 weeks by rupturing the membranes after 10mg diazepam had been given intravenously. Foetal scalp electrodes were applied and an intrauterine pressure catheter inserted so that the foetal heart rate and intrauterine contractions could be monitored at the same time. Oxytocin 2 units in 500 ml of 5% dextrose was given by intravenous infusion. An extradural catheter was inserted and 4 ml bupivacaine (0.5%) without adrenaline injected; the foetal heart rate was 130 beats per minute. The rate of the intravenous infusion was governed by the Cardiff pump, which delivers the oxytocin in milli-units per ml according to the strength of the uterine contractions, for this purpose 10 U oxytocin were added to 500 ml 5% dextrose in water. Three further doses of 7 ml bupivacaine were given during the first stage of labour which lasted for 7 hours. Labour was conducted with the patient supine but there was no evidence of aorto-caval compression : the maternal blood pressure, which was taken intermittently throughout labour by mercury manometer, never fell below 110/80 mmHg. The foetal heart rate was constant, the cardio-tachograph tracing showed no late deceleration patterns in relation to the intrauterine pressure graph. The second stage lasted for 1 hour and ended with the normal delivery of a female infant. The third stage of labour was completed in a further 8 minutes. The placenta (weight 700 g) was complete, healthy and had no retroplacental clots. B. M. Morgan, MB, BCh, FFARCS, Senior Lecturer, Department of Anaesthesia, Queen Charlotte’s Hospital for Women, London W6.
398
Neonatal flaccidity
399
The baby had an Apgar score of 2 at 1 minute with a heart rate of 80 beats per minute and blue extremities. There was no response to a nasal suction catheter and the muscle tone was very poor. No attempt was made to breathe. Endotracheal intubation was performed at 2 minutes and intermittent positive pressure ventilation commenced. The lungs were easy to inflate and had good air entry: the baby rapidly became pink on 100% oxygen with a heart rate of 120 beats per minute. The baby remained completely flaccid and was kept warm by a radiant heater. The pupils were equal and reacted to light. Intermittent positive pressure ventilation was required for I + hours. Extubation was performed when the infant attempted to breathe and she was now assessed by a paediatrician as mature with normal cardiovascular and respiratory systems and a normal abdomen but with very poor muscle tone for which no cause could be found. A presumptive diagnosis of intracranial haemorrhage was made. Blood-gases and pH were not measured. The infant was placed in an incubator in an atmosphere of 30”/, oxygen. Breathing was adequate but muscle tone was still poor and the child now made occasional attempts to cry. Improvement was steady and by 3+ hours the muscle tone was normal and the baby cried and sucked well. The birthweight was 3.310 kg. Discharge from the hospital took place at 13 days. Assessment at the paediatric out-patient clinic at 3 weeks of age and again at 15 weeks of age, showed a normal baby.
Discussion Foetal maturity The condition of the baby before the start of labour in a healthy mother depends entirely upon the function of the placenta. This can be assessed by tests which are designed to reveal the hormonal state of the mother. The most important of these tests is the 24 hour urinary oestriol levels (normal values at term are 2 M O mg/24 hours of urine). In this mother, these levels were normal, the last value being 39.3 mg/24 hour at 38 weeks. The measurement of human placental lactogen is another diagnostic test of the foeto-placental state after 28 weeks. The normal range at term is 5-10 mg/ml and was normal in this patient with the last value at 38 weeks being 8.1 mg/ml. In addition, the maternal weight gain pattern is important and failure to gain weight is an ominous sign. This mother gained 16 kg throughout pregnancy. It is well-known that dates are an unreliable indication of foetal maturity because the date of the last menstrual period may be inaccurately remembered or because ovulation may occur at unusual times within the cycle especially if contraceptive pills have been taken. Foetal maturity can be assessed by serial ultrasonic measurements of biparietal diameter. Tests on amniotic fluid may be useful. The ‘orange’ cell test counts the degenerated squames present: after staining these cells are orangecoloured and their number gives an indication of foetal maturity. Amniotic fluid creatinine levels of 1-5-2 mg/100 ml are associated with a baby of more than 36 weeks. The phospholipids in amniotic fluid can be measured, especially the lecithin and sphingomyelin, and the ‘L-S ratio’ is an indication of the amount of surfactant formed in the foetal lungs and, therefore, also of foetal maturity in a normal pregnancy. At term this ratio is 2: 1. Amniocentesis was not done in this patient as the baby war clinically a good size for dates.’
400
B. M . Morgan
Certain maternal conditions give rise to infants who are at greater risk than normal, for example, diabetes mellitus, Rhesus incompatibility and pre-eclamptic toxaemia. The patient reported here was admitted for bedrest with a very mild degree of pre-eclamptic toxaemia. This condition is associated with placental dysfunction with reduction of intervillous blood flow due to spasm of the uterine wall spiral arterioles; this may reduce exchange across the placenta but the hormonal tests of placental function were normal and it is unlikely that this condition had developed. The conclusion is that no abnormality in the infant was to be expected from evaluation of tests of placental function. Knowledge of the intrauterine environment can be increased during labour by monitoring intrauterine pressure changes during contractions and by some foetal measurements. The continuous combined recording of the foetal heart rate and intrauterine pressure has a value in predicting the condition of the neonate.’ Foetal cardiotachometry is the technique of monitoring of the foetal heart rate with simultaneous monitoring of uterine contractions. Uterine contractions represent repetitive stresses to the foetus and it is the responses to these repeated episodes of stress which indicate the state of the foetus. In the established terminology, acceleration and deceleration refer to periodic changes in the foetal heart rate associated with uterine contractions. Bradycardia and tachycardia refer to ‘base-line’ changes sustained for more than 10 minutes. Variations in heart rate and amplitude are observable on a beat basis. In the healthy foetus the cardiotachograph shows a heart rate of 120-160 beats per minute with average beat to beat variability and possibly some periodic tachycardia but no periodic deceleration^.^ Periodic deceleration patterns, however, do occur and indicate a limitation of foetal reserve in that the momentary decrease in foetal oxygenation, associated with uterine contractions is not tolerated by the foetus. There are three types of periodic deceleration depending on the wave form and time in relation to uterine contractions. Early decelerations begin with the onset of a contraction and return to the baseline with the uterine pressure curve. This pattern of deceleration is not ominous and is related to foetal head compression. It is mediated via the vagus. Neither changes in maternal posture nor increasing maternal oxygenation affect this pattern. Late decelerations are identical in form but begin later in the contraction and return to the base-line long after the uterine pressure curve. This deceleration pattern is related to foetal hypoxia caused by placental insufficiency. It is found in association with decreased placental function, with maternal hypotension and with excessive uterine activity. Variable decelerations bear no time-relationship to contractions, are inconstant in shape, the most common of decelerations and are believed to indicate cord compression. They can often be abolished by changing the mother’s position. Periodic accelerations are invariably benign. Persistent tachycardia not associated with late decelerations may represent the normal heart rate for that foetus, infection, or compensation for a previous hypoxic episode. Base-line tachycardia occurring with late or variable decelerations is important. Variability of frequency and amplitude occurs during labour and may be increased in the healthy foetus but decreased variability with late or variable deceleration indicates a poor foetal outcome. Decreased variability without periodic decelerations is seen in a premature foetus and following the administration of some drugs to the mother. In this foetus the cardiotachograph showed some increased variability and some periodic accelerations only.
Neonatal flaccidity
401
The cardiotachograph recording showed no evidence of uteroplacental insufficiency: the base-line rate was 140 beats per minute with average variability and no periodic decelerations. There was no meconium in the amniotic fluid. Neonatal flaccidity
The differential diagnosis of neonatal flaccidity includes cerebral depression caused by drugs which have crossed the placental barrier. This mother received only 10 mg diazepam intravenously 7 hours before delivery. Diazepam quickly crosses the placental barrier and then accumulates in the foetal circulation, because binding of the drug to foetal plasma proteins is presumed to occur: 6 hours after intravenous administration to the mother, the concentration of the drug in foetal brain and liver is still high.4 There are reports of foetal hypoactivity and hypotonicity in infants whose mothers received diazepam in labour, even in doses as small as that received by this patient.’ Cerebral damage from birth injury may cause a neonate to fail to breathe. This child presented a picture very similar to that of classical pallid asphyxia, in which the infant is pale instead of blue, flaccid instead of rigid. It is either impossible to induce spontaneous ventilation at all or if the infant does breathe it does so in a feeble, shallow fashion. The pulse is rapid and the fontanelles are soft. This is regarded as shock resulting from haemorrhage into the posterior fossa or injury to the medulla. These babies, however, seldom survive more than a few hours. The baby reported here had none of the other stigmata of cerebral injury but it is possible that she had a small degree of cerebral injury which resulted in cerebral oedema from which recovery was complete. Congenitally defective nervous systems may react excessively to mild birth trauma. Other symptoms of defective development might not become evident until several months after birth. Peripheral disorders may result in failure to breathe and cause flaccidity. Diseases like amyotonia congenita or Werdnig-Hoffmann’s disease can cause a ‘floppy baby syndrome’ in the newborn. Drugs affecting the neuromuscular junction must also be considered. The fact that all local anaesthetics cross the placental barrier is well-established. Bupivacaine has a low umbilical vein/maternal venous blood ratio of 0.2-0.4 because it is 90-95% bound to plasma protein in the maternal blood.6 The amount of the drug that does cross the placental barrier is itself bound to foetal plasma protein, which lowers the amount of active drug in the foetal circulation by 45-70%.’ Metabolites of bupivacaine, whose effects have not been fully investigated, are also present in the foetal circulation. The time taken to metabolise these drugs by the relatively inefficient foetal liver is much greater than in the adult. Local anaesthetics are known to effect impulse transmission at the neuromuscular junction in adults in doses higher than those found in the infant but the available studies in animals indicate a significant difference between adult and infant neuromuscular transmission.* The mechanism of this action of local anaesthetics is unknown but it appears to involve both pre- and post-junctional transmission. The total amount of bupivacaine injected into the extradural space was 125 mg (25 ml of 0.5%) bupivacaine without adrenaline over a period of 7 hours. The mother showed no untoward effects due to bupivacaine, was not excessively drowsy and had only moderate motor paralysis of her legs.
402
B. M. Morgan
It is not possible to exclude the action of bupivacaine on the neuromuscular junction as the cause for flaccidity in this infant. Prediction about the outcome of extreme flaccidity and respiratory failure is difficult and decision about the fate of any neonate should not be precipitate. summary
The birth of a flaccid neonate is described. Oxytocin, diazepam and extradural bupivacaine were used during labour, The baby survived 13 hours of artificial ventilation and was subsequently healthy. An account is given of the assessment of foetal maturity and the diagnosis of neonatal flaccidity is discussed. Acknowledgments Thanks are due to Mr A. Amias, Consultant Obstetrician, St George’s Hospital, London, for permission to describe the patient admitted under his care, and to Dr D. M. Davies, Consultant Anaesthetist, St George’s Hospital, London, for his help with the preparation of this paper. References 1. GLUCK,L. & KULOVICH, M.V. (1973) Lecithin/sphingomyelin ratios in amniotic fluid in normal and abnormal pregnancy. American Journal of Obstetrics and Gynecology, 115, 539. B.S. &DAME,L. (1972) Foetal heart rate patterns. Prediction of Apgar score. Journal of 2. SCHIFRIN, the American Medical Association, 219, 1322. B.S. & SMITH,T.S. (1 973) Foetal surveillance during labour. International Anesthesiology 3. SCHIFRIN, Clinics, 11, 17. 4. INDANPAAN-HEIKKILA, J.E., JOUPPILA, P.I., POULAKKA, J.O. & VORNE,M.S. (1971) Placental
transfer and fetal metabolism of diazepam in early human pregnancy. AmericanJournalofObstetrics & Gynecology, 109, 1011. 5. FLoweRs, C.E., RUDOLPH, A.J. & DESMOND, M.M. (1969) Diazepam (Valium) as an adjunct in obstetric analgesia. Obstetrics & Gynecology, 34, 68. F. & TAYLQR, G. (1970) Maternal and neonatal blood concentrations of bupivacaine. 6. REYNOLDS, A comparison with lignocaine during continuous extradural analgesia. Anaesthesia, 25, 14. B.R. (1974) Obstetric analgesia and the newborn baby. Lancet, i, 1283. 7. BLOGG,C.E.& SIMPSON, P.A. (1970) Neuromuscular transmission in newborn rats. Journal of Physiology, 209, 8. REDFERN, 701.
