Neonatal Jaundice and Maternal Oxytocin Infusion

A prospective study of 78 neonates provides evidence for an association between maternal oxytocin infusion and neonatal jaundice. On the second and fifth days infants of mothers whose labour had been induced by amniotomy followed immediately by intravenous oxytocin (group C) had mean total bilirubin levels significantly higher (P <0·05) than did infants whose mothers had had a spontaneous onset of labour and did not require oxytocin (group A). Bilirubin levels in infants of mothers whose onset of labour was spontaneous but required oxytocin to accelerate progress (group B) did not differ significantly from group A.Though these findings suggest a dose dependent effect of oxytocin, other possible explanations are suggested which take into account other drugs administered to the mother and also differences in the corticosteroid status of the groups of infants.     

The syndrome of inappropriate antidiuretic hormone secretion

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the commonest form of normovolaemic or dilutional hyponatraemia. The diagnosis of SIADH should be considered if the five cardinal criteria are fulfilled (hypotonic hyponatraemia, natriuresis, urine osmolality in excess of plasma osmolality, absence of oedema and volume depletion, normal renal and adrenal function). The clinical features are principally neuro-muscular and gastro-intestinal, the severity of which is related to both the absolute serum sodium concentration and its rate of fall, particularly if greater than 0.5 mmol/1/h. The dilutional hyponatraemia of SIADH develops due to persistent detectable or elevated plasma arginine vasopressin (AVP) concentrations in the presence of continued fluid intake. Osmoregulated inhibition of thirst failures to curb fluid intake. The major groups of causes of SIADH are: (i) neoplasia, (ii) neurological diseases, (iii) lung diseases and (iv) a wide variety of drugs. Inappropriate infusion of hypotonic fluids in the post-operative state remains a common cause. Four categories of osmoregulated AVP secretion have been described: (i) erratic AVP release, (ii) reset osmostat, (iii) persistent AVP release at low plasma osmolality and (iv) normal osmoregulated AVP secretion. For symptomatic patients with chronic SIADH, the mainstay of therapy remains fluid restriction. New antagonists to the antidiuretic action of AVP offer a new therapeutic approach.     

Severe hypernatraemia in adults.

In a prospective study of abnormalities of plasma sodium concentration carried out over one year 20 patients were identified who had a concentration exceeding 154 mmol(mEq)/1. Of these, eight patients had diabetes mellitus, eight had primary intracranial disorder, and four had become dehydrated. Five of the eight diabetics presented with hyperosmolar, non-ketotic precoma, and in all eight hypernatraemia developed despite treatment with hypotonic (0.45%) saline. There was a good correlation (r = -0.93) between the rates of change of plasma sodium and blood glucose concentrations, and thus a rise in plasma sodium concentration appeared to be a consequence of the treatment. In the early phase of treatment urinary sodium loss was extremely low despite a brisk diuresis, the infused sodium then predisposing the patients to hypernatraemia. All of the eight patients with intracranial disorders showed evidence of abnormal production of the antidiuretic hormone, six having frank diabetes insipidus. Severe hypernatraemia in this group was associated with a high mortality, fluid balance being difficult to maintain. Two of the four patients who had become dehydrated had had a recent gastrointestinal haemorrhage. In these patients infusion of 0.9% saline contributed to the hypernatraemia since urinary sodium loss was low. Severe hypernatraemia in adults is uncommon, but in established cases plasma and urinary biochemical indices should be measured frequently. Monitoring of the central venous pressure is usually necessary, and patients are best managed in an intensive care unit.     

Plasma trace element (Se,Zn, Cu) concentrations in maternal and umbilical cord blood in Poland

Selenium (Se), copper (Cu), and zinc (Zn) concentrations were determined in plasma of 64 mothers at delivery, 58 nonpregnant women, 64 neonates, and 12 infants, aged 2–12 mo. Se and Zn concentrations in mothers at delivery were significantly lower, and Cu higher than in nonpregnant women. Mean Se and Cu concentrations in newborns were statistically lower than those in mothers at delivery, and Zn and Cu concentrations in preterm infants (n=13) were significantly higher than in fullterm infants (n=51). Maternal parity had no significant influence on the distribution of plasma trace element levels. No significant differences were observed in Se and Zn levels in maternal and cord blood plasma according to birth weight, contrary to maternal Cu concentration. Significant correlations were found between maternal and cord blood Se content, and between maternal plasma Cu concentration and birth weight of neonates.     

Dynamics of prostaglandin secretion, intrauterine fluid and uterine clearance in reproductively normal mares and mares with delayed uterine clearance

Two experiments were performed to investigate relationships between oxytocin, prostaglandin release, uterine emptying and fluid accumulation in the uterus. In Experiment 1, the effect of oxytocin on the pattern of prostaglandin release during uterine clearance of radiocolloid was measured in 5 normal mares and 5 mares with delayed uterine clearance. Uterine clearance was measured during estrus by scintigraphy at 0, 60 and 120 min after colloid infusion. After the 120-min reading, 20 IU, i.v., oxytocin were given, and the amount of colloid cleared was measured at 135, 150 and 180 min. Plasma was obtained prior to and during scintigraphy at 5- and 15-min intervals to measure concentrations of 15-keto-13,14-dihydro-PGF2 alpha metabolite (PGFM) by RIA. In Experiment 2, plasma PGFM levels were compared after administration of oxytocin in 8 normal mares and 6 mares with delayed uterine clearance to determine if intrauterine fluid stimulated prostaglandin release. Mares received 2 treatments in a cross-over design. Treatment 1 consisted of 20 IU, i.v., oxytocin during estrus. Treatment 2 consisted of an infusion of 10 mL, i.u., saline 15 min prior to oxytocin administration. Treatments were performed 4 to 6 h apart. Blood was collected and PGFM was measured as in experiment 1. Data were analyzed by least squares analysis of variance. In Experiment 1, regression analysis of scintigraphy and PGFM profiles indicated that time response curves differed between groups (P < 0.01). At 120 min, normal mares retained 40.4 +/- 4.9% (mean +/- SEM) of the radiocolloid while mares with delayed clearance retained 88 +/- 5%. Fifteen minutes after oxytocin administration (135 min), all normal mares and 4 of 5 mares with delayed clearance retained only < 6% of the colloid. During the first 120 min, plasma PGFM concentrations did not differ between the 2 groups. After oxytocin was given, plasma PGFM concentrations increased in 4 of 5 mares with delayed uterine clearance (80 to 3,096 pg/mL) but not in normal mares (13 to 46 pg/mL). In Experiment 2, plasma PGFM concentrations did not rise in normal mares but rose in 3 of 6 mares with delayed clearance (135 to 483 pg/mL) independent of treatment or period. The results suggest that intrauterine clearance of radiocolloid after oxytocin administration appears to be independent of PGF2 alpha release in normal mares during estrus. The difference in prostaglandin release response after oxytocin administration between the 2 groups was unrelated to the presence of intrauterine fluid.     

Effects of labour and medication on major lymphocyte subsets in cord

It is envisaged that flow cytometric analysis of lymphocyte subsets in cord blood may be used as a biomarker for effects on the immune system of exposure to environmental factors. In order to investigate the possible application of this parameter, we first studied the effects of other factors that may influence the outcome of subset analysis in cord blood. FACS analysis was performed in 112 pairs of umbilical cord blood and of peripheral maternal blood sampled at labour. Whereas in maternal blood no statistically significant effects of medication during labour on T lymphocyte numbers and NK cells were found, in oxytocin and in oxytocin and prostaglandin treated mothers B cell numbers showed a statistically significant increase. In cord blood, the course of labour and or medication during labour were identified as the most important factors determining distribution of major lymphocyte subsets. In cord blood after deliveries without medication or after neuroplegic analgesia NPA, the mean percentage of cord blood T lymphocytes CD3 was highest 59 and that of NK lymphocytes CD3- CD16 56 lowest 20 . The mean percentage of T lymphocytes was significantly lower 52 and that of NK lymphocytes higher 28 in cord blood where deliveries were done under NPA in combination with infusion of oxytocin. The combination of NPA with oxytocin and induction of labour by prostaglandin E2 led to a further reduction of T lymphocytes and an increase of NK cells 39 and 38 respectively. The changes in ratio of T and NK lymphocytes were due both to decreasing absolute counts of T lymphocytes and increasing counts of NK lymphocytes. Thus, the effects of labour and or medication during labour must be taken into account when this parameter is applied as a potential biomarker of effects of environmental factors on the immune system.     

Effects of labour and medication on major lymphocyte subsets in cord

It is envisaged that flow cytometric analysis of lymphocyte subsets in cord blood may be used as a biomarker for effects on the immune system of exposure to environmental factors. In order to investigate the possible application of this parameter, we first studied the effects of other factors that may influence the outcome of subset analysis in cord blood. FACS analysis was performed in 112 pairs of umbilical cord blood and of peripheral maternal blood sampled at labour. Whereas in maternal blood no statistically significant effects of medication during labour on T lymphocyte numbers and NK cells were found, in oxytocin and in oxytocin and prostaglandin treated mothers B cell numbers showed a statistically significant increase. In cord blood, the course of labour and or medication during labour were identified as the most important factors determining distribution of major lymphocyte subsets. In cord blood after deliveries without medication or after neuroplegic analgesia NPA , the mean percentage of cord blood T lymphocytes CD3 was highest 59 and that of NK lymphocytes CD3- CD16 56 lowest 20 . The mean percentage of T lymphocytes was significantly lower 52 and that of NK lymphocytes higher 28 in cord blood where deliveries were done under NPA in combination with infusion of oxytocin. The combination of NPA with oxytocin and induction of labour by prostaglandin E2 led to a further reduction of T lymphocytes and an increase of NK cells 39 and 38 respectively . The changes in ratio of T and NK lymphocytes were due both to decreasing absolute counts of T lymphocytes and increasing counts of NK lymphocytes. Thus, the effects of labour and or medication during labour must be taken into account when this parameter is applied as a potential biomarker of effects of environmental factors on the immune system.     

Leptin concentrations in cord blood in normal newborn infants and offspring of diabetic mothers.

Leptin has been implicated in the regulation of body weight and energy balance; Leptin is produced by adipocytes and placental tissue. Chronic fetal hyperinsulinemia and accelerated fetal growth with increased amounts of body fat are frequent findings in the offspring of diabetic mothers. In this study, we examined whether leptin levels in cord blood of infants of type 1 diabetic mothers (n = 29), gestational diabetic mothers (n = 6 and controls (n = 96) correlated with level of maternal glucose control, maternal leptin level at delivery, gender, fetal and placental size, and C-peptide in cord blood at birth. Leptin was significantly elevated in infants of type 1 diabetic (24.7 ng/ml) and gestational diabetic mothers (29.3 ng/ml) as compared to controls (7.9 ng/ml). C-peptide was also significantly higher in infants of type 1 diabetic (0.91 nmol/l) and gestational diabetic mothers (0.99 nmol/l) vs controls (0.34 nmol/l). Infants of type 1 diabetic mothers with a leptin level in cord blood above the upper normal range, i.e. > 30 ng/ml (n = 13), had an average maternal HbA1c level of 5.4% (normal < 5.5%) that was not different from 5.2% in infants with a leptin level < 30 ng/ml (n = 15). In both neonatal groups of diabetic mothers, leptin in cord blood did not correlate with maternal leptin concentrations, placental weight, birthweight, gender and cord blood C-peptide. In controls, leptin in cord blood was higher in girls than in boys (p = 0.044) and correlated significantly with birthweight (p = 0.41, p < 0.001) and cord blood C-peptide (p = 0.44, p < 0.001) but not with maternal leptin level or placental weight. The 3-4 times higher leptin levels in the offspring of diabetic mothers than normal could reflect increased adipose tissue mass and/or increased contribution from other sources such as placental tissue.     

A method for maintaining normoglycemia during labour and delivery in insulin-dependent diabetic women.

The effectiveness of combining the subcutaneous administration of short- and intermediate-acting insulin with the intravenous infusion of glucose in maintaining normoglycemia during labour and delivery in insulin-dependent diabetic women was tested. Fifty women were given intermediate-acting insulin twice daily in doses that were fractions of their usual dose, based on the projected duration of labour. In addition, they were given regular (i.e., short-acting) insulin every 6 hours, the dose being 1% of their total daily insulin dose for every increase of 10 mg/dl above 100 mg/dl (5.6 mmol/l) in the plasma glucose level 1 hour previously; the levels were measured every 3 hours. All the patients were fasting and received a basal intravenous infusion of 6 g/h of glucose; the rate of infusion was increased by 1 g/h for every decrease of 10 mg/dl in the plasma glucose level below 100 mg/dl. The mean plasma glucose levels (+/- standard deviation) were 90 +/- 46 mg/dl after 3 hours of labour, 92 +/- 35 mg/dl after 6 hours, 97 +/- 49 mg/dl after 9 hours and 107 +/- 65 mg/dl after 12 hours. With only one exception, in a premature infant, the 5-minute Apgar scores were identical to those of the infants of nondiabetic women.     

Mathematical simulation of the body fluid regulating system in dog

A mathematical model of body fluid volume and osmolality regulation was developed which incorporated the major nonlinearities of fluid assimilation, exchange, distribution and excretion. The non-linear differential equations define compartmental material balances for water, urea, sodium, protein and antidiuretic hormone (ADH). The parameters of these equations were calculated using analytical solutions and available steady-state experimental data. The model was used to simulate the renal response to five input forcings: (1) intraesophageal water infusion; (2) water ingestion; (3) intravenous ADH injection; (4) intravenous water infusion; and (5) intermittent water loading. The model yielded continuous simulation curves which agreed reasonably well with the available transient and steady-state experimental data. The model predicted that stimulating volume receptors via changes in left atrial pressure accounts for only 15–20% of changes in ADH secretion rate, whereas stimulation of the osmotic receptors via changes in plasma osmolality accounts for the remaining 80–85% of changes. Thus, it appears that regulation of ADH secretion is largely dependent upon plasma osmolality during forcings which do not appreciably alter the cardiovascular blood volume.     

Hypoalbuminaemic hyponatraemia: a new syndrome?

Six patients with severe hyponatraemia had neurological features of hyponatraemia and pronounced hypoalbuminaemia. All had biochemical features typical of the syndrome of inappropriate secretion of antidiuretic hormone with low serum osmolality and an inappropriately high urinary osmolality. All were given infusions of whole plasma or albumin solution, or both, to restore their plasma albumin concentrations to normal, which led to a dramatic increase in plasma sodium concentrations and serum osmolality, with a concomitant fall in urinary osmolality in all patients. Neurological features were reversed in four patients. It is suggested that severe hypoalbuminaemia is an important cause of appreciable hyponatraemia; infusions of plasma and albumin in such patients may reverse the biochemical and clinical features and should form the basis of management.     

Osmotic Regulation of Toad Bladder Responsiveness to Neurohypophyseal Hormones

The effect of dilution of the interstitial fluids on the responsiveness of the toad urinary bladder to antidiuretic hormones has been examined in vivo and in vitro. Toads were given periodic injections with vasopressin while in water so that their plasma osmolality fell below 190 mosmoles/kg H₂O. The hydraulic conductivity of bladders which had been removed from the animal and fixed with 1% glutaraldehyde was 10-fold less in overhydrated toads than in normally hydrated controls. A similar inhibitory phenomenon was observed in in vitro studies, when the tonicity of Ringer's fluid in which the bladders were suspended was lowered from its isotonic value. Mannitol, but not urea, could be effectively substituted for one-half of the NaCl content of Ringer's fluid. In other experiments it has been shown that the responsiveness of the bladder to vasotocin is depressed during bulk water movement across the tissue. This "flux inhibition" was found to depend upon the velocity and the duration of water flow from mucosa to the serosa. It is suggested that the responsiveness of the toad bladder to antidiuretic hormones diminishes as the effective osmotic pressure of the interstitial fluids declines.     

Maternal Oxytocin Is Linked to Close Mother-Infant Proximity in Grey Seals (Halichoerus grypus)

Maternal behaviour is a crucial component of reproduction in all mammals; however the quality of care that mothers give to infants can vary greatly. It is vital to document variation in maternal behaviour caused by the physiological processes controlling its expression. This underlying physiology should be conserved throughout reproductive events and should be replicated across all individuals of a species; therefore, any correlates to maternal care quality may be present across many individuals or contexts. Oxytocin modulates the initiation and expression of maternal behaviour in mammals; therefore we tested whether maternal plasma oxytocin concentrations correlated to key maternal behaviours in wild grey seals (Halichoerus grypus). Plasma oxytocin concentrations in non-breeding individuals (4.3 ±0.5 pg/ml) were significantly lower than those in mothers with dependent pups in both early (8.2 ±0.8 pg/ml) and late (6.9 ±0.7 pg/ml) lactation. Maternal plasma oxytocin concentrations were not correlated to the amount of nursing prior to sampling, or a mother’s nursing intensity throughout the dependant period. Mothers with high plasma oxytocin concentrations stayed closer to their pups, reducing the likelihood of mother-pup separation during lactation which is credited with causing starvation, the largest cause of pup mortality in grey seals. This is the first study to link endogenous oxytocin concentrations in wild mammalian mothers with any type of maternal behaviour. Oxytocin’s structure and function is widely conserved across mammalian mothers, including humans. Defining the impact the oxytocin system has on maternal behaviour highlights relationships that may occur across many individuals or species, and such behaviours heavily influence infant development and an individual’s lifetime reproductive success.     

Pathogenesis of neonatal hyperbilirubinaemia after induction of labour with oxytocin.

To determine the pathogenesis of neonatal hyperbilirubinaemia after oxytocin-induced labour venous cord blood from 95 healthy newborn infants was examined. Of these, 15 were delivered by elective caesarean section, 40 after spontaneous labour, and 40 after oxytocin-induced labour. There was no significant difference in any haematological or biochemical variable between the first two groups. Infants born after oxytocin-induced labour, however, showed clear evidence of increased haemolysis associated with significantly decreased erythrocyte deformability (P less than 0.001). In-vitro studies showed a time- and dose-related reduction in erythrocyte deformability in response to oxytocin. The findings suggest that the vasopressin-like action of oxytocin causes osmotic swelling of erythrocytes leading to decreased deformability and hence more rapid destruction with resultant hyperbilirubinaemia in the neonate.     

The influence of gestational age and onset of labour on determinants of fetal-maternal fluid and electrolyte balance in sheep.

Our aim was to compare the effects of gestational age and the timing of the onset of labour on factors influencing fetal fluid and electrolyte balance and urine production in fetal sheep. We measured the volume and composition of fetal urine and amniotic and allantoic fluids, as well as fetal and maternal plasma composition and micturition episodes in sheep during late gestation until the onset of labour. We found that daily fetal urine production and urethral urine flow per micturition episode increased significantly in relation to the onset of labour but not to gestational age (P < 0.05). In the 2 days preceding the onset of labour fetal urine and amniotic fluid K+ concentrations and urine osmolality increased significantly and the Na+/K+ ratio in allantoic fluid decreased significantly (P < 0.05). There was also a significant fall in fetal arterial SaO2 (P < 0.05) but no significant changes occurred in fetal plasma electrolyte composition, osmolality or AVP concentrations. Fetal plasma cortisol and prolactin concentrations and amniotic and allantoic fluid prolactin concentrations increased significantly and progressively in association with both advancing gestation and the onset of labour whereas maternal plasma prolactin concentrations increased significantly only in the 2 days before the onset of labour (P < 0.05). We conclude that some developmental aspects of fetal fluid and electrolyte balance, including renal function, are more closely related to the timing of parturition than to gestational age per se.     

Influence of simultaneous low amniotomy and oxytocin infusion and other maternal factors on neonatal jaundice: a prospective study.

In a prospective study of 196 consecutive single births a significant increase in serum bilirubin concentrations was found in infants born after low amniotomy induction and oxytocin infusion compared with those born spontaneously. This relationship was not dose-dependent and may have been associated with artificial interruption of pregnancy rather than the oxytocin itself. Infants delivered after spontaneous labour accelerated by oxytocin showed no such increase. The hormonal surge at the spontaneous onset of labour may affect fetal enzyme induction, but other factors, such as methods of infant feeding and oral contraceptive use, were found not to be significant.     

Delivery after caesarean section: review of 2176 consecutive cases.

A total of 2176 consecutive patients who had had one previous caesarean section were studied retrospectively. A repeat elective caesarean section was performed in 395 (18.2%). Labour started spontaneously in 1363 patients, 301 of whom were given oxytocin to accelerate inert labour, and was induced by amniotomy and infusion of oxytocin in 418 women; 1618 of these 1781 patients (90.8%) delivered vaginally. Patients who had had a previous vaginal delivery were more likely to deliver vaginally again. Those women in whom the initial caesarean section had been performed during labour before the cervix was 4 cm dilated were less likely to deliver vaginally than those who had progressed further in labour or those who had had an elective caesarean section. Similarly, those who received oxytocin to stimulate inert labour were more likely to require a repeat caesarean section than those who did not. The uterine scar ruptured in only eight (0.45%) of the 1781 patients allowed into labour. The risk of rupture of the scar was not increased by the use of oxytocin alone either to induce or to accelerate labour. The combination of oxytocin to accelerate labour and epidural analgesia to provide pain relief, however, was associated with an increased incidence of scar rupture. Labour may be safely allowed in women who have had a previous caesarean section, most of whom will deliver vaginally. Induction of labour does not increase the risk of either a repeat caesarean section or rupture of a uterine scar.     

Plasma oxytocin during third stage of labour: comparison of natural and active management.

The incidences of postpartum haemorrhage and retained placenta have decreased with the use of synthetic oxytocin and controlled cord traction. Whether such treatment is valuable is open to question because of the lack of clinical and physiological studies. The physiological effects of synthetic oxytocin on plasma concentrations of oxytocin and events during delivery were assessed. Plasma oxytocin concentration was determined in serial samples during the late second stage and throughout the third stage of labour in 25 women. Ten women received combined ergotamine and synthetic oxytocin intramuscularly and 15 were not treated. The geometric mean plasma oxytocin concentration significantly increased in the women given oxytocin when measured before and after delivery of the fetal anterior shoulder (3.1 (SD 2.0) pmol/l before and 15.9 (2.7) pmol/l after). Six of the women who did not receive treatment showed a significant increase in geometric mean plasma oxytocin concentration before and after delivery of the fetal shoulder (3.2 (2.0) pmol/l before and 6.4 (2.0) pmol/l after) and nine did not show an increase (geometric mean 2.4 (3.1) pmol/l before and 2.2 (2.2) pmol/l after). Of these nine women, two had an abnormal third stage of delivery; one woman had a postpartum haemorrhage and one required manual removal of the placenta. As it is impossible to predict which women will show a rise in the plasma concentration of endogenous oxytocin, intramuscular oxytocin should be given routinely.     

Clinical Trials of Different Concentrations of Oxygen and Nitrous Oxide for Obstetric Analgesia: Report to the Medical Research Council of the Committee on Nitrous Oxide and Oxygen Analgesia in Midwifery

Trials have been organized by a Medical Research Council committee to assess the effectiveness and safety for analgesia in labour of oxygen and nitrous oxide mixtures in different proportions. In a preliminary trial concentrations of 50% and 60% v/v nitrous oxide were compared, but, as the replies of 409 mothers revealed little difference between the two, the results of administering either 50% or 70% nitrous oxide to 778 mothers were then compared. The data relating to normal labour, obtained on 501 of the mothers in this main trial, showed that the relief of pain given was much the same. There was a suggestion, however, that the higher concentration of nitrous oxide might be useful in abnormal labour. The proportion of mothers with normal deliveries who lost consciousness, though very small, was significantly higher with 70% nitrous oxide than with the lower concentration. Ninety-two per cent. of mothers found the gas and oxygen machine helpful, and midwives reported complete or good co-operation by 77% of those using it. It is concluded that the 50% oxygen and 50% nitrous oxide mixture can safely be used by unsupervised midwives.     

Urea for long-term treatment of syndrome of inappropriate secretion of antidiuretic hormone.

The efficacy of oral urea in producing a sufficiently high osmotic diuresis was tested in seven patients with the syndrome of inappropriate secretion of antidiuretic hormone. In all patients urea corrected the hyponatraemia despite a normal fluid intake. Five patients were controlled (serum sodium concentration greater than 128 mmol(mEq)/1) with a dose of 30 g urea daily, and two with 60 g daily. The patients who needed 30 g drank 1-2 1 of fluid daily, while those who needed 60 g drank up to 3.1 per day. No major side effects were noted, even after treatment periods of up to 270 days. These findings suggest that urea is a safe and efficacious treatment of the syndrome of inappropriate secretion of antidiuretic hormone.