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The effect of oxytocin in induced labour on neonatal jaundice
Abstract
SummaryA prospective study in 180 mothers and babies examined the effects of oxytocin in induced labour on plasma bilirubin levels in cord blood, as well as on the incidence of neonatal jaundice. Raised plasma bilirubin levels in cord blood, probably enhanced by breakdown of fetal red cells, appeared to be a dose dependent effect of oxytocin. Commensurate with this was the finding that a larger proportion of babies in the induced group manifested a greater severity of jaundice.
... Similar findings presented by JEFFARES [13] again raised the question äs to whether induction itself, rather than the effect of oxytocin might be a contributory factor in the causation of neonatal jaundice. Evidence of a dose dependent effect -of oxytocin on the severity of neonatal jaundice and on the level of bilirubin in cord blood has been recently presented [8]. The widespread liberal use of oxytocin to induce or accelerate labour, often without medical necessity , inspite of the aforementioned contradictory experiences, prompted us to prospectively re- 033-5577/81/0009-0002$02.00 © by Walter de Gruyter & Co. · Berlin -New York examine the relative role of oxytocin versus artificial induction of labor per se äs alleged causes of neonatal hyperbilirubinemia. ...
... This is not surprising in view of the ready transfer of unconjugated bilirubin across the placenta from the fetal to maternal circulation before birth [17]. This finding apparently contradicts that of D'SouzA et al. [8] who related higher doses of oxytocin to higher levels of plasma bilirubin in cord blood. However, our material is different in 2 respects: 1) The "oxytocin induced" group included only readily inducable patients who ...
... 2) Early amniotomy was not performed in our patients, thus presumably we have preserved the "buffer-effect" of amniotic fluid between the fetus and the uterine wall. By this we may have lessened fetal trauma and reduced the rate of red cell breakdown which was hypothesized s the cause of increased cord blood bilirubin levels that follow oxytocin induced labors [8]. Neonatal hyperbilirubinemia, however, was significantly more common following labors induced by oxytocin. ...
Numerous studies have demonstrated the increased incidence of neonatal jaundice among newborns of mothers to whom oxytocin was administered during labor, the more so with induced labors. The question äs to whether the hyperbilimbinemia is the result of the induction itself, owing to relative fetal liver immaturity, versus the possibility of oxytocin drug effect is still a matter of debate. We attempted to shed some light on this question by measuring bilirubin and protein concentrations in cord blood and correlating the results with the occurrence of hyperbilirubinemia in the neonates. The tests were performed in 71 randpmly selected füll term parturients, with uncomplicated pregnancies, delivered of normal healthy infants. The subjects were divided into 3 groups: Group I — normal vaginal delivery, following spontaneous onset of labor (n = 42); Group II – normal vaginal delivery following induction of labor by oxytocin drip (n = 14), and Group III – Elective cesarean section (n = 15). Group I and II were matched for the mean values of maternal age, gestational age at delivery and infants birthweights (Tab. I). Blood was drawn directly from the umbilical artery and analyzed for total bilirubin and total protein. Protein electrophoresis was also applied. Total bilirubin was measured at least daily in the venous blood of 38 neonates who appeared jaundiced during their stay at the neonatal unit.No significant difference was found between the mean values of total bilirubin in the serum of the umbilical artery in the three groups. Mean total protein concentration was, however, higher in Group I than in Groups II and III, the difference between groups I and III being statistically significant (P < 0.05). Neonatal serum bilirubin level greater than 208 /liter occurred in 33.3 per cent of the oxytocin group (Group II) äs compared to only 6.8 per cent and 12.5 per cent in Groups I and III, respectively. Maximal bilirubin levels in neonates who appeared jaundiced bore no significant correlation to their total protein levels in cord blood (Fig. 2). The lack of correlation between serum bilirubin concentration in the umbilical artery and the type of onset of labor and route of delivery is conceivable in view of the ready transfer of unconjugated bilirubin across the placenta from the fetal to maternal circulation before birth. The significantly lower concentration of total protein that was found in the “Cesarean section group” could be explained by the relative immaturity of the fetuses born prior to the date of spontaneous onset of parturition. The easiness of successful induction of labor in the “oxytocin group” may implicate fetal maturity comparable to that found in the “spontaneous onset group”, äs reflected by similar total protein levels in these groups. In spite of this, neonatal hyperbilirubinemia was significantly more common following labors induced by oxytocin. No similar association was found between elective operative termination of pregnancy and neonatal jaundice, thus apparently invalidating the concept of fetal immaturity in this context, and implying a direct effect of oxytocin on the causation of hyperbilirubinemia. It appears from our study that drug effect in an äs yet unidentified mechanism is responsible for the increased incidence of neonatal jaundice among newborn infants of oxytocin induced labors, with ensuing longer hospilization periods. It is concluded that oxytocin administration should be applied only when medically indicated, and owing to the possibility of dose dependeiicy, the minimal effective dose should be used.
... The present study was undertaken in order to compare bilirubin levels of vacuum extracted neonates with those of non-instrumentally delivered babies during the first 72 hours of life. Since controversy exists with regard to the effect of oxytocin induction of labor on the course of neonatal jaundice [3] [4] [8] [11] [21] we have also analyzed the effect of oxytocin induction on the bilirubin levels of our patients. ...
Various fetal scalp lesions are related to the use of the vacuum extractor. Blood sequestered in these lesions could result in an increased bilirubin load on the functionally limited neonatal liver, leading to the development of hyperbilirubinemia. In the present study bilirubin levels of vacuum extracted neonates were compared with those of non-instrumentally delivered babies during the first 72 hours of life. Sixty-nine vacuum extracted neonates had higher bilirubin levels than 56 non-instrumentally delivered babies at 24 (114 mumol/l vs. 96 mumol/l), 48 (163 vs. 141) and 72 (194 vs. 144) hours of age. The p values were 0.05, less than 0.025 and less than 0.001 respectively. This trend was apparent in both oxytocin induced and non-induced deliveries and whether or not phototherapy cases were included in the analysis. The incidence of hyperbilirubinemia requiring phototherapy was higher after vacuum extraction than after non instrumental delivery (27.5% vs. 12.5%; p less than 0.04). Analysis of our results unexpectedly indicated that oxytocin induction was generally associated with an attenuation of bilirubin levels after both vacuum extraction and spontaneous delivery. The clinician attending newborn babies should be aware of the higher incidence of neonatal hyperbilirubinemia associated with vacuum extraction.
A total of 200 women planned for labour induction were randomised to receive high-dose oxytocin (6 mU/min with similar increments every 45 min) or intermediate-dose oxytocin (3 mU/min with similar increments every 45 min). Oxytocin solution was prepared with 30 units in 500 ml saline with which the infusion rate in ml/h is numerically equal to oxytocin in mU/min. We observed that the caesarean rate (18% vs 6%, p = 0.009), contraction abnormalities (35% vs 14%, p = 0.0005) and neonatal bilirubin levels (7.99 ± 2.70 vs 6.80 ± 2.65, p = 0.002) were higher with high-dose than with intermediate-dose. The induction-delivery interval (IDI) was similar (10 h 13 min with high-dose and 11 h 5 min with intermediate-dose; p = 0.237, NS). Nulliparous women benefited more with intermediate-dose as the caesarean rate was higher with high-dose (24.6% vs 7.9%, p = 0.011). Although the caesarean rate was higher in multiparous women with high-dose oxytocin, it was statistically not significant (5.7% vs 2.7%; p = 0.609). Oxytocin regimens for labour induction are usually high-dose (4-6 mU/min) or low-dose (1-1.5 mU/min). The former is associated with more contraction abnormalities and the latter with prolonged IDI; both result in an increased caesarean rate. In order to offset these disadvantages, an intermediate- dose regimen was selected. The increment interval of 45 min was selected in accordance with the pharmacokinetics of oxytocin. We observed a lower caesarean rate when compared with the high-dose regimen, without any increase in the IDI. Hence, we propose that the intermediate-dose oxytocin regimen should be preferred to the high-dose regimen for labour induction.
Summary Four patients had a grand mal convulsion following the occurrence of hyponatraemia during pregnancy. In 3, the problem was caused by the haemodilution consequent upon infusion of oxytocin and 5 per cent dextrose solution in labour. In a prospective survey of 30 subjects treated with this regimen, asymptomatic hyponatraemia developed in 3. Hyponatraemia has risks for mother and baby. Limitation of fluid, given by a separate intravenous line, and 4-hourly plasma sodium estimations might eliminate the problem.
Summary Damage can be caused to the fetal scalp by the application of a spiral electrode in routine fetal heart rate monitoring. In a prospective study of 192 randomly selected mothers with low-risk labours, complications occurred in 4 babies (2 per cent). In the neonatal period these babies had excessive scalp bruising surrounding an area of skin damage and subcutaneous necrosis where the spiral electrode had been applied. The scalp bruising had apparently contributed to severe jaundice, which was treated by phototherapy.
In a prospective randomized study, 20 patients with term pregnancies underwent induction of labor with either continuous or pulsed (every 8 minutes) intravenous oxytocin infusion. There were no significant differences with respect to induction-labor interval, induction-delivery interval, cesarean section rates, need for pain relief and Apgar scores. Sixty percent of patients receiving continuous oxytocin infusion developed uterine hyperstimulation but only 10% receiving pulsed oxytocin did so. However, the difference was not significant. The mean +/- SEM total amount of oxytocin given by continuous infusion was 4237 +/- 1066 mU which was 70% more than by pulsatile infusion (2454 +/- 808 mU). The highest rate of oxytocin infused was significantly lower by pulsatile administration (5.2 +/- 0.8 mU/min) than by continuous infusion (9.2 +/- 1.8 mU/min, p = less than 0.05). Our study demonstrates that pulsed administration of oxytocin every 8 minutes is as effective and safe as continuous intravenous infusion of oxytocin for induction of labor, requires less oxytocin with therefore, a wider margin of safety and is consistent with the pulsatile release of oxytocin during normal labor.
To ascertain the effect of isotonic saline and glucose infusions of oxytocin on neonatal bilirubin levels.
Eighty-two parturient Nigerian women requiring oxytocin infusion in labor were randomized into two groups receiving 0.9% saline or 5% glucose, respectively. A group of 82 women not requiring oxytocin were recruited for comparison. All had sodium and bilirubin estimations in cord plasma and neonatal bilirubin assay on Day 3.
Analysis of variance revealed higher mean cord and neonatal bilirubin levels in the glucose group compared with the other two (P < 0.05). Significant inverse correlation was observed between cord plasma sodium and neonatal bilirubin levels in all groups. Hyperbilirubinemia occurred in 55% of babies in the glucose group compared with 21% and 22% in the saline and control groups, respectively (P < 0.001).
The use of isotonic saline rather than 5% glucose solution as vehicle for oxytocin infusion in labor appears to be associated with lower neonatal bilirubin levels.
A retrospective study of 12 461 single births confirmed an association between maternal oxytocin infusion and neonatal jaundice. The effect of oxytocin on jaundice was independent of gestational age at birth, sex, race, epidural anaesthesia, method of delivery, and birth weight, each of which was significantly associated with neonatal jaundice. The effect of oxytocin was, however, small, producing a calculated mean increase in peak plasma bilirubin concentration of 8.6 mumol/1 (0.5 mg/100 ml); this excess was independent of sex and less than the effect of the baby being born one week earlier.
The use of oxytocin in the induction of labour has been implicated as a cause of neonatal hyperbilirubinaemia. Neonatal hyperbilirubinaemia, however, does not seem to result from induction with prostaglandin E2 (PGE2), though some studies suggest differently. The present study compares the incidence of neonatal hyperbilirubinaemia in patients who are induced with oxytocin with the incidence in those who are induced with PGE2.
A prospective study of 1353 labours and the relevant newborn failed to reveal any significant difference between the incidence of neonatal hyperbilirubinaemia (defined as a level of 12 mg. or more per 100 ml.) following spontaneous labour, and after labour induced or accelerated by oxytocin. The incidence of unexplained neonatal hyperbilirubinaemia after spontaneous labour was 6-3 per cent. Following induced labour however there was a highly significant (P less than 0-001) association between the mean total dose of oxytocin used for induction and the incidence of neonatal hyperbilirubinaemia. The proportion of babies who developed hyperbilirubinaemia increased in direct relation to the total dose of oxytocin used for the induction. In this series the incidence of hyperbilirubinaemia increased sharply when the total dose of oxytocin exceeded 20 units as it did hyperbilirubinaemia and birthweight, or duration of spontaneous labour. When labour was induced, however, the proportion on newborn babies with hyperbilirubinaemia increased with the duration of labour. The significance of these findings is discussed.
A retrospective controlled study using data from the Cardiff Births Survey examined a possible relation between oxytocin administration to induce or accelerate labour and the subsequent development of neonatal jaundice. Among 10 591 infants born in Cardiff between 1970 and 1972 the incidence of neonatal jaundice was higher in infants born after oxytocin administration than among others. Analysis by gestational age at delivery, birth weight, Apgar score, length of labour, sedative and analgesic therapy during labour, and suppression of lactation showed that this association held within all these categories except among small immature infants, who are at high risk of jaundice in any case.
The relation between fetal distress and the subsequent condition at birth was studied in 2791 pregnancies. Fetal distress was defined as a heart rate greater than 160 or less than 120/min between uterine contractions, with or without meconium-stained liquor. Infants of 28 to 42 weeks' gestational age were examined at 1 and 5 minutes after birth when the heart rate, respiration, and skin colour was recorded. Birth scores of 0, 1, or 2 were given respectively if respirations were absent, gasping, or regular; if the heart rate was undetectable, less than 100/min, or greater than 100/min; and if the colour was white, blue, or pink. Fetal distress was associated with low birth scores in infants at 1 and 5 minutes of age. Among those who had not suffered fetal distress a significantly greater proportion of preterm infants had low birth scores compared with term or post-term infants at 5 minutes of age. Infants did not score equally for colour, heart rate, and respiration at 1 and 5 minutes of age. Colour usually gave a birth score of 5 and heart rate was recordable when infants scored 0 for colour and respiration. The reduction in birth scores was greater in the presence of meconium-stained liquor and abnormal fetal heart rate than meconium-stained liquor alone; the latter being an early sign of fetal distress. Since fetal distress was not diagnosed by conventional methods in 93 term infants who probably suffered prenatal asphyxia, more sophisticated techniques are necessary for an accurate assessment of fetal condition during labour.
PIP
4 groups of 30 primigravidas and their infants were studied prospectively. No patient with rhesus incompatibility was included in the study. The 4 groups went into labor in the following ways: 1) induced by intravenous oxytocin; 2) induced by intravenous prostagladin (PG)E2; 3) induced by extraamniotic PGE2; and 4) spontaneous labor. Mean infant bilirubin levels on day 5 were significantly higher (p.005 and p.025 respectively) for the 1st 2 groups than for the spontaneous group. Levels for the group whose labor was induced with extraamniotic PGE2 infusion were not significantly different from those in the 1st 2 groups or the spontaneous group. The mean serum-bilirubin level was significantly lower (p.025) after caesarean section than after assisted vaginal delivery. Serum-bilirubin levels were not affected by previous maternal use of oral contraceptives, maternal smoking, or methods of infant feeding. Serum bilirubin levels below 10 mg/100 ml. are considered within the normal phsyiological limits during the neonatal period. Measured by this criteria, 14, 10, 9, and 6 babies in groups 1-4 respectively had abnormally high levels. The difference between groups 1 and 4 was significant at the p.05 level. Mean Apgar scores were significantly lower for the babies whose mothers had induced delivery with extraamniotic PGE2 infusion. These results suggest that the observed hyperbilirubinemia may be due to interruption of pregnancy rather than to any direct drug effect. There is no evidence to suggest that such high bilirubin levels are harmful to the child in the long run.
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.
Study of 182 newborn babies has shown that among bottle-fed infants the mean plasma bilirubin concentration was slightly but significantly higher (P <0.01) in those whose mothers had previously used steroid contraceptives. A similar finding was not noted among breast-fed infants.A further 16 infants whose mothers had received progestogen therapy during their pregnancy had a mean plasma bilirubin concentration which was significantly higher than each of the four other groups of infants studied (P <0.01). Icterus occasionally reached clinically important levels in these babies.
A prospective study of serum bilirubin levels on the first and sixth days of life in a series of 181 infants has failed to provide evidence to suggest that previous maternal oral contraception, maternal oxytocin infusion, epidural anaesthesia, or breast-feeding are factors influencing neonatal jaundice.