Neonatal Adverse Effects Research Articles

Maternal and Neonatal Fentanyl and Bupivacaine Concentrations After Epidural Infusion During Labor

Labor analgesia using continuous epidural infusions of low-dose bupivacaine and fentanyl may be maintained for many hours. We examined the potential for drug accumulation in both mother and neonate after these long-term infusions. Pregnant women receiving a 10-mL/h continuous infusion of labor analgesia with 0.125% bupivacaine and 2 micrograms/mL of fentanyl were evaluated. Maternal venous and umbilical venous drug concentrations were measured at delivery. Umbilical artery blood gases were obtained. Scanlon neurobehavioral testing was performed on all infants. Length of infusion times varied from 1 to 15 h. Maternal and neonatal drug concentrations remained relatively constant throughout the infusion period. All umbilical blood gas values and neurobehavioral scores were within normal limits. In conclusion, even when maintained for many hours, continuous infusion labor analgesia does not appear to result in significant fetal drug accumulation. No adverse neonatal effects were seen.

Labor induction with intravaginal misoprostol versus intracervical prostaglandin E 2 gel (Prepidil gel): Randomized comparison

OBJECTIVE: Our purpose was to compare the safety and efficacy of intravaginal prostaglandin E 1, misoprostol, with that of intracervical prostaglandin E 2 (Prepidil gel) for labor induction. STUDY DESIGN: One hundred three patients with an indication for induction of labor were randomly assigned to induction with prostaglandin E 1, 50 μg intravaginally, or with Prepidil gel, 0.5 mg intracervically, every 4 hours until active labor. RESULTS: Four patients were excluded, leaving 49 patients who received prostaglandin E 1 and 50 who received prostaglandin E 2. The time from start of induction to vaginal delivery was significantly shorter in the prostaglandin E 1 group (11.4 vs 18.9 hours, p < 0.001), and fewer patients in the prostaglandin E 1 group required oxytocin augmentation (23% vs 55%, p < 0.005). No significant differences were noted in mode of delivery or in adverse maternal, fetal, or neonatal effects. CONCLUSION: Intravaginal prostaglandin E 1 is a more effective, lower-cost agent for induction of labor than is intracervical prostaglandin E 2 gel and is comparable in safety.

5 Prevention of preterm birth

Preterm labour and delivery remain a major cause of perinatal morbidity, mortality and long-term adverse neurodevelopmental outcome. An effective primary prevention strategy is desirable, but current approaches appear largely ineffective at present. Understanding the aetiology of the onset of preterm labour continues to improve with the recognition of the role played by subclinical infection in a significant proportion of cases. The investigation of hormonal influences in the aetiology of preterm labour is at an early stage, but there appears to be a relationship between raised serum relaxin concentrations and preterm delivery (Petersen et al, 1992). The naturally occurring phospholipase A2-inhibitor gravidin, believed to be important in pregnancy maintenance, is found in a reduced concentration in women delivering preterm (Wilson, 1993). The relationship between hormonal levels, socio-economic influences, subclinical infection and actual preterm labour and delivery remains to be established. Secondary prevention with tocolysis remains unsatisfactory, owing to the low therapeutic index of currently available agents and their varied maternal and neonatal adverse effects. The investigation of newer tocolytic agents remains a worthwhile pursuit, whilst the underlying aetiology of preterm labour and effective prevention remains to be elucidated. The widespread recognition of the benefits of antenatal corticosteroid administration and subsequent adoption into clinical practice has reduced, and will continue to reduce, the morbidity associated with preterm birth while newer methods of accelerating fetal maturation are explored and applied in clinical practice.

EPIDURAL ANALGESIA FOR LABOUR IN ARMED FORCES HOSPITALS: A PRELIMINARY STUDY TO ASSESS FEASIBILITY AND ACCEPTANCE

A pilot project to assess the feasibility of using epidural analgesia for labour was undertaken in an Armed Forces hospital. Effectiveness of the technique, acceptability by patients and nursing staff was assessed. Forty parturients were offered labour analgesia after explaining the procedure. A single-use 16 G Romson epidural catheter was placed in L2-3 or L3-4 space. Injection bupivacaine (0.25%) 10-14 mL was used as an initial dose. An hourly dose of 0.125% bupivacaine (10-12 mL) was given till the onset of second stage. Good to excellent analgesia during first stage was experienced by 34 patients. Marginal second stage prolongation was noticed but without any adverse neonatal effects. Analgesia was unsatisfactory during second stage in 25% patients. Instrumental delivery was required in 17% patients (LSCS - 10% and vacuum extraction - 7%). Procedure was accepted very well by 37 patients and they were satisfied with the pain relief.

Anaesthetic agents and excretion in breast milk.

This review is an update on anesthetic agents and their excretion into breast milk; it presents the reported effects on suckling infants, and discusses the precautions which should be considered. For most anaesthetic agents, there is very sparse information about breast milk excretion and even less published knowledge about the possible effects on the suckling infant. Generally, when an anaesthetic agent is given on a single-dose basis, there is no evidence that it is excreted in breast milk in clinically significant amounts, even if there are detectable concentrations of the drug in the milk. Most anaesthetics are rapidly cleared from the mother, and, consequently, it should be possible to allow suckling as soon as practically feasible after surgery. However, repeated administration of certain opiates and benzodiazepines has been reported to cause adverse effects in neonates, with premature neonates apparently being more susceptible. Thus, in long-term treatment with these drugs, the importance of uninterrupted breast feeding should be assessed against possible adverse drug effects in the neonate.

PLASMA CATECHOLAMINES AND NEONATAL CONDITION AFTER INDUCTION OF ANAESTHESIA WITH PROPOFOL OR THIOPENTONE AT CAESAREAN SECTION

Increased maternal sympathetic nervous system activity may decrease placental perfusion and cause adverse neonatal effects. We have studied the catecholamine response and neonatal outcome in Chinese patients with uncomplicated, singleton pregnancies undergoing Caesarean section. Anaesthesia was induced with thiopentone 4 mg kg-1 (n = 32) or propofol 2 mg kg-1 (n = 30) followed by suxamethonium. Laryngoscopy was performed after 1 min and tracheal intubation completed by 2 min. Anaesthesia was continued with atracurium, nitrous oxide and isoflurane. Maternal venous blood samples were taken at 0, 1, 2, 3, 4 min and at delivery for assay of catecholamines. The increase from baseline values in mean arterial pressure after tracheal intubation was greater in the thiopentone group (29 (SD 15) mm Hg) compared with the propofol group (18 (14) mm Hg) (P < 0.01). The concentrations of noradrenaline and adrenaline increased in both groups after tracheal intubation. Maximum noradrenaline concentrations were greater in the thiopentone group (413 (177) pg ml-1) compared with the propofol group (333 (108) pg ml-1) (P < 0.05), but there were no differences between groups in adrenaline concentrations. Neonatal Apgar scores, neurobehavioural testing and umbilical catecholamine, blood-gas tension and oxygen content analysis were similar between groups. Propofol attenuated the hypertensive and catecholamine response associated with laryngoscopy and tracheal intubation but there was no improvement in neonatal outcome.

The use of low dose aspirin in pregnancy.

Pregnancy-induced hypertension (PIH) in general and preeclampsia in particular are major causes of maternal and perinatal morbidity. Data from our studies and from a number of prospective controlled trials have suggested that aspirin in doses of 60-150 md/day during the second and third trimester reduces the risk of PIH and improves maternal and neonatal outcomes. The number of patients enrolled in these studies is relatively small. However, meta-analysis of existing trials suggests that low dose aspirin reduces the risk of PIH and severe low birth weight. Although no maternal or neonatal adverse effects associated with aspirin were observed, the use of aspirin in the third trimester has been reported to cause hemostatic abnormalities in both mother and neonate. Other complications associated with prostaglandin synthetase inhibitors include premature closure of the ductus and neonatal primary pulmonary hypertension. The use of aspirin in the first trimester is not associated with increased risk of structural malformations. On the basis of these findings and pending the results of ongoing large-scale randomized multicenter trials, we suggest that daily low dose aspirin (1 to 2 mg/kg/day) be recommended only for select women at high risk for developing PIH and its associated complications.

Nifedipine for treatment of preterm labor: A historic prospective study

The purpose of this study was to ascertain whether adverse fetal and/or neonatal effects occurred during nifedipine treatment of preterm labor and to assess maternal tolerance of nifedipine therapy in patients intolerant of a beta-sympathomimetic agent. We undertook historic prospective review of medical records of 102 women admitted to an antepartum ward for treatment of preterm labor who received nifedipine. Data were collected regarding maternal side effects, fetal surveillance, and neonatal outcome. The number and severity of reported maternal side effects were significantly reduced when patients were switched from terbutaline to nifedipine. No discontinuance of nifedipine occurred because of maternal side effects. Fetal surveillance testing and neonatal outcome data failed to reveal deleterious in utero effects of nifedipine. Nifedipine was a well-tolerated and safe tocolytic in this population and warrants further investigation.

Bupivacaine versus bupivacaine plus fentanyl for epidural analgesia: Effect on maternal satisfaction

OBJECTIVE--To compare a combination of epidural fentanyl and bupivacaine with bupivacaine alone for epidural analgesia in labour and to evaluate factors in addition to analgesia that may influence maternal satisfaction. DESIGN--A prospective randomised pilot study. SETTING--Birmingham Maternity Hospital. SUBJECTS--85 primiparous women who requested epidural analgesia in labour and their babies. INTERVENTIONS--Group 1 mothers were treated with bupivacaine conventionally, group 2 mothers with bupivacaine and fentanyl in a more complex way designed to provide satisfactory analgesia but with less troublesome side effects. MAIN OUTCOME MEASURES--Overall maternal satisfaction, maternal perception of epidural analgesia and its side effects, and aspects of mothers9 psychological states during labour, quantified using 100 mm visual linear analogue scales; the frequency of normal and operative deliveries; and measurements of neonatal wellbeing. RESULTS--Satisfaction was higher in group 2 mothers (median group difference +3 mm, 95% confidence interval +1 to +5, p = 0.012): this was associated with more normal deliveries (difference between proportions 0.23, 95% confidence interval +0.03 to +0.42); greater self control (median group difference -7 mm, -17 to -2, p = 0.003); and reduced unpleasantness of motor blockade (-10 mm, -19 to -5, p less than 0.001), sensory blockade (-5 mm, -11 to -2, p = 0.002) and shivering (-5 mm, -18 to 0, p = 0.046) at the expense of mild itching (0 mm, 0 to 0, p less than 0.001). Group 1 mothers found restricted movements more unpleasant (-1 mm, -11 to 0, p = 0.006) and were more sleepy (-4 mm, -20 to 0, p = 0.032). The addition of fentanyl to bupivacaine reduced the requirement for local anaesthetic (-33 mg, -55 to -15, p less than 0.001) without compromising analgesia. No adverse effects in neonates were attributed to the use of fentanyl. CONCLUSIONS--The already high maternal satisfaction from conventional epidural analgesia can be improved; epidural fentanyl may be combined with bupivacaine to reduce operative deliveries and confer other advantages that may increase maternal satisfaction. Further investigations should be performed to determine the exact mechanisms of these findings and, in particular, to develop a safe method of delivering such analgesia to women.

Fetal and neonatal adverse effects profile of amiodarone treatment during pregnancy

During pregnancy amiodarone has been used for treatment of arrhythmias in both the motherleg and the fetus.i0-14 Although the initial data on the use of amiodarone in pregnancy revealed no teratogenicity and only few minor adverse effects,‘-* other recent reports93 l3 described two cases of neonatal hypothyroid goiter, casting doubts on the safety of amiodarone during pregnancy. We report a clinical case of maternal amiodarone treatment for ventricular tachycardia (VT) during conception and throughout two successive pregnancies. A 29-year-old woman with a history of symptomatic ventricular arrhythmia refractory to treatment with beta blockers, quinidine, procainamide, and tocainide underwent extensive evaluation of arrhythmia because of worsening symptoms before she became pregnant with her third child. Previously she had had two normal pregnancies (both births at 40 week’s gestation; birth weight 2945 gm and 3000 gm, respectively) and two abortions. She also had mitral and tricuspid valve prolapse and a history of right upper lobectomy for drug-resistant pulmonary tuberculosis. Left and right ventricular size and function were normal, and there was no evidence of cardiomyopathy or right ventricular dysplasia. The diagnosis of arrhythmia was confirmed by ambulatory ECG (Holter) monitoring, which revealed up to 759 runs of nonsustained VT. During electrophysiologic testing she had inducible sustained monomorphic VT that degenerated into ventricular fibrillation. The patient was started on a regimen of amiodarone, which effectively suppressed the VT and completely relieved the symptoms. After 2 years of treatment the patient became pregnant while taking amiodarone, 400 mglday. The patient and her husband were informed in detail about the uncertainty and potential danger of amiodarone treatment during pregnancy; abortion was considered and discussed on several occasions, and the patient refused. Because of symptomatic relief the patient elected to continue amiodarone therapy during pregnancy. The patient was first seen in our clinic at 12 weeks’ gestation; at that time, to decrease the risk of adverse effects, the dosage of amiodarone was decreased to 200 mglday, and the patient was maintained on this dosage. Throughout the pregnancy se-

A meta-analysis of low-dose aspirin for the prevention of pregnancy-induced hypertensive disease

Background. —Pregnancy-induced hypertension (PIH), defined as either isolated hypertension after the 20th week of gestation or hypertension with proteinuria (preeclampsia), occurs in 5% to 15% of pregnancies and is associated with maternal and neonatal morbidity. Previous clinical trials with small numbers of patients have suggested that aspirin in doses of 60 to 150 mg/d during the second and third trimesters reduces the risk of PIH and improves maternal and neonatal outcomes. Objective. —We performed a meta-analysis of the six published controlled trials to estimate more precisely (1) the magnitude of protection of aspirin from PIH; (2) the effect of aspirin on severe low-birth-weight infants, cesarean section, and perinatal mortality; and (3) the risk of adverse effects. Methods. —We critically and independently evaluated study methods, assigned a quality score to each trial, and abstracted quantitative outcomes data. For each outcome, both relative risk (RR) and the number needed to be treated were calculated. Results. —Among 394 subjects from six trials, the RR of PIH among women who took aspirin was 0.35 (95% confidence interval [Cl], 0.22 to 0.55) and the number needed to be treated was 4.4, meaning that between four and five highrisk women would need to be treated with aspirin to prevent one case of PIH. Aspirin reduced the risk of severe low birth weight among newborns by 44% (RR = 0.56; 95% Cl, 0.36 to 0.88) and reduced the risk of cesarean section by 66% overall (RR = 0.34; 95% Cl, 0.25 to 0.48), although the specific indications for cesarean section were generally not described. There was no effect on fetal and neonatal death (RR=0.88; 95% Cl, 0.32 to 2.46), and there were no maternal or neonatal adverse effects associated with taking aspirin. Conclusion. —This meta-analysis suggests that low-dose aspirin reduces the risks of PIH and severe low birth weight, with no observed risk of maternal or neonatal adverse effects. (JAMA. 1991;266:261-265)

A Meta-analysis of Low-Dose Aspirin for the Prevention of Pregnancy-Induced Hypertensive Disease

--Pregnancy-induced hypertension (PIH), defined as either isolated hypertension after the 20th week of gestation or hypertension with proteinuria (preeclampsia), occurs in 5% to 15% of pregnancies and is associated with maternal and neonatal morbidity. Previous clinical trials with small numbers of patients have suggested that aspirin in doses of 60 to 150 mg/d during the second and third trimesters reduces the risk of PIH and improves maternal and neonatal outcomes. --We performed a meta-analysis of the six published controlled trials to estimate more precisely (1) the magnitude of protection of aspirin from PIH; (2) the effect of aspirin on severe low-birth-weight infants, cesarean section, and perinatal mortality; and (3) the risk of adverse effects. --We critically and independently evaluated study methods, assigned a quality score to each trial, and abstracted quantitative outcomes data. For each outcome, both relative risk (RR) and the number needed to be treated were calculated. --Among 394 subjects from six trials, the RR of PIH among women who took aspirin was 0.35 (95% confidence interval [CI], 0.22 to 0.55) and the number needed to be treated was 4.4, meaning that between four and five high-risk women would need to be treated with aspirin to prevent one case of PIH. Aspirin reduced the risk of severe low birth weight among newborns by 44% (RR = 0.56; 95% CI, 0.36 to 0.88) and reduced the risk of cesarean section by 66% overall (RR = 0.34; 95% CI, 0.25 to 0.48), although the specific indications for cesarean section were generally not described. There was no effect on fetal and neonatal death (RR = 0.88; 95% CI, 0.32 to 2.46), and there were no maternal or neonatal adverse effects associated with taking aspirin. --This meta-analysis suggests that low-dose aspirin reduces the risks of PIH and severe low birth weight, with no observed risk of maternal or neonatal adverse effects.

Phenylephrine in the prevention of hypotension following spinal anesthesia for cesarean delivery

Study Objective: Phenylephrine and ephedrine were compared in the prevention of maternal hypotension following spinal anesthesia for elective cesarean delivery. Design: Randomized, double-blind trial. Setting: Obstetric suite at a university-affiliated hospital. Patients: Sixty healthy patients electively scheduled for cesarean delivery under spinal anesthesia. Interventions: Patients were randomly assigned to receive either ephedrine (n = 29) in 10 mg intravenous (IV) bolus injections or phenylephrine (n = 31) in 80 μg IV bolus injections to maintain systolic blood pressure (SBP) above 100 mmHg. Measurements and Main Results: Maternal venous, umbilical artery, and umbilical vein blood gases were measured, and neonatal Apgar scores and Early Neonatal Neurobehavior Scale scores were assessed. In the ephedrine group, umbilical artery pH was 7.28 ± 0.01 (mean ± SEM), umbilical artery partial pressure of carbon dioxide (PCO 2) was 56.6 ± 1.4 mmHg, and umbilical artery base deficit was 2.2 ± 0.04 meq. In the phenylephrine group, umbilical artery pH was 7.32 ± 0.01, umbilical artery PCO 2 was 52.1 ± 1.3 torr, and umbilical artery base deficit was 0.38 ± 0.35 meq. There were significant differences between the groups in mean umbilical artery pH, PCO 2 and base deficit, although all values obtained were within normal limits. There were no significant differences between the groups in the remaining acid-base values, neonatal Apgar scores, Early Neonatal Neurobehavior Scale scores, or frequency of maternal nausea and vomiting. Conclusions: Phenylephrine is as effective as ephedrine in the treatment of maternal hypotension, and when used in small incremental bolus injections, it appears to have no adverse neonatal effects in healthy, nonlaboring parturients.

Bupivacaine versus bupivacaine plus fentanyl for epidural analgesia: effect on maternal satisfaction.

To compare a combination of epidural fentanyl and bupivacaine with bupivacaine alone for epidural analgesia in labour and to evaluate factors in addition to analgesia that may influence maternal satisfaction. A prospective randomised pilot study. Birmingham Maternity Hospital. 85 primiparous women who requested epidural analgesia in labour and their babies. Group 1 mothers were treated with bupivacaine conventionally, group 2 mothers with bupivacaine and fentanyl in a more complex way designed to provide satisfactory analgesia but with less troublesome side effects. Overall maternal satisfaction, maternal perception of epidural analgesia and its side effects, and aspects of mothers' psychological states during labour, quantified using 100 mm visual linear analogue scales; the frequency of normal and operative deliveries; and measurements of neonatal wellbeing. Satisfaction was higher in group 2 mothers (median group difference +3 mm, 95% confidence interval +1 to +5, p = 0.012): this was associated with more normal deliveries (difference between proportions 0.23, 95% confidence interval +0.03 to +0.42); greater self control (median group difference -7 mm, -17 to -2, p = 0.003); and reduced unpleasantness of motor blockade (-10 mm, -19 to -5, p less than 0.001), sensory blockade (-5 mm, -11 to -2, p = 0.002) and shivering (-5 mm, -18 to 0, p = 0.046) at the expense of mild itching (0 mm, 0 to 0, p less than 0.001). Group 1 mothers found restricted movements more unpleasant (-1 mm, -11 to 0, p = 0.006) and were more sleepy (-4 mm, -20 to 0, p = 0.032). The addition of fentanyl to bupivacaine reduced the requirement for local anaesthetic (-33 mg, -55 to -15, p less than 0.001) without compromising analgesia. No adverse effects in neonates were attributed to the use of fentanyl. The already high maternal satisfaction from conventional epidural analgesia can be improved; epidural fentanyl may be combined with bupivacaine to reduce operative deliveries and confer other advantages that may increase maternal satisfaction. Further investigations should be performed to determine the exact mechanisms of these findings and, in particular, to develop a safe method of delivering such analgesia to women.

Perinatal zidovudine does not appear to have adverse neonatal effects

Perinatal zidovudine does not appear to have adverse neonatal effects

Disposition of Meperidine and Normeperidine Following Multiple Doses During Labor. I. Mother

Abstract Normeperidine, the active meperidine metabolite, has been implicated in adverse neonatal effects that may occur following administration of meperidine to parturients. However, recent studies have suggested that normeperidine levels are not high enough to have adverse effects following single low doses of meperidine. It is not clear what occurs following multiple injections. Therefore the purpose of this study was to quantitate plasma levels of meperidine and normeperidine in the mother following multiple doses of meperidine over long time periods and to determine the half-life of normeperidine. Twelve mothers who received multiple intravenous doses of meperidine were studied. The results show that both meperidine and normeperidine accumulate in matermal plasma following multiple injections and that the half-life of normeperidine averages 20.6 hours. The data suggest that maximum exposure of the fetus to both meperidine and normeperidine would result from multiple doses to the mother because of a continued diffusion gradient from mother to fetus.

Disposition of meperidine and normeperidine following multiple doses during labor: I. Mother

Normeperidine, the active meperidine metabolite, has been implicated in adverse neonatal effects that may occur following administration of meperidine to parturients. However, recent studies have suggested that normeperidine levels are not high enough to have adverse effects following single low doses of meperidine. It is not clear what occurs following multiple injections. Therefore the purpose of this study was to quantitate plasma levels of meperidine and normeperidine in the mother following multiple doses of meperidine over long time periods and to determine the half-life of normeperidine. Twelve mothers who received multiple intravenous doses of meperidine were studied. The results show that both meperidine and normeperidine accumulate in matermal plasma following multiple injections and that the half-life of normeperidine averages 20.6 hours. The data suggest that maximum exposure of the fetus to both meperidine and normeperidine would result from multiple doses to the mother because of a continued diffusion gradient from mother to fetus.

Effect of Magnesium Sulfate on Maternal and Fetal Hemodynamics and Fetal Brain Function and Metabolism

This noteworthy study of magnesium sulfate (MgSO4) administered to pregnant sheep further clarifies its effects on maternal/ fetal hemodynamics, fetal cerebral metabolism, and brain function. Intravenous MgSO4 was infused to produce serum levels of 8.3 ± 1.03 mg./dl. without significant changes in maternal acid-base values or uterine blood flow. Mild transient falls in maternal blood pressure and heart rate corrected rapidly. We take exception with the assertion that the observed falls in fetal carotid arterial oxygen saturation and pH from 68.3 to 39.1 and 7.37 to 7.18, respectively, are benign. These values would be indicative of moderately severe asphyxia and acidosis. Clinical studies in humans have found that MgSO4 administered to preeclamptics in appropriate doses does not produce adverse neonatal effects. However, clinicians will note that MgSO4 crosses the human placental barrier far more readily than in sheep and must anticipate adverse effects on the neonate following maternal magnesium overdose. These effects can include hypotension, tachycardia, hypotonus, and occasionally cardiorespiratory depression.

Lack of Adverse Neonatal Neurobehavioral Effects of Lidocaine

Lack of Adverse Neonatal Neurobehavioral Effects of Lidocaine

Lack of Adverse Neonatal Neurobehavioral Effects of Lidocaine

The effects of epidural anesthesia on the early neonatal neurobehavioral scale (ENNS) following delivery were studied in 22 parturients given 1.5% lidocaine epidural anesthesia during labor and delivery. These results were compared to those obtained in a control group of 17 neonates whose mothers received no analgesics, medications, or local anesthetics for labor or delivery. There was no significant difference in ENNS in the two groups of neonates. Lidocaine as administered in this study has no adverse effects on the early neurobehavioral status of the neonate.