L’articolo è tratto da: J Midwifery Womens Health. 2007;52(3):262-272. © 2007 Elsevier Science, Inc.
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Effect of Maternal Analgesia on Newborn Transition
Most analgesic agents commonly used to alleviate labor pain readily transfer to the fetus via the placenta.
Usually, the effects of the analgesic agents are subtle, as most full term infants transition easily from fetus to newborn. However, some specific medications have the potential to disturb normal neonatal transition. 
Although there is a large body of literature on the various effects of analgesic agents, the reports of neonatal outcomes are often incomplete or inconclusive. The ethical and practical implications of assigning women to various pain management modalities make randomized control trials (RCTs) on pharmacologic management of labor pain and its effect on the neonatal transition difficult to conduct.
A comprehensive literature review (English only) using a combination of search terms (maternal analgesia, effects on newborn, newborn transition, labor drugs, newborn, epidural, first 4 hours, and neonatal outcomes) resulted in three Cochrane Reviews, [3-5] nine systematic reviews (includes RCTs and other types of studies), [6-14] six RCTs,[15-20] a case control study, a retrospective cohort study, and three observational studies. [23-25]
These studies compared types of parenteral opioids (dosages, route of administration, and codrugs), epidural versus parenteral opioids, epidural versus combined spinal-epidural analgesia, epidural dosing (traditional vs. light), and parenteral opioids versus epidural analgesia versus no analgesia. Neonatal outcomes in these studies include Apgar scores, umbilical cord pH, respiratory depression, neonatal sepsis evaluation, breastfeeding success, neurobehavioral effects, and admission to a neonatal special care unit.
Apgar Scores and Umbilical Cord pH Most studies report no effect of analgesic agents (parenteral opioids or epidurals with local anesthetics, with or without opioids) on Apgar scores or umbilical cord pH values. [6,11,13,14,17,20]
One systematic review of RCTs and well designed prospective cohort studies found that newborns exposed to parenteral opioids (5 trials, N = 2015 infants) had a higher incidence of 1-minute Apgar score < 7 compared to newborns exposed to epidural analgesia. However, at 5 minutes, the Apgar scores did not differ significantly (6 trials, N = 2545).
In a Cochrane review by Anim-Somuah et al.,  newborns exposed to epidural analgesia had a decreased risk of having an umbilical cord pH < 7.2 compared to newborns whose mothers had nonepidural analgesia.
However, there was no significant difference between groups in 5-minute Apgar scores. Findings from the PEOPLE study, a multicenter RCT (N = 1862), which examined delayed pushing and prolonged second stage of labor in primigravidas with continuous epidural analgesia, found lower umbilical cord pH (<7.15 venous or <7.10 arterial; RR, 2.45; 95% CI, 1.35-4.43) in the newborns whose mothers delayed the start of pushing as compared to the control group who began pushing at the start of second stage. 
Yet, no newborns in the delayed pushing group had any sign of perinatal asphyxia as measured by the Neonatal Morbidity Index. These data suggest that Apgar scores and umbilical cord pH are common gross measures of newborn well-being that may not adequately assess the subtle effects of maternal analgesic agents on the newborn.
Morphine, meperidine (Demerol; Sanofi-Aventis, Bridgewater, NJ), and fentanyl are the opioids that have been studied the most in labor analgesia research. These opioids, as well as newer alternatives, such as nalbuphine (Nubain; Endo Pharmaceuticals, Chadds Ford, PA) and butorphanol (Stadol; Bristol-Meyers Squibb, New York, NY), have been associated with newborn respiratory depression. However, there is insufficient evidence to clarify the relationship between medication dosage and respiratory depression at birth. Opioids are known for their high lipid solubility, which allows rapid transfer of the drug through the placenta and into the fetus. The risk of respiratory depression is highest if birth occurs at the time of peak fetal uptake — between 1 and 4 hours after administration of drug to the mother. 
Naloxone (Narcan; Endo Pharmaceuticals) is currently used in clinical practice to reverse respiratory depression following administration of opioids. One systematic review reported that naloxone administration to the newborn is more common when parenteral opioids and patient-contro led opioid analgesia is used, compared to epidural analgesia. [9,18,19]
Another review found no differences in naloxone use between types of analgesia. 
Many of the studies included were too small to draw conclusions for clinical practice recommendations. Naloxone should not be given routinely at the time of birth. 
Neonatal Sepsis Evaluation
Lieberman and O’Donoghue  found that epidural use was associated with a higher incidence of maternal fever and subsequent neonatal sepsis evaluation. However, Capogna  suggested that, while the number of neonates receiving sepsis evaluations varies between institutions, there is no evidence that epidural exposure increases the incidence of neonatal sepsis.
There has been a longstanding concern about the negative impact of labor analgesic agents on breastfeeding success. Analgesic effects are known to include suckling inhibition, delay in the establishment of breastfeeding, decreased neonatal alertness, and diminished neurobehavioral function. [6,12]
However, most of these effects were noted in observational studies that were published more than 30 years ago.
In a review  of two prospective cohort studies done more recently (N = 2364), there was no correlation between breastfeeding success and use of either parenteral opioids or epidural/spinal analgesia during labor.
Capogna reports that “theoretically,” the types and amount of epidural analgesia may affect breastfeeding success, but suggests early maternal infant bonding may have a greater effect on breastfeeding than does the type of maternal analgesic agent used during labor. The results of a small observational study (N = 28) revealed that neonates not exposed to pain medication exhibited an important prebreastfeeding behavior (spontaneously moving towards the breast and massaging the mother’s nipple), which is believed to contribute to suckling. 
Newborns (n = 12) in the first 120 minutes after birth, exposed to either intravenous (IV) meperidine, epidural with local anesthetic, or a combination of both had increased amounts of crying and a delay in developing breastfeeding behaviors. 
In a study of 129 infants, Riordan found that fetal exposure to labor analgesia agents (IV opioids or epidural or IV opioids plus epidural) diminished early suckling but did not effect duration of breastfeeding through 6 weeks. Radzyminski  observed no difference in breastfeeding behaviors when comparing neonates exposed to ultra-low dose anesthetics via labor epidurals (n = 28) to neonates with no exposure to pain medication (n = 28). Beilin reported that women (n = 58) who received an epidural with high dose fentanyl (>150 mcg) had more difficulty breastfeeding in the first 24 hours compared to women (n = 59) with either an intermediate dose (1-150 mcg) or no fentanyl (n = 60), although the difference did not reach statistical significance. Yet, at 6 weeks postpartum, a greater number of the women in Beilin’s high-dose fentanyl group were no longer breastfeeding. In a retrospective cohort study (N = 99), Volmanen  found that more women who had an epidural in labor described not having enough milk when compared to women without an epidural (15 vs. 6, P = .006) in the first 12 weeks postpartum. Lieberman and O’Donoghue  caution in their systematic review that further study is needed to evaluate breastfeeding success rates with the use of epidural analgesia.
Early Neurobehavioral Effects
Studies of the effect of maternal analgesic agents on early neonatal neurobehavior showed minimal differences in the neurobehavioral scores of newborns exposed to epidural opioids versus newborns exposed to parenteral opioids. 
Even results comparing epidural-exposed newborns to newborns with little or no medication exposure did not show a clear difference between groups. Beilin found lower neurobehavioral scores in newborns exposed to high versus low (or none) dose fentanyl (>150 mcg) epidurals.  Intravenous fentanyl just before spinal anesthesia for elective cesarean birth had no impact on neurobehavioral scores. 
Admission to a Neonatal Intensive Care Unit
No differences were found in neonatal intensive care unit (NICU) admissions of infants exposed to epidural versus nonepidural or no analgesia in labor  or in comparing epidural and combined spinal-epidural analgesia. 
Exposure to maternal analgesia does not appear to increase an infant’s risk for admission to the NICU. In summary, the current evidence on the safety of maternal analgesia (parenteral opioids or epidural or combined epidural/spinal) and the effects on the neonate are limited, and at times confusing, making it difficult to draw conclusions for clinical practice. Newborns not exposed to any labor analgesic agents appear to exhibit important prebreastfeeding behaviors necessary for successful suckling sooner than analgesiaexposed newborns, but the effects of labor analgesic agents on early suckling and breastfeeding duration is unclear. The long-term impact of neurobehavioral effects from maternal analgesia is uncertain. Future studies must look beyond gross measures, such as Apgar scores and umbilical cord pH, and focus on longterm neonatal outcomes, such as attachment, breastfeeding duration, and neurobehavioral effects.
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