A Review of the Impact of Obstetric Anesthesia on Maternal and Neonatal Outcomes

Grace Lim, M.D., M.S.; Francesca L. Facco, M.D., M.S.; Naveen Nathan, M.D.; Jonathan H. Waters, M.D.; Cynthia A. Wong, M.D.; Holger K. Eltzschig, M.D., Ph.D.

Disclosures

Anesthesiology. 2018;129(1):192-215. 

In This Article

Obstetric Anesthesia Outcomes

Effects of Labor Analgesia on the Fetus

Fetal bradycardia is occasionally observed after initiation of neuraxial labor analgesia. One trial found the incidence of fetal bradycardia was higher after combined spinal-epidural than epidural analgesia (32% vs. 6%), although the study was limited by nonstandardized spinal dosing and monitoring for only 15 min after injection.[8] One trial found fetal bradycardia was higher after intrathecal sufentanil 7.5 μg only compared with sufentanil 1.5 μg combined with epinephrine 2.5 μg and bupivacaine 2.5 mg. Although the authors concluded that the rate of fetal bradycardia was directly related to the intrathecal sufentanil dose, this conclusion requires further study; the low-dose sufentanil was administered in combination with other drugs (i.e., more than one variable was manipulated among groups). Importantly, there were no differences in neonatal outcomes (Apgar score, umbilical artery pH).[78] A 2016 meta-analysis of 17 randomized trials found that fetal heart rate abnormalities are more likely to occur with combined spinal-epidural techniques; however, a sensitivity analysis including only studies that used low-concentration epidural bupivacaine was underpowered to determine whether a difference in fetal bradycardia exists.[164] Whether the observed fetal heart rate abnormalities are tied to worse neonatal outcomes is unclear. The mechanism of analgesia-mediated bradycardia is thought to be rapid decrease in circulating epinephrine concentration with the onset of neuraxial analgesia. Epinephrine is a tocolytic, and its acute withdrawal may contribute to uterine tachysystole, reducing placental perfusion time (only occurs in uterine diastole). Reassuringly, studies have not found a difference between combined spinal-epidural and epidural techniques and emergency cesarean delivery.[78,165] The usual measures of in utero fetal resuscitation (change in maternal position, intravenous fluid bolus, discontinuation of exogenous oxytocin) are usually successful in restoring fetal heart rate. Occasionally, administration of a tocolytic (nitroglycerin, terbutaline) is necessary.

Breastfeeding

Neuraxial analgesia's effect on breastfeeding is controversial. Most studies are observational and results are conflicting; some have identified a negative association, some found no relationship, and some found a positive relationship.[166] Studies lack control for multiple confounding variables (e.g., dosing and type of analgesia, intrapartum interventions, timing and method of breastfeeding measurements, social support, maternal return-to-work status) known to influence breastfeeding success. Factors likely more important than labor epidural analgesia include early maternal-infant bonding, skin-to-skin contact, and breastfeeding support.[167] A randomized trial found that epidural infusion solutions containing fentanyl concentrations as high as 2 μg/ml for maintenance of labor analgesia did not impact rates of successful breastfeeding at six weeks postpartum.[168]

Breastfeeding outcomes after general versus neuraxial anesthesia for cesarean delivery are also unclear. In one study, women receiving general and neuraxial anesthesia for cesarean delivery were similarly successful at breastfeeding in the immediate postpartum period (96% regional vs. 89% general); however, at 6 months, fewer women who received general anesthesia were breastfeeding (39% vs. 71%).[169] Results were similar from an observational trial in Turkey, where women self-select either general or neuraxial anesthesia for cesarean delivery.[170] However, women who self-select general anesthesia likely differ in other factors known to affect breastfeeding success. Postoperative pain control is likely important; postoperative epidural analgesia is linked to successful breastfeeding and infant weight gain.[171]

Fever and Neonatal Sepsis Workup

Labor neuraxial analgesia is associated with intrapartum fever of noninfectious inflammatory origin. Multiple studies support that labor epidural analgesia is linked to clinical fever (temperatures greater than 38.0° C).[172] Study limitations include uncontrolled factors such as obstetric management, selection bias, crossover and dropout, and measurement error.[172] Concerningly, maternal fever in general (not restricted to epidural-associated fever) is associated with poor neonatal outcomes, including assisted ventilation, low 1- and 5-min Apgar scores, seizures, and hypotonia.[172] These outcomes occur more commonly in women who receive epidural analgesia and had a fever, but not among women who received epidural analgesia and remained afebrile.[173]

Neonatal sepsis evaluation and maternal and neonatal antibiotic exposure is significantly increased among mother-infant dyads with labor epidural-associated fever.[174–176] Current evidence supports that maternal fever related to labor epidural analgesia is noninfectious and inflammatory in origin, mediated by cytokines. Among women receiving labor epidural analgesia, those with elevated IL-6 levels on admission are more likely to develop fever.[172] Other proposed theories include local anesthetic agonism of the TRPV-1 ("capsaicin") receptor, triggering the release of IL-6 and other inflammatory cytokines.[172] Besides increased risk for neonatal sepsis evaluation and prophylactic treatment, it is not clear whether labor epidural-associated fever impacts short- or long-term adverse infant outcomes. Research is now focusing on the implications of noninfectious inflammation on neonatal outcomes. Future work should also emphasize diagnostic means to differentiate labor epidural-associated fever from fever caused by chorioamnionitis and funisitis (inflammation within the umbilical cord), as the latter are known to be linked to poor neonatal outcomes.

Infant and Childhood Neurocognitive Outcomes

Some observational studies have linked intrapartum anesthetic exposure to autism spectrum disorders; others have failed to demonstrate this relationship.[177–179] The challenges in conducting and interpreting these studies lie in the multiple confounders which independently impact risk for autism spectrum disorders (e.g., maternal conditions requiring anesthetic exposure, social environments dictating the same). An imperative exists to determine the effects of maternal anesthetic exposure on fetal, neonatal, and childhood neurocognitive outcomes,[180] but currently there is little evidence that these considerations should change anesthetic clinical decision-making during labor and delivery.

Depression

Several studies suggest labor analgesia interventions may be associated with reduced postpartum depression risk.[181,182] In 2014, Ding et al. found that epidural labor analgesia in Chinese women was associated with a reduced risk for postpartum depression (odds ratio 0.31; 95% CI, 0.12 to 0.82).[181] There were several methodologic limitations to the study. The cohort may not have been depression-free upon enrollment and there was a high loss-to-follow-up rate in the epidural analgesia group, possibly inflating the protective effect of epidural analgesia.

Nevertheless, an established relationship between pain and depression exists in the nonobstetric population,[182] and given the dearth of data on this relationship in obstetrics, additional research is needed. The link between labor pain and postpartum depression may be biologic; activation of neural networks in psychologic pain overlap with physical pain neural networks.[182] Pain catastrophizing is known to be linked to severity of the experienced physical pain.[182] Other data suggest that analgesia may explain the protective relationship between the use of labor neuraxial analgesia and postpartum depression symptoms, although the relative influence of labor analgesia on postpartum depression may be less than other established risk factors such as baseline anxiety or depression, obesity, and genital tract trauma during delivery.[183] An observational study noted a protective interaction effect for depression among women who planned and actually used labor epidural analgesia; women who planned to avoid labor epidural analgesia, but ultimately requested and used it, had higher risk for positive postpartum depression screening, but this relationship was thought mediated by difficult labor rather than unmet expectations.[184] In view of the uncertainty in existing literature, coupled with plausible psychologic and biologic mechanisms explaining the relationship between labor pain and postpartum depression, additional research is clearly indicated to determine the true relationship between labor pain, labor analgesia, and postpartum depression; if a link is established, targeted approaches using preventative labor analgesic therapies for vulnerable women may prove to be protective for postpartum depression.

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