Recently there has been considerable media attention regarding neonatal sepsis work-up (SWU) in infants born to mothers who receive epidural analgesia for pain relief in labor. Maternal and neonatal temperatures may increase in women who have received lumbar epidural analgesia (LEA) during labor and delivery (1). Lieberman et al. (1) reported an SWU rate of 34% in neonates born to mothers who had received labor epidural analgesia compared with 9.8% in neonates born to mothers who did not receive epidural analgesia. In this article, we report risk factors for newborn SWU in our institution. We also compare newborn SWU rates in parturients given LEA or parenteral narcotics (controls) for labor analgesia.
Magee-Women’s Hospital is a tertiary care maternity facility with more than 7500 annual deliveries and a >80% labor epidural analgesia rate. At our institution, epidural blocks are usually initiated at 3- to 4-cm cervical dilation. All patients routinely received lactated Ringer’s solution at 125 mL/h during labor. The epidural blocks are performed in the sitting position at the L3-4 or L2-3 intervertebral space by using the loss of resistance to air technique. A 17-gauge Hustead needle is used for inserting the catheter 3–4 cm into the epidural space. The catheter is aspirated with a 3-mL syringe. If no blood or cerebrospinal fluid is aspirated, the catheter is secured. A test dose of lidocaine 3 mL of 1.5% with 1:200,000 epinephrine is administered to eliminate the possibility of intrathecal or IV injection. Bupivacaine 0.25% or ropivacaine 0.2% is administered in 5-mL increments to a total of 10 mL. The block is deemed successful if the sensory level reaches at least a T10 level bilaterally and there is at least a 70% reduction in the visual analog score for pain (0–100). The patient is then placed on a continuous epidural infusion of either bupivacaine 0.125% with fentanyl 2 μg/mL at 10–12 mL/h or ropivacaine 0.1% with fentanyl 2 μg/mL at the same rate. This is the standard epidural analgesia protocol at our hospital. Patients who refuse epidural analgesia receive parenteral analgesics: either 2 mg butorphanol or 5–10 mg nalbuphine IV as needed.
We maintain a computerized database (Corel Paradox 8; Corel Corp., Ottawa, Ontario, Canada) for internal continuous quality improvement (CQI). A dedicated database manager enters data pertaining to analgesia and maternal and neonatal outcomes into the database. The medical record number (MR#) is set as the key field for the database, and further data entry is not possible without the MR#. The MR# facilitates the retrieval of relevant outcome data from the hospital records of the mother and neonate. We attempt to generate a CQI form for every obstetric patient. The CQI forms are screened the next morning, and forms with a missing MR# or other relevant clinical information are discarded.
From this database, 1177 primiparous patients who delivered between January 1998 and December 1999 with one of the two standard epidural infusion protocols (bupivacaine and ropivacaine) were identified. The database search excluded women who received a combined spinal-epidural technique because we use it in primiparous women in advanced labor (cervical dilation >8 cm) and in multiparous women in early and advanced labor. All patients received perinatal care, which included a low vaginal and anal swab for group B β-hemolytic streptococcus (GBBS) culture. The following data were retrieved: maternal height, weight, age, maternal temperature before conduction block (baseline) and at 10-cm dilation and at delivery, rupture of membranes to delivery (R-D) time, epidural insertion to delivery time, and neonatal temperatures at birth and 6 h after delivery. Maternal and neonatal tympanic membrane temperatures were recorded with the First Temp Genius® thermometer (Sherwood Medical, St. Louis, MO).
A secondary database to record neonatal data was constructed from the original database by using MR# as the cross-reference index. The Department of Neonatology in our hospital uses the following guidelines to initiate an SWU in the neonate: maternal conditions including prolonged rupture of membranes (>18 h), gestational age <37 wk, and chorioamnionitis; and neonatal conditions including hypo- or hyperthermia at 6 h after birth, apneic spells, respiratory distress or pneumonia, central cyanosis, lethargy, listlessness, convulsions, poor feeding or vomiting, and cardiovascular instability. For SWU to be initiated at our institution, one or more of the neonatal factors should be present regardless of the maternal condition. A neonatal SWU includes a complete blood count and blood, urine, and spinal fluid cultures for pathogens. Depending on the results of the evaluation, the neonate could be assigned to one of the three following diagnostic subsets: 1) definite sepsis proven by a positive blood, urine, or cerebrospinal fluid culture; 2) presumed sepsis, as shown by only indirect evidence of sepsis, including immature polymorphonuclear white cells (band cells; >10% of the total white count), cardiovascular instability requiring inotropic support, or pneumonia (verified by chest radiograph) with no direct positive culture; or 3) absence of sepsis, as evidenced by negative cultures and rapidly improving neonatal condition.
Neonates were started on IV antibiotics (ampicillin 50–150 mg/kg and gentamicin 2.5 mg/kg) when the SWU was initiated and discontinued at 48 h if sepsis was ruled out. For the purposes of the study, prematurity is defined as a birth weight of ≤2.5 kg; neonatal hypothermia is defined as being <36°C and hyperthermia as being >38°C (2).
Results were expressed as mean ± sd. Data were analyzed by using χ2 with Yates’s correction or unpaired Student’s t-tests. A multiple logistic regression model was used to calculate odds ratios (Statistica for Windows version 5.1; Statsoft, Tulsa, OK) to detect significant associations between SWU and various maternal and neonatal factors that might have triggered an SWU. A P < 0.05 was considered significant.
Of the 1177 women, 78% (n = 922) received LEA during labor, and the remaining 22% (n = 255 controls) received IV analgesia. The two groups were comparable in age, height, and racial distribution (Table 1). Mothers who received LEA tended to weigh more; however, this difference was considered clinically insignificant. There were no neonatal deaths in either the LEA group or the Control group, and no neonate from either group had proven sepsis. The R-D time interval, as well as the numbers of instrumental deliveries and cesarean deliveries, was statistically significantly increased in the LEA group compared with Controls (Table 1).
The mean maternal and neonatal delivery temperatures in the LEA group were slightly higher than in the Control group; however, this increase of temperature was not considered to be of clinical consequence (Fig. 1). In addition, at 6 h after birth the neonatal temperatures were not significantly different between groups. More mothers with LEA had a fever (temperature >38°C) at delivery than Controls. However, there was no statistical difference between LEA and Control groups in the number of neonates with a temperature >38°C at birth (Table 1).
Although the neonates in the LEA group tended to be statistically heavier than those in the Control group (Table 1), this difference was not considered clinically significant. A total of 93 neonates received an SWU, and there was no significant difference in the number of neonates requiring SWU between the LEA (7.5%) and the Control groups (9.4%) (Table 1). Mothers of 69 of these 93 neonates received epidural analgesia for labor, and the rest received IV analgesia. Nineteen neonates in the LEA group were diagnosed as having “presumed sepsis,” and five neonates in the control group were similarly diagnosed (not significant).
Logistic regression analysis failed to show any significant association between epidural analgesia and SWU. The conditions most frequently associated with neonates in the entire study group (n = 1177) who had an SWU were birth weight, gestational age, meconium or respiratory distress at birth, hypothermia at birth, GBBS colonization, and maternal preeclampsia or hypertension. The time of initiation of SWU with respect to delivery time is presented in Table 2. In the majority of cases with each condition, the SWU was started at <6 h after birth, with the exception of GBBS colonization and preeclampsia or hypertension, in which the SWU occurred at 6–24 h.
Maternal temperature at either 10 cm dilation or at delivery also had no predictive value for SWU. Although chorioamnionitis was clinically suspected in 45 cases, it triggered an SWU in only nine instances without any significant relationship with SWU. Other conditions less frequently associated with neonatal SWU were intrauterine growth retardation, hypoglycemia, maternal diabetes, and cardiovascular instability of the neonate (n = 4 in each instance, not significant).
The retrospective nature of our study does not permit a randomized design, and consequently there may be a strong selection bias with respect to the type of labor analgesia. For instance, certain obstetricians might use epidural analgesia more frequently than others. It is also possible that only patients with certain obstetric conditions may be considered suitable candidates for LEA. We strongly believe that these factors did not influence our results because the rate of LEA is frequent in our institution and the choice of analgesia is usually made by the patient and not by the obstetrician. Parity is another confounding variable that determines the duration of labor, and the duration of labor may influence the SWU rate by increasing the number of medical interventions. Multiparous women usually have shorter labors than primiparous women. To keep our study population homogeneous, we studied only primiparous women who were given the standard institutional epidural infusion protocol. Although we noticed an association between LEA and operative deliveries, this does not imply a cause-effect relationship, because only women with prolonged, painful labors are likely to receive LEA (2), thus making it virtually impossible to eliminate a selection bias.
The R-D time interval is longer in patients with LEA compared with Controls in our study. At first glance, one might suspect that only patients with prolonged labors and ruptured membranes were given epidural analgesia to avoid maternal exhaustion. However, in this study, 76% of patients who received LEA had their membranes ruptured after the epidural was administered as a part of active management of labor, and none received LEA to treat maternal exhaustion.
Our data show that several maternal and neonatal conditions predispose to SWU. These include birth weight, gestational age, meconium aspiration or respiratory distress at birth, hypothermia at birth, GBBS colonization, and maternal preeclampsia or hypertension. These factors or triggers must be taken into consideration along with maternal and neonatal temperatures. The time of SWU initiation perhaps reflects the time at which clinical deterioration was noted. Low birth weight, low gestational age, meconium aspiration, and neonatal hypothermia tend to trigger SWU earlier rather than later, because these conditions may cause rapid deterioration of the neonatal condition.
Our data show that epidural analgesia per se does not predispose to increased SWU in neonates, although patients who received epidural analgesia and their neonates had an increased body temperature at delivery. We could not demonstrate a clear-cut relationship between maternal temperature and SWU rate. We found a significant relationship between hypothermia at birth and SWU. It is interesting to note that hypothermia is a common clinical finding in prematurity and low-birth-weight neonates (3). Fetal temperature increases pari passu with maternal temperature (4). However, after birth the neonate equilibrates with the ambient temperature, as evidenced by the fact that the number of neonates with temperature >38°C decreases from seven at birth to zero at six hours.
Lieberman et al. (1) found an association between LEA and SWU. However, in their study, 67.3% of SWUs were ordered in infants born to mothers without fever. In addition, they do not explain the indications for SWU in these infants. Neither do they mention other important causes of SWU. In the study by Philip et al. (5), the SWU rate was 20% compared with an overall SWU rate of 8% in ours. The main focus of the study of Philip et al. is the differing rates of maternal fever in the epidural versus IV analgesia groups. They found an association between LEA and maternal fever. In their study, infants born to women with fever had an increased SWU rate and antibiotic therapy. However, unlike our study, they did not identify other maternal and neonatal risk factors for SWU in neonates. The main difference between our study and the studies by Lieberman et al. (1) and Philip et al. (5) is that we describe several other important maternal and neonatal risk factors, apart from epidural analgesia, that lead to SWU. It is surprising that neither of the other two studies comments on any association between neonatal temperature at birth and SWU.
With all the SWU triggers taken into consideration, at our institution a full-term baby weighing more than 2.5 kg at birth, without any meconium or respiratory distress at birth, and born to a mother without GBBS colonization of the genital tract would have a negligible chance of receiving a SWU regardless of what analgesia the mother receives for labor. The lack of a predictive association between chorioamnionitis and SWU was surprising. Clinical diagnosis of chorioamnionitis is often inaccurate and can be confirmed histopathologically in only 38% of cases (6,7). It is interesting to note in this connection that Dashe et al. (8) found that LEA was associated with fever only in those patients with histologically proven placental inflammation.
In summary, neither maternal temperature nor epidural labor analgesia was found to be a predictor of the need for neonatal SWU. Birth weight, gestational age, meconium aspiration or respiratory distress at birth, hypothermia at birth, GBBS colonization of maternal birth canal, and preeclampsia or hypertension are strong predictors of neonatal SWU in our institution.
1. Lieberman E, Lang JM, Frigoletto F Jr, et al. Epidural analgesia, intrapartum fever, and neonatal sepsis evaluation. Pediatrics 1997; 99: 415–9.
2. Polley LS. What’s new in obstetric anesthesia, 1999? Int J Obstet Anesth 2001; 10: 46–54.
3. Klein JO. Bacterial sepsis and meningitis. In: Remington JS, Klein JO, eds. Infectious diseases of the fetus and newborn infant. Philadelphia: WB Saunders, 2001: 943–98.
4. Morishima HO, Glaser B, Niemann WH, James LS. Increased uterine activity and fetal deterioration during maternal hyperthermia. Am J Obstet Gynecol 1975; 121: 531–9.
5. Philip J, Alexander JM, Sharma SK, et al. Epidural analgesia during labor and maternal fever. Anesthesiology 1999; 90: 1271–5.
6. Hammer GS, Hirschman SZ. Infections in pregnancy. In: Cherry SH, Merkatz IR, eds. Complications of pregnancy: medical, surgical, gynecologic, psychosocial and perinatal. Baltimore: Williams & Wilkins, 1991: 302–35.
7. Smulian JC, Shen-Schwarz S, Vintzileos AM, et al. Clinical chorioamnionitis and histologic placental inflammation. Obstet Gynecol 1999; 94: 1000–5.
8. Dashe JD, Rogers BB, Mcintire DD, Leveno KJ. Epidural analgesia and intrapartum fever: placental findings. Obstet Gynecol 1999; 93: 341–4.