Neonatal CRP Question

[Stitch]

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I was curious as to your input, especially OldBearProf.

First, a little context. I moonlight in a level I nursery that gets your average term kids, many of whom end up being discharged withing 24-48 hours without complications. The other day I got sign out from one of the (very good) NPs who covers for us.
Term infant. Mom was GBS positive and ruptured for 20 hours for the last few hours ran a fever of 102. She had received 3 doses of ampicillin during labor and was born vaginally without further complications. The kid had a temperature of 101 initially so the NP got a CBC. WBC of 25k and I:T ration of 0.28. She was reassured but repeated the CBC six hours later. WBC of 45k and I:T of 0.24.

AT this point I got sign out. The kid was doing well without any signs of distress and no temperature instability, but I was concerned enough with maternal fever and the elevated I:T that I tapped the kid to be sure (maybe a bit too conservative?). 6 WBCs and 2 RBCs, overall reassuring. I start amp and gent, but as mom received amp during delivery I wasn't sure what my end point would be.

Talked to our neonatologist on call, who I know from residency. He agreed with all of the above and wanted to add a CRP. CRP was 3.8, and based on that lab, he suggested treating for 10 days, regardless of cultures.

My question is can you put that much stock in a CRP? The tap was reassuring to me that the kid didn't have meningitis. I looked at an article by Karen Puopolo on early onset sepsis, and found a few other CRP references. In the context of maternal fever is it still reliable? How about a difficult delivery? Any other thoughts?

 

[oldbearprofessor]

I was curious as to your input, especially OldBearProf.

First, a little context. I moonlight in a level I nursery that gets your average term kids, many of whom end up being discharged withing 24-48 hours without complications. The other day I got sign out from one of the (very good) NPs who covers for us.
Term infant. Mom was GBS positive and ruptured for 20 hours for the last few hours ran a fever of 102. She had received 3 doses of ampicillin during labor and was born vaginally without further complications. The kid had a temperature of 101 initially so the NP got a CBC. WBC of 25k and I:T ration of 0.28. She was reassured but repeated the CBC six hours later. WBC of 45k and I:T of 0.24.

AT this point I got sign out. The kid was doing well without any signs of distress and no temperature instability, but I was concerned enough with maternal fever and the elevated I:T that I tapped the kid to be sure (maybe a bit too conservative?). 6 WBCs and 2 RBCs, overall reassuring. I start amp and gent, but as mom received amp during delivery I wasn't sure what my end point would be.

Talked to our neonatologist on call, who I know from residency. He agreed with all of the above and wanted to add a CRP. CRP was 3.8, and based on that lab, he suggested treating for 10 days, regardless of cultures.

My question is can you put that much stock in a CRP? The tap was reassuring to me that the kid didn't have meningitis. I looked at an article by Karen Puopolo on early onset sepsis, and found a few other CRP references. In the context of maternal fever is it still reliable? How about a difficult delivery? Any other thoughts?

Over the years (decades), folks have tried all sorts of ways to sort out this scenerio. None are reliable. There is some evidence for the use of a CRP, but it is very unreliable. Probably is more reliable as a "negative" or for late-onset sepsis than for this situation. I'm more likely to get one in the setting of an inpatient baby with vague symptoms of sepsis than this one.

Remembering that early treatment does not prevent late-onset GBS and that 10 days of antibiotics poses its own set of risks, I would not do that in a totally asymptomatic baby. I am not impressed by the white count or the band count you described either.

The LP is really a tough one. The literature goes back and forth on this without good resolution. In general, the rule of thumb is that the less likely a newborn is to NEED an LP (i.e. the less sick they are), the more likely they are to GET an LP (easy to do).

 

[Stitch]

Over the years (decades), folks have tried all sorts of ways to sort out this scenerio. None are reliable. There is some evidence for the use of a CRP, but it is very unreliable. Probably is more reliable as a "negative" or for late-onset sepsis than for this situation. I'm more likely to get one in the setting of an inpatient baby with vague symptoms of sepsis than this one.

Remembering that early treatment does not prevent late-onset GBS and that 10 days of antibiotics poses its own set of risks, I would not do that in a totally asymptomatic baby. I am not impressed by the white count or the band count you described either.

The LP is really a tough one. The literature goes back and forth on this without good resolution. In general, the rule of thumb is that the less likely a newborn is to NEED an LP (i.e. the less sick they are), the more likely they are to GET an LP (easy to do).

Thanks, that's helpful, and makes me feel less cavalier about not wanting to treat for 10 days.

What do you make of maternal fever? Here we tend to do cultures on any kid whose mom had a temp greater than 101 (some say 101.5). That usually includes a 48 hour rule out with antibiotics, and I generally trust my cultures as an end point. Is it reasonable to just check a CBC (and maybe now a CRP) and be reassured?

 

[J-Rad]

I know I'm going to be accused of being overly algorithmically inclined, but shouldn't the baby have been started on abx and screened out of the gate (i.e. didn't Mom have chorio by definition + prolonged ROM) regardless of the 101? I think where I trained is uber-conservative (also quant. CRPs didn't come back for a few days, so we didn't routinely use them) so if the kid had spiked a temp later, many of the residents would send off an HSV PCR (blood/CSF) and start acyclovir (along w/ Amp/Gent) until negative. But if this fever was in the first few minutes of life I don't think I would have tapped (the pendulum was swinging the other way in my program, however, as I got into third year) or sent HSV studies. I think I would have screened, started abx regardless of the screening results and watched closely for signs of sepsis.

 

[oldbearprofessor]

Thanks, that's helpful, and makes me feel less cavalier about not wanting to treat for 10 days.

What do you make of maternal fever? Here we tend to do cultures on any kid whose mom had a temp greater than 101 (some say 101.5). That usually includes a 48 hour rule out with antibiotics, and I generally trust my cultures as an end point. Is it reasonable to just check a CBC (and maybe now a CRP) and be reassured?

I know I'm going to be accused of being overly algorithmically inclined, but shouldn't the baby have been started on abx and screened out of the gate (i.e. didn't Mom have chorio by definition + prolonged ROM) regardless of the 101? I think where I trained is uber-conservative (also quant. CRPs didn't come back for a few days, so we didn't routinely use them) so if the kid had spiked a temp later, many of the residents would send off an HSV PCR (blood/CSF) and start acyclovir (along w/ Amp/Gent) until negative. But if this fever was in the first few minutes of life I don't think I would have tapped (the pendulum was swinging the other way in my program, however, as I got into third year). I think I would have screened, started abx regardless of the screening results and watched closely for signs of sepsis.

Chorio gets a 48 hour r/o based on most algorithms, so I wouldn't rely on the CBC or CRP in the first 24 hours of life at all. CBC is very unreliable in the first hours of life. With symptomatic GBS early onset sepsis the total WBC will go very low rapidly, but by then you know the baby has GBS from the fact they are in septic shock. Fortunately, this is rarely seen anymore.

The problem you are both alluding to is figuring out who has chorio. Low grade fevers can be associated with maternal dehydration and MAYBE with the epidural. High fevers are obvious. But what about the large group of moms with 100-102 temps and "soft" signs of chorio?

Keep in mind that a 48 hour r/o is not entirely benign. It has large costs, affects bonding and disrupts breastfeeding.

Bottom line is that algorithms are great, but in the end some judgment is needed about the chorio part. My general perception is that places with residencies and big hospitals treat more babies and in the community they tend to watch more.

 

[bks524]

I am glad you mentioned the epidural/fever association. In my experience (short time) every maternal fever late in labor is associated with epidural. Now many women opt for epidurals these days, but the maternal fever without epidural would get my attention.

I read an article at one time that looked at outcome of sepsis evaluation for maternal fever with epidural. I remember the incidence of positive culture being extremely low (like 1 in 500 as I recall). I tried to find the article to review, but I couldn't-its been a few years. Can anyone reference anything that may help guide investigations in this matter.

 

[simpel]

Robbins CW, Slawson DC. Epidural analgesia in labor. J Fam Pract 1996; 42:227-8.

Unfortunately, no abstract available.

 

[oldbearprofessor]

: Pediatrics. 1997 Mar;99(3):415-9.Click here to read Links
Epidural analgesia, intrapartum fever, and neonatal sepsis evaluation.
Lieberman E, Lang JM, Frigoletto F Jr, Richardson DK, Ringer SA, Cohen A.

Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

OBJECTIVE: Although several studies have documented an increase in maternal temperature associated with use of epidural analgesia during labor, none have investigated the impact of epidural use on the rate of intrapartum fever or the consequences for the fetus and newborn of this elevated maternal temperature. This study evaluates the impact of epidural analgesia use during labor on the rate of intrapartum fever and the performance of neonatal sepsis evaluations and treatment with antibiotics. METHODS: We studied 1657 nulliparous women with term pregnancies and singleton vertex fetuses who were afebrile at admission for delivery. The rates of maternal intrapartum fever >100.4 degrees F, neonatal sepsis evaluation, and neonatal antibiotic treatment according to use of epidural analgesia during labor were determined. Rate ratios and 95% confidence intervals (CI) were calculated. Multiple logistic regression was used to examine associations while controlling for confounding factors. RESULTS: Intrapartum fever >100.4 degrees F occurred in 14.5% of women receiving an epidural but only 1.0% of women not receiving an epidural (adjusted odds ratio (OR) = 14.5, 95% CI = 6.3, 33.2). Without epidural, the rate of fever remained low regardless of length of labor; with epidural, the rate of fever increased from 7% for labors < or = 6 hours to 36% for labors >18 hours. Neonates whose mothers received epidurals were more often evaluated for sepsis (34.0% vs 9.8%; adjusted OR = 4.3, 95% CI = 3.2, 5.9) and treated with antibiotics (15.4% vs 3.8%; adjusted OR = 3.9, 95% CI = 2.1, 6.1). Although 63% of women received epidurals, 96.2% of intrapartum fevers, 85.6% of neonatal sepsis evaluations, and 87.5% of neonatal antibiotic treatment occurred in the epidural group. CONCLUSIONS: Use of epidural analgesia during labor is strongly associated with the occurrence of maternal intrapartum fever, neonatal sepsis evaluations, and neonatal antibiotic treatment.

Pediatrics. 2001 Nov;108(5):1099-102.Click here to read Links

Comment in:
Pediatrics. 2002 Jul;110(1 Pt 1):196-7; author reply 196-7.

Maternal epidural use and neonatal sepsis evaluation in afebrile mothers.
Goetzl L, Cohen A, Frigoletto F Jr, Ringer SA, Lang JM, Lieberman E.

Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77098, USA.

OBJECTIVE: Epidural use has been associated with a higher rate of neonatal sepsis evaluation. Epidural-related fever explains some of the increase but not the excess of neonatal sepsis evaluations in afebrile women METHODS: We studied 1109 women who had singleton term pregnancies and who presented in spontaneous labor and were afebrile during labor (<100.4 degrees F). Neonatal sepsis evaluation generally was performed on the basis of the presence of 1 major or 2 minor criteria. Major criteria included rupture of membranes for >24 hours or sustained fetal heart rate of >160 beats per minute. Minor criteria included a maternal temperature of 99.6 degrees F to 100.4 degrees F, rupture of membranes for 12 to 24 hours, maternal admission white blood cell count of >15 000 cells/mL(3), or an Apgar score of <7 at 5 minutes. RESULTS: Infants of afebrile women with epidural analgesia were more likely to be evaluated for sepsis than infants of women without epidural (20.4% vs 8.9%), although not more likely to have neonatal sepsis. An increased risk of sepsis evaluation persisted in regression analysis (odds ratio: 3.1; 95% confidence interval: 2.0, 4.7) after controlling for confounders and was not explained by longer labors with epidural. Women with epidural were significantly more likely to have major and minor criteria for sepsis evaluation, including fetal tachycardia (4.4% vs 0.4%), rupture of membranes for >24 hours (6.2% vs 3.4%), low-grade fever of 99.6 degrees F to 100.4 degrees F (24.3% vs 5.2%), and rupture of membranes for 12 to 24 hours (21.4% vs 5.2%) than women without epidural. CONCLUSIONS: Epidural analgesia is associated with increased rates of major and minor criteria for neonatal sepsis evaluations in afebrile women.

: Am J Obstet Gynecol. 2002 May;186(5 Suppl Nature):S31-68.Click here to read Links

Comment in:
Am J Obstet Gynecol. 2002 May;186(5 Suppl Nature):S78-80.

Unintended effects of epidural analgesia during labor: a systematic review.
Lieberman E, O'donoghue C.

Center for Perinatal Research, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Epidural analgesia is used by more than half of laboring women, yet there is no consensus about what unintended effects it causes. To evaluate the state of our knowledge, we performed a systematic review of the literature examining the unintended maternal, fetal, and neonatal effects of epidural analgesia used for pain relief in labor by low-risk women. Our review included randomized and observational studies appearing in peer review journals since 1980.Much of the evidence is equivocal. Existing randomized trials are either small or do not allow clear interpretation of the data because of problems with protocol compliance. In addition, few observational studies control for the confounding factors that result because women who request epidural are different from women who do not.There is considerable variation in the association of epidural with some outcomes, particularly those that are heavily practice-based. Despite this variation, there is sufficient evidence to conclude that epidural is associated with a lower rate of spontaneous vaginal delivery, a higher rate of instrumental vaginal delivery and longer labors, particularly in nulliparous women. Women receiving epidural are also more likely to have intrapartum fever and their infants are more likely to be evaluated and treated for suspected sepsis. There is insufficient evidence to determine whether epidural does or does not tend to increase the risk of cesarean delivery or fetal malposition. Adverse effects on the fetus may occur in the subset of women who are febrile.Women should be informed of unintended effects of epidural clearly supported by the evidence, especially since epidural use is almost always an elective procedure. Further research is needed to advance our understanding of the unintended effects of epidural. Improved information would permit women to make truly informed decisions about the use of pain relief during labor.

 

[oldbearprofessor]

The obstetrical and anesthesia literature also has conflicting data as well that says that there is no increased fever with epidural. In my experience, we see a lot of 100.4-100.8 fevers with epidurals that have soft "other" evidence for chorio and get sepsis w/u. I've not seen any positives in this range, although for temps > 102 I have seen lots of positives.

YMMV

 

[bks524]

thanks, I had seen the B and Y studies before. neither is the specific one I was thinking of, but thanks for the hits