Lumbar Puncture Frequency and Fluid Analysis in the Neonate
Cerebrospinal
Jeffrey Schwersenski, MD; Lester McIntyre, MD; Charles R. Bauer, MD \s=b\ A prospective study was performed to assess the frequency and diagnostic utility of lumbar punctures in neonates both during their first week of life and thereafter. During the two 6-month periods from January 1,1985 to June 30,1985, and February 1,1986 to July 31,1986,712 neonates underwent 728 lumbar punctures during their first week of life primarily as part of the evaluation for suspected infection, either congenital or postnatal. There were eight patients with positive spinal fluid cultures in the first week of life, but only one patient simultaneously had a positive blood culture and a clinical course consistent with meningitis. In con-
trast, a considerably higher yield, approxi-
mating five times that of the first week of life, was obtained in patients undergoing a lumbar puncture after the first week of life.
(AJDC. 1991;145:54-58)
the procedure is performed with the at¬ tendant risks involved. Complications of the procedure that have been de¬ scribed include trauma, introduction of
infection, spinal epidermoid tumors, brain-stem herniation in older children, and contamination of cerebrospinal fluid
marrow cells.1"7 The of techniques for the continuous, noninvasive monitoring of measures such as Po2 and Pco2 and oxygen satura¬ tion has demonstrated that significant hypoxemia occurs during handling for routine procedures, especially in sick, preterm neonates. The manipulation and positioning required for lumbar punctures have been associated with rapid clinical deterioration in neo¬
(CSF) with bone use
nates.^10
Sepsis, with or without meningitis, is of the more commonly encountered problems in the newborn. The incidence of systemic bacterial infection is re¬ ported to vary between one and eight per 1000 live births.1112 Meningitis can one
umbar punctures are considered a routine part of the evaluation of neo¬ nates who are thought to exhibit signs of generalized infection. The signs of sep¬ sis, particularly in the preterm neonate, are vague and less specific than in the term neonate or older patient. The pre¬ term neonate is thus more likely to have a course of antibiotic treatment insti¬ tuted because of clinical signs of sepsis or because of the presence of risk factors that are known to be associated with an increased incidence of sepsis. In many such cases, the lumbar puncture is often delayed because of the neonate's "un¬ stable" condition, and antibiotic admin¬ istration is begun empirically, or else Accepted for publication June 4,1990. From the Division of Neonatology, Department of Pediatrics, University of Miami, Fla. Read in part before the Southern Society for Pediatric Research, New Orleans, La, February 7,1986.
Reprint requests to Department of Pediatrics (R-131), University of Miami, PO Box 016960, Miami, FL 33101 (Dr Bauer).
coexist in up to one third of neonates with sepsis. During the first month of life, the mortality for sepsis is reported to be between 10% and 30% but exceeds 30% when meningitis is superimposed. Statistically, however, the highest risk of death occurs during the first week of life, when mortality associated with in¬ fection may approach 50%.1112 To evaluate the frequency and diag¬ nostic utility of lumbar puncture and CSF analysis in the newborn, this pro¬ spective study was undertaken. The study was approved by the Subcommit¬ tee for the Protection of Human Sub¬ jects in Research at the University of Miami (Fla)/Jackson Memorial Medical Center. PATIENTS AND METHODS All neonates born at
or
transferred to the
University of Miami/Jackson Memorial Med-
Downloaded From: http://archpedi.jamanetwork.com/ by a Oakland University User on 06/13/2015
ical Center who, during the two 6-month pe¬ riods from January 1, 1985 to June 30, 1985, and February 1,1986 to July 31,1986, under¬ went a lumbar puncture were identified and enrolled in the study. Ventricular and shunt taps were excluded. The clinical course and treatment of the neonates were prospectively followed up. Daily records were kept of diagnoses and the results of hématologie, bactériologie, and other significant laborato¬ ry data. Total cell counts were performed on a hemocytometer on unspun, unstained CSF specimens. Differential cell counts were per¬ formed on spun specimens, and the sediment was stained with gentian violet. The cerebrospinal fluid protein level was determined by the trichloroacetic acid method (Dupont ACA Instrument, Dupont Co, Wilmington, Del). The glucose level was measured using a glucose oxidase method (Beckman Astra In¬ strument, Beckman Instruments, Ine, Brea, Calif). Cerebrospinal fluid was inoculated onto thioglycolate broth, chocolate agar, 5% sheep blood agar, and an enriched 5% sheep blood agar plate. The chocolate agar plates were incubated in 4% carbon dioxide, blood agar plates were incubated aerobically, and the enriched blood agar plates were incu¬ bated anaerobically. All cultures were incu¬ bated for 72 hours before a final negative
report was generated. The neonates who underwent lumbar
punctures were subclassified into two groups
by their age at the time of the procedure: within the first week of life and determined
thereafter.
RESULTS
During these two 6-month periods, there were a total of 11035 admissions to the newborn services at the Universi¬ ty of Miami/Jackson Memorial Medical Center. Of these, 826 neonates, or 7.5% of all neonatal admissions, underwent 1104 lumbar punctures. Eighty-six per¬ cent of these neonates received their lumbar punctures during the first week of life. The remaining 14%, who had their first lumbar puncture after 7 days of age, averaged slightly more than
three lumbar punctures per
patient
(Table 1). Forty-three percent of the
during the first week oflow birth weight («2500 g), with 17.6% being of very low birth weight («1500 g) (Table 2). These low-birth-
Table 1 .—Patients
Lumbar Puncture and
Undergoing
neonates studied
Study Period 1, Study Period 2,
were
weight
only represent those at greatest risk for sepsis but are neonates not
also those in whom the chances of ad¬ verse effects due to the procedure are
Total No. of admissions
In the first week of life, it should be noted that an amount of CSF adequate for culture only was obtained in 103 pa¬ tients, who were 14.5% of the total num¬ ber of neonates studied. This was usual¬ ly because of technical difficulties, which occurred most often (51.5%) in neonates of low birth weight. An addi¬ tional 98 patients (13.8%) had a "bloody" CSF sample, which was defined using the criteria of Visser and Hall,13 that is, having a red blood cell count higher than 10 x 10YL. This finding was again more frequent in the low-birth-weight neo¬ nates, accounting for 63.1% of the total cases
355 484
(6.5)
Total 11 035
(8.4)
471 620
826
(7.5)
1104
s7
Patients, No. (%) Lumbar punctures, No.
298
(84)
304
414 424
(88)
57
(12)
712
(86)
728
>7
Patients, No. (%) Lumbar punctures, No.
57
(16)
180
Study Period 1 (n 298) Birth weight, g >2500
156
72
"Values
are
number
Total
(n 712)
(n 414) =
(52.3) (47.7) (26.8) (20.8)
248
(58.7) (31.5) (9.7)
273
166 103
63
106 35
(14)
Weight
Study Period 2
=
114
376
196
Table 2.—Patients in First Week of Life by Birth and by Age at Initial Lumbar Puncture*
=
(59.9) (40.1) (24.9) (15.2)
404
(65.9) (25.6) (8.5)
448
308 183
125
(56.7) (43.3) (25.7) (17.6)
(62.9) (28.1) 64 (9.0)
200
(percent). Table 3.—Indications for Lumbar Puncture
Age, d >7
Indication
Suspected infection
Positive
serologie study
Both
(Table 4).
Of the total of 712 patients having a lumbar puncture performed during the first week of life, only nine CSF cultures were positive. This represents a yield (by patients) of 1.3% (Table 5). Of these nine positive cultures, six yielded Staphylococcus epidermidis. In all of them, this was believed to be a contami¬ nant, as the neonates had neither cyto¬ logie results consistent with infected CSF nor a clinical course consistent with meningitis. Four of the neonates whose cultures yielded S epidermidis
5612
5423
(%) of patients undergoing lumbar puncture performed Age, d
with raised intracranial pressure was the indication in the remaining cases
(Table 3).
Feb 1 to
Jul31,1986
No. of lumbar punctures
Of the lumbar punctures performed during the first week of life, approxi¬ mately 63% were done on the first day, with the percentage increasing to 91%
week, posthemorrhagic hydrocephalus
Jan 1 to
Jun30,1985 No.
most likely.
within the first 72 hours (Table 2). Irre¬ spective of age, suspected infection was the overwhelming indication for per¬ forming a lumbar puncture, accounting for 90% of the procedures in the first week oflife and for 93% in those patients older than 1 week. In the group less than 1 week of age, the remaining lum¬ bar punctures were performed predom¬ inantly because of a positive serologie test for syphilis. In those older than 1
Age at Initial Lumbar Puncture
Raised intracranial pressure
Study
0-24 h
25-72 h
>72 h
1
170
59
23
252
2
269
32
386
439
85 144
55
638
1
29
4
34
Total 1
Total 51 55
(90%)
106
2
3
18
2
23
Total
4
47
57
1
4
6
6 2
2
1
3
1
5
Total
5
9
3
17
1
0
0
0
0
6
2
0
0
0
0
2
Total
0
0
0
0
8
treated with intravenous antibiot¬ ics for 3 days; the other two neonates were treated for 7 and 10 days, respec¬ tively. None of the six neonates had a simultaneously positive blood culture. The remaining three cultures yielded Streptococcus viridans in one case, were
Downloaded From: http://archpedi.jamanetwork.com/ by a Oakland University User on 06/13/2015
(93%)
0 0
(8%)
12
0 0 0
(2%)
0
(7%)
Streptococcus in another, and a Bacillus species in one of the neonates whose culture yielded S epidermidis 24 hours later on a repeated CSF culture. Cytologie results in two of these neo¬ nates were not consistent with an in¬ fected CSF, and simultaneous blood cuigroup
Table 4.—Inadequate
Specimens in First Week of Life by Birth Weight Groupings Study 1 (n 298)
Weight Group, g
Birth
Study 2 (n 414) Culture
Total in group >2500
43 15
==2500
28
1501-2500
11
s 1500
17
Total in group >2500
39 13
S2500
26
1501-2500
17
s 1500
9
Total
(n 712)
=
=
Only
(14.4) (34.9) (65.1) (25.6) (39.5) Bloody Specimen (13.1) (33.3) (66.7) (43.6) (23.1)
60 35 25
15 10 59 33 26 16 10
=
(14.5) (58.3) (41.7) (25) (16.7)
103
(14.3) (55.9) (44.1) (27.1) (17.0)
98
(14.5) (48.5) (51.5) (25.2) (26.2)
50 53 26 27
(13.8) (46.9) 52 (53.1) 33 (33.7) 19 (19.4) 46
ic therapy. The patient with Serratia infection died within 24 hours of the di¬ agnosis and shortly after the initiation of treatment. Of the remaining five pa¬ tients with negative blood cultures, four were considered to have contaminated specimens. The fifth patient was clini¬ cally symptomatic at the time of the positive culture and received antibiotic therapy. Symptoms and signs in this patient included seizures, apnea, and increases in both CSF white blood cell count and CSF protein level (Table 6). COMMENT A number of lumbar
punctures
are
performed in most neonatal special care centers for indications such Table 5.—Lumbar Puncture Yields
Age, d s7
Study 1 patients No. of lumbar punctures No. of positive cultures % yield by patient % yield by procedure Organisms No. of
"Infants in whom both
Study 2
Total
Study 1
Study 2
Total
712
304
414 424
728
57 180
196
376
3
6
9
4
4
8
1.2
1.4
1.3
7.0
7.0
7.0
1.0
1.4
1.2
2.2
2.0
2.1
248
Streptococcus, * 6 Staphylococcus epidermidis, 1 Streptococcus viridans, 1 Bacillus species 1 group
57
114
2S
epidermidis (1 *), group Streptococcus,*
1 1 Serratia marcescens* 1 Corynebacterium species, 1 Acinetobacter, 1 Pseudomonas aeruginosa, 1 combined S epidermidis and Corynebacterium species
cerebrospinal fluid and blood cultures were simultaneously positive.
tures were negative. These two neo¬ nates were treated with antibiotics for 5 and 3 days, respectively. In the third neonate, group Streptococcus grew in
cultures from both the blood and the CSF; this patient had an increased CSF white blood cell count, a positive urine
Wellcogen (latex particle agglutination for B-hemolytic Streptococcus), and clinical signs consistent with a central
system infection (Table 6). Of the 712 neonates who underwent lumbar punctures in the first week of life, 63 (8.8%) had mothers who had been treated with antibiotics immedi¬ ately preceding delivery. One of these neonates had a culture positive for S epidermidis, but this was thought to be a contaminant, as the cytologie study results and clinical status of the neonate were benign. All of these neonates were treated for 7 to 18 days with broad-
nervous
>7
spectum antibiotics because of the ma¬ ternal indication, as well as the lack of culture reliability due to circulating ma¬ ternal antibiotics. In contrast, after the first week of life, 376 lumbar punctures were performed in 114 patients. There were eight positive CSF cultures in this group, giving a yield of 7.0%, more than five times that ob¬ served during the first week of life (Table 5). Three of these eight cultures had si¬ multaneously positive blood cultures (group Streptococcus, Serratia marcescens, and S epidermidis). The one patient with group streptococcal meningitis had three documented episodes of sepsis with this organism. The meningitis was associated with the second episode. The neonate with S epi¬ dermidis infection had a clinical and hé¬ matologie course consistent with sepsis and received a 21-day course of antibiot-
Downloaded From: http://archpedi.jamanetwork.com/ by a Oakland University User on 06/13/2015
as
suspect¬
ed sepsis, positive serologie results, and relief of increased intracranial pressure in neonates with posthemorrhagic hydrocephalus. Often the procedure is performed by transient or junior nurs¬ ery staff who may not yet fully appreci¬ ate the risks involved in performing the procedure. In addition, the procedure often provides fluid sufficient for cul¬ ture only, or a blood-contaminated spec¬ imen. These problems have been re¬ ported in some series to account for up to 50% of specimens, thereby potential¬ ly reducing the amount of information that may help in reaching diagnostic and therapeutic conclusions.13 In this study, approximately 28% of the samples ob¬ tained within the first week of life were limited by either the amount of fluid obtained or blood contamination. We did not design the study to evalu¬ ate the risk-benefit ratio of this proce¬ dure. We did not specifically monitor neonates clinically or electronically dur¬ ing or after the procedure to determine their tolerance. Hence, we cannot com¬ ment on the incidence of complications in this population as compared with pre¬
viously reported occurrences. If, indeed, the co-occurrence of men¬ ingitis and sepsis in the neonate ap¬ proaches 30%, the performance of a lumbar puncture as part of the complete evaluation for infection can be readily justified. In this series, however, the incidence of meningitis associated with sepsis, particularly in the first week of life, was extremely low. Even in the nine instances where positive spinal flu¬
id cultures had been obtained in neo¬ nates who were in their first week of
Table 6.-Positive CSF Cultures* Patient No./Gestational
Age, wk/Blrth Weight, g
Indication for Workup
Laboratory Results
Outcome
Patients s7 d Old 1/40/3360
2/38/3170
Maternal temperature 39°C, 1 dose ampicillin before delivery; C section for fetal distress 2
cyanotic episodes after birth with opisthotonus; R/O seizures
Repeated workup 24 h after stopping antibiotic administration
3/43/4045
Prolonged ruptured membranes 45 h 30 min
4/38/3435
Tachypnea, lethargy, opisthotonus at 24 h,
R/O
seizures
5/40/2750 6/40/3760
Maternal temperature 32.3°C before delivery
Tachypnea, hypoxemia, acidosis at 24 h
7/40/3840
8/40/3360
CSF (culture only): Staphylococcus epidermidis: gastric aspirate: group
Streptococcus: urine Wellcogen: positive; blood culture: negative CSF: Bacillus species, WBCs 3 10VL (100% monocytes), glucose 2.2 mmol/L, protein 0.92 g/L; CBC count: normal; urine Wellcogen: negative; blood culture: negative CSF: S epidermidis, WBCs 3 10«/L (100% monocytes), protein 0.24 g/L, glucose QNS CSF: S epidermidis, WBC 11
10«/L
(100%
monocytes), glucose 2.5 mmol/L, protein 0.47 g/L CSF: group streptococcus, WBCs 689 10e/L (27% PMNs), glucose 0.0 mmol/L, protein 2.56 g/L; urine Wellcogen: positive; blood culture: group Streptococcus CSF: S epidermidis (broth only), RBCs 81 000 x 10e/L, WBCs 68 x 10e/L CSF: S epidermidis, bloody tap; CBC count: left shift; blood culture: negative
Maternal temperature 38.9°C before delivery
CSF: Streptococcus viridans (broth only),
Marked tachypnea after birth, R/O pneumonia
CSF: S epidermidis (broth only); WBCs
bloody tap; blood culture: negative 1
(100% monocytes), glucose 2.0
106/L
Ampicillin sodium and gentamicin sulfate for 7 d
Ampicillin and gentamicin for 3 d
Vancomycin hydrochloride for 3 d; repeated LP: WBCs 6 x10e/L, culture
negative Ampicillin and gentamicin for 3 d Penicillin sodium for 14 d
Ampicillin and gentamicin for 3 d Ampicillin and gentamicin for 10 d Ampicillin and gentamicin for 5 d; repeated CSF: WBCs 0 10«/L, culture negative Ampicillin and gentamicin for 3 d
mmol/L, protein 0.93 g/L; urine Wellcogen:
negative; blood culture: negative 1/31/950
1 mo old: apnea and
bradycardia, abdominal distention, hypoactive; required
Patients >7 d Old CSF: Serratia: gram-negative rods; blood culture: Serratia
Seizures: died within 24 h; treated with oxacillin sodium, amikacin sulfate, and cefotaxime sodium
intubation
2/28/830
6
w
old: apnea,
pallor, bulging
fontanelle; required intubation; group at birth 3/26/930
5
Streptococcus sepsis
old; chronic lung disease, grade 4 IVH on daily LPs,
mo
increasing apnea,
left shift on
CBC count 6
4/32/1500
old: LPs
mo
asymptomatic on daily
2VÍ! wk old: apnea and
bradycardia, seizures; required intubation
5/27/840
6/28/900
28 d old: apnea and bradycardia, abdominal distention, pneumatosis of intestine 2
mo
old: abdominal distention,
necrotizing enterocolitis 7/26/800
8 d old: lethargy, acidosis, carbon dioxide retention
CSF: group
Streptococcus, WBCs 349 106/L (14% PMNs); blood culture: group Streptococcus: CBC count:
Penicillin for 21 d
neutropenia
CSF: Corynebacterium (broth only), WBCs 5 106/L (100% monocytes), glucose 3.4 mmol/L, protein 1.24 g/L (Pseudomonas grew from ET tube culture)
Oxacillin and tobramycin sulfate for 7 d; repeated CSF: culture
CSF: Acinetobacter, RBCs 162 106/L, WBCs 1 x 10e/L (100% monocytes), glucose 4.2 mmol/L, protein 1.20 g/L CSF: Pseudomonas, WBCs 4500 10»/L (78% monocytes), glucose 0.2 mmol/L,
Cefotaxime sodium for 3 d; repeated CSF: culture negative
protein 5.41 g/L
CSF: S epidermidis (broth only), WBCs 5 10e/L (100% monocytes),
glucose protein 1.96 g/L CSF: S epidermidis and Corynebacterium (late growth), WBCs 13 106/L (100% monocytes), glucose 1.3 mmol/L, protein 0.26 g/L CSF: S epidermidis, WBCs 4 10«/L (98% monocytes), glucose 6.8 mmol/L, protein 2.31 g/L; CBC count: 12.0 mmol/L,
negative
Tobramycin for 21 d; CSF after 48 h: negative Ampicillin, gentamicin, and oral kanamycin sulfate for 9 d; perforated NEC; died
Ampicillin, gentamicin, and oral kanamycin for 14 d Vancomycin hydrochloride for 21 d
left shift; blood culture: S epidermidis and Enterobacter
*CSF indicates cerebrospinal fluid; C section, cesarean section; R/O, rule out; WBCs, white blood cells; CBC, complete blood cell; QNS, quantity not sufficient; LP, lumbar puncture; PMNs, polymorphonuclear leukocytes; RBCs, red blood cells; IVH, intraventricular hemorrhage; ET, endotracheal; and NEC, necrotizing
enterocolitis.
Downloaded From: http://archpedi.jamanetwork.com/ by a Oakland University User on 06/13/2015
were considered to be con¬ taminated. None of these eight patients had simultaneously positive blood cul¬ tures, nor were they treated specifically for meningitis. After the first week of life, three neonates had simultaneously positive blood and spinal fluid cultures, accounting for a 2.5% incidence of co¬ existing sepsis and meningitis in this
life, eight
study. Group streptococcal sepsis is a fre¬ quently reported cause of very early neonatal sepsis that often results in sig¬ nificant morbidity and mortality.14 Ear¬ ly-onset disease occurs in one to four per 1000 live births, the incidence and mor¬ tality being higher in smaller, prema¬ ture neonates. It also has a reportedly high incidence of coexistent meningitis. In this study, only one of the lumbar punctures done in the first week of life
yielded a group Streptococcus, al¬ though there were 27 cases of blood cul¬ ture-proved group streptococcal sep¬ sis in the first week, accounting for
24.3% of all
positive blood cultures. In a positive blood only culture performed after the first week of life did the culture yield group Streptococcus, and this patient also had coexisting meningitis. In summary, during two separate 6month periods, nine of 712 patients un¬ dergoing lumbar puncture during the first week of life had positive cultures. On the other hand, eight of 114 patients undergoing lumbar puncture after the first week of life had positive cultures, most of which were clinically signifi¬ cant, although only three were accom¬ panied by simultaneously positive blood one
neonate with
cultures. This fivefold difference in inci¬ dence might be explained by the neona¬ tal vs the maternal indication for the sepsis evaluation. The percentage of neonatal infections masked by maternal antibiotic treatment could not be deter¬ mined and may have an impact on the interpretation of these data. The results of this study suggest that
the routine inclusion of lumbar punc¬ ture, performed in the first week of life as part of the workup for suspected in¬ fection in the asymptomatic but at-risk neonate, may not be indicated or justi¬ fied. In contrast, when a lumbar punc¬ ture is performed for specific clinical indications in the older neonate to rule out an acquired infection, the yield is significant. The problems of blood con¬ tamination, inadequate amounts of flu¬ id, and administration of antibiotics to the mother limit the interpretation of the results. The routine use of lumbar puncture as a part of the workup for infection during the first week of life in an asymptomatic neonate should be reassessed. This project was supported in part by a grant from the Division of Children's Medical Services, State of Florida Department of Health and Reha¬ bilitative Services. We are grateful to Eduardo Bancalari, MD, and Gwendolyn Scott, MD, for their review and sugges¬ tions, and to Rose Wesley for preparation of the
manuscript.
References 1. Hildebrand WL, Stevens DC, Gosling CG, Sternecker CL, Schreiner RL. Lumbar puncture in infants. Am Fam Physician. 1983;27:157-159. 2. Choremis C, Economos D, Papadatos C, Gargoulas A. Intraspinal epidermoid tumours (cholesteatomas) in patients treated for tuberculous meningitis. Lancet. 1956;2:437-439. 3. Shaywitz BA. Epidermoid spinal cord tumors and previous lumbar punctures. J Pediatr.
1972;80:638-640. 4. Batnitzky S, Keucher TR, Mealey J Jr, Campbell RL. Iatrogenic intraspinal epidermoid tumors. JAMA. 1977;237:148-150. 5. Teele DW, Dashefsky B, Rakusan T, Klein JO. Meningitis after lumbar puncture in children
with bacteremia. N Engl J Med. 1981;305:1079\x=req-\ 1081. 6. Kruskall MS, Carter SR, Ritz LP. Contamination of cerebrospinal fluid by vertebral bonemarrow cells during lumbar puncture. N Engl J Med. 1983;308:697-700. 7. Lane PA, Githens JH. Contamination of cerebrospinal fluid with bone marrow cells during lumbar puncture. N Engl J Med. 1983;309:434-435. 8. Long JG, Philip AGS, Lucey JF. Excessive handling as a cause of hypoxemia. Pediatrics.
1980;65:203-207.
9. Speidel BD. Adverse effects of routine procedures on preterm infants. Lancet. 1978;1:864-865. 10. Weisman LE, Merenstein GB, Steenbarger
JR. The effect of lumbar puncture position in sick neonates. AJDC. 1983;137:1077-1079. 11. Remington JS, Klein JO. Infectious Diseases of the Fetus and Newborn Infant. Philadelphia, Pa: WB Saunders Co; 1983:680-687. 12. Gnehm H, Klein JO. Management of neonatal sepsis and meningitis. Pediatr Ann. 1983;12: 195-204. 13. Visser VE, Hall RT. Lumbar puncture in the evaluation of suspected neonatal sepsis. Pediatrics. 1980;96:1063-1067. 14. Pyati SP, Pildes RS, Jacobs NM, et al. Penicillin in infants weighing two kilograms or less with early-onset group B streptococcal disease. N Engl J Med. 1983;308:1383-1389.
In Other AMA Journals JAMA The Efficacy of Preemployment Drug Screening for Marijuana and Cocaine in Predicting Employment Outcome C. Zwerling; J. Ryan; E. J. Orav (JAMA. 1990;264:2644)
Legal Interventions During Pregnancy
AMA Board of Trustees Report (JAMA. 1990;264:2663)
Another Side Effect of NSAIDs G. R. Gay (JAMA. 1990;264:2677)
Downloaded From: http://archpedi.jamanetwork.com/ by a Oakland University User on 06/13/2015
Cerebrospinal
Jeffrey Schwersenski, MD; Lester McIntyre, MD; Charles R. Bauer, MD \s=b\ A prospective study was performed to assess the frequency and diagnostic utility of lumbar punctures in neonates both during their first week of life and thereafter. During the two 6-month periods from January 1,1985 to June 30,1985, and February 1,1986 to July 31,1986,712 neonates underwent 728 lumbar punctures during their first week of life primarily as part of the evaluation for suspected infection, either congenital or postnatal. There were eight patients with positive spinal fluid cultures in the first week of life, but only one patient simultaneously had a positive blood culture and a clinical course consistent with meningitis. In con-
trast, a considerably higher yield, approxi-
mating five times that of the first week of life, was obtained in patients undergoing a lumbar puncture after the first week of life.
(AJDC. 1991;145:54-58)
the procedure is performed with the at¬ tendant risks involved. Complications of the procedure that have been de¬ scribed include trauma, introduction of
infection, spinal epidermoid tumors, brain-stem herniation in older children, and contamination of cerebrospinal fluid
marrow cells.1"7 The of techniques for the continuous, noninvasive monitoring of measures such as Po2 and Pco2 and oxygen satura¬ tion has demonstrated that significant hypoxemia occurs during handling for routine procedures, especially in sick, preterm neonates. The manipulation and positioning required for lumbar punctures have been associated with rapid clinical deterioration in neo¬
(CSF) with bone use
nates.^10
Sepsis, with or without meningitis, is of the more commonly encountered problems in the newborn. The incidence of systemic bacterial infection is re¬ ported to vary between one and eight per 1000 live births.1112 Meningitis can one
umbar punctures are considered a routine part of the evaluation of neo¬ nates who are thought to exhibit signs of generalized infection. The signs of sep¬ sis, particularly in the preterm neonate, are vague and less specific than in the term neonate or older patient. The pre¬ term neonate is thus more likely to have a course of antibiotic treatment insti¬ tuted because of clinical signs of sepsis or because of the presence of risk factors that are known to be associated with an increased incidence of sepsis. In many such cases, the lumbar puncture is often delayed because of the neonate's "un¬ stable" condition, and antibiotic admin¬ istration is begun empirically, or else Accepted for publication June 4,1990. From the Division of Neonatology, Department of Pediatrics, University of Miami, Fla. Read in part before the Southern Society for Pediatric Research, New Orleans, La, February 7,1986.
Reprint requests to Department of Pediatrics (R-131), University of Miami, PO Box 016960, Miami, FL 33101 (Dr Bauer).
coexist in up to one third of neonates with sepsis. During the first month of life, the mortality for sepsis is reported to be between 10% and 30% but exceeds 30% when meningitis is superimposed. Statistically, however, the highest risk of death occurs during the first week of life, when mortality associated with in¬ fection may approach 50%.1112 To evaluate the frequency and diag¬ nostic utility of lumbar puncture and CSF analysis in the newborn, this pro¬ spective study was undertaken. The study was approved by the Subcommit¬ tee for the Protection of Human Sub¬ jects in Research at the University of Miami (Fla)/Jackson Memorial Medical Center. PATIENTS AND METHODS All neonates born at
or
transferred to the
University of Miami/Jackson Memorial Med-
Downloaded From: http://archpedi.jamanetwork.com/ by a Oakland University User on 06/13/2015
ical Center who, during the two 6-month pe¬ riods from January 1, 1985 to June 30, 1985, and February 1,1986 to July 31,1986, under¬ went a lumbar puncture were identified and enrolled in the study. Ventricular and shunt taps were excluded. The clinical course and treatment of the neonates were prospectively followed up. Daily records were kept of diagnoses and the results of hématologie, bactériologie, and other significant laborato¬ ry data. Total cell counts were performed on a hemocytometer on unspun, unstained CSF specimens. Differential cell counts were per¬ formed on spun specimens, and the sediment was stained with gentian violet. The cerebrospinal fluid protein level was determined by the trichloroacetic acid method (Dupont ACA Instrument, Dupont Co, Wilmington, Del). The glucose level was measured using a glucose oxidase method (Beckman Astra In¬ strument, Beckman Instruments, Ine, Brea, Calif). Cerebrospinal fluid was inoculated onto thioglycolate broth, chocolate agar, 5% sheep blood agar, and an enriched 5% sheep blood agar plate. The chocolate agar plates were incubated in 4% carbon dioxide, blood agar plates were incubated aerobically, and the enriched blood agar plates were incu¬ bated anaerobically. All cultures were incu¬ bated for 72 hours before a final negative
report was generated. The neonates who underwent lumbar
punctures were subclassified into two groups
by their age at the time of the procedure: within the first week of life and determined
thereafter.
RESULTS
During these two 6-month periods, there were a total of 11035 admissions to the newborn services at the Universi¬ ty of Miami/Jackson Memorial Medical Center. Of these, 826 neonates, or 7.5% of all neonatal admissions, underwent 1104 lumbar punctures. Eighty-six per¬ cent of these neonates received their lumbar punctures during the first week of life. The remaining 14%, who had their first lumbar puncture after 7 days of age, averaged slightly more than
three lumbar punctures per
patient
(Table 1). Forty-three percent of the
during the first week oflow birth weight («2500 g), with 17.6% being of very low birth weight («1500 g) (Table 2). These low-birth-
Table 1 .—Patients
Lumbar Puncture and
Undergoing
neonates studied
Study Period 1, Study Period 2,
were
weight
only represent those at greatest risk for sepsis but are neonates not
also those in whom the chances of ad¬ verse effects due to the procedure are
Total No. of admissions
In the first week of life, it should be noted that an amount of CSF adequate for culture only was obtained in 103 pa¬ tients, who were 14.5% of the total num¬ ber of neonates studied. This was usual¬ ly because of technical difficulties, which occurred most often (51.5%) in neonates of low birth weight. An addi¬ tional 98 patients (13.8%) had a "bloody" CSF sample, which was defined using the criteria of Visser and Hall,13 that is, having a red blood cell count higher than 10 x 10YL. This finding was again more frequent in the low-birth-weight neo¬ nates, accounting for 63.1% of the total cases
355 484
(6.5)
Total 11 035
(8.4)
471 620
826
(7.5)
1104
s7
Patients, No. (%) Lumbar punctures, No.
298
(84)
304
414 424
(88)
57
(12)
712
(86)
728
>7
Patients, No. (%) Lumbar punctures, No.
57
(16)
180
Study Period 1 (n 298) Birth weight, g >2500
156
72
"Values
are
number
Total
(n 712)
(n 414) =
(52.3) (47.7) (26.8) (20.8)
248
(58.7) (31.5) (9.7)
273
166 103
63
106 35
(14)
Weight
Study Period 2
=
114
376
196
Table 2.—Patients in First Week of Life by Birth and by Age at Initial Lumbar Puncture*
=
(59.9) (40.1) (24.9) (15.2)
404
(65.9) (25.6) (8.5)
448
308 183
125
(56.7) (43.3) (25.7) (17.6)
(62.9) (28.1) 64 (9.0)
200
(percent). Table 3.—Indications for Lumbar Puncture
Age, d >7
Indication
Suspected infection
Positive
serologie study
Both
(Table 4).
Of the total of 712 patients having a lumbar puncture performed during the first week of life, only nine CSF cultures were positive. This represents a yield (by patients) of 1.3% (Table 5). Of these nine positive cultures, six yielded Staphylococcus epidermidis. In all of them, this was believed to be a contami¬ nant, as the neonates had neither cyto¬ logie results consistent with infected CSF nor a clinical course consistent with meningitis. Four of the neonates whose cultures yielded S epidermidis
5612
5423
(%) of patients undergoing lumbar puncture performed Age, d
with raised intracranial pressure was the indication in the remaining cases
(Table 3).
Feb 1 to
Jul31,1986
No. of lumbar punctures
Of the lumbar punctures performed during the first week of life, approxi¬ mately 63% were done on the first day, with the percentage increasing to 91%
week, posthemorrhagic hydrocephalus
Jan 1 to
Jun30,1985 No.
most likely.
within the first 72 hours (Table 2). Irre¬ spective of age, suspected infection was the overwhelming indication for per¬ forming a lumbar puncture, accounting for 90% of the procedures in the first week oflife and for 93% in those patients older than 1 week. In the group less than 1 week of age, the remaining lum¬ bar punctures were performed predom¬ inantly because of a positive serologie test for syphilis. In those older than 1
Age at Initial Lumbar Puncture
Raised intracranial pressure
Study
0-24 h
25-72 h
>72 h
1
170
59
23
252
2
269
32
386
439
85 144
55
638
1
29
4
34
Total 1
Total 51 55
(90%)
106
2
3
18
2
23
Total
4
47
57
1
4
6
6 2
2
1
3
1
5
Total
5
9
3
17
1
0
0
0
0
6
2
0
0
0
0
2
Total
0
0
0
0
8
treated with intravenous antibiot¬ ics for 3 days; the other two neonates were treated for 7 and 10 days, respec¬ tively. None of the six neonates had a simultaneously positive blood culture. The remaining three cultures yielded Streptococcus viridans in one case, were
Downloaded From: http://archpedi.jamanetwork.com/ by a Oakland University User on 06/13/2015
(93%)
0 0
(8%)
12
0 0 0
(2%)
0
(7%)
Streptococcus in another, and a Bacillus species in one of the neonates whose culture yielded S epidermidis 24 hours later on a repeated CSF culture. Cytologie results in two of these neo¬ nates were not consistent with an in¬ fected CSF, and simultaneous blood cuigroup
Table 4.—Inadequate
Specimens in First Week of Life by Birth Weight Groupings Study 1 (n 298)
Weight Group, g
Birth
Study 2 (n 414) Culture
Total in group >2500
43 15
==2500
28
1501-2500
11
s 1500
17
Total in group >2500
39 13
S2500
26
1501-2500
17
s 1500
9
Total
(n 712)
=
=
Only
(14.4) (34.9) (65.1) (25.6) (39.5) Bloody Specimen (13.1) (33.3) (66.7) (43.6) (23.1)
60 35 25
15 10 59 33 26 16 10
=
(14.5) (58.3) (41.7) (25) (16.7)
103
(14.3) (55.9) (44.1) (27.1) (17.0)
98
(14.5) (48.5) (51.5) (25.2) (26.2)
50 53 26 27
(13.8) (46.9) 52 (53.1) 33 (33.7) 19 (19.4) 46
ic therapy. The patient with Serratia infection died within 24 hours of the di¬ agnosis and shortly after the initiation of treatment. Of the remaining five pa¬ tients with negative blood cultures, four were considered to have contaminated specimens. The fifth patient was clini¬ cally symptomatic at the time of the positive culture and received antibiotic therapy. Symptoms and signs in this patient included seizures, apnea, and increases in both CSF white blood cell count and CSF protein level (Table 6). COMMENT A number of lumbar
punctures
are
performed in most neonatal special care centers for indications such Table 5.—Lumbar Puncture Yields
Age, d s7
Study 1 patients No. of lumbar punctures No. of positive cultures % yield by patient % yield by procedure Organisms No. of
"Infants in whom both
Study 2
Total
Study 1
Study 2
Total
712
304
414 424
728
57 180
196
376
3
6
9
4
4
8
1.2
1.4
1.3
7.0
7.0
7.0
1.0
1.4
1.2
2.2
2.0
2.1
248
Streptococcus, * 6 Staphylococcus epidermidis, 1 Streptococcus viridans, 1 Bacillus species 1 group
57
114
2S
epidermidis (1 *), group Streptococcus,*
1 1 Serratia marcescens* 1 Corynebacterium species, 1 Acinetobacter, 1 Pseudomonas aeruginosa, 1 combined S epidermidis and Corynebacterium species
cerebrospinal fluid and blood cultures were simultaneously positive.
tures were negative. These two neo¬ nates were treated with antibiotics for 5 and 3 days, respectively. In the third neonate, group Streptococcus grew in
cultures from both the blood and the CSF; this patient had an increased CSF white blood cell count, a positive urine
Wellcogen (latex particle agglutination for B-hemolytic Streptococcus), and clinical signs consistent with a central
system infection (Table 6). Of the 712 neonates who underwent lumbar punctures in the first week of life, 63 (8.8%) had mothers who had been treated with antibiotics immedi¬ ately preceding delivery. One of these neonates had a culture positive for S epidermidis, but this was thought to be a contaminant, as the cytologie study results and clinical status of the neonate were benign. All of these neonates were treated for 7 to 18 days with broad-
nervous
>7
spectum antibiotics because of the ma¬ ternal indication, as well as the lack of culture reliability due to circulating ma¬ ternal antibiotics. In contrast, after the first week of life, 376 lumbar punctures were performed in 114 patients. There were eight positive CSF cultures in this group, giving a yield of 7.0%, more than five times that ob¬ served during the first week of life (Table 5). Three of these eight cultures had si¬ multaneously positive blood cultures (group Streptococcus, Serratia marcescens, and S epidermidis). The one patient with group streptococcal meningitis had three documented episodes of sepsis with this organism. The meningitis was associated with the second episode. The neonate with S epi¬ dermidis infection had a clinical and hé¬ matologie course consistent with sepsis and received a 21-day course of antibiot-
Downloaded From: http://archpedi.jamanetwork.com/ by a Oakland University User on 06/13/2015
as
suspect¬
ed sepsis, positive serologie results, and relief of increased intracranial pressure in neonates with posthemorrhagic hydrocephalus. Often the procedure is performed by transient or junior nurs¬ ery staff who may not yet fully appreci¬ ate the risks involved in performing the procedure. In addition, the procedure often provides fluid sufficient for cul¬ ture only, or a blood-contaminated spec¬ imen. These problems have been re¬ ported in some series to account for up to 50% of specimens, thereby potential¬ ly reducing the amount of information that may help in reaching diagnostic and therapeutic conclusions.13 In this study, approximately 28% of the samples ob¬ tained within the first week of life were limited by either the amount of fluid obtained or blood contamination. We did not design the study to evalu¬ ate the risk-benefit ratio of this proce¬ dure. We did not specifically monitor neonates clinically or electronically dur¬ ing or after the procedure to determine their tolerance. Hence, we cannot com¬ ment on the incidence of complications in this population as compared with pre¬
viously reported occurrences. If, indeed, the co-occurrence of men¬ ingitis and sepsis in the neonate ap¬ proaches 30%, the performance of a lumbar puncture as part of the complete evaluation for infection can be readily justified. In this series, however, the incidence of meningitis associated with sepsis, particularly in the first week of life, was extremely low. Even in the nine instances where positive spinal flu¬
id cultures had been obtained in neo¬ nates who were in their first week of
Table 6.-Positive CSF Cultures* Patient No./Gestational
Age, wk/Blrth Weight, g
Indication for Workup
Laboratory Results
Outcome
Patients s7 d Old 1/40/3360
2/38/3170
Maternal temperature 39°C, 1 dose ampicillin before delivery; C section for fetal distress 2
cyanotic episodes after birth with opisthotonus; R/O seizures
Repeated workup 24 h after stopping antibiotic administration
3/43/4045
Prolonged ruptured membranes 45 h 30 min
4/38/3435
Tachypnea, lethargy, opisthotonus at 24 h,
R/O
seizures
5/40/2750 6/40/3760
Maternal temperature 32.3°C before delivery
Tachypnea, hypoxemia, acidosis at 24 h
7/40/3840
8/40/3360
CSF (culture only): Staphylococcus epidermidis: gastric aspirate: group
Streptococcus: urine Wellcogen: positive; blood culture: negative CSF: Bacillus species, WBCs 3 10VL (100% monocytes), glucose 2.2 mmol/L, protein 0.92 g/L; CBC count: normal; urine Wellcogen: negative; blood culture: negative CSF: S epidermidis, WBCs 3 10«/L (100% monocytes), protein 0.24 g/L, glucose QNS CSF: S epidermidis, WBC 11
10«/L
(100%
monocytes), glucose 2.5 mmol/L, protein 0.47 g/L CSF: group streptococcus, WBCs 689 10e/L (27% PMNs), glucose 0.0 mmol/L, protein 2.56 g/L; urine Wellcogen: positive; blood culture: group Streptococcus CSF: S epidermidis (broth only), RBCs 81 000 x 10e/L, WBCs 68 x 10e/L CSF: S epidermidis, bloody tap; CBC count: left shift; blood culture: negative
Maternal temperature 38.9°C before delivery
CSF: Streptococcus viridans (broth only),
Marked tachypnea after birth, R/O pneumonia
CSF: S epidermidis (broth only); WBCs
bloody tap; blood culture: negative 1
(100% monocytes), glucose 2.0
106/L
Ampicillin sodium and gentamicin sulfate for 7 d
Ampicillin and gentamicin for 3 d
Vancomycin hydrochloride for 3 d; repeated LP: WBCs 6 x10e/L, culture
negative Ampicillin and gentamicin for 3 d Penicillin sodium for 14 d
Ampicillin and gentamicin for 3 d Ampicillin and gentamicin for 10 d Ampicillin and gentamicin for 5 d; repeated CSF: WBCs 0 10«/L, culture negative Ampicillin and gentamicin for 3 d
mmol/L, protein 0.93 g/L; urine Wellcogen:
negative; blood culture: negative 1/31/950
1 mo old: apnea and
bradycardia, abdominal distention, hypoactive; required
Patients >7 d Old CSF: Serratia: gram-negative rods; blood culture: Serratia
Seizures: died within 24 h; treated with oxacillin sodium, amikacin sulfate, and cefotaxime sodium
intubation
2/28/830
6
w
old: apnea,
pallor, bulging
fontanelle; required intubation; group at birth 3/26/930
5
Streptococcus sepsis
old; chronic lung disease, grade 4 IVH on daily LPs,
mo
increasing apnea,
left shift on
CBC count 6
4/32/1500
old: LPs
mo
asymptomatic on daily
2VÍ! wk old: apnea and
bradycardia, seizures; required intubation
5/27/840
6/28/900
28 d old: apnea and bradycardia, abdominal distention, pneumatosis of intestine 2
mo
old: abdominal distention,
necrotizing enterocolitis 7/26/800
8 d old: lethargy, acidosis, carbon dioxide retention
CSF: group
Streptococcus, WBCs 349 106/L (14% PMNs); blood culture: group Streptococcus: CBC count:
Penicillin for 21 d
neutropenia
CSF: Corynebacterium (broth only), WBCs 5 106/L (100% monocytes), glucose 3.4 mmol/L, protein 1.24 g/L (Pseudomonas grew from ET tube culture)
Oxacillin and tobramycin sulfate for 7 d; repeated CSF: culture
CSF: Acinetobacter, RBCs 162 106/L, WBCs 1 x 10e/L (100% monocytes), glucose 4.2 mmol/L, protein 1.20 g/L CSF: Pseudomonas, WBCs 4500 10»/L (78% monocytes), glucose 0.2 mmol/L,
Cefotaxime sodium for 3 d; repeated CSF: culture negative
protein 5.41 g/L
CSF: S epidermidis (broth only), WBCs 5 10e/L (100% monocytes),
glucose protein 1.96 g/L CSF: S epidermidis and Corynebacterium (late growth), WBCs 13 106/L (100% monocytes), glucose 1.3 mmol/L, protein 0.26 g/L CSF: S epidermidis, WBCs 4 10«/L (98% monocytes), glucose 6.8 mmol/L, protein 2.31 g/L; CBC count: 12.0 mmol/L,
negative
Tobramycin for 21 d; CSF after 48 h: negative Ampicillin, gentamicin, and oral kanamycin sulfate for 9 d; perforated NEC; died
Ampicillin, gentamicin, and oral kanamycin for 14 d Vancomycin hydrochloride for 21 d
left shift; blood culture: S epidermidis and Enterobacter
*CSF indicates cerebrospinal fluid; C section, cesarean section; R/O, rule out; WBCs, white blood cells; CBC, complete blood cell; QNS, quantity not sufficient; LP, lumbar puncture; PMNs, polymorphonuclear leukocytes; RBCs, red blood cells; IVH, intraventricular hemorrhage; ET, endotracheal; and NEC, necrotizing
enterocolitis.
Downloaded From: http://archpedi.jamanetwork.com/ by a Oakland University User on 06/13/2015
were considered to be con¬ taminated. None of these eight patients had simultaneously positive blood cul¬ tures, nor were they treated specifically for meningitis. After the first week of life, three neonates had simultaneously positive blood and spinal fluid cultures, accounting for a 2.5% incidence of co¬ existing sepsis and meningitis in this
life, eight
study. Group streptococcal sepsis is a fre¬ quently reported cause of very early neonatal sepsis that often results in sig¬ nificant morbidity and mortality.14 Ear¬ ly-onset disease occurs in one to four per 1000 live births, the incidence and mor¬ tality being higher in smaller, prema¬ ture neonates. It also has a reportedly high incidence of coexistent meningitis. In this study, only one of the lumbar punctures done in the first week of life
yielded a group Streptococcus, al¬ though there were 27 cases of blood cul¬ ture-proved group streptococcal sep¬ sis in the first week, accounting for
24.3% of all
positive blood cultures. In a positive blood only culture performed after the first week of life did the culture yield group Streptococcus, and this patient also had coexisting meningitis. In summary, during two separate 6month periods, nine of 712 patients un¬ dergoing lumbar puncture during the first week of life had positive cultures. On the other hand, eight of 114 patients undergoing lumbar puncture after the first week of life had positive cultures, most of which were clinically signifi¬ cant, although only three were accom¬ panied by simultaneously positive blood one
neonate with
cultures. This fivefold difference in inci¬ dence might be explained by the neona¬ tal vs the maternal indication for the sepsis evaluation. The percentage of neonatal infections masked by maternal antibiotic treatment could not be deter¬ mined and may have an impact on the interpretation of these data. The results of this study suggest that
the routine inclusion of lumbar punc¬ ture, performed in the first week of life as part of the workup for suspected in¬ fection in the asymptomatic but at-risk neonate, may not be indicated or justi¬ fied. In contrast, when a lumbar punc¬ ture is performed for specific clinical indications in the older neonate to rule out an acquired infection, the yield is significant. The problems of blood con¬ tamination, inadequate amounts of flu¬ id, and administration of antibiotics to the mother limit the interpretation of the results. The routine use of lumbar puncture as a part of the workup for infection during the first week of life in an asymptomatic neonate should be reassessed. This project was supported in part by a grant from the Division of Children's Medical Services, State of Florida Department of Health and Reha¬ bilitative Services. We are grateful to Eduardo Bancalari, MD, and Gwendolyn Scott, MD, for their review and sugges¬ tions, and to Rose Wesley for preparation of the
manuscript.
References 1. Hildebrand WL, Stevens DC, Gosling CG, Sternecker CL, Schreiner RL. Lumbar puncture in infants. Am Fam Physician. 1983;27:157-159. 2. Choremis C, Economos D, Papadatos C, Gargoulas A. Intraspinal epidermoid tumours (cholesteatomas) in patients treated for tuberculous meningitis. Lancet. 1956;2:437-439. 3. Shaywitz BA. Epidermoid spinal cord tumors and previous lumbar punctures. J Pediatr.
1972;80:638-640. 4. Batnitzky S, Keucher TR, Mealey J Jr, Campbell RL. Iatrogenic intraspinal epidermoid tumors. JAMA. 1977;237:148-150. 5. Teele DW, Dashefsky B, Rakusan T, Klein JO. Meningitis after lumbar puncture in children
with bacteremia. N Engl J Med. 1981;305:1079\x=req-\ 1081. 6. Kruskall MS, Carter SR, Ritz LP. Contamination of cerebrospinal fluid by vertebral bonemarrow cells during lumbar puncture. N Engl J Med. 1983;308:697-700. 7. Lane PA, Githens JH. Contamination of cerebrospinal fluid with bone marrow cells during lumbar puncture. N Engl J Med. 1983;309:434-435. 8. Long JG, Philip AGS, Lucey JF. Excessive handling as a cause of hypoxemia. Pediatrics.
1980;65:203-207.
9. Speidel BD. Adverse effects of routine procedures on preterm infants. Lancet. 1978;1:864-865. 10. Weisman LE, Merenstein GB, Steenbarger
JR. The effect of lumbar puncture position in sick neonates. AJDC. 1983;137:1077-1079. 11. Remington JS, Klein JO. Infectious Diseases of the Fetus and Newborn Infant. Philadelphia, Pa: WB Saunders Co; 1983:680-687. 12. Gnehm H, Klein JO. Management of neonatal sepsis and meningitis. Pediatr Ann. 1983;12: 195-204. 13. Visser VE, Hall RT. Lumbar puncture in the evaluation of suspected neonatal sepsis. Pediatrics. 1980;96:1063-1067. 14. Pyati SP, Pildes RS, Jacobs NM, et al. Penicillin in infants weighing two kilograms or less with early-onset group B streptococcal disease. N Engl J Med. 1983;308:1383-1389.
In Other AMA Journals JAMA The Efficacy of Preemployment Drug Screening for Marijuana and Cocaine in Predicting Employment Outcome C. Zwerling; J. Ryan; E. J. Orav (JAMA. 1990;264:2644)
Legal Interventions During Pregnancy
AMA Board of Trustees Report (JAMA. 1990;264:2663)
Another Side Effect of NSAIDs G. R. Gay (JAMA. 1990;264:2677)
Downloaded From: http://archpedi.jamanetwork.com/ by a Oakland University User on 06/13/2015
