Lumbar puncture in the evaluation of suspected neonatal sepsis

Volume 96 Number 6

Brief clinical and laboratory observations

was mediated directly through an increase in arterial blood pressurel since there was no significant difference in ABP between groups. Expansion of blood volume may increase cerebral blood flow, and secondarily, cerebral capillary pressure enough to rupture already dilated and possibly damaged subependymal vessels. The association of volume expansion and IVH may be related to increased venous pressure. Some degree of left ventricular failure may be present in infants exposed to perinatal asphyxia? ~ This heart failure may be worsened by rapid excessive volume expansion or transfusions, with resultant increases in pulmonary capillary and central venous pressures. This may explain the frequent association of IVH and pulmonary hemorrhage? 6 It is possible that there was some intraventricular bleeding in Group I prior to 8 and 24 hours of life, and that blood was given to correct anemia. However, this is unlikely in that there was no evidence of hemorrhage or sudden drop in hematocrit prior to 8 and 24 hours of life in either group. The two patients who bled prior to 24 hours were excluded from the 24-hour calculations. A small amount of intraventricular bleeding that was not recognized clinically was equally likely to occur in either group. The differences in the amount of blood transfused in the two groups probably represents differences in transfusion practices in low-birth-weight infants. In this retrospective study, arterial blood pressure data for infants less than 1,000 gm were used which were not available when the study patients were cared for. In the past, physicians caring for infants less than 1,000 gm have extrapolated normative blood pressure values from infants greater than 1,000 gin. They have also used less quantitative measures, such as skin perfusion, to guide therapy. This may explain why some infants in this study received more colloid infusions than others. These data support the hypothesis that excessive volume expansion with colloid is another of several already known factors associated with an increased incidence of IVH. Therefore, we stress the importance of a conservative, rational approach to volume replacement, whether

10 6 3

related to blood transfusions or treatment of hypotension, in infants at risk for developing IVH. Based on these results we have changed our policy of volume expansion so as to avoid rapid infusions and to accept lower arterial blood pressure values as normal. Coincident with these changes we have noted a significant decrease in the incidence of massive IVH over comparable 6-month periods from 31% (40/125) in 1978 to 18.7% (25/33) in 1979 in infants weighing between 750 and 1,500 gm (P <0.001). The authors express their appreciation to Yolanda M. Ruiz for her excellent secretarial help, to Janet Cassidy for her statistical assistance, and to Dr. Mary Jane Jesse for her critical review of this manuscript and for her support. REFERENCES

1. Cole VA, Durbin GM, Alaffson A, et al: Pathogenesis of intraventricular hemorrhage in newborn infants, Arch Dis Child 49:722, 1974. 2. Simmons MA, Adcock EW III, Bard H, et al: Hypernatremia and intracranial hemorrhage in neonates, N Engl J Med 291:6, 1974. 3. Hambleton G, and Wigglesworth JS: Origin ofintraventricu l a r hemorrhage in the preterm infant, Arch Dis Child 51:651, 1976. 4. Arant BS Jr, and Gooch WIII: Effects of acute hyperglycemia on brains of neonatal puppies, Pediatr Res 13:488, 1979. 5. Reynolds ML, Evans CAN, Reynolds EOR, et al: Intracranial hemorrhage in the preterm sheep fetus, Early Hum Dev 3:163, 1979. 6. Tsiantos A, Victorin L, Relier JP, et al: Intracranial hemorrhage in the prematurely born infant, J PEDIATR85:854, 1974. 7. Versmold HT, Kitterman JA, Phibbs RH, et al: Normal aortic blood pressures in newborn infants weighing less than 1000 grams (in preparation). 8. Kitterman JA, Phibbs RH, and Tooley WH: Aortic blood pressure in normal newborn infants during the first 12 hours of life, Pediatrics 44:959, 1969. 9. McMahon B, and Pugh TF: Epidemiology, Boston, 1970, Little, Brown & Co. p 268. 10. ColeVA, Normand ICS, Reynolds EOR, et al: Pathogenesis of hemorrhagic pulmonary edema in the newborn, Pediatrics 51:175, 1973.

Lumbar puncture in the evaluation of suspected neonatal

sepsis Valya E. Visser, M.D.,* and Robert T. Hall, M.D., Kansas City, Kan.

From The Children's Mercy Hospital, University of Missouri, Kansas City School of Medicine, *Reprint address: Department of Pediatrics, University of Kansas Medical Center, Kansas City, KS 66103~

0022-3476/80/061063 + 05500.50/0 9 1980 The C. V. Mosby Co.

EARLY DETECTION of neonatal meningitis is a continuing concern in the Neonatal Intensive Care Unit. Clinical findings alone cannot be relied upon to identify infants with infection, and a high index of suspicion is necessary

10 6 4

Brief cfinical and laboratory observations

for early diagnosis and treatment? 4 In most instances the clinician evaluating the sick neonate performs a lumbar puncture in addition to obtaining other cultures, and antibiotic therapy is initiated pending culture results. However, recent experience with continuous oxygen monitoring has demonstrated precipitous drops in Po2 to hypoxic levels when ill newborn infants are handled or m a n i p u l a t e d Y When a lumbar puncture represents a significant hypoxic stress to an infant in whom cultures are indicated, routine examination and culture of the cerebrospinal fluid in every infant with possible sepsis may be questioned. The present review was undertaken to re-examine the value of a lumbar puncture in the diagnostic evaluation of suspected neonatal infection. Abbreviations used NICU: Neonatal Intensive Care Unit CSF: cerebrospinal fluid GBS: group B streptococcus MATERIALS

AND

METHODS

Two groups of clinical records from a large metropolitan NICU were reviewed retrospectively. The first group consisted of all neonates admitted between July, 1975, and June, 1976, in whom CSF and blood cultures were obtained on one or more occasions as part of evaluation for possible infection. Hospital records were reviewed in detail to determine the incidence of positive blood and CSF cultures, results of CSF analysis, and clinical information. The second group consisted of all infants with positive CSF cultures who were admitted between January, 1971, and June, 1977. Records of these infants were reviewed briefly for age, blood, and CSF culture results, and results of CSF analyses. No attempt was made to retrieve records of infants with meningitis in whom the diagnosis was based on evidence other than a positive CSF culture. The second group included ten cases from the 12-month period initially reviewed in detail. The study groups include both medical and surgical patients, excluding those with congenital anomalies of the central nervous system. During the time periods reviewed, a lumbar puncture was routinely performed prior to antibiotic therapy in all patients in whom sepsis was considered a possible diagnosis. Cerebrospinal fluid was obtained by lumbar puncture in all instances. Samples were transported promptly to the laboratory and inoculated on sheep blood agar and into thi0glycolate broth. An additional aliquot was plated on chocolate agar and incubated in CO.,. Cultures were examined at 24 and 48 hours. CSF protein and glucose concentrations were determined by routine clinical laboratory methods. Cells Were counted unstained in a micro

The Journal of Pediatrics June 1980

counting chamber. Blood cultures were drawn from a peripheral vein after preparation of the skin with povidone iodine. Samples were incubated in trypticase soy broth and subcultured at 24 hours onto chocolate agar for incubation in CO2. A Gram stain was done at 24 hours, and broth and plates were observed for growth daily with final readings taken at seven days. Micrococci and diphtheroids isolated from blood or CSF were considered contaminants. Staphylococcus epidermidis was considered a pathogen if it occurred in multiple cultures or in an infant with an indwelling foreign body (umbilical artery catheter, central venous catheter). Spinal fluid samples were considered inadequate for analysis when there were more than 10,000 red blood cells per mm "~or the quantity of fluid was insufficient for determination of glucose and protein content. RESULTS During the 12-month period reviewed in detail, 522 sets of concurrent blood and CSF cultures were obtained from 400 infants. Birth weights of the infants ranged from 634 to 5,650 gin, and gestational ages from 25 to 42 weeks. Postnatal age at the time of evaluation for possible sepsis ranged from 4 hours to 79 days. Clinical findings and indications for culture did not distinguish those infants with positive blood or CSF cultures from those with negative cultures, nor those with meningitis from those who had septicemia without meningitis. Blood or CSF was contaminated in six instances; those episodes were excluded. From the remaining 516 sets of cultures, 40 (7.8%) episodes of sepsis or meningitis were identified (Table I). Organisms were isolated from the blood in 39 (7.6%) instances. One additional infant had Escherichia coli isolated from the CSF but had a negative blood culture; the reason for the negative blood culture was not clear, but no source for meningitis other than the hematogenous route was present. He was felt to have septicemia in spite of the failure to isolate organisms from his blood, and was the only infant with meningitis whose blood culture was negative among the 516 sets of cultures surveyed. Organisms were isolated from 10 (!.9%) of the CSF specimens. In addition, there was one infant with group B streptococcus septicemia in whom the CSF culture was negative but CSF pleocytosis was present (1,100 WBC/ mm 3, 20 RBC/mm3). He had received a dose of penicillin prior to transfer to the NICU and was felt to have partially treated meningitis. When this infant is included in the meningitis group, a total of 11 of the 516 (2.1%) episodes surveyed proved to be meningitis, and 11 of 40 infants (27.5%) with septicemia had meningitis. Cerebrospinal fluid was re-examined in 13 of 29 infants With

Volume 96 Number 6

septicemia in whom initial CSF culture was negative. Repeat culture was negative in all instances, and there were no samples with pleocytosis suggestive of partially treated meningitis. In four cases, portmortem examination confirmed the absence of infection in the meninges and brain. A larger number of cultures (323) was obtained in infants less than 72 hours of age (early-onset age group) than in older infants (193 cultures), but the incidence of septicemia was similar in both age groups, 19 of 323 (5.9%) and 21 of 193 (10.8%), respectively. The incidence of meningitis among infants with septicemia did not differ in the early and in the late-onset groups, occurring in six of 19 early-onset and five of 21 with late-onset disease. In no instance were different organisms isolated from concurrent blood and CSF cultures. Clinical details of infected patients from the 12-month survey are available from the authors on request. During the six and one-half-year period surveyed, 39 instances of meningitis were identified by positive CSF culture, including the ten from the group initially reviewed in detail (Table II). In 33 of 39 cases (85%) the organism was also isolated from the blood, but in six of 39 instances (15%) the concurrent blood culture was negative. In no case were different organisms isolated from blood and CSF. Infants less than 72 hours of age (early-onset meningitis) accounted for 20 of the 39 (51%) cases. Nine of these infants were less than 24 hours of age at the time cultures were obtained. Three of the infants with negative blood cultures were found in this group, two from infants with GBS meningitis and the third from the infant with Enterobacter meningitis. T h e three remaining patients with meningitis whose concurrent blood cultures were negative were an 11-day-old infant with E. coli meningitis, a 48-day-old infant with S. aureus meningitis, and a 24-day-old infant with a gram-negative rod which could not be identified with certainty. Blood cultures were positive in the remaining 16 of 19 infants with late onset meningitis. Initial CSF samples from 21 of the 39 infants with meningitis were adequate for analysis. Protein content greater than 200 mg/dl and a WBC greater than 25 cells/mm3 were found in 12 of 21 (57%) samples. Glucose concentration was less than 25 mg/dl in seven of the 12. Concomitant blood glucose was not determined in most cases, but a Dextrostix (Ames Co., Inc.) estimate of greater than 45 mg/dl was recorded within one hour of the lumbar puncture in all instances. One Sample had an elevated protein concentration but a normal WBC count and glucose, and two samples contained an increased number of WBCs but normal protein and glucose con-

B r i e f clinical a n d laboratory observations

10 6 5

Table I. Results of concurrent blood and CSF cultures from 516 episodes of suspected neonatal sepsis in 400 infants

Group B streptococcus Eseherichia coli Staphyloeoceus epidermidis Staphylococcus HUMUS Klebsiella sp

Enterococcus Hemophilus influenzae Listeria monocvtogenes Enterobacter

Early onset

Late onset

Blood I CSF

Blood ] CSF

8

Total Blood

CSF

2+ It

0

0

8

3

3 + 1*

3

2

1

6

4

2

0

6

2

8

2

1

0

4

0

5

0

0 1

0 0

5 3

1 0

5 4

1 0

2

0

0

0

2

0

1

0

0

0

l

0

0

0

1

l

1

1

19

6

21

5

40

11

sp

*One additional infant felt to have E. coli septicemia, see text. t O n e additional infant felt to have GBS meningitis, see text.

Table II. Results of concurrent blood and CSF cultures from 39 neonates with meningitis Early onset Blood

Group B streptococcus Escherichia coli Staphylococcus epidermidis Staphylococcus aureus Klebsiella sp Streptococcus pneumoniae

a-Hemolytic streptococcus Hemophilus influenzae Enterobaeter sp Proteus sp

Gram-negative rod

[ CSF

Late onset Blood

CSF

0 7 a

0 8 4

7 7 0 0 0

9 7 0 0 0

1 1 1

1 1 1

0 0 0

1 0 0

0

1

I7

20

16

19

1

2

2 0 0 0

2 0 0 0

1 1

1 1

tents. The remaining 6 (29%) adequate samples of CSF from which organisms were isolated (E. coli (2), Klebsiella, S. pneumoniae, S. epidermidis, and the unidentified gram-negative rod) showed no evidence of infection on chemical analysis or cell count. Subsequent examination of the CSF from 12 to 48 hours later in five of the six infants revealed pleocytosis > 25 cells/mm 3, protein > 200 mg/dl, or both. The sixth patient and two of those

10 6 6

Brief clinical and laboratory observations

with repeat lumbar punctures died; postmortem examination confirmed the presence of meningitis in those three infants. There was no relationship of these six infants with the six infants whose blood Cultures were negative. Cerebrospinal fluid samples from the six infants with positive CSF cultures accompanied by negative blood cultures resembled those in the total group. Three samples were inadequate for interpretation; two contained elevated protein content and pleocytosis, and one was normal. DISCUSSION Previous reports of neonates with proven sepsis have consistently indicated that meningitis was present in approximately one third of patients. In Dunham's 7 series of infants with sepsis prior to antibiotic usage, nine of 39 had meningitis. In a later report from the same institution, Nyhan and Fousek ~ found 31 of 106 infants with sepsis to have concurrent meningitis. More recently, sepsis caused by group B streptococci has been accompanied-by meningitis in about.30% of cases? In the present review, 27.5% of neonates with proven sepsis also had meningitis. Infants who acquired septicemia whilehospitalized in the NICU under constant supervision of trained personnel (lateonset group) still had a 23.8% incidence of meningitis (5/21). This observation is consistent with the data of Hemming et al 1~who found meningitis in 9 of 31 infants (29%) with nosocomial bacteremia. Thus, the incidence of meningitis among septicemic neonates is unchanged since the preantibiotic era and regardless of predominating organisms. Increased awareness of the possibility of infection in neonates with n0nspecific clinical signs, accompanied by prompt attention to obtaining cultures and beginning antibiotic therapy, has done little to alter the spread of infection to the meninges in the neonatal age group. The large percentage of infants (6/39) with normal CSF chemistry and cell count whose cultures were positive has not been previously reported. Subsequent examination of the CSF and autopsy data confirmed the diagnosis, excluding contaminated specimens as the cause of the findings. It is likely that the lumbar puncture was performed at the first clinical sign of infection, at which time the CSF had been seeded with bacteria but had not yet developed an inflammatory response. Long-term records of Gram stains were not available, but are generally less than uniformly positive in infants with positive cultures. These findings indicate that the diagnosis of meningitig cannot be excluded by normal CSF Chemistry and cells and that antibiotic therapy should be given as clinically indicated until culture results are available.

The Journal of Pediatrics June 1980

An additional problem is presented by the infant with respiratory insufficiency who is at risk for infection but whose clinical condition suggests that the risk of hypoxia from performing a lumbar puncture may be greater than the likelihood of detecting meningitis. Currently admissions to the NICU include large numbers of such acutely ill neonates in whom infection is nearly always a possibility, especially in the first fewdays of life. In the earlyonset group in the present series, approximately 50 negative lumbar punctures were performed for every one that was positive. Thus, the practice of performing a lumbar puncture routinely in every infant at r i s k for infection might be questioned. However, the results of the present review substantiate traditional recommendations. Failure to obtain a lumbar puncture unless a blood culture was positive woUld have resulted in missing 6 of the 39 (15%) cases of meningitis in the present group. Furthermore, this finding was not confined to the earlyonset age group, in which indications for culture are present in a higher percentage of infants tha n in the older age group. Lumbar puncture should not be omitted from the routine evaluation for infection in any neonate Unless clinical judgment dictates that performance would potentiate dramatic and irreversible changes in the infant's condition. However, gentle manipulation and careful attention to ensure adequate oxygen administration during the procedure must be provided. I f lumbar puncture must be postponed because of an infant's unstable condition, a single negative blood culture does not rule out the poss!bility ~)f meningitis, and CSF should be examined for evidence of partially treated meningitis as soon as the condition permits a lumbar puncture. Appropriate therapy for meningitis should be continued if analysis of the CSF suggests partially treated disease.

REFERENCES

1. Ziai M, and Haggerty RJ: Neonatal meningitis, N Engl J Med 259:314, 1958. 2. Groover RV, Suthertand JM, and Landing BH: Purulent meningitis of newborn infants, N Engl J Med 264:1115, 1961. 3. Fosson AR,. and Fine RN: Neonatal meningitis, Clin Pedlatr 7:404, 1968: 4. Overall JC: Neonatal bacterial meningitis, J PEOIATR 76:499,. 1970. 5. Huch R, Huch A, Albani M, Gabriel M, Shulte F J, Wolf H, Rupprath G, Emmrich P, Stechele U, Duc (3, and. Bucher D: Transcutaneous pO~ monitoring in routine management of infants and children with cardiorespiratory problems, Pediatrics 57:681, 1976. 6. Speidel BD: Adverse effects of routine procedures on preterrn infants, Lancet 1:864, 1978.

Volume 96 Number 6

Brief clinical and laboratory observations

7.

Dunham EC: Septicemia in the newborn, Am J Dis Child 45:229, 1933. 8, Nyhan WL, and Fousek MD: Septicemia of the newborn, Pediatrics 22:268, 1958. 9. Wientzen RL, and McCracken GH: Pathogenesis and

10.

10 6 7

management of neonatal sepsis and meningitis, Curr Probl Pediatr 8:1, 1977. Hemming VG, Overall JC, and Britt MR: Nosoeomial infections in a newborn intensive care unit, N Engl J Med 294:1310, 1976.

Contractures in a newborn infant of a mother with myasthenia gravis Lewis B. Holmes, M.D.,* Shirley G. Driseoll, M.D., and Walter G. Bradley, D.M., F.R.C.P.,

Boston, Mass.

N E O N A T A L MY A ST H E N I A occurs transiently in about 12% o f infants b o r n to mothers with myasthenia gravis. 1 The s y m p t o m s o f generalized muscle weakness, difficulty with feeding, and an expressionless face usually begin within the first 24 hours after birth and last a few weeks. W e report a n e w b o r n infant with multiple flexion contractures, born after a p r e g n a n c y in which his m o t h e r ' s

weeks of pregnancy she could appreciate no fetal movement for about four weeks. Thereafter, she thought the fetal movement was not as strong as in her first two pregnancies, and the movement had a fluttering quality. The mother had an unexplained febrile illness at about three weeks of gestation, but did not record her body temperature, She had a brief episode of vaginal bleeding and cramping abdominal pain 36 days after her last menstrual period.

s y m p t o m s exacerbated soon after conception. This observation, c o m b i n e d with an earlier report that a w o m a n

See related article, p. 1052.

with myasthenia gravis had two stillborn fetuses with multiple flexion contractures, 2 suggests that maternal myasthenia gravis may produce contractures in some exposed fetuses.

CASE REPORT This 2,360 gram male infant was born to a 29-yearTold, gravida 3 mother at 37 to 38 weeks of gestation. In retrospect the mother believed that she could determine the exact date of conception. She noted the sudden onset of muscular weakness "the morning after .conception" including slurring of her Speech, inability to extend her fourth and fifth fingers, ptosis, and diplopia. These symptons fluctuated in severity from day to day, but became progressively worse as the pregnancy continued. She noted fetal movement at about 13 weeks of pregnancy. Beginning at 20

From the Children's Service, Massachusetts General Hospital, the Departments of Pediatrics and Pathology, Boston Hospital for Women and the Departments of Pediatrics and Pathology, Harvard Medical School," the Department of Neurology, Tufts-New England Medical Center and Tufts University School of Medicine. Supported in part by National Institutes of Health Grants (HD 09689 and HD 10910) and a grant from the National Foundation-March of Dimes. *Reprint address: Genetics Unit, Massachusetts General Hospital. Boston, MA 02114.

0022-3476/80/061067+03500.30/0 9 1980 The C. V. Mosby Co.

At birth the infant had flexion contractures of the metacarpalphalangeal and proximal interphalangeal joints of all fingers: lack of flexion (symphalangism) of the distal interphalangeal joints of the second, third, and fourth fingers with absence of the flexion creases; overlapping by the second and fifth fingers of the adjacent medial fingers (Figure); everted feet; prominent heels; syndactyly of toes 2 and 3; short sternum (5 cm; less than third percentile0; small chin; prominent occiput (head circumference 34.4 cm; fiftieth percentile0; narrow palpebral fissures (width 1.6 cm; third percenti!e:~) and cryptorchidism. The Apgar scores were 2 at one minute and 4 at five minutes. Resuscitation was necessary to initiate breathing. A pneumothorax occurred and the infant died at 14 hours of age. The autopsy showed a normal lung weight (27 gin); there were no abnormalities of spinal cord or of skeletal muscle, and no visceral anomalies. Anoxic changes were present in the cerebellum and hippocampus. The placenta was bipartite and congested, but otherwise normal. Chromosome analysis on peripheral lymphocytes showed no abnormalities on quinacrine and Giemsa-trypsin banding. The mother's muscle weakness improved markedly after delivery. A neurologic evaluation a few weeks later demonstrated weakness of several muscle groups; a Tensilon test showed recovery of the paresis of the right medial rectus muscle. The serum level of antibodies to acetylcholine receptors (Clinical Immunology Laboratories, Santa Monica, Calif.) were 50 to 100 times normal on two occasions. Her symptoms improved drama-