Neurological Sequelae of Group B Streptococcal Neonatal Infection

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Neurological

Sequelae

of Group

B Streptococcal

Neonatal

Infection

Kenneth A. Horn, M.D., Robert A. Zimmerman, Ph.D.,

James D. Knostman, M.D., and

w.

Terrence Meyer, M.D.

From the Fort Collins Laboratories, Ecological Investigations Program, Center for Disease

Control, Health Services and Mental Health Administration, Public Health Service,

Depart-n2ent of Health, Education, and Welfare

ABSTRACT. Eighteen survivors from a series of 44 in-fants with neonatal group B streptococcal infection were

examined from eight weeks to four years later for possible long-term neurological sequelae. Of six infants with lab-oratory-validated group B streptococcal meningitis, one

died at 1 1 months of age as a result of complications of hydrocephalus, and another infant was found to have minor neurological sequelae. Of the remaining 12 infants with

documented or probable group B sepsis, two were found

to have neurological residua. The combined morbidity and mortality rate in the group of 44 infants was 50% (18 deaths and four sequelae). Pediatrics, 53:501, 1974, NEU-ROLOCICAL SEQUELAE, GROUP B STREPTOCOCCAL INFECTION, 50% MORBIDITY AND MORTALITY, NEWBORN INFANTS,

PEE-MATURE INFANTS.

Neonatal septicemia with or without meningitis still presents a major problem to the pediatrician with regard to outcome. Studies concerning mor-bidity associated with neonatal meningitis, specifi-cally long-term neurological sequelae, have demon-strated a 20% to 1J%1.5-8 incidence of permanent

residua. To our knowledge, no comparable studies of neonatal sepsis without meningitis have ap-peared. During the past year, a reemergence of neonatal group B streptococcal infection has been documented,24 with infection rates estimated to be as high as 3/1,000 live births and mortality at

1/ 1,000 live births.2 The only previously documented incidences of sequelae to group B infection were reported as 4.4% by Baker et al.3 and 11.0% by Bar-ton et al.4

We here review the clinical course of survivors among 44 neonates with group B infection with respect to possible neurological sequelae. The epi-demiology and clinical presentations of 43 of these cases, accumulated over a two-year period, have been recently presented.2

MATERIALS AND METHODS

The original study group of 43 infants was

di-vided into three separate categories based on age of pnset, clinical presentations, and specific group B culture findings.2 All clinical material was oh-tamed from two Denver hospitals.

Group l-.Acute Onset Sepsis

Seventeen infants with onset of symptoms with-in the first 24 hours of postnatal life were diagnosed as having sepsis by positive blood culture. All pre-sented with respiratory distress and had congenital pneumonia on x-ray or at postmortem examination. Six of the 17 had positive cerebrospinal fluid

(

CSF) cultures in addition to the positive blood culture. Five of these died, but only one had evidence of leptomeningeal inflammation on autopsy. The over-all mortality in group I was 71%

(

12 of 17) with essentially equal rates in premature

(

seven of nine) and full-term (five of eight) infants. Of the five survivors, two were premature and had B-Il in-fections; the remaining three survivors had B-Ill serotypes. No infants with B-I serotypes survived.

Group Il-Delayed Onset Sepsis

Eleven infants with onset of symptoms between the ages of 2 and 8 weeks were diagnosed as hay-ing meningitis on the basis of positive CSF

cul-ture, pleocytosis, elevated protein and decreased glucose.

The mortality rate in these infants was 45%, with

all four prematures dying as contrasted to one

( Received July 10; revision accepted for publication

Sep-tember 27, 1973.)

ADDRESS FOR REPRINTS: (K.A.H.) Fort Collins

Lab-oratories, P.O. Box 2087, Fort Collins, Colorado 80521.

at Viet Nam:AAP Sponsored on September 8, 2020 www.aappublications.org/news

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I-12 Zso7 U 1h N ass’ as1o Signs 4

Grt lag rospirat ton #{149} dane-sia, acidosis. shock. CU

-bilateral 1sf iliratas.

Grti.1 rasplrstion,

cyano-ste. - .s1b1. pssn1a. Crsseisg respiration,

cyane-sin, icteric, V! 3500, T. p1.4#{176},CU - bilatersi

iaflltrstss.

Type of

Anti-Group I biotlc 1’ at asu1ts of

Isolated Thsrapy ?ollovup Follow-up PigLo

11 V iii:

16 sos. 13 sos. 2-7/12 years Sorasi ezss hovel ex Sorsal ezss V V N V I 1, as 27 a so 31 4171 Moo 3774 Mu 314

w i7,, T. 103#{176}.

Positive Culture for

Group B Streptococcus

ACt’!! SFPSIS

Hood, CS:, throat;

astersal vagina.

Blood; asternal

vagina.

Stood, gastric

aspi-rate: asternal vagina

DfLAYED WPSIS

CS,, throat.

CS,, blood; asternal

vagina.

CS?, blood.

CSF, blood, nose, throat.

CS,, blood; asternal vagina.

PROMBLE SFPSIS

Throat.

Urine, nose. throat.

Throat. vagina,

bil-icus; aatsrnal vagina.

Throat #{149},nbilicu..

Throat. urine, chest

tube drainage; maternal vagina. Gastric aspirate. Gastric aspirate, throat. rine, bi1icus, azilLary lesion. , hr 4 hr Uhv 14 4. S vhs 14 4. 4 vhs 17 4. so hr 4 hr 4$ hr 0 6 hr 0 0 S hr ‘4. 24.

32 V Mo7

III III UI III III III III III Ic ‘a ‘a ‘a ‘a I’ I’ I’’ I’’ lb A, K A, K A, K p p A, P A, K A A, K p. K P P P p P A A A,K 18 sos. 20 sos. 3-6/12 years 19 sos. 8 sos. 2-8/12 years 22 sos. 20 sos. 21 sos. 12 sos. 12 sos. 2-6/12 years 19 sos. 15 sos. 33 3’ 3, 30 so 40 44 V N V V V N N 1501 2504 23 229$ 2334 2300 Nornel ez Infantile speech, norsal audiogrea

Delayed sotor

sue-stones ; poor lasguae

and fine sotor skills

Noraal ez

Weight <third

perc.s-tile, othervise neraal

ez

Noraal ezas

Itorsal ez

Cleft lip, palate;

bilateral congssital

hip dislocation; club foot; norsal netor 4

intellectual function

Sorsal ezss

Norsal az lafused feedings, cyanosis,

WN: 36,000, T. 102#{176},CXI - nag.

Poor fssdin, lethargy,

jaun-dice, - KLL pnawionta.

a Antibiotic Therapy: A - Anpicillin, K #{149}Kmnycin, P #{149}Penicillin G.

4 Qsst I-ray.

4 Cerebrospinal Fluid.

)bther and father positive for Group 8-Ill during second pregnancy - treated. I ite lined Count.

. Zzisations perforasd by private physician. ProIos$ed Rupture of Mbrana..

502 STREPTOCOCCAL INFECTION

TABLE I

CLINICAL DATA ON 18 SuRvlvoas OF GROUP B STREPTOCOCCAL NEONATAL SEPSIS

Birth Ass

e.s

() .t

Fswsr, trsat.d vith 1ci11in

for 10 dais; at S .ska

lsth-irgy, bulgiog faota*wll., sitzur#{149}s.

IrrIt.sb1, v1t1o$.

T. 102.6

Irritable, fevor, s.izur.., T. 102.40.

Poor fssdia, cyanosis.

w 6, T. 9.$#{176}.

Cyanosis. apono, T. 99.5#{176}.

Cu - bilateral infiltrates.

0

Raspiratory distress, T. 97 cxi - Rp1ratory Distress

5yndr.

Ictesic at birth, purulent

ohs1itis and vaginitis.

Fbrils noth.r, breech;

icteric.

Cyanotic, T. 99#{176},cxi

-tension pn.thoraz.

Tviu, P1f516 25 lirs: C-section;

jittery: positive gastric.

Yvin, seconita stained; positive gastric.

Wultiple congenital anosalies, siniasi respiratory distress, pustular azillary lesion.

Stool; saternal

vagina.

go5., throat, azilLs, stool; asternal vagina.

Died at

11 sos.

Hydrocephalus ; sbt.d at 2 sos., severs psychtor retarda

t ion

1orssl ez

Norsal ez

Perceptual probl,

e.otropi.a, bead cir ciaference >97 per-centile, delayed si lestooss.

Nornel ez

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death in seven full-term infants. The only serotype isolated in all cases was a B-Ill.

Group Ill-Probable Sepsis

Fifteen infants were clinically diagnosed as prob-able sepsis but without confirmation of a positive blood culture. All infants did, however, have at least one positive culture for group B from a site other than blood or CSF. There was only one death in this group, giving a mortality rate of 6.6%. Ten

full-term infants survived, the only death being in

one of five prematures who was positive for a B-Ia from umbilicus, pharynx, and trachea.

FOLLOW-UP EXAMINATIONS

Of the 25 survivors from all three groups, 17 were examined, plus one additional infant not included in the original group but in the category of prob-able sepsis. The 18 survivors examined included 16 full-term infants and two premature infants. All infants were white. Histories as to severe illnesses, hospitalizations, and general development were

obtained from private physicians. All infants

studied had general physical examinations and were evaluated developmentally by the Denver Screen-ing Test.#{176}All screening was done by one of us

(

K. H., a pediatrician) in the home of the patient, except for cases 13, 19, and 40, where examinations and screening were performed by private

pediatri-cians.

RESULTS

Listed in Table I by case number are the per-tinent data concerning each of the infants ex-amined.

Meningitis Follow-up

Six infants with group B meningitis were studied; five of them had delayed onset illness and one

(

case 12) had acute onset. Two of these six were found to have sequelae.

The patient in case 18, as described in Table I, developed hydrocephalus as a result of her men-ingitis. Her death at 11 months was thought sec-ondary to a shunt infection; no postmortem ex-amination was performed.

A 3,660-gm male infant

(

case 27) was delivered by cesarean section because of prolonged labor and premature rupture of membranes for 26 hours. At 4 weeks of age he presented with a history of poor feeding, cyanosis, and fever. The hospital course related to the meningitis was uneventful; however, the infant was found to have bilateral hydronephrosis secondary to ureteral-pelvic oh-struction and a pyelostomy was performed. The infant has since been hospitalized twice : once for bilateral pyeloplasty and once for strabismus repair.

Sepsis Follow-up

Of the 12 infants studied, two were found to have neurological problems. Case 31 is a 3,149-gm male infant born of an uncomplicated pregnancy whose Apgar score was 9,9. At 4 hours of age he developed respiratory distress and hypothermia. Chest x-ray was compatible with RDS. Cultures

of urine (suprapubic), nose, and throat were

posi-tive for B-Ia. He was treated with penicillin and kanamycin for ten days and had an uneventful hospital course.

At 18 months of age he had poor speech and language development, though an audiogram was normal. Examination at 32 months still demon-strated speech and language problems with grossly normal hearing.

Case 32 is a 3,887-gm female infant who was the product of an uncomplicated delivery, Apgar 9,10. Jaundice was noted at 48 hours of age as well as a purulent discharge from the umbilicus and va-gina. Cultures of cord and throat were positive for B-Ia. The patient was treated with penicillin

for five days. The hospital course was uneventful. At 22 months, the infant showed delayed motor milestones, poor speech, and poor fine motor skills.

DISCUSSION

Thirty-three percent of the infants with sequelae in the B-Ill meningitis group compare to previous

reports of morbidity by Dodge8 (20%), Watson5

(

31%

)

, Sell7

(

44%) , Sproles#{176}

(

47%

) ,

and OveralP

(

50%), where etiologic agents of meningitis were other than group B streptococci.

Of the two meningitis patients with sequelae, one (case 18) emphasizes several aspects of mor-bidity and mortality in neonatal infection. The in-fant was febrile at 2 weeks of age and was treated

with orally administered ampicillin until the time

of hospital admission 2% weeks later. Otherwise unexplained fever in a neonate almost always

re-quires a complete sepsis work-up, which includes

a spinal tap and blood and urine cultures. Delay in diagnosis, specifically when one is dealing with meningitis, probably plays a great role in increas-ing mortality and morbidity.5’1#{176} Almost certainly the delay in this child’s diagnosis and appropriate therapy led to the major complication of hydro-cephalus and eventual death.

With little or no reference data concerning mor-bidity in neonatal sepsis without meningitis, it is

difficult to draw any conclusions from two infants

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504 STREPTOCOCCAL INFECTION

of 9,10 and were products of normal, uncompli-cated pregnancies. The patient in case 31 did have

respiratory difficulties, was mildly acidotic, and

re-quired 60% oxygen for a short period of time. The patient in case 32 did not have any evidence of

acid-base imbalance; and although she was

jaun-diced

(

mother A+

,

baby A-), her bilirubin peak

was only 11.7 mg/100 ml. Neither infant has had any subsequent major illnesses or hospitalizations.

Overall morbidity and mortality in our series of 44 patients is 50%

(

18 deaths and four sequelae).

We recognize the lack of a control group of

in-fants in this series. The possibility of chance

asso-ciation of neurological problems in these infants with their group B infection, rather than a true association, is also appreciated. We are recording our small experience with the hope that others with similar experiences will do the same.

SUMMARY

Eighteen survivors from a series of 44 infants with neonatal group B streptococcal infection were examined for neurological sequelae. Four of the 18 were found to have some neurological residua

(22%) . Combined morbidity and mortality in the

series was 50%.

REFERENCES

1. Overall, J. C., Jr. : Neonatal bacterial meningitis. J.

Pediat., 76:499, 1970.

2. Franciosi, R. A., Knostman, J. D., and Zimmerman, R. A. : Group B streptococcal neonatal and infant

infections. J. Pediat., 82:707, 1973.

3. Baker, J. C., Barnett, F. F., Gordon, R. C., and Yow, M. D. : Suppurative meningitis due to streptococci of Lancefield Group B : A study of 33 infants. J.

Pediat., 82:724, 1973.

4. Barton, L. L., Feigin, R. D., Lins, R. : Group B beta hemolytic streptococcal meningitis in infants. J.

Pediat., 82:719, 1973.

5. Watson, D. G. : Purulent neonatal meningitis: A study of 45 cases. J. Pediat., 50:352, 1957.

6. Sproles, E. J., Azerrad, T., Williamson, C., and Merrill, R. E. : Meningitis due to hemophilus influenzae: Long-term sequelae. J. Pediat., 75:782, 1969. 7. Sell, S.H.W., Merrill, R. E., Dayre, E. 0., Zimsky,

E. P., Jr. : Long-term sequelae of hemophilus in-fluenza meningitis. Pediatrics, 49:206, 1972. 8. Dodge, P. R., and Swartz, M. N. : Bacterial meningitis:

A review of selected aspects: II. Special neurologic

problems, post meningitic complications and din-icopathologic correlations. New Eng. J. Med., 272: 954, 1965.

9. Frankenborg, W. K., and Dodds, J. B. : The Denver

developmental screening test. J. Pediat., 71:181, 1967.

10. McCracken, G. H. : The rate of bacteriologic response to antimicrobial therapy in neonatal meningitis.

Amer. J. Dis. Child., 123:547, 1972.

ACKNOWLEDGMENT

We would like to thank all the private physicians who cooperated with us in the study, as well as Dr. Ralph A.

Franciosi, an investigator in the original study.

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1974;53;501

Pediatrics

Kenneth A. Horn, Robert A. Zimmerman, James D. Knostman and W. Terrence Meyer