The prevalence of bacteriuria in full-term and premature newborn infants

FETAL AND NEONATAL M E D I C I N E RichardE. Behrman, Editor

The prevalence of bacteriuria in full-term and premature newborn infants Examinations o/urine were performed in 836 full-term and 206 prematurely born infants, using specimens obtained by a clean-voided technique and by suprapubic puncture. Persistent proteinuria, leukocyturia, or hematuria was found in none, and none o/these findings correlate well with bacteriologic studies. Bacteriuria was found in 0.7 per cent of the full-term and 2.9 per cent of the premature infants, mostly in asymptomatic subjects. Bacteriuria occurs with sufficient frequency in prematurely born infants to warrent repeated examinations of the urine during their nursery stay. In view o/the difficulty in obtaining adequate specimens of urine, as well as the paucity o/positive findings, routine screening of full-term infants does not appear to be indicated.

Chester M. Edelmann, Jr., M.D., * Joseph E. Ogwo, M.D.,

Burton P. Fine, M.D., and A r m i d a B. Martinez, M.S., Bronx, N. Y.

A N A P P R E C I A B L E, proportion of the female population has had urinary tract infection before adult life?, 2 R a n d o l p h and Greenfield 3 reported bacteriuria in 4.5 per cent of female and 0.5 per cent of male infants during the first 24 months of life, indicating that even at this early age, baeteriuria in the female is a c o m m o n occurFrom the Department o/Pediatrics, Division o/ Pediatric Nephrology, and the Rose F. Kennedy Center, Albert Einstein College o/Medicine. Supported in part by Public Health Service Contract 86-67-299, National Institutes o/ Health Grant No. AM 14877 and HE 05267, The Kidney Foundation o/New York, Inc., The Sylvan League, Inc., and the Health Research Council of the City of New York, 1-605. aReprint address: Rose F. Kennedy Center, 1410 Pelham Parkway S., Bronx, N. Y. 10461.

rence. Several studies have reported the frequency of bacteriuria in the newborn infant to range from as low as 0.1 per cent to as high as 25 per cent. ~-1~ Since young infants are unusually prone to infection, and they may exhibit remarkably little systemic response to serious degrees of infection, it is important to know if asymptomatic bacteriuria in fact is c o m m o n in this population.

MATERIAL AND METHODS T h e initial plan was to survey infants using a bag technique, to re-examine (with a bag collection) all infants with bacterial counts > 10 4, and then to perform suprapubic aspiration of urine on those infants with two positive cultures. Since full-term infants remain in our nursery no more than two to Vol. 82, No. 1, pp. 125-132

12 6

Ede[mann et al.

three days, there was no opportunity to do suprapubic punctures in some of those with one or two positive bag specimens. Therefore, the protocol subsequently was changed so that full-term infants whose initial examination revealed 104 or more organisms per milliliter were examined the second time using urine obtained by suprapubic puncture. In premature infants, with prolonged stays in the nursery, this was not a problem and suprapubic punctures were reserved for infants with two or more positive cultures from "bag urines" and those about to be started on antibiotic therapy. Clean-voided urine was collected by one nurse, according to the following technique. The perineum was washed thoroughly. Initially this was done with pHisoHex and benzalkonium chloride. Subsequently, cleansing with green soap was substituted. The washing was followed by thorough rinsing with sterile saline. The perineum was then patted dry with a sterile gauze pad, and a sterile plastic bag (Pediatric Urine Collector, PUC-10S) was affixed over the vulva or penis. Each infant was examined frequently thereafter to assure removal of the bag within five to ten minutes after voiding had occurred. If a stool was passed or if more than 60 to 90 minutes had elapsed without obtaining a specimen, the bag was removed, the perineum was cleansed again, and a new bag was applied. Most specimens were obtained within 30 minutes following feeding. The urine samples were stored in the refrigerator for 10 to 60 minutes (and in rare instances up to 120 minutes) prior to their being taken to the laboratory. Urine examination was then performed immediately. For urinalysis, 5 ml. of urine was centrifuged for five minutes at 3,000 r.p.m. The supernatant urine was tested for protein with Albustix. Sediment was examined under a coverslip, and numbers of cellular elements and casts were counted per high-power field. Quantitative bacterial counts were done using 1 : 2 and 1 : 1,000 dilutions of urine and counting of colonies on pour plates. Urine was incubated for bacterial growth and identi-

The Journal o[ Pediatrics January 1973

fication on MacConkey, trypticase soy, and blood agar. Identification was performed using the Imvic procedure. ~ Antibiotic sensitivity testing was done with a Muller-Hinton medium. Statistical analyses were performed by chi square and analysis of proportions? a RESULTS

Full-term infants. The study included 836 infants, 384 males and 452 females.

Proteinuria, Ieukocyturia, and hematuria (Table I). Trace proteinuria was found in 22.6 per cent of males and 24.6 per cent of females. Forty-three per cent of infants with bacterial counts =>104 and oniy 25 per cent of those with counts <104 had proteinuria. This difference is statistically significant (X2 = 7.08, p < 0 . 0 1 ) . Seventeen infants (2.0 per cent) had 1 + or more proteinuria on one specimen. Only three of these had bacterial counts >_-1@ on their initial specimen, and they had no growth or < 1 0 a on subsequent examinations. Repeat urinalysis failed to demonstrate persistent proteinuria in any infant. Only two infants had more than 2 to 3 white blood cells or 0 to 1 red blood cells per high-power field. These findings were transient and did not correlate with other evidence of disease, including bacteriuria. Many infants had large numbers of epithelial cells in the urine, which could easily have been mistaken for abnormal leukocyturia. Bacteriuria (Table I). Initial cultures in 77.6 per cent revealed no growth. An additional 9.4 per cent had bacterial counts ranging up to 103 per milliliter, and 7.1 per cent had counts ranging from 10a to l0 w per milliliter. Thus 94.1 per cent of the entire group had bacterial counts considered nonsignificant. No subsequent systematic attempt was made to obtain urine from these infants. The bacteriologic findings in the 49 fullterm infants with initial counts ~104 are *The mnemonic refers to a series of reactions involvong testing for Indol production, using ether and Ehrlich's reagent; detection of pH changes with Methyl red; use of the Voges-Proskauer procedure for identification of anaerobic organisms; and final pit testing during growth on medium containing sodimn Citrate.

Volume 82 Number 1

12 7

Prevalence of bacteriuria

Table I. Initial urinalyses in full-term infants

Bacterial

Entire group Female

Male

counts per ml.

No.

No growth 10-10 a 105-104 104-105 105 Total

303 31 23 19 8 384

I% 78.9 8.1 6.0 4.9 2.1 100

No

I%

346 48 36 14 8 452

summarized in Table II. No differences were found between males and females. A follow-up was obtained within two days in 24 of the 33 infants with initial counts between 104 and 105 per milliliter, including all those with initial counts approaching 105 . I n 11 there was no growth; 8 others had counts < 1 0 4 ; 2 had a different organism in the second culture; and 3 had counts of 15,000, 60,000, and 80,000 per milliliter, respectively, the latter in an infant with diarrhea. All repeat urine cultures obtained with suprapubic puncture revealed no growth. Repeat examination was obtained within two days in 11 of the 16 infants who had initial counts _->105. Nine of these revealed no growth, one had 1,000 organisms per milliliter, and one had >105 of the same organism as in the first culture (E. coli). Thus 49 of 836 or 5.9 per cent of infants had suspicious counts (_>-104) on their initial exam. Repeat examination of 35 of them excluded infection in all but four. Three infants with equivocal results on the first examination had equivocal results on the second. Only one infant had >105 organisms on two successive occasions, both in cultures of bag collections. If one extrapolates these results to include the 14 infants in whom repeat urine could not be obtained, it would be anticipated that repeat examinations would have excluded infection in 12 of these 14, leaving a total of six infants out of the group of 836 suspicious for infection, or 0.72 _+ 0.03 per cent (95 per cent confidence limits). However, it should be noted that no infant was confirmed to have bacteriuria on suprapubic examination, and only

Those with proteinuria

Total No. 649 79 59 33 16 836

76.5 10.6 8.0 3.1 1.8 100

I

% 77.6 9.4 7.1 3.9 1.9 100

No. 162 14 18 13 8 215

I

% 75.3 6.5 8.4 6.0 3.7 100

Table II. Full-term infants with initial bacterial counts ~ 104 per milliliter of urine i

Technique Repeat negative Bag~ Suprapubict

Initial count I Initial count 10~-105 ] >= 10 s 16 5

Repeat positive Bag~ Suprapubiew

3 0

0

No repeat

9

5

Total

33

16

1

~No growth, < 104, or different organism. tNo growth. w

> 10~. growth,

two infants of the entire series had two collections with 105 or more organisms. I n one of these, a third examination by suprapubic puncture revealed no growth. Thus it appears likely that true bacteriuria in the fullterm infant occurs at most in a small fraction of one per cent. Premature infants. This study included 109 males and 97 females. Seventy-eight per cent had two or more examinations of urine, and 34 per cent had four or more examinations. A total of 648 urinalyses were performed, including 571 specimens collected by bag and 77 collected by suprapubic aspiration. Proteinuria, leukocyturia, and hematuria (Table H I ) . Proteinuria was recorded on at least one occasion in 58 infants, or in 28.2 per cent. Only six of these had more than trace protelnuria, and no reaction greater than 2+

1 2 8 EdeImann et aI.

The Journal o[ Pediatrics January 1973

Table I I I . Urinalysis and bacteriologic data in urine from premature infants

Bacterial count

pet ml. 10~ 10'-10 ~ >= 10~ Total

Proteinuria Male J Female Pos. I Neg. [ % Pos. Pos. I Neg, 1 % Pos. 56 16 1 73

185 26 12 223

23.2 38.1 7.7 24.7

was recorded. In all instances, proteinuria was a transient finding, and there was at best a weak correlation with culture results (X2 = 2.37, p = 0.1 to 0.25). Forty-four specimens from 12 females and 22 specimens from 6 males revealed leukocyturia (more than 2 to 3 white blood cells per high-power field), representing 6.0 per cent of the males and 14.8 per cent of the females examined. Leukocyturia correlated with the results of urinary culture (X2 = 4.42, p < 0.05), but was not persistent in any infant. Microscopic hematuria was detected in only 6 of 181 patients examined and was persistent in none. There was no correlation with the presence or absence of white cells or with the results of urine culture. Bacteriuria (Table IV). In almost half the group the initial cultures were sterile. Bacterial counts >_-104 were obtained in one fifth. However, 76 infants or 36.9 per cent either initially or subsequently had bag urines with counts _->104. These included 25 males and 25 females with counts of 104 to 105 and 9 males and 17 females with counts >=105. The higher proportion of females with bacterial counts >=104 is highly significant (X2 = 4.46, p <0.05). Table V shows the results of repeat urine cultures in these infants. In 54, subsequent culture revealed no growth. In another eight, a repeat bag specimen revealed <104 organisms per milliliter. An additional eight infants had positive repeat cultures, four of these in urine obtained by suprapubic puncture, four by bag. Of the latter, however, a subsequent urine culture in three (without treatment) revealed no growth. The final six infants, with initial counts ranging between 14,000 and 26,000

56 t0 8 74

145 25 7 177

27.9 28.6 53.3 29.5

All Pos. I Neg. 1 % Pos. 112 26 9 147

330 51 19 400

32.7 33.8 32.1 26.9

organisms per milliliter, were discharged from the nursery before repeat urine specimens could be obtained. Thus of 76 infants with a positive bag specimen at any time during their nursery stay, bacteriuria was ruled out in 93 per cent of those who had repeat examinations (65 of 70). Bacteriuria was confirmed by suprapubic aspiration in four and was possible on the basis of bag examinations in one. One additional infant had a positive culture following suprapubic aspiration without preceding studies. Of the entire series of 206 infants, therefore, bacteriuria was confirmed in 5, or 2.4 per cent, and may have been present in another one, increasing the frequency to 2.9 _+ 0.32 per cent (95 per cent confidence limits). Of particular interest are those infants from whom urine obtained by bag yielded growths ->_104 organisms on several occasions, whereas there was no growth in urine obtained subsequently by suprapubic aspirations. The most dramatic example of this was in a female infant who had a total of nine examinations. Six bag specimens revealed bacterial counts ranging from 6,000 to 75,000, with changing organisms. The third, fifth, and seventh examinations were done on urine obtained by suprapubic puncture. There was no growth in any of these cultures. This indicates the great uncertainty in establishing the diagnosis of bacteriuria in an infant on grounds other than suprapubic puncture. DISCUSSION

It seems clear that the earlier studies reporting a prevalence of bacteriuria of several

Volume 82 Number 1

Prevalence of bacteriuria 1 29

Male

Po,

I Neg

14 5 3 22

215 35 16 266

Leukocyturia Female

]

I

Pos 6.1 12.5 15.8 7.6

1Neg 32 9 3 44

All

I

162 20 14 196

Table IV. Initial urine cultures in premature infants

Bacterial Males count perml. N o . l %

I

1 16.5 31.0 17.6 18.3

46 14 6 66

42.3 101 49.0 16.5 24 11.6 17.5 40 19.4 14.4 26 12.6 9.3 15 7.3 100 206 100

Initial bacterial count

Technique

Culture

Total

Repeat by suprapubic

No growth Positive

29 4

20 0

49 4

Repeat by bag

No growth < 104 --> 104

4 4

1 4

5 8

3

1

4~

6

0

6t

No

per cent in apparently healthy full-term infants were misleading, in that their results were based on inadequately collected urine specimens. T h e data in this study and others provide ample evidence that a bag or cleanvoided urine is satisfactory only if the result is negative; confirmation of bacteriuria must rest on examination of urine obtained by suprapubic puncture or bladder catheterization. It should be pointed out that the latter procedure has a distinct disadvantage, namely, the necessity of relying on the bacterial count to differentiate between contamination and infection. This is of particular importance in infants, since it is far from clear whether 10 ~ or 105 should be taken as the critical level in these subjects who void frequently. Nevertheless, when suprapubic puncture cannot be done, catheterization of the bladder remains a valuable procedure. As judged from recent studies, including the one reported here, the true prevalence of bacteriuria in full-term infants appears to be somewhere between 0 and 1 per cent, most likely closer to the first figure (Table V I ) . Studies of full-term infants in w h o m bacteriuria was established by repeated bag ex-

,os 10.9 20.3 16.7 12.5

Table V. Repeat bacteriologic d a t a in premature infants with previously positive cultures in bag collected urine

Females Total No.l% No.I%

No growth 60 55.1 41 10~ 8 7.3 16 10a-104 23 21.1 17 104-105 12 i1.0 14 105 6 5.5 9 Total 109 100 97

1 377 55 30 462

repeat

"X'Three of these infants h a d a subsequent culture showing no growth. I n one infant the initial result was 36,000 p e r milliliter Klebsiella. O n repeat there were 11,000 per milliliter of the same organism. t i n these six patients, whose initial bag counts were >-l0 g per milliliter, cultures were not repeated before discharge from the hospital. T h e initial counts ranged between 14,000 and 26,000 per milliliter.

amination 9, 11, 14 or suprapubic puncture s' 15 generally have revealed infection in 0 to 0.1 per cent. An exception to this is the study of O ' D o h e r t y 1~ in which 1.1 per cent of infants were shown to have bacteriuria on suprapubic puncture. However, infants were examined only when the clean-voided urine revealed leukocyturia, so that this represents a selected series of patients. Similarly, Gower and associates 16 studied 229 neonates (including some premature infants) in a special care nursery. Their finding of 0.9 per cent bacteriuria m a y relate to another highly selected population. Littlewood and associates 12 reported finding infection in 8 of 600 infants. In only two were suprapubic punctures done, but repeated bag examinations demonstrated persistent bacteriuria in the other six. Five of these were males, and the authors comment that " . . . it was apparent

130

EdeImann et al.

The Journal of Pediatrics January 1973

T a b l e VI. Bacteriuria in p r e m a t u r e a n d full-term n e w b o r n infants

Reference No. Full-term infants 4 5 8 9 10 11 12 I4

Method of collection o.( urine Bag + Cath Bag Bag + SP Bag SP

PTeualen ce

Sex Male IFemale ] Total 100 298 99 579 410

100 286 63 421 42O

- -

Bag Bag

15

Bag

15 Present study

Bag + SP Bag + SP

309 90 --

- -

384

1 8 0

1 1 0

1

9 5 7 0

--

452

Male [Female ] Total

--

--

3

--

--

--

--

0

--

--

0

6

0.8

0.7

0.7

- -

- -

--

--

-

-

8 , 0 0 0

600 200 268 100 836

(%)

1.0 1.5 0 0.1 1.1 0.1 1.3 0 1.1

200 584 162 1,000 830

291 110 --

--

Bacteriuria Male [Female I Total

3

2 9 0

1.0 2.6 0

1.0 0.3 0

0

1

0.2

0

0 4 1 0

9 9 8 0

2.2 -2.3 0

0 -0.3 0

3

Premature infants 7 17 18 Present study

Bag SP Bag + SP Bag + SP

29 97

72 102 54 206

--

---

229

--

--

---

--

25 109

-

- -

- -

--

--

-

-

-

t8 10 3

-

4

2

---

-

-

25.0 9.8 5.6

6

3.7

2.1

2.9

--

2

--

--

--

2

--

--

0.9 3.4

Full-term and premature in[ants 16 19 Cath

~

Bag + SP SP

59

catheter, SP ---- suprapubic aspiration.

that some were recovering spontaneously before t r e a t m e n t was instituted." T h e possibility of c o n t a m i n a t i o n from the p r e p u t i a l folds, therefore, as suggested by Lincoln a n d Winberg, 5 must be considered in this series. I n the study of M c C a r t h y and Pryles 4 a nonselected p o p u l a t i o n was examined a n d bacteriuria was confirmed by e x a m i n a t i o n of urine obtained by b l a d d e r catheterization. T w o of 200 infants, or 1.0 p e r cent, were found to be bacteriuric. Since the 95 p e r cent confidence interval of this value includes zero, it is difficult to determine if the higher prevalence of bacteriuria in this study relates to the technique of urine collection or if it is simply fortuitous. I n the present study, a survey of 836 fullterm infants revealed bacterial counts =>104 p e r miIliliter in 49, or 5.9 p e r cent. Bacteriuria was ruled out in every infant with an initially positive result who was re-exa m i n e d by means of suprapubic puncture. Bacteriuria was established unequivocally in none, a n d incompleteness of examination left equivocal the status of six infantts. If all of these did in fact have b a c t e r i u r i a - - a most

unlikely s i t u a t i o n - - t h e over-all prevalence would have been 0.7 per cent. O n the other hand, true bacteriuria m a y have been present in none. T h e frequent occurrence of positive results on bag urine samples a n d negative results on repeat examinations raises the question of the possibility of intermittency of bacteriuria. W e did not collect bag specimens at the time of p e r f o r m i n g s u p r a p u b i c punctures. I t would seem an e x t r a o r d i n a r y coincidence, however, that intermittent bacteriuria was present only when a bag was applied, a n d was absent each time we decided to do a suprapubic puncture. A l t h o u g h the prevalence of bacteriuria in p r e m a t u r e infants is probably nowhere n e a r the figure of 25 p e r cent reported by H o d g m a n and associates, 7 it seems to be considerably greater than in full-term infants. Pendarvis and associates, 17 using suprapubic puncture, found bacteriuria in 10 of 102, or 9.8 p e r cent of p r e m a t u r e infants. Zies a n d associates is reported positive results in 3 of 54 infants, or 5.6 p e r cent. Nelson a n d Peters 19 studied both full-term a n d p r e m a -

Volume 82 Number 1

ture infants and found infection in two of 59, or 3.4 per cent of the total. However, both infected infants were premature. It is difficult to be certain of the number of premature infants in the total of 59, but if there were no more than the 25 shown in their Table I, the rate of positive cultures in the premature infants may have been as high as 8.0 per cent. T h e present series of 206 premature infants is the largest reported to date. Five infants or 2.4 per cent were shown by suprapubic puncture to have bacteriuria. In another one or two, in whom urine was obtained only by bag, bacteriuria may have been present. We conclude, therefore, that bacteriuria was present in our series in at least 2.4, and perhaps in as many as 3.4 per cent. With either estimate, the 95 per cent confidence limit of the m a x i m u m estimate of the true mean is 5 to 6 per cent. It has been suggested by a number of authors that the finding of leukocyturia should strongly suggest the possibility of bacteriuria and lead to appropriate examination of the urine. Thus O ' D o h e r t y 1~ recommends performing suprapubic bladder aspirations only in infants in whom clean-voided urines have shown leukocyturia. However, no data are given to support this recommendation. In the present study, only two of the fullterm infants had more than 2 to 3 white blood cells per high-power field. Neither was infected. None of the infants suspicious for infection had leukocyturia. In the premature infants, leukocyturia was found in 9.9 per cent, twice as often in females as in males. It was not persistent but was found more often in infants with urinary bacterial counts of 10 ~ or more per milliliter. Pryles and Eliot 21 compared the results of urine cultures and leukocyte counts in a group of infants and children and showed that bacteriuria may be present in the absence of significant leukocyturia, and that leukocyturia frequently was present in the absence of bacteriuria. Similar dissociation has been reported by others, s, 16, 22-24 T h e question is raised repeatedly if urinalyses should be performed routinely in young infants, in order to detect asymptomatic in-

Prevalence o/ bacte'riuria

13 1

fection and other possible renal disease. T h e findings in this and other studies suggest that this is not a profitable undertaking in the healthy, full-term neonate. In the present study, no significant proteinuria or hematuria was detected in 836 infants. T h e predictable prevalence of bacteriuria in only a small fraction of one per cent does not seem to warrant the enormous amount of work required to screen these infants adequately. T h e situation in premature infants would appear to be quite different and it can be anticipated that bacteriuria will be detected in several per cent. It is of interest that three of the premature infants reported here with bacteriuria were totally asymptomatic. A fourth infant had had loose stools, abdominal distension, poor feeding, and lethargy. All cultures except that of the urine were negative. T h e fifth infant was jittery and had a history of poor feeding. I n addition to that of the urine, culture of the blood was reported to be positive, although with a different organism. O u r experience thus indicates that in the premature infant asymptomatic urinary tract infection may occur more frequently than symptomatic infection. The natural history of asymptomatic bacteriuria is unknown. One can speculate that detection and treatment of these infants might prevent extension of infection and septicemia. The authors acknowledge the invaluable help of DorelIa Simpkins, R.N., who was responsible for collection of urine specimens, the cooperation of Winifred Minott, R.N., Nursing Supervisor, and the excellent technical assistance provided by Marie Toussaint. REFERENCES

1. Kunin, C. M., Zacha, E., and Paquin, A. J., Jr.: Urinary tract infections in school children. I. Prevalence of bacteriuria and associated urologic findings, N. Engl. J. Med. 266: 1287, 1962. 2. Kunin, C. M., Deutscher, R., and Paquin, A,, Jr.: Urinary tract infection in school children: an epidemiologie, clinical and laboratory study, Medicine 43: 91, 1964. 3. Randolph, M. F., and Greenfield, M.: The incidence of asymptomatic baeteriuria and pyuria in infancy, J. PEDIATR.65: 57, 1964'. 4. McCarthy, J. M., and Pryles, C. V.: Clean voided and catheter neonatal urine specimens.

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The Journal o[ Pediatrics January 1973

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able urine specimen, J. PEDIATR. 79: 463, 1971. Biasini, G. C., Cenciotti, L., Montaguti, A., and Vullo, C.: Battariuria negli immaturi, Minerva Pediatr. 22: 310, 1970. Gower, P. E., Husband, P., Coleman, J. C., and Snodgrass, G. J. A. I.: Urinary infection in two selected neonatal populations, Arch. Dis. Child. 45: 259, 1970. Pendarvis, B. C., Jr., Wenzl, J. E., and Chitwood, L.: Bacteriuria in premature infants detected by aspiration cultures. Interscience Conference on Microbial Agents and Chemotherapy, Washington, D. C., 1970, reported in Pediatric News 4: 33, 1970. Zies, L., Ramirez, J., and Jannach, J. R.: Incidence of bacteriuria in the premature infant as determined by suprapubic aspiration, J. Fla. Med, Assoc. 55: 452, 1968. Nelson, J. D., and Peters, P. C.: Suprapubic aspiration of urine in premature and term infants, Pediatrics 36: 132, 1965. Aas, K.: The cellular excretion in the urine of normal newborn infants, Acta Paediatr. 50: 361, 1961. Pryles, C. V., and Eliot, C. R.: Pyuria and bacteriuria in infants and children. The value of pyuria as a diagnostic criterion of urinary tract infections, Am. J. Dis. Child. 110: 628, 1965. Houston, I. B.: Pus cell and bacterial counts in the diagnosis of urinary tract infections in childhood, Arch. Dis. Child. 38: 600, 1963. Lincoln, K., and Winberg, J.: Studies of urinary tract infections in infancy and childhood. III. Quantitative estimation of cellular excretion in unselected neonates, Aeta Paediatr, Scan& 5:3: 447, 1964. Littlewood, J. M.: White cells and bacteria in voided urine of healthy newborns, Arch. Dis. Child. 46: 167, 1971.