Volume 118 Number 2

were negative. The patient was referred by her pediatrician for possible endocarditis. Ten days before the onset of fever, her orthodontist had adjusted her braces. Physical examination revealed her to be thin, pale, well-developed, and in no distress. Heart rate was 128 beats/min; respiratory rate, 12 breaths/min; blood pressure, 82/60 mm Hg; and temperature 38.4 ~ C. The patient had halitosis. Funduscopic examination showed no hemorrhages. There were no carotid bruits, and the lungs were clear. The precordium was quiet; there were no lifts or thrills. The heart sounds were normal; there were no gallops, rubs, or clicks. A grade II1/VI pansystolic murmur was heard maximally at the mid-left sternal border, with some radiation along the sternal border. Peripheral pulses were normal and equal in all extremities. No hepatosplenomegaly was present. The skin had no rashes or petechiae. Significant admission laboratory data included a hemoglobin level of 11.3 gm/dl and a leukocyte count of 9200 mm 3, with 67% segmented cells, 17% band cells, 12% lymphocytes, 3% monocytes, and 1 atypical cell. The platelet count was normal, sedimentation rate was 85 mm/hr, and antistreptolysin O titers were normal. A chest roentgenogram and an electrocardiogram were normal. An echocardiogram showed a small vegetation on the septal leaflet of the tricuspid valve. Three blood cultures were positive for Streptococcus viridans. The patient was treated intravenously for 5 weeks with penicillin (3 weeks in the hospital and 2 weeks at home) and for 17 days with gentamicin. The vegetation disappeared, and she remains well 7 months after the onset of fever. DISCUSSION In both children, bacterial endocarditis developed because of organisms known to inhabit the oropharynx. Except for the manipulation of their orthodontic appliances, neither had undergone other dental procedures for at least 6 months before the onset of fever. These patients represented two of the three cases of bacterial endocarditis seen in our institution in a 13-month period. Guntheroth 2 pointed out that cultures of blood specimens

Clinical a n d laboratory observations

249

from 38% of patients after mastication and from 25% after brushing or oral irrigation are positive for bacteria. Therefore one could certainly question whether these two cases were related to the orthodontic manipulation, even though the time course suggests a relationship. Other factors may contribute to the risk of bacteremia in children with orthodontic appliances, such as the status of the teeth and gums, the success of oral hygiene habits, and the duration of orthodontic therapy. Maintenance of adequate oral hygiene decreases the incidence of gingival disease, which is a major factor in transient bacteremia after dental manipulation.l, 3 Children with orthodontic appliances have two factors that work against the maintenance of oral hygiene. Compliance is a well-known problem in this age group, and the physical presence of the appliances makes "plaque removal extremely difficult because bands generally have subgingival overhangs at the apical band b o r d e r - - a n area from which plaque removal is difficult." 4 Current practice in our area is for the orthodontic appliances to be in place for about 2~/~ years and to be adjusted at approximately 5-week intervals. These adjustments may be associated with mucosal injury (S. Alexander, personal communication, October 1989). 5 Perhaps bacterial endocarditis prophylaxis should be considered when mucosal trauma is likely. The data on which to base such a recommendation are lacking, and a large study is warranted. REFERENCES

1. Shulman ST. Prevention of bacterial endocarditis. Circulation 1984;70:1127A. 2. Guntheroth WG. How important are dental procedures as cause of infective endocarditis?.Am J Cardiol 1984;54:797801. 3. Murray M, Moosnick BS. Incidence of bacteremia in patients with dental disease. J Lab Clin Med 1941;26:801-2. 4. Wei SHY. Pediatric dentistry: total patient care. Philadelphia: Lea & Febiger, 1988:550.

Pupil dilation at the first well baby examination for documenting choroidal light reflex Robert Adler, MD, Murray L a p p e , MD, a n d A, Linn M u r p h r e e , MD From the Divisionsof Ophthalmology and General Pediatrics, Childrens Hospital Los Angeles, and the Departments of Ophthalmology and Pediatrics, University of Southern California School of Medicine, Los Angeles Supported in part by a grant from the Children's National Eye Care Foundation (Dr. Lappe). Submitted for publication May 1, 1990; accepted Sept. 17, 1990.

Reprint requests: Robert Adler, MD, Division of General Pediatrics, Childrens Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027. 9/22/25469

250

Clinical and laboratory observations

CLR

Choroidallight reflex

The Journal of Pediatrics February 1991

I

Clinical studies have demonstrated that early diagnosis and surgery to correct or treat some congenital eye diseases may prevent irreversible loss of vision. Failure to diagnose and treat a visually obstructive lesion, such as a congenital cataract or persistent hyperplastic primary vitreous, within the first 3 months of life may result in permanent loss of vision in that eye. 13 Examination of the newborn infant's eye should include an inspection of the gross appearance of the eyes, the pupils, the brightness and clarity of the choroidal l!ght reflex (red reflex), and the visualization of some fundus details. The vitreous may be cloudy for a few days after birth, so the eye examination should be delayed for several days. It may be difficult to elicit the CLR, because the pupil of the newborn infant's eye is small. It has been suggested that a CLR examination be performed through a dilated pupil during the first year of life. 4 Because of the current knowledge of a critical period of visual development and an improved Prognosis for congenital cataract surgery, we believe that this examination should be performed in the first few weeks of life. We examined the efficacy, safety, and acceptability of the application of small doses of a mydriatic agent, tropieamide, to the open or closed eyelids of the newborn infant at the time of the first pediatric office examination. METHODS The study was approved by the human protective committee at Childrens Hospital Los Angeles. Tropicamide 0.5% (Mydriaeyl) was used to dilate the pupil through an aerosol drug delivery system. The cap and dropper tip of the 15 ml bottle were removed and replaced with a sterile pump-sprayer cap (No. LP-19-72-05, Specialty Packaging Products, Bridgepor t , Conn.), and silicone was removed under sterile conditions. The pump sprayer produced a fine mist of aerosolized microdroplets when compressed. Thirty-five healthy newborn infants, 2 to 8 weeks of age, were seen in the ambulatory pediatric clinic at Childrens Hospital Los Angeles for their first health maintenance examination and, after an informed consent was obtained, were admitted to the study. An external eye examination was initially performed to rule out eyelid or other abnormalities and to check for initial pupil diameter and normal pupillary response. Each eye was sprayed in either the open or closed position with tropicamide 0.5%, from a distance of approximately 15 cm, while the infant was held by the mother, either upright or supine, whichever was most comfortable. When the infant's eyes were closed, the upper and lower lids were sprayed in the usual fashion from the same distance,

and then the lower lid was gently moved after some of the spray had accumulated on the eyelashes. This maneuver ensures that medication at the base of the lashes has access to the tear film. Five minutes after the first application, the eyes were sprayed a second time unless the patient's pupil already measured ~ 6 mm after the first administration of tropicamide. After each spray, excess medication was wip ed from the infant's face with a tissue. Twenty minutes after the first administration of tropicamide, the pupils were remeasured for the degree of dilation with a hand-held pupil ruler and the ocular structures examined for adverse reactions such as redness, tearing, or swelling. The CLR examination of the eye was then performed through the dilated pupil in dim light. An ophthalmoscope was the source of pupil illimination; it was held approximately 46 cm from the baby. The circle of light from the instrumentcovered most of the baby's face. The focus wheel on the ophthalmoscope was adjusted to give the brightest, most distinct "glow" in the pupils when they were viewed through the instrument. The focus wheel was never adjusted individually for each eye. Any significant asymmetry in the color, brightness, position, or presence of the pupillary "glow" constituted an abnormal CLR. The mean volume of an individual sprayed dose was measured by spraying an absorbable filter paper cut to the dimensions of the normal newborn infant's palpebral area, 18 X 12 mm. 5 The filter paper was weighed on a Metier balance (Metler Inc., Hightstown, N.J.). A single dose of 0.5% tropicamide was sprayed onto the filter paper from a distance of 15 cm, and the paper was then reweighed. The volume of spray was determined from the weight and specific gravity of a sprayed dose of 0.5% tropicamide. At~ter 5 weeks of use, cultures of material from three bottles of medication and their sprayer caps were grown for aerobic and anaerobic bacteria and for fungi.

RESULTS Each of the 35 infants had a normal external ocular examination. The mean ( + SD) pupil diameter of the 70 eyes before treatment was 3.0 mm (range 2 to 4 _+ 0.5 mm). Six eyes required only one spray of tropicamide because a significant dilated pupil diameter (>__6 mm) was achieved for an adequate CLR examination 5 minutes after the initial application. The resultant mean (_+ SD) pupil diameter 20 minutes after treatment for eyes sprayed only once was 6.7 mm (range 4 to 8 + 1.2 ram). Sixty-four eyes were sprayed twice, but because there was no difference in postspray dilation, the two groups were combined. Twenty minutes after the initial spray was administered, the mean pupil diameter of the 70 eyes measured 6.6 mm, a mean increase in pupil diameter of 3.6 mm. In 15 instances

Volume 118 Number 2

the spray was applied both times with the infant's eyes closed; the result was a mean pupil diameter of 5.8 mm, or a mean increase of 2.8 mm. All the children tolerated the procedure well. The eyelids were visually examined for erythema, edema, or other signs of allergic or toxic reaction. No adverse reactions were noted, and parental interview after the procedure elicited no negative reports. Seventy sprayed doses were weighed to estimate the quantity of medication that actually reached the patient's eye and tear film. The mean volume of an individual sprayed dose was 8.3 lzl, or approximately IAdrop. The range of doses varied from 2 to 15 #1. All cultures of material from the three bottles of medication and their sprayer caps were negative. The pupil size after dilation was sufficient to examine the red reflex of each of the infants in the study. No abnormal CLRs were found. The pupillary area increased 4.8-fold after dilation for all patients. The pupillary area of the infants sprayed with eyelids closed was 3.7 times larger than the area of the pupil before dilation. DISCUSSION The human visual system is incompletely developed at birth, and several months of focused visual stimulation of the retina appear to be a necessary component of normal visual development. These early months of development of the visual system have been termed the "critical period."That the period is a critical one is best illustrated by the current approach to congenital cataracts, which cause 15% to 30% of blindness beginning in infancy.6 The treatment of monocular congenital cataracts was generally unsuccessful until 1981, when Beller et al. 2 reported good visual results after early surgery and aphakic correction with extended-wear contact lenses in eight neonates with total monocular congenital cataracts. All eight neonates were operated on before 6 weeks of age; the best results (20/20) were obtained in a neonate operated on 7 hours after birth~ This result is in stark contrast to the previous resuits, in which half the children who were operated on for congenital cataracts later attended a school for the visually impaired] These results led our group to examine ways to encourage the use of pupil dilation in the newborn infant. One adequate eye examination through a dilated pupil during the first 2 to 3 months of life should be sufficient to detect the majority of congenital abnormalities. One should not be concerned about inducing glaucoma by pupil dilation in the normal neonate. No other pupil dilation needs to be considered in the first year of life unless ocular concerns are raised by the parents or new physical findings are present. The technique had to be safe, reliable, easily applied in the office, acceptable to the family, and not time-consuming.

Clinical and laboratory observations

251

The risk of systemic toxic effects is important in a consideration of the use of eye drops, especially in newborn infants. Although the tear film of an adult holds only 7 to I0 #1 of fluid, commercially available eye drops may contain as much as 70 #1 per drop. 8 That volume of drug which cannot be held in the tear film to exert a local effect on the eye is either lost or systemically absorbed. Systemic absorption of ophthalmic preparations has been reported. 9, 10 Systemic absorption of eye drops may be transconjunctival or via the nasolacrimal system through the nasal or pharyngeal mucosa. The latter absorption can be decreased by firm pressure of the lacrimal sac against the nasal bone for 1 to 2 minutes. Combination drops of cyclopentolate, tropicamide, and phenylephrine are commonly used to dilate pupils to rule out retinopathy of prematurity. Tropicamide was chosen for this study because it has the fewest reported side effects and because it is commercially available. A literature review produced only a single reported adverse reaction, in a 10-year-old boy who had a syncopal episode after receiving one drop of 1% tropicamide.ll The degree of dilation achieved allowed the investigators to document a normal CLR in all the infants studied. The dose was effective even when the neonate's eyes were closed and therefore can be used for all first office examinations of newborn infants. The spray delivery system is not commercially available but was used to demonstrate that even in the most uncooperative child a minimal amount of medication is sufficient for the desired dilation. Extra effort to hold the eyelids open is not necessary. In lieu of the current unavailability of the aerosol spray preparation, we recommend applying 1 or 2 drops of 0.5% Mydriacyl to create a "lake" of medication between the eyelids and nose at a convenient time at the beginning of the office visit. Slight movement of the upper lid will cause the lashes and the lid fissure to become wet in a "wicklike" manner. This capillary action is sufficient to deliver adequate medication to the tear film, and the remainder can be gently blotted away. The parents readily accepted this intervention and were genuinely pleased that a thorough ocular examination was undertaken. Although it remains to be shown that more effective dilation can enhance early detection of significant ocular lesions in the newborn infant, we believe that pupil dilation can be achieved safely, easily, and reliably in the office setting, is tolerated by the patients and parents, and should be undertaken. REFERENCES

1. Karr D, Scott W. Visual acuity results followingtreatment of persistent hyperplastic primary vitreous. Arch Ophthalmol 1986;104:662-7. 2. Beller R, Hoyt C, Marg E, Odom J. Good visual function after neonatal surgery for congenital monocular cataracts. Am J Ophthalmol 1981;91:559-65.

252

Clinical and laboratory observations

3. Von Noorden GK, Crawford ML. The sensitive period. Trans Ophthalmol Soc UK 1979;99:442-6. 4. Robb R. Children's ophthalmologic problems. Hospital Pract April 1977:107-15. 5. Merlob P, Sivan Y, Reisner SH. Anthropomorphic measurements of the newborn infant. Birth Defects 1984;20(7):8-14. 6. Neweomb R. The causes of blindness in children: a review of the literature. J Am Optom Assoc April 1977:48(4). 7. Francois J. Surgical results of congenital cataract: the Belgian experience. Ophthalmic Forum 1984;2(3):126-8.

The Journal of Pediatrics February 1991

8. Brown C, Hanna C. Use of dilute drugs for routine cycloplegia and mydriasis. Am J Ophthalmol 1978;86:820-4. 9. Palmer E. Drug toxicity in pediatric ophthalmology. J Toxicol Cutan Ocul Toxicol 1982;1(3):181-210. 10. Palmer EA. How safe are ocular drugs in pediatrics? Ophthalmology 1986;93:1038-40. 11. Caputo AR, Sehnitzer RE. Systemic response to mydriatic eyedrops in neonates: mydriatics in neonates. J Pediatr Ophthalmol Strabismus 1978;15:109-22.

Transient infantile osteopetrosis Bruce A. Monaghan, BA, Frederick S. Kaplan, MD, Charles S. August, MD, Michael D. Fallon, MD, and David B, Flannery, MD From the Departments of Orthopaedic Surgery and Pediatrics, University of Pennsylvania School of Medicine, Philadelphia; the Department of Pathology, Thomas Jefferson University School of Medicine, Philadelphia, Pennsylvania; the Department of Pediatrics, Medical College of Georgia, Augusta; and Children's Hospital of Philadelphia, Philadelphia, Pennsylvania

T h e osteopetroses are a group of rare heritable disorders t h a t result from a failure to resorb calcified cartilage and bone. A relatively mild form with an autosomal d o m i n a n t p a t t e r n of inheritance is diagnosed by early adulthood, when pathologic fractures occur in sclerotic bone.1 A more severe form ( m a l i g n a n t infantile osteopetrosis) with a n autosomal recessive p a t t e r n of inheritance is diagnosed in infancy a n d is distinguished clinically by anemia, t h r o m b o cytopenia, leukoerythroblastosis, recurrent infections, compressive cranial neuropathies, skeletal fragility, growth retardation, rickets, upper airway obstruction, and, if untreated, a progressive fatal course. L 2 Some intermediate phenotypes a n d extremely rare familial forms associated with carbonic a n h y d r a s e II deficiency have also been described. 3-6 In all the h u m a n cases, however, the a b n o r m a l radiographic features persist throughout life. 7 In this article we describe a neonate with asymptomatic, biopsyproven osteopetrosis whose radiographic abnormalities resolved spontaneously by the age of 28 months.

Supported in part by grants R01-DK-32760-01, SCOR 1-P50AR39226, and RR00240 from the General Clinical Research Center Program of the Division of Research Resources, National Institutes of Health, by a Student Research Fellowship grant from the American Heart Association, and by a Fellowship grant in Research on Aging from the Hartford Foundation. Submitted for publication March 27, 1990; accepted Aug. 30, 1990. Reprint requests: Charles S. August, MD, Children's Hospital, 3400 Civic Center Blvd., Philadelphia, PA 19104.

9/22/25093

C A S E REPORT A male infant weighing 4.1 kg was the first child born to a healthy 26-year-old mother after an uncomplicated 40-week gestation. The infant was thought to have a subluxed hip. Radiographs showed no signs of hip subluxation but revealed markedly sclerotic bone with medullary cavities that were decreased in size, compatible with the diagnosis of osteopetrosis (Fig. 1, D). Findings of a second physical examination were unremarkable, and the hips were normally positioned. Neurologic examination findings and a complete blood cell count were normal. A complete skeletal survey at the age of 10 days was interpreted as showing infantile osteopetrosis characterized by diffuse osteosclerosis and poorly defined medullary canals (Fig. 1, A and D). During pregnancy the mother had taken no medication except prenatal vitamins and had no antepartum illnesses or any known exposure to heavy metals. There was no family history of spontaneous abortion, osteopetrosis, dwarfism, skeletal fragility, or other bone disease. At 10 weeks of age the child was admitted to the clinical studies unit of Children's Hospital of Philadelphia for confirmation of the diagnosis and evaluation of his suitability for treatment with calcitriols or steroids. 9 The infant had not been irritable, had eaten well, and had shown no signs of infection. On physical examination, he appeared well. Height and weight were at the 90th and 85th percentiles, respectively, for age. Neither the liver nor the spleen was enlarged. Neurologic examination findings, vision, and hearing were normal. Laboratory examination revealed a normal complete blood cel! count, and normal serum levels of inorganic phosphorus, total calcium, albumin, urea nitrogen, creatinine, parathyroid hormone, 25-hydroxyvitamin D, and erythrocyte carbonic anhydrase. Serum biochemical abnormalities included elevations of alkaline phosphatase, 372 U / L (6.2 #kat/L); tartrate-resistant acid phos-