PRENATAL RUBELLA
Dr. Williams is a Research Fellow supported by
William Beaumont Hospital, Royal Oak, Michigan.
ADDRESS FOR REPRINTS : (R.D.L.
)
Depart-ment of Pediatrics, Harbor General Hospital, 1000 West Carson Street, Torrance, California 90509.REFERENCES
1. Hall, R. T., and Oliver, T. K. : Aortic blood pressure in infants admitted to a neonatal intensive care unit. Amer. J. Dis. Child, 121:145, 1971.
2. Goldring, D., and Wohltmann, H. : Flush method for blood pressure determinations in newborn infants. J. Pediat., 40:285, 1952. 3. Ashworth, A. M., Neligan, C. A., and Rogers,
J. E. : Sphygnomanometer for the newborn.
Lancet, 1:801, 1959.
4. Celander, 0., and Thunell, G. : A plethysmo-graphic method for measuring the systolic
and diastolic blood pressure in newborn
in-fants. Acta Paediat., 49:497, 1960.
5. Kafka, H. L., and Oh, W. : Direct and indirect blood pressure measurements in newborn infants. Amer. J. Dis. Child., 122:426, 1971. 6. McLaughlin, C. W., Kirby, R. R., Kemmerer,
W. T., and deLemos, R. A. : Indirect
meaS-urement of blood pressure in infants
utiliz-ing Doppler ultrasound. J. Pediat., 79:300, 1971.
7. Walker, C. H., and West, P. J.: Indirect esti-mation of systolic and diastolic blood pres-sure in the newborn. Pnimics, 50:387, 1972.
8. Cochran, W. D., Davis, H., and Smith, C. A.:
Advantages and complications of umbilical artery catheterization in the newborn.
P&n-ATRICS, 42:769, 1968.
9. Wigger, H. J., Bransilver, W., and Blanc, W. A. : Thrombosis due to catheterization in in-fants and children. J. Pediat., 76: 1, 1970. 10. Egan, E. A., and Eitzman, D. V. : Umbilical
vessel catheterization. Amer. J. Dis. Child.,
121:213, 1971.
Can
Language
Disorder
Not
Due
To
Peripheral
Deafness
Be
An
Isolated
Expression
Of
Prenatal
Rubella?
Rubella embryopathy may not be clinically
evident at birth because of covert symptoms,
progressive abnormality, or the normal delay in
expression of certain functions, such as speech.
In 1968, we treated a child with autism
whose mother had rubella during the first tri-mester. The patient was not considered to have
had the congenital rubella syndrome.
Subse-quently, others1’2 described autism, and other behavioral disorders in children with docu-mented prenatal rubella infection.
These observations led us to ask whether
evidence for prenatal rubella could be obtained in a sample of autistic children, under the age of 6 years, without overt signs of this infection.
One of the control groups assembled for this
purpose was composed of children under the
age of 6 years in whom language delay was a
major locus of maldevelopment. These control
subjects had an increased frequency of signifi-cant rubella antibody titres in their sera, and
they form the focus of this report.
SUBJECTS AND METHODS
Patients
Seven with autism and five with significant
autistic traits composed the study group. A
patient was excluded from the study if serum
from his natural mother was not available at
the same time. These 12 patients, referred from
three child psychiatry day-treatment centers in Montreal, represented the total number of such patients available to us during conduct of this
study
from September 1970 to June 1971.Dur-ing the same period of time, two control groups
were assembled.
Psychiatric Controls
These individuals, all under the age of 6
years, were derived from the centers which re-ferred the autistic patients. Their diagnostic
labels were assigned at source, and we did not
perform independent evaluations. They were
divided into two subgroups: (1) 25 patients
with a variety of diagnoses, not including
Ian-guage
delay, and (2) 21 patients withlanguage delay as a major diagnostic label.
Normal Controls:
This group contained 26 children, under age
6, attending a clinic for various acute,
non-psychiatric illnesses.
Serology
Rubella antibody was measured in cod’d
samples of serum by the hemagglutination-L hibition (HAl) procedure of Stewart as modi-field by Liebhaber and Feldman4.
Seropositiv-ity was defined as inhibition by a 1:8
297 EXPERIENCE AND REASON-BRIEFLY RECORDED
TABLE I
RESULTS OF RUBELLA HA! ANTIBODY DETERMINATIONS
DI AGNOSTIC CATEGORY SERO (+)* SERO (_) TOTAL
%
SERO(+)
1. Behavior disorder 2 9 11 18.2
2. Developmental deviation 0 10 10 0
3. Mental retardation 0 3 3 0
4. Prepsychotic 0 1 1 0
5. Autism, autistic traits 3 9 12 25.0
6. Language delay
(± other diagnoses) 8 13 21 38.1
Groups 1-4 2 23 25 8.0
Groups5+6 11 22 33 33.3
Normal controls 3 23 26 11.5
* Inhibition of hemagglutination by a 1 :8 dilution of serum defined seropositivity.
For statistical analysis of the results, the
patients were divided into those with and
those without language disorder. The
“lan-guage disorder” group (groups 5 and 6, Table
I) included those with language delay and
those diagnosed as autistic, since major
(lan-guage) communication deficits are character-istic of the latter children.
RESULTS
Serology
(Table
I).
Two of the 25 psychiatric controls without
language delay and three of the 26 normal
con-trols were seropositive. In contrast, three of the
12 autistic patients and eight of the 21
psy-chiatric controls with language delay were seropositive. All the mothers of the seropositive
patients were also seropositive.
Clinical Investigation of the
Seropositive Children
Despite directed questioning, historical
evi-dence for maternal gestational rubella could
not be obtained for any child. None had
micro-cephaly, cardiovascular defects, or cataracts.
One had patchy retinal pigmentation
com-patible with rubella retinopathy. Nonspecific
congenital anomalies were noted in three
chil-dren.
Dermatoglyphic analysis revealed at least
one “unusual” feature in five of the ten
pa-tients available for this study (Table II) . Two
of the patients had two unusual features; a
third had three. The following were considered unusual: a simian or bridged distal transverse
palmar crease; bilateral distal (t”) pahnar
ax-ial triradii or absent triradius; seven or more
whorl patterns on the
digits
of the hands; anda radial loop on a
digit
other than the second.Pure tone audiometry was normal in ten
patients. One was recorded as having mild
hypoacusis on the right and a moderate deficit on the left by means of
electroencephaloaudi-ography; another had chronic ear infections.
The remaining seropositive patient was not
available for formal audiological evaluation,
al-though she was not considered to be deaf.
Eight patients had normal
electroencephalo-grams.
One was reported to have “generalizedslowing of background activity” and a second
had a pattern compatible with “immaturity or
nonlocalized organic pathology.” None had electrocardiographic abnormalities.
DISCUSSION
The frequencies of seropositivity in the
nor-mal controls (11.5%) and in the psychiatric
controls without language delay (8%) were
comparable to those in a Montreal population
sample aged 3 to 6 years (15%) , and a North
American population sample aged 1 to 5 years
(
14.5%) 6 However, the frequency ofseroposi-tivity in the “language disorder” group (33%;
group 5 and 6; Table I) was greater than in
the psychiatric controls without language
de-lay (P<0.05) or in the general population of
children
below age 6 (P<zO.01). It approachedthe level of significance in comparison with
the local group of normal controls.
This study was begun with the
foreknowl-edge that abnormal speech development not
ascribable exclusively to peripheral hearing
rec-PRENATAL
RUBELLA
298RONALD B. FELDMAN, M.D., FRCP (C)
TABLE II
DERMATOGLYPHIC FINDINGS
No. OF PALMAR PALMAR RADIAL
PATIENT WHORLS AXIAL
TRIRADIUS
RIGHT LEFT
CREASES LOOP
OTHER
THAN DIGIT 2
MiSCELLANEOUS
M.W. 10 t” t” N 0 Double palmar axial triradii;
bilateral hypothenar ulnar loops
B.O. 0 t t N 0 Right hypothenar radial loop
R.B. 0 t’ t’ N 4 (right) Multiple minor palmar creases,
left
I.M. 3 t’ t’ N 0 Complex thenar pattern, left;
right hypothenar radial loop
M.R. 0 t’ 0 Branched 4 (left) Left hypothenar radial arch (right)
S.D. 2 t” t” Simian
(right)
0 Bilateral hypothenar proximal loops
J.O. 3 t t’ N 0 Right hypothenar ulnar loop
L.N. 0 t’ t’ N 0 0
B.K. 7 t t N 0 0
E.G. 0 t t’ N 0 Multiple minor palmar creases,
bilaterally
ognized in children with multiple stigmata of
rubella embryopathy.7#{176} But, only
after
thepresent results were obtained did we become
aware of the study by Ames et which
in-cluded 30 children with language delay in
whom rubella retinopathy was the only somatic
stigma of the congenital rubella syndrome. As
an extension of their observation, the present
results are compatible with the suggestion that
prenatal rubella may be responsible for lan-guage delay with or without behavior
disor-ders, in some children who do not even have
retinopathy. We acknowledge that the
appar-ent association between rubella HAl
seroposi-tivity and language disorder need not be
cas-ual. Nevertheless, the fact that the language
disorder group contained four children who had unusual dermatoglyphic features
previous-ly identified nonspecifically with prenatal
ru-bella infection’12 as well as one child with
retinopathy, at least, supports the suggestion of causality.
Future attempts to gather data bearing on
the important question raised by the present
study should include more subjects and due at-tention to close matching of patients and con-trols. We have recently initiated such a study
in Canada.
LEONABD PINSEY,
M.D., FRCP (C)
JACK MENDELSON, M.D., FRCP (C) REAL LAJOXE, M.D., FRCP (C) Jewish General Hospital3755 Cote Saint Catherine Road Montreal, Quebec, Canada
This paper is a preliminary report of a project
currently supported by Project No. 604-7-835 from
the Department of National Health and Welfare
of Canada. We would 111cc to express our thanks
to Dr. June Cwnberland, Montreal Children’s Hos-pital, Dr. Simon Richer, Hospital Ste. Justine, and Dr. Douglas Betts, Jewish General Hospital, and
to various members of the psychiatric
day-treat-ment centers of these hospitals for
their
generoushelp in referring patients for this study. We are
also grateful to Dr. Howard Tanenbaum for the
ophthahnological examinations, and to Mr. Patrick
Quennec for technical assistance.
REFERENCES
1. Chess, S.: Autism in children with congenital
rubella. J. Autism Childhood Schizophrenia,
1:33, 1971.
2. Desmond, M. M., Wilson, G. S., Melnick, J. L.,
Singer, D. B., Zion, T. E., Rudolph, A. J.,
Pineda, R. G., Ziai, M.-H., and Blattner,
B. J.: Congenital rubella encephalitis.
Course and early sequelae. J. Pediat., 71:
299 EXPERIENCE AND REASON-BRIEFLY RECORDED
A 153k-year-old white female, previously in ex-cellent health, was brought to the University of 3. Liebhaber, H. : Measurement of rubella
anti-body by hemagglutination inhibition. II. Characteristics of an improved HAl test employing a new method for the removal
of nonimmunoglobulin HA Inhibitor from
serum. J. Immun., 104:826, 1970. 4. Feldman, H. A. : Removal by
Heparin-MnCL, of nonspecific rubella hemagglutinin serum inhibitor. Proc. Soc. Exp. Biol. Med., 127:570, 1968.
5. Chagnon, A., and Pavilanis, V: Epidemiologi-cal studies on rubella. Canad. Med. Assoc.
J., 102:933, 1970.
6. Smith, Kline and French: Epidemiologic Study, 1969.
7. Desmond, M. M., Montgomery, J. R., Melnick,
J. L., Cochran, C. C., and Verniaud, W.:
Congenital rubella encephalitis. Effects on growth and early development. Amer. J.
Dis. Child., 118:30, 1969.
8. Weinberger, M. M., Masland, M. W. Asbed,
R.-A., and Sever J. L. : Congenital rubella presenting as retarded language develop-ment. Amer. J. Dis. Child., 120: 125, 1970. 9. Hardy, J. B., McCracken, C. H. Jr., Gilkeson,
M. R., and Sever, J. L. : Adverse fetal
out-come following maternal rubella after the
first trimester of pregnancy. JAMA, 207:
2414, 1969.
10. Ames, M. D., Plotldn, S. A., Winchester, R.
A., and Atkins, T. E. : Central auditory fin-perception. A significant factor in congenital rubella deafness. JAMA, 213:419, 1970. 11. Achs, R., Harper, R. G., and Harrick, N. J.:
Unusual dennatoglyphics associated with
major congenital malformations. New Eng.
J. Med., 275:1273, 1966.
12. Alter, M., and Schulenberg, R. : Dermato-glyphics in the rubella syndrome. JAMA,
197:685, 1966.
Acute
Dextropropoxyphene
Hydrochloride
(Darvon)
Poisoning
This case report of attempted suicide by a 153k-year-old girl by ingestion of a large quan-tity of dextropropoxyphene hydrochloride (Darvon
)
illustrates the dire and diverse effectsof overdosage with this drug and the difficulties and frustrations encountered in treating such a patient.
CASE HISTORY
Florida Medical Center Emergency Room
approxi-mately 30 minutes after ingesting an unknown
number of Darvon 65 capsules (containing 65 mg dextropropoxyphene hydrochloride), probably as many as 88. Attempted administration of syrup of Ipecac at home was unsuccessful. She became lethargic and eventually unresponsive during a 20-minute period. During the ten-minute trip to the emergency room she suddenly vomited and had
complete cardiorespiratory arrest. Closed chest
massage and mouth-to-mouth resuscitation by a
physician were carried out during the next four to five minutes. When she arrived she had no spon-taneous respirations and no ECG electrical activity.
She was intubated and given positive pressure-as-sisted respiration. Good cardiac electrical activity developed within two minutes after intravenous administration of sodium bicarbonate; epine-phrine and calcium chloride were given. She
be-came normotensive with a regular cardiac rate of
85/mm. Gastric lavage obtained 800 ml of fluid
which contained 12.4 g/ml of propoxyphene hy-drochloride (total 9.9 mg). Initial blood gases showed a profound combined respiratory and met-abolic acidosis which responded well to intraven-ously administered sodium bicarbonate and as-sisted respirations. Initial serum electrolyte
de-terminations 60 minutes after Darvon ingestion
re-vealed sodium of 133 mEq/liter; potassium, 2.8
mEq/liter; and chloride, 89 mEq/liter. The BUN was 13 mg/i#{174} ml.
Physical examination revealed a flaccidity, bi-lateral dilated nonreactive pupils, no response to painful stimuli, ankle clonus, and scattered fine
rales throughout the right chest.
She was given 5, 10, and 15 mg nalorphine
in-travenously on three occasions without respiratory
response, and then placed on a volume-controlled respirator.
A chest x-ray 2% hours after Darvon ingestion showed diffuse bilateral basilar bronchopneumonia which cleared in six days. Subsequent lung prob-lems were a left pneiifflothorax, intermittent bilat-era! areas of interstitial infiltrates, and areas of atelectasis.
Six hours after Darvon ingestion she developed generalized tonic-clonic seizures responding tern-porarily to 1, 2.5, and 9 mg of intravenously
ad-ministered diazepam. The seizures continued over a period of about 12 hours, gradually subsiding on phenobarbital, 5 mg/kg/day. Later seizures were controlled by the addition of diphenylhydantoin
(Dilantin), 4 mg/kg/day. The administration of
both drugs were continued throughout her hos-pitalization.
During the second hospital day she produced
