Vaccines, Apparent Life-Threatening Events, Barlows Disease, and Questions about Shaken Baby Syndrome
Michael D. Innis, MBBS
Apparent Life-Threatening Events (ALTEs), as defined by the
National Institutes of Health, encompass all the findings hitherto
attributed to Shaken Baby Syndrome (SBS), and may follow
routine vaccination. Vaccines may also induce vitamin C deficiency
(Barlows disease), especially in formula-fed infants or infants
whose mothers smoke. This could account for some of the changes
seen in these infants, including hemorrhages, bruises, and
fractures. Vitamin C deficiency should be excluded in patients
suspected to have SBS.
Shaken baby syndrome (SBS) is a collection of findings, not
all of which may be present in any individual infant diagnosed to
have the condition. Findings include intracranial hemorrhage,
retinal hemorrhage, and fractures of the ribs and at the ends of the
long bones. Impact trauma may produce additional injuries such as
bruises, lacerations, or other fractures.
The National Institutes of Health, at its 1986 Health Consensus
Development Conference on Infantile Apnea and Home
Monitoring, defined Apparent Life-Threatening Event (ALTE)
as an episode that is frightening to the observer and is characterized
by some combination of apnea (central or occasionally
obstructive), color change (usually cyanotic or pallid but
occasionally erythematous or plethoric), marked change in muscle
tone (usually marked limpness), and choking or gagging. In some
cases, the observer fears that the infant has died. ALTE is not so
much a specific diagnosis as a description of an event.
SBS is often suspected in infants who present with unexplained
bruising, subdural hemorrhages, and retinal hemorrhages. Manual
shaking with whiplash-induced intracranial and intraocular bleeds
is thought to be the most likely cause of these injuries. However,
on questioning, most parents and caregivers vehemently deny
having shaken or harmed the baby. Could the symptoms classically
attributed to SBS actually have another cause?
In the case reports that follow, further analysis of the clinical,
laboratory, and postmortem features in infants diagnosed with SBS
suggests the possibility of an alternate explanation for their
subdural hemorrhages, retinal hemorrhages, and bony lesions or
bruises. In each of these instances, an ALTE occurred. All the
caregivers involved in these cases have strongly and repeatedly
rejected the notion of nonaccidental injury or SBS.
Geddes et al. have hypothesized that in the immature brain,
hypoxia alone is sufficient to activate the pathophysiologic cascade
that culminates in dural hemorrhage. Is it possible thatALTE, when
associated with anoxia and cyanosis, could cause subdural
hemorrhage in conformity with the Geddes hypothesis?
Moreover, the clinical picture of Barlows disease, infantile
vitamin C deficiency, resembles that of battered baby or child
abuse, as it may also present with multiple hemorrhages and fractures.
A male infant was born to a 20-year-old mother after a 41-week
gestation by normal vaginal delivery. His Apgar scores were 8 at
one minute and 9 at five minutes. Injections of vitaminK1mg (IM)
and hepatitis B vaccine (Hep B) were given. During pregnancy the
mother had a urinary tract infection and iron-deficiency anemia and
had been treated with an antibiotic and ferrous sulfate. The infant
was breastfed for two months and then fed formula. The mother
smoked about 10 cigarettes per day
At the infants routine check at age 2 months, his navel had still
not healed, and some bright red discharge was noted.
Immunizations consisting of diphtheria, tetanus, and acellular
pertussis (DTaP),Hemophilus influenzae,B (Hib), and Hep B
vaccines were given. These were repeated two months later.
On the night after the second set of immunizations, the mother
said the infant was fussy, and she gave him Tylenol. The
following day the babys father gave him a bath and put him on the
bed while he attended to some other matter for about two minutes.
When he returned, he found that the infant was limp, unresponsive,
and not breathing. Shortly thereafter the infant became blue.
On arrival at the nearest hospital, the infant was found to be
pulseless. He was intubated and mechanically ventilated, and his
pulse was restored. Examination revealed evidence of an
intracranial bleed and bilateral retinal hemorrhages. The magnetic
resonance imaging (MRI) report stated: There is abnormal
restricted diffusion and decreased apparent diffusion coefficient in
the entire territory of the bilateral anterior and posterior cerebral
arteries and partial left greater than the right middle cerebral
arteries. These findings are consistent with acute ischemic
infarction. Minimal extra-axial parafalcine interhemispheric
hyperintense signal on T1 and diffusion weighted images is likely a
small [acute] subdural hemorrhage. Effacement of the sulci in the
areas of infarction is consistent with edema. No evidence to suggest
posterior fossa infarct is demonstrated.
In addition, another report noted subdural hemorrhages
[presumed to be acute] extending from the posterior fossa, through
the foramen magnum, and along the dorsal cord to the inferior endplate
of C3.Nocord compression or deformity.
Multiple computerized axial tomographic (CAT) sections of the
head were obtained without contrast and showed findings
consistent with sub-arachnoid hemorrhage as well as cerebral
edema associated with anoxia.
A skeletal survey showed findings consistent with a
nondisplaced fracture of the distal left tibia, and two weeks later
the report stated, the previously noted nondisplaced left distal
tibial fracture is not well seen. The possibility of temporary brittle
bone disease as described by Paterson et al., who attributed it to a
temporary deficiency of an enzyme in the post-transitional
processing of collagen, was apparently not considered.
Blood studies showed a prothrombin time of 17.9 sec (normal
range, 8.214.1); partial thromboplastin time, 35.5 sec (28.050.0);
aspartate aminotransferase, 97 U/L (2060); glycine, 131 µmol/L
(224514); lysine, 66 µmol/L (114269); hemoglobin, 11.0 g/dL (10-
13.5); platelets, 382 x 10 /L (150450); pH, 7.26 (7.35-7.45);
bicarbonate, 18.2 mmol/L(2129); and glucose, 188 mg/dL(6080).
The recorded diagnoses were non-accidental injury and
shaken baby syndrome. The infant survived, but was
developmentally delayed and required a gastrostomy.
A female infant was born at term weighing 2.9 kg. The mother
had almost daily vomiting throughout the pregnancy and weighed
less after delivery than she did before she became pregnant.
Because of the persistent vomiting, she was unable to consume the
vitamin and iron supplements she was advised to take. She also
smoked during her pregnancy. The infant was given an IM injection
of 1mg vitaminKat birth. She was formula fed.
At about three weeks of age the infant suddenly awakened from
her sleep, screaming. The mother interpreted the scream as a cry of
pain rather than hunger. The infant vomited, and then settled after a
While bathing the infant the next morning, the mother noticed a
deep purple bruise on her arm. Another bruise appeared about 2 cm
from the first one. No investigations were done to establish the
cause of these bruises.
Following this episode the infant was reasonably well, and at
age 7 weeks weighed 4.25 kg. She was given DTaP, Hib, and
meningitis C vaccines at 8 weeks. From then on, she refused her
regular feedings and started vomiting, and was therefore admitted
to the hospital six days after the vaccinations.
After discharge from hospital, while being bottle-fed by the
father 11 days after being vaccinated, she suddenly collapsed,
stopped breathing, and went floppy. The physician on emergency
call found the baby very blue initially and said she may have been
hypoxic for 6-8 minutes. CPR was attempted and the infant was
admitted to the hospital, where she was intubated and resuscitated,
but died shortly afterward.
Radiological findings included a subdural hemorrhage, 12
fractures involving all four limbs, and seven rib fractures of
varying ages. These findings were confirmed at post-mortem
Radiologic and postmortem examinations showed that the
anterior ends of the third through tenth ribs were broadened
bilaterally. This is consistent with the typical scorbutic rosary
alluded to in Nelsons Textbook of Pediatrics in which, referring to
infantile scurvy, it is stated: A rosary at the costochondral
junctions and depression of the sternum are other typical features.
Other relevant laboratory results were as follows: Factor VIII,
221 IU/dL (normal range 50125); vonWillebrand factor antigen,
253 IU/dL (50246); fibrinogen, 4.0 g/L (1.74.0); alkaline
phosphatase, 321 U/L (65265); alanine transaminase, 59 U/L
(545); lactate, 6.6 mmol/L (1.12.2); calcium, 2.32 mmol/L
(2.372.74); albumin, 28 g/L (3555); lysine, 55 µmol/L
(100300); hemoglobin, 9.0 g/L (1013.5); lymphocytes, 2.80
x10 /L (313.5); and eosinophils, 0.01 x 10 /L(0.1-0.3). In addition
to lysine, the levels of six other essential amino acids were reduced.
Levels of glutamine and two other nonessential amino acids were
Autopsy revealed subdural and subarachnoid hemorrhages,
cerebral edema, and widespread acute ischemic changes.
There was general agreement among the pediatricians,
radiologists, and pathologists that the varying age of the lesions
indicated repeated episodes of violent abuse such as shaking, and
that death was caused by nonaccidental injury. Yet there had been
no evidence of injury or other reason to suspect abuse at the time of
hospitalization, or in the many visits to the doctors office. The
origin of the fractures remains undetermined; however, given the
compromised nutritional status of the baby in utero, fractures could
be caused by temporary brittle bone disease.
The current concept of SBS includes intracranial bleeding,
usually in the form of a subdural hematoma, which may be acute or
chronic; parenchymal injury and/or anoxic changes in the brain;
skull fracture (if impact occurred); and retinal hemorrhages.
Constant features are subdural and retinal hemorrhages. Various
fractures including those of the long bones and ribs are often used to
support an impression of child abuse, but it should not be forgotten
that Barlows disease can resemble battered baby.
As far as we are aware, no one has measured the blood levels of
vitamin C or histamine in cases of suspected SBS. The possible
existence of vitamin C deficiency is therefore hypothesized from
clinical, radiological, and other laboratory findings. There are
several features, common to both cases, that predispose to or are
consistent with a diagnosis of vitaminCdeficiency:
1. The mothers had documented nutritional problems and were
unwell during their pregnancies.
2. The mothers smoked during their pregnancies, thereby
lowering their own and their infantsvitaminClevels.
3. Both infants were being formula fed at the time of their
illnesses, and the mothers were not advised to give supplemental
4. Both parents reported early evidence consistent with
Barlows disease: spontaneous bruising in one infant and delayed
wound healing in the other.
5. Both infants had deficiencies in essential and nonessential
amino acids necessary for the production of normal collagen, which
is essential to prevent scurvy.
6. Both infants had evidence of liver dysfunction.
7. Unexplained fractures were recorded in both children.
In addition to the low amino acid levels, the second infant had
additional evidence of malnutrition in that the serum albumin,
calcium, and hemoglobin levels were all low.
Animal experiments have demonstrated that administration of
vitamin C can counter some of the ill effects of nicotine in
newborns. This suggests that mothers who smoke may
compromise vitaminClevels in their children.
One essential function of vitamin C is maintenance of normal
connective tissue by the hydroxylation of proline and lysine in
procollagen, using the enzyme prolyl hydroxylase with vitamin C
as a cofactor. While vitamin C has numerous other functions, this
one maintains the integrity of the blood vessels, bones, and dentine,
which is compromised in scurvy, leading to the manifestations that
might be mistaken for SBS. A lack of normal collagen causes
capillary walls to break down, and hemorrhaging may occur from
any site in the body. Expansion at the ends of the costochondral
junctions is highly suspicious for scurvy, and should in itself have
raised questions about the diagnosis of SBS.
Formula feedings are often heated before being given to the
infant, and heat destroys vitamin C. Under such circumstances,
vitamin C supplements are needed to prevent scurvy. Neither infant
received a supplement.
The increased level of von Willebrand factor antigen in the
second infant could be the result of the release of the antigen from
scurvy-disrupted capillary endothelial cells in which it is
produced. Alternatively, von Willebrand factor is a known acute
phase reactant that is possibly increased in response to the
stimulus of vaccination.
Clemetson has shown that increasing levels of blood histamine
are accompanied by lower vitaminClevels. As part of the immune
response to vaccines, mast cells liberate histamine, causing further
widening of the intercellular spaces between the vascular
endothelial cells in children who may have subclinical scurvy.
Although it has not been established that vaccinations cause
vitamin C deficiency, the inverse relationship between histamine
and vitamin C levels in the blood would support the hypothesis that
vaccinations could lead to vitamin C deficiency, and might explain
Follis, reporting the sudden deaths of three infants with scurvy,
observed that the liver was yellowish and showed atrophy of the
central cells and a good deal of fatty infiltration. As noted, some
liver enzymes in both infants were abnormal.
Post-immunization deaths in aboriginal children in Australia were
greatly reduced when Kalokerinos administered vitamin C by IM
injection before, and sometimes after, immunizing the child. Many
of these children had the classical signs and symptoms of scurvy.
Although neither vitamin C levels nor histamine in the blood
were measured, clinical, radiological, and laboratory findings
suggest that the diagnosis of SBS should be questioned in these two
cases. Poor nutrition and possible vaccine-induced vitamin C
deficiency associated with temporary brittle bone disease may
represent alternative explanations. Infantile scurvy, while
uncommon in affluent countries, should nevertheless be routinely
excluded before a diagnosis of SBS is made.
Michael D. Innis, MBBS, DTM&H, FRCPA, FRCPath
is honorary consultant hematologist, Princess Alexandra Hospital, Brisbane,
Queensland, Australia. Contact: 1 White-Dove Court, Wurtulla,
Queensland, Australia 4575. Phone +61 (0)7.5493.2826. Fax +61
(0)7.5493. 2826. Contact: firstname.lastname@example.org.
I wish to thank the parents of the children reported
here for sendingmethe records of the children and allowingmeto report the
results of the investigation.
Potential Conflict of Interest:
Dr. Innis has have been paid consulting fees
in three cases of alleged child abuse, but in none of them was the question
of vaccination raised. He has given his opinion pro bono in several others.