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Vaccines, Apparent Life-Threatening Events,
Barlow's Disease,
and Questions about "Shaken Baby Syndrome"
Michael D. Innis, MBBS
ABSTRACT
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
(Barlow?s 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.
Definitions
Overview
"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. 1, 2 -6
Michael D. Innis, MBBS 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 Barlow?s 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 infant's 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),
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 baby?s 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.
No cord compression or deformity." 6, 7, 8
Case 1
Hemophilus influenzae
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,
8.2-14.1); partial thromboplastin time, 35.5 sec (28.0-50.0); aspartate
aminotransferase, 97 U/L (20?60); glycine, 131 µmol/L (224?514);
lysine, 66 µmol/L (114?269); hemoglobin, 11.0 g/dL (10- 13.5);
platelets, 382 x 10 /L (150?450); pH, 7.26 (7.35-7.45); bicarbonate,
18.2 mmol/L(21?29); and glucose, 188 mg/dL(60?80).
The recorded diagnoses were "non-accidental injury" and
"shaken baby syndrome." The infant survived, but was
developmentally delayed and required a gastrostomy.
A emale 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 short interval.
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 examination. 9
Case 2
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 Nelson's
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 50-125); vonWillebrand factor antigen, 253 IU/dL
(50-246); fibrinogen, 4.0 g/L (1.7-4.0); alkaline phosphatase, 321
U/L (65-265); alanine transaminase, 59 U/L (5-45); lactate, 6.6 mmol/L
(1.1-2.2); calcium, 2.32 mmol/L (2.37-2.74); albumin, 28 g/L (35-55);
lysine, 55 µmol/L (100-300); hemoglobin, 9.0 g/L (10-13.5);
lymphocytes, 2.80 x10 /L (3-13.5); and osinophils, 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 also reduced. 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 doctor's 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
Barlow's 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 vitamin C deficiency:
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 infants' vitamin C levels.
3. Both infants were being formula fed at the time of their illnesses,
and the mothers were not advised to give supplemental vitamin C.
4. Both parents reported early evidence consistent with Barlow's 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 vitamin C levels 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 vitamin C levels. 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 spontaneous
bleeding.
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.
Conclusion
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 11, 1
2, 1 3, 1 4, 15 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: micinnis@ozemail.com.au.
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.
Acknowledgements:
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.
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