07july13-17

13 July 07 - Respiration and circulation during and after birth, ongoing...

Thurlow JA, Kinsella SM. Intrauterine resuscitation: active management of fetal
distress. Int J Obstet Anesth. 2002 Apr;11(2):105-16.

Abstract: Acute fetal distress in labour is a condition of progressive

fetal asphyxia with hypoxia and acidosis. It is usually diagnosed by

finding characteristic features in the fetal heart rate pattern, wherever

possible supported by fetal scalp pH measurement. Intrauterine

resuscitation consists of applying specific measures with the aim of

increasing oxygen delivery to the placenta and umbilical blood flow, in

order to reverse hypoxia and acidosis. These measures include initial

left lateral recumbent positioning followed by right lateral or knee-elbow

if necessary, rapid intravenous infusion of a litre of non-glucose

crystalloid, maternal oxygen administration at the highest practical

inspired percentage, inhibition of uterine contractions usually with

subcutaneous or intravenous terbutaline 250 microg, and intra-

amniotic infusion of warmed crystalloid solution. Specific manoeuvres

for umbilical cord prolapse are also described. Intrauterine

resuscitation may be used as part of the obstetric management of

labour, while preparing for caesarean delivery for fetal distress, or at

the time of establishment of regional analgesia during labour in the

compromised fetus. The principles may also be applied during inter-

hospital transfers of sick or labouring parturients.

Ibrahim HM, Krouskop RW, Lewis DF, Dhanireddy R. Placental transfusion:
umbilical cord clamping and preterm infants. J Perinatol. 2000 Sep;20(6):351-4.

OBJECTIVE: To investigate the clinical effects of early versus late cord

clamping in preterm infants. STUDY DESIGN: A total of 32 premature

infants were prospectively randomized. The following parameters were

measured: Initial spun hematocrit (Hct), hemoglobin (Hgb), red blood

cell (RBC) counts, frequency of blood transfusions, peak serum

bilirubin, mean blood pressure (MBP), oxygen index, intraventricular

hemorrhage, and significant patent ductus arteriosus (PDA).

RESULTS: Over the 4-week study period, the delayed cord clamping

(DCC) group exhibited a decrease in the frequency of blood

transfusion (p < 0.001) and also a decrease in albumin transfusions

over the first 24 hours (p < 0.03). MBP in the first 4 hours was higher in

the DCC group (p < 0.01), and there were statistically significant

increases in Hct (21%), Hgb (23%), and RBC count (21%) compared

with the early cord clamping group. The risks of patent ductus

arteriosus, hyperbilirubinemia, or intraventricular hemorrhage were

similar in both groups. Late clamping of the umbilical cord had little or

no effect on the oxygen index. CONCLUSION: DCC significantly

reduced the requirement for blood and albumin transfusion. It also

increased the initial Hct, RBC count, Hgb levels, and MBP.

STALLABRASS P. UMBILICAL CORD. Br Med J. 1964 Oct 24;2(5416):1070-1.

GAISFORD W. OBSTETRICS IN GENERAL PRACTICE. CARE OF THE
NEWBORN INFANT. Br Med J. 1964 Jul 4;2(5400):35-6.

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14 July 07 - Is autism a variant of kernicterus? Ongoing...

Shapiro SM. Definition of the clinical spectrum of kernicterus and bilirubin-
induced neurologic dysfunction (BIND). J Perinatol. 2005 Jan;25(1):54-9.

There have also been suggestions of a relationship of moderate

levels of hyperbilirubinemia to the subsequent development of

other disorders such as attention deficit hyperactivity disorder

(ADHD), Parkinson disease, and even autism, but so far, there is

no evidence to support these contentions. [p 57]

Auditory-predominate kernicterus may manifest as moderate or

severe AN, with or without a hearing loss, with minimal or mild

motor symptoms and perhaps a normal or slightly abnormal

globus pallidus or a subthalamic nucleus as seen in MRI. [p57]

Langen M, Durston S, Staal WG, Palmen SJ, van Engeland H. Caudate Nucleus
Is Enlarged in High-Functioning Medication-Naive Subjects with Autism. Biol
Psychiatry. 2007 Jan 12 -- Biological Psychiatry, Volume 62, Issue 3, 1 August
2007, Pages 262-266.

IN THIS ISSUE-AUGUST 1ST

Abnormal Patterns of Brain Development in Autism

Langen et al. (pages 262–266) investigated the involvement

of the basal ganglia in autism. They examined magnetic

resonance imaging (MRI) brain scans from two independent

samples of children and adolescents with autism and matched controls

and found enlarged caudate nucleus volumes in the autism group in

both samples. As both samples were medication-naive, this implicates

the basal ganglia in the expression of this disorder.

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17 July 07 - Myers patterns of perinatal brain damage

Myers RE. Two patterns of perinatal brain damage and their conditions of
occurrence. Am J Obstet Gynecol. 1972 Jan 15;112(2):246-76.

Excerpts:

"Term monkey fetuses are exposed to rigorously timed episodes of

total asphyxia by slipping a thin, saline-filled, rubber sac over the fetal

head at surgical delivery and clamping the umbilical cord. The

envelopment of the fetal head prevents the onset of air breathing while

the clamping of the umbilical cord abruptly halts fetal placental

circulation." [p247]

"The first evidence for damage to the brain following resuscitation and

extended survival occurs in unanesthetized term fetuses subjected to

10 min. of total asphyxia. Term fetuses asphyxiated for longer than 25

min. die in the early hours in the intensive care u nit of progressive and

intractable heart failure due to injury of the myocardium" [p251]

"The brain center earliest damaged are the inferior colliculi as

illustrated in Fig. 3. Thereafter, in a monotonously repetitive rank

order, follow other brainstem structures including the superior olives,

the sensory nuclei of the trigeminal nerve, the gracile and cuneate

nuclei, the medial and spinal vestibular nuclei, and the posterior and

lateral ventral thalamic nuclei. These structures are injured by

asphyxial episodes lasting for only 10 to 13 min." [p251]

"The ultrastructural changes include mitochondrial shrinkage and loss

of the structural integrity of all constituent membranes. The cell-limiting

membrane appears most sensitive in this regard while the nuclear

membrane is most resistant.

... Zones of destructive change after a time lag, stimulate an infiltration

of mononuclear cells from the bloodstream.

... The rank order of involvement of the various brainstem structures

following total asphyxia remains constant from animal to animal" [p253]

"The ranking of brain structures in their order of susceptibility to injury

following total asphyxia duplicates, in general, their ranking with regard

to their volume flow of blood per unit time as determined by 14C-

labeled antipyrine diffusion studies. The inferior colliculus, the

structure most outstandingly vulnerable to total asphyxia, is also the

structure most highly perfused with blood (fig. 7

- see below

... The brainstem injury pattern produced in the monkey fetus by total

asphyxia bears no relation to the brain pathology typifying human

perinatal damage. In actuality, this distinctive brainstem injury pattern

appears only rarely in the human brain. When seen, it appears almost

exclusively in infants or young children following cardiac arrest." [p254]

"The fetus, still in uter, may be subjected to an entirely different type of

asphyxial assault characterized by a

partial

rather than a

total

interference with its respiratory gas exchange." [p256]

"In utero, partial asphyxia of the fetus may be brought about in a variey

of ways. Infusion of excessive oxytocin into the maternal bloodstream

was the method first used experimentally in our laboratory.

... Subsequently, fluorothane hypotension, mechanical constriction of

the maternal abdominal aorta, and experimental partial placental

ablation have also proved effective in producing asphyxia.

... The greatest experience has been achieved with maternal aortic

constriction." [p257]

IN PROGRESS...

Myers RE. Four patterns of perinatal brain damage and their conditions of
occurrence in primates. Adv Neurol. 1975;10:223-34.

Abstract:

The findings described in the present study are summarized

in Table 1. It may be noted that anoxia or total asphyxia, whether in the

newborn animal or in the (see article) adult, leads to patterns of injury

in the brainstem. Hemispheral structures outside the thalamus seem to

be entirely spared in those animals which survive. In contrast to this,

situations leading to hypoxia associated with severe acidosis, usually of

a mixed respiratory and metabolic type, cause brain edema; and when

the edema is limited in its distribution, the damage is restricted to

specific cortical loci. When the cerebral edema becomes more

generalized owing to spread of the process, more and more extensive

regions of the hemispheres are damaged until the entire cerebrum may

become necrotic. On the other hand, clinical circumstances which lead

to hypoxia but without acidosis of any great magnitude--usually due to

the indolence of the process or to an associated hyperventilation of the

mother--produce lesions which may be restricted to the white matter.

These processes may be characterized by perivenular white matter

hemorrhage and/or focal areas of periventricular leucomalacia. Finally,

those clinical circumstances which lead to combined episodes of

hypoxia plus anoxia with acidosis favor a predominance of lesions that

affect the basal ganglia.

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18 July 07 - Milieu Research, and visit from Cardinal Sean O'Malley
Assigned to work in our Intensive Treatment Unit (ITU) today, a gray rainy day, with
several patients in acute distress. I went out to check up on a patient who has
been refusing to eat or drink, and reluctant to talk with anyone. To my surprise,
there was Cardinal Sean O'Malley of the Catholic Archdiocese of Boston,
bestowing a blessing on this patient. Our hospital superintendent, Karin Bergeron,
introduced me to Cardinal O'Malley, who then spoke briefly with me, and told me
he spent two years as a prison chaplain. This was a very moving experience --
and the patient appeared much less despondent later this afternoon, and
agreeable to finally trying a medication he has steadfastly been refusing.

18 July 07 - Myers' Two Patterns excerpts, continued

Myers RE. Two patterns of perinatal brain damage and their conditions of
occurrence. Am J Obstet Gynecol. 1972 Jan 15;112(2):246-76.

"Alterations in blood flow in the brains of term monkey fetuses

subjected to in utero partial asphyxia have been objectively

demonstrated with the use of 14C-labeled antipyrine (Reivich M et al. in

Meyer JS, ed, Research on the cerebral circulation, Fourth Salzburg

Conference on Cerebral Flow, 1970, LOC call #

RC388.5 .I5 1968).

These studies show that the brunt of blood flow alterations is felt by the

hemispheres." [p265]

"When an episode of partial aspphyxia endures for from 1/2 hr. to

several hours (depending on its severity), injury to the fetal brain may

result. The observed patterns of injury are variable and form a

spectrum extending from, at one extreme, a total hemispheral necrosis

(fig 21), usually associated with a failure to survive beynond the first

hours of birth, to circumscribed damage to the middle third of the

paracentral cortical region (fig 22).

... Animals with restricted injury may also die early or may survive into

adult life as palsied individuals.

... basal ganglia damage may occur both with or without concomitant

injury to the cerebral cortex.

... When episodes of total asphyxia are superimposed upon episodes

of partial asphyxia, the characteristic brainstem injury pattern may also

be manifest." [p267]

... "The close similarities between the brain pathology of in utero partial

asphyxia in the monkey and the pathology of cerebral palsy in the

human being suggest that in utero partial asphyxia may play a major

role in the pathogenesis of cerebral palsy in the human being.

... No treatment can recover the usefulness of cerebral tissue which

has become necrotic following the development of brain swelling and

the exclusion of cerebral circulation. Thus the combination of

depressed consciousness, decerebrate posturing, seizures, bulging

fontanels, and retinal hemorrhages in the newly born infant associated

with a history of asphyxia during birth bespeaks a grave prognosis."

[p269]

"All delivery rooms and infant intensive care units should be provided

with ventilators designed for human infant use

... However, the lungs of newborn infants, particularly of premature

ones, may be overinflated to the point of mechanical injury...." [p 272]

"Following asphyxia, cardiovascular performance may be so depressed

that it provides the infant with little or no circulation despite ECG

evidence of heart action. Under such circumstances, the institution of

artificial pulmonary ventilation alone is without result. The second step

of crucial importance, then, is the provision of a sufficient blood flow to

return the oxygenated by stagnant blood to the heart." [p273]

Figures 19 and 7 below, from Myers (1972) paper, show how blood flow in the
brain is affected by what he termed "partial asphyxia," or oxygen insufficiency
caused by impaired maternal circulation to the placenta (figure 19). With
diminished oxygen, circulation to the inferior colliculi and other brainstem nuclei
of high metabolic rate is increased (a protective mechanism), while blood flow to
the metabolically less active cerebral cortex is severely diminished.

Compare figure 19 B with figure 7, showing normal blood flow pattern, which is
highest in the brainstem, especially the inferior colliculi.

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Fig 19. Autoradiographs
demonstrating alterations
in fetal cerebral blood flow
produced by in utero fetal
partial asphyxia. The fetus
exposed to less severe
asphyxia (A) exhibited
decreases in blood flow
throughout major extents of
the cortical gray matter and
the centrum semiovale.
Only the striated cortex
region manifested
minimally in the way of
blood flow alteration. In
some areas, blood flow
reductions as large as 50
percent are observed in
this brain. With the
development of severe
hemispheral swelling as
indicated by the
compressions of the
superior cerebellar
surfaces, a total loss in
hemispheral perfusion
results (B). while the
brainstem is little affected,
the cerebellum may exhibit
symmetrical zones of
diminished perfusion.

Fig. 7. Autoradiograph of coronal brain section of normal newborn monkey. Just prior to being killed,
this animal sustained an intravenous infusion of 14C-labeled antipyrine. Staining density relates to
volume flow of blood per unit of tissue per unit of time. The central nuclei of the inferior colliculi stand out
due to their high-volume blood flow. (Courtesy C. Kennedy and L. Sokoloff, Laboratory of Cerebral
Metabolism, National Institute of Mental Health.)

21 July 2007 - Alex F. Robertson on errors in neonatology, III

Robertson AF.Reflections on errors in neonatology III. The "experienced" years,
1970 to 2000. J Perinatol. 2003 Apr-May;23(3):240-9.

Excerpts:

NEO-MUL-SOY FORMULA

"One of the swiftest responses to an error began on July 26, 1979

when three cases of failure to thrive and metabolic alkalosis were

reported to the Center for Disease Control (CDC). All three infants

were being fed a soy-based formula, Neo-Mul-Soy. On July 30, CDC

investigators surveyed a sample of pediatric nephrologists in the US

and found an additional 15 cases and another 16 cases from other

sources. All the infants had received either Neo-Mul-Soy or Cho-

Free, formulas produced by the same company. By August 2, the

company had analyzed the suspect formulas, met with the FDA,

halted manufacture, ordered a recall, and notified health-care

professionals throughout the country about the problem.7

Fortunately, the children recovered quickly when supplemented

with another formula or chloride.

The most complete discussion of the epidemic is contained in

an article by Dr. Shane Roy, the originator of the initial report

to the CDC.8 The metabolic alkalosis was caused by the renal

effects of chloride deficiency." [pp240-241]

"The factors leading to the deficiency of chloride in the formula

are very interesting. In the 1950s and 1960s, the concern surfaced

that hypertension might result from increased sodium intake in

infancy.9 Although this correlation was never verified, in 1971 the

American Academy of Pediatrics (AAP) recommended that the ‘‘salt

content’’ of infant foods be reduced." [p241]

ERYTHROMYCIN

"In February 1999, in Knoxville, TN, there was an outbreak of

pertussis involving six newborn infants. Since the most likely

source of infection was a hospital worker, the local health

department suggested prophylaxis of about 200 infants who may

have been exposed to that worker. The prophylaxis was the

antibiotic erythromycin as recommended by the American Academy

of Pediatrics.25 Approximately 6 weeks later, local pediatric

surgeons had a cluster of seven cases of pyloric stenosis, all of

whom had been born in the hospital where the erythromycin was

given and all had received the drug.26 The results of a cohort study

showed that none of the infants who had not received erythromycin

in that time period developed pyloric stenosis." [p241]

PROPYLENE GLYCOL

"In 1983, Glasgow et al.36 reported four infants with serum

hyperosmolality (4300 mosm/l) related to elevated levels of

propylene glycol in the blood. The source was a parenteral

multivitamin preparation (MVI-12) containing propylene glycol. As

mentioned in the article, the authors had changed multivitamin

preparations in their NICU to one containing biotin and had

increased the volume of vitamin solution given to provide adequate

amounts of the other vitamins.36 This change led to a 10-fold

increase in the propylene glycol dose. The vitamin preparation used

was not recommended for patients under 11 years of age." [p243]

BENZYL ALCOHOL

"In 1981, at the SSPR meeting Gershanik et al.38 reported five

preterm infants with severe metabolic acidosis, hepatic and

renal failure, and signs of neurological deterioration. A striking

clinical aspect was the onset of gasping respirations and the

authors named the illness the ‘‘gasping’’ syndrome. Unmetabolized

benzyl alcohol was found in the urine. An additional 10 babies

with the ‘‘gasping’’ syndrome died in Oregon that year and were

reported by Brown et al.39 The infants were all of very low birth

weight, in the first days of life and had central venous catheters

(umbilical artery and/or vein) that were flushed frequently using

bacteriostatic normal saline containing 0.9% benzyl alcohol. These

cases were reported to the FDA, which recommended the exclusion

of benzyl alcohol from flush solutions and diluents used in

newborns." [p243]

"On May 28, 1982, the Food and Drug Administration (FDA) sent

letters recommending that flush solutions used in newborns should

not contain benzyl alcohol or any other preservative." [p244]

INTRAVENOUS (I.V.) VITAMIN E

"In 1949, before the implication of oxygen as a cause of retrolental

fibroplasia (RLF), Owens and Owens56 postulated that RLF

was related to vitam

in E deficiency.

...Although further trials during the 1970s on the efficacy of

vitamin E in ameliorating RLF were conflicting, many nurseries

administered the vitamin orally to their premature infants.

... In December 1983,

E-Ferol Injection for intravenous administration was introduced

... Within months of E-Ferol’s introduction to neonatal care,

neonatologists began to note clusters of premature babies who

developed hepatomegaly, thrombocytopenia, cholestatic jaundice,

ascites, and azotemia.

... On

April 16, 1984, the FDA issued an Urgent Class I Drug Recall letter,

indicating that the drug was being voluntarily recalled by the

company." [pp244-245]

STEROIDS

"There is controversy about the relation between steroid therapy

(used for the treatment or prevention of bronchopulmonary

dysplasia (BPD)) and cerebral palsy." [p245]

"BPD was first described by Northway et al.68 in 1967.

With improvements in infant ventilators, more small infants

survived and more infants had chronic lung disease. BPD was

(and still is) the greatest disappointment in neonatal care..." [p246]

" ... I was ready to accept any treatment and

remember exactly when I started using corticosteroids. The year

was 1985 and Dr. Spencer Brudno had just joined our faculty. In

January, he had co-authored with Avery, Fletcher, and Kaplan an

article describing the beneficial results of dexamethasone in infants

with BPD.69 The treatment caused improvement in pulmonary

compliance and rapid weaning from the respirator. This early

study, and the few preceding it, did not provide developmental

follow-up data." [p246]

"Yeh et al.74 in 1998 and O’Shea et al.75 in 1999 showed an increase

in neuromotor dysfunction and cerebral palsy in dexamethasone

treated

infants. An excellent review of the many aspects of this

question is presented by Watterberg.

Evaluating this subject as a possible error is difficult at this

time and this discussion is not complete. Infants with BPD are at

risk for poor neurodevelopmental outcome regardless of the

treatment."

[p246]

CAUSES OF ERRORS

"In all these episodes, excluding the vitamin E tragedy, the

motivation leading to harmful treatments was an honest desire to

improve the care of infants." [p246]

"Many of these events, regardless of the process error, have

resulted from the use of pharmacological agents (synthetic vitamin

K, sulfisoxazole, chloramphenicol, novobiocin, hexachlorophene,

erythromycin). New pharmacological agents have been and will

continue to be a danger in neonatology. Many adverse effects may

not be seen in small population studies performed for licensing." [p247]

"The greatest hazard since the ‘‘Hands Off’’ years has been

unexpected reactions to drugs." [p247]

"I hope that by studying these mistakes, we will avoid some

future problems or at least recognize the problems early in their

course." [p247]

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23 July 2007 - Alex F. Robertson on errors in neonatology, II

Robertson AF.Reflections on errors in neonatology: II. The "Heroic" years, 1950 to
1970. J Perinatol. 2003 Mar;23(2):154-61.

In this paper, Robertson summarized innovations in neonatal care that had come
about since the 1920s. Most notable were (1) exchange transfusions for infants with
"Rh isoimmunization," and (2) use of antibiotics.

(1)

Rh isoimmuniaztion had formerly been known as erythroblastosis fetalis,

or jaundice

and anemia caused by destruction of red blood cells of the

infant by maternal

antibodies to the Rh factor.

By the 1960s, RhoGam (or anti-D) immune globulin had been developed,

which

given to an Rh-negative mother after the birth of her first child,

prevents formation of

anti-bodies to the Rh factor. The maternal-placental

barrier prevents any fetal blood

from getting into the mother's circulation

throughout gestation. It appears

unquestioned why this barrier is breached

during the process of birth, but clamping

of the umbilical cord (also

unquestioned as possibly dangerous) suddenly shuts off

blood flow from

the placenta to the newborn infant. Blood backing up in the placenta

causes bursting of capillaries, with leakage of fetal blood into the mother's

blood

stream. Waiting for the placenta to be born, with the umbilical cord

intact, allows

placental blood to be completely transferred to the infant.

Placental blood is respiratory blood, and would appear by nature's plan

intended to

be transferred to the capillaries that supply the infant's alveoli.

Carbon dioxide

previously exchanged for oxygen in the placenta is then

released into the alveoli for

exhalation. The first breath then refills the

alveoli newly expanded by carbon

dioxide.

For more on reflexes involved in

breathing, s

Marsh MJ

et al.

Pediatr Pulmonol. 1994 Sep;18(3):163

What human hubris

ever led to

interference with this plan for all placental

mammals?

(2)

Antibiotic medications had been enthusiastically adopted without any

question of how

they might produce adverse reactions. However,

antibiotics disrupt metabolism in

bacteria, and they likewise can disrupt

metabolism in mitochondria, which are

thought to have been a primeval

symbiotic inclusion (or infection) in

early

multicelluar

organisms, symbiotic

because they contain enzymes of aerobic metabolism. See for

instance

Zhang L

et al.

FEBS Lett. 2005 Nov 21;579(28):6423

In this paper Robertson also discussed the Bloxsom air-lock incubator, epsom salt
enemas, the antibacterial soap Hexachlorophene, laundry detergents, and
disinfectant cleaning agents.

Excerpts:

"These years were

exciting. Silverman (1) refers to ‘‘therapeutic exuberance’’; Baker

describes a ‘‘great spirit of innovation, somewhat lacking in

discipline’’ and refers to the ‘‘heroic’’ era (2). All treatments were

new, untested, and we marched on without fear! As a result of our

uncritical enthusiasm for treatment, many errors occurred." [p154]

(1)

Silverman WA. Retrolental Fibroplasia: a modern parable. New York:

Grune

& Stratton, 1980.

ANTIBIOTIC ERRORS

"In 1879, Pasteur demonstrated bacteria in the

blood and lochia of puerperal sepsis victims. The organism was

Group A Streptococcus. The use of careful antiseptic practices was

the only recourse against infection until the introduction of

sulfonamides in the 1930s and then penicillin in the 1940s." [p155]

"In 1953, a newly available sulfonamide,

sulfisoxazole, was introduced and had the advantage of requiring

less frequent dosing to maintain adequate blood levels. No

problems were recognized with its use. When the use of

subcutaneous oxytetracyclene was suggested, a controlled study was

begun comparing this drug to the accepted regimen of penicillin

and sulfisoxazole. ‘Much to our amazement, the first trial gave a

definitive result. To our horror, the mortality rate was highest (and

strikingly so) in infants who received the established treatment!’

The cause of the increased mortality rate was kernicterus which, at

aut

opsy, was nine times increased." [p155]

"Sutherland published the first description of three cases of

cardiovascular collapse in newborn infants receiving large doses of

chloramphenicol. The infants were treated because of prolonged

rupture of the membranes and concern about infection. A few days

after the treatment began, the infants developed abdominal

distention, slate-colored or pallid cyanosis (the ‘gray baby’

syndrome), cold moist skin, and weak pulse; they died shortly

thereafter.

" [p156]

... The tragic

practice of using chloramphenicol ended in about 1960 as these

reports became common knowledge in medical circles.

" [pp156-157]

In 1959, there was a staphylococcal infection epidemic in a

term newborn nursery at the Cincinnati General Hospital. To abort

the outbreak, novobiocin was given to all infants admitted to the

nursery since the organism was resistant to penicillin and

erythromycin. An increase in the number of infants with

hyperbilirubinemia was quickly noted by Dr. Sutherland, who had

earlier been one of the first to recognize chloramphenicol toxicity.

... Fortunately, none of the infants in the Cincinnati epidemic

developed kernicterus during their hospitalization and only 12

babies required exchange transfusion. It was fortunate that this

effect was recognized before the drug was used widely in newborn

infants."

[p157]

EQUIPMENT CLEANING

"In 1972, doctors at a New Jersey hospital performed five exchange

transfusions for hyperbilirubinemia in a period of 36 hours.

... Staff members

reported that, in preparation for one of their colleagues delivery,

they cleaned the bassinet reserved for that baby several times with

their routine disinfectant detergent (Vestal LpH, Vestal Laboratories,

St. Louis MO). That baby needed three exchange transfusions for

jaundice. This led to an investigation of the disinfectant which

contained several phenolic compounds. "

[p160]

"These cases demonstrate the

unique susceptibility of newborn infants. As the investigators

mention,56 newborn infants absorb materials easily through their

epidermis. Also, their respiratory rate is higher than adults so

newborn infants may inhale larger amounts of environmental

contaminants." [p160]

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24 July 2007 - Alex F. Robertson on errors in neonatology, I

Robertson AF. Reflections on errors in neonatology: I. The "Hands-Off" years, 1920
to 1950. J Perinatol. 2003 Jan;23(1):48-55.

Excerpts:

SUPPLEMENTAL OXYGEN

"However, as the survival of smaller infants improved, the

incidence of RLF continued to be significant in very small premature

infants and was renamed retinopathy of prematurity (ROP) to

indicate its relation to gestational age. The search for ROP’s etiology

continues." [p 52]

SMA FORMULA CHANGE

"In December 1952, the FDA received a letter from a nurse in Arkansas

whose 3-month- old infant had developed convulsions. The

attending pediatrician apparently suspected that the condition was

related to the formula, SMA liquid. The formula was changed to an

evaporated milk formula and the child recovered. The mother heard

of eight similar cases and that led to her letter. Upon further

investigation, the FDA found that the manufacturer had heard of the

problem and knew of 12 cases.

... A detailed review of several additional

cases showed only one common factor: the infants had all been fed

liquid SMA formula and no solids.

... As SMA was the presumed culprit, the FDA began extensive

investigations for toxic materials.

Vitamin assays were performed and the level of

vitamin B6 was found to be quite low. Wyeth sent a general notice to

all physicians describing this problem with their formula. A national

survey revealed 300 cases of formula- induced vitamin B6

deficiency."

[p53]

SYNTHETIC VITAMIN K PROPHYLAXIS

"The prophylactic use of vitamin K in newborns began in the early

1940s and was the second routine pharmacological treatment of

newborn infants; the first being the use of silver nitrate to prevent

ophthalmia neonatorum begun by Crede´ in 1881. In 1954, the

American Academy of Pediatrics recommended a dose of 5 mg of

synthetic vitamin K for all newborn infants."

"In 1955, Allison,42 in a short letter to The Lancet, mentioned his

experience of seeing cases of hemolytic anemia, hyperbilirubinemia,

and kernicterus in premature infants treated with large doses of

synkavit, a water - soluble vitamin K analogue. ...

... I can find no publication that gave a rationale for or advocated

the use of increased doses of vitamin K. Again, it is impossible to

quantitate the damage done but, considering the broad use of large

doses of synthetic vitamin K and the years of use (1945–1961), I

believe it was extensive."

[p53]

Comments:
(1) More on retinopathy of prematurity. Is ischemia the real cause? See, for
example, Jandeck C et al. Retinopathy of prematurity in infants of birth weight > 2000
g after haemorrhagic shock at birth. Br J Ophthalmol. 1996 Aug;80(8):728-31.

(2) Blood-brain barrier damage is more likely the real cause of kernicterus, from
multiple toxic factors, or ischemia. Bilirubin is not directly disruptive to the blood-
brain barrier, but stains the nuclei in which the blood-brain barrier has been
breached. More and more on this ongoing...

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