M e d i c a l L i a b i l i t y a n d H e a lt h C a r e L a w
Chorioamnionitis
By Walter J. Price III
Recent studies may
provide an objective
causation defense to
claims of negligence in
labor and delivery care.
An Alternative
Cause for
Cerebral Palsy
Lawyers defending health-care providers have long recognized that many, many cases arise from labor and delivery.
Some of the more significant cases include claims involving cerebral palsy. “Unexpected adverse outcomes” represent one of the most frequent reasons for litigation. Baergen, The Placenta as Witness,
34 Clin. Perinatol. 393 (2007). Generally,
in cerebral palsy cases plaintiffs question
predelivery monitoring and treatment,
especially in the face of “nonreassuring”
fetal monitoring results. Plaintiffs associate cerebral palsy with asphyxia allegedly
demonstrated by fetal monitor strips. However, emerging medical evidence points to
infection and an associated inflammatory
process as an alternative, significant cause
of cerebral palsy in infants.
Background
Cerebral palsy occurs in 1 to 2.4 cases per
1,000 live births. Muraskas, et al., A Proposed Evidence-­Based Neonatal Work-Up to
Confirm or Refute Allegations of Intrapartum Asphyxia, 116 Obstetrics and Gynecology 261 (2010); Wu, et al., Chorioamnionitis
and Cerebral Palsy in Term and Near-Term
Infants, 290 JAMA 2677 (2003). Cerebral
palsy is a group of nonprogressive motor
■ Walter J. Price III is an attorney with Huie Fernambucq & Stewart LLP
in Birmingham, Alabama, where he practices in the areas of medical malpractice, professional errors and omissions, product liability, and insurance
defense. Mr. Price is a member of DRI, the Alabama Defense Lawyers Association, and the International Association of Defense Counsel.
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© 2012 DRI. All rights reserved.
impairment syndromes characterized by
spasticity, movement disorders, muscle
weakness, ataxia, and rigidity. Koman, et
al., Cerebral Palsy, 363 The Lancet 1619
(2004). Birth asphyxia can cause cerebral
palsy, though it does not account for most
cases. Nelson, Causative Factors in Cerebral Palsy, 51 Clinical Obstetrics and Gynecology 751 (2008). Indeed, studies estimate
the number of such cases as only 20 percent, or even as low as 8 to 10 percent. Yoon,
Intrauteran Infection and the Development
of Cerebral Palsy, 110 (Suppl. 20) BJOG 124
(2003); Perlman, Intrapartum Hypoxic-­
Ischemic Cerebral Injury and Subsequent
Cerebral Palsy: Medicolegal Issues, 99 Pediatrics 851 (1997). A majority of cases of
cerebral palsy occur in term infants. Nelson, supra, at 749.
As noted, in litigation plaintiffs generally
claim that fetal heart-rate monitoring can
identify inutero asphyxia occurring in connection with delivery, and poor outcomes,
including cerebral palsy, resulting from the
failure of the involved health-care providers
to recognize this condition and accelerate
delivery. Fetal monitoring has become an
accepted part of predelivery care. Similarly,
delivery by Cesarean section has continued
to increase. Nonetheless, researchers have
noted that despite the use of fetal heart-rate
monitoring, as well as other improvements
in care, the rate of cerebral palsy has not
declined over the past 30 years. Id. A “fivefold” increase in delivery by Cesarean section accompanies this. Muraskas, supra, at
261. This evidence calls into question the
causal relationship between birth asphyxia
and the failure to recognize it during the delivery process and injury.
Notably some scientists have not only
questioned this connection but also the use
of fetal heart-rate monitoring tracings and
their interpretation as evidence supporting
liability. For example, the terms generally
used to assess negative changes reflected by
fetal monitoring, such as “fetal distress” and
“nonreassuring pattern,” are vague and subjective. Schifrin, et al., Medical Legal Issues
in Fetal Monitoring, 34 Clin. Perinatol, 330
(2007). Moreover, the alleged injury mechanism, birth asphyxia, also involves an
“imprecise” definition. Perlman, Intrapartum Asphyxia and Cerebral Palsy: Is There
a Link? 33 Clin Perinatol. 336 (2006). In addition, the often poor quality of fetal heart
tracings during the expulsive stage of labor
further reduces the ability to assess poor oxygenation at that point. Schifrin, supra, at
332. Thus, liability may rest upon opinions
that rely on inexact concepts. In fact, one
study calls into question whether someone
could assess and confirm that a poor neurologic outcome was actually avoidable:
Thus, the inability to assess prospectively: a) the fetal adaptive mechanisms
to maintain cerebral perfusion and
metabolism, or b) the inherent tolerance
or resistance of the fetal brain to intrapartum asphyxia using current markers render it almost impossible, with any
degree of certainty, to offer a legal opinion as to whether an alternative medical
strategy could have altered the neurologic outcome or whether the outcome
was an unavoidable act.
Perlman, Intrapartum Hypoxic-­Ischemic
Cerebral Injury in Subsequent Cerebral
Palsy: Medicolegal Issues, 99 Pediatrics 857
(1997).
As suggested above, questions also persist about the causal link between birth asphyxia, as purportedly shown through fetal
monitoring, and cerebral palsy. Emerging
research findings indicate that maternal infection and associated inflammation frequently alternatively could cause cerebral
palsy. Maternal infection may affect the placenta resulting in inflammation of the inner two layers of the lining of the placenta,
the chorion, and the amnion. Research has
linked the resulting infection-­induced inflammation, chorioamnionitis, with cerebral palsy. As discussed further below,
the exact cause of injury remains unclear,
though researchers have identified a firm
relationship between chorioamnionitis and
cerebral palsy. Not only does this cast doubt
on the medical cause of injury that plaintiffs
often assert, chorioamnionitis frequently is
clinically silent and requires a pathologic
study of the placenta to identify it, which
challenges proof of liability.
Involved Anatomy
A placenta is a temporary organ that
attaches to the wall of a mother’s uterus.
It provides oxygen and nutrients to a fetus,
as well as removes waste products from
the fetal blood. A placenta also protects a
fetus from infection, trauma, and toxins.
Redline, Disorders of Placental Circulation
and the Fetal Brain, 36 Clin. Perinatol. 549
(2009). A placenta has two internal layers,
the chorion and the amnion; the amnion
makes contact with the amniotic fluid in
which the fetus is maintained.
The umbilical cord attaches the placenta
and the fetus. It is made up of three blood
vessels. These include two smaller arteries that carry blood from a fetus to the placenta and a larger vein that returns blood
from the mother to the fetus. WilliamsObstetrics 107 (17th ed. 1985). In supplying
oxygen and nutrients to a fetus, maternal
blood leaves the mother’s arterial vessels
and forms “lakes” near the chorionic plate
where the exchange takes place. Id. at 108.
Inflammation is the body’s response
to an insult. Chorioamnionitis is inflammation of the chorion and the amnion.
Acute chorioamnionitis is identifiable by
the presence of leukocytes, or white blood
cells, in the amnion and the chorion. Baergen, Manual of Pathology of the Human
Placenta 284 (2d ed. 2011). Funisitis is
inflammation of the umbilical cord. It, too,
represents an inflammatory response. It
indicates a fetal response to a maternal
insult. The fetal response follows that of
the mother in time. Redline, Infections and
Other Inflammatory Conditions, 24 Seminars in Diagnostic Pathology 8 (2007).
Thus, finding funisitis establishes that an
infection and an inflammatory process
have persisted for a longer period of time,
which originated before delivery and birth.
Effects of Chorioamnionitis
and Funisitis
Acute chorioamnionitis has been associated with preterm deliveries, as well as
Chorioamnionitis
frequently is clinically silent
and requires a pathologic
study of the placenta to
identify it, which challenges
proof of liability.
“lung disease, poor long-term neurologic
outcome, and cerebral palsy.” Baergen, supra, at 282. Researchers have noted that an
infection “always” causes acute chorioamnionitis. Id. Bacteria in the cervicovaginal
tract usually initiates the infection. Reilly
& Faye-­Petersen, Chorioamnionitis and Funisitis: Their Implications for the Neonate, 9
NeoReviews 411 (2008). Interestingly, the
infection “occurs most often in the presence
of intact fetal membranes.” Baergen, supra,
at 283. Thus, contrary to the beliefs that lay
persons generally hold, an infection may invade a placenta, and even the amniotic sac,
causing an inflammatory response, even before a mother’s membranes have ruptured.
This, also, is significant to an inflammatory
process’ onset, which can even begin before
a health-care provider admits a mother to a
hospital in anticipation of a delivery. Various microorganisms may cause the infection. Baergen, supra, at 289.
Initially, a mother’s body responds to
an infection by releasing leukocytes. This
reaction begins in the intervillous space
and the maternal vessels of the decidua.
Baergen, supra, at 287. However, these leukocytes “always” migrate toward the amniotic sac. Id. Therefore, an inflammatory
response, as reflected by the presence of
leukocytes, can directly affect a fetus. In
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M e d i c a l L i a b i l i t y a n d H e a lt h C a r e L a w
addition, a fetus normally swallows and
breathes the amniotic fluid, exposing it to
the organisms contained in the amniotic
fluid. Id. However, studies have shown that
injury may occur even when a mother’s
infection hasn’t directly infected her fetus;
instead, a fetal inflammatory response
can trigger fetal inflammatory response
syndrome (FIRS). FIRS is a condition
Trained and experienced
placental pathologists
can… categorize the
inflammatory response into
“stages” by completing a
pathologic examination.
hypothesized to involve a “systemic fetal
inflammatory response” that can cause
multiple organ dysfunction, septic shock,
and death. Bashiri, et al., Cerebral Palsy
Fetal Inflammatory Response Syndrome: A
Review, 34 J. Perinat. Med. 9 (2006).
Finding neutrophils, a type of white
blood cells that attack invasive bacteria,
in the walls of the vein or arteries of an
umbilical cord indicates that something
has stimulated this fetal response. Redline, Inflammatory Response in Acute Chorioamnionitis, 17 Seminars in Fetal and
Neonatal Medicine 22 (2012). These neutrophils generally first appear in the chorionic vessels and the umbilical vein. As
discussed further below, pathologic review
identifies this as “Stage 1.” The next stage,
“Stage 2,” finds neutrophils in the wall
of the umbilical artery. Later, “Stage 3”
finds neutrophils in the Wharton’s jelly,
which surrounds the umbilical vessels. Id.
Chorioamnionitis and funisitis stages are
important because studies have associated
more severe responses with more severe
injuries, and finding that a process has
progressed as time passed could suggest
that the condition existed before labor or
a mother or a child received delivery care.
One study demonstrated that chorioamnionitis is “independently associated with a
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four-fold increase of CP [cerebral palsy] in
term infants.” Wu, supra, at 2680–81. This
same study noted that often birth asphyxia
was diagnosed despite finding chorioamnionitis. Id. at 2681. Significantly, for purposes of birth injury litigation, studies have
shown that conditions traditionally associated with hypoxic-­ischemic encephalopathy, such as low Apgar scores, meconium
in amniotic fluid, and neonatal seizures,
may actually result from the infectious or
the inflammatory process as opposed to a
hypoxic-­ischemic event. Nelson, supra, at
752. In other words, the effects of chorioamnionitis and funisitis may mirror those
associated with birth asphyxia, which
plaintiffs in litigation assert that poor fetal
heart tracings demonstrate.
The exact cause of inflammatory process
injury is not certain. Several noted theories include
1.Elevated levels of fetal cytokines in
the presence of maternal infection can
cause direct injury to a fetal brain by
stimulating the fetal inflammatory
response;
2.Inflammation of the placental membranes leads to interruption of placental gas exchange and blood flow
resulting in hypoxic-­ischemic brain
injury in a fetus;
3. Maternal fever raises the core temperature of a fetus, which, in turn, may
harm the developing brain, especially
when accompanied by cerebral ischemia; and
4.Maternal intrauterine infection leads
to direct infection of the fetal brain
or meninges, although this is rarely
seen.
Wu, supra, at 2682.
Regarding the first theory, cytokines are
proteins released by the immune system;
they regulate immune response. Studies
have identified increased concentrations of
cytokines in children with cerebral palsy.
Shalak, et al., 110 Clinical Chorioamnionitis, Elevated Cytokines, and Brain Injury in
Term Infants, Pediatrics 673 (2002). These
cytokines may cross the blood-brain barrier that protects brain cells from insults
from invading organisms. Id. at 677. However, these same proteins may be “toxic” to
the fetal central nervous system. Holcroft,
et al., Are Histopathologic Chorioamnionitis and Funisitis Associated with Met-
abolic Acidosis in the Preterm Fetus? 191
Am. J. Obstet. Gynecol. 2011 (2004). The
young fetal brain is particularly susceptible to injury by these inflammatory mediators. Nelson, supra, at 755. Complicating
the effort to locate the cause of injury is that
brain injury resulting from the inflammatory process “mimics the neuroradiological
findings of hypoxic-­ischemic brain injury
in term infants.” Wu, supra, at 2682.
Regarding the second theory, some
researchers suggest that the inflammatory
response may affect the placenta and cause
hypoxic-­ischemic brain injury. Others have
suggested that the fetal inflammatory
response could alone cause hypotension
with decreased perfusion to the watershed
regions of the brain. Id. Other potential
causes of reduced fetal perfusion associated with the inflammatory process include
vasoconstriction of the umbilical cord vessels and intravascular coagulation with
cerebral arteriolar obstruction. Id. In such
a scenario, a child would actually receive a
hypoxic-­ischemic injury, though the shocklike condition would cause it as opposed to
asphyxia resulting from some other insult.
Of course, someone would expect that a
plaintiff’s counsel would counter this theory by suggesting that the fetal monitor
was, by exhibiting signs of distress, reflecting the effects of the inflammatory process. Although, as alluded to previously, a
fetus may have experienced those effects
for some time preceding the period that the
fetal monitor recorded.
One study has referred to a maternal
fever; however, while fever may be associated with acute chorioamnionitis, as
noted, this condition mostly is “clinically
silent” and “diagnosed only after pathologic examination of the placenta.” Reilly
& Petersen, supra, at 411.
Practical Considerations
Since doctors may not always discover chorioamnionitis before birth, a substantial
issue to explore when litigating involves
whether the placenta has undergone pathologic review, which is the sole means of
confirming chorioamnionitis. Unfortunately, obstetricians do not always send a
placenta for a pathologic review. Muraskas, supra, at 262. Clinical issues also can
become relevant. For example, in most
cases intrapartum asphyxia “deprives all
other organs of oxygenated blood before
the flow of oxygen to the brain is diminished.” Muraskas, supra, at 266. As such,
an attorney must closely review the clinical picture to look for reduced urine output
indicative of renal failure, the presence of
liver enzymes, or cardiac enzymes, among
other things. In addition, meconium-­
stained amniotic fluid may not be an indicator of hypoxic-­ischemic encephalopathy.
In the United States, 15 percent of births
annually involve meconium-­stained amniotic fluid. Id. at 265. As such, finding it does
not settle the causal question.
Trained and experienced placental
pathologists can, as indicated, categorize
the inflammatory response into “stages” by
completing a pathologic examination. This
assists in defining the time of an event. A
child may have suffered harmful effects of
the inflammatory process before the period
purportedly identified by a fetal monitor
record, and, indeed, it may have happened
before the mother’s admission to the hospital. A child many have experienced direct
cellular damage for some time before he or
she was born.
Chorioamnionitis and funisitis involve
three stages, and the maternal response
precedes that of the fetus. Pathological
examination pinpoints the stages by identifying the number and the location of
the neutrophils. Dr. Redline has opined
that “Stage 1” chorioamnionitis, noted
as subchorionitis and chorionitis, may
develop six to 12 hours after exposure to
the infectious agent. Redline, Inflammatory Responses in the Placenta and Umbilical Cord, 11 Seminars in Fetal & Neonatal
Medicine 297 (2006). Chorioamnionitis,
or “Stage 2,” can develop within 12 to 36
hours. Id. Necrotising chorioamnionitis
signals “Stage 3,” which develops 36 hours
or more after exposure. Id. Again, in terms
of stages, funisitis begins when neutrophils appear in the chorionic vessels and
umbilical vein, then, during the next stage
they appear in the umbilical artery, and
finally, they appear in the Wharton’s jelly.
Severe fetal inflammatory response may
even “develop as a consequence of subacute
processes beginning days before delivery.”
Redline, Placental Pathology and Cerebral
Palsy, 33 Clin. Perinatol. 569 (2006). Note,
however, that these stages are not exact and
can overlap. Experienced placental pathologists can estimate the length of time that
an inflammatory process continued or how
long a stage persisted by examining placental samples in comparison with historical
knowledge. More severe inflammation suggests not only that more time has passed,
but, also, it is associated with a poor outcome. The severity of the fetal response is
particularly relevant to the degree of injury.
Redline, Infections and Other Inflammatory Conditions, 24 Seminars on Diagnostic Pathology 9 (2007).
The medicine involved in these issues,
especially regarding the means of injury,
is complex. Defense attorneys need to identify knowledgeable and experienced expert
witnesses to address the pathological confirmation of chorioamnionitis and funisitis, as well as to discuss the effects of the
inflammatory process. Only a few placental
pathologists have experience in this field,
and a defense of a birth injury case involving cerebral palsy will require a focused
effort to obtain the appropriate assistance.
Conclusion
Dr. Baergen’s article, “The Placenta as Witness” is aptly titled. Pathologic review of
a placenta may yield information vital to
a defense of a birth injury case involving
cerebral palsy. These claims create substantial exposure, and the health-care providers’ conduct is often judged based on
nothing more than fetal monitoring records
and an assertion that these records depict
fetal birth asphyxia. However, emerging
science has revealed that cerebral palsy is
often associated with infection and inflammation initiated by bacteria or other microorganisms affecting the placenta. Studies
have firmly linked inflammation of the placenta, chorioamnionitis, and inflammation
of the umbilical cord, funisitis, to the development of cerebral palsy, and confirming
their existence with a pathologic review of
a placenta may provide an objective causation defense to claims of negligence in labor
and delivery care.
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