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4 Acute Abdomen-Induced Preterm Labor
oxalate complex that is more soluble than calcium oxalate [203]. This role could be less
important in pregnancy because pregnant women
are twice as likely to have calcium phosphate
stones than age-matched nonpregnant women
and are two to three times more likely to have
calcium phosphate stones than oxalate stones
[204].
4.6.2.2 Progesterone
Adnexal Torsion/Ovariectomy
The tocolysis includes oral or IM progesterone in
the rst trimester and oral or IV ritodrine in the
second and third trimesters [205]. With the ovariectomy during the rst trimester, the patient
should receive 17α-hydroxy progesterone caproate 250mgim. weekly for four weeks as progestogen support for the pregnancy [206] and
protection from uterine contractions and
PTL.After this period, progesterone is produced
by the placenta, and there is no need for its
substitution.
There are no data about the specic inuence
of isolated Fallopian tube torsion on uterine irritability during pregnancy. Therefore, prophylactic tocolysis is unnecessary and should be
administered when uterine contractions are present [207].
Abdominal Trauma
Instead of magnesium sulfate, slow-released progesterone should also be considered for uterine
contractions after abdominal trauma in pregnancy [208].
4.6.2.3 Anti-Inammatory Agents
NSAIDs/Indomethacin
Because bacterially induced PTL is associated
with increased prostaglandin production, inhibiting the synthesis of prostaglandins is recommended in cases of (potential) infection-induced
PTL. The administration of nonsteroidal antiinammatory drugs (NSAIDs) curtails the progression of both term labor and PTL [209, 210].
Currently used NSAIDs, such as indomethacin,
block COX-1 and COX-2. Treatment with these
drugs is associated with fetal and maternal side
effects that have precluded their use [209, 211].
Prostaglandin synthetase inhibitors were blamed
for reversible closure/constriction of ductus arteriosus, with minimal danger when used between
26 and 34 weeks of pregnancy [212, 213].
Although antenatal indomethacin may provide
enough time for antenatal steroids to improve
fetal maturation, these benets are associated
with periventricular leukomalacia in premature
infants [213]. The results also suggest that indomethacin exposure within 72h before delivery is
associated with necrotizing enterocolitis in premature infants. Antenatal indomethacin is not
associated with patent ductus arteriosus, respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, and mortality
in premature infants. Also, no teratogenesis
[188], altered hematological indices, or transient
renal insufciency [214] were detected.
Observations indicate that COX-2-derived
prostaglandins are important for bacterially
induced PTL and that COX-2 is a potentially
important target for stopping PTL [215]. There
are still unresolved issues about the duration and
the dosage of selective cyclooxygenase inhibitors
on PTL.
One of the drawbacks of prostaglandin synthetase inhibitors is their anti-inammatory and
antipyretic effect, which might mask the clinical
presentation of the acute abdomen and give the
surgeon a false sense of security. Therefore, it
should be used once the diagnosis is established.
Experimental Anti-Inammatory Agents
The following sections consider some promising
anti-inammatory agents potentially used to prevent infection-induced PTL.
NF-kB Inhibitors
N-acetylcysteine is a nonspecic free radical
scavenger and NF-kB inhibitor, but is currently
not in clinical use.
Sulfasalazine, a salicylate drug that blocks
NF-kB activation by directly inhibiting the IKK
kinases, is well tolerated and approved in pregnancy, with no discernible increase in the risk of
congenital fetal defects and morbidity or mortal-
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99
ity [216]. However, increased levels of chorionic
apoptosis have been reported in a human membrane model, suggesting that prolonged treatment may result in eventual membrane
degradation and loss of function and structural
integrity [30]. Potential use with extrauterine,
intraperitoneal (acute abdomen) -induced PTL is
its short-course use in addition to antibiotics and
infection source control.
TLR4 Antagonists
Inhibition using a monoclonal anti-TLR4 antibody was effective in vivo in reducing proinammatory mediator (TNF-α, IL-8, and PGE2)
production in amniotic uid [217] and the incidence of LPS-induced PTL [218]. Alternate TLR4
antagonists include eritoran tetrasodium [219]
and TAK-242 [220], neither of which have been
examined. TLR4 antagonism is only appropriate
in cases of Gram-negative bacteria-induced PTL.
Anti TNF-α Antibodies
The complexity of cytokine interactions associated with PTL suggests that targeting individual
cytokines may not be the most optimal therapeutic intervention (Fig.4.11). Interestingly, maternal administration of these agents (iniximab)
persists in the neonatal circulation for many
weeks after birth [221] and may, therefore,
dampen intrauterine and fetal inammation protecting the fetus from the adverse sequelae of
intrauterine infection and inammation. Also,
these agents could be used for treating some of
the causes of acute abdomen during pregnancy
(Crohn's disease). There is little evidence for
congenital abnormalities with anti-TNF-a therapy during pregnancy [222], but high levels in
fetal circulation may increase the risk of neonatal
infection. These facts should be weighed against
the consequences of PTL caused by the acute
abdomen.
Cytokine Suppressive Anti-Inammatory
Drugs (CSAIDs)
CSAIDs target the NF-kB and p38 MAPK signaling pathways with demonstrated efcacy in
animal models [223–225]. These agents can be
more effective and selective than NSAIDs in
inhibiting infection-induced PTL. They directly
target signaling molecules without interfering
with prostanoids' constitutive/homeostatic roles
(Fig.4.12). Depending on the route of administration and placental transfer properties, CSAIDs
may potentially block IAI and fetal inammation, thereby protecting the fetus from the adverse
sequelae of exposure to inammatory mediators.
Resveratrol
Resveratrol is a natural polyphenol capable of
reducing LPS-induced PTL to 36% (versus 85%
without the drug) and stillbirth to 34% (versus
62% without the drug) when administered orally
to pregnant mice [227]. The suggested mechanism is the downregulation of the expression of
pro-inammatory mediators such as iNOS and
COX-2in macrophages and suppression of the
production of eicosanoids such as prostaglandins. It was not tested on acute abdomen-induced
PTL. Trans isoform should be avoided. The
reduction in the DNA replication rate is one of
the mechanisms by which trans-resveratrol
impacts embryoid body development [228].
4.6.2.4 Betamimetics
Betamimetics are not indicated in patients with
an acute abdomen. Ritodrine should not be used
in a bowel obstruction or toxic megacolon due to
its inuence on colonic dilation [229, 230].
4.6.3 Combination Treatment
4.6.3.1 Combination Tocolysis
It is unclear whether a combination of tocolytic
drugs for PTL is superior to a single-agent tocolysis due to a lack of trials in patients with acute
abdomen.
4.6.3.2 Tocolysis andNon-Tocolytic
Agents
There is only one study in non-acute abdomen
patients. Using rigorous entry criteria, a therapeutic cocktail of interventions, including antibiotics, steroids, and tocolytics, demonstrated
neonatal benet primarily by prolonging gestation [231].
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4 Acute Abdomen-Induced Preterm Labor
Flagellin
TLR5 TLR2-TLR1
Cytoplasm
Nucleus
Anti-TLR-4 antibodies
1
2
lipopeptides
MKKs
4
p38 MAPK
MSK1/2
CREB
IRAK1
2
lipopeptides
IRAK4
IRAK2
TRAF6
TAK1
CBP
3
4
LPS
TLR2-TLR6
IKKy
(NEMO)
IKKα IKKβ
P
IkB IkB
5
NF-kB
NF-kB
IKK complex inhibitors
P38 MAPK inhibitorsOxZnl
Degradation
1
TLR4
dsRNA
TLR3
IKK complex
Endosome
ssRNA
TLR7
IRAK4
IRAK1 IRAK2
TRAF3
3
P
Non-specific NF-kB inhibitors
5
TNF biologics
6
CpG DNA
TLR9
Pro-inflammatory cytokines
(IL-6, IL-8, IL-1β and TNF-α)
COX-2 expression
Matrix metalloproteinase
Myometrial contraction
Cervical ripening
Fetal membrane rupture
Preterm labour
6
Fig. 4.12 Infection-induced preterm labor triggered by
activation of TLR-mediated NF-kB and p38 MAPK
inammatory signaling cascades. Targets for the selected
A single antenatal course consists of
2×12mg betamethasone IM, 24h apart, or
4 × 6mg dexamethasone IM every 12h,
after 24weeks of gestation.
The duration of fetal benet after a course of
glucocorticoids is uncertain. A repeat course
might confer a modest additional neonatal benet, whereas multiple courses can reduce fetal
growth [232]. Benecial effects include a reduced
rate of respiratory distress syndrome, intraventricular hemorrhage, neonatal death, necrotizing
enterocolitis, patent ductus arteriosus, and bronchopulmonary dysplasia [233].
In patients with acute abdomen, antibiotics are
used as indicated for the underlying disease as
prevention or treatment.
anti-inammatory agents are in red circles. (Reproduced
with permission from [226] under the CC BY 4.0)
4.6.4 Placental Abruption
Treatment
Immediate CS is indicated with a viable live fetus
in traumatic-induced (See Sect. 25.3.6.1) and
infection- induced placental abruption.
4.7 Prognosis
PTB ranges from 5% of births in European countries to 18% in certain African countries [234]. It
is the leading cause of childhood mortality in
children under 5 years [235]. All-cause PTB
accounts for 75% of perinatal mortality and more
than half of long-term morbidity [236]. PTB has
an increased risk of cognitive and neurological
impairment, such as cerebral palsy and respira-
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tory and gastrointestinal complications [4]. There
is also an increased risk of chronic diseases in
adulthood, such as obesity, diabetes, and hypertension [1]. Interestingly, premature males are at
greater risk of mortality and neurological and
respiratory morbidity when followed up at
2years of age [237].
Several critical questions remain unanswered:
(1) the identication of a causative infectious
agent(s), (2) the role of polymicrobial infection,
(3) the critical locus of infection, 4) the burden of
infection, and (4) the central immune cells and
immune pathways.
Most premature infants exposed to one or
more postnatal gram-negative bacteria or
coagulase- negative staphylococci,
Staphylococcus aureus, and group B streptococcus are associated with an increased risk of cere-
bral palsy and adverse neurodevelopmental
outcomes at 2years [238–240]. Fetal bacteremia
was found in 33% of fetuses with positive amniotic uid cultures and 4% of those with negative
amniotic uid cultures in the context of
PPROM.Therefore, subclinical fetal infection is
far more common than traditionally recognized.
Recently, 23% of neonates born between 23 and
32 weeks of gestation had positive umbilical
blood cultures for genital mycoplasmas [241].
The fetal mortality rate and the type of fetal
morbidity differ between acute and (the type of)
chronic maternal abdominal conditions. Acute
abdominal conditions mainly result in spontaneous abortion, stillbirth, or PTL, while chronic
inammatory conditions result in congenital
anomalies and PTL.Even acute abdominal conditions resemble chronic conditions if treated
conservatively, which could result in recurrences
with a chronic impact on the fetus.
4.7.1 Fetal Inammatory Response
Syndrome
4.7.1.1 Pathophysiology
Most fetuses exposed to chorioamnionitis
develop a systemic inammatory response known
as the fetal inammatory response syndrome
(FIRS) [242, 243]. This is due to the fetus being
in direct contact with the infected amniotic uid
or inammatory cell transfer from the uteroplacental circulation. FIRS can be clinical or subclinical. Clinical FIRS is dened by a fetal
plasma IL-6 >11pg/mL [244], while subclinical
FIRS is dened histologically by funisitis and
fetal vasculitis [243]. Fetuses with elevated
plasma IL-6 had a higher rate of severe neonatal
morbidity and a shorter cordocentesis-to-delivery
interval than those with <11pg/mL.The disorder
can also be diagnosed by measuring CRP in
umbilical cord blood. Fetuses with FIRS have
more systemic involvement, including hematologic abnormalities (neutrophilia) and a higher
median nucleated red blood cell count than those
without elevated IL-6. Also, fetal stress is determined by the fetal plasma ratio of cortisol to
dehydroepiandrosterone sulfate (DHEAS), congenital fetal dermatitis, fetal cardiac dysfunction,
involution of the thymus, and abnormalities of
the fetal lung and brain. Among patients with
PPROM, elevated fetal plasma IL-6 is associated
with the impending onset of PTL, regardless of
the inammatory state of the amniotic uid. This
suggests that the human fetus plays a role in initiating the onset of labor.
However, maternal-fetal cooperation must
occur for parturition to be completed. Fetal
inammation has been linked to the onset of
labor associated with ascending intrauterine
infection. However, systemic fetal inammation
may occur in the absence of labor if the inammatory process does not involve the chorioamniotic membranes and decidua. Such instances may
take place in the context of hematogenous viral
infections or other disease processes (e.g., rhesus
alloimmunization).
Affected fetuses have evidence of multiorgan
involvement with a higher rate of severe neonatal
morbidity after adjustment for gestational age,
and PPROM results in a shorter cordocentesis-todelivery interval. Neutrophilia is present in twothirds of fetuses with FIRS, whereas neutropenia
in 7%. FIRS is associated with BPD.The fetus
can inhale amniotic uid and its contents which
can reach the distal parts of the airways and the
alveoli. FIRS is found in 76% of infants with
atypical chronic lung disease, dened as chronic
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lung disease without respiratory distress syndrome. Bacterial products and cytokines may
contribute to myocardial depression. Fetuses that
cannot modify their cardiac compliance or maintain ventricular cardiac output may suffer inadequate brain perfusion, predisposing them to
hypotension and brain ischemia in utero. This
can result in periventricular leukomalacia and
brain injury.
4.7.1.2 Prevention andTreatment
Treating maternal bacterial infection eliminates
potentially inoculated bacteria in the fetus or
amniotic uid. There is no effective treatment to
prevent infection/inammation-related fetal
brain injury. Prophylactic antibiotics given to
mothers at risk of PTL who have ruptured membranes are still associated with an increased risk
of fetal death and disability [245]. Killing bacteria will release even more inammatory bacterial
fragments and, in addition to hypoxia and hyperthermia, could result in brain injury despite prophylactic antibiotics.
Inhibitors of the IL-1RI decrease proinammatory cytokine IL-1β production, curbing
the inammatory process. The commercially
available drug anakinra (Kineret) competitively
blocks the receptor and inhibits all its intracellular pathways [246]. It protects the fetal brain
from inammatory damage [247].
chorioamnionitis has enough time to develop in
the acute abdomen. Also, cases of subclinical
chorioamnionitis are missed resulting in an
underestimation of this condition.
The risk of fetal death from maternal pyrexia,
distinct from infection, may have been overstated
[250]. Some drugs for treating severe infections
may be teratogenic, thus compounding the effect
of pyrexia. For effects of maternal pyrexia on
fetal and neonatal development, see Sect. 4.7.3.
4.7.2.2 Fetal Trauma
See Chap. 5.
4.7.2.3 Placental Abruption
For fetal outcome from traumatic placental
abruption, see Sect. 25.3.6.1. Neonates of the
placental abruption with histologic chorioamnionitis group had increased neonatal adverse outcomes than the group with placental abruption
from chronic vascular insufciency on the
maternal- fetal interface [251]. No comparisons
of placental abruptions exist between specic
intra-abdominal infections or maternal abdominal trauma. Placental abruption rate from specic
acute abdominal causes is described in the chapters dealing with these conditions.
4.7.3 Fetal Morbidity
4.7.2 Fetal Mortality
4.7.2.1 Fetal Infection
In 1912, it was observed that the infection might
extend to the uterus from the Fallopian tubes, the
broad ligaments, and then from the uterine wall
to the placenta [248]. With diffuse peritonitis,
transplacental bacterial diffusion could result in
intrauterine fetal death [249]. Fetal microbial
invasion results in FIRS that can progress toward
multiple organ dysfunction, septic shock, and
death without timely delivery. Due to the small
number of patients, it is difcult to compare the
inuence of therapeutic delay, the type of microorganism involved, and the proven route of infection. It is questionable whether acute
The type of fetal morbidity partly depends on the
cause of the maternal acute abdomen. There are
three distinctive etiologic groups: (1) IAI, (2)
bleeding, and (3) direct or indirect fetal trauma.
Also, the presence of these etiologic groups
makes both maternal and fetal prognoses worse.
Fetal injuries common for all etiologic groups are
described. For specic fetal traumatic injuries,
see Chap. 5.
4.7.3.1 Brain Injury
Perinatal brain injuries, particularly cerebral
palsy, periventricular leukomalacia, and intraventricular hemorrhage, are linked to intrauterine
inammation [252–254]. Exposure to histological chorioamnionitis combined with impaired
placental perfusion increases the risk of poor
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neurological and neurocognitive outcomes at
2years [255] and 8years [256] of corrected age
in children born very preterm. Histological chorioamnionitis is also associated with increased
speech delay and hearing loss at 18 months of
corrected age in infants born very preterm [257].
Furthermore, histological chorioamnionitis
caused by bacterial and viral infection has
increased the risk of autism and schizophrenia
[258]. Schizophrenia may result from post-acute
latent inammation, whereas autism may be due
to persistent inammation [258].
Several potential mechanisms could connect
chorioamnionitis and adverse neurological outcomes. Intrauterine inammation is linked with
diffuse white matter injury in the brain of preterm
neonates due to TNF-α signaling and has been
described as toxic to developing oligodendrocytes
[124, 259, 260]. Chorioamnionitis has been associated with impaired fetal and newborn cardiac
function [261, 262], which may compromise
brain blood ow due to lower blood pressure
[261, 263, 264]. This results in altered cerebral
oxygen delivery. Impaired cerebral autoregulation
is considered one of the main contributors to brain
injury in preterm neonates [253, 265]. Impaired
cerebral autoregulation may be more prevalent in
neonates born after exposure to intrauterine
inammation [264, 265]. Data from animal experiments are consistent with human studies in showing the effects of intrauterine inammation (with
various routes of microbe inoculation) on the
developing brain in the form of (1) karyorrhexis
(nuclear fragmentation) of glial cells and reduced
density and disorganization of white matter [266],
(2) astrocytosis and a reduction in oligodendrocyte number in subcortical white matter [267], (3)
diffuse damage and focal periventricular leukomalacia [268], and (4) decrease in myelination,
potentially due to reduced numbers or function of
oligodendrocytes [269]. Currently, it is unknown
whether the: (a) location of the primary infective
focus, (b) the route of infection dissemination, or
(c) duration and severity of infection have different central nervous system (and other organs)
consequences.
Women who experience abdominal trauma
have an increased incidence of birth defects,
mostly damage/defects of the central nervous
system, especially hydrocephaly [270, 271]. In 2
out of 7 blunt abdominal traumas, movement disorders and cerebral palsy were detected [270,
272].
Cerebral Palsy
Although previously described, in 1861, William
John Little (Fig.4.13), an orthopedic, described
the association of prematurity with cerebral palsy
and the development of spastic diplegia. He
hypothesized that, even without apparent external trauma, an inadequate supply of “oxygen and
materials for nutrition” from the placenta to the
fetus or an “insufcient removal of carbon and
other residues” from the fetus through the placenta could lead to brain injury [273]. One-third
of all neonates who later have signs of cerebral
palsy weigh less than 2500 g. Newborns with
birth weights less than 1500g have a rate of cerebral palsy 25–31 times higher than those with
normal birth weights. The most common form of
cerebral palsy affecting preterm babies is spastic
diplegia. In turn, preterm babies who develop
spastic diplegia have a high rate of periventricular leucomalacia.
Infection/Inammation
In 1955, Eastman and Deleon observed that intrapartum maternal fever was associated with a sev-
Fig. 4.13 William John Little ((1810–1894), an orthopedic surgeon, lectured at the Obstetric Society of London
and accentuated the association of prematurity with cerebral palsy in Lancet in 1861. (Reproduced with permission from [280])
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4 Acute Abdomen-Induced Preterm Labor
enfold increase in the risk of cerebral palsy [274].
The prolonged temperature rise increases the
metabolic rate and the oxygen requirements of the
fast-developing tissues. When the demand outstrips the supply, placental efciency diminishes.
Also, fast-growing tissues are especially susceptible to noxious stimuli [275]. For each degree of
body temperature over 37°C, the oxygen required
for tissue metabolism, including the brain, rises
by 7%. Therefore, an intrapartum infection is a
cause of cerebral palsy through the effects of bacterial toxins and the mechanism of hypoxia/
anoxia. In 1977, chorioamnionitis increased the
risk of cerebral palsy among low- birth weight
infants from 12/1000 to 39/1000 live births [276].
Trauma
William Osler, who coined the term cerebral
palsy, favored the hypothesis that trauma leading
to meningeal hemorrhage and brain and spinal
cord compression was a major cause of cerebral
palsy [273]. The risk of cerebral palsy after MVA
is 1.8/1000 [277]. MVAs during pregnancy may
be associated with an increased risk of cerebral
palsy in neonates with PTB [277]. Possible
mechanisms for the association between pregnancy trauma and cerebral palsy include reduced
placental blood ow, placental embolization, and
placental abruption. Kleihauer-Betke testing at
the time of trauma and histological examination
of the placenta at the delivery might clarify the
role of placental separation [278]. The correlation between the type of cerebral palsy and
maternal trauma during pregnancy is not claried, but the spastic form is predominant in term
infants [279]. In term babies, the type of MRI
abnormality corresponds with the timing of the
antenatal injury: trauma at 20 weeks results in
extensive cortical dysplasia; trauma between 24
and 30 weeks results in periventricular white
matter abnormality; trauma after 30weeks results
in cystic encephalomalacia [279].
Epilepsy
Epilepsy is childhood's most common severe
neurologic disorder [281–283]. Before the age of
15, 1–1.7% of all children will have at least one
unprovoked seizure, and up to 0.8% will have
repeated seizures [282]. The incidence of childhood epilepsy is highest in the rst year of life—
150/100,000 person-years, falling to 50/100,000
person-years after the age of 9 [282].
Generalized epilepsies can often be traced to
infection [282]. In particular, insults acting during the prenatal and to single-gene mutations or
chromosomal abnormalities, while partial epilepsies are frequently triggered by external insults to
the central nervous system, including brain injury
and central nervous system neonatal period, are
thought to contribute to some types of epilepsies
[281, 282, 284]. A seasonal pattern, i.e., an excess
of births during winter months among children
who develop epilepsy [285, 286], suggested prenatal exposure to maternal infection may be a
risk factor. Any maternal infection during pregnancy (method of measurement unspecied) was
associated with a 1.0- to 1.6-fold increase in the
risk of childhood epilepsy [284]. Maternal selfreported history of cystitis, pyelonephritis, vaginal yeast infection, or symptoms of infection
(diarrhea, coughs) during pregnancy was associated with a 1.2- to 2.6-fold increased risk of epilepsy among offspring [287]. Risk varied by type
of infection and was the highest for a self-reported
vaginal yeast infection (2.6-fold) and
pyelonephritis (2.3-fold) [287]. Therefore, a 40%
increased risk of epilepsy is associated with prenatal exposure to maternal systemic infection
[288]. The infection could be caused by its antecedents, consequences, or antibiotic treatment.
However, the similar magnitude of increased risk
observed for different types of antibiotics argues
against the role of specic types of infections or
specic therapies. Various maternal infections,
measured by self-report collected twice during
pregnancy and 6 months after delivery, were
associated with epilepsy in offspring [287].
Children with prenatal exposure to more than
two maternal fever episodes, maternal fever with
urinary symptoms, or maternal fever of 39 °C
have an increased risk of epilepsy—suggesting
that the underlying causes of fever rather than
elevated temperature, such as sauna use, play a
role [289]. Inammation may be involved in linking fever and epilepsy [290]. Inammatory reactions in the brain can enhance neuronal
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excitability [291], and anti-inammatory treatments reduce seizures in experimental models.
Cytokines are key players in the modulation
of neuronal excitability, leukocyte recruitment,
and inammatory central nervous system infections [290], yet their role in the pathogenesis of
epilepsy is unclear. In response to infection during pregnancy, maternal cytokine production
may induce fetal neurological injury [292]. A
nearly threefold increased risk for epilepsy
among children born to mothers with epilepsy
suggests that infants genetically predisposed to
epilepsy may be more susceptible to inammatory reactions [288].
Premature births result in 75% of neonatal
deaths and most neonatal intensive care unit
admissions [293]. A substantial effect of premature birth on long-term physical and mental
health is observed [294]. Babies born at
<28weeks gestational age spend 85 times longer
in the hospital than babies born at term [295].
Even among babies born after 32weeks, educational and behavioral problems can occur in 33%
at 7years of age [296], with 25% born between
32 and 35 weeks of gestational age requiring
nonteaching assistants at school [297].
4.7.3.2 Lung Injury
IAI is also associated with lung injury. Elevated
levels of TNF-α, IL-1β, IL-6, and IL-8 in the
amniotic uid have been found in women who
had babies with bronchopulmonary dysplasia
(BPD), a chronic lung disease affecting infants.
There are no data about fetal lung injury associated with acute extrauterine IAI.
4.7.3.3 Low Gestational Weight
andBirth Defects
Low birthweight is associated with poor outcomes in cognitive function, academic achievement, behavior, and social adaptation [298, 299].
Low birthweight is also associated with an
increased risk of cardiovascular and chronic diseases [300].
Domestic Violence
Minor trauma during pregnancy may lead to the
subclinical chronic placental disruption that per-
sists during pregnancy, which may cause an
increase in the risk for induced abortion, acute
placental abruption, PTL, PPROM, and placental
insufciency that restricts fetal growth and lower
Apgar score [301].
1/3 of the studies reported a positive association between intimate partner violence and low
birth weight or PTB [302–304]. Rates of low
birth weight among battered women were 1.5–
2.5 times higher [302–304] than those among
nonbattered women, and rates of PTB were 2.5–4
times higher [302–304]. Others lacked sufcient
power to address most pregnancy outcomes [305,
306]. Many studies have reported increased rates
of low birth weight, reduction in mean birth
weight, or PTL in bivariate analyses. However,
the associations became nonsignicant when
adjusted for tobacco use and other substances
[307, 308].
Stratication by intention suggests three
associations- longitudinal limb deciency, gastroschisis, and hypoplastic left heart syndrome—
possibly driven by intentionally inicted injuries
[309]. The majority of intentional injuries result
from intimate partner abuse, and these types of
injuries could be more stressful for the mother
[310].
Motor Vehicle Accidents
The estimation is that 9% of survivors of serious
crashes develop signicant post-traumatic stress
symptoms and that many other survivors have
post-traumatic stress disorder-like reactions
[311]. Associations have been observed between
maternal stress during pregnancy, especially during the periconceptional period and conotruncal
heart defects, interrupted aortic arch type B,
atrioventricular septal defect, pulmonary atresia,
tricuspid atresia, hypoplastic left heart syndrome,
anorectal atresia/stenosis, longitudinal limb deciency, gastroschisis, neural tube defects [312,
313], and orofacial clefts [312, 313]. One should
be cautious with conclusions because there is a
higher prevalence of alcohol and cigarette use
during pregnancy among women who reported
an intentional injury [310]. Alcohol and cigarette
use during pregnancy is associated with an
increased risk of birth defects [314, 315].
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One thread suggests that stress, either very
early in pregnancy or in the 24–28th weeks of
pregnancy, leads to a twofold increase in the risk
of autism [316]. Since autism is usually not
apparent until 1–3years of age, it may be difcult
to trace back to the primary events.
4.7.4 Maternal Outcome
In the late nineteenth century, maternal and fetal
mortality from maternal diffuse peritonitis was
100% [130, 317].
4.7.4.1 Placental Abruption
Maternal mortality associated with all-cause placental abruption decreased from 8% in 1919 to
<1% in 1995 [318]. After placental abruption
with a survived newborn, 59% of women had a
subsequent delivery, compared with 71% of those
without abruption. After the perinatal loss, the
corresponding rates were 83 and 85% [319]. This
may reect maternal anxiety and distress from
further pregnancies caused by prior placental
abruption. For trauma-induced placental abruption outcomes, see Sect. 25.3.7.2.
4.7.4.2 Intrauterine Fetal Death
The issue with intrauterine fetal death is whether
to deliver on an emergent basis by CS or wait for
spontaneous delivery. The argument for late spontaneous delivery is avoiding CS with all its potential complications without benet for the dead
fetus. On the contrary, intrauterine retention of a
dead fetus for >5weeks may result in potentially
hazardous hypobrinogenemia in 25% of patients.
Prolonged retention is unusual since spontaneous
delivery occurs within 3weeks of fetal death in
>90% of patients [320]. If hypobrinogenemia
develops, the onset is gradual. At least before the
delivery, it may be asymptomatic or show clinical
evidence of abnormal hemostasis, such as gingival bleeding or extensive ecchymoses. If hypobrinogenemia develops, it persists until the uterus
is emptied. Fibrinogen administration has a transient effect and can result in hepatitis.
4 Acute Abdomen-Induced Preterm Labor
There is no indication for emergent delivery
before 3weeks after fetal death, but not longer than 5weeks [320] if there are no maternal indications for emergent delivery.
4.7.4.3 Intra-abdominal Infection
A CS due to IAI exposes the uterine wound to
infection. This can result in endometritis, increasing the risk of opening the hysterorraphy [321].
Moreover, such uterine scars transform subsequent pregnancies into high-risk pregnancies for
uterine rupture.
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