PROLONGED RUPTURE OF PROLONGED RUPTURE OF
MEMBRANESMEMBRANES
ANDAND
NEONATAL INFECTIONNEONATAL INFECTION
Ayman Abou Mehrem, MD, CABP
Staff Physician
Department of Pediatrics
King Abdulaziz National Guard Hospital
Pathogenesis of Ascending Pathogenesis of Ascending
Bacterial InfectionBacterial Infection
In most casesIn most cases the fetus or neonate is the fetus or neonate is
not exposed to potentially pathogenic not exposed to potentially pathogenic
bacteria until the membranes rupture bacteria until the membranes rupture
and the infant passes through the birth and the infant passes through the birth
canal and/or enters the extra uterine canal and/or enters the extra uterine
environmentenvironment
TheThe human birth canal is colonized with human birth canal is colonized with
aerobic and anaerobic organisms that aerobic and anaerobic organisms that
may result in ascending amniotic may result in ascending amniotic
infection and/or colonization of the infant infection and/or colonization of the infant
at birthat birth
VERTICAL TRANSMISSIONVERTICAL TRANSMISSION of bacterial of bacterial
agents that infect the amniotic fluid agents that infect the amniotic fluid
and/or vaginal canal may occur in utero and/or vaginal canal may occur in utero
or or more commonlymore commonly during labor and/or during labor and/or
deliverydelivery
CHORIOAMNIONITISCHORIOAMNIONITIS results from results from
microbial invasion of amniotic fluid as a microbial invasion of amniotic fluid as a
result of prolonged rupture of the result of prolonged rupture of the
chorioamniotic membranechorioamniotic membrane
On occasionOn occasion, ,
amniotic infection occurs with apparently amniotic infection occurs with apparently
intact membranes or with a relatively intact membranes or with a relatively
brief duration of membrane rupturebrief duration of membrane rupture
Amniotic fluid infection may be Amniotic fluid infection may be
asymptomatic or may produce maternal asymptomatic or may produce maternal
fever with or without local or systemic fever with or without local or systemic
signs of chorioamnionitissigns of chorioamnionitis
THE DURATION OF MEMBRANE THE DURATION OF MEMBRANE
RUPTURERUPTURE is directly correlated with the is directly correlated with the
development of chorioamnionitisdevelopment of chorioamnionitis
LONGER THAN 18 HOURS is the
current cut off for increased risk of
neonatal infection
OTHER FACTORSOTHER FACTORS that associated with that associated with
increased frequency of increased frequency of NEONATAL NEONATAL
INFECTIONINFECTION
Difficult DeliveryDifficult Delivery
Traumatic DeliveryTraumatic Delivery
Preterm DeliveryPreterm Delivery
Resuscitation at BirthResuscitation at Birth
In most casesIn most cases, ,
bacterial colonization of the newborn bacterial colonization of the newborn
does notdoes not result in disease result in disease
What are the factors influencing which What are the factors influencing which
colonized infant will develop disease?colonized infant will develop disease?
These are not well understood, but include:These are not well understood, but include:
PrematurityPrematurity
Underlying illnessUnderlying illness
Invasive proceduresInvasive procedures
Inoculum sizeInoculum size
Virulence of infecting organismVirulence of infecting organism
Transplacental maternal antibodiesTransplacental maternal antibodies
AspirationAspiration or or ingestion ingestion of bacteria in of bacteria in
amniotic fluid may lead to congenital amniotic fluid may lead to congenital
pneumonia or systemic infection, with pneumonia or systemic infection, with
manifestations become apparent before manifestations become apparent before
delivery or after a latent period of a few delivery or after a latent period of a few
hours. Aspiration or ingestion of bacteria hours. Aspiration or ingestion of bacteria
during the birth process may lead to during the birth process may lead to
infection after an interval of 1-2 days.infection after an interval of 1-2 days.
Prematurity and InfectionPrematurity and Infection
Preterm infants have 3- to 10-fold Preterm infants have 3- to 10-fold
higher incidence of infection than full higher incidence of infection than full
term, normal birth weight infants doterm, normal birth weight infants do
is considered to be an important is considered to be an important
cause of preterm labor with an cause of preterm labor with an
increased risk of vertical increased risk of vertical
transmission to the newborntransmission to the newborn
Maternal genital tract infectionMaternal genital tract infection
gestational agegestational age
The frequency of intra-amniotic The frequency of intra-amniotic
infection is inversely related toinfection is inversely related to
immune dysfunctionimmune dysfunction
Premature infants have documentedPremature infants have documented
Premature infants often require Premature infants often require
prolonged intravenous access, prolonged intravenous access,
endotracheal intubation or other endotracheal intubation or other
invasive procedures that provide ainvasive procedures that provide a
portal of entry or impair portal of entry or impair
clearance mechanismsclearance mechanisms
The most common bacterial organisms The most common bacterial organisms
causing neonatal infection are:causing neonatal infection are:
Group B streptococcus (Streptococcus Group B streptococcus (Streptococcus
agalactiae)agalactiae)
Enteric organismsEnteric organisms
Listeria monocytogenesListeria monocytogenes
GonococciGonococci
ChlamydiaChlamydia
Group B StreptococcusGroup B Streptococcus
GBSGBS
GBS is encapsulated Gram positive GBS is encapsulated Gram positive
coccus colonizes the gastrointestinal coccus colonizes the gastrointestinal
and genital tracts in the humansand genital tracts in the humans
Approximately Approximately 25%25% of pregnant women of pregnant women
carried this organism in their genital carried this organism in their genital
and/or gastrointestinal tracts and this and/or gastrointestinal tracts and this
carriage was the most critical carriage was the most critical
determinant of risk for early onset GBS determinant of risk for early onset GBS
infection in their offspringinfection in their offspring
Approaches for GBS Prevention in the NewbornApproaches for GBS Prevention in the Newborn
Eradication of colonizationEradication of colonization in pregnant women with in pregnant women with
antibiotics given during pregnancyantibiotics given during pregnancy
Active screeningActive screening of pregnant women with of pregnant women with
antibiotics during labor only for those with positive antibiotics during labor only for those with positive
screening culturesscreening cultures
AntibioticsAntibiotics during labor for all pregnant women during labor for all pregnant women
with one or more factors leading to an increased with one or more factors leading to an increased
risk for GBS infection in their offspringrisk for GBS infection in their offspring
Development of vaccinesDevelopment of vaccines which could be which could be
administered to women before pregnancyadministered to women before pregnancy
The first guidelines for Intrapartum Antibiotic The first guidelines for Intrapartum Antibiotic
Prophylaxis (IAP) were published by the Prophylaxis (IAP) were published by the
AAP in 1992AAP in 1992
A CDC survey of a population of almost 30 A CDC survey of a population of almost 30
million documented a significant decrease in million documented a significant decrease in
early onset infection (i.e. < 7 days of age) early onset infection (i.e. < 7 days of age)
between 1993 and 1998 (1.7 to 0.6 cases between 1993 and 1998 (1.7 to 0.6 cases
per 1000 births)per 1000 births)
All pregnant womenAll pregnant women should be screened should be screened
for GBS colonization with swabs of both for GBS colonization with swabs of both
the lower vagina and rectum at 35 to 37 the lower vagina and rectum at 35 to 37
weeks of gestation. The only patients who weeks of gestation. The only patients who
are are excludedexcluded from screening are those from screening are those
with GBS bacteriuria earlier in the current with GBS bacteriuria earlier in the current
pregnancy or those who gave birth to a pregnancy or those who gave birth to a
previous infant with invasive GBS disease. previous infant with invasive GBS disease.
These are not included in the screening These are not included in the screening
recommendation because they should recommendation because they should
receive IAP regardless of the colonization receive IAP regardless of the colonization
statusstatus
SwabsSwabs should be obtained from the lower should be obtained from the lower
vagina vagina (not cervix)(not cervix) and rectum and rectum (not anal (not anal
orifice)orifice) and should be promptly placed into and should be promptly placed into
non-nutrient transport medianon-nutrient transport media
Susceptibility testingSusceptibility testing to erythromycin and to erythromycin and
clindamycin, if feasible, should be clindamycin, if feasible, should be
performed for GBS isolates performed for GBS isolates
Patients recommended for Patients recommended for
IAPIAP
Pregnant women with a positive screening culture from Pregnant women with a positive screening culture from
either vagina or rectum either vagina or rectum unlessunless a planned cesarean delivery a planned cesarean delivery
is performed in the absence of labor or membrane ruptureis performed in the absence of labor or membrane rupture
Pregnant women who gave birth to a previous infant with Pregnant women who gave birth to a previous infant with
invasive GBS diseaseinvasive GBS disease
Pregnant women with documented bacteriuria during the Pregnant women with documented bacteriuria during the
current pregnancycurrent pregnancy
Pregnant women whose culture status is unknown (culture Pregnant women whose culture status is unknown (culture
not performed or results not available) and who have any of not performed or results not available) and who have any of
the following:the following:
Delivery at <37 weeks of gestationDelivery at <37 weeks of gestation
Amniotic membrane rupture for ≥18 hoursAmniotic membrane rupture for ≥18 hours
Intrapartum temperature ≥38°CIntrapartum temperature ≥38°C
Patients not recommended Patients not recommended
for IAPfor IAP
Positive GBS screening culture in a previous Positive GBS screening culture in a previous
pregnancy (unless the infant had invasive GBS pregnancy (unless the infant had invasive GBS
disease or the screening culture is also positive in disease or the screening culture is also positive in
the current pregnancy)the current pregnancy)
Patient who undergoes a planned cesarean Patient who undergoes a planned cesarean
delivery without labor or rupture of membranesdelivery without labor or rupture of membranes
Pregnant women with negative GBS screening Pregnant women with negative GBS screening
culture at 35 to 37 weeks of gestation even if they culture at 35 to 37 weeks of gestation even if they
have one or more of the above intrapartum risk have one or more of the above intrapartum risk
factors.factors.
The use of broad spectrum intrapartum The use of broad spectrum intrapartum
antibiotics for the treatment of presumed antibiotics for the treatment of presumed
chorioamnionitis in febrile women in labor chorioamnionitis in febrile women in labor
is left to the discretion of the obstetricianis left to the discretion of the obstetrician
IAP IAP regimensregimens
Penicillin GPenicillin G (5 million units IV initial dose, then (5 million units IV initial dose, then
2.5 million units IV Q4h)2.5 million units IV Q4h)
Ampicillin Ampicillin (2 g IV initial dose, then 1 g IV Q4h). (2 g IV initial dose, then 1 g IV Q4h).
Penicillin is preferred based upon its narrower Penicillin is preferred based upon its narrower
spectrum of activity and theoretical reduced spectrum of activity and theoretical reduced
opportunity for development of ampicillin-opportunity for development of ampicillin-
resistant organismsresistant organisms
Cefazolin Cefazolin (2 g initial dose, then 1 g Q8h) is (2 g initial dose, then 1 g Q8h) is
recommended for women with a history of non-recommended for women with a history of non-
immediate-type penicillin-allergy, i.e. at low risk immediate-type penicillin-allergy, i.e. at low risk
for anaphylaxisfor anaphylaxis
Clindamycin Clindamycin (900 mg IV Q8h) or(900 mg IV Q8h) or Erythromycin Erythromycin
(500 mg IV Q6h) are recommended for patients (500 mg IV Q6h) are recommended for patients
at high risk for anaphylaxis to penicillins at high risk for anaphylaxis to penicillins only ifonly if
their GBS culture screening isolate is their GBS culture screening isolate is
documented to be susceptible to one of themdocumented to be susceptible to one of them
Vancomycin Vancomycin (1 g Q12h) is recommended for (1 g Q12h) is recommended for
patients at high risk for anaphylaxis and a GBS patients at high risk for anaphylaxis and a GBS
isolate resistant to clindamycin or erythromycin; isolate resistant to clindamycin or erythromycin;
or with unknown susceptibilityor with unknown susceptibility
IAP is continued from hospital IAP is continued from hospital
admission through deliveryadmission through delivery
The greatest efficacy is achieved The greatest efficacy is achieved
if penicillin G, ampicillin, or if penicillin G, ampicillin, or
theoretically cefazolin is theoretically cefazolin is
administered ≥4 hours before administered ≥4 hours before
deliverydelivery
Approach to Threatened Preterm DeliveryApproach to Threatened Preterm Delivery
No GBS cultureNo GBS culture GBS +
Onset of labor or rupture of membranes at <37 weeks gestationOnset of labor or rupture of membranes at <37 weeks gestation
with significant risk for imminent preterm delivery with significant risk for imminent preterm delivery
GBS -
Penicillin IV
for >=48 hrs
(during tocolysis)
Obtain vaginal
and rectal GBS
culture and
initiate IV penicillin
No GBS
prophylaxis
IAP at delivery
Stop penicillin
GBS +
No growth at 48 hrs
Management of the infant Management of the infant
whose mother has whose mother has
received IAPreceived IAP
Any gestational ageAny gestational age
If the infant is ill-appearing or sepsis is If the infant is ill-appearing or sepsis is
otherwise strongly suspected, a full diagnostic otherwise strongly suspected, a full diagnostic
evaluation including a CBC with differential, a evaluation including a CBC with differential, a
blood culture, and a lumbar puncture (unless blood culture, and a lumbar puncture (unless
the clinical status dictates otherwise) should be the clinical status dictates otherwise) should be
done and empiric antibiotic treatment initiated done and empiric antibiotic treatment initiated
using ampicillin and gentamicin until laboratory using ampicillin and gentamicin until laboratory
results are known. A chest radiograph should be results are known. A chest radiograph should be
obtained if respiratory symptoms are presentobtained if respiratory symptoms are present
Infants born at <35 wks of gestationInfants born at <35 wks of gestation
there is a clinical suspicion for sepsisthere is a clinical suspicion for sepsis
a change occurs in clinical statusa change occurs in clinical status
the blood culture yields GBSthe blood culture yields GBS
IAP administered <4 hrs prior to delivery IAP administered <4 hrs prior to delivery
If the infant is healthy-appearing and IAP with
penicillin, ampicillin, or cefazolin was
administered to the mother at least 4 hrs prior
to delivery, a CBC with diff. and blood culture
should be obtained and the infant observed
without antibiotic treatment for at least 48 hrs
Empiric antibiotics are initiated if:
Infants born at ≥35 wks of gestationInfants born at ≥35 wks of gestation
If the infant is healthy-appearing and IAP with
penicillin, ampicillin, or cefazolin was
administered to the mother at less than 4 hrs
prior to delivery, a CBC with diff. and blood
culture should be obtained and the infant
observed without antibiotic treatment for at least
48 hrs
Empiric antibiotics are initiated if:
a change occurs in clinical statusa change occurs in clinical status
the blood culture yields GBS the blood culture yields GBS
If the infant is healthy-appearing and IAP with
penicillin, ampicillin, or cefazolin was
administered to the mother at least 4 hrs prior
to delivery, the infant does not need further
evaluation but should be observed in the
hospital without antibiotic treatment for at least
48 hrs
Maternal IAP
for GBS?
Maternal antibiotics
for suspected
chorioamnionitis?
Limited evaluation
Observe ≥48hrs
If sepsis is suspected, full
diagnostic evaluation and
empiric therapy
Full diagnostic evaluation
Empiric therapy
Signs of neonatal sepsis?
GA <35 weeks?
No evaluation
No therapy
Observe ≥48 hrs
Duration of IAP before
delivery <4 hrs?
Yes
Yes
Yes
Yes
Yes
No
No
No
Management of the infant
whose mother has
received IAP
Management of the infant whose mother has Management of the infant whose mother has
prolonged rupture of membranesprolonged rupture of membranes
Rupture of Membranes ≥ 18 hrs
Mother has Chorioamnionitis?
Sings of Neonatal Sepsis?
GBS Screening at 35-37 wks gestation
Negative
No Evaluation
No Therapy
Observe ≥ 48 hrs
Positive
or Unknown
Mother received IAP ≥ 4 hrs prior to delivery
GA < 35 wks
Limited Evaluation (CBC with differential, and
blood culture)
Observe ≥ 48 hrs
Full Septic Screen and Start I.V. Antibiotics if:
1- Change in clinical status
2- Blood culture yields GBS
GA < 35 wks
Full Septic Screen:
CBC with differential, blood
culture, LP, and chest X-ray (if
indicated).
Start I.V. Antibiotics
Yes
Yes
Yes
Yes
Yes
No
No
No
No
No
Prepared by:
Dr. Ayman Abu Mehrem
Approved by:
Dr. Hesham Al-Girim
Reference: