INFECTIONS IN

PREGNANCY AND

PUERPERIUM

Krzysztof Drews

Division of Perinatology and Women Diseases



Infection - pathogens’ invasion,
colonization and immune response of
the host organism.
This process depends on pathogenicity
and defense mechanisms of the host.



Prenatal infections:

– vertical
– ascending

Changes in immune system in

pregnancy



Progesterone - decreases activity of lymphocytes
T

- activates function of Ts and NK



HCG - decreases activity of NK cells

- activates proliferation of
lymphocytes T



Estrogens - activate function of Ts cells



PGE2 - decreases activity of lymphocytes
T

Vertical infections

TORCH - main vertical infection

with
similar symptoms:



T - toxoplasmosis



O - others (syphilis)



R - rubella



C - cytomegalovirus



H - herpes simplex, hepatitis,
human immunodeficiency virus

oth b

acterial and viral

infections can result

in:



spontaneous abortion



stillbirth



preterm delivery



intrauterine growth retardation



congenital anomalies of the fetus
(hydrocephalus, chorioretinitis, cataract
hepatosplenomegaly, purpura, ascites, heart
defects)



congenital infections

About

2 - 3%

of congenital infections are

caused by

viruses.

Prenatal diagnosis



serological screening of syphilis,
toxoplasmosis, hepatitis B



ultrasound examination



amniocentesis and isolation of
pathogenes (HSV, CMV, Rubella virus,
T.gondi)



cordocentesis and detection of the
cord - blood specific immunoglobulins

Rubella

The virus causes cytolysis and decreases

mitotic activity.

Incubation period:

14 - 21 days.

Symptoms:

flu-like symptoms and after 1-

5 days macular rash with postauricular

and suboccipital lymphadenopathy

Specific IgM anti-bodies occur 14 days

after infection and are present for 3

months. IgG appear later and usually

persist for the whole life.

Congenital rubella



maternal infection in the first
trimester can induce spontaneous
abortion,



risk of transplacental infection: 22%
neonates born to mothers who
suffered from rubella in the first
trimester are affected and 10% as the
effect of rubella in the second
trimester

Classical triad of congenital

rubella symptoms described

by Gregg:



cataract



perceptive deafness



congenital heart defect

Other symptoms:



intrauterine growth retardation



retinopathy



meningoencephalitis



purpura



splenomegaly



mental retardation



pneumonia



hepatitis

Rubella - prevention /

treatment

There is no specific therapy.
Vaccinations: school children and

women at the reproductive age
who have no specific IgG anti -
bodies.

CMV

is considered to be the

most common viral cause of

congenital infection



10% of infected neonates develop
classical congenital CMV infection



5% have non - typical symptoms



85% are asymptomatic

Transmission to the fetus occurs in

40% pregnencies with primary
CMV. Infection acquired earlier in
gestation results in a more severely
affected infant.

Symptoms of congenital

CMV infection:



intrauterine growth retardation



microcephaly



periventricular calcifications



hepatosplenomegaly



non - immune hydrops



ascites



thrombocytopenia and purpura



perceptive deafness



pneumonia



jaundice

CMV

Approximately 5 - 15% of the
initially asymptomatic infants
develop the symptoms, such as
mild mental retardation or
hearing loss, by the age of two.

Hepatitis B



Fulminant hepatitis is more often during

pregnancy

(ascites,

encephalopathy,

rapidly shrinking liver, jaundice). The
mortality rate is 90%.



Infection:

transplancental or during

delivery



Most neonates at the time of delivery are

seronegative and asymptomatic but
within

months

they

become

seropositive.



Teratogenic effect is not proved.

Hepatitis B -

prevention



All pregnant women should be screened for
HBsAg.



Women with a definite exposure to HBV
should be given HBIG within 7 days and
the second dose after a month.



Infants born to HBsAg - positive women
should receive HBIG and the first dose of
the recombinant HBV vaccine within 12
hours after birth. The second dose should be
given after a month and the third after 3
months. This treatment protects

70 - 75%

the infants.

Hep

titis

75%

patients are asymptomatic

25%

develop symptoms of past

hepatitis B

50%

of cases become a chronic

infection

of fetuses born to HCV – positive

mothers are infected and even more if
there is a co-infection of HCV and HIV

Human

Immunodeficiency

Virus

Pregnancy provokes rapid progression of
HIV infection and developing symptoms,
mainly Pn. carini pneumonia.
There is also higher risk of spontaneous
abortion, preterm delivery, IUGR, PROM.
HIV is usually transmitted during
delivery, but also transplancetal infection
and infection through breast - feeding are
possible (risk of about 20%).

Prevention

vertical

HIV

infection



Zidovudine prophylaxis since 14th week of
pregnancy and elective caesarean section
reduce transmission rate to 6 - 7% (but
some researches revealed no differences
in the infection rate during spontaneous
delivery and caesarean section)



Prophylaxis of Pn. carini pneumonia:
trimetoprim/ sulphametoxazol



Avoid amniocentesis, chorionic villous
sampling, cordocentesis and other invasive
procedures (also spontaneous delivery)



Avoid breast - feeding

Toxoplasmosis

Fetal infection occurs only with
acute maternal toxoplasmosis.
The likelihood of transmission
varies with gestational age - it
is more frequent, but less
severe in late weeks of
pregnancy.
Maternal reinfection is not
dangerous for the fetus.

Acute primary

toxoplasmosis can result

in:



spontaneous abortion



preterm delivery



intrauterine growth retardation



central nervous system defects



hepatosplenomegaly

Symptoms of congenital

toxoplasmosis:



chorioretinitis



periventricular calcifications



hydrocephaly

– microcephaly

– jaundice

– anaemia

– hepatosplenomegaly

– thrombocytopenia

– lymphadenopathy

– mental retardation

– visual deficits

classical
triad

Toxoplasmosis - treatment

In early pregnancy: spiramycin -
without side

effects in first trimester
In the second and third trimester:

pyrimethamine

and sulfadiazine

- the most effective

treatment,

but

teratogenic

Syphylis

Treponema palidum passes
through the placenta and
attacks the fetus after the 5

month of pregnancy.
It can cause preterm delivery,
stillbirth and congenital
infection even 2 - 3 years after
mother's infection.

Each pregnant woman

should be screened for

syphilis infection

Serological tests:



VDRL (Venereal Disease Research
Laboratory) sensitivity

50 - 70%



TPHA

(Treponema

Palidum

Haemaglutination Assay) – sensitivity

70 - 90%



FTA – ABS (Fluorescent Treponemal
Antibody Absorbed) - sensitivity

70 -

90%

Ascending infections –

risk factors of intra-

amniotic infection (IAI)



duration of labor



duration of PROM



number of vaginal examinations



coexistence of bacterial vaginosis (BV)



amniocentesis, cordocentesis



internal fetal monitoring



malnutrition



nulliparity

Premature rupture of membranes

is associated with increased risk
of infection concerning both fetus
and mother.

Microorganisms are present in

amniotic

fluid

66,6%

patients with PROM

IAI -

definition



Acute clinical infection of the amniotic fluid
and intrauterine contents during pregnancy.



Occurs in 0,5 – 10% of all pregnancies



Risk of:

– Premature delivery
– PROM – the cause or consequence of IAI?
– Neonatal complications (prematurity, pneumonia,

sepsis, NEC, intraventricular hemorrhage)

– Puerperal infections

Potential pathways of infection

Goldenberg et al. N Eng J Med. 2000

Bacterial colonization and

preterm delivery

Goldenberg et al. N Eng J Med. 2000

Probiot

ics



Hydrogen peroxide (H

)-producing strains

of Lactobacillus have been found in 61% of
pregnant women with normal flora, yet in only
5%
of women with BV.



has been shown to be toxic to BV-causative

organisms, namely, Gardnerella vaginalis and
Prevotella bivia.

Diagnosis of IAI



The

early

stage

IAI

asymptomatic



Later - symptoms are neither
sensitive nor specific



Only results of laboratory tests
enable to diagnose an early
infection.

IAI

SYMPTOMS



fever



leukocytosis



uterine tenderness



tachycardia of the

fetus and/or

mother



foul amniotic fluid

(in cases with

PROM)

TREATMENT



antibiotic therapy



elective cesarean
section, that
enables to
eliminate the
possibility of
spreading of the
infection.

IAI – strategy of

antibiotic therapy



result

bacteriological

examination



most

frequent

microorganisms

associated with IAI



drug administration as early as
possible



combination of two antibiotics with
various anti-bacterial spectrum

Cytokiny Il-1, Il-6, TNF

Arachidonic acid

Prostaglandins E

i F2

Fosfolipase A

i C

Arachidonic acid

Prostaglandins

, F



Bacterial toxins

Contractions

Il-8

Cervical dilatation

Intra-amniotic infection

Management

Antibiotic treatment

Start of treatment – as quick as possible,

even before pathogen identification.

 2 or 3 antibiotics
 Duration of treatment – 2 days longer than

the symptoms are present.

Treatment - newborn

Treatment decision depends on the

symptoms developed by the infant and
results of examinations.

If antibiotic therapy is necessary,

recommended drugs are ampicilin with
gentamycin.

FIRS as a predictor of impared

neurologic outcome



FIRS (Fetal Inflammatory Response Syndrome) – usually
subclinical activation of fetal immune system, defined by
elevations in the levels of specific cytokines, especially
interleukin-6 (Il-6) in amniotic fluid and fetal plasma



Histological funisitis is more specific predictor of
neurologic outcome than Il-6 (PPV 86% vs 59%)

Mittendorf 2004

FIRS as a predictor of

impared neurologic

outcome

Fetal plasma Il-6 concentration > 10pg/mL and
histological funisitis are associated with variety of adverse
neonatal outcomes: intraventricular hemorrhage, sepsis,
meningitis, cerebral palsy, perinatal death

Mittendorf 2004

Fetal

Inflammatory

Response

Fetal

Inflammatory

Response

Preterm

birth

Preterm

birth

Intrauterine

infection

Intrauterine

infection

WMD/CP

Dammann et Leviton, Early Hum Develop, 2004

Hypoxic obstetric events and

cerebral palsy

1862 William John Little

- the link between cerebral

palsy and events complicating the perinatal period

Hypoxic obstetric events are responsible for only 8–10%

of the cases of cerebral palsy and in most cases the

condition remains unexplained

Intraamniotic infection ?

Chorioamnionitis and

cerebral palsy

Clinical chorioamnionitis was associated with:



cerebral palsy RR 1,9 Cl (1,4-2,5)



periventricular leukomalacia RR 3,0 Cl (2,2-4,0)



cerebral palsy

RR 1,9

Cl (1,4-2,5)



periventricular leukomalacia

RR 3,0

Cl (2,2-4,0)

Histologic chorioamnionitis was associated with:



cerebral palsy RR 1,6 Cl (0,9-2,7)



periventricular leukomalacia RR 2,1 Cl (1,5-2,9)



cerebral palsy

RR 1,6

Cl (0,9-2,7)



periventricular leukomalacia

RR 2,1

Cl (1,5-2,9)

Wu et Colford, JAMA 2000

BRAIN DAMAGE

PVL

The role of TNF-



the pathophysiology of PVL

fetal hypotension

and brain ischaemia

stimulating the production

of a tissue factor

activation of the

haemostatic system

coagulation

necrosis of white matter

release of platelet

activating factor

direct cytotoxic effect of

TNF on oligodendrocytes

Leviton A. Dev Med Child Neurol 1993

Infections in puerperium



Infection of perineum



Infection of wounds



Endometritis



Sepsis



Mastitis

Infections in puerperium

Fever is the most common symptom of infections in puerperiumist

Body temperature
>38 C



Early

<48h after delivery



Late

>48h after delivery

Infections in puerperium



Reasons of fever in puerperium:



Retention of lochia



Endometritis



Complicated healing of wound



Mastitis



Thrombophlebitis



Pyelonephritis



Sepsis



Pneumonia

Infection of episiotomy wound



Is not very common but very uncomfortable

post-partum complication.



Concern 0,035 - 3% of every delivery



It may lead to more serious complications

(sepsis, necrotizing fasciitis)



Treatment: surgical + antibiotics

Infections in puerperium

Post Caesarean Section Wound Infection

• Concern 1,6 - 10% of cesarean sections
• Increased risk: long operation time, increased blood lost,
obesity, age, intraaniotic infection, bacterial vaginosis.
• Treatment: surgical + antibiotics