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Infection in pregnancy
TORCH: was the acronym use before for infections which cause congenital
abnormalities.
TO=Toxoplasmosis, R= Rubella, C= Cytomegalovirus and H= Herpes
Later they were classified as STORCH
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(which can adversely affecting fetus,
neonates and mothers).
S= Syphilis, T= Toxoplasmosis
O= Others (Bacterial Vaginosis, Trichomoniasis vaginalis, Gp B
Strep., E. Coli, Ureaplasma urealyticum, Haemophilus
influenza, Varicells, Listeria monocytogenes)
R= Rubella
C= Cytomegalovirus
H
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= (Herpes, HIV, Hepatitis B, Human Papilloma virus, Human Parvovirus)
Parvovirus)
However pregnancy loss may occur in the first trimester, in association with any
acute infections in the mother, e.g. influenza.
Syphilis:
Is a sexual transmitted disease (STI), caused by spirochaete
Treponema pallidum. Common in many developing countries where up to 10% of
pregnant women may have positive serological test.
Primary infection: presents as painless genital ulcer 3-6 weeks after the
infection is acquired + local lymphadenopathy. The ulcer usually on the cervix
and will pass unnoticed. At this stage the infection is highly contagious.
Secondary manifestations: occur 6 weeks-6 months after infection, presents as
non-itchy maculopapular rash affecting the palms of the hands and soles of the
feet. While that affecting the mucous membrane are warty growth called
Condylomata lata; If no treatment, the lesion will regress after 2-4 weeks, but the
infected patient may suffer relapses in the following 2 years, when lesion may
reappear. This stage called early latent, as it may transmit during relapse. Late
infection ensues and syphilis can’t be transmitted sexually.
Tertiary syphilis: If untreated 20% will develop symptomatic cardiovascular
tertiary syphilis & 5-10% will develop neurosyphilis.
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Up to 70% of the fetuses become infected with the primary and secondary
infection during pregnancy. Later it will be less around 14%, 5 years after the
mother has acquired infection.
The spectrum of congenital infection varies form a severe fetal infection causing
intrauterine death, to neonate with symptomatic disease (early congenital
syphilis), a child who subsequently develop the stigmata of congenital syphilis
(late congenital syphilis), and a child who is asymptomatically infected. The
mother may got abortion or preterm labour.
Any woman presenting during pregnancy with a small genital ulcer should be
screened for syphilis and herpes.
Investigations:
1- Dark ground examination from the ulcer for T. pallidum.
2- Serology (FTA-fluorescent treponemal Ab. Absorption test, is the 1
st
test
become positive in early syphilis), other is TPHA; T. Pallidum
haemagglutination assay. Both these tests are specific for Treponemal
Ab., and remain +ve even after treatment and confirm exposure to syphilis
at some stage of life.
3- VDRL, Venereal Diseases Research laboratory, is quantitative. A high titer
1:64 or more is found in 2ndry or early latent dis. It fall after treatment and
will be unreactive in most individual after 2 years. False +ve test may be
seen in SLE and antiphospholipid syndrome.
Treatment: Penicillin is the treatment of choice, erythromycin less reliable.
The husband and older children need to be screened.
Toxoplasmosis:
The causative organism is Toxoplasma gondii which is
protozoan parasite that may be acquired from exposure to cat feces or from
eating uncooked meat. The prevalence varies from country to another. In
countries with high prevalence, then high percentage of pregnant women will
acquired the infection before pregnancy and were already immune. It may
cause a glandular fever like illness with atypical lymphocytes seen on blood
film, but rarely it cause fulminating pneumonitis or fatal encephalomyelitis.
Eye infection, presenting with chorioretinitis can occur from either congenital
or acquired infection. Most infection is asymptomatic.
Trimester
Risk of transmission
to the fetus
Risk of fetal damage
1
st
10-25 %
65%
3
rd
75-90 %
Zero (if near the time of
delivery)
Severely infected infants may have the classic tetrad of hydrocephaly or
microcephaly, chorioretinitis, convulsions & cerebral calcifications. In such
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case extensive neurological damage occurs and the neonates may die. The
majority of the infected infants are asymptomatic at birth but develop sequel
several years later. Since the prevalence of severe congenial toxoplasmosis
now is rare in many countries so routine screening in pregnancy is not
undertaken.
Diagnosis: many serological tests are available:
- The Sabin-Feldman dye test
- ELIZA demonstrating IgG & IgM
- Definite diagnosis by demonstrating the parasite in CSF and Lymph node.
- Clinical diagnosis of congenital infection, can be demonstrated if full
spectrum clinical features are present and the baby have elevated
toxoplasma antibody titer and if the titer remain positive for at least 6
months, then the diagnosis is definite. But the presence of IgM in cord
blood doesn’t mean definite diagnosis and its absence doesn’t exclude the
disease.
Treatment:
- Combination of sulphadiazine and pyrimethamine is used in symptomatic
adults. Pyrimathamine is teratogenic and should not be used in the first
trimester.
- Spiramycin, can be used safely in pregnancy.
Prevention:
- Avoid eating not well cocked steaks and humbergurs.
- Hand washing.
- Pregnant women avoid handling cats.
Cytomegalovirus: CMV
CMV: is type of herpes virus, so has the ability to establish latency.
Spreads is through the GT, respiratory tract, and urine. The primary infection
may produce no symptoms or mild non-specific symptoms, so the incidence in
pregnancy is not accurate but it’s around 1/200 pregnancies and 40% result in
fetal infection and 90% of infected infants are asymptomatic. Infection later in
pregnancy is more likely to result in fetal morbidity.
Main features are: microcephaly, blindness and deafness. Others are
pneumonitis, chorioretinitis, cerebral calcification & developmental delay. Some
time the only presentation is a child born with sensorineural hearing loss.
The diagnosis is rare before delivery since most of the cases are asymptomatic.
After infection the virus is excreted for weeks or months by adult and for years by
infants. Can be transmitted by blood transfusion and transplantation. Intermittent
reactivation occurs with shedding in the genital, urinary or respiratory tract. In
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temperate countries it can be transmitted by sexual contact. In tropical countries
most children are infected at childhood so few pregnant women are susceptible.
Features in infant are hepatosplenomegaly, jaundice & purpura.
Diagnosis:
1- Definitive diagnosis of congenital infection: by isolating the virus in cell
culture from throat swab, urine, blood or CSF in the first 3 weeks of life.
2- Serological test by rising titer of IgG Ab. Or specific IgM Abs persists for
few weeks to a few months. And specific IgA antibodies from a few
months to a year.
3- In utero by amniocentesis and PCR as it is concentrated in the urine.
4- Differential diagnosis of congenital manifestations: are Toxoplasmosis,
rubella, HS, & syphilis.
Treatment:
1- Specific antiviral available but not use in pregnancy only in
immunosuppressed patient and
it’s not indicated in infants with congenital
defect. Rehabilitation may be needed for congenital abnormalities.
Rubella:
The cause is Togavirus, which cause insignificant infection in adults or
adolescents but can cause severe infection in infant. Mostly around 70-90% of
young adult are immune.
Incubation period is 2-3 weeks. Clinical features are fever, sore throat, enlarged
cervical gland and rash with painful joints are common in adult and the symptoms
persist for 3-7 weeks.
Any infection suggestive of rubella in pregnancy should be investigated.
Congenital infection
characterized by Gregg’s triad of cardiovascular defects, eye
defects & deafness. Also hepatitis, thrombocytopenia, bone involvement,
microcephaly, behavioral changes and mental retardation. Also abortion,5
stillbirth & preterm labor can occur. In any case of small for gestational age baby
with congenital abnormalities, should suspect rubella infection.
Congenital infection is most common early in pregnancy, 50% following infection
in the 1
st
month, dropping to 10% following infection in the 4
th
month.
Diagnosis:
1- Serological test: maternal antibodies at booking done and if Ab. Titer is
low (
˂ 15 IU/ml) then booster vaccine should be given after labour. Very
high IgG titer suggestive of recent infection and specific IgM is only
detected for 4-6 weeks in most of the cases.
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2- Congenital rubella is diagnosed by detecting the virus in the secretion
from the throat, feces and urine. It can also be found in the CSF, blood,
eyes & ears.
Children deafness and blindness could be attributed to congenital rubella. If
the diagnosis confirm during the first trimester, then the risk of congenital
infection is so high, so many women elect to have termination of pregnancy.
However vaccination program during the secondary school in adolescent has
resulted in decrement in the incidence of congenital rubella.
Varicella zoster:
Varicella zoster is another herpes virus, transmitted easily from adult with
chickenpox or shingles (herpes zoster). Most of the adult are already immune
to chickenpox. Shingles is a reactivation that can occur in pregnancy but does
not cause any harm to the fetus. Pregnant women are more vulnerable to
chicken pox and may develop pneumonitis (especially in smokers) which can
be fatal and there is a need for intravenous acyclovir and intensive care
support.
Diagnosis: usually clinical but can be confirmed by electron microscope or
culture from scraping taken from the vesicles. Serological test are negative
during the acute presentation but if the Abs are absent then this confirm that
the mother is susceptible to infection.
Listeria monocytogenes:
This bacterium is widely isolated from more than 50 specious of animals,
sewage, water, meet, eggs and dairy products. Asymptomatic carriage in
human is common. Cooking destroyed the bacterium. Pregnant woman is
more susceptible to infection which probably is subclinical.
Features during pregnancy include: episodes of malaise, headache, fever,
backache, conjunctivitis, diarrhea with abdominal and loin pain. In animal
recurrent and persistent Listeria infection cause habitual abortion and may do
the same in human.
Fetal effects:
- If early, may cause preterm labour, RDS, septicemia within 2 days of birth
with rash sometime and may be stillborn.
- Late form present with meningoencephalitis after the 5
th
day. Usually the
organism tend to affect the CNS.
Diagnosis: in the neonates needs high index of suspension and specimens from
affected site, throat, liver, CSF, vagina, placenta, urine, feces and blood.
Infantile listeriosis mortality is as high as 90% and the prognosis is worse in
preterm birth.
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Malaria:
Is prevalent in the tropics and a major cause of mortality in children and adults.
Pregnant women are at increased risk of severe manifestation of malaria,
infection may trigger miscarriage or preterm labour and IUGR and the fetus may
have congenital malaria. It is uncommon in Iraq.
Bacterial vaginosis:
Is the commonest cause of vaginal discharge in woman of child bearing age.
Causing offensive fishy smelling vaginal discharge that is usually more apparent
during menstruation. It is believed that it is due to that the usually dominant
lactobacilli are overwhelmed by overgrowth of predominantly anaerobic organism
including, Gardnerella vaginalis, Bacteroides spp., Mycoplasma hominis.,
Mobiluncus spp., it is not sexually transmitted infection so no need to treat the
male partner.
Many observational studies confirm that infection with bacterial vaginosis may
increase the risk of second trimester abortion and preterm labour, it may be the
most important cause of idiopathic preterm labour. It associated with
chorioamnionitis, which can progress to deciduitis or amniotic fluid infection
which may result in fetal pneumonitis and ultimately fetal death may follow this
from sepsis. Chorioamnionitis is associated with elevated levels of pro-
inflammatory cytokines as tumour necrosis factor
–alpha(TNF-α), interleukin 6
(IL6)& ( IL12), these can stimulate the metabolism of arachidonic acid to
prostaglandin, which is the final pathway for cervical ripening and the onset of
labour. Symptomatic woman should be treated with metronidazole.
Herpes simplex virus:
Primary infection usually presents within 7 days of exposure and may be
accompanied by a wide spread lesions around the mouth and oropharynx and in
case of genital herpes around the vulva, vagina and cervix. In many population
70-80% are exposed to oral herpes; HSV 1 during childhood which give some
cross- protection against HSV 2; the causative agent for genital herpes.
Primary genital herpes presents with soreness and irritation of the affected part, it
may be passed unnoticed or manifested with wide spread eruption of painful
ulcers preceded by vesicles. Severe dysuria and peripheral nerve involvement
may lead to urinary retention and require admission for analgesia, and may be
suprapubic catheter.
Initial diagnosis is clinical but should always be confirmed taking swab from the
vesicles
There are insufficient data to confirm that acyclovir is safe in pregnancy.
However to date, there are no access of birth defect associated with its use.
Topical application is not effective in the treatment of genital herpes.
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Important to be diagnosed in pregnancy because neonatal infection can occur
with involvement of the skin, liver, and CNS and neonatal mortality is 75% but if
acyclovir administered rapidly, this can be reduced to 40%. The majority is
associated with primary infection in the mother in the weeks prior to delivery and
the baby has no protective antibody and will have disseminated infection or
localized herpes encephalitis.
If primary herpes present around the time of labour, the case should be
discussed with the pediatrician, caesarean section will give protection if rupture
of membrane occurred in no more than 4 hours, taking genital swab from the
mother and throat swab from the baby and giving intravenous acyclovir to the
neonate. And if herpes is recurrent herpes and the attack return around labour
then caesarean section need to be done, although the risk of fetal infection is low
in such cases.
Infection in the first trimester may cause miscarriage, and the congenital herpes
characterized by microcephaly, micro-ophthalmia and chorioretinitis.
Group B Streptococcus:
The organism is commensal in the gut and genital tract and may found in 20-40
%. May cause severe infection leading to neonatal death and can cause upper
genital tract infection progressing to septicemia and occasionally maternal death.
Carriage of the organism is asymptomatic, colonized the vagina from the gut and
even after treatment recolonization of the vagina will occur for that reason the
current recommendation is that the organism should be sought by culture of
vaginal swabs in complicated pregnancies or when there has been a prior
preterm labour and if the organism is present, penicillin should be administered
intravenously at the time of labour. Infants at risk; are the premature, or have
undergo delivery after prolong rupture of the membranes, growth restricted and
have birth asphyxia.
If there is a high prevalence of neonatal infection in a hospital then better to have
a screening protocol for mothers whose pregnancies considered at high risk and
to treat them at 28 weeks gestation with penicillin if the organism is detected on
vaginal swab.
Chlamydia Trachomatis
Chlamydia trachomatis is an obligate intracellular parasite. Genital infection with
serotypes D-K is the comments bacterial sexually transmitted infection in
developed countries and very common in developing countries also.
It’s important in pregnancy, since it cause neonatal eye infection (ophthalmia
neonatorum) and neonatal pneumonitis.
Pelvic inflammatory disease that can be a squeal of this organism is rare in
pregnancy and many women carrying Chlamydia trachomatis are only diagnosed
after the neonate develops clinical disease.
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Previous infection by Chlamydia may cause tubal damage and is a predisposing
factor for ectopic pregnancy.
Around 50% of the babies born to women affected with Chlamydia infection
develop ophthalmia neonatorum, which presents about a week after birth with a
red sticky eye, which may be bilateral. Swab from the affected eye or the
nasopharyngeal aspirate.
Diagnosis:
By detecting the organism, by DNA detection-based test or direct
immunofluorescence. The organism can be detected with such tests in the
endocervical swabs, first pass urine samples and self administered vaginal
swabs. Important differential diagnosis of cervicitis is gonorrhea.
Treatment:
Doxycyclin which is contraindicated in the second and third trimester because it
bind to developing bones and teeth in the fetus causing brown stain of the teeth
and developing bones, Erythromycin 500mg twice a day for 2 weeks will be
given. Azithromycin as a single 1 g dose is licensed for such treatment. The
neonate is treated with tetracycline ointment and 2 weeks coarse of erythromycin
syrup because of the risk of Chlamydia pneumonitis.
This organism may cause subclinical enodmetritis which may predispose to early
pregnancy loss, chorioamnionitis and preterm birth and clinical postpartum
endometritis with failure of implantation of IVF. Such women and their partner
should be screened.
Gonorrhoea:
Neisseria gonorrhea is a sexual transmissible agent causing cervicitis, urethritis,
endometritis, salpingitis (PID) and perihepatitis in women. Infection in both sexes
is often asymptomatic. Its importance in obstetrics is due to a neonatal eye
infection which if untreated can progress to blindness due to corneal scarring.
Diagnosis:
Gram stain microscope of cervical, urethral & rectal swabs and culture on
selective media as blood agar. DNA detection based test are now available.
This organism has greater ability to acquired resistance to antibiotics.
Treatment:
In pregnancy, if the woman is penicillin allergic, then cephalosporin used and if
the neonate develop eye infection then topical and systemic antibiotics according
to the sensitivity.
It associated with chorioamnionitis and preterm birth.
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Trichomoniasis:
Trichomonas vaginalis causes severe vulvo-vaginitis in susceptible women.
Usually sexually transmitted although infection may persist asymptomatic for
many months in women and in some men.
Transient infection can be transmitted to female infants who will present with
purulent vaginal discharge.
Its prevalence remains high in many developing countries where are many as 20-
30% carrying the infection. Newborn girls have stratified squamous epithelium in
the vagina similar to that of the adult due to influence of high levels of maternal
estrogen in the uterus, they are therefore susceptible to infection and may
develop asymptomatic discharge and as the eostrogen level wanes with time
over the first few weeks of life such infection will resolve spontaneously and
mostly without treatment.
Trichomoniasis often coexists with disturb vaginal flora that develops into
bacterial vaginosis. The only treatment for Trichomoniasis is systemic
metronidazole 400 mg twice a day. For 5 days. But it has been shown to carry a
risk of teratogenicity.
Vaginal candidiasis:
More than ¾ of women have at least one episode of vaginal candidiasis during
their life. The causative organism is Candida albicans in more than 80% of the
cases. Sexual causation is rarely important. Symptomatic episodes are common
in pregnancy; growth of the organism is favored by high level of estrogen,
increase availability of sugar and subtle alteration in the immunity. For treatment
in general better to use topical application as it has fewer side effects than
systemic treatment.
Genital warts:
The causative organism is HPV (human papillpoma virus). More than 100 strains
has so far been identified and certain strain generally are transmitted sexually,
producing genital warts on the mucosa of the genital tract. Most symptomatic
infection start within 8 months of starting sexual relationship with a new partner.
Cell mediated immunity is important for suppression of wart viral infection, while
this immunity is suppressed in pregnancy so previously asymptomatic infection
may become obvious in pregnancy or become more florid in pregnancy.
Treatment with topical application of podophyllin or podophyllotoxin is often used
as first line treatment but is contraindicated in pregnancy. So surgical excision is
the only treatment available for pregnant woman.
Any baby delivered to a woman harboring warts virus will be exposes to the virus
during delivery but it appear that few neonates will acquire the infection from their
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mother and rarely the infant will have laryngeal warts due to the genital strain of
the wart virus.
Other infections:
With altered immune system of the pregnant woman, chronic infection requiring
cell-mediated immunity may flare up. These include warts virus and tuberculosis
as more women may present with severe disease as miliary TB.
Vertically transmissible viral infection:
1- Hapatitis A: caused by RNA virus, which spread through the oral-fecal
route. The majority of people in developing countries acquired the
infection during childhood. Usually it is a benign illness. But occasionally
fulminating hepatitis had been described in pregnant women although it
has not been associated with congenital abnormalities.
2- Hepatitis B: is a more severe infection that may follow by chronic carriage
and disease ending in cirrhosis. Transmitted sexually through blood
products and through vertical transmission from infected mother. The
earlier in life the infection, the more likely the person becomes a carrier.
80 % of infant infected perinatally become carrier. In some countries,
pregnant women are screened at booking.
In In acute infection: (HBsAg) & (HBeAg) are detectable in the serum.
Hepatitis B core Ab appear after 6 weeks and remain detectable thereafter
as a marker of exposure.
Immunity develops, when anti-e Ab developed and the e antigen become
undetected.
Clearance of the virus, when HBsAg disappeared and HBsAb is detected.
Infectious person: If Hepatitis-e Ag is present, then the individual is highly
infectious. But small proportion who are HBsAg positive but HBeAg
negative are infectious also.
Chronic infection: Anti-Core Ab is positive and then testing the other
markers for the degree of infectivity.
Treatment: Interferon under the guidance of liver specialist with antiviral
drug with special activity against hepatitis B.
Vertical transmission can be prevented by vaccination of the neonate born
to the mother with hepatitis B. Haptitis B Ig at birth if the mother is e Ag
positive. Countries with high rate of hepatitis infection has a policy of
universal vaccination of all infants.
3- Hepatitis C: RNA virus which causes chronic hepatitis. The prevalence
varies widely across the world, with the highest incidence in Egypt and in
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patients with a history of intravenous drug use with low occasion
transmitted sexually. Vertical transmission also uncommon.
4- HIV infection: which cause major challenge to the obstetric team. The
target is to reduce the vertical transmission to the fetus and maintain the
woman health.
Transmission: In most developing countries, HIV is principally spread
through vaginal intercourse. In developed countries, the majority of
infection acquired through homosexual sex or intravenous drug use.
Genital infection are risk factors, include genital ulcer, Chlamydia and
gonorrhea and Bacterial vaginosis.
Vertical transmission: occur in 25-40% of pregnancies if there are no
intervention to reduce the risk. The minority or the infections occur during
gestation. Babies can present with AIDS in the neonatal period. Majority of
the infection occur during parturition and breast feeding account for 15%of
transmission during pregnancy. Risk of vertical transmission increase is
still being assessed. The role of genital infection in vertical transmission is
still being assessed. Many children infected with HIV will survive into
adolescence. To reduce the risk of vertical transmission of HIV:
- Avoiding breast feeding
- Elective cesarean section
- Antiviral medication prescribed during the latter half of pregnancy and to
the neonate for 6 weeks.
If all these intervention are taken then the risk of transmission will be less
than 1%.
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