Congenital Viral Infection

Congenital Viral Infections
TEVFİK YOLDEMİR MD. BSc. MA. PhD.
tyoldemir
profdrdryoldemir

Viruses which are perinatally acquired and
which can cause fetal/neonatal damage.Table 17.1 Viruses which are perinatally acquired and which can cause fetal/neonatal damage.
Virus Perinatal/neonatal effects
Known teratogenic viruses See text for perinatal effects
Cytomegalovirus
Rubella virus
Varicella zoster virus
Herpes simplex virus (HSV1, HSV2)
Parvovirus B19
Venezuelan equine encephalitis virus
Viruses that have been shown to cause fetal damage after transmission
Coxsackieviruses (group B) Myocarditis, meningoencephalitis, pleurodynia
Dengue virus Fever, leucopenia, thrombocytopenia
Echovirus (14 and 19) Apneic spells, hepatitis, thrombocytopenia
Hepatitis B virus Hepatitis
Clinical obstetrics : the fetus & mother 3rd edition 2007 p.249
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Non-A, non-B, non-C hepatitis viruses
Rabies virus
Smallpox virus
Table 17.2 Frequency of teratogenic viral infections in pregnant
women and their children.
Virus Mother Child
(per 10000) (per 10000)
Cytomegalovirus 300–500 50–150
Rubella virus
Epidemic 200–400 20–40
Nonepidemic 10–20 1–2
Currently in the USA < 1 < 0.1
Herpes simplex virus 50–150 0.5–5.0
Parvovirus B19 25 5–10
Varicella zoster virus 1–2 < 0.01–1.0
Venezuelan equine encephalitis With epidemics With epidemics
approximately 40000 infants are born annually with either
clinical or laboratory evidence of CMV infection. Worldwide,
it is estimated that 1% of all newborns are infected with CMV.

Viruses that cause fetal damage
Known teratogenic viruses See text for perinatal effects
Cytomegalovirus
Rubella virus
Varicella zoster virus
Herpes simplex virus (HSV1, HSV2)
Parvovirus B19
Venezuelan equine encephalitis virus
Viruses that have been shown to cause fetal damage after transmission
Coxsackieviruses (group B) Myocarditis, meningoencephalitis, pleurodynia
Dengue virus Fever, leucopenia, thrombocytopenia
Echovirus (14 and 19) Apneic spells, hepatitis, thrombocytopenia
Hepatitis B virus Hepatitis
Hepatitis C virus Hepatitis
Human immunodeficiency virus Growth restriction, leukopenia, failure to thrive, hypogammaglobulinemia, AIDS-relate
Human papillomavirus Laryngeal papilloma
Influenza virus Endocardial fibroelastosis (?)
Mumps virus Pneumonitis, endocardial fibroelastosis (?)
Parvovirus B19 Nonimmune fetal hydrops, anemia
Poliovirus Paralysis
Rubeola (measles) virus Premature delivery, measles, otitis media
Vaccinia virus Spontaneous miscarriage, fetal death
Variola virus Spontaneous miscarriage, fetal death
Western equine encephalitis virus Meningitis
Viruses that have not been shown to cause fetal damage after transmission or when data on fetal transmission are inconclusive
Coxsackieviruses (group A)
Epstein–Barr virus

Viruses that do not cause fetal damage
cytomegalic inclusion disease (CID), occ
approximately 1 in 5000 to 1 in 20000 bi
Perinatal transmission of CMV has bee
cases where the pregnant woman develops
recurrent CMV infection. Transmission ra
primary infection range from 15% to 50%
Mumps virus Pneumonitis, endocardial ﬁbroelastosis (?)
Parvovirus B19 Nonimmune fetal hydrops, anemia
Poliovirus Paralysis
Rubeola (measles) virus Premature delivery, measles, otitis media
Vaccinia virus Spontaneous miscarriage, fetal death
Variola virus Spontaneous miscarriage, fetal death
Western equine encephalitis virus Meningitis
Viruses that have not been shown to cause fetal damage after transmission or when data on fetal transmission are inconclu
Coxsackieviruses (group A)
Epstein–Barr virus
Hepatitis A virus
Non-A, non-B, non-C hepatitis viruses
Rabies virus
Smallpox virus
Table 17.2 Frequency of teratogenic viral infections in pregnant
women and their children.
Virus Mother Child
(per 10000) (per 10000)
Cytomegalovirus 300–500 50–150

Consequences of viral infections during pregnancy
VIRAL INFECTIONS IN PREGNANCY OTHER THAN HIV
Table 17.1 Consequences of viral infections during pregnancy
Viruses by predominant
clinical consequences
Abortion, stillbirth Prematurity Symptomatic congenital
infection
Developmental abnormalities/
birth defects
Neonatal disease
Fetal
CMV ϩ ϩ ϩϩ1
ϩϩϩ ϩ
Rubella ϩ Ϫ ϩϩϩ1
ϩϩϩ ϩ
Parvo BϪ19 ϩϪ Ϫ ϩ Ϫ Ϫ
LCV ϩ Ϫ ϩ ϩϩ ϩ
Mumps ϩϩ Ϫ Ϫ ϩ Ϫ
Materno-fetal
Measles ϩ ϩϩ Ϫ Ϫ ϩ
Neonatal
Coxsackie (mostly B1-B5
strains)
ϩ Ϫ Ϫ ϩ2
ϩϩ
Echovirus serotype 11 ϩ3
Ϫ Ϫ Ϫ ϩϩ4
Maternal-neonatal
Primary VZV Ϫϩ Ϫ5
Ϫ ϩ6
ϩϩϩ7
HSV Ϫ Ϫ ϩ8
Ϫ6
ϩϩ9
HPV Ϫ Ϫ Ϫ Ϫ ϩ10
Maternal
Influenza Ϫ Ϫ Ϫ Ϫ Ϫ
EBV11
Ϫ ϩ Ϫ Ϫ Ϫ
Ϫ No documented association.
ϩ Documented association but true incidence unknown.
ϩϩ Well-documented association (prospective, histopathologic correlation and/or molecular data).
ϩϩϩ Most clinically relevant association.
de Swiet’s Medical Disorders in Obstetric Practice 5th edition 2010 p 433

Summary and characteristics of the laboratory tests
used for assessment of viral infections in pregnancy
Reproductive Toxicology 21 (2006) 350–382

Clinical syndromes associated with viral
infections in pregnancy and diagnostic tests
Table 17.2 Clinical syndromes associated with viral infections in pregnancy and diagnostic tests
Clinical syndrome Potential viral infections Direct viral detection Antibodies
Undifferentiated fever CMV, rubella1
, enteroviruses2,6
,
influenza, EBV, measles3
,
parvo B-19, WNV4
CMV, parvo B-195
NAAT blood
Nasopharyngeal wash for influenza
Throat swab for viral NAAT6
Urine for viral culture
Stool for viral culture6
Single serum:
CMV, EBV IgM, IgG7
WNV IgM
Monospot
Paired serum:
Rubella IgM, IgG8
Parvo B-19 IgM, IgG
Measles IgM, IgG
Fever and nonvesicular rash Rubella, measles, echoviruses2
,
EBV, parvo B-19, CMV
Throat swab for viral NAAT 6
Stool for viral culture 6
Parvo B-19 NAAT blood
EBV IgM, IgG
Monospot
Paired serum:
Rubella IgM, IgG
Parvo B-19 IgM, IgG
Measles IgM, IgG, CMV
Fever and arthritis Rubella, parvo B-19, enteroviruses2
Parvo B-19 IgM, IgG
Fever and neurologic signs HSV, WNV4
, polio WNV NAAT blood
CSF for HSV, polio, WNV NAAT
or viral culture
Vesicle fluid/scraping for HSV
Single serum:
WNV IgM, IgG
Vesicular rash VZV, HSV Vesicle fluid/scraping for VZV/HSV VZV IgM , IgG9
Genital ulcers HSV, VZV Vesicle fluid/scraping for HSV/VZV HSV type-specific serology
Hepatitis CMV, EBV, hepatitis A, B, C and E CMV NAAT blood CMV, EBV IgM, IgG
NAAT: nucleic acid amplification test
PCR is a type of NAAT

Clinical syndromes associated with viral
infections in pregnancy and diagnostic tests
Measles IgM, IgG
Fever and nonvesicular rash Rubella, measles, echoviruses2
,
EBV, parvo B-19, CMV
Throat swab for viral NAAT 6
EBV IgM, IgG
Monospot
Paired serum:
Rubella IgM, IgG
Parvo B-19 IgM, IgG
Measles IgM, IgG, CMV
Fever and arthritis Rubella, parvo B-19, enteroviruses2
Parvo B-19 IgM, IgG
Fever and neurologic signs HSV, WNV4
, polio WNV NAAT blood
CSF for HSV, polio, WNV NAAT
or viral culture
Vesicle fluid/scraping for HSV
Single serum:
WNV IgM, IgG
Vesicular rash VZV, HSV Vesicle fluid/scraping for VZV/HSV VZV IgM , IgG9
Genital ulcers HSV, VZV Vesicle fluid/scraping for HSV/VZV HSV type-specific serology
Hepatitis CMV, EBV, hepatitis A, B, C and E CMV NAAT blood CMV, EBV IgM, IgG
Monospot
HAV IgM
HBsAg10
anti-HBc IgM11
Anti-HCV
HEV IgM, IgG12
Mononucleosis-like illness
(recurrent fever, myalgias,
sore throat ϩ/Ϫ arthritis or
rash)
CMV, LCV, EBV, HIV13
CMV, EBV NAAT blood EBV IgM, IgG
Monospot
HIV IgG
Travelϩ/Ϫ any of the above Hepatitis E, Japanese encephalitis,
hemorrhagic fevers
Consultation with reference
laboratory advised
1
Direct viral isolation of rubella not routinely done as very difficult to culture and rapid methods are not widely available.
2
Enteroviruses – polio, coxsackie and echoviruses – to be considered particularly in the third trimester, during summer/fall season and/or in the context of
aseptic meningitis.
3
Direct viral isolation of measles not routinely done; in low-prevalence countries (USA/Canada) use paired acute and convalescent serum for anti-measles
IgM and IgG: a fourfold increase in anti-measles antibody titer is indicative of infection.
4
WNV to be considered in areas with known WNV transmission.
5
NAAT: nucleic acid amplification test
PCR is a type of NAAT

Common prenatal ultrasound findings of
certain viral infections
which affects 10–40% of the general population over a 6-week
period every winter in temperate climates, but year round in
the tropics. Pregnant patients are more susceptible to develop-
ing influenza complications, particularly pneumonia. Although
influenza vaccine is widely recommended for all pregnant
women throughout the flu season, vaccination rates remain low.
Clinical presentation
The most common clinical course is abrupt onset of fever,
malaise, headache, severe myalgias and cough. Fever typically
lasts 3 days and most people recover within a week. Influenza
pneumonia is more common among patients with pre-existing
Table 17.3 Common prenatal ultrasound findings of certain viral infections
Virus CNS Cardiac Abdominal Placenta Other
CMV Ventriculomegaly
Calcifications
Microcephaly
Cerebellar aplasia
Cardiomegaly
Septal defects
Calcifications
Hepatomegaly
Splenomegaly
Calcifications
Ascites
Echogenic bowel
Placentomegaly IUGR
Hydrops
Demise
Oligohydramnios
Rubella Calcifications
Encephalocele
Microcephaly
Microphthalmia
Ventriculomegaly
Septal defects
Pulmonic stenosis
Coarctation of aorta
Hepatomegaly
Hepatic Calcifications
Splenomegaly
Meconium peritonitis
Calcifications IUGR
Cleft palate
VZV Ventriculomegaly
Calcifications
Microphthalmia
Retinal Calcifications
– Hepatomegaly
Calcifications
Ascites
Small placenta
Calcifications
IUGR
Limb deformities
Oligohydramnios
HSV Hydranencephaly
Ventriculomegaly
Calcifications
Microcephaly
Microphthalmia
– Hepatomegaly
Splenomegaly
Calcifications IUGR
Limb hypoplasia
Parvo B-19 – – – – Hydrops
Polyhydramnios
Increase in MCA-
Doppler velocity
CMV, cytomegalovirus; CNS, central nervous system; HSV, herpes simplex virus; IUGR, intrauterine growth retardation; VZV, varicella-zoster virus.

Infant outcome following cytomegalovirus
(CMV) maternal infection in pregnancy506 SECTION FOUR • Infection
Pregnant women of
higher income group
55%
immune
45%
susceptible
0.15%
congenital
infection (recurrent
maternal infection)
1–4%
primary infection
0–1%
infected infants may
have clinically apparent
disease or sequelae
10–15%
disease (mild to severe)
0–1%
disease or sequelae
0.5–1%
congenital
infection (recurrent
maternal infection)
85–90%
infected infants
are asymptomatic
40%
transmit
infection to fetus
10%
develop normally
90%
develop sequelae
5–15%
develop sequelae
85–95%
develop normally
Pregnant women of
lower income group
85%
immune
15%
susceptible
FIGURE 30–1
Infant outcome following cytomegalovirus
(CMV) maternal infection in pregnancy.
(Adapted from Stagno S: Cytomegalovirus. In
Remington JS, Klein JO (eds): Infectious
Diseases of the Fetus and Newborn Infant, 4th
ed. Philadelphia, Saunders, 1995, p 322.)
additional training.68
In a different study, only 14% of
women had heard of CMV, indicating the potential of pre-
ventional behavior education.77
disease (mild to severe)
10%
develop normally
90%
develop sequelae
5–15%
develop se
T A B L E 3 0 – 1
Sequelae in Children with Congenital
Cytomegalovirus Infection According to Type of
Maternal Infection
PRIMARY RECURRENT
Symptomatic disease at birth 24/132 (18%) 0/65 (0%)
Any sequelae 31/125 (25%) 5/64 (8%)
More than one sequela 7/125 (6%) 0/64 (0%)
Sensorineural hearing loss 18/120 (15%) 3/56 (5%)
Bilateral hearing loss 10/120 (8%) 0/56 (0%)
Microcephaly 6/125 (5%) 1/64 (2%)
Seizures 6/125 (5%) 0/64 (0%)
IQ < 70 9/68 (13%) 0/32 (0%)
Death 3/125 (2%) 0/64 (0%)
From Fowler KB, Stagno S, Pass RF, et al: The outcome of congenital cyto-
megalovirus infection in relation to maternal antibody status. N Engl J Med
1992;326:663–667.
High risk pregnancy : management options 5th edition 2011 p. 506
CMV

Cytomegalovirus
Relative changes in CMV IgM, IgG, and IgG avidity levels
over time following primary CMV infection.
IgM pattern A represents the typical IgM response
pattern, whereas IgM pattern B represents long-term
IgM persistence.
In a CMV IgG-positive individual, an IgM-positive result
of 20 indicates infection around 3 months previously if
the individual exhibits IgM pattern A but around 6
months previously if the individual exhibits IgM pattern
B.
By employing CMV IgG avidity testing, the correct time
since infection can be determined;
a low-avidity result (expected to be about 30 based on
this figure) indicates primary infection about 3 months
previously,
whereas a high-avidity result (expected to be about 70)
indicates primary infection more than 6 months
previously.
CMV

Algorithm for assessment of CMV infection in pregnancy

Cytomegalovirus
CMV

VZV in pregnancy: treatment and preventionCHAPTER 17
Table 17.4 VZV in pregnancy: treatment and prevention
Clinical situation Maternal intervention Fetal surveillance Intervention for newborn
Susceptible mother with close
exposure at any point in
pregnancy
• Confirm susceptible status:
VZV serology
• If susceptible, consider
administration of VZ IG
(presently only available in the
US as lyophilized purified
varicella immune globulin
(VariZIG™) or immune
globulin (IVIG)) within 96 hours
of exposure
• No intervention necessary if
mother not susceptible or
mother does not develop
clinical syndrome
• No intervention necessary if mother
not susceptible or mother does not
develop clinical syndrome
Uncomplicated maternal
chickenpox in the first 20 weeks
of pregnancy
• Symptom control for fever,
pruritus and volume depletion
• May consider oral acyclovir
800 mg 5 times/day for 7 days
to reduce duration of rash and
number of lesions
• Contact (gloves, gowns) and
air-borne precautions if
in hospital
• Discussion on risk of
congenital varicella syndrome
(CVS) and continuation of
pregnancy is warranted
• Level II ultrasound
at 18–20 weeks and/or 5 weeks
after onset of maternal rash, plus
• Sequential ultrasound over the
course of pregnancy to detect
features of in utero recurrent
fetal infection
• Consider fetal MRI for CNS
abnormalities not seen on
ultrasound
• Ophthalmologic exam at birth
highly recommended
chickenpox any time between
20 weeks of gestation to 5 days
• Not an indication for
termination of pregnancy as
risk of CVS is extremely low
VZV

VZV in pregnancy: treatment and prevention
number of lesions
air-borne precautions if
in hospital
• Discussion on risk of
congenital varicella syndrome
(CVS) and continuation of
pregnancy is warranted
• Sequential ultrasound over the
course of pregnancy to detect
features of in utero recurrent
fetal infection
• Consider fetal MRI for CNS
abnormalities not seen on
ultrasound
chickenpox any time between
20 weeks of gestation to 5 days
prior to delivery
number of lesions
air-borne precautions if in
hospital
• Not an indication for
termination of pregnancy as
risk of CVS is extremely low
• Level II ultrasound at
18–20 weeks and/or 5 weeks
after onset of maternal rash
chickenpox 5 days before
delivery or 2 days post partum
As above No special monitoring required • VZ IG at birth or as soon as
maternal rash is recognized
• IV acyclovir if severe illness
• Contact (gloves, gowns) and air-
borne precautions in the nursery
Complicated maternal
chickenpox (pneumonia, CNS
disease) or disseminated zoster
• Admit to hospital: respiratory
support may be required
• IV Acyclovir
• Consider IV antibiotics for
pneumonia superinfection
• Contact and air-borne
precautions
As above for relevant
gestational age
As above for relevant gestational age
Maternal zoster in late
pregnancy
• Confirm diagnosis if
lumbosacral area with PCR
or DFA
• Consider use of acyclovir
800 mg PO 5 times/day within
first 72 hours of rash appearing
No special monitoring required Contact (gloves, gowns) and air-borne
precautions in the nursery if zoster
confirmed
VZV

Management of pregnant women with VZV
exposure and infection.
wborns
livery,
following
ephalitis,
bulbar
ts,
ephalus,
ns over
, limb
ities
ome,
logical
Table 17.7 Management of pregnant women with VZV exposure
and infection.
Pregnant women with VZV exposure, within 96h of exposure
Test for VZV IgG
If IgG positive, confirms previous immunity, discontinue evaluation
If IgG negative, administer VZIG, 0.125mg/kg i.m.
Observe for symptoms of chickenpox
Pregnant women with VZV exposure, more than 96h after
exposure
Test for VZV IgG
If IgG negative, efficacy of VZIG questionable, weigh risks and
benefits of vaccine administration
Observe for symptoms of chickenpox
Pregnant women with primary chickenpox
Isolate from susceptible persons
Test for VZV IgG
Treat symptoms
Infection within the first 20 weeks of gestation:
Counsel approximately 2–5% risk of congenital varicella
syndrome, miscarriage, prematurity, low birthweight
Observe for complications (e.g., varicella pneumonia)
Consider acyclovir for pneumonia
VZIG not necessary Clinical obstetrics : the fetus & mother 3rd edition 2007 p.254
lymphocyte transformation after stimulation with different
VZV antigens.24
Treatment and prevention
In adults and children, acute infection with VZV is self-limited
and treatment is generally directed at the symptoms. Table
Both pregnant and nonpregnant patients with herpes zoster
benefit from a short course of antiviral therapy to shorten the
Limb disorder: limb hypoplasia ipsilateral to skin scarring, limb
paresis, hypotonia, areflexia, flexion contracture deformities
Gastrointestinal: duodenal stenosis, colon atresia
Miscellaneous: Horner syndrome, hydroureter
Clinical findings
Mother: chickenpox, pneumonia, encephalitis, Reye syndrome,
aseptic meningitis, Guillain–Barré syndrome, ophthalmological
complications (conjunctivitis, uveitis), hepatitis, shingles (zoster),
pneumonitis, esophagitis, myocarditis, herpes gangrenosum;
laboratory diagnoses include VZV-specific IgG and IgM, virus
culture, viral antigen, detection of viral DNA using PCR
Infant: four distinct clinical presentations:
(1) Congenital varicella syndrome
(2) Disseminated varicella; generalized lesions, pneumonia,
hepatitis, viremia
(3) Neonatal varicella
(4) Neonatal zoster (shingles)
Laboratory diagnoses include VZV-specific IgG and IgM, virus
culture, detection of viral DNA using PCR
Test for VZV IgG
Treat symptoms
Infection within the first 20 weeks of gestation:
Counsel approximately 2–5% risk of congenital varicella
syndrome, miscarriage, prematurity, low birthweight
Observe for complications (e.g., varicella pneumonia)
Consider acyclovir for pneumonia
VZIG not necessary
Infection from 20 to 5 days before delivery:
Counsel about risk for neonatal chickenpox
Observe infant for chickenpox
VZIG not necessary
Infection from 5 days before and up to 2 days after delivery
Counsel approximately 30% risk of disseminated varicella
Observe infant for disseminated varicella
Administer VZIG to infant at birth, 1.25–2mL i.m.
Consider acyclovir for symptomatic infant
Consider delaying birth until mother recovers from acute
infection
Pregnant women with herpes zoster (shingles)
Counsel theoretical risk of neonatal infection
Isolate from susceptible persons (vesicular fluid is infectious)
Treat symptoms
Administer famciclovir for postherpetic neuralgia
VZV

Algorithm for assessment of VZV infection in pregnancy

Rubella
Adapted from Freij BJ, South MA, Sever JL, et al: Maternal rubella and the
congenital rubella syndrome. Clin Perinatol 1988;15:247–257.
Labor, Delivery, and Postnatal
Acute infection during these time periods is unlikely. If sus-
pected, appropriate infection control measures should be
instituted. The neonate should be evaluated for infection
following birth.
T A B L E 2 9 – 2
Fetal Consequences of Symptomatic Maternal Rubella during Pregnancy
INFECTION DEFECTS
STAGE OF
PREGNANCY (WK) NO. TESTED NO. POSITIVE NO. FOLLOWED RATE (%)
OVERALL RISK OF DEFECT (RATE OF
INFECTION × RATE OF DEFECTS) (%)
<11 10 9 (90%) 9 100 90
11–12 6 4 (67%) 4 50 33
13–14 18 12 (67%) 12 17 11
15–16 36 17 (47%) 14 50 24
17–18 33 13 (39%) 10 0 0
19–22 59 20 (34%)
23–26 32 8 (25%)
27–30 31 11 (35%)
31–36 25 15 (60%) 53 0 0
>36 8 8 (100%)
Total 258 117 (45%) 102 20 9
From Miller E, Cradock-Watson JE, Pollock TM: Consequences of conﬁrmed maternal rubella at successive stages of pregnancy. Lancet 1982;2:781–784.
Abnormalities in Congenital Rubella: Triad
of Gregg
ABNORMALITY DESCRIPTION
Eye
Cataract Usually bilateral and present at
birth.
Retinopathy “Salt and pepper” appearance, may
have a delayed onset, frequently
bilateral, visual acuity is not
affected.
Microphthalmia Often associated with cataract.
Glaucoma Rare but leads to blindness if not
recognized.
Heart
Patent ductus arteriosus Common, often associated with
persistence of the foramen ovale.
Pulmonary valvular stenosis Common, due to intimal
proliferation and arterial elastic
hypertrophy.
Pulmonary artery stenosis
Coarctation of the aorta Infrequent.
Ventricular septal defects Rare.
Atrial septal defects Rare.
Ear
Commonly damaged Injury of cells of the middle ear
leading to sensorineural deafness
may also have a central origin.
Bilateral and progressive May be present at birth or develop
later in childhood. Severe enough
for the child to need education at a
special school; rare when maternal
rubella occurs after the fourth mo of
pregnancy.
Adapted from Freij BJ, South MA, Sever JL, et al: Maternal rubella and th
congenital rubella syndrome. Clin Perinatol 1988;15:247–257.
Rubella

Rubella
Rubella

Algorithm for assessment of rubella infection in pregnancy

Herpes Simplex Virus
HSV

Algorithm for assessment of HSV infection in pregnancy
and in neonates

Risk factors for transmission of HSV from
mother to infant.
contrast, infants who acquire HSV at the time of birth
become clinically symptomatic within 1–2 weeks. One-half of
the infants with CNS manifestations will also have SEM
of approximately 50%. Disseminated HSV with en
carries the worst prognosis for infants, with a mor
of approximately 80%.
Diagnosis
In adults and adolescents, genital infections with
usually diagnosed clinically. Up to one-fourth of pat
present with a first-episode infection show serologica
of a previous infection; these patients are, in fact, e
ing a recurrent infection. Commercial assays fo
specific antibodies are useful in confirming a
infection; however, cross-reactivity with HSV1 ant
possible. HSV2-specific IgG is detectable 2–12 we
exposure, with a mean seroconversion time of 2
Therefore, many patients with primary infection
demonstrate serological evidence of infection at th
symptomatic clinical presentation. Virus isolation fro
fluid obtained from fresh lesions or from the cervix is
specific laboratory method for detection of HSV.
Diagnosis of neonatal herpes includes a maternal
HSV infection (primary or recurrent), clinical sympto
Table 17.8 Risk factors for transmission of HSV from mother to
infant.
Incidence of neonatal HSV 1/3000–1/20000 live births
Primary methods of infection
Transplacental (in utero) 5%
Intrapartum 85%
Postpartum 10%
Risk of perinatal transmission
Primary infection 30–50%
Nonprimary first episode 33%
Recurrent < 5%
Percentage of infants with clinical syndrome at birth
SEM disease 30%
CNS disease only 30%
Disseminated HSV 30%
SEM, neonatal herpes involving skin, eyes, and mouth.
Table 17.9 Clinical manifestations HSV infection in infants.Clinical obstetrics : the fetus & mother 3rd edition 2007 p.256
HSV

Antiviral treatment options for HSV infection
in adults
three antiviral drugs. Topical treatments for both genital and
oral lesions have not been shown to be effective.
Acyclovir has been shown to be effective in the treatment
of neonatal HSV infections. Vidarabine, another nucleoside
virus isolation, detection of viral DNA using PCR
Infant: see Table 17.9; laboratory diagnoses include HSV1- and
HSV2-speciﬁc IgG and IgM, virus isolation, detection of viral
DNA using PCR
Table 17.11 Antiviral treatment options for HSV infection in adults.29
Type of infection Drug Dosage Pregnancy category
First episode (primary or nonprimary)
Treat for 7–10 days Acyclovir 400mg p.o. t.i.d. B
Acyclovir 200mg p.o. 5 × /day
Valaciclovir 1g p.o. b.i.d. B
Famciclovir 250mg p.o. t.i.d. B
Recurrent disease
Treat for 5 days Acyclovir 400mg p.o. t.i.d.
Acyclovir 200mg p.o. 5 × /day
Valaciclovir 500mg p.o. b.i.d.
Valaciclovir 1g po q.d.
Famciclovir 125mg p.o. b.i.d.
Suppressive therapy
May be given for several years Acyclovir 400mg p.o. b.i.d.
Valaciclovir 0.5–1g p.o. b.i.d.
Famciclovir 250mg p.o. b.i.d.
Herpes zoster (recurrent VZV)
Treat for 7–10 days Acyclovir 800mg p.o. 5 × /day
Valaciclovir 1g p.o. t.i.d.
Famciclovir 500mg p.o. t.i.d.
HSV

Parvovirus B19

Algorithm for assessment of parvovirus B19 infection in
pregnancy

Hepatitis A
Hepatitis A

Hepatitis B
Hepatitis B

Hepatitis C
Hepatitis C

Hepatitis
CREASY AND RESNIK’S MATERNAL-FETAL MEDICINE: PRINCIPLES AND PRACTICE, SIXTH EDITION
2009 p738
HSV

Human Immunodeficiency Virus
CHAPTER 28 • Human Immunodeficiency Virus
Management Options
Evidence Quality and
Recommendation Refere
Recommend against conception until HIV RNA level
undetectable and no indication for opportunistic
infection prophylaxis (CD4+ cell count >200/mm3
for >6 mo).
IIa/B 29,79
Complete other routine preconception assessments
such as genetic screening, evaluation for other
medical conditions.
IIa/B 29
If partner is HIV-negative, discuss methods to avoid
unprotected intercourse: male condoms for all
intercourse and artiﬁcial insemination for
conception.
GPP
Recommend folate supplementation. Ia/A 29
Prenatal Screening Policy
HIV

such as genetic screening, evaluation for other
medical conditions.
If partner is HIV-negative, discuss methods to avoid
unprotected intercourse: male condoms for all
intercourse and artificial insemination for
conception.
GPP
Recommend folate supplementation. Ia/A 29
Prenatal Screening Policy
Offer opt-out testing for HIV to all pregnant women,
rescreen in third trimester in high-prevalence areas
and in women with ongoing risk.
—/GPP —
Prenatal HIV-positive Patients
Assess immunization status and update as needed
for pneumococcus, influenza, hepatitis A and B,
tetanus.
Ia/A 79
Assess antibody status to hepatitis C, Toxoplasma
gondii, and CMV if not previously documented.
IIa/B 79
Perform tuberculin skin test if not done in past year. Ia/A 79
Counsel regarding risk of transmission, methods to
minimize risk (antiretroviral therapy with scheduled
cesarean delivery if HIV RNA >1000 copies/mL after
34 wk), lack of impact of pregnancy on maternal
disease progression, symptoms of drug toxicity,
possible effects of therapy on infant, evaluation of
infant after birth for HIV status.
Ia/A 29
Assess indications for antiretroviral therapy and
opportunistic infection prophylaxis with HIV RNA
level, CD4+ lymphocyte count. For women already
on therapy, discuss risks/benefits of continuing or
Ia/A 29,79
HIV

Counsel regarding risk of transmission, methods to
minimize risk (antiretroviral therapy with scheduled
cesarean delivery if HIV RNA >1000 copies/mL after
34 wk), lack of impact of pregnancy on maternal
disease progression, symptoms of drug toxicity,
possible effects of therapy on infant, evaluation of
infant after birth for HIV status.
Ia/A 29
Assess indications for antiretroviral therapy and
opportunistic infection prophylaxis with HIV RNA
level, CD4+ lymphocyte count. For women already
on therapy, discuss risks/benefits of continuing or
stopping. Modify regimen if first trimester and on
efavirenz. If not on therapy, recommend highly
active antiretroviral regimen including zidovudine for
all women starting after first trimester, regardless of
HIV RNA and CD4+ cell count. Provide opportunistic
infection prophylaxis according to adult guidelines.
Ia/A 29,79
Monitor HIV RNA levels monthly after changing or
initiating therapy. Level should drop by ≥1 log in
first 4–8 wk.
II/B 28
Monitor CD4+ lymphocyte counts each trimester. Ia/B 29
Perform complete blood count, liver enzymes, renal
function frequently (every 2–4 wk) on new regimen,
monthly in third trimester.
Ia/A 29
Perform HIV resistance testing for women with
detectable HIV RNA levels before initiating therapy
or if not responding appropriately to therapy or if
rebound from undetectable.
II/B 28,82
Perform ultrasound at 18–20 wk’ gestation to rule
out anomalies and confirm dates
—/GPP —
Discuss risks versus benefits of scheduled Ia/A 29,86High risk pregnancy : management options 5th edition 2011 p. 489
HIV

detectable HIV RNA levels before initiating therapy
or if not responding appropriately to therapy or if
rebound from undetectable.
Perform ultrasound at 18–20 wk’ gestation to rule
out anomalies and conﬁrm dates
—/GPP —
Discuss risks versus beneﬁts of scheduled
cesarean delivery. Recommend for HIV RNA levels
>1000 copies/mL after 34 wk. Schedule at or after
38 wk’ gestation if dating criteria adequate. Perform
vaginal delivery only if on antiretroviral therapy with
undetectable HIV RNA.
Ia/A 29,86
HIV

HIV

Algorithm for assessment of HIV infection in pregnancy
and in newborns to infected mothers

Rubeola (measles)
CHAPTER 29 • Rubella, Measles, Mumps, Varicella, and Parvovirus 497
Management Options
Evidence Quality and
Recommendation References
Prenatal
Treat acute infection symptomatically. —/GPP —
Antibiotics are given if secondary bacterial infection is suspected. —/GPP —
Immunoglobulin should be considered for the susceptible woman
exposed to the infection.
III/B 13
Inadvertent vaccination is not an indication for termination. III/B 13
Labor, Delivery, and Postnatal
Appropriate isolation precautions must be taken when in
hospital.
—/GPP —
GPP, good practice point.
High risk pregnancy : management options 5th edition 2011 p. 496-7
Rubeola

Mumps
Mumps

Adenovirus

Coxsackievirus

Human Papilloma Virus

HPV

Immunization: pregnancy and breastfeeding
recommendations
CHAPTER 17
Table 17.5 Immunization: pregnancy and breastfeeding recommendations
Product
(type & schedule)
Pregnancy Post partum Breastfeeding Comments
Varicella
• Live
• 2 doses (0, 4–8 weeks)
Contraindicated Immunize susceptible women
post partum before hospital
discharge or shortly thereafter
whether or not they intend to
breastfeed
Breastfeeding is not a
contraindication or
precaution to vaccination
Inadvertent use in pregnancy
has not resulted in fetal or
neonatal disease; not a reason
for termination of pregnancy.
Pregnancy to be avoided until
28 days after vaccination
Measles, mumps, rubella
• Live
• 1 dose
Contraindicated Immunize susceptible women
breastfeed
contraindication or
has not resulted in fetal or
neonatal disease; not a reason
for termination of pregnancy.
Pregnancy to be avoided until
28 days after vaccination
Vaccinia (smallpox)
• Live
• 1 dose
Contraindicated Contraindicated if intention to
breastfeed
Contraindicated Has been reported to cause
fetal and neonatal infection
Poliomyelitis (aka IPV
or Salk vaccine)
• Live attenuated
• 3 doses (0, 1, 6 months)
Precaution: consider if
pregnant woman needs
immediate protection
(high-risk situation, travel)
Immunize susceptible women
breastfeed as per routine adult
immunization schedule
contraindication or
No known fetal effects.
Ideally defer vaccination until
after 12 weeks gestation
Yellow fever
• Live attenuated
• 1 dose
Precaution: vaccinate
during pregnancy in cases
of unavoidable travel to area
Precaution if intention to
breastfeed due to lack of data
Breastfeeding is a
precaution due to lack of
data
Very limited data on
pregnancy: has not resulted in
fetal disease; not a reason for

recommendations
Vaccinia (smallpox)
• Live
• 1 dose
Contraindicated Contraindicated if intention to
breastfeed
Contraindicated Has been reported to cause
fetal and neonatal infection
Poliomyelitis (aka IPV
or Salk vaccine)
• Live attenuated
Precaution: consider if
pregnant woman needs
immediate protection
(high-risk situation, travel)
breastfeed as per routine adult
contraindication or
No known fetal effects.
Ideally defer vaccination until
after 12 weeks gestation
Yellow fever
• Live attenuated
• 1 dose
Precaution: vaccinate
during pregnancy in cases
of unavoidable travel to area
where exposure is likely
Precaution if intention to
breastfeed due to lack of data
Breastfeeding is a
precaution due to lack of
data
Very limited data on
pregnancy: has not resulted in
fetal disease; not a reason for
termination of pregnancy
Rabies
• Live attenuated
• 5 doses (0, 3, 7, 14 &
28 days)
Precaution: vaccinate during
pregnancy only after possible
exposure (postexposure
prophylaxis)
Immunize women post
partum at any time, whether
or not they intend to
breastfeed, as per routine
recommendations:
pre-exposure prophylaxis
contraindication or
Prudent to delay pre-
exposure immunization unless
substantial risk of exposure
Influenza
• Inactivated
• 1 dose annually
Recommended: for all
pregnant women during the
flu season, and all pregnant
women as per routine
recommendations based on
co-morbidities or occupation
(see text)
Immunize women post
recommendations based on
(see text)
contraindication or
Hepatitis A
• Inactivated
• 2 doses (0, 6 months)
pregnancy if unavoidable
travel to area where exposure
is likely to happen
whether or not they intend
to breastfeed as per routine
adult immunization
schedule
contraindication or
Hepatitis B
• Recombinant inactivated
Precaution: recommended
only for pregnant women
at risk
contraindication or

recommendations
456
(see text)
(see text)
Hepatitis A
• Inactivated
• 2 doses (0, 6 months)
pregnancy if unavoidable
travel to area where exposure
is likely to happen
adult immunization
schedule
contraindication or
Hepatitis B
• Recombinant inactivated
Precaution: recommended
only for pregnant women
at risk
adult immunization
schedule
contraindication or
• Recombinant
Precaution: not recommended
in pregnancy but inadvertent
use has not resulted in adverse
outcomes
Immunize as per adult
Breastfeeding is not
a contraindication or
has not resulted on fetal or
neonatal disease

recommendations
Table 17.5 (Continued)
Product
(type & schedule)
Pregnancy Post partum Breastfeeding Comments
Pneumococcus
• Inactivated
• 2 doses (0, 4–8 weeks)
Recommended: only for
pregnant women at risk
based on co-morbidities
(see text)
Immunize women post
recommendations (see text)
contraindication or
Meningococcus
Polysaccharide
• Inactivated
• 2 doses (0, 5 years)
Recommended: only for
pregnant women at risk
(see text)
Immunize women post
contraindication or
Meningococcus
Conjugate
• Inactivated
• 1 dose
Precaution: pregnancy is a
precaution due to lack of data.
Consider in situations where
benefit outweighs risk
Breastfeeding is a precaution
due to lack of data
due to lack of data
Japanese encephalitis
• Inactivated
• 3 doses (0, 1, 4 weeks)
pregnancy only in cases of
unavoidable travel to area where
exposure is likely to happen
due to lack of data
due to lack of data
Typhoid
• Some preparations live
pregnancy in cases of
unavoidable travel to area
due to lack of data
due to lack of data

recommendations
• Inactivated
• 2 doses (0, 5 years)
(see text)
Meningococcus
Conjugate
• Inactivated
• 1 dose
Precaution: pregnancy is a
precaution due to lack of data.
Consider in situations where
benefit outweighs risk
due to lack of data
due to lack of data
Japanese encephalitis
• Inactivated
• 3 doses (0, 1, 4 weeks)
pregnancy only in cases of
unavoidable travel to area where
exposure is likely to happen
due to lack of data
due to lack of data
Typhoid
• Some preparations live
pregnancy in cases of
unavoidable travel to area
where exposure is likely
due to lack of data
due to lack of data
Tetanus diphtheria
• Inactivated
Recommended: susceptible
women to be vaccinated as
per general guidelines for
nonpregnant women.
adult immunization schedule
contraindication or precaution
to vaccination
Pertussis (usually given in
combination with tetanus
and diphtheria but also
available by itself)
• Inactivated
• One-time dose as adult
as booster to childhood
pertussis immunization
Precaution: likely safe but
limited pregnancy data
Recommended for all
postpartum mothers prior to
discharge from hospital to help
protect them from acquiring
pertussis and transmitting it to
their infant
contraindication or
Tetanus diphtheria pertussis
combination is only to be
used if it has been more than
2 years since the last tetanus
vaccine, otherwise there is an
increased risk of reaction to
the tetanus component
will be pregnant during the influenza season [33]. In addition,
influenza vaccination is even more important for all pregnant
women at increased risk of influenza-related morbidity on
and environmental (prison inmates, refugees, international
travelers) [208,209].
Other inactivated or recombinant vaccines include hepatitis

Indications for immunoglobulins in pregnancy
virus. A reformulated vaccine produced by cell-culture technique is being
developed.
Table 34.6 Indications for immunoglobulins in pregnancy
Infection or
condition
Indication Preparation Dose
Rh negative Prevent isoimmunization Ig 250 mg IM at 28 wk &
postpartum
Botulism Treatment or prophylaxis for
ingestion of botulinus toxin
Equine
antibodies
Consult CDC, telephone
404-639-6370
Hepatitis A Family contacts, sexual
contacts, daycare outbreaks,
international travel
Ig 0.02 mL/kg IM protects 2 mo.
0.06 mL/kg IM protects 6 mo.
Hepatitis B Percutaneous or mucosal
exposure. Sexual contacts
of person with acute or
chronic HBV
HBIG 0.5 mL IM at birth, vaccinate
with HBV vaccine
Measles Non-immune contacts of
acute cases exposed less
than 6 days previously
Ig 0.25 mL/kg IM up to 15 mL for
normal; 0.5 mL/kg up to 15 mL
for immunocompromised
Rabies Persons exposed to rabid or
potentially rabid animals
HRIG 20 IU/kg IM
Varicella-zoster Immunosuppressed,
pregnant or newborn
contact
VZIG 125 IU/10 kg; up to 625 IU IM
Protocols for high-risk pregnancies 5th edition 2010 p.283

Investigation and management of symptomatic
infective illness during pregnancy
MJA 2002; 176: 229–236

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Congenital Viral Infection

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