The clinical content of preconception care: infectious diseases in preconception care.
ABSTRACT A number of infectious diseases should be considered for inclusion as part of clinical preconception care. Those infections strongly recommended for health promotion messages and risk assessment or for the initiation of interventions include Chlamydia infection, syphilis, and HIV. For selected populations, the inclusion of interventions for tuberculosis, gonorrheal infection, and herpes simplex virus are recommended. No clear evidence exists for the specific inclusion in preconception care of hepatitis C, toxoplasmosis, cytomegalovirus, listeriosis, malaria, periodontal disease, and bacterial vaginosis (in those with a previous preterm birth). Some infections that have important consequences during pregnancy, such as bacterial vaginosis (in those with no history of preterm birth), asymptomatic bacteriuria, parvovirus, and group B streptococcus infection, most likely would not be improved through intervention in the preconception time frame.
- Citations (89)
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Cited In (0)
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Article: Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group.
E M Connor, R S Sperling, R Gelber, P Kiselev, G Scott, M J O'Sullivan, R VanDyke, M Bey, W Shearer, R L Jacobson[show abstract] [hide abstract]
ABSTRACT: Maternal-infant transmission is the primary means by which young children become infected with human immunodeficiency virus type 1 (HIV). We conducted a randomized, double-blind, placebo-controlled trial of the efficacy and safety of zidovudine in reducing the risk of maternal-infant HIV transmission. HIV-infected pregnant women (14 to 34 weeks' gestation) with CD4+ T-lymphocyte counts above 200 cells per cubic millimeter who had not received antiretroviral therapy during the current pregnancy were enrolled. The zidovudine regimen included antepartum zidovudine (100 mg orally five times daily), intrapartum zidovudine (2 mg per kilogram of body weight given intravenously over one hour, then 1 mg per kilogram per hour until delivery), and zidovudine for the newborn (2 mg per kilogram orally every six hours for six weeks). Infants with at least one positive HIV culture of peripheral-blood mononuclear cells were classified as HIV-infected. From April 1991 through December 20, 1993, the cutoff date for the first interim analysis of efficacy, 477 pregnant women were enrolled; during the study period, 409 gave birth to 415 live-born infants. HIV-infection status was known for 363 births (180 in the zidovudine group and 183 in the placebo group). Thirteen infants in the zidovudine group and 40 in the placebo group were HIV-infected. The proportions infected at 18 months, as estimated by the Kaplan-Meier method, were 8.3 percent (95 percent confidence interval, 3.9 to 12.8 percent) in the zidovudine group and 25.5 percent (95 percent confidence interval, 18.4 to 32.5 percent) in the placebo group. This corresponds to a 67.5 percent (95 percent confidence interval, 40.7 to 82.1 percent) relative reduction in the risk of HIV transmission (Z = 4.03, P = 0.00006). Minimal short-term toxic effects were observed. The level of hemoglobin at birth in the infants in the zidovudine group was significantly lower than that in the infants in the placebo group. By 12 weeks of age, hemoglobin values in the two groups were similar. In pregnant women with mildly symptomatic HIV disease and no prior treatment with antiretroviral drugs during the pregnancy, a regimen consisting of zidovudine given ante partum and intra partum to the mother and to the newborn for six weeks reduced the risk of maternal-infant HIV transmission by approximately two thirds.New England Journal of Medicine 12/1994; 331(18):1173-80. · 53.30 Impact Factor -
Article: Guidelines for the management of HIV infection in pregnant women and the prevention of mother-to-child transmission.
E G Lyall, M Blott, A de Ruiter, D Hawkins, D Mercy, Z Mitchla, M L Newell, S O'Shea, J R Smith, J Sunderland, R Webb, G P Taylor[show abstract] [hide abstract]
ABSTRACT: AIMS OF THE GUIDELINES: These guidelines, drawn up by a multidisciplinary group of clinicians and lay workers active in the management of pregnant women infected with HIV, aim to give up-to-date information on interventions to reduce the risk of mother to child transmission of the virus. The evidence on the use of interventions to prevent mother to child transmission of HIV has been graded according to the strength of the data as per the definitions of the US Agency for Health Care Policy and Research [1]. Weighted evidence on the use of combination antiretroviral therapy (ART) for the treatment of HIV infection per se is presented in the BHIVA guidelines for adults [2,3]. The highest level evidence (i.e. randomised controlled trials (RCTs) or large, well conducted meta-analyses) is only available for formula feeding, prelabour caesarean section and zidovudine monotherapy. The need to treat mothers for HIV infection has led to the widespread use of ART in pregnancy which in turn results in new questions such as how to deliver when the mother, on therapy, has no detectable plasma viraemia with the most sensitive assays. In addressing many common and/or difficult clinical scenarios in the absence of 'best evidence' the guidelines rely heavily on 'expert opinion'. Recommendations for management are given in the section on clinical scenarios, and summarized in Table 3. An expanded version of these guidelines with an appendix on safety and toxicity data is available on the BHIVA website http://www.bhiva.org. The authors are available to discuss individual cases.HIV Medicine 11/2001; 2(4):314-34. · 3.01 Impact Factor -
Article: Failure to detect vertical transmission of hepatitis C virus.
[show abstract] [hide abstract]
ABSTRACT: To search for transmission of hepatitis C virus (HCV) from infected mothers to their infants. Prospective clinical, serologic, and molecular biologic follow-up (at least 3 months) of the infants of mothers with anti-HCV antibody. A county hospital providing primary and referral care in high-risk obstetrics (perinatology). Twenty-three mothers with anti-HCV antibody and their 24 infants. An enzyme-linked immunosorbent assay (EIA) and a four-antigen recombinant immunoblot assay (RIBA) were used to test for anti-HCV antibody; serum HCV RNA was measured in two independent laboratories by reverse transcription and polymerase chain reaction (PCR) using nested primers in the 5'-noncoding region. Infant samples were tested for HCV RNA by PCR at delivery and after 3 to 6 months of follow-up. Each sample was tested at least four times in two independent laboratories. Twenty-nine of 648 mothers (4.5%; 95% Cl, 3.0% to 6.4%) had anti-HCV antibody; these women had 30 babies. Twenty-three mothers and their 24 babies were followed at least 3 months (mean follow-up, 52 weeks). Of the 23 mothers, 21 (91%; Cl, 72% to 99%) had a reactive RIBA; one woman had an indeterminate RIBA and was positive for HCV RNA by PCR. In 16 of 23 mothers (70%; Cl, 47% to 87%), PCR yielded a positive result in both laboratories. The mean maternal alanine aminotransferase (ALT) level was 1.6 times the normal value. All the babies had anti-HCV antibody in cord-blood samples, but antibody disappeared or diminished in strength in interval samples, and no infant had evidence of active production of anti-HCV antibody. Only 1 of 24 (4%; Cl, 0.1% to 21%) cord-blood samples was HCV RNA positive, and none of 24 (0%; Cl, 0% to 14%) follow-up samples was positive for HCV RNA by PCR in either laboratory. Four mothers and one baby had antibody to HIV. Infant anti-HCV antibody is most likely acquired passively in utero, and vertical transmission of HCV is uncommon.Annals of internal medicine 01/1993; 117(11):881-6. · 16.73 Impact Factor
Page 1
The clinical content of preconception care: infectious
diseases in preconception care
Dean V. Coonrod, MD, MPH; Brian W. Jack, MD; Phillip G. Stubblefield, MD; Lisa M. Hollier, MD, MPH;
Kim A. Boggess, MD; Robert Cefalo, MD, PhD; Shanna N. Cox, MSPH; Anne L. Dunlop, MD, MPH;
Kam D. Hunter, MD, PhD; Mona R. Prasad, DO, MPH; Michael C. Lu, MD, MS, MPH;
Jeanne A. Conry, MD, PhD; Ronald S. Gibbs, MD; Vijaya K. Hogan, DrPH
I
productivehealthofwomen.Some,such
asgonorrhealandchlamydialinfections,
mayimpacttheabilitytoconceiveorthe
site of implantation. Others, such as
group B streptococcus (GBS) infection,
nfectious diseases can impact preg-
nancy-related outcomes and the re-
can have important clinical conse-
quencesduringpregnancybutarenotpre-
ventablethroughpreconceptionstrategies
soarenotaddressedthroughpreconcep-
tion care. Others, such as bacterial vagi-
nosis (BV) and periodontal disease, are
linkedwithadversepregnancyoutcomes
in some studies; however, screening and
treatment for asymptomatic disease,
when initiated during pregnancy, is not
associated unequivocally with improved
outcomes. Because many prenatal inter-
ventions might have more impact when
initiated in the preconception period,
there is considerable interest in the eval-
uationofwhetherscreeningandtreating
these 2 conditions in the preconception
period proves efficacious. Screening for
particular infections as part of the pre-
conceptionriskassessmentcanidentifya
numberofpotentialriskstowomen’sre-
productive health and their future preg-
nancy outcomes and allows for those
risks to be addressed before conception.
This article discusses those infectious
diseases that are important for consider-
ation in preconception care.
HIV
Burdenofsuffering: Humanimmunode-
ficiency virus (HIV) can be transmitted
FromtheDepartmentsofObstetricsandGynecology(DrCoonrod)andFamilyandCommunityMedicine(DrHunter),MaricopaMedicalCenter,
Phoenix,AZ;DepartmentsofFamilyMedicine(DrJack)andObstetricsandGynecology(DrStubblefield),BostonUniversityMedicalCenter,
BostonMA;DepartmentofObstetrics,GynecologyandReproductiveSciences,UniversityofTexas-Houston,Houston,TX(DrHollier);
DepartmentsofObstetricsandGynecology(DrsBoggessandCefalo)andMaternalandChildHealth,SchoolofPublicHealth(DrHogan),
UniversityofNorthCarolina,ChapelHill,NC;CentersforDiseaseControl,DivisionofReproductiveHealth/NCCDPHP,Atlanta,GA(DrCox);
DepartmentofFamilyandPreventiveMedicine,EmoryUniversitySchoolofMedicine,Atlanta,GA(DrDunlop);DepartmentofObstetrics&
Gynecology,TheOhioStateUniversity,Columbus,OH(DrPrasad);DepartmentsofObstetrics&GynecologyandCommunityHealthSciences,
UCLASchoolsofMedicine&PublicHealth,LosAngelesCA(DrLu);DepartmentofWomen’sHealth,KaiserPermanente,Roseville,CA(Dr
Conry);DepartmentofObstetricsandGynecology,UniversityofColoradoHealthSciencesCenter.Denver,CO(DrGibbs).
Received June 13, 2008; accepted Aug. 29, 2008.
Reprints: Dean V Coonrod, MD, MPH, Chair, Department of Obstetrics and Gynecology, Maricopa Medical Center, OBGYN Dept, 2nd Floor Admin,
2601 E Roosevelt St, Phoenix, AZ 85008. dean_coonrod@MedProDoctors.com.
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease
Control and Prevention.
Conflict of Interest: Dean V. Coonrod, MD, MPH, is a Grant Recipient from the March of Dimes Arizona Chapter to develop an internatal Care Clinic.
He has funding from CMS (#1HOCMS030207 101) working on compliance with the 6 week postpartum visit as a strategy to improve preconception
care and funding from Cellestis Inc (Valencia, CA) to study Quantiferon Gold in pregnancy. Brian W. Jack, MD; Phillip G. Stubblefield, MD; Lisa M.
Hollier, MD, MPH; Kim A. Boggess, MD; Robert Cefalo, MD, PhD; Shanna N. Cox, MSPH; Anne L. Dunlop, MD, MPH; Kam D. Hunter, MD, PhD;
Michael C. Lu, MD, MS, MPH; Jeanne A. Conry, MD, PhD; Ronald S. Gibbs, MD; and Vijaya K. Hogan, DrPH have no conflict of interest including
grants, honoraria, advisory board membership, or share holdings. Mona R. Prasad, DO, MPH is the recipient of a $25,000 service grant from the
March of Dimes for the year 2008.
0002-9378/$34.00 • © 2008 Mosby, Inc. All rights reserved. • doi: 10.1016/j.ajog.2008.08.062
A number of infectious diseases should be considered for inclusion as part of clinical
preconception care. Those infections strongly recommended for health promotion mes-
sages and risk assessment or for the initiation of interventions include Chlamydia
infection, syphilis, and HIV. For selected populations, the inclusion of interventions for
tuberculosis, gonorrheal infection, and herpes simplex virus are recommended. No clear
evidence exists for the specific inclusion in preconception care of hepatitis C, toxoplas-
mosis, cytomegalovirus, listeriosis, malaria, periodontal disease, and bacterial vaginosis
(in those with a previous preterm birth). Some infections that have important conse-
quences during pregnancy, such as bacterial vaginosis (in those with no history of
preterm birth), asymptomatic bacteriuria, parvovirus, and group B streptococcus infec-
tion, most likely would not be improved through intervention in the preconception time
frame.
Key words: infectious disease, preconception, screening
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S296
American Journal of Obstetrics & Gynecology Supplement to DECEMBER 2008
Page 2
from an infected woman to her fetus
during pregnancy, labor, and delivery or
through breastfeeding.1It has been esti-
mated that approximately 280-370 in-
fantsintheUnitedStateswerebornwith
HIVinfectionin2000.2Worldwidethere
are ? 1900 infant lives lost to HIV daily
and ? 700,000 lost annually. Perinatal
HIV transmission still accounts for ?
90% of the cases of pediatric acquired
immunodeficiency syndrome in the
United States; 40% of these infants are
born to mothers who are unaware of
their HIV status.
How detectable is the condition? Primary
prevention includes early education for
bothmenandwomenaboutriskysexual
behavior, such as unprotected inter-
course and multiple partners, intrave-
nous drug use, transfusions before 1985,
and the benefit of the identification of
HIV status before conception. Evalua-
tionof2programs,theopt-invstheopt-
out approach, identifies the effect of 2
differentconsentdesignsandtheimpact
onearlydetectionofHIV.Theopt-inap-
proach includes informing women of
their risk of HIV transmission to their
newborn infant and of the ability to test
for HIV and offering them the HIV test.
The opt-out approach informs women
that HIV testing is part of the standard
battery of laboratory tests, unless they
actively decline testing. Women who are
given the opt-out approach tend to test
more often, potentially resulting in re-
duced perinatal transmission.3Current
recommendations are for a 2-stage ap-
proach to laboratory diagnosis of HIV
diseaseinwhichaninitialenzyme-linked
immunosorbent assay (ELISA) screen
(sensitivity, ? 99.5%; specificity, ?
99.8%) is followed by a confirmatory
Western blot analysis (sensitivity, ?
96%; specificity, ? 99.9%).4
How effective are the current treatments?
An important turning point occurred in
1994 when the AIDS Clinical Trial
Group demonstrated that zidovudine,
which was administered to a group of
HIV-infected women during pregnancy
and labor and to their newborn infants,
reduced the risk of perinatal HIV infec-
tion by two-thirds, from 25.5-8.3%.5
Studies confirm that treating HIV-posi-
tive mothers with antiretrovirals can re-
duce perinatal transmission to ? 2% in
those women with a low viral load who
do not breastfeed.6-8
Impact of preconception care. Knowing
the HIV status of a woman before preg-
nancy allows for treatment and reduc-
tion of viral load, which decreases the
risk of fetal transmission during preg-
nancy and labor. Women in the United
States with HIV are advised not to
breastfeed. If HIV infection is identified
before conception, antiretroviral treat-
ment can be administered, and women
orcouplescanbegivenadditionalinfor-
mation to reduce the risk of mother-to-
child transmission. It could also be ar-
guedthatproviding
information about their HIV status be-
fore conception could alter their repro-
ductive plans, with some women choos-
ingnottobecomepregnantasaresultof
a positive diagnosis.
women with
Recommendations by other groups. Be-
cause early identification and treatment
initiation is the optimal method for re-
ducing the risk of HIV infection among
infants, the American College of Obste-
tricians and Gynecologists (ACOG), the
AmericanAcademyofPediatrics,theUS
Preventive Services Task Force (USP-
STF), and the Centers for Disease Con-
trol and Prevention (CDC) recommend
universal HIV testing in pregnancy as a
routinecomponentofthebatteryofpre-
natal blood tests, unless the test is de-
clined. Outside of pregnancy, the CDC
recommends screening all men and
women from age 13-64 years for HIV.9
Testing is to be repeated annually for
those who are at high risk of acquisition.
The USPSTF considers screening adults
withriskfactorstobean“A”recommen-
dation and those without risk factors to
be a “C” recommendation based on an
updated systematic review.10For HIV-
infected women, the USPSTF recom-
mends the following components of
preconception care: (1) effective contra-
ception to prevent unintended preg-
nancy,(2)educationabouttransmission
risks and ways of decreasing them, (3)
antiretrovirals with low reproductive
toxicity, which can decrease vertical
transmission and achieve a low viral
load, with care to avoid adverse effects,
(4) management of potential opportu-
nistic infections (prophylaxis and im-
munization), (5) optimal nutritional
status, (6) standard preconception care,
(7) screening for psychologic and sub-
stance use disorders, and (8) possible
consultation with a maternal fetal medi-
cinespecialist.11TheBritishHIVAssoci-
ation makes recommendations for dis-
cordant couples who wish to achieve
pregnancy: self-insemination for an in-
fected woman with an uninfected male
partner, and sperm washing for infected
male and uninfected female partners.12
Recommendation. All men and women
shouldbeencouragedtoknowtheirHIV
status before pregnancy and should be
counseled about safe sexual practices.
Those women who test positive must be
informed of the risks of vertical trans-
mission to the infant and the associated
morbidity and mortality rates. These
womenshouldbeofferedcontraception.
Those women who choose pregnancy
should be counseled about the availabil-
ityoftreatmenttopreventverticaltrans-
missionandthattreatmentshouldbegin
beforepregnancy.Strengthofrecommen-
dation: A; quality of evidence: I-b.
Hepatitis C
Burden of suffering. Hepatitis C is be-
comingthesilentepidemicintheUnited
States. Nearly 4 million people in the
UnitedStatesareinfected,andmanypa-
tients are unaware that they are carriers.
Hepatitis C is transmitted through con-
taminated blood and blood products.
The most efficient modes of transmis-
sion include intravenous drug use and
receipt of blood products or an organ
transplant before 1992. Of intermediate
risk of infection are patients on chronic
hemodialysis,patientswithundiagnosed
liver disorders, and infants who were
born to infected mothers. Less efficient
modes of transmission occur in health
care workers, people with multiple sex-
ual partners, people in monogamous re-
lationships with an infected partner,
people who participate in tattooing and
body piercing (with the use of common
www.AJOG.org
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Supplement to DECEMBER 2008 American Journal of Obstetrics & Gynecology S297
Page 3
household products like razors), and
people who share straws for intranasal
cocaine use. Sporadic transmission has
been reported in 5% of cases of acute
hepatitis and approximately 30% of
cases of chronic hepatitis C. Women
who test positive for anti–hepatitis C vi-
rus (HCV) antibody in pregnancy range
from 0.1-4.5%.13-15Of note, there are
settings in which the seroprevalence of
hepatitis C is much higher, up to
50-90%, which include incarceration,
homelessness,intravenousdruguse,and
migration from endemic areas.
How detectable is the condition? Screen-
ing for HCV is accomplished with tests
todetectHCVantibody(anti-HCV)fol-
lowed by a confirmatory test, which is
usually1thatdetectsHCVRNAbecause
a low level of viremia is present in those
with HCV.16There are no current rec-
ommendations for universal screening
of women for hepatitis C, and this is not
a cost-effective endeavor in low-risk
women. However, screening that is
based on risk factors seems to be appro-
priate, although long-term data that
show improved outcomes are lacking.
How effective are the current treatments?
Current recommended treatment for
HCV consists of peginterferon and riba-
virin for 24-48 weeks, with the dosages
and duration dependent on HCV geno-
type. Sustained virologic response, which
isdefinedastheabsenceofHCVRNAat
the end of treatment and 6 months later,
occurs in 40-70%, depending on HCV
genotype. Currently,
whether such treatment prevents long-
term sequelae of the disease.
it is unclear
Impact of preconception care. Women
whotestpositiveshouldbecounseledon
the risk of transmission to others and
possible risk to the newborn infant. The
neonatal transmission rate in pregnancy
isapproximately5%.HepatitisCmaybe
transmitted through breastfeeding. The
risk of vertical transmission increases in
HIV-positive women (15%) and in the
presence of maternal viremia, because
verticaltransmissionisnotknowntooc-
cur in absence of detectable viral RNA.
Currently, we do not have treatment for
mother or infant or means to decrease
perinatal transmission.17Because treat-
ment is contraindicated in pregnancy
and treatment duration may be up to 48
months, a woman’s reproductive plans
should be taken into account when con-
sidering therapy that includes a discus-
sion of contraception while receiving
treatment.
Recommendations by other groups. The
USPSTFrecommendsnotscreeningthose
women without risk factors. It states that
there is insufficient evidence to screen in
those women with risk factors, citing the
lack of long-term data. The American As-
sociation for the Study of Liver Disease
(AASLD) recommends both screening
for those at high risk and treatment
with evidence of liver inflammation.16
Recommendation. There are no data
thatpreconceptionscreeningforhepati-
tis C in low-risk women will improve
perinatal outcomes. Screening for high-
risk women is recommended. Women
who are positive for hepatitis C and de-
sire pregnancy should be counseled re-
gardingtheuncertaininfectivity,thelink
between viral load and neonatal trans-
mission, the importance of avoiding
hepatotoxic drugs, and the risk of
chronic liver disease. Women who are
being treated for HCV should have their
reproductive plans reviewed and use ad-
equate contraception while receiving
therapy. Strength of recommendation: C;
quality of evidence: III.
Tuberculosis
Burden of suffering. Worldwide, tuber-
culosisisthenumber1infectiousdisease
killer.TheCDCreported?15,000active
cases of tuberculosis in 2001 and 10-15
million latent infections. Tuberculosis
affectsallpartsofthebodyincludingthe
pulmonary, skeletal, gastrointestinal,
genitourinary, and cutaneous systems.
The case fatality rate approaches 50% in
untreated patients, multidrug resistant
infections, and infants with congenital
disease. Tuberculosis during pregnancy
is a risk factor for low birthweight and
subsequently poor perinatal outcomes’
conversion to active disease is more
common in the postpartum period.
How detectable is the condition? Tuber-
culosis may be screened with the tuber-
culinskin testor
ERON-TB Gold (Cellestis Inc, Valencia,
CA), an ELISA test that detects interfer-
on-gammainbloodfromsensitizedper-
sons. Both have equal sensitivity; how-
ever, the QuantiFERON-TB Gold test is
believed to have greater specificity. As a
result,thislattertesthasbeenfoundtobe
usefulinrecentimmigrantswhohavere-
ceived the bacille Calmette-Guérin vac-
cine, health care workers, and contact
investigations.18
withQuantiF-
How effective are the current treatments?
Based on clinical trials, treatment of la-
tent tuberculosis infection is effective
with isoniazid monotherapy (65% effi-
cacy for 6 months and 75% efficacy for
12 months).19More advanced cases,
whichincludemultidrugresistanttuber-
culosis,requiremoreextensiveandtoxic
therapy.
Impact of preconception care. Screening
fortuberculosisbeforepregnancyallows
for prophylaxis completion, the oppor-
tunity to reduce the risk of poor preg-
nancy outcomes, and the avoidance of
conversiontoactivedisease.High-prior-
itygroupsfortreatmentforlatenttuber-
culosis infection include persons who
converted within the past 2 years; per-
sons with personal contact with some-
one who has active tuberculosis; illicit
drug users; foreign-born persons from
high-riskcountrieswhohavebeeninthe
UnitedStates?5years;theelderly;chil-
dren who are ?4 years old and who are
exposedtohigh-riskadults;personswith
chronicmedicalconditionssuchasHIV,
diabetesmellitus,organtransplantation,
end-stage renal disease, cancer, chronic
steroid use, or underweight; health care
workers; persons who are incarcerated;
and persons who work in correction in-
stitutions.20Persons with a positive
screeningtestresultandwhodonothave
evidence of active disease usually are
treated with a 9-month regimen of
isoniazid.21
Recommendations by other groups. The
CDC recommends screening and treat-
mentforlatenttuberculosisinthosewho
are at high risk for disease.21Pregnant
Supplement
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S298
American Journal of Obstetrics & Gynecology Supplement to DECEMBER 2008
Page 4
women may be treated for latent tuber-
culosis infection while pregnant.
Recommendation. All high-risk women
should be screened for tuberculosis and
treated appropriately before pregnancy.
Strength of recommendation: B; quality of
evidence: II-2.
Toxoplasmosis
Burden of suffering. Toxoplasmosis is a
disease that is caused by infection with
the protozoan Toxoplasma gondii that
can be transmitted by an infected preg-
nant woman to her fetus. Raw meat and
the feces of newly infected cats are the
only other sources for the Toxoplasma
protozoa infection. Approximately one-
third of adult women in the United
States have antibodies to toxoplasmosis,
and the remainder may be at risk for a
primarymaternalinfectionduringpreg-
nancythatcanresultincongenitalinfec-
tion. Prospective studies that have been
performed in the United States have es-
tablishedanincidenceofcongenitaltox-
oplasmosisof1.1per1000livebirths.Of
children who are born to mothers who
had toxoplasmosis during pregnancy,
approximately 8% are severely affected
atbirth.Theremainderareaffectedwith
mild disease or subclinical infection but
are at risk for late sequelae such as cho-
rioretinitis,mentalretardation,andsen-
sorineural hearing loss, blindness, and
epilepsy. Severe fetal effects are more
likely if infection is acquired during the
first or second trimester.22,23
How detectable is the condition? Toxo-
plasmosis infection is usually asymp-
tomatic. Food and Drug Administra-
tion–approvedcommercial
availableforthedetectionofpastimmu-
noglobulinG(IgG)andrecentimmuno-
globulinM(IgM)infection.Thetestsfor
IgM have been noted to have limited
specificity that results in high false-posi-
tive rates, especially when the incidence
is low.
kits are
How effective are the current treatments?
Treatment of acute toxoplasmosis dur-
ing pregnancy may reduce but does not
eliminatetheriskofcongenitalinfection.
Should congenital infection be diag-
nosed, then multiple agent therapy is
recommended. There is some evidence
for improved outcomes when the af-
fected infant is treated.
Impactofpreconceptioncare. Preconcep-
tion testing for immunity to T gondii by
the measurement of IgG antibody titer
might provide physicians with useful in-
formationforcounseling
Womenwhoarealreadyimmunecanbe
reassured that they cannot become in-
fected during pregnancy. Women who
are susceptible should be counseled be-
fore pregnancy about cooking meat to a
safe temperature, peeling or thoroughly
washing fruits and vegetables before
consumption, and properly cleansing
utensils and cooking surfaces after con-
tactwithunwashedfruitorvegetablesor
rawmeat,poultry,orseafood.Iftheybe-
come pregnant, they should be coun-
seledtoeitheravoidchangingcatlitteror
to wear gloves and wash hands thor-
oughly afterwards, to keep cats inside,
and to not feed raw or undercooked
meat to cats.24Antibody testing during
pregnancy that demonstrates Toxo-
plasma infection in a woman who had
negative titers before pregnancy indi-
cates that infection has occurred. In the
absence of such preconception informa-
tion, interpretation of titers that are ob-
tained during pregnancy may be diffi-
cult. Thus, preconception testing might
lead to a prompt diagnosis and timely
treatment decisions.25There are no
studies to suggest such testing is cost-ef-
fective or efficacious.
women.
Recommendationsbyothergroups. ACOG
currently does not advocate testing for
Toxoplasmainfectionduringpregnancy,
citing a low prevalence of the disease. It
does advocate counseling women on
modes of prevention (level C recom-
mendation).26The CDC recommends
education and counseling as modes to
prevent infection. Testing for immunity
is not mentioned.27
Recommendation. There is no clear evi-
dence that preconception counseling
andtestingwillreduceTgondiiinfection
or improve treatment of those women
who are infected. However, if precon-
ception testing is done, those women
who test positive can be reassured that
they are not at risk of contracting toxo-
plasmosisduring
women who are negative can be coun-
seled about ways to prevent infection
during pregnancy. For those women
who convert during pregnancy, treat-
ment should be offered. Strength of rec-
ommendation: C; quality of evidence: III.
pregnancy; those
Cytomegalovirus
Burden of suffering. Human cytomega-
lovirus is the most common viral infec-
tion in pregnancy, with an estimated
birth prevalence of 0.6-2.2%. Primary
maternal infection occurs in approxi-
mately 1% of pregnancies. Congenital
cytomegalovirus is the leading cause of
hearing loss in children; 15% of infants
who are born to mothers who are in-
fected during pregnancy will manifest
hearing loss. The severity of fetal infec-
tion declines with gestational age, such
that 20-30% of fetuses that are infected
in the first one-half of pregnancy have
serious sequelae that include intrauter-
ine growth restriction, cerebral palsy,
mental retardation, hepatosplenomeg-
aly, petechiae, jaundice, chorioretinitis,
hearing loss, thrombocytopenia, and
anemia. The rate of infection increases
with gestational age; therefore, fetal in-
fection is more common later in preg-
nancy, but most infants are asymptom-
atic at birth. Cytomegalovirus infection
is endemic in the community, with
asymptomatic infections common dur-
ing childhood.
How detectable is the condition? Cyto-
megalovirus is usually asymptomatic.
Diagnosis is made by serologic confir-
mation of cytomegalovirus-specific IgM
anda4-foldriseincytomegalovirus-IgG
in paired sera. False-positive and -nega-
tive tests for cytomegalovirus-specific
IgM are not rare. Fetal infection is best
diagnosed by culture and/or polymerase
chain reaction (PCR) of amniotic fluid
after 21 weeks of pregnancy. Antenatal
ultrasound scanning may identify af-
fected fetuses but cannot exclude signif-
icant infection-related morbidity.28
How effective are the current treatments?
There is no effective current treatment
forprimarycytomegalovirusinfectionin
pregnancy. Ganciclovir crosses the pla-
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centa but has not been demonstrated
to improve outcomes for congenitally
infected fetuses. The administration of
cytomegalovirus-specific hyperimmune
globulin (passive immunization) was
promising in a small preliminary study
by decreasing the frequency and severity
of primary fetal infection.29Good per-
sonal hygiene, particularly hand-wash-
ing, is the most effective means of pre-
venting infection
women.30There is no evidence that
screening and/or treatment programs
prevent infection.31
among pregnant
Impact of preconception care. Thereisno
vaccine at present. Preconception testing
of cytomegalovirus is not recommended
because there is no evidence that this re-
ducesperinatalinfection.However,testing
forimmunitymightbeconsideredtostrat-
ifytheriskofconsequencesofcytomegalo-
virus infection in pregnancy and the need
forpreventioneffortsbecauseprimaryin-
fection poses a greater risk of sequelae of
congenitalinfection.
Recommendations by others. The CDC
and the ACOG recommend universal
hand-washing precautions for pregnant
women and education of reproductive-
age women about hand-washing. The
CDCrecommendsthefollowingprecau-
tions for prevention: (1) practice good
personal hygiene, especially hand-wash-
ing with soap and water (for 14-20 sec-
onds)aftercontactwithdiapersorsaliva
(particularly with a child who is in day-
care), (2) do not kiss children under the
age of 6 years on the mouth or cheek,
instead kiss them on the head or give
them a hug, (3) do not share food,
drinks,orutensils(spoonsorforks)with
young children, and (4) if pregnant and
working in a daycare center, reduce the
riskofgettingcytomegalovirusbywork-
ing with children who are ? 2½ years of
age, especially if you have never been in-
fectedwithcytomegalovirusorareunsure
if you have been infected.32Prenatal
screeningisnotrecommended.32
Recommendation. Women who have
youngchildrenorwhoworkwithinfants
and young children should be counseled
aboutreducingtheriskofcytomegalovi-
rus through universal precautions (eg,
the use of latex gloves and rigorous
hand-washing after handling diapers or
afterexposuretorespiratorysecretions).
Strengthofrecommendation:C;qualityof
evidence: II-2.
Listeriosis
Burden of suffering. Listeriosis is a food-
borneinfectionthatiscausedbythebac-
terium Listeria monocytogenes and typi-
cally affects pregnant women, newborn
infants, and individuals with compro-
mised immune systems. Although liste-
riosis is a rare disease in the United
States,thecasefatalityrateisveryhigh.33
IntheUnitedStates,approximately2500
cases and 500 deaths occur each year.34
Most cases are caused by ingestion of
contaminatedfoods.Hispanicwomenin
theUnitedStatesareespeciallyatriskbe-
cause of ethnic preference for soft fresh
cheeses, often made from raw milk. The
organism can multiply at 40°F, which is
thetemperatureofmanyrefrigerators.It
spreads hematogenously and infects the
placenta in pregnancy by producing mi-
croabscessesandfetalinfection.Lmono-
cytogenes is associated with numerous
adverse outcomes that include preterm
labor, amnionitis, spontaneous abor-
tion, stillbirth, and early-onset neonatal
sepsis syndrome.35The common pre-
sentation in pregnancy is preterm labor,
decreased fetal activity, or fetal death,
with an influenza-like illness in the
mother. Untreated, the fetal mortality
rate approaches 50%.
How detectable is the condition? Listeria
contamination of foods is detectable
readilybybacteriologicculture.Listerio-
sis in humans is detected by culture of
theproductsofconceptioninthecaseof
spontaneousabortion,byamniocentesis
withcultureoftheamnioticfluidinlater
pregnancy, or by culture from the pla-
centa after birth.
How effective are the current treatments? If
thediagnosisismadeantenatallyandthe
mother is treated with ampicillin, the
maternal and neonatal outcomes are
generally good.36
Impact of preconception care. Primary
prevention efforts include improve-
ments in food processing and consumer
education.37The disease is not a grave
problem before pregnancy in normal
women; however, because exposure in
early pregnancy can lead to pregnancy
loss and severe maternal illness, precon-
ceptional education is important to
avoid exposure.
Recommendations by other groups. The
CDC has investigated epidemics of liste-
riosis. Individual states have recom-
mended education to avoid consump-
tion of products that are implicated in
such outbreaks.38An ACOG patient ed-
ucationpamphlet
womenofthediseaseanddescribesmea-
sures for food preparation to avoid it.39
warnspregnant
Recommendation. Because it is not clear
at what point in pregnancy women who
are exposed to Listeria will become ill,
preconceptioncare
teaching women to avoid pâté and fresh
soft cheeses that are made from unpas-
teurized milk and to cook ready-to-eat
foods such as hotdogs, deli meats, and
left-over foods when trying to conceive
or pregnant. Strength of recommenda-
tion: C; quality of evidence: III.
shouldinclude
Parvovirusorfifthdisease
Burden of suffering. Fifth disease is
caused by infection with human parvo-
virusB-19.Infectionsaremostcommon
in school-aged children. The typical in-
fection is characterized by malaise, low-
grade fevers, and a facial rash (the
slapped-cheek appearance of child-
hood).40Although 60% of adults have
immunity,26in healthy adults, it can
cause arthritis, arthralgias, and rarely,
anemia.41Transmission occurs through
close association, such as respiratory se-
cretions and hand-mouth contact. Most
women who are infected during preg-
nancy have healthy babies; however, in-
fection during the first 20 weeks of preg-
nancy is associated with severe anemia,
miscarriage,andfetalhydrops.Serocon-
versionismorelikelythroughhousehold
than classroom exposure. The overall
risk of fetal loss after maternal exposure
is 6.5%. In an observational study of ?
1000womenwithacuteparvovirusB-19
exposure, the risk of hydrops was
3.9%,42and fetal death occurred only
withexposureat?20weeksofgestation.
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Parvovirus has not been associated with
congenital malformations.
Howdetectableisthecondition? BothIgG
andIgMantibodiescanbedetectedwith
ELISA techniques as evidence of parvo-
virusinfection.IgMcanbedetectedafter
symptoms approximately 10 days after
exposure; IgM antibody persists for ap-
proximately 3 months. IgG positivity
providesevidenceofpastinfection.Both
are 80-90% sensitive for clinical infec-
tion. Parvovirus B-19 DNA can be de-
tected with PCR in the amniotic fluid of
affected fetuses.
How effective are the current treatments? In
adults, parvovirus infection is usually
mild, and there is no specific treatment
for the condition unless anemia devel-
ops. There is concern for fetal effects.
Frequent ultrasound surveillance is jus-
tified because parvovirus infection can
leadtofetalanemiaandhydrops.Cordo-
centesis and transfusion have proved ef-
fective in treating severe hydrops.43,44In
fact, a survey of ? 500 perinatologists
with 539 cases of hydrops suggests that
89% used ultrasonography in initial
management of parvovirus infection.
Thirty-four percent of these cases of hy-
drops spontaneously resolved; 30% re-
sulted in a fetal death, and 29% of the
timetherewasaresolutionwithtransfu-
sion. Because of the possibility of spon-
taneous resolution, transfusion is re-
served for cases of severe anemia and
fetalcompromise.45Inuteroexposureto
parvovirus B-19 has not been associated
with neurodevelopmental delay in the
absence of fetal hydrops; however, a ret-
rospective study showed that 32% of
children who required in utero fetal
transfusion demonstrated mild-to-se-
vere neurodevelopmental delay.46,47
Impact of preconception care. No data
have emerged to suggest preconception
screening for immunity to parvovirus
infection would prove beneficial.
Recommendations by other groups. ACOG
hasnopreconceptionrecommendations.
Recommendation. There is not yet evi-
dence that screening for antibody status
against parvovirus or counseling about
waystoavoidinfectioninpregnancywill
improve perinatal outcomes. Good hy-
gienepracticesshouldbeencouragedfor
all pregnant women. Strength of recom-
mendation: E; quality of evidence: III.
Malaria
Burden of suffering. Globally, malaria is
1ofthemostcommoninfectionsduring
pregnancy. Malaria is endemic in ? 100
countries where ? 24 million pregnant
women are affected each year.48,49Ma-
laria infection during pregnancy can
have adverse effects on both mother and
fetusandincludesmaternalanemia,fetal
loss, premature delivery, intrauterine
growth restriction, and delivery of low
birthweight infants. In sub–Saharan Af-
rica,whichistheregionoftheworldthat
is hardest hit by malaria, malaria infec-
tion is estimated to cause 400,000 cases
of severe maternal anemia and 75,000-
200,000 infant deaths annually. Mater-
nal anemia contributes significantly to
maternal death and causes an estimated
10,000maternaldeathsperyear.50Inthe
UnitedStates,1324casesofmalariawere
reported in 2004; all but 4 of those cases
wereimported.Atotalof30casesofma-
laria were reported among pregnant
women in the United States in 2004.51
How detectable is the condition? In the
United States, screening is not used be-
cause malaria is not endemic. Diagnosis
restsonclinicalcriteriaandconfirmation
of malaria through microscopy52or re-
cently approved rapid diagnostic tests for
malariaantigens.53
How effective are the current treatments?
Guidelines exist for malaria infection
that is diagnosed in the United States54
that should be consulted. It is recom-
mended that treatment be initiated only
when confirmed with laboratory testing.
Treatment regimens vary based on the
disease severity, the species of malaria
that was identified, and the region in
which the disease was acquired (chloro-
quine resistant/sensitive). Specific regi-
mens are recommended for pregnant
women.55
Impact of preconception care. The trav-
eler can reduce her risk of acquiring ma-
laria by following several preventive
approaches that include personal pro-
tection to avoid infective mosquito bites
and the use of antimalarial chemopro-
phylaxis.56Women who are planning a
pregnancy should be advised to (1) re-
mainindoorsbetweenduskanddawn,if
mosquitoes are active outdoors during
this time, (2) if outdoors at night, wear
light-colored clothing, long sleeves, long
pants, shoes, and socks, (3) stay in well-
constructedhousingwithair-condition-
ing and/or screens, (4) use permethrin-
impregnated bed nets, and (5) use insect
repellents that contain N,N-diethyl-3-
methylbenzamide (DEET) as needed.
Permethrin and DEET have been
shown to reduce the risk of malaria in-
fection and are considered safe in
pregnancy.57-59
Antimalarial chemoprophylaxis should
beprovidedtowomenwhoareplanning
apregnancyandtravelingtomalaria-en-
demic areas. For pregnant women who
travel to areas with chloroquine-sensi-
tive Plasmodium falciparum malaria,
chloroquine has been used for malaria
chemoprophylaxis for decades with no
documented increase in birth defects.
For pregnant women who travel to areas
withchloroquine-resistantPfalciparum,
mefloquine can be used for chemopro-
phylaxisduringthesecondandthirdtri-
mesters. For women in their first tri-
mester, most evidence suggests that
mefloquineprophylaxiscausesnosignif-
icant increase in spontaneous abortions
or congenital malformations, if taken
during this period. Because there is no
evidence that chloroquine and meflo-
quine are associated with congenital de-
fects when used for prophylaxis, the
CDC does not recommend that women
whoareplanningpregnancyneedtowait
a specific period of time after their use
before becoming pregnant.60,61
safety of atovaquone/proguanil use in
early pregnancy has not been estab-
lished, and doxycycline should be
avoided in women who are planning a
pregnancy. Primaquine should also be
avoided because the drug may be passed
transplacentally to a glucose-6-phos-
phate dehydrogenase–deficient
and cause hemolytic anemia in utero.
Despite recent encouraging results, a
vaccine against malaria infection in
pregnancy is currently unavailable.62
The
fetus
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Recommendations by other groups. The
CDC publishes up-to-date information
on malaria prevention for travelers for
providers for adults and pregnant wom-
en.63,64In addition their online “Yellow
Book” can be consulted.
Recommendation. Womenwhoareplan-
ning a pregnancy should be advised to
avoid travel to malaria-endemic areas. If
travel cannot be deferred, the traveler
should be advised to defer pregnancy
and use effective contraception until
traveliscompletedandtofollowpreven-
tive approaches. Antimalarial chemo-
prophylaxis should be provided to
women who are planning a pregnancy
and traveling to malaria-endemic areas.
Strengthofrecommendation:C;qualityof
evidence: III.
Gonorrhea
Burden of suffering. According to the
CDCin2005,gonorrheaoccursinabout
116 per 100,000 persons;65infection
with Neisseria gonorrhea is the second
most common reportable disease in the
UnitedStates.Somewomenwithgonor-
rhea can be asymptomatic; however,
gonorrhea is a major cause of cervicitis
andpelvicinflammatory
Women with pelvic inflammatory dis-
ease are at risk for internal infections,
chronicpelvicpain,anddamagetofallo-
pian tubes, which can cause infertility
and increased risk of ectopic pregnan-
cy.66Gonorrhea in pregnancy is associ-
ated with chorioamnionitis, premature
rupture of membranes, and preterm la-
bor. Perinatal transmission to the infant
can result in severe conjunctivitis that
leads to blindness if untreated and,
rarely, meningitis and endocarditis.66
disease.
Howdetectableisthecondition? Avariety
of tests are available for the detection of
gonorrhea that include culture, ampli-
fied nucleic acid assays, direct immuno-
fluorescence, and direct hybridization
techniques. Sensitivity for amplification
tests ranges from 66.7-100%, and speci-
ficity ranges from 96.8-100%.66Screen-
ingcanbedoneinbothmen(fromswabs
of the urethra) and women (from swabs
of the endocervix) or noninvasively in
urine samples with amplified nucleic
acid assays.67
Howeffectivearethecurrenttreatments? Ef-
fective treatment for uncomplicated
gonorrhea is available, is updated regu-
larly, and can be accessed online.68Re-
cently, because of resistance to quino-
lones, these agents are no longer
recommended for treatment of gonor-
rhea infection.69
Impact of preconception care. Men and
women who are being treated for sexu-
ally transmitted infections should be
counseled about the risk of infertility
thatisimposedbyhavingsexuallytrans-
mitted diseases. Neonatal infection may
result in blindness, joint infections, or
blood infections. Currently, there are no
data to support the greater effectiveness
of screening before pregnancy over
screening during pregnancy in prevent-
ing pregnancy-related complications.
Recommendations by other groups. The
USPSTF recommends screening women
(pregnant or not) for gonorrhea infection
ifriskfactorsexist.70TheCDCmakessim-
ilarrecommendations.
Recommendation. High-riskwomenshould
be screened for gonorrhea during a pre-
conceptionvisit,andwomenwhoarein-
fected should be treated. Screening
should also occur early during preg-
nancy and be repeated in high-risk
women. Strength of recommendation: B;
quality of evidence: II-2.
Chlamydia
Burden of suffering. Chlamydia tracho-
matis is the most common bacterial sex-
uallytransmittedinfectionintheUnited
States. Approximately 3 million new
cases occur annually. Reported rates are
higherinwomenthanmen,probablybe-
cause women are more likely to receive
routine health care encounters, which
includetestingofasymptomaticindivid-
uals.71Seventy to 90% of women are
asymptomatic.71
If untreated, Chla-
mydia infection can lead to pelvic in-
flammatory disease, infertility, and an
increasedriskofHIVinfection.Withre-
lation to pregnancy, Chlamydia infec-
tion is associated with ectopic pregnan-
cies, neonataleye
pneumonia.
infections,and
How detectable is the condition? Numer-
ous testing options exist for Chlamydia
infection. The newer antigen detection
tests may provide improved sensitivity,
lower expense, and timeliness of results
over culture; a sensitivity of 70-80% and
a specificity of 96-100% have been re-
ported for antigen detection tests.67
Testing through urine specimens may
improve access to and convenience of
testing.
How effective are the current treatments?
A well-designed randomized trial dem-
onstratedthatscreeningwomenwhoare
atriskreducedtheincidenceofpelvicin-
flammatory disease from 28 per 1000
woman-years to 13 per 1000 woman-
years and that the prevalence of chla-
mydialinfectionhasdeclinedinpopula-
tions such as family planning clinics,
which have been targeted by screening
programs.67Reinfection is common;
therefore, identification and treatment
ofallsexualpartnersiswarranted.Effec-
tive treatments for Chlamydia infection
are available from the CDC and are up-
dated regularly.
Impact of preconception care. Identifica-
tionandtreatmentbeforepregnancyhas
thepotentialtoreduceinfertilityandec-
topic conceptions; identification and
treatment during pregnancy would be
necessary to prevent neonatal eye infec-
tionsandpneumonia.However,because
of the risk of infertility from Chlamydia
or gonorrhea infection, sexually active
persons should be counseled to prevent
transmissionofsexuallytransmitteddis-
eases and screened regularly for asymp-
tomatic infections.
Recommendations by other groups. The
USPSTF recommends screening non-
pregnant women aged ? 25 years and
older women who are at high risk for
Chlamydia infection as a strategy to pre-
vent pelvic inflammatory disease as an
“A”level recommendation.71
treatment leads to decreased risk of in-
fertility and ectopic pregnancy. They
state that there is no evidence to support
screening of men.72The CDC recom-
mends annual screening for Chlamydia
infectionforwomenwhoareathighrisk
and for all pregnant women.68ACOG
Early
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recommends routine screening for chla-
mydial infection for all sexually active
adolescents and other asymptomatic
womenwhoareathighriskforinfection.
Recommendation. All
women aged ? 25 and all women who
are at increased risk for infection with
Chlamydia(includingwomenwithahis-
tory of sexually transmitted infection,
new or multiple sexual partners, incon-
sistent condom use, sex work, and drug
use) should be screened annually at en-
counters before pregnancy. Strength of
recommendation: A; quality of evidence:
I-a, II-2.
sexually active
Syphilis
Burden of suffering. The World Health
Organization estimates that 12 million
new cases of syphilis occur annually. In
2002, the CDC reported 32,000 cases of
syphilis. Syphilis has declined in both
womenandneonates.Inadults,theclin-
ical presentation of syphilis ranges from
being asymptomatic (latent syphilis) to
local symptoms as in primary syphilis
(genital ulcers) to more widespread
symptoms such as skin rash, lymphade-
nopathy and mucocutaneous lesions
(secondary syphilis) and finally to com-
plications that are associated with ter-
tiary syphilis (gummatous lesions and
those that involve the neurologic, visual,
andauditorysystems).Congenitalsyph-
iliscancomewithdevastatingcomplica-
tions that include stillbirth, premature
birth,neonataldeath,developmentalde-
lay, blindness, deafness, bone and teeth
abnormalities, and seizures.
Howdetectableisthecondition? Identifi-
cation of syphilis usually begins with a
nonspecific nontreponemal test (Vene-
real Disease Research Laboratory or
rapidplasmareagin)withsensitivitythat
rangesfrom80-85%forprimarysyphilis
to 90-95% for latent infection. These
tests,whenpositive,areusuallyfollowed
byaconfirmatorytreponemaltest(fluo-
rescent treponemal antibody-absorp-
tion treponema pallidum particle agglu-
tination assay). This combination of
tests has been used successfully in
screening programs.
Howeffectivearethecurrenttreatments? An-
tibiotics (usually penicillin G) can be
used successfully to treat all stages of
syphilis.Importantly,congenitalsyphilis
can be treated and prevented with treat-
ment early in pregnancy.68
Impactofpreconceptioncare. Preconcep-
tion screening for syphilis in high-risk
populations is an important step in the
reduction of neonatal syphilis. Persons
who are at risk for syphilis include men
who have sex with men, persons in cor-
rectional facilities,
workers, persons who have sex with
high-risk individuals, and persons who
are diagnosed with other sexually trans-
mittedinfections.Syphiliscanbecuredif
treatedinitsearlystages.However,treat-
ment does not prevent reinfection. Even
if adequate treatment is established, re-
peat testing should occur during preg-
nancy in the first and third trimesters.
Studies show that most stillbirths occur
at about 30 weeks of gestation. There-
fore, even in unplanned pregnancies,
prompt and immediate treatment of
syphilis might decrease the risk of still-
birth and other perinatal morbidities.
Perinatal morbidity and mortality rates
canbeashighas40%inwomenwhoare
untreated. Preconception screening and
treatment may have the additional ad-
vantage of avoiding costly and compli-
cated penicillin desensitization in pa-
tients with penicillin allergies.
commercialsex
Recommendations by other groups. The
USPreventiveServicesTaskForce(USP-
STF) recommends screening all preg-
nant women for syphilis in the first tri-
mester (“A” level recommendation).
Theyalsorecommendscreeningwomen
at high risk for infection (“A” level rec-
ommendation). Many states require
syphilis screening as a requirement to
obtain a marriage license.73,74The CDC
also recommends screening pregnant
women, with repeat screening in the
earlythirdtrimesterforthoseathighrisk
(including those with a positive test ear-
lier in pregnancy), or in areas with high
morbidity from syphilis.
Recommendation. High-risk
should be screened for syphilis during a
preconceptionvisit,andwomenwhoare
women
infected should be treated. Because the
USPSTF and CDC recommend screen-
ing all women during pregnancy for
syphilis, screening for syphilis immedi-
ately before conception is recom-
mended. Strength of recommendation: A;
quality of evidence: II-1.
Herpessimplexvirus
Burden of suffering. At least 50 million
persons in the United States have genital
herpes infection. Neonatal transmission
occurs in approximately 1 in 3000 deliv-
eries. Forty percent of neonatal herpes
cases result in localized skin infections.
Encephalitis develops in 25% of cases,
with the poorest prognosis for 25% of
infectedneonateswhogoontohavedis-
seminated disease that can affect multi-
ple organ systems.
How detectable is the condition? When a
patient has clinical symptoms and char-
acteristiclesions,
straightforward; however, clinical diag-
noses should be confirmed with a cul-
ture. Although cultures have good spec-
ificity, sensitivity may be limited, as low
as 50% in some cases. PCR-based tests
have higher sensitivity. Evidence of past
infection may be detected through sero-
logic testing.
the diagnosisis
How effective are the current treatments?
Treatment for HSV infection consists of
antiviraltherapy,whichcannoteradicate
infection. Instead, treatment is aimed at
reducing symptoms, the duration of le-
sions, or the recurrence of lesions.
Impact of preconception care. The risk of
HSV-2 sexual transmission can be re-
ducedbythedailyuseofacyclovirorva-
lacyclovir by an infected person.75,76
Couples with an infected male partner
should be encouraged to consider sup-
pressive antiviral therapy as part of a
strategy to prevent transmission, in ad-
dition to consistent condom use and
avoidance of sexual activity during re-
currences. Most individuals with genital
herpes infection are asymptomatic, so it
is important to teach couples about the
signsandsymptomsofgenitalherpesin-
fections.77Womenwithahistoryofgen-
italherpesshouldbecounseledaboutthe
risk of vertical transmission to the fetus
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and newborn child. Women who have
activelesionsorprodromalsymptomsat
the time of delivery are offered cesarean
delivery to reduce perinatal transmis-
sion. To reduce the risk of recurrence at
delivery and of cesarean delivery for
women with a history of genital herpes,
prophylactic antiviral agents may be
used from 36 weeks until delivery.78
Both HSV-1 and -2 can cause perinatal
infection. Couples with a history of oro-
labial herpes should be counseled about
good hygiene practices, because orola-
bialdiseasecanalsobetransmittedtothe
newborn infant.
Recommendation by other groups. ACOG
recommendscesareandeliveryforwomen
withactivelesionsduringlaborandpossi-
ble suppressive therapy late in gestation.
TheUSPSTFrecommendsagainstroutine
serologicscreeningofpregnantwomenor
asymptomatic adults. The CDC recom-
mends against routine serologic screening
for HSV in pregnant women and states
thatthereisnotsufficientevidencetosup-
portroutinesuppressionforwomenwitha
historyofrecurrentHSV.
Recommendation. During a preconcep-
tion visit, women with a history of geni-
talherpesshouldbecounseledaboutthe
risk of vertical transmission to the fetus
and newborn child; those women with
no history should be counseled about
asymptomatic disease and acquisition of
infection. Although universal serologic
screening is not recommended in the
general population, type-specific sero-
logictestingofasymptomaticpartnersof
persons with genital herpes is recom-
mended. Strength of recommendation: B;
quality of evidence: II-1.
Asymptomaticbacteriuria
Burden of suffering. Asymptomatic bac-
teriuria occurs in 3-8% of pregnant
women and is a risk factor for low birth-
weight. Between 20% and 40% of preg-
nantwomenwithasymptomaticbacteri-
uria without adequate treatment or
follow-upexperienceacutepyelonephri-
tiswithanattendantincreasedriskoffe-
tal death and morbidity.
How detectable is the condition? Most
urinetestswithimmediateresults(urine
dipstickordirectmicroscopy)havepoor
predictive values, which limits their use
in screening for asymptomatic bacteri-
uria. Urine culture, although more ex-
pensive and time-consuming, is the test
of choice for screening.
Howeffectivearethecurrenttreatments? Ap-
propriate antibiotic treatment of bacte-
riuria is 90-95% effective in the preven-
tion of progression to pyelonephritis.
Impact of preconception care. Data are
not consistent as to whether treatment
has a significant positive effect on birth-
weight or on gestational age at birth in
women with asymptomatic bacteriuria
whodonotgoontohaveacutepyelone-
phritis.Areviewof17studiesthatinves-
tigated the relationship between asymp-
tomaticbacteriuriaandlowbirthweight/
prematurityconcludedthatwomenwith
asymptomatic bacteriuria have an in-
creased rate of low birthweight/prema-
turitywhencomparedwithwomenwith
sterile urine. They also concluded from
the 8 randomized clinical studies that
were available that women with asymp-
tomatic bacteriuria who are treated have
a lower rate of low birthweight than un-
treatedwomen.Therearenodatatosug-
gest that screening before pregnancy is
morebeneficialthanscreeningandtreat-
ing during pregnancy.
Recommendations by other groups. The
USPSTF concluded that early detection
of asymptomatic bacteriuria is of value
for pregnant women, but that screening
of asymptomatic adults is not justified
because of concerns that serious urinary
tractdisordersarerelativelyuncommon,
thepositivepredictivevalueofscreening
urinalysis is low, and the effectiveness
of early detection and treatment is
unproved.79
Recommendation. There have been no
studiestoshowthatwomenwithasymp-
tomatic bacteriuria who are identified
and treated in the preconception period
have lower rates of low birthweight
births. Further, women often have per-
sistent or recurrent bacteriuria despite
repeated courses of antibiotics; such re-
infection frequently occurs within a few
months of treatment. Thus, a woman
who is identified and treated for asymp-
tomatic bacteriuria before conception
must be screened again during preg-
nancy. For these reasons, screening for
this condition as part of routine precon-
ception care is not recommended.
Strength of recommendation: E; quality of
evidence: II-1.
Periodontaldisease
Burden of suffering. Periodontal disease
affects up to 40% of pregnant women,
with a disproportionate burden among
low income women. It has been pro-
posedthatchronicinfectionandinflam-
mationaroundtheteethmightstimulate
maternal or fetal responses that lead to
preterm birth. Two large prospective
studies have shown that maternal peri-
odontal disease was associated with a 2-
to7-foldincreaseinoddsforpretermde-
livery,withincreasingriskfordecreasing
gestationalage.80,81Anothersimilarpro-
spective study linked maternal peri-
odontal disease to preeclampsia.82
How detectable is the condition? Peri-
odontaldiseaseisdetectablebyadetailed
oral health examination that is performed
bytraineddentalprofessionals.
How effective are the current treatments?
Treatment of periodontal disease is
highlyeffectiveinreducingtheburdenof
oral disease, but treatment during preg-
nancy has not yet been proved clearly to
improve perinatal outcomes.
Impact of preconception care. Interven-
tionaltrialsduringpregnancyhavedem-
onstrated consistently improved mater-
nal oral health, but findings regarding
pretermbirthriskreductionareconflict-
ing.Arandomizedstudyfoundsomere-
duction in premature birth for women
who had scaling and root planning dur-
ing pregnancy, compared with women
who were treated with tooth cleaning
and polishing, but the results were not
statistically significant.81A subsequent
Chileanstudydidfindbenefitinagroup
of women who were treated for peri-
odontal disease compared with women
who were chosen randomly for treat-
ment after delivery.83However, a recent
largeUSmulticentertrialthatcompared
407 women who were treated at ? 21
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American Journal of Obstetrics & Gynecology Supplement to DECEMBER 2008
Page 10
weeks of gestation to 405 women who
wereassignedrandomlytotreatmentaf-
ter delivery found no reduction in pre-
term birth at ? 37 weeks of gestation,
although there was a trend for reduced
preterm birth at ? 32 weeks of gesta-
tion.84Thecurrentdatacannotallowfor
a definitive conclusion regarding cause
andeffectbetweenmaternalperiodontal
disease and preterm birth. Different
studieshaveuseddifferentdefinitionsof
periodontaldisease,andalltheinterven-
tion trials have initiated treatment after
the first trimester, which may be too late
to reduce the risk that is associated with
preterm birth. A randomized study of
preconception screening and treatment
of periodontal disease is needed.
Recommendations by other groups. The
American Academy of Periodontology
recommends that women who are preg-
nant or planning to become pregnant
undergo a periodontal examination.85
The Canadian Task Force of Periodic
Health Examination found fair (B level)
evidence for tooth brushing, good (A
level) evidence for flossing to prevent
gingivitis, and fair (B level) evidence to
support prophylaxis and scaling, de-
pending on periodontal status.86
Recommendation. There are no studies
that have evaluated the role of precon-
ception or interconception screening
andtreatmentofperiodontaldiseaseand
its effect on reproductive outcomes.
Routinescreeningandtreatmentofperi-
odontal disease during preconception
care is of considerable benefit to the
motherbutcannotyetberecommended
ashavingbenefitforthefetus.Strengthof
recommendation: C; quality of evidence:
I-b.
BV
Burden of suffering. BV results from a
shiftinthenormalvaginalbacterialflora
to1thatischaracterizedbyanincreasein
Gardnerella, Mycoplasma and anaerobic
bacteria, and a decrease in Lactobacilli.87
BV is a common cause of abnormal vag-
inaldischarge.ThetrueprevalenceofBV
in the community is not known, but
studies in academic medical centers and
public hospitals found that 9-23% of
pregnant women had BV, with infection
being more common among African
American women than white women.88
A data synthesis supports the idea that
BVorganismsarefoundintheupperre-
productive tract and contribute to the
risk for pelvic inflammatory disease.89
Observational studies consistently have
shown an association between BV and
adverse pregnancy outcomes that in-
cludepretermdelivery(relativerisk,1.4-
6.9), preterm premature rupture of
membranes(relativerisk,2.0-7.3),spon-
taneous abortion (relative risk, 1.3-2.0),
and preterm labor (relative risk, 2.0-
2.6).90-93Studies that find a higher rela-
tive risk of preterm delivery for BV are
those with the earliest gestational age for
BV screening. The risk of preterm deliv-
ery is ? 7-fold higher for women with
BV at ? 16 weeks of gestation and
greater than 4-fold higher for women
with BV at ? 20 weeks of gestation.94
How detectable is the condition? The
most common manner in which a diag-
nosis of BV is made clinically is with the
Amsel criteria, which were developed to
evaluate symptomatic women. The Am-
sel criteria are (1) presence of a homog-
enouswhitedischarge,(2)presenceofan
amineor“fishy”odor(whichmaybeac-
centuated with the addition of KOH to
the specimen), (3) the presence of “clue
cells” on microscopy, and (4) a vaginal
fluid of pH ? 4.5. Three of the 4 criteria
must be present to make a diagnosis of
BV.95Gram’s stain of vaginal discharge
can also be used to diagnose BV and of-
fers improved reproducibility and qual-
ity assurance, compared with the Amsel
criteria. The Gram’s stain method uses
the Nugent criteria and scores vaginal
flora from 1-10 on the basis of bacterial
types and quantities: 0-3, normal flora;
4-6, intermediate abnormal flora; 7-10,
BV.96Although these criteria are used
commonly in research settings, they are
not practical for clinical settings, given
the need to prepare and critically read
Gram’s stains.
How effective are the current treatments? A
shortcourseofantibiotictherapycanal-
terthemicrofloraimbalancethatisasso-
ciated with BV, but cure rates are vari-
able and recurrences are common.97A
review of the evidence has established
that the benefits of therapy for BV
among nonpregnant women are the re-
lief of vaginal symptoms and signs of in-
fection and the reduction in the risk of
infectious complications after induced
abortion or hysterectomy.89Many ran-
domized controlled trials have investi-
gated whether treating BV during preg-
nancy improves pregnancy outcomes,
with conflicting results.98-106Results of
15good-qualitytrialsthatinvolved5888
women are summarized in a recent
Cochrane review.107The Cochrane re-
view concluded that there is little evi-
dence that screening and treating all
pregnantwomenwithasymptomaticBV
prevents preterm delivery, but there is
somesuggestionthatearlyscreeningand
treatmentat?20weeksofgestationmay
reduce the risk of preterm delivery. The
review also concluded that, among
women with a previous preterm deliv-
ery,treatmentdoesnotaffecttheriskofa
subsequent preterm delivery but is asso-
ciated with a decrease in the risk of pre-
term premature rupture of membranes.
Further support for the potential effec-
tivenessofearlyscreeningandtreatment
of BV among asymptomatic pregnant
womencomesfromarecentlypresented
abstract from the Syracuse Healthy Start
Project.108This project encouraged pro-
vidersforpregnantwomenwhoresidein
high-risk zip codes of Syracuse to screen
for and treat BV at the first prenatal care
visit. They report that premature deliv-
ery (11.4% vs 13.2%; P ? .2), low birth-
weight (8.6% vs 11.5%; P ? .02), deliv-
ery at ? 32 weeks of gestation (2.1% vs
4.4%; P ? .001), and very low birth rate
(1.9% vs 3.8%; P ? .006) were lower in
the screened/treated group, compared
with the unscreened group. First screen-
ingandtreatmentwereatamedianof11
and 14 weeks of gestation, respectively.
Impactofpreconceptioncare. Todate,no
studies have evaluated the role of pre-
conceptionorinterconceptionscreening
and treatment of BV on subsequent
pregnancyoutcomes;thishasbeeniden-
tified as an important area for future re-
search, given its established association
with preterm delivery. BV is a particu-
larly appealing risk factor to target, be-
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cause it is potentially preventable and
treatable. Furthermore, because of its
higher prevalence among black women,
thepreventionandtreatmentofBVmay
help reduce at least part of the racial dis-
parity in preterm delivery.89However,
the frequency of recurrence of BV and
thevariablecureratemaybefactorsthat
limit the value of preconception detec-
tion and treatment in terms of the erad-
ication of BV before a subsequent preg-
nancy. Because
screening and treatment could subject a
substantial number of women to the in-
convenience and minor side-effects of
antibiotics. Although the regimens that
areusedtotreatBVgenerallyareconsid-
eredsafeinpregnancy,severalstudiesdo
raise the possibility of harm to some
women or their infants. In 2 studies, a
subgroup of women who did not have
BV, but who received treatment with
metronidazole or clindamycin, experi-
enced trends toward higher incidence of
preterm delivery at ? 34 weeks of gesta-
tion (12-13% vs 4-5%).109In addition,
neonatal sepsis was increased signifi-
cantly among women who received vag-
inal clindamycin therapy.110
BVis common,
Recommendations by other groups. Pres-
ently, the USPSTF,111the CDC,68and
theACOG112donotrecommendscreen-
ing and treatment for BV among preg-
nant women of any risk category. The
USPSTF states that “there is good evi-
dence that screening and treatment of
BV in asymptomatic women of average
risk does not improve outcomes such as
pretermlabororpretermbirth”andrec-
ommends against routinely screening
average-risk asymptomatic
women for BV. The USPSTF goes on to
statethatthereare“good-qualitystudies
with conflicting results that screening
and treatment of asymptomatic BV in
high-risk pregnant women reduces the
incidence of preterm delivery.” The
magnitudeofbenefitexceededtheriskin
several studies,113,114but the single larg-
est study reported no benefit among
high-risk pregnant women.115Thus, the
USPSTF concludes that the evidence is
insufficienttorecommendfororagainst
routinely screening high-risk pregnant
women for BV. The USPSTF does pro-
pregnant
vide clinical considerations when mak-
ing decisions to screen and treat or not
andstatesthat,forwomenwithahistory
of preterm delivery, screening for BV is
an option, noting that the optimal
screeningtestforBVisnotcertainnoris
the optimal time to screen and the opti-
mal treatment regimen. The 3 trials that
demonstratedareductioninpretermde-
livery screened in the second trimester
(13-24 weeks of gestation) and used oral
metronidazole or oral metronidazole
and erythromycin. Reasons for the con-
flicting results are not clear but may in-
volve differences in other risk factors for
pretermdelivery
women, which include variations in im-
munologic response to BV, or differ-
ences in drug regimens or timing of
therapy.116
amongenrolled
Recommendation. There are no studies
that evaluate the role of preconception
or interconception screening and treat-
ment for asymptomatic BV and its effect
on reproductive outcomes; such studies
are a high priority. Routine screening
and treatment of BV among asymptom-
atic pregnant women of average risk
should not be performed because of the
lack of demonstrated benefit and the
possibilityofadverseeffectsoftreatment
for women without BV. For pregnant
women with previous preterm delivery,
the inconsistent results of well-done
studies prevent a clear recommendation
for or against screening; however, some
studies support early screening and
treatment with a regimen containing
oral metronidazole. For women with
symptomatic BV infection, treatment is
appropriateforpregnantwomenandfor
women planning pregnancy. Strength of
recommendation: D (for women without
previous preterm delivery), C (for
womenwithpreviouspretermdelivery);
quality of evidence: I-b.
GBS
Burden of suffering. The gastrointestinal
tract serves as the natural reservoir for
GBS and is the likely source of vaginal
colonization. Genital tract colonization
is found in approximately 10-30% of
womenandcanbetransient,chronic,or
intermittent. GBS is a common cause of
early-onsetneonatalsepsis(1700casesin
theUnitedStatesin2001117)andmenin-
gitis and can be transmitted to the new-
born infant by passage through a colo-
nizedgenitaltract(0.4casesper1000live
births in 2006).118
How detectable is the condition? Culture
of the lower vagina/rectum is done with
traditional laboratory methods and de-
tectslowertractcolonization.Rapidtests
have been produced but may not detect
light colonization such that they have
not been incorporated into screening
programs.119PCR techniques appear to
have adequate sensitivity, but questions
arise regarding availability on a 24/7
basis.
Howeffectivearethecurrenttreatments? In-
trapartum antibiotics are 90% effective
atthepreventionofearly-onsetneonatal
sepsis.119
Impact of preconception care. Pregnant
women should be screened for vaginal/
rectal GBS colonization at 35-37 weeks
of gestation. Women who are colonized
should receive antibiotics in labor to re-
duce the risk of vertical transmission to
thenewborninfant.Thereisnoevidence
thatidentificationofgenitaltractcoloni-
zation in the nonpregnant patient pro-
videsclinicalbenefit.Infact,evengenital
tract colonization in early pregnancy is
not predictive of neonatal GBS sepsis.120
Recommendations by other groups. The
CDC has recommended a strategy of
universal screening for genital coloniza-
tion by GBS at 35-37 weeks of gestation,
with antibiotics in labor for those with
positive cultures. This strategy has been
endorsed by ACOG and other groups.
There are no recommendations for
screening nonpregnant adults.
Recommendation. Screening for GBS
colonization at a preconception visit is
not indicated and should not be per-
formed. Strength of recommendation: E;
quality of evidence: II-2.
Comment
As discussed in this article, there is ample
evidence that clinicians should address
many infectious conditions in their pre-
conceptioncareactivities.Riskassessment,
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screening,andtreatmentforspecificinfec-
tions should be a component of precon-
ceptioncare(strengthofrecommendation
of “A”) because there is convincing evi-
dence that treatment of these infections
before pregnancy prevents infertility, ec-
topic implantation, and neonatal infec-
tions (Chlamydia); consequences to the
developing fetus (syphilis); or transmis-
sion of an infectious agent with potential
for chronic infection of the offspring
(HIV). Infections with less strong recom-
mendation(“B”)forconsiderationinpre-
conceptioncareincludethedetectionand
treatment of tuberculosis, gonorrheal in-
fection, and HSV in selected individuals.
Those infections that lack clear evidence
for inclusion in preconception care
(strength of recommendation of “C”) in-
cludehepatitisC,toxoplasmosis,cytomeg-
alovirus,listeriosis,malaria,BVinwomen
with previous preterm birth, and peri-
odontaldisease.Insomecases,suchasfor
toxoplasmosis, the interventions are pri-
marily patient education; it is unclear
whether the recommendation by a pro-
vider(toavoidcertainfoodsandchanging
cat litter boxes) impacts patient behavior
or, ultimately, the pregnancy outcome. In
the case of periodontal disease and BV,
randomized trials that have been con-
ducted during pregnancy have had mixed
resultsforthepreventionofpretermbirth,
although data that have evaluated the po-
tential impact of intervention in the pre-
conception period are altogether lacking.
Given the association of periodontal dis-
ease and BV with preterm birth in obser-
vational studies, trials to evaluate specifi-
callytheeffectofpreconceptiontreatment
interventionsfortheseconditionsarewar-
ranted. A number of infections have im-
portant consequences during pregnancy
yet should be excluded from preconcep-
tioncare,forexamplewitha“D”levelrec-
ommendationforBVinthosewithnohis-
tory of preterm birth and “E” level
recommendations that include parvovi-
rus, asymptomatic bacteriuria, and GBS
infection.
f
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