Maternal vaccination: a review of current evidenceand recommendations
Melanie Etti, MRCP; Anna Calvert, MRCPCH; Eva Galiza, MBBS; Suzy Lim, MD, PhD; Asma Khalil, MD;Kirsty Le Doare, PhD; Paul T. Heath, FRCPCH
Maternal vaccination is an effective means of protecting pregnant women, their fetuses,and infants from vaccine-preventable infections. Despite the availability of sufficientsafety data to support the use of vaccines during pregnancy, maternal immunizationremains an underutilized method of disease prevention, often because of concerns fromboth healthcare providers and pregnant women about vaccine safety. Such concernshave been reflected in the low uptake of the COVID-19 vaccine among pregnant womenseen in many parts of the world. Here, we present an update of the current recom-mendations for the use of vaccines during pregnancy, including the evidence supportingthe use of novel vaccine platforms. We also provide an overview of the data supportingthe use of COVID-19 vaccines in pregnancy and an update of the status of vaccines thatare currently under development for use in pregnant women.
IntroductionPregnancy and infancy are both periodsof increased vulnerability to infection.1
Vaccinating women during pregnancyhas been shown to be effective inproviding protection against a numberof infections in pregnant women, whilealso providing protection for the fetusand the infant during early life. Despitethese benefits, low vaccine confidenceremains a significant barrier to vaccineuptake among pregnant women world-wide and has been a particular challengeduring the COVID-19 pandemic, whichhas seen low rates of vaccine uptakeamong this cohort. Although a smallnumber of vaccines are recommendedfor routine use during pregnancy, thereare many vaccines that have sufficientsafety data to support their use in preg-nant women in appropriate circum-
From the Paediatric Infectious DiseasesResearch Group, Institute for Infection andImmunity, St George’s University of London,London, United Kingdom (Dr Etti, Dr Calvert, DrGaliza, Dr Lim, Prof Le Doare); Fetal MedicineUnit, Department of Obstetrics andGynaecology, St. George’s University HospitalsNHS Foundation Trust, London, UnitedKingdom (Prof Khalil); and Vaccine Institute andPaediatric Infectious Diseases Research Group,Institute for Infection and Immunity, St George’sUniversity of London, London, United Kingdom(Prof Heath).
Received July 5, 2021; revised Oct. 27, 2021;accepted Oct. 29, 2021.
P.T.H. reports grant funding to his institutionfrom vaccine manufacturers, including Pfizer,Novavax, and Minervax. The other authorsreport no conflict of interest.
The authors received no specific funding for thiswork.
0002-9378/$36.00ª 2021 Elsevier Inc. All rights reserved.https://doi.org/10.1016/j.ajog.2021.10.041
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stances. In this review, we will provide anoverview of the current recommenda-tions and evidence supporting the use ofvaccinations in pregnancy, includingrecommendations for the use of novelCOVID-19 vaccines.
The Rationale for Vaccination DuringPregnancyVaccinating women during pregnancyhas 2 distinct potential benefits. Firstly, itprotects the woman from infections thatshe may be particularly susceptible toduring pregnancy, which in turn, pro-tects the fetus from congenital infectionand other harmful effects of maternalinfection. Secondly, maternal vaccina-tion may be used for the primaryintention of protecting the developingfetus and infant from infection duringthe first months of life through theplacental transfer of neutralizingimmunoglobulin G (IgG) antibodiesand/or secretory immunoglobulin A(IgA) antibodies in the mother’s breastmilk (Figures 1 and 2).The benefit of maternal vaccination
for infants was first demonstrated in1879 when it was recognized that theinfants born to women immunizedagainst the vaccinia virus during
pregnancy were immune to smallpoxduring early life.4 Neonatal vaccinationis an alternative measure for the pro-tection of infants from infection; how-ever, it relies on the infant’s ability toproduce neutralizing antibodies and isless likely to be effective in providingprotection against pathogens during thefirst few weeks of life.5 Importantly,many vaccines are not administered toinfants until they are at least 6 weeks ofage and often require �2 doses beforeachieving full protection, thus leaving acritical gapwhere they are at an increasedrisk of infection. Vaccinating the motherduring pregnancy can augment thetransfer of maternal antibodies, thusnarrowing the “window of vulnerability”to infections and prolonging the periodof protection from disease.1
There are many currently licensedvaccines that provide protective immu-nity that is beneficial for both mothersand infants, such as combined tetanus,diphtheria, and pertussis (althoughmaternal tetanus vaccination is primar-ily to protect neonates from disease), andinfluenza vaccines. There are also anumber of vaccine candidates currentlyunder investigation that could poten-tially be licensed for the principal
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FIGURE 1Placental transfer of IgG antibodies from maternal to fetal circulation
Maternal IgG antibodies are taken up into endosomes within the syncytiotrophoblast cells of the placenta and bind to the FcRn. Following acidification of
the endosome, the IgG antibodies are then transcytosed to the fetal side of the syncytiotrophoblast. The endosome fuses with the syncytiotrophoblast
membrane, and the IgG antibodies are then released into the fetal circulation. The higher physiological pH within the fetal circulation promotes
dissociation of the IgG from the FcRn (adapted from Palmeria et al).2 Figure created with BioRender.com, exported with publication and licensing rights.
Original figure held under a Creative Commons license.
FcRn, neonatal Fc receptors; IgG, immunoglobulin G.
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purpose of protecting the fetus and in-fant from infection, including vaccinesthat protect against cytomegalovirus(CMV), respiratory syncytial virus(RSV), and Group B Streptococcus(GBS).
The Assessment of Vaccine Safety inPregnancyThe first documented vaccine trial inpregnant women was conducted inPapua New Guinea in 1961, duringwhich administration of 2 or more dosesof fluid formalinized tetanus toxoidvaccine during pregnancy was shown tobe protective against neonatal tetanus.6
At the time, the United States Food andDrug Administration (FDA) guidelinesexcluded pregnant women from all drugand vaccine trials, and following thethalidomide tragedy in the 1950s to 60s,this exclusion was expanded to allwomen of childbearing potential.7 This
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decision was subsequently reversed bythe FDA in 1993 after it was deemed thatexclusion of this group of women hadled to a substantial lack of safety data fora number of drugs in women of child-bearing age.7 Even so, pregnant andlactating women still remain underrep-resented among vaccine trialparticipants.Generally, vaccines that are consid-
ered safe for administration duringpregnancy include killed or inactivatedvirus vaccines, protein subunit vaccines,toxoid-containing vaccines, and conju-gate vaccines (which includeproteinetoxoid, peptideeprotein andproteineprotein conjugated vaccines).Vaccines that contain live attenuated vi-ruses are generally not considered safebecause of the theoretical risk ofcongenital infection and the potentialincreased risk of miscarriage. Recentdata from a meta-analysis conducted by
Laris-González et al, however, did notidentify any evidence of increasedadverse pregnancy outcomes relating tothe use of live vaccines during pregnancyother than for smallpox vaccines(although the quality of evidenceincluded was low).8 In certain limitedcircumstances, a risk-benefit approachmay be reasonably taken as to theappropriateness of administering a livevaccine, particularly in situations wherethe risk posed to the mother is deemedto significantly outweigh the theoreticalrisks posed to the fetus (discussed infurther detail later).
With the advent of novel vaccineplatforms such as the messenger RNA(mRNA) and nonreplicating viral vectorplatforms used in the production of theCOVID-19 vaccines, the assessment ofvaccine safety in pregnancy has re-emerged as an area of high priorityowing to the limited historic data
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FIGURE 2Transfer of secretory IgA antibodies from maternal breast tissue to breast milk
Dimeric IgA molecules attach to the pIgR on the basolateral membrane of the mammary gland epithelium and are transcytosed through epithelial cells. At
the apical cell membrane, the IgA dimer is released into the breast milk with a portion of the pIgR molecule (the secretory chain) still attached (adapted
from Albrecht and Arck).3 Figure created with BioRender.com, exported with publication and licensing rights. Original figure held under a Creative
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supporting their use. The assessment ofvaccine safety in pregnant women re-quires additional safeguards to ensurethat the pregnancy and neonatal out-comes are appropriately monitored.Knowledge of the background rates ofadverse pregnancy and neonatal out-comes among the study population isalso needed for accurate causality as-sessments. This requirement may limitthe researchers’ ability to conductmaternal vaccine trials in resource-limited settings where such data are notroutinely reported.9 In the United States,the Vaccine Adverse Event ReportingSystem (VAERS) is used for post-licensure vaccine safety monitoring, inwhich data are collected on adverseevents after vaccination, such as still-birth, miscarriage, and birth defects.10 Ina recent study by Moro et al, VAERS re-ports relating to pregnant womenvaccinated between 2000 and 2014identified only 50 major birth defects,and no unusual clusters of birth defectswere seen among these reports.11
At present, vaccines undergo at leastPhase 1 and 2 studies in nonpregnantwomen of childbearing potential before
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they become eligible for Phase 1 evalu-ation in pregnant women. In circum-stances where the need for a vaccine isurgent, such as during disease outbreaks,this process can cause an undue delay inproviding sufficient safety data to sup-port the use of the vaccine in pregnantand lactating women. Both the SierraLeone Trial to Introduce a VaccineAgainst Ebola trial (ClinicalTrials.govIdentifier: NCT02378753), which eval-uated the recombinant vesicular stoma-titis viruseZaire Ebola virus vaccineagainst Ebola, and the recently con-ducted COVID-19 vaccine trials did notinitially include pregnant and lactatingwomen.12,13 In both circumstances, theinitial vaccine safety data in pregnancywere collected from pregnant womenwho either inadvertently or deliberatelyreceived the vaccine in/outside of trials,highlighting the need for a more coor-dinated approach to facilitate the earlierinclusion of pregnant women in thesetrials.12,14 Strategies that may enabletheir inclusion include the incorporationof developmental toxicology studies intothe vaccine programs at an early timepoint and the early use of vaccine
platforms that are already known to besafe in pregnancy.13
Increasing Vaccine ConfidenceAmong Pregnant WomenLow rates of vaccine confidence amongpregnant women remain a significantbarrier to increasing vaccinationcoverage among pregnant women, withpersistently low rates of vaccine uptakeduring pregnancy seen in the US andmany countries worldwide.15 A sys-tematic review by Kilich et al,16 whichreviewed the factors that influencedvaccine uptake in pregnant women,found that the main determinants wereawareness of the vaccine, diseaseseverity and susceptibility, vaccinebenefits, side effects and risk of harmduring pregnancy, history of previousvaccination, and recommendation fromhealthcare professionals. It is importantthat pregnant women are proactivelyoffered the vaccine by their healthcareproviders and are given ample time andopportunity to communicate any con-cerns they may have, while also beingprovided with sufficient information tohelp them make an informed decision.
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One dose Vaccine can be administered duringany trimester. Administration beforethe start of flu season isrecommended
Contraindicated in individuals with ahistory of severe allergic reaction(eg, anaphylaxis) or life-threateningreaction to a previous dose of aninfluenza vaccine
One dose Between 27 and 36 weeks’gestation (can be given earlier ifindicated, eg, for woundmanagement or pertussis outbreak)If no history of previous vaccinationand dose not administered duringpregnancy, give dose immediatelypostpartum
Contraindicated in individuals whohave had a severe allergic reaction(eg, anaphylaxis) after a previousdose of a Tdap vaccine or who havea severe allergy to any vaccinecomponent
Adapted from Centers for Disease Control and Prevention guidelines.20
CDC, Centers for Disease Control and Prevention.
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It is also important that healthcareprofessionals are provided with thetraining needed to be able to effectivelycounsel and support pregnant womenthrough this decision-making pro-cess.17 The additional solutions recom-mended for increasing vaccine uptakeamong pregnant women includeincreased healthcare provider endorse-ment of the vaccine; increased health-care provider and patient education asto the benefits of vaccination; improvedregulatory processes, including moretransparent labeling of vaccines; andmultichannel approaches that includecommunity education programs anduse of media to promote the vaccine.18
Marginalized members of society, suchas members of migrant communities,have also been identified as havinglower rates of vaccine uptake. Thus, it isalso imperative that barriers to access-ing healthcare are addressed for thesewomen to improve coverage ratesamong this particularly vulnerablecohort.19 Targeted messaging that spe-cifically highlights the benefits ofvaccination during pregnancy may helpwomen to feel more confident in theirdecision to take up these offers ofvaccination.
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Vaccines routinely recommendedduring pregnancyThe following vaccines are routinelyrecommended for administration dur-ing pregnancy by both international andnational health organizations. A sum-mary of the recommended dosingschedules and contraindications isshown in Table 1. A more detailedsummary of COVID-19 vaccines avail-able internationally is shown in Table 2.
Influenza.Current recommendation:
� Centers for Disease Control and Pre-vention (CDC): One dose of the sea-sonal influenza vaccine recommendedduring any trimester of pregnancy24
� World Health Organization (WHO):Pregnant women should be priori-tized to receive the seasonal influenzavaccine (1 dose). The influenza vac-cine should be made available topregnant women all year round.25
Many studies have shown that preg-nant women are at a greater risk of severedisease and death from seasonal influ-enza than nonpregnant women.27e29
Similar outcomes were seen during the2009 Influenza A pandemic, wherepregnant women were 7.2% more likelyto be hospitalized than nonpregnantwomen and were also found to have adisproportionally high risk of mortal-ity.30,31 One recently conducted pro-spective cohort study also found thatpregnant womenwho were infected withinfluenza during pregnancy were morelikely to experience adverse pregnancyoutcomes, including late pregnancy loss(adjusted hazard ratio, 10.7; 95% confi-dence interval [CI], 4.3e27.0) and areduction in the birthweight of theirinfants, compared with women whowere not infected.27
In light of the increased risks topregnant women, since 2012, the WHOhas advised that pregnant women shouldbe prioritized to receive the seasonalinfluenza vaccine all year round.25,32 Theinactivated virus vaccine, containingeither 3 (trivalent influenza vaccine) or 4(quadrivalent influenza vaccine) strainsof the influenza virus, is recommendedfor administration during pregnancy.
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TABLE 2Summary of COVID-19 vaccines and evidence of safety and recommendations for use in pregnancy
Vaccineplatform
Commercialdeveloper(candidate name) Mechanism of action
Assessment of safety inpregnancy
Recommendations for useduring pregnancy
mRNA Pfizer/BioNTech(BNT162b2)
Nucleoside-modified mRNAexpressed in lipid nanoparticlesthat encodes the spike proteinfor the SARS-COV-2 virus
Pfizer/BioNTech commenced aglobal Phase 3 study recruitingpregnant women in early 2021
Initial safety data supports thesafe use of mRNA vaccines inpregnant women
Moderna (mRNA-1237)
Nucleoside-modified mRNAencoding the pre-fusionstabilized spike (S) protein andthe S1eS2 cleavage siteencapsulated within a lipidnanoparticle
Real-world data from >90,000women have not identified anysafety signals22
Nonreplicatingviral vector
Oxford-AstraZeneca(AZD1222)
Modified chimpanzeeadenovirus (replication deficient)containing the gene encodingthe spike (S) protein
Pregnancies that occurred inclinical trials were recorded andfollowed up until 3 months afterbirth. Compared with womenwho received the controlvaccine, there was no increasedrisk of miscarriage and noinstances of stillbirth.23
No previous studies amongpregnant women. However,adenovirus-vectored Zikavaccine studies in pregnantmice did not identify any safetysignals
Janssen(Ad26.COV2.S)
Recombinant, replication-incompetent human adenovirustype 26 that encodes the fulllength of the stabilizedconformation of the spike (S)protein
Sputnik V (Gam-COVID-Vac)
Combined recombinantadenovirus-based vaccine (rAd5and rAd26), both containing thegene encoding the full-lengthspike (S) protein
Proteinsubunit
Novavax (NVX-Cov2373)
Full length recombinant spike (S)protein nanoparticleadministered with a saponin-based adjuvant (Matrix-M)
No direct safety data available Recombinant vaccines aregenerally considered safe foruse during pregnancySafety of saponin-basedadjuvant in pregnancyunknown
Aluminum hydroxide (used inhuman papillomavirus vaccine)and CpG 1018 (used inhepatitis B virus vaccineadjuvants) both consideredsafe for use during pregnancy
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The live attenuated influenza vaccine,which is administered intranasally, iscontraindicated during pregnancybecause of the theoretical risk ofplacental transmission of the virus to thefetus.
There is no current consensus on theoptimal gestational timing of vaccineadministration. In the United States,pregnant women are advised to receivetheir vaccination in anticipation of theinfluenza season.33 One systematic re-view and meta-analysis found that therate of seroconversion did not differsignificantly among pregnant womenwho received their vaccines duringdifferent trimesters, although the geo-metric mean titers of neutralizing anti-bodies against influenza in the cordblood were found to be 1.44 (95% CI,0.95e2.44) times higher among thewomen who were vaccinated during thethird trimester than those vaccinated inthe first trimester of pregnancy.34 How-ever, there is evidence that the risk offetal death and adverse birth outcomes isgreatest for women who are infectedduring their first trimester of preg-nancy,35 strengthening the rationale forvaccinating them earlier in pregnancy.
In addition to the placental transfer ofmaternal IgG antibodies, infants mayalso receive protection from influenzathrough secretory IgA antibodies presentin the vaccinated mother’s breast milk.In a study conducted by Schlaudeckeret al,36 sustained high levels of influenza-specific IgA antibodies were found in thebreast milk of women vaccinated againstinfluenza during pregnancy for up to 6months after birth.
Tetanus.Current recommendation:
� CDC: One dose (tetanus toxoid,reduced diphtheria toxoid, and acel-lular pertussis [Tdap]) recommendedbetween 27 and 36 weeks’ gestation
� WHO:B If previously received 1 to 4 doses
of tetanus toxoid with tetanus anddiphtheria (TT/Td), give 1 dose atleast 2 weeks before delivery
B If not previously received a doseof TT/Td or vaccination status is
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unknown, give 2 doses of TT/Tdat least 4 weeks apart, with thesecond dose given at least 2 weeksbefore delivery37
Vaccine coverage among pregnantwomen:
� United States: Tdap vaccine coverage56.6%26
� Worldwide: TT2þ/Td2þ coverage72%38
Maternal and neonatal tetanus is nowlargely not seen in high-income nations,but high mortality rates from the diseaseare still evident among women andchildren in many low- and middle-income countries.39 In response to this,the WHO launched the Maternal andNeonatal Tetanus Elimination initiativein 1999 in partnership with the UnitedNations Children’s Fund and the UnitedNations Population Fund.40 Since thistime, maternal and neonatal tetanus hasbeen eliminated in 47 out of 59 “at-risk”countries through a combination ofincreased maternal and neonatal vaccinecoverage, and improved hygiene duringdelivery (Figure 3).39,40
There are 4 tetanus toxoid-containingvaccines that are considered safe for usein pregnancy: tetanus toxoid (TT),tetanus toxoid and reduced-dose diph-theria toxoid (Td), (tetanus toxoid,reduced diphtheria toxoid, and acellularpertussis (Tdap), and Tdap in combi-nation with the inactivated polio vaccine(Tdap/IPV). TT was previously widelyused; however, the WHO now recom-mends that a tetanus-diphtheria com-bination vaccine should be administeredinstead of TT to provide early childhoodprotection against diphtheria.41 TheWHO recommends that a total of 5doses of TTor Td are required to provideprotection throughout the childbearingyears.37 If the pregnant woman has notpreviously received any doses of TT, Td,or Tdap, or her vaccination history isuncertain, additional doses are recom-mended after pregnancy to ensure fullprotection (Table 3).37 In high-incomenations where neonatal tetanus hasbeen eliminated, Tdap or Tdap/IPV isadministered during pregnancy with the
� CDC: One dose (Tdap) recom-mended between 27 and 36 weeks’gestation
� WHO: National programs mayconsider vaccination of pregnantwomen with a pertussis-containingvaccine as a strategy additional toroutine primary infant pertussis vacci-nation in countries or settingswith highor increasing infant morbidity or mor-tality from pertussis43
Vaccine coverage among pregnantwomen:
� United States: Tdap vaccine coverage56.6%26
� Worldwide: data not available
Pertussis is a highly infectious respi-ratory disease that can cause seriousillness in young infants. Pertussis vac-cines have been available since the 1950s,and their widespread use significantlyreduced the incidence of pertussis dis-ease globally. There has been a resur-gence of pertussis cases in manycountries, including in those with goodvaccine coverage, with high rates of thedisease in infants. In the United States,the cases of pertussis rose from 7857 in2000 to over 48,000 cases in 2012.44 In2005, “cocooning”was recommended bythe Advisory Committee on Immuniza-tion Practices in response to theincreasing number of cases, whereby theclose contacts of infants were advised toget vaccinated against pertussis. How-ever, this advice was later revised after itwas found that cocooning was poorlyeffective.45,46 The WHO recommendsvaccination of pregnant women as amore cost-effective means of preventionof pertussis in infants than cocooning.47
Many countries worldwide haveintroduced pertussis vaccination forpregnant women to protect infants fromthe disease. Although these programshave been shown to be effective in pre-venting severe pertussis disease in
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FIGURE 3Global elimination status of maternal and neonatal tetanus
As of December 2020, 12 out of 59 “at-risk” countries identified by the WHO in 2000 had not yet eliminated the disease.40 Figure reproduced with
permission from the World Health Organization.
Countries shaded in green represents maternal and neonatal tetanus eliminated between 2000 and December 2020
Countries shaded in red represents maternal and neonatal tetanus not eliminated.
WHO, World Health Organization.
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infants,48e51 there is uncertainty aboutthe best time during pregnancy to offervaccination to provide optimal protec-tion. Some investigators have suggestedthat later administration is preferable tocoincide with maximal antibody trans-fer, whereas others have reported higherantibody titers at birth in babies born tomothers who were vaccinated earlier inpregnancy.52e54 Studies evaluating thesafety of the Tdap vaccine have notidentified any serious adverse eventsassociated with its use duringpregnancy.55,56
Pertussis vaccination in pregnancyresults in higher antibody levels in theinfant at birth, and this persists for atleast 2e3 months. In addition, highlevels of pertussis-specific IgA antibodieshave been detected in the colostrum ofwomen vaccinated during pregnancyand are detectable in breast milk for upto 8 weeks postpartum.57 The increasedserum levels in infants born to
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vaccinated mothers may lead to areduced initial response to the infant’sown vaccinations against pertussis anddiphtheria,58e61 though this reductionmay not have any clinical implications,and the levels are generally restoredfollowing booster vaccinations.60,62
COVID-19.Current recommendation:
� CDC: COVID-19 vaccination is rec-ommended for all people aged �12years, including people who arepregnant, breastfeeding, trying to getpregnant currently, or might becomepregnant in the future63
� WHO: the use of the COVID-19vaccine in pregnant women is rec-ommended when the benefits ofvaccination to the pregnant womanoutweigh the potential risks. To helppregnant women make this assess-ment, they should be provided with
information about the risks ofCOVID-19 in pregnancy, the likelybenefits of vaccination in the localepidemiologic context, and the cur-rent limitations of safety data inpregnant women. WHO does notrecommend pregnancy testing beforevaccination. It also does not recom-mend delaying pregnancy or termi-nating it because of vaccination.64,65
Vaccine coverage among pregnantwomen:
� United States: 31%15
� Worldwide: data not available
Data from many countries haveidentified pregnant women as being at agreater risk of severe disease and deathfrom SARS-CoV-2 infection thannonpregnant women.66e70 In addition,COVID-19 in pregnancy is associatedwith an increased risk of adverse
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TABLE 3Tetanus toxoid vaccination schedule for pregnant women and women of childbearing age with no or uncertainprevious exposure to tetanus toxoid; tetanus toxoid and reduced-dose diphtheria toxoid; or diptheria, pertussisand tetanus37
Dose of TT or Td (accordingto card or history) When to give Expected duration of protection
1 At first contact or as early as possible in pregnancy None
2 At least 4 wk after TT1 1e3 y
3 At least 6 mo after TT2 or during subsequent pregnancy At least 5 y
4 At least 1 y after TT3 or during subsequent pregnancy At least 10 y
5 At least 1 y after TT4 or during subsequent pregnancy For all childbearing age years or possibly longer
Table reproduced with permission from the World Health Organization.
TT, tetanus toxoid, Td, tetanus toxoid and reduced-dose diphtheria toxoid.
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pregnancy outcomes.66,68,71 One largepopulation-based cohort study in En-gland found that among pregnantwomen who had SARS-CoV-2 infectionat the time of delivery, there was a greaterrisk of preeclampsia or eclampsia(adjusted odds ratio [aOR], 1.57; 95%CI, 1.44e1.72), preterm delivery (aOR,2.17; 95% CI, 1.96e2.42) and fetal death(aOR, 2.21; 95% CI, 1.58e3.11).72
Among the COVID-19 vaccines thathave been licensed for use internation-ally, there are 4 main vaccine platformsthat have been employed (Table 2). OnDecember 9, 2020, the Pfizer/BioNTechmRNA vaccine was granted emergencyuse authorization (EUA) by the FDAafter the Phase 3 study involving 43,000nonpregnant participants demon-strated 95.0% efficacy against COVID-1914,73 and was granted full FDAapproval on August 23, 2021.74 TheCOVID-19 vaccines manufactured byModerna (mRNA-1237) and Janssen(Ad26.COV2.S) were granted EUA bythe FDA on December 18, 2020 andFebruary 27, 2021, respectively.75,76
Given the initial lack of safety data inpregnancy, a risk-based approach tovaccination was initially implemented,and clinicians in countries such as theUnited Kingdom and the United Stateswere advised to recommend vaccinationfor “clinically vulnerable” womenfollowing an assessment of their expo-sure risk and clinical risk factors forsevere disease.77 In April 2021, the CDC
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announced that pregnant women whoare eligible for the COVID-19 vaccinecould receive the vaccines manufac-tured by Pfizer/BioNTech andModerna,after real-world data from 90,000pregnant women collected through theV-safe COVID-19 vaccine pregnancyregistry did not identify any safetysignals.78,22
There are currently no data to guiderecommendations for vaccine admin-istration at a particular gestational age,although in practice, many womenreceive the vaccine during the second orthird trimester, as they may wish toavoid any theoretical concerns aroundvaccination in the first trimester whenorganogenesis occurs.79 Recent studiesconducted in the United States andIsrael have demonstrated placentaltransfer of vaccine-specific anti-SARS-CoV-2 IgG antibodies, and anti-SARS-CoV-2 IgA and IgG antibodies havealso been detected in the breast milk oflactating women who were vaccinatedduring pregnancy for up to 6 weeks afterthe first vaccine dose.80e83 As sero-correlates of disease protection have notyet been defined, the antibody titersrequired to confer protection againstdisease in a pregnant woman or in theneonate are not known. Additional dataare needed to determine the benefit ofmaternal vaccination for the developingfetus and infant (which may in turnprovide guidance as to the optimaltiming of vaccination) and also to
determine the long-term safety of thesenovel vaccine technologies for offspringborn to the women vaccinated duringpregnancy. In February 2021, Pfizer/BioNTech began global recruitment totheir Phase 2 and 3 trials (ClinicalTrials.gov Identifier: NCT04754594) evalu-ating the safety, tolerability, andimmunogenicity of their COVID-19vaccine among pregnant women be-tween 27 and 34 weeks’ gestation, withtrial completion expected in July2022.84 Another Phase 2 trial hascommenced in the United Kingdom, inwhich the optimal schedule of vaccina-tion for pregnant women is beingassessed (https://doi.org/10.1186/ISRCTN15279830).
Vaccines safe for use in pregnancyunder special conditionsApart from vaccines in routine use inpregnancy, some vaccinations can beused in specific circumstances; forexample, in the context of an outbreak,before traveling, or after exposure to aninfection. We have summarized thesafety considerations and recommenda-tions for use for this group of vaccinesbelow.Commonly used.1. Hepatitis B
Vaccine platform: Recombinant sub-unit of the surface antigen protein
Safety considerations and recom-mendations for use:
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There is no evidence that adminis-tration of the hepatitis B virus (HBV)vaccine in pregnancy prevents infantinfection.85 Hepatitis B vaccination inpregnancy is not associated with an in-crease in adverse pregnancy outcomes.86
The CDC recommends that any preg-nant patient who is at high risk of con-tracting HBV or who would like toreceive the HBV vaccine can be offeredthe vaccine during pregnancy.20
Safety considerations and recom-mendations for use:
Meningococcal polysaccharide vac-cines are safe,87e91 immunogenic, andresult in higher antibody concentrationsin the infant.87e91
Meningococcal conjugate vaccineshave not been associated with any safetyconcerns in pregnancy.92e94 There is noevidence about their immunogenicity oreffectiveness when given in pregnancy.
Vaccination can be recommended ifa woman is at a high risk of menin-gococcal disease or in the context of anoutbreak.
Safety considerations and recom-mendations for use: The inactivated vi-rus vaccine (IPV) is routinely offered toall pregnant women in the UnitedKingdom and New Zealand (in combi-nation with the Tdap vaccine).95,96 TheCDC does not recommend its routineadministration to women who are not atan increased risk of exposure to thedisease.97 The live attenuated prepara-tion is contraindicated for use in preg-nancy, although no adverse birthoutcomes have been reported in womenwho received the oral polio vaccineduring pregnancy.98
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Safety considerations and recom-mendations for use: No association hasbeen shown between inadvertentanthrax vaccination in pregnancy andthe risk of birth defects.99,100 Because ofthe severity of anthrax infection, it isrecommended that pregnant womenshould receive the same postexposureprophylaxis as nonpregnant adults,including vaccination. If women are atrisk of inhalational anthrax, they shouldreceive anthrax vaccine regardless ofgestation.101
2. Cholera
Vaccine platform(s): Inactivated bac-terium (oral vaccine); live attenuatedSafety considerations and recom-
mendations for use:The inactivated vaccine is theoretically
safe, as bacteria within the vaccine arekilled and cannot replicate and the vac-cine antigens act locally on gastrointes-tinal mucosa and are unlikely to causesystemic toxicity. No increase in preg-nancy adverse outcomes in those womenwho inadvertently received choleravaccination in pregnancy have been re-ported in 3 retrospective studies whichincluded nearly 3000 women in 3countries,102e104 and a further observa-tional study showed no increase in risk ofpregnancy loss or of neonatal death.105
The WHO recommends that pregnantand lactating women are included incholera vaccination campaigns as there ishigh potential benefit and minimal po-tential risk.47 The inactivated vaccineshould also be considered on a case-by-case basis for women who are at highrisk for disease. The live attenuatedpreparation is contraindicated for use inpregnancy.102e104
3. Coxiella burnetii (Q fever)
Vaccine platform(s): InactivatedbacteriumSafety considerations and recom-
mendations for use: There are no studiesof Q fever vaccines in pregnancy and noofficial recommendations about theiruse.
Safety considerations and recom-mendations for use:
Both vaccine platforms are safe,immunogenic and result in increasedantibody concentrations in the infantwhen administered in pregnancy,although conjugate vaccines arepreferred because of the higher infantantibody concentrations at birth and at 2months of age.106,107 There is no evi-dence of effectiveness in reducing diseaseincidence in infants.108 Hib vaccinecould be used in pregnancy if considerednecessary, however control of invasiveHib disease in many countries isextremely good and thus the need forHib vaccination in pregnancy is likely tobe low.
Safety considerations and recom-mendations for use:
There is no evidence of an increase inadverse pregnancy outcomes followinginactivated hepatitis A vaccination inpregnancy. The inactivated virus vaccinecan be used after consideration of thelikely risks of exposure.109,110 The liveattenuated preparation is contra-indicated for use in pregnancy.
Safety considerations and recom-mendations for use:
There is no evidence about the use ofthe inactivated Japanese encephalitisvaccine in pregnancy. The inactivatedvaccine may be considered if traveling toan endemic area where one is likely toexperience significant exposure. The liveattenuated preparation is contra-indicated for use in pregnancy.
7. Rabies
Vaccine platform(s): Inactivated virusSafety considerations and recom-
mendations for use:
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Postexposure prophylaxis: There isno evidence of an increased risk ofadverse pregnancy outcome followingthe postexposure administration of therabies vaccine when compared with thebackground rate of adverseoutcomes.111e118
Preexposure prophylaxis: Althoughstudies have focused on the administra-tion of the vaccine following exposure,the safety of the vaccine demonstrated inthese studies would support its usebefore exposure for a pregnant woman athigh risk.
Given the high case fatality rate forrabies, pregnancy should not beconsidered a contraindication to post-exposure prophylaxis and may beconsidered for preexposure prophylaxisfor women at risk.
Safety considerations and recom-mendations for use:
Polysaccharide vaccines are safe119
and increase antipolysaccharide anti-bodies in infants,120e127 though there islittle evidence that this affects the colo-nization rates or disease incidence ininfants born to vaccinatedmothers.128,129
There is limited evidence for the use ofconjugate vaccines in pregnancy; theonly published study showed that infantsof vaccinated mothers had an increasedincidence of the primary outcome (acuteotitis media).130
Pneumococcal vaccinations can beused in pregnancy if protection of thewoman is considered necessary.
10. Tick-borne encephalitis virus
Vaccine platform(s): Inactivated virusSafety considerations and recom-
mendations for use:Theoretically, there are no contrain-
dications for the use of this vaccine inpregnancy. However, there are no studiesof tick-borne encephalitis virus vaccinesin pregnant women and no official rec-ommendations for their use.
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11. Typhoid
Vaccine platform(s): Oral live attenu-ated; polysaccharideSafety considerations and recom-
mendations for use:The safety of the polysaccharide vac-
cine has not been determined, but thetheoretical risk is low. Therefore, it maybe considered when the benefits arelikely to outweigh the risks. The liveattenuated preparation is contra-indicated for use in pregnancy.
12. Yellow fever
Vaccine platform(s): Live attenuatedSafety considerations and recom-
mendations for use:There is only a live attenuated vaccine
available for the prevention of yellowfever. Live vaccines are usually contra-indicated in pregnancy. However, thereis some evidence that yellow fevervaccination in pregnancy is not associ-ated with an increased incidence ofadverse pregnancy outcomes, thoughcongenital infection ispossible.110,131e133 Use of the live vac-cine can be considered if it is thoughtthat the risks of infection outweigh thepossible risks of vaccination.134 If therisks of vaccination are considered tooutweigh the risks of yellow fever, buttravel is required to an area that requiresvaccination, a medical waiver can beissued.
Vaccines currently under investigation1. Group B Streptococcus
GBS is one of the leading causes ofneonatal sepsis and meningitis glob-ally.135 Maternal rectovaginal GBS colo-nization has also been associated with anincreased risk of preterm delivery andstillbirth. Thus, there is a need to protectthe fetus and provide passive immunityto protect infants after birth.136
Six capsular polysaccharide serotypesof GBS (Ia, Ib, II, III, IV, and V) causeapproximately 98% of invasive GBSdisease in neonates, with serotype IIIcausing the greatest proportion of inva-sive disease.137,138 In 1988, Baker andKasper first demonstrated the feasibility
of maternal GBS vaccination, though theinitial observations were of poorimmunogenicity of their monovalentpolysaccharide-based GBS vaccine,which was targeted against serotypeIII.139 More promising results have beenseen with protein-conjugated capsularpolysaccharide GBS vaccines, though thetrivalent CRM197-conjugated capsularpolysaccharide GBS vaccine developedby Novartis (targeted against serotypesIa, Ib, and III) did not progress pastPhase 1/2 studies (ClinicalTrials.govIdentifier: NCT02046148). A recentPhase 1/2 trial conducted by Absalonet al (ClinicalTrials.gov Identifier:NCT03170609) demonstrated the safetyand immunogenicity of Pfizer’s novelhexavalent conjugate vaccine (GBS6) innonpregnant adults, with the GBSserotype-specific geometric mean anti-body concentrations remaining sub-stantially elevated among the vaccinatedgroups 6 months after vaccination (be-tween 10- and 56-fold higher than theplacebo group).140 Pfizer has subse-quently commenced the recruitment ofpregnant women to their Phase 1/2 trial(ClinicalTrials.gov Identifier:NCT03765073).
In June 2020, Minervax started Phase2 trials evaluating their recombinantprotein-based vaccine (GBS-NN), whichis based on the highly immunogenic N-terminals of the AlphaC and Rib GBSsurface proteins (ClinicalTrials.govIdentifier: NCT04596878).141 Thisstudy will evaluate the safety andimmunogenicity of the vaccine in preg-nant women with and without HIV,which will be of particular value in sub-Saharan Africa where the rates of inva-sive GBS disease in neonates and HIVamong women of reproductive age arehigh.142,143
2. Cytomegalovirus
CMV is a very common infection thatusually causes only a mild, self-limitingillness in healthy individuals but cancause more serious illness in those withreduced immunity; it is an importantcause of congenital infection if womenare infected during pregnancy. Congen-ital CMV is the most common cause of
ity de ClinicalKey.es por Elsevier en abril 07, sevier Inc. Todos los derechos reservados.
congenital deafness globally, and thedevelopment of a vaccine is a priority,which was recognized by the US Na-tional Academy of Medicine in 2000.144
Congenital infection can occur inwomenwho have never had CMV beforeand are infected during pregnancy (pri-mary infection); it can also occur inwomen who were infected with CMVbefore pregnancy and either have reac-tivation of infection or are infected witha different strain in pregnancy (second-ary infection), though the risk ofcongenital infection in infants is thegreatest in those with primary infec-tion.145 These different modes of infec-tion have made vaccine developmentcomplex, as has our limited under-standing of the exact mechanisms bywhich maternal immunity protects thefetus. It seems that antibodies are anecessary mediator of protection forseronegative women. However, T-cellresponses also play a vital role in sup-pressing viral reactivation inwomenwhoare seropositive.146 Therefore, a vaccinethat induces both antibody and cellularresponses is likely to be needed. Breastmilk can also transfer maternal immunecells to the infant. Leukocyte populationsin breast milk are distinct from thosefound in maternal blood, with anenrichment of CD8þ T cells, predomi-nantly of the effector memory sub-type.147 The exact function of these cellsin infants is not yet known, but evidencefrom animal models suggests that theymay be compensating for the infant’simmature adaptive immune system asthey localize in the Peyer’s patches; theircytolytic and inflammatory activity is 4times higher than that of the infant’s ownT cells.148 There is also evidence thatthese breast milk CD8þ T cells may becould confer passive cellular immunityeven after lysis in the infant gut.149
CMV vaccine development has beenongoing since the 1970s. Initial effortswere focused on live attenuated strains,the most extensively studied of whichwas the Towne strain. This was well-tolerated in nonpregnant adults butprovided only incomplete protection.150
Following this, glycoprotein B (gB)—asurface protein of CMV—was identified,and vaccines based on it were shown to
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produce a good neutralizing antibodyresponse with up to 50% efficacy againstthe disease. However, the antibodyresponse was not persistent.151,152 Sub-sequently, a pentameric complex wasdiscovered, which could produce highertiters of neutralizing antibodies than gBvaccines and which has been shown toprovide protection against placentaltransmission.151 CMV vaccines that arecurrently in advanced stages of devel-opment include a replication-defectivepentameric vaccine, an adjuvanted gB-based vaccine, viral vector vaccines,RNA vaccines, and a DNA plasmid vac-cine.153 Moderna completed enrolmentinto their Phase 2 study investigating thesafety and immunogenicity of theirCMV mRNA vaccine (mRNA-1647) inmen and women of childbearing age inMarch 2020 (ClinicalTrials.gov Identi-fier: NCT04232280). Enrolment into thePhase 3 study is expected to commencein late 2021.
3. Respiratory syncytial virus
RSV is a major cause of acute lowerrespiratory tract infection in infants andyoung childrenworldwide.154 Infants areparticularly vulnerable to RSV infectionduring early life; one population-basedstudy found that infants aged <2months old accounted for 44% of RSVhospitalizations, and very preterm in-fants (born at <30 weeks’ gestation)were 3 times more likely to be hospital-ized than infants born at term.155 Thetreatment of RSV infection is mainlysupportive, though palivizumab (Syna-gis, Sobi), a humanized monoclonalantibody that targets the antigenic site ofthe fusion (F) glycoprotein of RSV, hasbeen shown to be effective in reducingthe incidence of hospitalization amonghigh-risk children aged <24months.156,157
In the 1960s, a formalin-inactivatedRSV vaccine was trialed in infants andtoddlers. However, increased rates ofhospitalization and deaths because ofRSV were seen that winter among thesechildren due, in part, to the non-protective, low-avidity IgG response eli-cited by the vaccine.156 Maternalvaccination is believed to be a safer
means of conferring immunity in infantsagainst the virus, and although a numberof maternal RSV vaccine candidates havebeen developed, none have yet beenlicensed for use. The efficacy of pal-ivizumab against severe RSV infectionhas identified the F glycoprotein as apromising vaccine target. However, novaccines have yet shown sufficient effi-cacy in disease reduction in Phase 3 tri-als.158 One recent Phase 3 trialinvestigating the efficacy of the Novavaxrecombinant RSV fusion nanoparticlevaccine between 28 and 36 weeks’gestation (NCT02624947) did not showit to be sufficiently efficacious in pre-venting RSV-associated, medically-sig-nificant lower respiratory tractinfections during the first 90 days of life(efficacy 39%; 97.52% CI, �1.0 to 63.7;prespecified lower boundary of 97.52%CI �30%). However, fewer infantswithin the study group were hospitalizedbecause of RSV-associated lower respi-ratory tract infections than in the pla-cebo group (2.1% vs 3.5%, vaccineefficacy 44%; 95% CI, 19.6% to61.5%).159 Animal models and obser-vational human studies have morerecently demonstrated the superiority ofthe prefusion form of the F glycoproteinin stimulating the production ofneutralizing antibodies againstRSV.160,161 In 2020, Pfizer(ClinicalTrials.gov Identifier:NCT04424316) and GlaxoSmithKline(ClinicalTrials.gov Identifier:NCT04605159) both commencedPhase 3 studies of their respective re-combinant subunit prefusion RSV Fantigen vaccine candidates, withcompletion of both studies expectedbetween 2023 and 2024.
Vaccines contraindicated duringpregnancyThe vaccines that are not recommendedor contraindicated during pregnancy aresummarized in Table 4. The inadvertentadministration of these vaccines duringpregnancy, for example, before thewoman realizes she is pregnant, is not anindication for termination of pregnancy.However, there should be counselingregarding the potential risks to thefetus.20
erican Journal of Obstetrics & Gynecology 469ity de ClinicalKey.es por Elsevier en abril 07, sevier Inc. Todos los derechos reservados.
Contains live attenuated mumps,measles, and rubella viruses
No evidence of increased risk of adverse pregnancy or fetaloutcomes (including congenital rubella syndrome) followingadministration during pregnancy.98
Pregnancy testing is not recommended before vaccineadministration of vaccine. However, recipients are advised notto become pregnant for at least 28 days after vaccinedose.20,47
Varicella (live attenuatedvirus)
Contains live attenuated varicella-zoster virus. Data from Merck/CDC Pregnancy Registry have not identifiedany increased risk of congenital varicella syndrome.20,165
Zoster (recombinantglycoprotein)
No safety data available to support use inpregnancy. Not recommended by CDC foradministration during pregnancy.
Data from Merck/CDC Pregnancy Registry has not identifiedany increased risk of congenital varicella syndrome.20
BCG, Bacillus Calmette-Guerin; CDC, Centers for Disease Control and Prevention.
Etti. Maternal vaccination. Am J Obstet Gynecol 2022.
Expert Reviews ajog.org
ConclusionMaternal vaccination is an effective yetunderutilized means of infectious dis-ease prevention for pregnant women andtheir infants. Pregnant women should beinformed of the potential benefits ofvaccination for themselves, their fetuses,and infants and should be proactivelyoffered routinely recommended vaccinesto allow timely administration beforedelivery of the infant. Sufficient timeshould be allowed to address any con-cerns women may have regarding thesafety of these vaccine during pregnancy.In addition, healthcare providers shouldbe provided with sufficient training tosupport pregnant women throughoutthe decision-making process. Currently,it is recommended that all pregnantwomen should be routinely offeredinfluenza, tetanus, and pertussis-containing vaccines. Pregnant andlactating women, and also women whoare intending to get pregnant, shouldnow be routinely offered the COVID-19vaccine in view of themounting evidenceof its safety.
There are still a number of vaccinesunder development that may be licensedfor use in pregnancy within the next
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decade. Additional data are needed todetermine the long-term safety of newlydeveloped vaccine technologies that havenot been previously evaluated in preg-nancy, including RNA and non-replicating viral vector vaccineplatforms. -
REFERENCES
1. Jones C, Heath P. Antenatal immunizationsconcepts and challenges. Hum Vaccin Immun-other 2014;10:2118–22.2. Palmeira P, Quinello C, Silveira-Lessa AL,Zago CA, Carneiro-Sampaio M. IgG placentaltransfer in healthy and pathological pregnancies.Clin Dev Immunol 2012;2012:985646.3. Albrecht M, Arck PC. Vertically transferredimmunity in neonates: mothers, mechanismsand mediators. Front Immunol 2020;11:555.4. de Martino M. Dismantling the taboo againstvaccines in pregnancy. Int J Mol Sci 2016;17:894.5. Heath PT, Jardine LA. Neonatal infections:group B streptococcus. BMJ Clin Evid2014;2014:0323.6. Schofield FD, Tucker VM, Westbrook GR.Neonatal tetanus in New Guinea. Effect of activeimmunization in pregnancy. Br Med J 1961;2:785–9.7. Macklin R. Enrolling pregnant women inbiomedical research. Lancet 2010;375:632–3.8. Laris-González A, Bernal-Serrano D, Jarde A,Kampmann B. Safety of administering live
vaccines during pregnancy: a systematic reviewand meta-analysis of pregnancy outcomes.Vaccines (Basel) 2020;8:124.9. Kochhar S, Bonhoeffer J, Jones CE, et al.Immunization in pregnancy clinical research inlow- and middle-income countries - studydesign, regulatory and safety considerations.Vaccine 2017;35:6575–81.10. Centers for Disease Control and Prevention,Food and Drug Administration, US Departmentof Health and Human Services. Vaccine AdverseEvent Reporting System (VAERS). 2021. Avail-able at: https://vaers.hhs.gov/. Accessed June25, 2021.11. Moro PL, Cragan J, Lewis P, Sukumaran L.Major birth defects after vaccination reported tothe Vaccine Adverse Event Reporting System(VAERS), 1990 to 2014. Birth Defects Res2017;109:1057–62.12. Legardy-Williams JK, Carter RJ,Goldstein ST, et al. Pregnancy outcomes amongwomen receiving RVSVD-Zebov-GP Ebolavaccine during the Sierra Leone trial to introducea vaccine against Ebola. Emerg Infect Dis2020;26:541–8.13. Heath PT, Le Doare K, Khalil A. Inclusion ofpregnant women in COVID-19 vaccine devel-opment. Lancet Infect Dis 2020;20:1007–8.14. Polack FP, Thomas SJ, Kitchin N, et al.Safety and efficacy of the BNT162b2 mRNACovid-19 vaccine. N Engl J Med 2020;383:2603–15.15. Health Alert Network. COVID-19 vaccina-tion for pregnant people to prevent seriousillness, deaths, and adverse pregnancy out-comes from COVID-19. 2021. Available at:
ity de ClinicalKey.es por Elsevier en abril 07, sevier Inc. Todos los derechos reservados.
https://emergency.cdc.gov/han/2021/han00453.asp. Accessed October 9, 2021.16. Kilich E, Dada S, Francis MR, et al. Factorsthat influence vaccination decision-makingamong pregnant women: a systematic reviewand meta-analysis. PLoS One 2020;15:e0234827.17. WilsonRJ, Paterson P, Jarrett C, LarsonHJ.Understanding factors influencing vaccinationacceptance during pregnancy globally: a litera-ture review. Vaccine 2015;33:6420–9.18. Buchy P, Badur S, Kassianos G, Preiss S,Tam JS. Vaccinating pregnant women againstinfluenza needs to be a priority for all countries:an expert commentary. Int J Infect Dis 2020;92:1–12.19. Adeyanju GC, Engel E, Koch L, et al. De-terminants of influenza vaccine hesitancy amongpregnantwomen in Europe: a systematic review.Eur J Med Res 2021;26:116.20. Centers for Disease Control and Prevention.Pregnancy guidelines and recommendations byvaccine. 2016. Available at: https://www.cdc.gov/vaccines/pregnancy/hcp-toolkit/guidelines.html#hpv. Accessed October 9, 2021.21. Kalafat E, O’Brien P, Heath PT, et al. Ben-efits and potential harms of COVID-19 vaccina-tion during pregnancy: evidence summary forpatient counseling. Ultrasound Obstet Gynecol2021;57:681–6.22. Shimabukuro TT, Kim SY, Myers TR, et al.Preliminary findings of mRNA Covid-19 vaccinesafety in pregnant persons. N Engl J Med2021;384:2273–82.23. Hillson K, Clemens SC, Madhi SA,Voysey M, Pollard AJ, Minassian AM. OxfordCOVID Vaccine Trial Group. Fertility rates andbirth outcomes after ChAdOx1 nCoV-19(AZD1222) vaccination. Lancet 2021;6;398:1683–4.24. Centers for Disease Control and Prevention.Influenza (flu) vaccine and pregnancy. 2019.Available at: https://www.cdc.gov/vaccines/pregnancy/hcp-toolkit/flu-vaccine-pregnancy.html. Accessed October 16, 2021.25. Vaccines against influenza WHO positionpaper - November 2012. Wkly Epidemiol Rec2012;87:461–76.26. Razzaghi H, Kahn KE, Black CL, et al.Influenza and Tdap vaccination coverage amongpregnant women - United States, April 2020.MMWR Morb Mortal Wkly Rep 2020;69:1391–7.27. Dawood FS, Kittikraisak W, Patel A, et al.Incidence of influenza during pregnancy andassociation with pregnancy and perinatal out-comes in three middle-income countries: amultisite prospective longitudinal cohort study.Lancet Infect Dis 2021;21:97–106.28. Mertz D, Lo CKF, Lytvyn L, Ortiz JR,Loeb M; FLURISK-INVESTIGATORS. Preg-nancy as a risk factor for severe influenza infec-tion: an individual participant datameta-analysis.BMC Infect Dis 2019;19:683.29. Vousden N, Bunch K, Knight M. UKOSSInfluenza Co-Investigators Group. Incidence,risk factors and impact of seasonal influenza in
Descargado para Eilyn Mora Corrales (emorac172022. Para uso personal exclusivamente. No
pregnancy: a national cohort study. PLoS One2021;16:e0244986.30. Creanga AA, Johnson TF, Graitcer SB, et al.Severity of 2009 pandemic influenza A (H1N1)virus infection in pregnant women. ObstetGynecol 2010;115:717–26.31. Siston AM, Rasmussen SA, Honein MA,et al. Pandemic 2009 influenza A(H1N1) virusillness among pregnant women in the UnitedStates. JAMA 2010;303:1517–25.32. World Health Organization. How to Imple-ment Influenza Vaccination of Pregnant Women.2017. Available at: https://www.who.int/publications-detail-redirect/WHO-IVB-16.06.Accessed November 28, 2021.33. American College of Obstetricians and Gy-necologists. Influenza vaccination during preg-nancy. 2018. Available at: https://www.acog.org/clinical/cl inical-guidance/committee-opinion/articles/2018/04/influenza-vaccination-during-pregnancy. Accessed May 26, 2021.34. Cuningham W, Geard N, Fielding JE, et al.Optimal timing of influenza vaccine duringpregnancy: a systematic review and meta-analysis. Influenza Other Respir Viruses2019;13:438–52.35. Gunnes N, Gjessing HK, Bakken IJ, et al.Seasonal and pandemic influenza during preg-nancy and risk of fetal death: a Norwegian reg-istry-based cohort study. Eur J Epidemiol2020;35:371–9.36. Schlaudecker EP, Steinhoff MC, Omer SB,et al. IgA and neutralizing antibodies to influenzaA virus in human milk: a randomized trial ofantenatal influenza immunization. PLoS One2013;8:e70867.37. World Health Organization. Maternal im-munization against tetanus. 2002. Available at:https://www.who.int/reproductivehealth/publ icat ions/maternal_perinatal_health/immunizat ion_tetanus.pdf. Accessed May23, 2021.38. Njuguna HN, Yusuf N, Abid Raza AA,AhmedB, TohmeRA. Progress towardmaternaland neonatal tetanus elimination - worldwide,2000-2018. MMWR Morb Mortal Wkly Rep2020;69:515–20.39. Thwaites CL, Beeching NJ, Newton CR.Maternal and neonatal tetanus. Lancet2015;385:362–70.40. World Health Organization. Progress to-wards global MNT elimination. 2021. Availableat: https://www.who.int/initiatives/maternal-and-neonatal-tetanus-elimination-(mnte)/progress-towards-global-mnt-elimination. Accessed May 9,2021.41. World Health Organization/United NationsChildren’s Fund. Replacement of TT with Tdvaccine for dual protection. 2018. Available at:http://www.who.int/immunization/programmes_systems/procurement/v3p/platform/WHO_DT_global_market_study.pdf.42. Public Health England. Pertussis vaccina-tion programme for pregnant women update:vaccine coverage in England, July to September2020. Health Protection Report. 2020. Availableat: https://assets.publishing.service.gov.
uk/government/uploads/system/uploads/attachment_data/file/941297/hpr2320_prtsss-vc.pdf. Accessed June 23, 2021.43. World Health Organization. Immunization,vaccines and Biologicals. 2021. Available at:https://www.who.int/teams/immunization-vaccines-and-biologicals/diseases/pertussis.Accessed October 16, 2021.44. Centers for Disease Control and Prevention.Pertussis surveillance: cases by year. 2017.Available at: https://www.cdc.gov/pertussis/surv-reporting/cases-by-year.html. AccessedOctober 9, 2021.45. Blain AE, Lewis M, Banerjee E, et al. Anassessment of the cocooning strategy for pre-venting infant pertussis-United States, 2011.Clin Infect Dis 2016;63(Suppl4):S221–6.46. Centers for Disease Control and Prevention.Vaccinate pregnant patients to protect againstpertussis. 2017. Available at: https://www.cdc.gov/pertussis/pregnant/hcp/pregnant-patients.html. Accessed October 9, 2021.47. World Health Organization. Recommenda-tions for interrupted or delayed routine immuni-zation—summaryofWHOposition papers. 2015.Available at: http://www.who.int/immunization/policy/Immunization%7B_%7Droutine%7B_%7Dtable3.pdf?ua=1$%5C$n. AccessedNovember 11, 2021.48. Vygen-Bonnet S, Hellenbrand W, Garbe E,et al. Safety and effectiveness of acellularpertussis vaccination during pregnancy: a sys-tematic review. BMC Infect Dis 2020;20:136.49. Amirthalingam G, Andrews N, Campbell H,et al. Effectiveness of maternal pertussis vacci-nation in England: an observational study. Lan-cet 2014;384:1521–8.50. Amirthalingam G, Campbell H, Ribeiro S,et al. Sustained effectiveness of the maternalpertussis immunization program in England 3years following introduction. Clin Infect Dis2016;63(Suppl4):S236–43.51. Becker-Dreps S, Butler AM, McGrath LJ,et al. Effectiveness of prenatal tetanus, diph-theria, acellular pertussis vaccination in the pre-vention of infant pertussis in the U.S. Am J PrevMed 2018;55:159–66.52. Abu-Raya B, Giles ML, Kollmann TR,Sadarangani M. The effect of timing of teta-nus-diphtheria-acellular pertussis vaccineadministration in pregnancy on the avidity ofpertussis antibodies. Front Immunol 2019;10:2423.53. Naidu MA, Muljadi R, Davies-Tuck ML,Wallace EM, Giles ML. The optimal gestation forpertussis vaccination during pregnancy: a pro-spective cohort study. Am J Obstet Gynecol2016;215:237.e1–6.54. Eberhardt CS, Blanchard-Rohner G,Lemaître B, et al. Maternal immunization earlier inpregnancy maximizes antibody transfer andexpected infant seropositivity against pertussis.Clin Infect Dis 2016;62:829–36.55. Petousis-Harris H, Walls T, Watson D,Paynter J, Graham P, Turner N. Safety of Tdapvaccine in pregnant women: an observationalstudy. BMJ Open 2016;6:e010911.
erican Journal of Obstetrics & Gynecology 471ity de ClinicalKey.es por Elsevier en abril 07, sevier Inc. Todos los derechos reservados.
56. Halperin SA, Langley JM, Ye L, et al.A randomized controlled trial of the safety andimmunogenicity of tetanus, diphtheria, andacellular pertussis vaccine immunization duringpregnancy and subsequent infant immuneresponse. Clin Infect Dis 2018;67:1063–71.57. Abu Raya B, Srugo I, Kessel A, et al. Theinduction of breast milk pertussis specific anti-bodies following gestational tetanus-diphtheria-acellular pertussis vaccination. Vaccine2014;32:5632–7.58. Perrett KP, Halperin SA, Nolan T, et al.Impact of tetanus-diphtheria-acellular pertussisimmunization during pregnancy on subsequentinfant immunization seroresponses: follow-upfrom a large randomized placebo-controlledtrial. Vaccine 2020;38:2105–14.59. Ladhani SN, Andrews NJ, Southern J,et al. Antibody responses after primary im-munization in infants born to women receivinga Pertussis-containing vaccine during preg-nancy: single arm observational study with ahistorical comparator. Clin Infect Dis 2015;61:1637–44.60. Hardy-Fairbanks AJ, Pan SJ, Decker MD,et al. Immune responses in infants whosemothers received tdap vaccine during preg-nancy. Pediatr Infect Dis J 2013;32:1257–60.61. MaertensK, Caboré RN, HuygenK, HensN,Van Damme P, Leuridan E. Pertussis vaccina-tion during pregnancy in Belgium: results of aprospective controlled cohort study. Vaccine2016;34:142–50.62. Maertens K, Hoang TTH, Nguyen TD, et al.The effect of maternal pertussis immunization oninfant vaccine responses to a booster pertussis-containing vaccine in Vietnam. Clin Infect Dis2016;63:S197–204.63. Centers for Disease Control and Prevention.COVID-19 vaccines while pregnant orbreastfeeding. 2021. Available at: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/pregnancy.html. AccessedOctober 14, 2021.64. World Health Organization. The Pfizer Bio-NTech (BNT162b2) COVID-19 vaccine: whatyou need to know. 2021. Available at: https://www.who.int/news-room/feature-stories/detail/who-can-take-the-pfizer-biontech-covid-19–vaccine. Accessed October 14, 2021.65. World Health Organization. The ModernaCOVID-19 (mRNA-1273) vaccine: what youneed to know. 2021. Available at: https://www.who.int/news-room/feature-stories/detail/the-moderna-covid-19-mrna-1273-vaccine-what-you-need-to-know. Accessed October 14,2021.66. Allotey J, Stallings E, Bonet M, et al. Clinicalmanifestations, risk factors, and maternal andperinatal outcomes of coronavirus disease 2019in pregnancy: living systematic review andmeta-analysis. BMJ 2020;370:m3320.67. Zambrano LD, Ellington S, Strid P, et al.Update: characteristics of symptomatic womenof reproductive age with laboratory-confirmedSARS-CoV-2 infection by pregnancy status -United States, January 22-October 3, 2020.
472 American Journal of Obstetrics & GynecologyDescargado para Eilyn Mora Corrales (emorac17
2022. Para uso personal exclusivamente. No
MMWR Morb Mortal Wkly Rep 2020;69:1641–7.68. EngjomH, Aabakke AJM, Klungsøyr K, et al.COVID-19 in pregnancy-characteristics andoutcomes of pregnant women admitted tohospital because of SARS-CoV-2 infection in theNordic countries. Acta Obstet Gynecol Scand2021;100:1611–9.69. Elsaddig M, Khalil A. Effects of the COVIDpandemic on pregnancy outcomes. BestPract Res Clin Obstet Gynaecol 2021;73:125–36.70. Vousden N, Bunch K, Morris E, et al. Theincidence, characteristics and outcomes ofpregnant women hospitalized with symptomaticand asymptomatic SARS-CoV-2 infection inthe UK from March to September 2020: a na-tional cohort study using the UK Obstetric Sur-veillance System (UKOSS). PLoS One 2021;16:e0251123.71. Mullins E, Hudak ML, Banerjee J, et al.Pregnancy and neonatal outcomes of COVID-19: coreporting of common outcomes fromPAN-COVID and AAP-SONPM registries. Ul-trasound Obstet Gynecol 2021;57:573–81.72. Gurol-Urganci I, Jardine JE, Carroll F, et al.Maternal and perinatal outcomes of pregnantwomenwith SARS-CoV-2 infection at the time ofbirth in England: national cohort study. Am JObstet Gynecol 2021;225:522.e1–11.73. US Food and Drug Administration. FDAtakes key action in fight against COVID-19 byissuing emergency use authorization for firstCOVID-19 vaccine. 2020. Available at: https://www.fda.gov/news-events/press-announcements/fda-takes-key-action-fight-against-covid-19-issuing-emergency-use-authorization-first-covid-19. Accessed May 23, 2021.74. US Food and Drug Administration. FDAapproves first COVID-19 vaccine. 2021. Avail-able at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-covid-19-vaccine. Accessed October 9,2021.75. US Food and Drug Administration. ModernaCOVID-19 vaccine. 2021. Available at: https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/moderna-covid-19-vaccine. AccessedMay 4, 2021.76. US Food and Drug Administration. JanssenCOVID-19 vaccine. 2021. Available at: https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/janssen-covid-19-vaccine. Accessed June24, 2021.77. Royal College of Obstetricians and Gynae-cologists. Updated advice on COVID-19 vacci-nation in pregnancy and women who arebreastfeeding. 2020. Available at: https://www.rcog.org.uk/en/news/updated-advice-on-covid-19-vaccination-in-pregnancy-and-women-who-are-breastfeeding/. Accessed May 25, 2021.78. Centers for Disease Control and Prevention.V-safe COVID-19 Vaccine Pregnancy Registry.2021. Available at: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/vsafe
pregnancyregistry.html. Accessed April 25,2021.79. Poliquin V, Castillo E, Boucoiran I, et al.Statement on COVID-19 vaccination in preg-nancy. 2020. Available at: https://sogc.org/common/Uploaded files/Latest News/SOGC_Statement_COVID-19_Vaccination_in_Pregnancy.pdf. Accessed May 25, 2021.80. Collier AY, McMahan K, Yu J, et al. Immu-nogenicity of COVID-19 mRNA vaccines inpregnant and lactating women. JAMA2021;325:2370–80.81. Gray KJ, Bordt EA, Atyeo C, et al. Corona-virus disease 2019 vaccine response in preg-nant and lactating women: a cohort study. Am JObstet Gynecol 2021;225:303.e1–17.82. Perl SH, Uzan-Yulzari A, Klainer H, et al.SARS-CoV-2eSpecific antibodies in breast milkafter COVID-19 vaccination of breastfeedingwomen. JAMA 2021;325:2013–4.83. Beharier O, Plitman Mayo R, Raz T, et al.Efficient maternal to neonatal transfer of anti-bodies against SARS-CoV-2 and BNT162b2mRNA COVID-19 vaccine. J Clin Invest2021;131:e150319.84. Pfizer. Pfizer and BioNTech commenceglobal clinical trial to evaluate COVID-19 vaccinein pregnant women. 2021. Available at: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-commence-global-clinical-trial-evaluate. AccessedFebruary 21, 2021.85. Sangkomkamhang US, Lumbiganon P,Laopaiboon M. Hepatitis B vaccination duringpregnancy for preventing infant infection.Cochrane Database Syst Rev 2014;2014:CD007879.86. Moro PL, Zheteyeva Y, Barash F, Lewis P,Cano M. Assessing the safety of hepatitis Bvaccination during pregnancy in the VaccineAdverse Event Reporting System (VAERS),1990-2016. Vaccine 2018;36:50–4.87. de Andrade Carvalho A, Giampaglia CM,Kimura H, et al. Maternal and infant antibodyresponse to meningococcal vaccination inpregnancy. Lancet 1977;2:809–11.88. Shahid NS, Steinhoff MC, Roy E, Begum T,Thompson CM, Siber GR. Placental and breasttransfer of antibodies after maternal immuniza-tion with polysaccharide meningococcal vac-cine: a randomized, controlled evaluation.Vaccine 2002;20:2404–9.89. O’Dempsey TJ, McArdle T, Ceesay SJ,et al. Meningococcal antibody titres in infantsof women immunised with meningococcalpolysaccharide vaccine during pregnancy.Arch Dis Child Fetal Neonatal Ed 1996;74:F43–6.90. McCormick JB, Gusmão HH, Nakamura S,et al. Antibody response to serogroup A and Cmeningococcal polysaccharide vaccines in in-fants born of mothers vaccinated during preg-nancy. J Clin Invest 1980;65:1141–4.91. Letson GW, Little JR, Ottman J, Miller GL.Meningococcal vaccine in pregnancy: anassessment of infant risk. Pediatr Infect Dis J1998;17:261–3.
ity de ClinicalKey.es por Elsevier en abril 07, sevier Inc. Todos los derechos reservados.
92. Myers TR, McNeil MM, Ng CS, Li R,Lewis PW, Cano MV. Adverse events followingquadrivalent meningococcal CRM-conjugatevaccine (Menveo�) reported to the VaccineAdverse Event Reporting System (VAERS),2010-2015. Vaccine 2017;35:1758–63.93. Zheteyeva Y, Moro PL, Yue X, Broder K.Safety of meningococcal polysaccharide-pro-tein conjugate vaccine in pregnancy: a review ofthe Vaccine Adverse Event Reporting System.Am J Obstet Gynecol 2013;208:478.e1–6.94. Wak G, Williams J, Oduro A, Maure C,Zuber PLF, Black S. The safety of PsA-TT inpregnancy: an assessment performed Withinthe Navrongo health and demographic surveil-lance site in Ghana. Clin Infect Dis2015;61(Suppl5):S489–92.95. National Health Service. Whooping coughvaccination in pregnancy. 2019. Available at:https://www.nhs.uk/pregnancy/keeping-well/whooping-cough-vaccination/. AccessedOctober 9, 2021.96. Ministry of Health. Immunisation for preg-nant women. 2021. Available at: https://www.health.govt.nz/your-health/healthy-l iving/immunisation/immunisation-pregnant-women.Accessed October 9, 2021.97. Centers for Disease Control and Prevention.Contraindications and precautions for poliovaccination. 2018. Available at: https://www.cdc.gov/vaccines/vpd/polio/hcp/contraindications-precautions.html. AccessedOctober 9, 2021.98. World Health Organization. Safety of im-munization during pregnancy: a review of theevidence. 2014. Available at: www.who.int/vaccine_safety/.../safety_pregnancy_nov2014.pdf. Accessed May 4, 2021.99. Conlin AM, Bukowinski AT, Gumbs GR;Department of Defense Birth and Infant HealthRegistry Team. Analysis of pregnancy and infanthealth outcomes among women in the NationalSmallpox Vaccine in Pregnancy Registry whoreceived anthrax vaccine adsorbed. Vaccine2015;33:4387–90.100. Conlin AMS, Sevick CJ, Gumbs GR,Khodr ZG, Bukowinski AT. Safety of inadvertentanthrax vaccination during pregnancy: an anal-ysis of birth defects in the U.S. military popula-tion, 2003-2010. Vaccine 2017;35:4414–20.101. Meaney-Delman D, Zotti ME, Creanga AA,et al. Special considerations for prophylaxis forand treatment of anthrax in pregnant and post-partum women. Emerg Infect Dis 2014;20:e130611.102. Khan AI, Ali M, Chowdhury F, et al. Safetyof the oral cholera vaccine in pregnancy: retro-spective findings from a subgroup followingmass vaccination campaign in Dhaka,Bangladesh. Vaccine 2017;35:1538–43.103. Grout L, Martinez-Pino I, Ciglenecki I, et al.Pregnancy outcomes after a mass vaccinationcampaignwith an oral cholera vaccine inGuinea:a retrospective cohort study. PLoS Negl TropDis 2015;9:e0004274.104. Hashim R, Khatib AM, Enwere G, et al.Safety of the recombinant cholera toxin B
Descargado para Eilyn Mora Corrales (emorac172022. Para uso personal exclusivamente. No
subunit, killed whole-cell (rBS-WC) oral choleravaccine in pregnancy. PLoS Negl Trop Dis2012;6:e1743.105. Ali M, Nelson A, Luquero FJ, et al. Safety ofa killed oral cholera vaccine (Shanchol) in preg-nant women in Malawi: an observational cohortstudy. Lancet Infect Dis 2017;17:538–44.106. Mulholland K, Suara RO, Siber G, et al.Maternal immunization with Haemophilus influ-enzae type b polysaccharide-tetanus proteinconjugate vaccine in the Gambia. JAMA1996;275:1182–8.107. Englund JA, Glezen WP, Thompson C,Anwaruddin R, Turner CS, Siber GR. Haemo-philus influenzae type b-specific antibody in in-fants after maternal immunization. Pediatr InfectDis J 1997;16:1122–30.108. Salam RA, Das JK, Dojo Soeandy C,Lassi ZS, Bhutta ZA. Impact of Haemophilusinfluenzae type B (Hib) and viral influenzavaccinations in pregnancy for improvingmaternal, neonatal and infant health outcomes.Cochrane Database Syst Rev 2015;2015:CD009982.109. Moro PL, Museru OI, Niu M, Lewis P,Broder K. Reports to the Vaccine Adverse EventReporting System after hepatitis A and hepatitisAB vaccines in pregnant women. Am J ObstetGynecol 2014;210:561.e1–6.110. D’Acremont V, Tremblay S, Genton B.Impact of vaccines given during pregnancy onthe offspring of women consulting a travel clinic:a longitudinal study. J Travel Med 2008;15:77–81.111. Sudarshan MK, Madhusudana SN,Mahendra BJ. Post-exposure prophylaxis withpurified vero cell rabies vaccine during preg-nancy–safety and immunogenicity. J CommunDis 1999;31:229–36.112. Sudarshan MK, Madhusudana SN,Mahendra BJ, Ashwathnarayana DH,Jayakumary M, Gangaboriah. Post exposurerabies prophylaxis with Purified Verocell rabiesvaccine: a study of immunoresponse in pregnantwomen and their matched controls. Indian JPublic Health 1999;43:76–8.113. Sudarshan MK, Giri MS, Mahendra BJ,et al. Assessing the safety of post-exposurerabies immunization in pregnancy. Hum Vaccin2007;3:87–9.114. Chutivongse S, Wilde H,Benjavongkulchai M, Chomchey P,Punthawong S. Postexposure rabies vaccina-tion during pregnancy: effect on 202women andtheir infants. Clin Infect Dis 1995;20:818–20.115. Chutivongse S, Wilde H. Postexposurerabies vaccination during pregnancy: experi-ence with 21 patients. Vaccine 1989;7:546–8.116. Fayaz A, Simani S, Fallahian V, et al. Rabiesantibody levels in pregnant women and theirnewborns after rabies post-exposure prophy-laxis. Iran J Reprod Med 2012;10:161–3.117. HuangG, Liu H, CaoQ, Liu B, Pan H, Fu C.Safety of post-exposure rabies prophylaxisduring pregnancy: a follow-up study fromGuangzhou, China. Hum Vaccin Immunother2013;9:177–83.
118. Fescharek R, Quast U, Dechert G. Post-exposure rabies vaccination during pregnancy:experience from post-marketing surveillancewith 16 patients. Vaccine 1990;8:409.119. Clarke E, Kampmann B, Goldblatt D.Maternal and neonatal pneumococcal vaccina-tion - where are we now? Expert Rev Vaccines2016;15:1305–17.120. Quiambao BP, Nohynek H, Käyhty H, et al.Maternal immunization with pneumococcalpolysaccharide vaccine in the Philippines. Vac-cine 2003;21:3451–4.121. Quiambao BP, Nohynek HM, Käyhty H,et al. Immunogenicity and reactogenicity of 23-valent pneumococcal polysaccharide vaccineamong pregnant Filipino women and placentaltransfer of antibodies. Vaccine 2007;25:4470–7.122. Holmlund E, Nohynek H, Quiambao B,Ollgren J, Käyhty H. Mother-infant vaccinationwith pneumococcal polysaccharide vaccine:persistence of maternal antibodies and re-sponses of infants to vaccination. Vaccine2011;29:4565–75.123. LehmannD, PomatWS,CombsB, Dyke T,Alpers MP. Maternal immunization with pneu-mococcal polysaccharide vaccine in the high-lands of Papua New Guinea. Vaccine 2002;20:1837–45.124. O’Dempsey TJ, McArdle T, Ceesay SJ,et al. Immunization with a pneumococcalcapsular polysaccharide vaccine during preg-nancy. Vaccine 1996;14:963–70.125. Shahid NS, Steinhoff MC, Hoque SS,Begum T, Thompson C, Siber GR. Serum,breast milk, and infant antibody after maternalimmunisation with pneumococcal vaccine.Lancet 1995;346:1252–7.126. Berezin EN, Lopes CC, Cardoso MRA.Maternal immunization with pneumococcalpolysaccharide vaccine: persistence of maternalantibodies in infants. J Trop Pediatr 2017;63:118–23.127. Munoz FM, Englund JA, Cheesman CC,et al. Maternal immunization with pneumococcalpolysaccharide vaccine in the third trimester ofgestation. Vaccine 2001;20:826–37.128. Lopes CC, Berezin EN, Scheffer D, et al.Pneumococcal nasopharyngeal carriage in in-fants of mothers immunized with 23V non-con-jugate pneumococcal polysaccharide vaccine.J Trop Pediatr 2012;58:348–52.129. Lopes CR, Berezin EN, Ching TH, CanutoJde S, Costa VO, Klering EM. Ineffectiveness forinfants of immunization of mothers with pneu-mococcal capsular polysaccharide vaccineduring pregnancy. Braz J Infect Dis 2009;13:104–6.130. Daly KA, Scott Giebink G, Lindgren BR,et al. Maternal immunization with pneumococcal9-valent conjugate vaccine and early infant otitismedia. Vaccine 2014;32:6948–55.131. Robert E, Vial T, Schaefer C, Arnon J,Reuvers M. Exposure to yellow fever vaccine inearly pregnancy. Vaccine 1999;17:283–5.132. Nasidi A, Monath TP, Vandenberg J, et al.Yellow fever vaccination and pregnancy: a four-
erican Journal of Obstetrics & Gynecology 473ity de ClinicalKey.es por Elsevier en abril 07, sevier Inc. Todos los derechos reservados.
year prospective study. Trans R Soc Trop MedHyg 1993;87:337–9.133. Suzano CES, Amaral E, Sato HK,Papaiordanou PM. Campinas Group on YellowFever Immunization during Pregnancy. The ef-fects of yellow fever immunization (17DD) inad-vertently used in early pregnancy during a masscampaign in Brazil. Vaccine 2006;24:1421–6.134. Tsai TF, Paul R, Lynberg MC, Letson GW.Congenital yellow fever virus infection after im-munization in pregnancy. J Infect Dis 1993;168:1520–3.135. Le Doare K, Kampmann B, Vekemans J,et al. Serocorrelates of protection against infantgroup B streptococcus disease. Lancet InfectDis 2019;19:e162–71.136. Melin P. Neonatal group B streptococcaldisease: from pathogenesis to preventive stra-tegies. Clin Microbiol Infect 2011;17:1294–303.137. Berner R. Group B streptococcus vac-cines: one step further. Lancet Infect Dis2021;21:158–60.138. Madrid L, Seale AC, Kohli-Lynch M, et al.Infant Group B streptococcal disease incidenceand serotypes worldwide: systematic reviewand meta-analyses. Clin Infect Dis 2017;65:S160–72.139. Baker CJ, Rench MA, Edwards MS,Carpenter RJ, Hays BM, Kasper DL. Immuni-zation of pregnant womenwith a polysaccharidevaccine of Group B streptococcus. N Engl JMed 1988;319:1180–5.140. Absalon J, Segall N, Block SL, et al. Safetyand immunogenicity of a novel hexavalent groupB streptococcus conjugate vaccine in healthy,non-pregnant adults: a phase 1/2, randomised,placebo-controlled, observer-blinded, dose-escalation trial. Lancet Infect Dis 2021;21:263–74.141. Carreras-Abad C, Ramkhelawon L,Heath PT, Le Doare K. A vaccine against groupB streptococcus: recent advances. Infect DrugResist 2020;13:1263–72.142. Sinha A, Russell LB, Tomczyk S, et al.Disease burden of Group B streptococcusamong infants in sub-Saharan Africa: a sys-tematic literature review and meta-analysis.Pediatr Infect Dis J 2016;35:933–42.143. UNAIDS. Seizing the moment: tacklingentrenched inequalities to end epidemics j
474 American Journal of Obstetrics & GynecologyDescargado para Eilyn Mora Corrales (emorac17
2022. Para uso personal exclusivamente. No
global AIDS update. 2020. Available at: https://aids2020.unaids.org/report/. Accessed June13, 2021.144. Singh T, Otero CE, Li K, Valencia SM,Nelson AN, Permar SR. Vaccines for perinataland congenital infections-how close are we?Front Pediatr 2020;8:569.145. Fowler KB, Stagno S, Pass RF. Maternalimmunity and prevention of congenital cyto-megalovirus infection. J Am Med Assoc2003;289:1008–11.146. Plotkin S, Orenstein W, Offit P,Edwards KM. Plotkin’s vaccines, 7th ed. Elsev-ier; 2017.147. Sabbaj S, Ghosh MK, Edwards BH, et al.Breast milk-derived antigen-specific CD8þ Tcells: an extralymphoid effector memory cellpopulation in humans. J Immunol 2005;174:2951–6.148. Cabinian A, Sinsimer D, Tang M, et al.Transfer of maternal immune cells by breast-feeding: maternal cytotoxic T lymphocytes pre-sent in breastmilk localize in the Peyer’s patchesof the nursed infant. PLoS One 2016;11:e0156762.149. Myles IA, Datta SK. Frontline Science:breast milk confers passive cellular immunity viaCD8-dependent mechanisms. J Leukoc Biol2021;109:709–15.150. Plotkin S. The history of vaccinationagainst cytomegalovirus. Med Microbiol Immu-nol 2015;204:247–54.151. Plotkin SA, Boppana SB. Vaccinationagainst the human cytomegalovirus. Vaccine2019;37:7437–42.152. Jenks JA, Nelson CS, Roark HK, et al.Antibody binding to native cytomegalovirusglycoprotein B predicts efficacy of the gB/MF59vaccine in humans. Sci Transl Med 2020;12:eabb3611.153. Plotkin SA, Wang D, Oualim A, et al. Thestatus of vaccine development against the hu-man cytomegalovirus. J Infect Dis 2020;221:S113–22.154. Shi T, McAllister DA, O’Brien KL, et al.Global, regional, and national disease burdenestimates of acute lower respiratory infectionsdue to respiratory syncytial virus in young chil-dren in 2015: a systematic review and modellingstudy. Lancet 2017;390:946–58.
155. Hall CB, Weinberg GA, Blumkin AK, et al.Respiratory syncytial virus-associated hospi-talizations among children less than24 months of age. Pediatrics 2013;132:e341–8.156. Aranda SS, Polack FP. Prevention of pe-diatric respiratory syncytial virus lower respira-tory tract illness: perspectives for the nextdecade. Front Immunol 2019;10:1006.157. Palivizumab, a humanized respiratorysyncytial virus monoclonal antibody, reduceshospitalization from respiratory syncytial virusinfection in high-risk infants. The IMpact-RSVStudy Group. Pediatrics 1998;102:531–7.158. Chu HY, Englund JA. Maternal immuniza-tion. Clin Infect Dis 2014;59:560–8.159. Madhi SA, Polack FP, Piedra PA, et al.Respiratory syncytial virus vaccination duringpregnancy and effects in infants. N Engl J Med2020;383:426–39.160. Eichinger KM, Kosanovich JL, Lipp M,Empey KM, Petrovsky N. Strategies for activeand passive pediatric RSV immunization. TherAdv Vaccines Immunother 2021;9:2515135520981516.161. Capella C, Chaiwatpongsakorn S,Gorrell E, et al. Prefusion F, postfusion F, G an-tibodies, and disease severity in infantsand young children with acute respiratory syn-cytial virus infection. J Infect Dis 2017;216:1398–406.162. Centers for Disease Control and Preven-tion. Fact sheets j infection control & prevention.2016. Available at: https://www.cdc.gov/tb/publications/factsheets/prevention/bcg.htm.Accessed October 9, 2021.163. Bonde U, Joergensen JS, Lamont RF,Mogensen O. Is HPV vaccination in pregnancysafe? Hum Vaccin Immunother 2016;12:1960–4.164. Moro PL, Zheteyeva Y, Lewis P, et al.Safety of quadrivalent human papillomavirusvaccine (Gardasil) in pregnancy: adverse eventsamong non-manufacturer reports in the VaccineAdverse Event Reporting System, 2006-2013.Vaccine 2015;33:519–22.165. Wilson E, GossMA,MarinM, et al. Varicellavaccine exposure during pregnancy: data from10 years of the pregnancy registry. J Infect Dis2008;197(Suppl2):S178–84.
ity de ClinicalKey.es por Elsevier en abril 07, sevier Inc. Todos los derechos reservados.
