Congenital Rubella Syndrome in Infants of Women Vaccinated During or Just Before Pregnancy With Measles Rubella Vaccine

7/30/2019 Congenital Rubella Syndrome in Infants of Women Vaccinated During or Just Before Pregnancy With Measles Rube

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Rubella is an exanthematous illness characterized by

nonspecific signs and symptoms, including transienterythematous and sometimes pruritic rash, postauricularor suboccipital lymphadenopathy, arthralgia, and low-

grade fever1- 3. Clinically similar exanthematous illnessesare caused by parvovirus, adenoviruses, and enteroviruses2.

Moreover, 25-50 per cent of rubella infections aresubclinical3. Rubella is typically a mild disease with minor

morbidity and a few complications unless it is contracted

by a pregnant woman (particularly during the first

trimester)2,3. In such cases, rubella often leads to foetal

death or severe congenital defects including blindness,

deafness, cardiovascular anomalies, and mental retardation

[congenital rubella syndrome (CRS)]2-4.

Although the burden of CRS is not well

characterized in all countries, it is estimated that more

than 100,000 cases occur each year in developing

Congenital rubella syndrome in infants of women vaccinated during

or just before pregnancy with measles-rubella vaccine

Mohammad H. Namaei, Masood Ziaee & Narges Naseh

Birjand University of Medical Science, Birjand, Iran

Received September 26, 2006

Background & objectives: Measles and Rubella Control Campaign was conducted in Iran in December2003 targeting both males and females 5 to 25 yr old using measles-rubella vaccine. During the campaign,some pregnant women received vaccine during the first trimester of pregnancy or some others becamepregnant shortly thereafter. The goal of this study was to evaluate the risk of congenital rubella syndrome(CRS) among the infants born to the vaccinated mothers.

Methods: A total of 106 pregnant women, who had received vaccine during the first trimester of pregnancy orbecome pregnant less than three months after vaccination were included in the study for comparison 40 pregnant

women without rubella vaccine were also included. The mothers blood samples at the time of delivery, infantscord blood and blood samples at the end of the second month of birth of sixty children whose parents agreedabout blood sampling, were tested for rubella IgM and IgG antibodies using ELISA method.

Results: There were 107 live births in the exposed group and 42 in the control group. Serological studyshowed no IgM rubella antibody in the maternal and infant cord blood; it was not found in the secondblood specimens of 60 infants tested at 8 wk of age. IgG rubella antibody was positive in all infants cordblood but it decreased in the second blood specimens of the infants. None of the children exhibited signs ofcongenital rubella syndrome.

Conclusions: Finding of our study showed that none of the infants born to mothers vaccinated by MRvaccine during the first trimester of pregnancy or had become pregnant within three months aftervaccination, had CRS.

Key words CRS - congenital - pregnancy - rubella - vaccine - women

Indian J Med Res 127, June 2008, pp 551-554

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552 INDIAN J MED RES, JUNE 2008

countries alone5-7. Caring for CRS cases is costly

because of the permanent disabilities caused by the

condition8.

Rubella vaccination is included in national

immunization programmes in most countries and

territories of the world. The vaccines are highlyprotective and without significant adverse effects9.

However, as rubella vaccines contain live attenuated

viruses, there is concern that vaccination of women later

found to be pregnant might result in foetal infection

and deformity9-11. The currently recommended approach

to vaccinating women of childbearing age is to ask them

if they think they are pregnant or may become pregnant

in the next 3 months. If the answer is yes, they should

not receive the vaccine; if the answer is no, they

should be vaccinated9,10

.In December 2003, the Ministry of Health and

Medical Education of the Islamic Republic of Iran

implemented a nationwide campaign to vaccinate about

33,000,000 people aged between 5 and 25 yr with a

combined measles and rubella (MR) vaccine (Measles;

Edmonston Zagreb strain/Rubella; RA27/3 strain,

Serum Institute of India Ltd., Pune, India12.

Unfortunately, during the campaign some pregnant

women received vaccine during the first trimester of

pregnancy or some others became pregnant shortlythereafter.

We undertook this study to evaluate the risk of CRS

among the infants born to vaccinated mothers.

Material & Methods

The study conducted in Vali-e-Asr multispeciality

hospital affiliated to Birjand University of Medical

Sciences and Health Services, Birjand, East Iran,

receiving referral patients from South Khorasan

province.

For the purpose of the study, we followed up all

women who had received the MR vaccine during

nationwide campaign while they were in the first

trimester of pregnancy or had become pregnant within

3 months thereafter, during November 2003 - November

2004, and agreed for evaluation. The exclusion criterion

for the study group were documented previous history

of rubella infection or vaccination, and delivery outside

the hospital. During the initial counselling session,

details of the exposure were obtained, including the date

of rubella vaccination as well as maternal demographics

and obstetrical history.

The mothers were followed up until delivery.

At delivery the mothers blood and infants cord bloodsamples were collected aseptically. Another sample

of infants blood was collected at the 8 th wk of

age. Sera was separated and stored at -20oC untilanalyzed.

Relevant information regarding antepartum andintrapartum factors that could have a bearing onneonatal condition was collected. All infants were

examined during the first 24 h of life by a pediatricianto find any clinical signs of CRS.

IgM rubella antibody was evaluated qualitativelyin mothers and infants blood using indirect ELISA

method. IgG rubella antibody was also evaluatedquantitatively in cord blood and second blood specimen

of infants. All serologic tests were performed using thesame ELISA kits in the same laboratory by the sameperson. ELISA kits used were Enzygnost Anti-Rubella-Virus/IgM (Dade Behring, Marburg, Germany) and

Rubella IgG ELISA Kit (Genesis, UK).

The endpoint of interest was the incidence of CRS.CDCs clinical criteria for diagnosis of CRS wereused2,3.

Laboratory criteria for diagnosis of CRS were:demonstration of rubella-specific IgM antibody in cord

blood, or demonstration of rubella-specific IgMantibody in infant blood at 8 th wk of age, or infant rubellaantibody level persisting at a higher level and for a

longer period than expected from passive transfer ofmaternal antibody (i.e., rubella titre that does not dropat the expected rate of a two-fold dilution per month)2,3.

A comparison group of women who did not receive

rubella vaccine or received it more than 3 month beforeconception, were also followed up in a similar way.Outcomes of interest were compared between the study

and comparison groups with the t test, chi- square testand Fishers exact test.

The ethical committee of the university approvedthe study. A written informed consent was obtained fromeach participant after the study objectives were

explained.

Result

A total of 106 exposed women and 40 controls werefollowed. Of these, only 60 women (all in the exposed

group) agreed on their infants blood sampling at 8th

wk of age. There were no statistically significantdifferences in maternal age, rate of smoking, alcohol


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consumption and recreational drug use between the

exposed and control group. There were no statistically

significant differences in obstetric history, gravidity and

parity in the two groups.

Seventy one (66.98%) women in the exposed group

received MR vaccine before conception and theremaining received it during the first trimester.

There were 107 live births (two twins) and one still

birth in the exposed group and 42 live births (two twins)

in the control group. There were no significant

differences between the two groups in mean birth

weight, height and head circumference of newborns

(Table I).

None of the children exhibited signs of congenital

rubella syndrome. There were no significant differences

between the two groups in the rates of still birth and

major malformations or in rates of prematurity (Table

II). Two newborns had major malformations; one had

congenital hip dislocation and the other had chest

deformity with ascites. Mothers of these two malformed

children in the exposed group received the vaccine

during the first trimester.

Serological study showed no IgM rubella antibody

in the maternal and infant cord blood in any of study

subjects; it was not found in the second blood specimens

of 60 infants that were also tested. IgG rubella antibody

was positive in all infants cord blood but it decreased in

the 60 blood specimen of newborns tested after 8 wk.

Discussion

Data from earlier studies indicated no cases of

congenital rubella syndrome (CRS) among infants born

to women who were vaccinated inadvertently against

rubella within 3 months or early in pregnancy13-17. Based

on the Vaccine in Pregnancy (VIP) Registry report,between 1979 and 1988 no evidence of CRS occurred

in the offspring of the 272 susceptible women who

received the RA 27/3 rubella vaccine between 3 months

before and 3 months after conception and continued

their pregnancy to term18.

The primary end point of this study was the

occurrence of congenital rubella syndrome, which was

not seen in any of the cases exposed to the vaccine.

Based on the results, none of the children in the

exposed group showed serological evidence of CRS.However, our results are different from those of some

other studies in that a minority of newborns showed

serological evidence of CRS without clinical signs or

symptoms13,18,19. A possible explanation for this

disagreement may be that in our study all exposed

women, both susceptible against rubella before

vaccination, and those who were pre-immune, were

included, while in other studies, only susceptible women

were included. Many studies have shown that about

70-85 per cent of 15-25 yr old women had been immunewithout vaccination because of clinical or subclinical

infection, and thus their response to rubella vaccine

should be regarded as a secondary immune response6,12,

20-22. Though there are several reports of CRS due to

rubellare-infection after exposure to wild rubella virus

despite of previous history of vaccination or natural

immunity in mothers, there is no report of CRS due to

vaccination in such mothers23-26. In conclusion, none

of the infants born to mothers vaccinated during the

first trimester of pregnancy or those who became

pregnant less than three months after vaccination,showed serological evidences of CRS.

Acknowledgment

Authors thank Ms Narges Mohammady Ghanat and Mr Ali

Eftekhary for their assistance in the data collection and Vice

Chancellor for research affair of Birjand University of Medical

Sciences, Iran, for financial support.

References

1. Terada K. Rubella and congenital rubella syndrome in Japan:epidemiological problems.Jpn J Infect Dis 2003; 56: 81-7.

2. Banatvala JE, Brown DW. Rubella.Lancet2004; 363 : 1127-37.

Table I. Demographic data of newborns in the study and control

groups (Data are mean SD)

Variables Exposed Control

group group

(n=107) (n=42)

Weight(g) 3092.67493.777 3022.50427.418

Height(cm) 49.0743.647 48.9252.702

Head

circumference

(cm) 34.4702.812 34.0631.340

Table II. Pregnancy outcome in exposed and control groups

Variables Exposed Control

group group

N (%) N (%)

Still birth 1(0.94) 0

Rate of malformations 2(1.88) 0

Gestational age Term 98(92.45) 39(92.86)Pre term 8(7.55) 3(7.14)

NAMAEI et al: ABSENCE OF CRS IN INFANTS OF MOTHERS VACCINATED BY MR VACCINE 553


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3. Zimmerman L, Reef S. Congenital rubella syndrome. In:Manual for the surveillance of vaccine-preventable diseases.3rd ed. Atlanta: Centers for Disease Control and Prevention;2002.

4. Lanzieri TM, Parise MS, Siqueira MM, Fortaleza BM, SegattoTC, Prevots DR. Incidence, clinical features and estimatedcosts of congenital rubella syndrome after a large rubellaoutbreak in Recife, Brazil, 1999-2000. Pediatr Infect Dis J2004 ; 23 : 1116-22.

5. Ramamurty N, Murugan S, Raja D, Elango V, Mohana,Dhanagaran D. Serosurvey of rubella in five blocks of TamilNadu.Indian J Med Res 2006; 123 : 51-4.

6. Gandhoke I, Aggarwal R, Lal S, Khare S. Seroprevalence and

incidence of rubella in and around Delhi (1988-2002).IndianJ Med Microbiol 2005; 23 : 164-7.

7. Best JM, Castillo-Solorzano C, Spika JS, Icenogle J, GlasserJW, Gay NJ, et al. Reducing the global burden of congenitalrubella syndrome: report of the World Health Organization

Steering Committee On Research Related To Measles andRubella Vaccines and Vaccination, June 2004. J Infect Dis2005; 192 : 1890-7.

8. Sadighi J, Eftekhar H, Mohammad K. Congenital rubellasyndrome in Iran.BMC Infect Dis 2005; 5 : 44.

9. Watson JC, Hadler SC, Dykewicz CA, Reef S, Phillips L.Measles, mumps, and rubella-vaccine use and strategies forelimination of measles, rubella, and congenital rubellasyndrome and control of mumps: recommendations of theAdvisory Committee on Immunization Practices (ACIP).

MMWR Recomm Rep 1998; 47: 1-57.

10. Sur DK, Wallis DH, OConnell TX. Vaccinations in pregnancy.

Am Fam Physician 2003; 68: 299-304.11. De Santis M, Cavaliere AF, Straface G, Caruso A. Rubella

infection in pregnancy.Reprod Toxicol 2006; 21 : 390-8.

12. Hamkar R, Jalilvand S, Mokhtari-Azad T, Jelyani KN, Nategh

R. Evaluation of immunity against rubella in Iranian after masscampaign for measles-rubella vaccination on December 2003.

Am J Infect Control 2006; 34 : 588-92.

13. Hamkar R, Jalilvand S, Abdolbaghi MH, Esteghamati AR,Hagh-Goo A, Jelyani KN, et al. Inadvertent rubella vaccinationof pregnant women: evaluation of possible transplacentalinfection with rubella vaccine. Vaccine 2006; 24 : 3558-63.

14. Dubey AP, Banerjee S. Measles, mumps, rubella (MMR)

vaccine.Indian J Pediatr2003; 70 : 579-84.

15. Robertson SE, Cutts FT, Samuel R, Daz-Ortega JL. Controlof rubella and congenital rubella syndrome (CRS) indeveloping countries, Part 2: Vaccination against rubella.BullWorld Health Organ 1997; 75 : 69-80.

16. CDC. Control and prevention of rubella: evaluation andmanagement of suspected outbreaks, rubella in pregnantwomen, and surveillance for congenital rubella syndrome.

MMWR Recomm Rep 2001; 50 : 1-23.

17. Bar-Oz B, Levichek Z, Moretti ME, Mah C, Andreou S, KorenG. Pregnancy outcome following rubella vaccination: aprospective controlled study.Am J Med Genet A 2004; 130 :52-4.

18. Centers for Disease Control and Prevention. Current Trendsin Rubella Vaccination during Pregnancy-United States, 1971-1988.MMWR 1989; 38: 289-93.

19. Tookey PA, Jones G, Miller BH, Peckham CS. Rubellavaccination in pregnancy. CDR (Lond Engl Rev). 1991; 1 :R86-8.

20. Cutts FT, Robertson SE, Daz-Ortega JL, Samuel R. Controlof rubella and congenital rubella syndrome (CRS) indeveloping countries, part 1: burden of disease from CRS.

Bulletin OMS1997; 75 : 55-68.

21. Jarour N, Hayajneh WA, Balbeesi A, Otoom H, Al-ShurmanA, Kharabsheh S. Seroprevalence of rubella among Jordanianwomen of childbearing age. Vaccine 2007; 25 : 3615-8.

22. Miller E, Waight P, Gay N, Ramsay M, Vurdien J, Morgan-Capner P, et al. The epidemiology of rubella in England andWales before and after the 1994 measles and rubellavaccination campaign: fourth joint report from the PHLS andthe National Congenital Rubella Surveillance Programme.Commun Dis Rep CDR Rev. 1997 ; 7: R26-32.

23. Bullens D, Smets K, Vanhaesebrouck P. Congenital rubellasyndrome after maternal reinfection. Clin Pediatr2000; 39 :113-6.

24. Banerji A, Ford-Jones EL, Kelly E, Robinson JL. Congenitalrubella syndrome despite maternal antibodies. CMAJ 2005;172 : 1678-9.

25. Kaneko M, Sameshima H, Ikenoue T, Minematsu T, KusumotoK, Ibara S, et al. Rubella outbreak on Tokunoshima Island in2004: serological and epidemiological analysis of pregnantwomen with rubella.J Obstet Gynaecol Res 2006; 32 : 461-7.

26. Ushida M, Katow S, Furukawa S. Congenital rubella syndromedue to infection after maternal antibody conversion with

vaccine.Jpn J Infect Dis 2003; 56: 68-9.

Reprint requests : Dr Masood Ziaee, Assistant Professor, Faculty of Medicine, Birjand University of Medical Science

Ghafary Ave, Birjand, South Khorasan, Iran, P.O.Box: 379 - postal code: 9717853577

e-mail: [email protected]

554 INDIAN J MED RES, JUNE 2008

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Congenital Rubella Syndrome in Infants of Women Vaccinated During or Just Before Pregnancy With Measles Rubella Vaccine