- Email: [email protected]
Measles in pregnancy in Lyon France, 2011
Measles in pregnancy in Lyon France, 2011 Jean-Sebastien Casalegno, Cyril Huissoud, Rene Rudigoz, Jerome Massardier, Pascal Gaucherand, Yahia Mekki PII: DOI: Reference:
S0020-7292(14)00230-6 doi: 10.1016/j.ijgo.2014.03.021 IJG 7964
To appear in:
International Journal of Gynecology and Obstetrics
Received date: Revised date: Accepted date:
5 September 2013 4 March 2014 24 April 2014
Please cite this article as: Casalegno Jean-Sebastien, Huissoud Cyril, Rudigoz Rene, Massardier Jerome, Gaucherand Pascal, Mekki Yahia, Measles in pregnancy in Lyon France, 2011, International Journal of Gynecology and Obstetrics (2014), doi: 10.1016/j.ijgo.2014.03.021
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT CLINICAL ARTICLE
T
Measles in pregnancy in Lyon France, 2011
IP
Jean-Sebastien Casalegno a,*, Cyril Huissoud b, Rene Rudigoz b, Jerome Massardier , Pascal Gaucherand b, Yahia Mekki a
SC R
b
Laboratory of Virology, Hospices Civils de Lyon, Lyon, France
b
Department of Gynecology and Obstetrics, Hospices Civils de Lyon, Lyon, France
MA
NU
a
* Corresponding author: Jean-Sebastien Casalegno
D
Hospices Civils de Lyon, Laboratory of Virology, 59 Boulevard Pinel, 69677 Bron
TE
Cedex, France. Tel.: +33 472 12 96 16; fax:+33 472 12 95 00.
CE P
E-mail address: [email protected]
Keywords: France; Human polyvalent immunoglobulin; Measles; Pneumonia;
AC
Pregnancy; Vaccination
Synopsis: Although measles infections during pregnancy can have a deleterious effect on both mother and child, in many cases hospitalization is not required.
ACCEPTED MANUSCRIPT ABSTRACT Objective: To identify women who had measles while being pregnant during the
T
2011 epidemic peak in Lyon, France, and to document maternal characteristics and
IP
fetal outcomes.
SC R
Methods: In a retrospective survey, women who had measles while being pregnant between January and December 2011 were identified from the records of the Laboratory of Virology, Hospices Civils de Lyon. Epidemiologic data, clinical
NU
characteristics, and measles outcomes were assessed.
MA
Results: In total, 11 pregnant women and 2 women who had just delivered were hospitalized with measles infection in Lyon. The most severe maternal complication
D
was pneumonia, which occurred in 4 women (30.8%). Other maternal complications
TE
included fever (11 women; 84.6%) and elevated liver enzymes (2/6 women; 33.3%). All women delivered healthy newborns. Post-exposure prophylaxis using human
CE P
polyvalent immunoglobulin was initiated for three newborns whose mothers acquired measles in the immediate postpartum period. None of these newborns subsequently
AC
acquired measles, although breastfeeding was maintained. Conclusion: Although measles infections during pregnancy can have a deleterious effect on both mother and child, in many cases hospitalization is not required. Unnecessary admission should be avoided given the high risk of transmission of measles in an obstetrics ward.
ACCEPTED MANUSCRIPT 1. Introduction As in many European countries [1], France has been affected by successive
T
measles epidemics since 2008 [2]. A one-dose measles vaccination was introduced
IP
into the French routine childhood immunization program in 1983, and a second dose
SC R
was added in 1996. According to the French Institute for Public Health Surveillance, the vaccination coverage for one dose of measles among children aged 24 months was 90.1% in 2007, and therefore failed to reach the recommended level of 95% [3].
NU
This low vaccination coverage allowed the development of large pockets of
MA
susceptible population [4].
D
Between autumn 2010 and mid-2013, France and the surrounding European region
TE
experienced the most extensive measles outbreak for 10 years [2]. In France, 22 000 notified cases and 6 fatal cases of measles were reported between January 2008
CE P
and May 2011, with a peak occurring at the beginning of 2011, making France one of the hardest-hit countries in Europe at that time [2]. The highest incidence occurred in
AC
the Rhone-Alpes region in eastern France (estimated incidence, 77.6 cases per 100 000 individuals). One of the main features of this outbreak was the shift in affected age groups toward the young adult population (16–35 years) [5]. As a consequence, women of reproductive age and pregnant women were at considerable risk of acquiring measles [6].
The aim of the present study was to identify women who had measles while being pregnant during the 2011 peak in Lyon, France, in order to assess the epidemiology, clinical characteristics, and outcome of measles during pregnancy.
ACCEPTED MANUSCRIPT 2. Materials and methods In a retrospective descriptive study, the records of the Laboratory of Virology of the
T
Hospices Civils de Lyon, France, were used to identify cases of measles diagnosed
IP
among pregnant and postpartum women between January 1 and December 31,
SC R
2011. Neither ethical approval nor informed consent was required for the study.
All diagnosed cases of measles were confirmed either by detecting measles virus-
MA
viral RNA by reverse transcription-PCR.
NU
specific IgM antibodies (Enzygnost IgM Dade Behring, Siemens, France) or specific
D
For each confirmed case of measles, the medical records were used to obtain
TE
information including clinical characteristics and laboratory findings, in addition to
CE P
gestational age and fetal outcomes.
In addition, a literature review was performed to compare data from the 2011
AC
epidemic with previously described cases. PubMed (National Center for Biotechnology Information, Bethesda, MD, USA) was searched for articles published up to June 20, 2012, via the search terms “measles” and “pregnancy” in either English or French. Additional studies were identified by searching references listed in the studies identified. Relevant case series including more than five patients were retrieved in this way.
The present study was a descriptive survey with no statistical analysis. Data are reported as the mean ± SD or absolute number (percentage).
ACCEPTED MANUSCRIPT 3. Results During the study period, there were 507 diagnosed cases of measles, 151 of which
T
occurred among women aged 17–50 years at the study institution. The mean ± SD
IP
age of these women was 28.9 ± 5.2 years. Further review of the medical records
SC R
identified 11 women who had measles while being pregnant and 2 who had measles in the immediate postpartum period.
NU
The 11 pregnant women were aged 25–42 years (mean, 30 ± 4.6 ± years), and the
MA
gestational age at presentation ranged from 13 to 41 weeks (median, 26 weeks) (Table 1). Most women were diagnosed with measles in the second (5/11) and third
D
(4/11) trimester. Regarding the immediate postpartum period, one woman contracted
TE
measles 3 days after delivery and one woman contracted it 1 week after delivery. All
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pregnancies had been considered normal up to the development of measles.
Overall, seven women were unaware of their measles vaccination status, four were
AC
not vaccinated, one had received only a single dose, and one reported having had measles in the past. The source of infection was identified for six women: two cases were contracted via the professional environment, two via family relatives, and two via friends.
The patients initially presented with nonspecific symptoms such as asthenia (2/13), headache (2/13), fever (11/13), catarrh (2/13), rhinorrhea (3/13), conjunctivitis (2/13), swollen lymph node (2/13), dyspnea (2/13), and cough (7/13), which were followed by maculopapular eruption (13/13) and Koplick spots (2/13) 1–5 days later.
ACCEPTED MANUSCRIPT The majority of women (8/13; 61.5%) were hospitalized for a median of 5.8 days (range, 1–10 days). One woman contracted measles while hospitalized just before
T
delivery. The most severe complication was pneumonia (4/13; 30.8%). The others
IP
complications included fever (11/13; 84.6%) with a mean duration of 3.6 days, and
SC R
elevated hepatic enzymes (2 of 6 women tested; 33.3%). One patient developed a transient mild thrombocytopenia 1 day after onset of the rash (platelets count,
NU
127.109 per L) but spontaneously recovered on day 5.
MA
Regarding fetal outcomes, no congenital malformations were reported. For three patients, information on the pregnancy follow-up and on the newborn health status was not available. One child was prematurely born at 26 weeks of gestation, but this
TE
D
might have been due to a concomitant maternal Escherichia coli urinary tract infection. Post-exposure prophylaxis using human polyvalent immunoglobulin had to
CE P
be initiated for three neonates: two whose mothers acquired measles after delivery, and one whose mother acquired measles 2 weeks before delivery. A respiratory
AC
swab from one newborn of the women infected postpartum tested positive for measles by PCR. The two other newborns tested negative for measles by PCR. Although breastfeeding was maintained, none of these three newborns subsequently acquired measles.
The literature review identified four studies comprising a total of 119 cases of measles during pregnancy that were relevant to the present review [6–9]. The most recent study was conducted by Chiba et al. [6] in Japan between 2000 and 2001 (8 cases). Ali and Albar [7] reported 40 cases during 1993 in Saudi Arabia, and
ACCEPTED MANUSCRIPT Eberhar-Phillips et al. [8] and Altmar et al. [9] reported 58 and 13 cases, respectively,
T
between 1988 and 1991 in the USA.
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The women affected tended to be older in the two more recent case series of Chiba
SC R
et al. [6] and Ali and Albar [7] (mean age, 26.5 ± 4.8 years and 26.0 ± 1.6 years, respectively), as compared with the Eberhart-Phillips et al. [8] series (median age, 23 years) (Table 2). Measles infections were reported throughout pregnancy, but
MA
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almost half of the cases (37/79; 46.8%) occurred in the third trimester.
Hospitalization occurred in nearly 80% of cases reported by both Chiba et al. [6] in
D
Japan and Ali and Albar [7] in Saudi Arabia. Fever was the most frequent
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complication, reported in nearly 60% of all cases except for the Ali and Albar [7] study (32.5%). Pneumonia was the most serious and frequent complication reported
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for the mother, ranging from 10% in Japan to 53.8% in the USA. Elevated hepatic enzymes were reported in nearly 62% of all cases in the Ali and Albar [7] and Atmar
AC
et al. [9] studies. The two US studies reported a case fatality ratio of 3.4% and 7.7%, respectively [8,9], whereas the two more recent studies reported no maternal deaths [6,7].
Adverse pregnancy outcomes included premature birth (3.5%–25%) and abortion (1.7%–25.0%). No congenital malformations related to measles were reported in any of the cases series.
4. Discussion
ACCEPTED MANUSCRIPT Measles during pregnancy has a substantial risk of mortality for both mother and child, and is a common disease. PubMed was used to identify four other studies
T
reporting a total of 119 cases of measles acquired during pregnancy [6–9]. The
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increasing age of childbearing in high-resource countries over the past decade
SC R
probably explains why affected women tended to be older in the more recent of these case series. However, it remains unclear how this shift in age might affect the outcome of measles infection among a pregnant population. There was no main
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difference in mean gestational age at presentation: most cases of measles occurred
MA
in the second or third trimester.
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Patients in the present study presented with a milder clinical course compared with
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those in previous studies [6–9]. Although the frequency of fever was higher among women in the present study, the frequency of pneumonia was concordant with
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previous data. No mortality, adverse pregnancy outcomes, or newborn complications were observed. These results suggest that, although measles infections during
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pregnancy can have a deleterious effect on both mother and child, in many cases hospitalization is not required.
Overall, the hospital admission rate was lower in the present study (58.3%) than in any of the previous studies. Rapid implementation of appropriate respiratory isolation measures is essential, but insufficient to prevent measles outbreaks. Unnecessary hospitalization should be avoided given the high risk of transmission of measles in an obstetrics ward for both healthcare workers and patients. For three patients, measles occurred while being hospitalized. In this context, prompt clinical suspicion and viral testing are important.
ACCEPTED MANUSCRIPT
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Although measles is a notifiable disease in France, pregnancy status is not reported.
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As a result, it is difficult to obtain the full picture and measure the impact of measles
SC R
for pregnant women. A national prospective cohort study would provide valuable information on the true prevalence, mortality, and morbidity, in addition to the
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incidence of complications during pregnancy.
MA
The resurgence of measles exposes pregnant women to a significant risk of morbidity for both mother and child [7]. There is an urgent need to achieve high
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vaccine coverage in the susceptible population and to increase the awareness of this
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Conflict of interest
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disease among women of childbearing age.
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The authors have no conflicts of interest.
ACCEPTED MANUSCRIPT References [1]
World Health Organization. Global Alert and Response (GAR). Measles
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outbreaks: Regions of the Americas, Europe and Africa.
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http://www.who.int/csr/don/2011_10_07/en/index.html. Published October 07, 2011.
[2]
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Accessed July 17, 2013.
ECDC. Surveillance Report Volume 4: European monthly measles monitoring
(EMMO).
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http://ecdc.europa.eu/en/publications/Publications/111018_EMMO_SEPT_2011.pdf.
[3]
MA
Published September 2011. Updated November 2011. Accessed July 17, 2013. Lopalco PL, Martin R. Measles still spreads in Europe: who is responsible for
de Melker H, Pebody RG, Edmunds WJ, Lévy-Bruhl D, Valle M, Rota MC, et
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[4]
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the failure to vaccinate? Euro Surveill 2010;15(17).
al. The seroepidemiology of measles in Western Europe. Epidemiol Infect
[5]
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2001;126(2):249–59.
Corbin V, Beytout J, Auclair C, Chambon M, Mouly D, Chamoux A, et al. Shift
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of the 2009-2011 measles outbreak from children to adults: an observational review at the University Hospital of Clermont-Ferrand, France. Infection 2013;41(6):1157– 61. [6]
Chiba ME, Saito M, Suzuki N, Honda Y, Yaegashi N. Measles infection in
pregnancy. J Infect 2003;47(1):40–4. [7]
Ali ME, Albar HM. Measles in pregnancy: maternal morbidity and perinatal
outcome. Int J Gynecol Obstet 1997;59(2):109–13. [8]
Eberhart-Phillips JE, Frederick PD, Baron RC, Mascola L. Measles in
pregnancy: a descriptive study of 58 cases. Obstet Gynecol 1993;82(5):797–801.
ACCEPTED MANUSCRIPT [9]
Atmar RL, Englund JA, Hammill H. Complications of measles during
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pregnancy. Clin Infect Dis 1992;14(1):217–26.
ACCEPTED MANUSCRIPT
Table 1 Clinical characteristics and laboratory findings among patients with measles in pregnancy in Lyon, France, 2011. Patient 1
2
3
4
5
6
7
Age, y
36
27
32
33
31
26
26
Gestational age at presentatio n, wk
17
22
13
30
31
3 d after delivery
26
Vaccine status
Not Known
Not immune
Not immune
History of measles
Not known
Not immune
Source of infection
Family relative
Friend
Profession al environme nt
Not known
Not known
Family relative
Asthenia
Yes
Yes
No
No
No
Headache
Yes
Yes
No
No
No
Catarrh
No
Yes
No
No
No
Rhinorrhea
No
No
No
No
No
Conjunctivit is
No
No
No
Yes
No
Swollen lymph Node
Yes
No
No
No
Dyspnea
No
No
No
Cough
Yes
Yes
No
Maculopap ular rash
Yes
Yes
Hospital admission
Yes
Length of
8
8
9
10
11
12
13
27
29
41
24
25
30
7 d after delivery
26
31
26
31
22
Not known
Not immune
Vaccinated (1 dose)
Not known
Not known
Not known
Not known
Not known
Not known
Family relative
Not known
Not known
Not known
Profession al environme nt
Initial presentatio n
CE P
TE D
MA N
US
CR
IP
Maternal characterist ics
T
Characteris tic
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
Yes
No
No
No
No
No
No
No
No
No
Yes
No
No
No
Yes
No
Yes
No
No
No
No
No
No
No
Yes
No
No
No
No
No
No
No
No
Yes
Yes
No
No
No
No
No
No
No
No
Yes
Yes
No
Yes
Yes
No
Yes
No
No
No
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
No
Yes
Yes
Yes
Yes
Yes
No
Yes
Yes
No
No
0
0
9
6
8
7
3
0
3
2
0
0
AC
No
ACCEPTED MANUSCRIPT
stay, d
Yes
Yes
Yes
Yes
Yes
Yes
No
Yes
Pneumonia
Yes
No
No
Yes
Yes
No
Yes
No
Elevated liver Enzymes
No
Not tested
Not tested
Yes
Yes
Not tested
Yes
Thrombocy topenia
No
Not tested
Not tested
Yes
No
No
No
Abortion
No
No
No
No
No
No
Prematurity
No
No
No
No
No
Congenital malformati on
No
No
No
No
No
Neonatal mortality
No
No
No
No
No
IUFD
No
No
No
No
No
Newborn prophylaxis
No
No
No
No
No
Yes
Yes
No
No
No
No
No
No
Not tested
No
Not tested
Not tested
Not tested
MA N
US
Yes
No No
No
No
No
No
No
No
Yes
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
Yes
Yes
Yes
No
No
No
No
No
TE D
CE P
AC
Not tested
Yes
No
Fetal characterist ics
Abbreviation: IUFD, intrauterine fetal death.
CR
Fever
IP
T
Maternal complicatio n
ACCEPTED MANUSCRIPT
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CE P
TE
D
MA
NU
SC R
IP
T
Table 2 Comparison of present findings with those of other studies of patients with measles during pregnancy. Study Study characteristics Present study Chiba et al. Ali and Albar EberharAtmar et al. [6] [7] Phillips et al. [9] [8] Study period January 1 to Late 2000 to January 1 to January 1, 1988 to December 31, early 2001 December 1988, to 1990 2011 31, 1993 December 31, 1991 Nationality France Japan Saudi Arabia USA Houston, USA Study type Case series Case series Case series Case series Case series and review No. of cases 13 8 40 58 13 b Maternal age, y 30 ± 4.6 26.5 ± 4.8 26 ± 1.6 23 – Gestational age 26 ± 6.8 26.2 ± 11.1 24 ± 1.2 – – at presentation, wk 1st trimester 2 2 – 13 – 2nd trimester 5 2 – 20 – 3rd trimester 4 4 – 25 – No. of hospital 8 (61.5) 7 (87.5) 32 (80.0) – – admissions Maternal complication Fever 11 (84.6) 5 (62.5) 13 (32.5) 35 (60.3) Pneumonia 4 (30.8) 2 (25.0) 4 (10.0) 15 (25.9) 7 (53.8) Elevated liver 2/6 (33.3) 26 (65.0) 0 7 (53.8) enzymes Death 0 0 0 2 (3.4) 1 (7.7) Other 1 asthmatic 1 hemorrhagic decompensation shock Fetal outcome Abortion 0 2 (25.0) 6 (15.0) 1 (1.7) 1 (7.7) Prematurity 1 (7.7) 1 (12.5) 10 (25.0) 2 (3.5) 2 (15.4) Congenital 0 0 0 0 0 malformation Neonatal 0 0 3 (7.5) 0 0 mortality IUFD 0 1 (12.5) 2 (5.0) 1 (1.7) 1 (7.7) Abbreviation: IUFD, intra-uterine fetal death. a Data are mean ± SD or number (percentage) unless stated otherwise. b Median maternal age at presentation.
S0020-7292(14)00230-6 doi: 10.1016/j.ijgo.2014.03.021 IJG 7964
To appear in:
International Journal of Gynecology and Obstetrics
Received date: Revised date: Accepted date:
5 September 2013 4 March 2014 24 April 2014
Please cite this article as: Casalegno Jean-Sebastien, Huissoud Cyril, Rudigoz Rene, Massardier Jerome, Gaucherand Pascal, Mekki Yahia, Measles in pregnancy in Lyon France, 2011, International Journal of Gynecology and Obstetrics (2014), doi: 10.1016/j.ijgo.2014.03.021
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT CLINICAL ARTICLE
T
Measles in pregnancy in Lyon France, 2011
IP
Jean-Sebastien Casalegno a,*, Cyril Huissoud b, Rene Rudigoz b, Jerome Massardier , Pascal Gaucherand b, Yahia Mekki a
SC R
b
Laboratory of Virology, Hospices Civils de Lyon, Lyon, France
b
Department of Gynecology and Obstetrics, Hospices Civils de Lyon, Lyon, France
MA
NU
a
* Corresponding author: Jean-Sebastien Casalegno
D
Hospices Civils de Lyon, Laboratory of Virology, 59 Boulevard Pinel, 69677 Bron
TE
Cedex, France. Tel.: +33 472 12 96 16; fax:+33 472 12 95 00.
CE P
E-mail address: [email protected]
Keywords: France; Human polyvalent immunoglobulin; Measles; Pneumonia;
AC
Pregnancy; Vaccination
Synopsis: Although measles infections during pregnancy can have a deleterious effect on both mother and child, in many cases hospitalization is not required.
ACCEPTED MANUSCRIPT ABSTRACT Objective: To identify women who had measles while being pregnant during the
T
2011 epidemic peak in Lyon, France, and to document maternal characteristics and
IP
fetal outcomes.
SC R
Methods: In a retrospective survey, women who had measles while being pregnant between January and December 2011 were identified from the records of the Laboratory of Virology, Hospices Civils de Lyon. Epidemiologic data, clinical
NU
characteristics, and measles outcomes were assessed.
MA
Results: In total, 11 pregnant women and 2 women who had just delivered were hospitalized with measles infection in Lyon. The most severe maternal complication
D
was pneumonia, which occurred in 4 women (30.8%). Other maternal complications
TE
included fever (11 women; 84.6%) and elevated liver enzymes (2/6 women; 33.3%). All women delivered healthy newborns. Post-exposure prophylaxis using human
CE P
polyvalent immunoglobulin was initiated for three newborns whose mothers acquired measles in the immediate postpartum period. None of these newborns subsequently
AC
acquired measles, although breastfeeding was maintained. Conclusion: Although measles infections during pregnancy can have a deleterious effect on both mother and child, in many cases hospitalization is not required. Unnecessary admission should be avoided given the high risk of transmission of measles in an obstetrics ward.
ACCEPTED MANUSCRIPT 1. Introduction As in many European countries [1], France has been affected by successive
T
measles epidemics since 2008 [2]. A one-dose measles vaccination was introduced
IP
into the French routine childhood immunization program in 1983, and a second dose
SC R
was added in 1996. According to the French Institute for Public Health Surveillance, the vaccination coverage for one dose of measles among children aged 24 months was 90.1% in 2007, and therefore failed to reach the recommended level of 95% [3].
NU
This low vaccination coverage allowed the development of large pockets of
MA
susceptible population [4].
D
Between autumn 2010 and mid-2013, France and the surrounding European region
TE
experienced the most extensive measles outbreak for 10 years [2]. In France, 22 000 notified cases and 6 fatal cases of measles were reported between January 2008
CE P
and May 2011, with a peak occurring at the beginning of 2011, making France one of the hardest-hit countries in Europe at that time [2]. The highest incidence occurred in
AC
the Rhone-Alpes region in eastern France (estimated incidence, 77.6 cases per 100 000 individuals). One of the main features of this outbreak was the shift in affected age groups toward the young adult population (16–35 years) [5]. As a consequence, women of reproductive age and pregnant women were at considerable risk of acquiring measles [6].
The aim of the present study was to identify women who had measles while being pregnant during the 2011 peak in Lyon, France, in order to assess the epidemiology, clinical characteristics, and outcome of measles during pregnancy.
ACCEPTED MANUSCRIPT 2. Materials and methods In a retrospective descriptive study, the records of the Laboratory of Virology of the
T
Hospices Civils de Lyon, France, were used to identify cases of measles diagnosed
IP
among pregnant and postpartum women between January 1 and December 31,
SC R
2011. Neither ethical approval nor informed consent was required for the study.
All diagnosed cases of measles were confirmed either by detecting measles virus-
MA
viral RNA by reverse transcription-PCR.
NU
specific IgM antibodies (Enzygnost IgM Dade Behring, Siemens, France) or specific
D
For each confirmed case of measles, the medical records were used to obtain
TE
information including clinical characteristics and laboratory findings, in addition to
CE P
gestational age and fetal outcomes.
In addition, a literature review was performed to compare data from the 2011
AC
epidemic with previously described cases. PubMed (National Center for Biotechnology Information, Bethesda, MD, USA) was searched for articles published up to June 20, 2012, via the search terms “measles” and “pregnancy” in either English or French. Additional studies were identified by searching references listed in the studies identified. Relevant case series including more than five patients were retrieved in this way.
The present study was a descriptive survey with no statistical analysis. Data are reported as the mean ± SD or absolute number (percentage).
ACCEPTED MANUSCRIPT 3. Results During the study period, there were 507 diagnosed cases of measles, 151 of which
T
occurred among women aged 17–50 years at the study institution. The mean ± SD
IP
age of these women was 28.9 ± 5.2 years. Further review of the medical records
SC R
identified 11 women who had measles while being pregnant and 2 who had measles in the immediate postpartum period.
NU
The 11 pregnant women were aged 25–42 years (mean, 30 ± 4.6 ± years), and the
MA
gestational age at presentation ranged from 13 to 41 weeks (median, 26 weeks) (Table 1). Most women were diagnosed with measles in the second (5/11) and third
D
(4/11) trimester. Regarding the immediate postpartum period, one woman contracted
TE
measles 3 days after delivery and one woman contracted it 1 week after delivery. All
CE P
pregnancies had been considered normal up to the development of measles.
Overall, seven women were unaware of their measles vaccination status, four were
AC
not vaccinated, one had received only a single dose, and one reported having had measles in the past. The source of infection was identified for six women: two cases were contracted via the professional environment, two via family relatives, and two via friends.
The patients initially presented with nonspecific symptoms such as asthenia (2/13), headache (2/13), fever (11/13), catarrh (2/13), rhinorrhea (3/13), conjunctivitis (2/13), swollen lymph node (2/13), dyspnea (2/13), and cough (7/13), which were followed by maculopapular eruption (13/13) and Koplick spots (2/13) 1–5 days later.
ACCEPTED MANUSCRIPT The majority of women (8/13; 61.5%) were hospitalized for a median of 5.8 days (range, 1–10 days). One woman contracted measles while hospitalized just before
T
delivery. The most severe complication was pneumonia (4/13; 30.8%). The others
IP
complications included fever (11/13; 84.6%) with a mean duration of 3.6 days, and
SC R
elevated hepatic enzymes (2 of 6 women tested; 33.3%). One patient developed a transient mild thrombocytopenia 1 day after onset of the rash (platelets count,
NU
127.109 per L) but spontaneously recovered on day 5.
MA
Regarding fetal outcomes, no congenital malformations were reported. For three patients, information on the pregnancy follow-up and on the newborn health status was not available. One child was prematurely born at 26 weeks of gestation, but this
TE
D
might have been due to a concomitant maternal Escherichia coli urinary tract infection. Post-exposure prophylaxis using human polyvalent immunoglobulin had to
CE P
be initiated for three neonates: two whose mothers acquired measles after delivery, and one whose mother acquired measles 2 weeks before delivery. A respiratory
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swab from one newborn of the women infected postpartum tested positive for measles by PCR. The two other newborns tested negative for measles by PCR. Although breastfeeding was maintained, none of these three newborns subsequently acquired measles.
The literature review identified four studies comprising a total of 119 cases of measles during pregnancy that were relevant to the present review [6–9]. The most recent study was conducted by Chiba et al. [6] in Japan between 2000 and 2001 (8 cases). Ali and Albar [7] reported 40 cases during 1993 in Saudi Arabia, and
ACCEPTED MANUSCRIPT Eberhar-Phillips et al. [8] and Altmar et al. [9] reported 58 and 13 cases, respectively,
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between 1988 and 1991 in the USA.
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The women affected tended to be older in the two more recent case series of Chiba
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et al. [6] and Ali and Albar [7] (mean age, 26.5 ± 4.8 years and 26.0 ± 1.6 years, respectively), as compared with the Eberhart-Phillips et al. [8] series (median age, 23 years) (Table 2). Measles infections were reported throughout pregnancy, but
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almost half of the cases (37/79; 46.8%) occurred in the third trimester.
Hospitalization occurred in nearly 80% of cases reported by both Chiba et al. [6] in
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Japan and Ali and Albar [7] in Saudi Arabia. Fever was the most frequent
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complication, reported in nearly 60% of all cases except for the Ali and Albar [7] study (32.5%). Pneumonia was the most serious and frequent complication reported
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for the mother, ranging from 10% in Japan to 53.8% in the USA. Elevated hepatic enzymes were reported in nearly 62% of all cases in the Ali and Albar [7] and Atmar
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et al. [9] studies. The two US studies reported a case fatality ratio of 3.4% and 7.7%, respectively [8,9], whereas the two more recent studies reported no maternal deaths [6,7].
Adverse pregnancy outcomes included premature birth (3.5%–25%) and abortion (1.7%–25.0%). No congenital malformations related to measles were reported in any of the cases series.
4. Discussion
ACCEPTED MANUSCRIPT Measles during pregnancy has a substantial risk of mortality for both mother and child, and is a common disease. PubMed was used to identify four other studies
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reporting a total of 119 cases of measles acquired during pregnancy [6–9]. The
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increasing age of childbearing in high-resource countries over the past decade
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probably explains why affected women tended to be older in the more recent of these case series. However, it remains unclear how this shift in age might affect the outcome of measles infection among a pregnant population. There was no main
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difference in mean gestational age at presentation: most cases of measles occurred
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in the second or third trimester.
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Patients in the present study presented with a milder clinical course compared with
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those in previous studies [6–9]. Although the frequency of fever was higher among women in the present study, the frequency of pneumonia was concordant with
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previous data. No mortality, adverse pregnancy outcomes, or newborn complications were observed. These results suggest that, although measles infections during
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pregnancy can have a deleterious effect on both mother and child, in many cases hospitalization is not required.
Overall, the hospital admission rate was lower in the present study (58.3%) than in any of the previous studies. Rapid implementation of appropriate respiratory isolation measures is essential, but insufficient to prevent measles outbreaks. Unnecessary hospitalization should be avoided given the high risk of transmission of measles in an obstetrics ward for both healthcare workers and patients. For three patients, measles occurred while being hospitalized. In this context, prompt clinical suspicion and viral testing are important.
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Although measles is a notifiable disease in France, pregnancy status is not reported.
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As a result, it is difficult to obtain the full picture and measure the impact of measles
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for pregnant women. A national prospective cohort study would provide valuable information on the true prevalence, mortality, and morbidity, in addition to the
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incidence of complications during pregnancy.
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The resurgence of measles exposes pregnant women to a significant risk of morbidity for both mother and child [7]. There is an urgent need to achieve high
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vaccine coverage in the susceptible population and to increase the awareness of this
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Conflict of interest
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disease among women of childbearing age.
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The authors have no conflicts of interest.
ACCEPTED MANUSCRIPT References [1]
World Health Organization. Global Alert and Response (GAR). Measles
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outbreaks: Regions of the Americas, Europe and Africa.
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http://www.who.int/csr/don/2011_10_07/en/index.html. Published October 07, 2011.
[2]
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Accessed July 17, 2013.
ECDC. Surveillance Report Volume 4: European monthly measles monitoring
(EMMO).
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http://ecdc.europa.eu/en/publications/Publications/111018_EMMO_SEPT_2011.pdf.
[3]
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Published September 2011. Updated November 2011. Accessed July 17, 2013. Lopalco PL, Martin R. Measles still spreads in Europe: who is responsible for
de Melker H, Pebody RG, Edmunds WJ, Lévy-Bruhl D, Valle M, Rota MC, et
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[4]
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the failure to vaccinate? Euro Surveill 2010;15(17).
al. The seroepidemiology of measles in Western Europe. Epidemiol Infect
[5]
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2001;126(2):249–59.
Corbin V, Beytout J, Auclair C, Chambon M, Mouly D, Chamoux A, et al. Shift
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of the 2009-2011 measles outbreak from children to adults: an observational review at the University Hospital of Clermont-Ferrand, France. Infection 2013;41(6):1157– 61. [6]
Chiba ME, Saito M, Suzuki N, Honda Y, Yaegashi N. Measles infection in
pregnancy. J Infect 2003;47(1):40–4. [7]
Ali ME, Albar HM. Measles in pregnancy: maternal morbidity and perinatal
outcome. Int J Gynecol Obstet 1997;59(2):109–13. [8]
Eberhart-Phillips JE, Frederick PD, Baron RC, Mascola L. Measles in
pregnancy: a descriptive study of 58 cases. Obstet Gynecol 1993;82(5):797–801.
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Atmar RL, Englund JA, Hammill H. Complications of measles during
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pregnancy. Clin Infect Dis 1992;14(1):217–26.
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Table 1 Clinical characteristics and laboratory findings among patients with measles in pregnancy in Lyon, France, 2011. Patient 1
2
3
4
5
6
7
Age, y
36
27
32
33
31
26
26
Gestational age at presentatio n, wk
17
22
13
30
31
3 d after delivery
26
Vaccine status
Not Known
Not immune
Not immune
History of measles
Not known
Not immune
Source of infection
Family relative
Friend
Profession al environme nt
Not known
Not known
Family relative
Asthenia
Yes
Yes
No
No
No
Headache
Yes
Yes
No
No
No
Catarrh
No
Yes
No
No
No
Rhinorrhea
No
No
No
No
No
Conjunctivit is
No
No
No
Yes
No
Swollen lymph Node
Yes
No
No
No
Dyspnea
No
No
No
Cough
Yes
Yes
No
Maculopap ular rash
Yes
Yes
Hospital admission
Yes
Length of
8
8
9
10
11
12
13
27
29
41
24
25
30
7 d after delivery
26
31
26
31
22
Not known
Not immune
Vaccinated (1 dose)
Not known
Not known
Not known
Not known
Not known
Not known
Family relative
Not known
Not known
Not known
Profession al environme nt
Initial presentatio n
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US
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Maternal characterist ics
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Characteris tic
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
Yes
No
No
No
No
No
No
No
No
No
Yes
No
No
No
Yes
No
Yes
No
No
No
No
No
No
No
Yes
No
No
No
No
No
No
No
No
Yes
Yes
No
No
No
No
No
No
No
No
Yes
Yes
No
Yes
Yes
No
Yes
No
No
No
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
No
Yes
Yes
Yes
Yes
Yes
No
Yes
Yes
No
No
0
0
9
6
8
7
3
0
3
2
0
0
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No
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stay, d
Yes
Yes
Yes
Yes
Yes
Yes
No
Yes
Pneumonia
Yes
No
No
Yes
Yes
No
Yes
No
Elevated liver Enzymes
No
Not tested
Not tested
Yes
Yes
Not tested
Yes
Thrombocy topenia
No
Not tested
Not tested
Yes
No
No
No
Abortion
No
No
No
No
No
No
Prematurity
No
No
No
No
No
Congenital malformati on
No
No
No
No
No
Neonatal mortality
No
No
No
No
No
IUFD
No
No
No
No
No
Newborn prophylaxis
No
No
No
No
No
Yes
Yes
No
No
No
No
No
No
Not tested
No
Not tested
Not tested
Not tested
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US
Yes
No No
No
No
No
No
No
No
Yes
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
Yes
Yes
Yes
No
No
No
No
No
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Not tested
Yes
No
Fetal characterist ics
Abbreviation: IUFD, intrauterine fetal death.
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Fever
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Maternal complicatio n
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Table 2 Comparison of present findings with those of other studies of patients with measles during pregnancy. Study Study characteristics Present study Chiba et al. Ali and Albar EberharAtmar et al. [6] [7] Phillips et al. [9] [8] Study period January 1 to Late 2000 to January 1 to January 1, 1988 to December 31, early 2001 December 1988, to 1990 2011 31, 1993 December 31, 1991 Nationality France Japan Saudi Arabia USA Houston, USA Study type Case series Case series Case series Case series Case series and review No. of cases 13 8 40 58 13 b Maternal age, y 30 ± 4.6 26.5 ± 4.8 26 ± 1.6 23 – Gestational age 26 ± 6.8 26.2 ± 11.1 24 ± 1.2 – – at presentation, wk 1st trimester 2 2 – 13 – 2nd trimester 5 2 – 20 – 3rd trimester 4 4 – 25 – No. of hospital 8 (61.5) 7 (87.5) 32 (80.0) – – admissions Maternal complication Fever 11 (84.6) 5 (62.5) 13 (32.5) 35 (60.3) Pneumonia 4 (30.8) 2 (25.0) 4 (10.0) 15 (25.9) 7 (53.8) Elevated liver 2/6 (33.3) 26 (65.0) 0 7 (53.8) enzymes Death 0 0 0 2 (3.4) 1 (7.7) Other 1 asthmatic 1 hemorrhagic decompensation shock Fetal outcome Abortion 0 2 (25.0) 6 (15.0) 1 (1.7) 1 (7.7) Prematurity 1 (7.7) 1 (12.5) 10 (25.0) 2 (3.5) 2 (15.4) Congenital 0 0 0 0 0 malformation Neonatal 0 0 3 (7.5) 0 0 mortality IUFD 0 1 (12.5) 2 (5.0) 1 (1.7) 1 (7.7) Abbreviation: IUFD, intra-uterine fetal death. a Data are mean ± SD or number (percentage) unless stated otherwise. b Median maternal age at presentation.