Accepted Manuscript Rubella Monitoring in Pregnancy as a Means for Evaluating a Possible ReEmergence of Rubella Jill Hutton , MD Paul Rowan , PhD, MPH Anthony Greisinger , PhD Melanie Mouzoon , MD PII:
S0002-9378(14)00514-6
DOI:
10.1016/j.ajog.2014.05.046
Reference:
YMOB 9856
To appear in:
American Journal of Obstetrics and Gynecology
Received Date: 29 January 2014 Revised Date:
15 March 2014
Accepted Date: 8 May 2014
Please cite this article as: Hutton J, Rowan P, Greisinger A, Mouzoon M, Rubella Monitoring in Pregnancy as a Means for Evaluating a Possible Re-Emergence of Rubella, American Journal of Obstetrics and Gynecology (2014), doi: 10.1016/j.ajog.2014.05.046. 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 1
Rubella Monitoring in Pregnancy as a Means for Evaluating a Possible Re-Emergence of Rubella
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Jill Hutton, MD; Paul Rowan, PhD, MPH; Anthony Greisinger, PhD; Melanie Mouzoon, MD Houston, Texas, USA
Jill Hutton, MD, The Woman’s Hospital of Texas
SC
The Woman's Hospital of Texas
M AN U
Paul Rowan, PhD, MPH, The University of Texas-Houston School of Public Health Anthony Greisinger, PhD, Kelsey Research Foundation Melanie Mouzoon, MD, Kelsey-Seybold Clinic The authors report no conflicts of interest.
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Preliminary findings of this paper (when the project had enrolled 257 of 300 participants) were presented as a poster at the 14th Annual Health Services and Outcomes Research Conference
EP
on December 10, 2013, held at the Houston Medical Center Marriott, in Houston, Texas, USA, sponsored by the Kelsey Research Foundation.
serology.
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We acknowledge The Woman’s Hospital of Texas for funding laboratory costs of rubella
Corresponding Author: Jill Hutton, MD, [email protected] Jill Hutton, MD; 2617 W. Holcombe #C, #285, Houston, TX 77025; tel: 281-772-7861; fax: 281-817-7549; [email protected]
ACCEPTED MANUSCRIPT 2
Abstract word count 224
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Manuscript word count 2307
ACCEPTED MANUSCRIPT 3
This study followed women who were rubella non-immune in pregnancy to estimate the
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current incidence of rubella exposure in pregnancy.
AC C
EP
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M AN U
SC
Rubella Monitoring in Pregnancy
ACCEPTED MANUSCRIPT 4
Rubella Monitoring in Pregnancy as a Means for Evaluating a Possible Re-Emergence of Rubella Objective: While it is commonly accepted that rubella is well-controlled, a recent reemergence of both pertussis and measles might also predict a reemergence of rubella. This study was
RI PT
designed to estimate the current incidence of rubella exposure in pregnancy.
Study Design: This was a prospective, descriptive study, conducted in Houston, Texas, at The
SC
Woman's Hospital of Texas. Women are typically screened for rubella immunity at the
beginning of pregnancy. Rubella non-immunity is defined as a titer less than 10 IU/ml in the
M AN U
U.S. Women who were non-immune early in pregnancy (less than 20 weeks) were recruited for this study and asked to be tested again for rubella immunity at the time of delivery. Results: Of 298 women who were rubella non-immune (IgG < 10 IU/ml) early in pregnancy, 19 converted to immune status (IgG > 40 IU/ml, defined as at least a four-fold increase) at time of
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delivery, a rate of 6.38% (4.12 to 9.75%%, 95% Wilson-Score confidence interval). For the 19 patients who converted to immune status at time of delivery, 8 patients had levels of 40-150
EP
IU/ml, 6 patients had levels of 151-300 IU/ml, 2 patients had levels of 301-500 IU/ml, and 3 patients had levels >500 IU/ml.
AC C
Conclusions: Pregnancy is a critical time to evaluate rubella exposure. This study estimated the current incidence of rubella exposure in pregnancy to be 6.38%.
Key words: Obstetrics, pregnancy complications infectious/etiology, rubella immunology, rubella transmission, rubella virus
ACCEPTED MANUSCRIPT 5
Rubella Monitoring in Pregnancy as a Means for Evaluating a Possible Re-Emergence of
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Rubella
SC
Jill Hutton, MD, Paul Rowan, PhD, MPH, Anthony Greisinger, PhD, Melanie Mouzoon, MD
M AN U
Introduction
Rubella can cause severe disabilities in children born to mothers who contract rubella in pregnancy. After widespread vaccination in the U.S., the rate of congenital rubella diminished. Surprisingly, 9-14% of women are rubella non-immune at their first prenatal visit.[1-3] Although some of these mothers have never been vaccinated, the majority of
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susceptible patients represents women with low residual titers years after vaccination. There are case reports of women with low residual titers who contract rubella in pregnancy, but this is
EP
thought to be a very infrequent event.[4-8] However, the frequency is unknown and the outcomes have not been followed and reported. Because 9-14% of pregnant women are
AC C
susceptible to rubella, and the U.S. is a very diverse nation with an influx of people from different regions of the world with varied exposures, congenital rubella is most likely under recognized in the age of vaccination. The aim of this study was to estimate the current incidence of rubella exposure in pregnancy.
ACCEPTED MANUSCRIPT 6
Materials and Methods This was a prospective, descriptive study, conducted in Houston, Texas, at The Woman's
RI PT
Hospital of Texas, a large maternity hospital with approximately 9,000-10,000 deliveries per year. Women delivering at The Woman's Hospital of Texas are typically screened for rubella immunity early in pregnancy by their individual obstetricians at their first prenatal visit. Rubella
SC
non-immunity is defined as a titer less than 10 IU/ml in the USA. Women who were rubella non-immune early in pregnancy (less than 20 weeks), as documented in their prenatal records,
M AN U
were recruited for this study and asked if they would agree, by informed consent, to be tested again for rubella immunity at the time of delivery. To be eligible for the study, rubella nonimmunity must have been documented at least 10 weeks prior to delivery. All women were recruited in the hospital during the postpartum period, within the first three days after giving
TE D
birth. There was no added risk to participants, because blood was required to be drawn in accordance with state guidelines, and some of this blood would be used to retest for rubella immunity (Siemens rubella quantitative IgG chemiluminescent EIA run on the Advia Centaur
EP
CP). The cost of the additional rubella titer was not charged to the patient. Enrolled patients
AC C
were offered routine Measles, Mumps and Rubella vaccination postpartum regardless of the study. Patients' medical treatment was not altered regardless of whether they consented to participate in the study or not. Recruitment was conducted from November 2012 to December 2013.
This study aimed to retest 300 non-immune mothers at time of delivery. The hypothesis was that if a low percentile (1 – 5%) of women converted, then the confidence intervals would be
ACCEPTED MANUSCRIPT 7
.34 – 2.90% and 3.05 – 8.08%, 95% Wilson-Score. These calculations were used to estimate the sample size beforehand; no representative sample was obtained prior to the study.
RI PT
The following were initial reasons for exclusion: deliveries without prenatal care or patients without prior documented serology, women under 18 years of age, fetal demises or deliveries less than 24-weeks. For this study, rubella exposure in pregnancy was defined as a titer rising
SC
above 40 IU/ml. This definition represents at least a 4-fold increase as rubella non-immunity is
M AN U
S0002-9378(14)00514-6
DOI:
10.1016/j.ajog.2014.05.046
Reference:
YMOB 9856
To appear in:
American Journal of Obstetrics and Gynecology
Received Date: 29 January 2014 Revised Date:
15 March 2014
Accepted Date: 8 May 2014
Please cite this article as: Hutton J, Rowan P, Greisinger A, Mouzoon M, Rubella Monitoring in Pregnancy as a Means for Evaluating a Possible Re-Emergence of Rubella, American Journal of Obstetrics and Gynecology (2014), doi: 10.1016/j.ajog.2014.05.046. 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 1
Rubella Monitoring in Pregnancy as a Means for Evaluating a Possible Re-Emergence of Rubella
RI PT
Jill Hutton, MD; Paul Rowan, PhD, MPH; Anthony Greisinger, PhD; Melanie Mouzoon, MD Houston, Texas, USA
Jill Hutton, MD, The Woman’s Hospital of Texas
SC
The Woman's Hospital of Texas
M AN U
Paul Rowan, PhD, MPH, The University of Texas-Houston School of Public Health Anthony Greisinger, PhD, Kelsey Research Foundation Melanie Mouzoon, MD, Kelsey-Seybold Clinic The authors report no conflicts of interest.
TE D
Preliminary findings of this paper (when the project had enrolled 257 of 300 participants) were presented as a poster at the 14th Annual Health Services and Outcomes Research Conference
EP
on December 10, 2013, held at the Houston Medical Center Marriott, in Houston, Texas, USA, sponsored by the Kelsey Research Foundation.
serology.
AC C
We acknowledge The Woman’s Hospital of Texas for funding laboratory costs of rubella
Corresponding Author: Jill Hutton, MD, [email protected] Jill Hutton, MD; 2617 W. Holcombe #C, #285, Houston, TX 77025; tel: 281-772-7861; fax: 281-817-7549; [email protected]
ACCEPTED MANUSCRIPT 2
Abstract word count 224
AC C
EP
TE D
M AN U
SC
RI PT
Manuscript word count 2307
ACCEPTED MANUSCRIPT 3
This study followed women who were rubella non-immune in pregnancy to estimate the
RI PT
current incidence of rubella exposure in pregnancy.
AC C
EP
TE D
M AN U
SC
Rubella Monitoring in Pregnancy
ACCEPTED MANUSCRIPT 4
Rubella Monitoring in Pregnancy as a Means for Evaluating a Possible Re-Emergence of Rubella Objective: While it is commonly accepted that rubella is well-controlled, a recent reemergence of both pertussis and measles might also predict a reemergence of rubella. This study was
RI PT
designed to estimate the current incidence of rubella exposure in pregnancy.
Study Design: This was a prospective, descriptive study, conducted in Houston, Texas, at The
SC
Woman's Hospital of Texas. Women are typically screened for rubella immunity at the
beginning of pregnancy. Rubella non-immunity is defined as a titer less than 10 IU/ml in the
M AN U
U.S. Women who were non-immune early in pregnancy (less than 20 weeks) were recruited for this study and asked to be tested again for rubella immunity at the time of delivery. Results: Of 298 women who were rubella non-immune (IgG < 10 IU/ml) early in pregnancy, 19 converted to immune status (IgG > 40 IU/ml, defined as at least a four-fold increase) at time of
TE D
delivery, a rate of 6.38% (4.12 to 9.75%%, 95% Wilson-Score confidence interval). For the 19 patients who converted to immune status at time of delivery, 8 patients had levels of 40-150
EP
IU/ml, 6 patients had levels of 151-300 IU/ml, 2 patients had levels of 301-500 IU/ml, and 3 patients had levels >500 IU/ml.
AC C
Conclusions: Pregnancy is a critical time to evaluate rubella exposure. This study estimated the current incidence of rubella exposure in pregnancy to be 6.38%.
Key words: Obstetrics, pregnancy complications infectious/etiology, rubella immunology, rubella transmission, rubella virus
ACCEPTED MANUSCRIPT 5
Rubella Monitoring in Pregnancy as a Means for Evaluating a Possible Re-Emergence of
RI PT
Rubella
SC
Jill Hutton, MD, Paul Rowan, PhD, MPH, Anthony Greisinger, PhD, Melanie Mouzoon, MD
M AN U
Introduction
Rubella can cause severe disabilities in children born to mothers who contract rubella in pregnancy. After widespread vaccination in the U.S., the rate of congenital rubella diminished. Surprisingly, 9-14% of women are rubella non-immune at their first prenatal visit.[1-3] Although some of these mothers have never been vaccinated, the majority of
TE D
susceptible patients represents women with low residual titers years after vaccination. There are case reports of women with low residual titers who contract rubella in pregnancy, but this is
EP
thought to be a very infrequent event.[4-8] However, the frequency is unknown and the outcomes have not been followed and reported. Because 9-14% of pregnant women are
AC C
susceptible to rubella, and the U.S. is a very diverse nation with an influx of people from different regions of the world with varied exposures, congenital rubella is most likely under recognized in the age of vaccination. The aim of this study was to estimate the current incidence of rubella exposure in pregnancy.
ACCEPTED MANUSCRIPT 6
Materials and Methods This was a prospective, descriptive study, conducted in Houston, Texas, at The Woman's
RI PT
Hospital of Texas, a large maternity hospital with approximately 9,000-10,000 deliveries per year. Women delivering at The Woman's Hospital of Texas are typically screened for rubella immunity early in pregnancy by their individual obstetricians at their first prenatal visit. Rubella
SC
non-immunity is defined as a titer less than 10 IU/ml in the USA. Women who were rubella non-immune early in pregnancy (less than 20 weeks), as documented in their prenatal records,
M AN U
were recruited for this study and asked if they would agree, by informed consent, to be tested again for rubella immunity at the time of delivery. To be eligible for the study, rubella nonimmunity must have been documented at least 10 weeks prior to delivery. All women were recruited in the hospital during the postpartum period, within the first three days after giving
TE D
birth. There was no added risk to participants, because blood was required to be drawn in accordance with state guidelines, and some of this blood would be used to retest for rubella immunity (Siemens rubella quantitative IgG chemiluminescent EIA run on the Advia Centaur
EP
CP). The cost of the additional rubella titer was not charged to the patient. Enrolled patients
AC C
were offered routine Measles, Mumps and Rubella vaccination postpartum regardless of the study. Patients' medical treatment was not altered regardless of whether they consented to participate in the study or not. Recruitment was conducted from November 2012 to December 2013.
This study aimed to retest 300 non-immune mothers at time of delivery. The hypothesis was that if a low percentile (1 – 5%) of women converted, then the confidence intervals would be
ACCEPTED MANUSCRIPT 7
.34 – 2.90% and 3.05 – 8.08%, 95% Wilson-Score. These calculations were used to estimate the sample size beforehand; no representative sample was obtained prior to the study.
RI PT
The following were initial reasons for exclusion: deliveries without prenatal care or patients without prior documented serology, women under 18 years of age, fetal demises or deliveries less than 24-weeks. For this study, rubella exposure in pregnancy was defined as a titer rising
SC
above 40 IU/ml. This definition represents at least a 4-fold increase as rubella non-immunity is
M AN U
