https://orcid.org/0000-0002-6028-8451
ABSTRACT
Background: The infection of rubella in pregnancy is worrisome due to the fact that it causes miscarriages, congenital defects, and Congenital Rubella Syndrome (CRS). The purpose of this study was to determine the status of Rubella IgG antibody levels both during the antenatal and postnatal periods among pregnant women nonimmune to rubella and the incidence of exposure to rubella in pregnancy.
Methods: This was a prospective cohort study that included 4770 pregnant, who attended the obstetric clinics and delivered in Women’s Specialized Hospital, King Fahad Medical City, between January and December 2015. The study utilized the following measures for rubella screening tests (IgG and IgM) during the antenatal and postnatal period. Pregnant women with recent rubella infection (IgM antibody positive), history of rubella infection, or had immunity against rubella (IgG antibody concentration ≥10 IU/ml) were excluded from the study.
Results: The prevalence of pregnant women nonimmune to rubella was 6.3% (n = 301). The majority (93.7%) were immune (IgG antibody concentration ≥10 IU/ml). No patients tested positive for rubella (IgM +ve). Overall, The Median (IQR) Rubella (IgG) in the antenatal period (6.3 (8.30–5.00) IU/m) was significantly less in comparison to the postnatal period (5.0 (6.40–5.00) IU/m). The difference was statistically significant, p <.001.
Conclusion: There is a significant decrease in the Rubella (IgG) titer between antenatal and postpartum periods, and we report a very low incidence of rubella infection and CRS among pregnant women nonimmune to rubella.
Introduction
Rubella is a virus from the Togaviridae family.Citation1,Citation2 It is also known as German Measles.Citation1,Citation2 The transmission of this illness is by direct contact or by droplet transmission. Rubella infection is usually asymptomatic. It can cause mild illness, which is characterized by low-grade fever, rash, fatigue, and lymphadenopathy, and 50% of infections are typically subclinical.Citation1,Citation2
The infection of rubella in pregnancy is worrisome since it causes severe disabilities in the unborn fetus. During antenatal visits, all pregnant women are tested for immunity to rubella. It is well known that rubella infection, especially in the first trimester, causes miscarriages, congenital defects, and Congenital Rubella Syndrome (CRS). It is a constellation of birth defects which, includes hearing loss, cataract, congenital heart defects, and microcephaly. The risk of congenital malformations is highest before 12 weeks of pregnancy.Citation3,Citation4
The introduction of the vaccine and its widespread use has reduced the rubella infection significantly.Citation5–7 It is quite surprising that 9–14% of women in the United States are nonimmune at their first prenatal visit.Citation5–7 The presence of IgG antibodies means immunity has been received through either vaccination or past infection.
In Saudi Arabia, 91.6% of pregnant women are rubella immune.Citation8 However, it has been seen that the number of pregnant women nonimmune to rubella has not decreased since the introduction of vaccination in school girls since 1978. The reemergence of Measles and Pertussis and the high incidence of rubella non-immunity in the prenatal period is a substantial factor in focusing on the reemergence of Rubella infection. Thus, we wanted to assess if the reemergence of Rubella became prevalent among our pregnant and postpartum women. We chose to determine the status of Rubella IgG antibody titer between antenatal and postnatal period among pregnant women nonimmune to rubella and the incidence of exposure to rubella in pregnancy.
Material and methods
Data sources and study population
An analytical prospective cohort study was carried out, which included all pregnant women who attended Women’s Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia, were enrolled in this study between January and December 2015. We examined the rubella screening tests between 6 and 20 weeks of pregnancy (antenatal) and within 24 hours after the delivery (postnatal). A test dose of 5 ml of blood samples was collected from pregnant women by venipuncture. The study utilized the following measures for rubella screening tests, IgG and IgM rubella antibody titer levels were detected by immunoassay method (chemiluminescence test, Abbott Alinity I). The rubella IgG and IgM levels were run on the same day. (Samples with IgG antibody concentration ≥10 IU/ml were regarded as immune while samples <10 IU/ml were considered as nonimmune). Pregnant women with recent rubella infection (IgM antibody positive), history of rubella infection, or previous immunity against rubella (IgG antibody concentration ≥10 IU/ml) were excluded from the study.
Data were collected from the perinatal database, which consists of information collected uniformly according to predefined criteria immediately after delivery by an obstetrician. Coding is done after assessing the medical prenatal care records and the routine hospital documents. We analyzed the following characteristics: maternal age, gravidity (number of pregnancies), parity (number of deliveries), and the number of abortions (before 24 weeks of gestation or weighing < 500 grams). In addition, we investigated preterm labor (defined as birth before 37 completed weeks of gestation) or term (more than 37 weeks). A detailed history of exposure to rubella or recent infection was recorded during antenatal followed up. Enrolled patients were offered routine Measles, Mumps, and Rubella vaccination postpartum if they were nonimmune.
The primary outcome measure was to identify the association of Rubella IgG Antibody titer between antenatal and postnatal period among pregnant women nonimmune to rubella, and the incidence of exposure to rubella in pregnancy.
Statistical analyzes
All Categorical variables such as gestational age, parity, gravida, abortion and number of miscarriages presented as numbers and percentages. Non-parametric tests used when data were skewed by using Kolmogorov Smirnov test. Whereas continuous variables such as antenatal and postnatal rubella expressed as median and interquartile range (IQR). The Mann Whitney U test was applied to compare the differences between antenatal and postnatal rubella titers with respect to study characteristics. Whereas for the paired data; Wilcoxon Sign test to find the difference between antenatal and postnatal rubella titers. P – value less than 0.05 was considered statistically significant. All data entered and analyzed through statistical package SPSS 22 (SPSS Inc., Chicago, IL, USA).
Ethical approval
Ethical approval for this study was granted by the Institutional review board in king Fahad medical city (14–305). (December 07, 2014, and reactivated on May 09, 2019).
Results
During the study period between January to December 2015, there were around 4770 deliveries in our institute. 301 pregnant women were confirmed as nonimmune to rubella, with a prevalence of 6.3%. The majority (93.7%) were immune to rubella (IgG antibody concentration ≥10 IU/ml). None of the patients tested positive for rubella (IgM +ve).
Patient clinical characteristics are shown in (). Most of the participants (57.8%, n = 174) were younger than 30 years. Regarding the gravidity, the majority of cases were (≥ 3) (52.5%, n = 158), whereas the parity was less than three in 74.1% (n = 223) of the pregnant women. History of miscarriages was reported in 95 (31.6%) participants. Regarding the Gestational age at delivery, the majority of cases were a term (94%, n = 283), whereas preterm delivery was reported in 18 (6%) cases. The Median Interquartile Range (IQR) of antenatal rubella (IgG) titer was 6.3 (8.30–5.00) IU/m, whereas postnatal rubella (IgG) titer was 5.0 (6.40–5.00) IU/m.
Table 1. Clinical characteristics of pregnant nonimmune to rubella (n = 301)
The association between Antenatal Rubella (IgG) and the studied factors among pregnant women nonimmune to rubella are presented in (). Pregnant women with age of less than 30 years have a Median (IQR) Rubella (IgG) of (6.30 (8.30–5.00) IU/m) compared with (6.20 (8.20–5.00) IU/m) in an age more than 30 years during the antenatal period. The difference was not statistically significant, p = .815. Similarly, Rubella (IgG) titer in the antenatal period among the patients who delivered preterm (5.00 (8.40–5.00)) IU/m or term (6.30 (8.30–5.00)) IU/m, (p = .397). It is evident that no statistically significant results were found among all study parameters.
Table 2. Association between antenatal rubella (IgG) titer and the studied factors among pregnant nonimmune to rubella
From , it is evident that the postnatal rubella (IgG) titer was not statistically significant among all study parameters. Postnatal rubella (IgG) titer was reported by (5.00 (6.22–5.00) IU/m) of pregnant women age (<30) years, compared to (5.00 (6.70–5.00) IU/m) in age (>30) years (p = 0.082). About (5.00 (5.90–5.00) IU/m) of postnatal rubella (IgG) titer was reported in preterm deliveries, compared to (5.00 (6.40–5.00) IU/m) in term deliveries. This was not statistically significant (p = .216).
Table 3. Association between postnatal rubella (IgG) titer and the studied factors among pregnant nonimmune to rubella
shows the difference in Rubella (IgG) titer between antenatal and postnatal periods among pregnant women nonimmune to rubella. The Median (IQR) Rubella (IgG) in the antenatal period (6.3 (8.30–5.00) IU/m) was significantly less in comparison to the postnatal period (5.0 (6.40–5.00) IU/m). The difference was statistically significant, p < .001.
Table 4. Comparative analysis of antenatal and postnatal rubella (IgG) titer among pregnant nonimmune to rubella
Discussion
Rubella virus can cause a variety of congenital defects when a pregnant woman gets exposed to it, particularly in the early gestational weeks. In Saudi Arabia, routine screening is performed during the antenatal visit for rubella IgG antibody during the first antenatal visit, and postnatal vaccination for women nonimmune to rubella is given. However, universal postpartum immunization is not recommended in all countries due to it is an expense on the payors.Citation9
The result of this study revealed a Rubella virus seroprevalence rate of 93.7% among pregnant women who delivered in our institute. The prevalence rate in the developing countries ranges between 32% and 95.3%.Citation10 In addition, some immigrants from the Balkans, North and Central Africa, and Southern Asia have high rates of rubella susceptibility, and they are at high risk for delivering infants affected by CRS. We report a low incidence of rubella infection and CRS among the women who attended antenatal and postnatal in our clinics, and this is likely due to the vigilant vaccination program at a national level.
A vaccination program that is implemented plays an essential role in decreasing the circulation of the virus in the community. Consequently, the fact that 6.3% of these women were nonimmune may have been because of the absence of the vaccination, an incomplete antibody response, or a decline in the antibodies over time. The best time to detect any risk associated with CRS would be early in pregnancy. In this study, we did not find any pregnant women with positive rubella, nor were any affected by CRS. However, The IgM test can lead to false-positive results in patients with other active infections (parvovirus or mononucleosis) or rheumatoid factor.Citation11 In contrast, during the years 2001 to 2004, only five infants with CRS were reported in the USA.Citation12
Importantly, this study found that antenatal and postnatal rubella (IgG) titer among pregnant women nonimmune to rubella did not show any statistically significant differences when the study parameters such as maternal age, gravidity, parity, and gestational age at delivery were compared. Maternal age had proved to be an influencing factor among Indian women since the Rubella (IgG) titer in those pregnant women increased.Citation13 Also, In Jordan,Citation14 the immunity rate to rubella was significantly lower in women aged 15–19 years (83%) compared with women aged 40–49 years (92.2%). On the other hand, Alsibiani SACitation8 stressed an important point that the immunity rate among women decreased significantly and progressively with increasing age, and older Saudi women had a potentially increased risk for CRS.
In the present study, Rubella (IgG) titers levels dropped between antenatal and postpartum decreased significantly. There are several factors to be considered to elicit the importance of these findings among the current population. The immune system is one of the most important systems protecting the mother and preventing damage to the fetus. It is during pregnancy when the maternal immune system is characterized by a reinforced network of recognition, communication, trafficking, and repair; it is able to raise the alarm, if necessary, to maintain the well-being of the mother and the fetus. On the other side is the fetus that provides a developing active immune system that will modify the way the mother responds to the environment, providing the uniqueness of the immune system during pregnancy. Therefore, it is appropriate to refer to pregnancy as a unique immune condition that is modulated, but not suppressed.Citation15 The postpartum immunization strategy is an opportunity to protect women during reproductive age, and to increase vaccination coverage against rubella and other vaccine preventable diseases. As it is a live virus vaccine, Adult women of childbearing age should be counseled to avoid pregnancy for at least four weeks after receiving the MMR vaccine.Citation16
The limitations of our study were that it was limited to Women’s Specialized Hospital, and information extracted from the charts was incomplete, particularly regarding babies’ data (the neonatal intensive care unit admission, early neonatal death, developmental assessment) and umbilical artery Doppler during pregnancy. Health education during antenatal visits needs to be enhanced and should provide information, education, and counseling about this disease. This information might aid physicians in guiding their patients and taking optimal clinical decisions together for the benefit of both the child and the mother.
Conclusion
There is a significant decrease in the Rubella (IgG) titer between antenatal and postpartum periods and we report a very low incidence of rubella infection and CRS among pregnant women nonimmune to rubella.
Abbreviations
| CRS | = | Congenital Rubella Syndrome. |
| IgG | = | Immunoglobulin G |
| IgM | = | Immunoglobulin M |
| IU/ml | = | International Units Per Milliliter |
| IQR | = | Interquartile range |
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
Contributors
All authors have contributed to conception and design of the study, drafting the article, revising it critically for important intellectual content. All authors have approved the final article
Ethical approval
Ethical approval for this study was granted by the Institutional review board in king Fahad medical city (14-305). (December 07, 2014 and reactivated on May 09, 2019).
Additional information
Funding
References
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