Materials and Methods

This was a prospective, descriptive study, conducted in Houston, TX, at The Woman’s Hospital of Texas, a large maternity hospital with approximately 9000-10,000 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 nonimmunity is defined as a titer less than 10 IU/ml in the US. Women who were rubella nonimmune early in pregnancy (<20 weeks), as documented in their prenatal records, 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 before delivery. All women were recruited in the hospital during the postpartum period, within the first 3 days after giving 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 CP; Seimens Medical Solutions Diagnostics of Tarrytown, NY). The cost of the additional rubella titer was not charged to the patient. Enrolled patients 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 nonimmune mothers at time of delivery. The hypothesis was that if a low percentile (1-5%) of women converted, then the confidence intervals would be 0.34–2.90%, and 3.05–8.08% , 95% Wilson-Score. These calculations were used to estimate the sample size beforehand; no representative sample was obtained before the study.

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 above 40 IU/mL. This definition represents at least a 4-fold increase as rubella nonimmunity is <10 IU/mL.

Results

Among women delivering at The Women’s Hospital of Texas during the study time span, 356 met the study criteria and were invited to participate. Of these, 350 consented and 6 refused participation. During the review of data, it became apparent that we needed to exclude 52 of the 350 women for the following reasons. First, women found to be rubella nonimmune in pregnancy should be offered the rubella vaccine after delivery. A total of 39 patients were excluded because they received their second test for rubella after their postpartum rubella vaccine had been given. Another patient was excluded because she had no blood in the laboratory, other than blood drawn after she received her rubella vaccine. Second, efforts were made to be certain that women enrolled in the study were rubella nonimmune and 10 patients were excluded because their initial rubella screens were low-normal (11-14 IU/mL). Although a rubella booster may be prudent in these patients, they did not clearly meet criteria for rubella nonimmunity. Third, initially 300 patients completed the study procedures and were eligible to be included in the data set, and 21 of these patients converted from rubella nonimmune to immune. However, 2 of these patients were later excluded because their medical records had questionable written interpretations. Actual prenatal laboratory values were acquired which showed they had been immune. No other entries had such uncertainty.

After these patients were excluded, a total of 298 women were eligible to be included in the data set. Among these 298 women who were rubella nonimmune when screened earlier in pregnancy, 19 converted to immune status (IgG >40 IU/mL defined as at least a 4-fold increase) at time of delivery, which is a rate of 6.38% (95% Wilson-Score confidence interval, 4.12–9.75%). For the 19 patients who converted to immune status at time of delivery, 8 patients had levels of 40-150 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.

Patients’ ages averaged 29.7 years (range, 18-44 years), and their gestational ages at delivery averaged 38 weeks 5 days (range, 28–41 weeks). Time between rubella titers averaged 28 weeks 5 days (range, 10-36 weeks). Nine patients had early prenatal care, but the exact time between rubella titers could not be determined. There were 11 sets of twins and 1 set of triplets.

We did not have access to the infant’s charts. In reviewing maternal charts, 2 of the women who converted from rubella nonimmune to immune during pregnancy had ultrasound findings of singular fetal cardiac echogenic foci without other anomalies. One woman who remained nonimmune had fetal ultrasound findings of multiple cardiac echogenic foci and clubbed feet. The prevalence of echogenic foci is 3.6% in the general population. Isolated echogenic foci are of uncertain significance, echogenic foci with other findings may signify genetic syndromes. One woman who converted from rubella nonimmune to immune during pregnancy had fetal enlargement of the left ventricle of uncertain significance. Of the 19 mothers who converted, 1 infant was small for gestational age, 3 pregnancies had unexplained polyhydramnios, 1 pregnancy had oligohydramnios, and 1 mom had Bell’s palsy. In the 279 mothers who did not convert, there were 4 pregnancies with unexplained oligohydramnios (2 also with intrauterine growth restriction), 1 pregnancy with oligohydramnios explained by maternal chronic hypertension, 2 intrauterine growth restricted infants without oligohydramnios, 2 pregnancies with unexplained polyhydramnios, and 1 infant with fetal pyelectasis. These findings are small in number and are included for interest only.

During the study, 7 women volunteered that they had received rubella vaccinations after a recent prior delivery, most approximately 2-3 years ago. One of these patients claimed to have had the vaccine 2 and 4 years ago with both her prior children, but she remained nonimmune until she naturally converted during her third pregnancy. Of these 7 women, she was the only 1 to have converted in pregnancy. These patients were nonimmune early in their more-recent pregnancies showing nonresponses to the vaccine. Of the 7 patients who had recent vaccinations, only 1 converted in pregnancy which would not seem to be related to vaccination.

Of the 19 patients who converted from rubella nonimmune to immune in pregnancy, 11 were nulliparous and 10 had at least 1 prior child, all carried singleton pregnancies. Many of these women likely had young children undergoing their vaccination series, but this would not account for their conversion to rubella immune. A prior study examined maternal and child rubella vaccinations and showed that of 3990 nonimmune women paired with children being vaccinated, none of the women converted from nonimmune to immune.

Patients from 70 different obstetricians entered the study; 4 doctors had 1 patient convert, 3 doctors had 2 patients convert, and 3 doctors had 3 patients convert. This may show clustering of exposures.