We analyzed 41,692 NCPP mother-child pairs for whom information about prenatal care and child outcomes were available. The data on exposure to maternal UTIs were recorded in the medical record and coded (month and year). The clinical diagnosis was supported by laboratory tests and recorded by the attending physician. The diagnoses of mental retardation or developmental delay were based on standardized scores on the Stanford-Binet Intelligence Scale Form L-M, which was administered to children aged 4 years in the NCPP data set.20 Children with scores lower than 70 were classified as having mental retardation.
Information about fetal deaths was available for the NCPP; however, these data were limited by the late entry into the study. Only a small number of women entered the NCPP study in the first trimester, so first trimester terminations were not available. The case definition for fetal death was death occurring before and up to birth. We included neonatal deaths (deaths during the first 28 days of life) in our analysis; some infections occurred late in pregnancy, and the deaths did not occur until the postnatal period. A 35-day critical period following the date of infection was used to allow for detection of either a fetal death at the monthly prenatal examination or spontaneous fetal loss.
We analyzed the data with chi-square tests, logistic regression modeling, and survival analysis procedures using SAS software (SAS Institute, Cary, NC). Chi-square tests were used to compare the distribution of independent variables to the 2 outcome variables (death and mental retardation or developmental delay). The woman’s age when the infant was born, infant birth weight, infant sex, maternal education, gestational age at study entry, and race were considered potential confounders. When the final logistic regression models were developed to measure the impact of exposure to maternal UTI on the relative risk for mental retardation or developmental delay compared with survivors without mental retardation or developmental delay, the control variables were woman’s age at the time of the birth of the infant, infant birth weight, and race. This was based on standard data-based variable selection procedures. We conducted survival analysis using Cox proportional hazard models by applying Lifetest and PHreg Procedures from SAS.
Results
Demographics and other baseline characteristics of the NCPP mother-child pairs are shown in Table 1. The mother and child characteristics reflect the study entry criteria of an equal proportion of black and white participants from poor economic environments. More than half the women had less than a high school education, and 13.4% of the infants were born weighing less than 2500 g. The fetal death rate was 1.9%, and the UTI rate was 15.6%.
The overall risk for mental retardation in the children of pregnant women with UTI was 16% higher than for women without a UTI Table 2. The only trimester that indicated a statistically significant increased risk was the third trimester (relative risk [RR]=1.40; 95% confidence interval [CI], 1.01-1.95). Because of late entry into the NCPP study, there were only 8 mothers with UTI in the first trimester who had infants with MR; thus, this estimate of risk was unstable. Also, we did not have treatment data for the NCPP group.
Table 3 shows the death risk associated with UTI exposure. There was a two-fold increased overall risk for death (RR=2.02; 95% CI, 1.32-3.07) when the fetus was exposed to a maternal UTI. Survival analysis was used to predict the risk for death 35 days after exposure to maternal UTI when taking into account the interaction of time and the UTI exposure. When the actual time of exposure is taken into account, the relative hazard was 1.41 (95% CI, 1.07-1.76) in the second trimester and 2.23 (95% CI, 1.40-3.55) in the third trimester.
Discussion
Our analyses suggest that maternal UTIs are associated with MR and fetal death in the third trimester. The NCPP study recruited poor women, and 56% had less than a high school education. The infant birth weight proportions are similar to those reported nationally in 1970, with the low birth weight proportion 7.9% for all races and 13.9% for blacks.26 Analyses of more highly educated women with different access to care would be required to ascertain whether this result is reproducible in other population groups. Support for the observed associations are strengthened, however, by the consistency between these data and the more recent analysis of women and children funded by Medicaid in South Carolina during 1994 to 1996.24
We analyzed the relationship between maternal UTI and mental retardation or developmental delay using logistic regression models for both the NCPP and Medicaid. The Medicaid data included information about whether a prescription for antibiotics was filled following the diagnosis of a UTI. Thus, in the Medicaid data set we were able to identify women who probably did and did not have treatment following the diagnosis. In the NCPP and the Medicaid models we determined the risk for mental retardation or developmental delay in children after controlling for gestational age at entry into the study, maternal age, maternal race, and birth weight. These confounders control for the effect of factors already known to be associated with both the exposure and the outcome, and are not believed to be in the causal pathway. The Medicaid data revealed an increased relative risks for mental retardation or developmental delay of 1.47 (95% CI, 1.08-2.01) in the first trimester and an RR of 1.42 (95% CI, 1.12-1.81) in the third trimester, when there was no documentation of an antibiotic prescription being filled. When medication prescriptions were filled there were no increased risks for mental retardation or developmental delay.