The Centers for Disease Control and Prevention estimate that 2 million lower genital tract infections (LGTI) occur each year among pregnant women in the United States.1 LGTI may be associated with adverse pregnancy outcomes (APO). Most studies evaluating the association of LGTI and APO recruited women after the first trimester of pregnancy and predominantly from antenatal care settings.2–6
Pregnant women may elect to seek care for LGTI in family planning clinics, emergency departments, and public sexually transmitted diseases (STD) clinics for a variety of reasons.7–9 Approximately 350 pregnant women attend Baltimore City STD clinics each year.10 STD clinics provide care for underserved and uninsured populations with higher rates of sexually transmitted infections (STIs) and substance abuse than the general population.11–13 As such, risk factors from antenatal care settings may not generalize to STD clinic populations. We characterized the antenatal care patterns and evaluated the association of LGTI and APO among a high-risk inner city STD clinic population.
MATERIALS AND METHODS
We conducted a retrospective electronic medical record review of pregnant women age 13 to 49 years who attended Baltimore City STD clinics between 1996 and 2002, a period for which complete electronic records were available. Routine clinical data collected included demographics, STI history, risk behaviors, symptoms, physical examination and laboratory findings, and treatment. Data were maintained in an electronic medical record system. All women who sought clinic services and either identified themselves as pregnant or had a positive urine pregnancy test (Wampole Laboratories, Princeton, NJ) were included if they were tested for bacterial vaginosis (BV), Neisseria gonorrhea (NG), early syphilis (ES), Trichomonas vaginalis (TV), and Chlamydia trachomatis (CT). Laboratory testing for these infections was done routinely and described elsewhere.10,14–15 Treatment for each infection was dispensed at no cost.
Personal identifying information from the 1531 pregnant women meeting inclusion criteria were submitted to the Maryland Department of Hygiene and Mental Health Vital Statistics Administration. Identifiers included the following: first name, last name, date of birth, and social security number. We used DataFlux dfPower Studio 6.2 (SAS Inc, Cary, NC) software to match birth records for live births occurring in the State of Maryland from 1996 to 2003 within 12 months of the STD clinic visit.
We used a case-control study design to test the associations of each of the 5 treatable LGTI and pregnancy outcomes independently using multiple logistic regression analyses in Stata software (Stata Version 9.1, Stat Corp, College Station, TX). APOs of interest included the following: (1) preterm birth (delivery of a newborn <37 weeks gestational age) and (2) low birth weight (<2500 g) of any gestational age. Term delivery of a low birth weight infant was used as a proxy for intrauterine growth restriction. Gestational age was determined by clinical estimate of gestation as recorded on the birth certificate. Cases were defined as women who delivered a live singleton newborn with an APO. Controls were women who delivered a live singleton newborn without an APO. We compared LGTI prevalence between cases and controls. We used Student t test for continuous variables and χ2 test and logistic regression for categorical variables to compare risk factors between groups.
We controlled for potential predictors of APO and LGTI including the following information obtained from birth record data: maternal education (completion of tertiary level education) and marital status (married/nonmarried), parity, history of termination or preterm delivery of newborn, maternal weight gain, medical disease complicating pregnancy (e.g., hypertension, diabetes, anemia, maternal genital herpes present at time of delivery, mother febrile at delivery), maternal use of tobacco, timing of initiation of antenatal care, number of antenatal visits, and abnormal conditions of the newborn (e.g., congenital anomalies, fetal alcohol syndrome, meconium aspiration). Following are other potential predictors obtained from STD clinic data: maternal age and race, prior history of STI, other LGTI diagnosed at STD clinic visit (BV, CT, NG, TV, ES, HIV, genital herpes, and genital warts), trimester of pregnancy at time of infection (determined by date of STD clinic visit), and maternal use of alcohol and illicit drugs (cannabis, cocaine, and intravenous drugs). Only risk factors associated with LGTI diagnosed at STD clinic visit or any APO found to be marginally significant (P ≤ 0.10) in simple logistic regression analyses were included in the multivariate logistic regression models. Multivariate logistic regression models tested the association of individual LGTI (BV, CT, NG, TV, ES) with each APO.
This protocol was approved by the institutional review boards of the participating institutions.
Matched live birth records were identified for 805 of the 1531 women (52.6%). We excluded women with multiple births (N = 17), with more than one pregnancy during the study period (N = 37), and those without recorded birth weight or gestational age (N = 21), for a final sample of 730 women with singleton live births. All matched birth records occurred within the expected range of time based on date of maternal STD clinic visit.
Overall Characteristics of the Population
Characteristics of the cases, controls, and the pregnant women who were unmatched and excluded from this analysis are summarized in Table 1. The 730 women were predominantly black between the ages of 13 and 24 years. Most were in their first trimester of pregnancy (62%) when they attended the STD clinic. Women attended the STD clinic in their third trimester because they were symptomatic or because they were a contact to someone known to have a STI. Typical symptoms reported were vaginal discharge, abdominal pain, genital itching, or genital irritation/odor. Approximately half of the symptomatic women attended the STD clinic ≥10 days after onset of symptoms. Prevalence of LGTIs was high: 13.8% CT, 7.1% NG, 14.9% TV, 30.1% BV, and 18.0% of women had concomitant LGTIs, most often coinfection with BV. Similarly, prevalence of APO was high: 18.9% preterm birth, 4.2% very preterm birth (<32 weeks gestation), 16.0% low birth weight, and 2.9% very low birth weight (birth weight: <1500 g). Twenty-four percent of low birth weight newborns were delivered at term.
Patterns of Antenatal Care
Most women received antenatal care early in pregnancy and care was typically provided by a hospital clinic or private medical office. Seven percent of women (54/730) had either missing information or reported no antenatal care on the birth record. This was associated with a greater than 2-fold increase in odds of both preterm birth (adjusted odds ratio [aOR]: 2.70, 95% confidence interval [CI]: 1.47–4.97) and low birth weight (aOR: 2.58, 95% CI: 1.33–5.00), after adjustment for maternal age (Table 2). The number of antenatal visits was known for most women (640/730) and each additional antenatal visit reduced the odds of delivering a preterm birth or low birth weight newborn by approximately 10% (Table 2). Pregnant women who attended the STD clinic during the same trimester as initiation of antenatal care had 65% lower odds of experiencing an APO independent of trimester of antenatal care initiation (Table 2).
The Associations Between LGTI and APO
Recent maternal use of any alcohol, tobacco, and cocaine was associated with having an APO, but after adjustment for LGTI prevalence, the effects of these behaviors were no longer significant and they were not included in the final models (Table 2). Maternal age and medical disease complicating pregnancy were both associated with a greater than 2-fold increased odds of preterm birth and low birth weight and were included in the final models (Table 2).
We observed a 2-fold increased odds of preterm birth associated with NG diagnosed at clinic visit (Table 2). In analyses stratified by timing of STI diagnosis, this association was strengthened if NG was diagnosed in the first trimester of pregnancy (aOR: 2.95, 95% CI: 1.30–6.70). No other LGTI were found to be associated with preterm birth.
CT was associated with delivery of a low birth weight newborn (aOR: 2.09, 95% CI: 1.01–4.24). The odds doubled when restricting the analysis to women with term delivery of a low birth weight newborn (proxy for intrauterine growth restriction) (aOR: 4.61, 95% CI: 1.47–14.44). We did not find a significant effect of timing of STI diagnosis with CT.
In this study, diagnosis of NG and CT was associated with delivery of a preterm and low birth weight newborn, respectively, confirming reports from antenatal care clinics.6,16–18 Not all studies, however, have reported these associations.4,19 The etiology of NG-associated preterm birth is hypothesized to be related to maternal cytokine response to infection, premature rupture of membranes, and increased fetal production of corticotropin-releasing hormone.20–22 Recent in vitro studies suggest that CT may cause intrauterine growth retardation through chlamydial heat shock protein 60-induced placental apoptosis in the setting of persistent infection.23–26
An intriguing finding in our study is the apparent association between timing of GC infection and the risk of APO. GC infection diagnosed in the first trimester of pregnancy increased the likelihood of preterm birth as compared with infections diagnosed later in pregnancy (no association in later trimesters). This suggests that timing of infection during pregnancy may be an important determinant of outcome, and that the effectiveness of GC screening may be dependent on timing. This finding may also explain some of the discrepant results observed among the various studies, and suggests that timing of screening and treatment is an important factor to be considered when evaluating the association between LGTI and APO.
Our study has several limitations. The low matching rate may have reduced our ability to detect differences in associations with other LGTIs. Possible reasons for the low matching rate include spontaneous and therapeutic terminations of pregnancy as well as false or changed identifier information. Approximately one-third of pregnant women with matched live birth records had a previous termination of pregnancy and most unmatched women were not aware of their pregnancy when they sought care at the STD clinic. In addition, many had used contraceptives in the 30 days before STD clinic visit; therefore, it is possible that either spontaneous or therapeutic pregnancy termination in this group led to unmatched birth records. Information obtained at STD clinic visit was an assessment at one point in time. Women may have acquired new STIs or received treatment for STIs in the time from STD clinic until time of delivery, and this might have an effect on our study results, particularly, if this information led to misclassification or under-adjustment for confounding variables.
Pregnant women attending public STD clinics represent a high-risk population. They have elevated rates of illicit drug use, unprotected sex, and LGTI, including GC and CT that increased their risk for APO. Most of these women, however, reported attending antenatal care clinics and, from our data, prompt and frequent antenatal care reduced the likelihood of having an APO. Attending both the STD clinic and antenatal care in the same trimester of pregnancy, irrespective of gestational age, was also associated with reduced APO. These data suggest that comprehensive clinic-based interventions targeting pregnant women who seek care at STD clinics, such as enhanced case and partner management, facilitation of communication with the patient's antenatal care provider, and enrollment in substance abuse treatment programs should be developed and studied as they may have a significant positive impact on pregnancy outcomes.
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