Mark A. Klebanoff

Trichomonas vaginalis associated with Low birth weight and preterm delivery

Background: Several studies have suggested that pregnant women infected with Trichomonas vaginalis may be at increased risk of an adverse outcome. Goal: To evaluate prospectively the association between T. vaginalis and risk of adverse pregnancy outcome in a large cohort of ethnically diverse women. Study Design: At University‐affiliated hospitals and antepartum clinics in five United States cities, 13,816 women (5,241 black, 4,226 Hispanic, and 4,349 white women) were enrolled at mid‐gestation, tested for T. vaginalis by culture, and followed up until delivery. Results: The prevalence of T. vaginalis infection at enrollment was 12.6%. Race‐specific prevalence rates were 22.8% for black, 6.6% for Hispanic, and 6.1% for white women. After multivariate analysis, vaginal infection with T. vaginalis at mid‐gestation was significantly associated with low birth weight (odds ratio 1.3; 95% confidence interval 1.1 to 1.5), preterm delivery (odds ratio 1.3; 95% confidence interval 1.1 to 1.4), and preterm delivery of a low birth weight infant (odds ratio 1.4; 95% confidence interval 1.1 to 1.6). The attributable risk of T. vaginalis infection associated with low birth weight in blacks was 11% compared with 1.6% in Hispanics and 1.5% in whites. Conclusions: After considering other recognized risk factors including co‐infections, pregnant women infected with T. vaginalis at mid‐gestation were statistically significantly more likely to have a low birth weight infant, to deliver preterm, and to have a preterm low birth weight infant. Compared with whites and Hispanics, T. vaginalis infection accounts for a disproportionately larger share of the low birth weight rate in blacks.

Trial of calcium to prevent preeclampsia

Background Previous trials have suggested that calcium supplementation during pregnancy may reduce the risk of preeclampsia. However, differences in study design and a low dietary calcium intake in the populations studied limit acceptance of the data. Methods We randomly assigned 4589 healthy nulliparous women who were 13 to 21 weeks pregnant to receive daily treatment with either 2 g of elemental calcium or placebo for the remainder of their pregnancies. Surveillance for preeclampsia was conducted by personnel unaware of treatment-group assignments, using standardized measurements of blood pressure and urinary protein excretion at uniformly scheduled prenatal visits, protocols for monitoring these measurements during the hospitalization for delivery, and reviews of medical records of unscheduled outpatient visits and all hospitalizations. Results Calcium supplementation did not significantly reduce the incidence or severity of preeclampsia or delay its onset. Preeclampsia occurred in 158 of the 2295 wome...

Risk factors for preeclampsia, abruptio placentae, and adverse neonatal outcomes among women with chronic hypertension

Background Women with chronic hypertension who become pregnant have an increased risk of preeclampsia and adverse neonatal outcomes. However, within this group, the risk factors for these adverse events are not known. Methods We analyzed data on outcomes for 763 women with chronic hypertension enrolled in a multicenter trial of low-dose aspirin for the prevention of preeclampsia. Preeclampsia was defined as new-onset proteinuria (urinary protein excretion, ≥300 mg per 24 hours) in the 682 women without proteinuria at base line. It was defined according to strict clinical criteria in the 81 women who had proteinuria at base line. The end points were maternal and neonatal outcomes. Results Among the 763 women, 193 (25 percent) had preeclampsia. The frequency of preeclampsia was not affected by the presence of proteinuria at base line (27 percent among women with proteinuria, vs. 25 percent among those without it), but it was greater in women who had had hypertension for at least four years (31 percent vs. 2...

Maternal Cytokine Levels during Pregnancy and Adult Psychosis

We investigated levels of maternal cytokines in late pregnancy in relation to the subsequent development of adult schizophrenia and other psychoses in their offspring. The sample included the mothers of 27 adults with schizophrenia and other psychotic illnesses and 50 matched unaffected controls from the Providence cohort of the Collaborative Perinatal Project. Serum samples were analyzed for interleukin 1 beta (IL-1-beta), interleukin 2 (IL-2), interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor alpha (TNF-alpha) by enzyme immunoassay. Maternal levels of TNF-alpha were significantly elevated among the case series (t = 2.22, p =.04), with evidence of increasing odds of psychosis in relation to higher cytokine levels. We did not find significant differences between case and control mothers in the serum levels of IL-1, IL-2, IL-6, or IL-8. These data support previous clinical investigations reporting maternal infections during pregnancy as a potential risk factor for psychotic illness among offspring.

Use of Multiple Imputation in the Epidemiologic Literature

The authors attempted to catalog the use of procedures to impute missing data in the epidemiologic literature and to determine the degree to which imputed results differed in practice from unimputed results. The full text of articles published in 2005 and 2006 in four leading epidemiologic journals was searched for the text imput. Sixteen articles utilizing multiple imputation, inverse probability weighting, or the expectation-maximization algorithm to impute missing data were found. The small number of relevant manuscripts and diversity of detail provided precluded systematic analysis of the use of imputation procedures. To form a bridge between current and future practice, the authors suggest details that should be included in articles that utilize these procedures.

Bacterial Vaginosis Assessed by Gram Stain and Diminished Colonization Resistance to Incident Gonococcal, Chlamydial, and Trichomonal Genital Infection

BACKGROUND We sought to assess the relationship between bacterial vaginosis (BV) assessed by Gram stain and incident trichomonal, gonococcal, and/or chlamydial genital infection. METHODS This longitudinal study included 3620 nonpregnant women aged 15-44 years who presented for routine care at 12 clinics in Birmingham, Alabama. Participants were assessed quarterly for 1 year. Vaginal smears were categorized by the Nugent Gram stain score (0-3, normal; 4-6, intermediate state; 7-10, BV). Pooled logistic regression was used to estimate the hazard ratios for the comparison of trichomonal, gonococcal, and chlamydial infection incidence in participants by Nugent score at the prior visit. Participants were censored at their first visit with a positive test result for trichomonal, gonococcal, and/or chlamydial infection. RESULTS Of the 10,606 eligible visits, 37.96% were classified by BV and 13.3% by positive detection of trichomonal, gonococcal, and/or chlamydial infection. An intermediate state or BV at the prior visit was associated with a 1.5-2-fold increased risk for incident trichomonal, gonococcal, and/or chlamydial infection (adjusted hazard ratio [AHR] for intermediate state, 1.41 [95% confidence interval {CI}, 1.12-1.76]; AHR for BV, 1.73 [95% CI, 1.42-2.11]; P= .058 for trend). Estimates were similar for trichomonal-only, gonococcal-only, and chlamydial-only infection outcomes. CONCLUSION BV microbiota as gauged by Gram stain is associated with a significantly elevated risk for acquisition of trichomonal, gonococcal, and/or chlamydial genital infection.

Vulvovaginal symptoms in women with bacterial vaginosis.

OBJECTIVE: A substantial, but highly variable, percentage of women with bacterial vaginosis are said to be asymptomatic. The purpose of this study was to estimate the prevalence of symptoms among women with bacterial vaginosis compared with women without bacterial vaginosis by direct, explicit, and detailed questioning of these women. METHODS: Women presenting for a routine health care visit at 12 health department clinics in Birmingham, Alabama, were recruited to participate in a longitudinal study of vaginal flora. At the first visit, they underwent a pelvic examination, lower genital tract microbiological evaluation, and an interview that included detailed questions regarding lower genital tract symptoms. The prevalence of symptoms among women with and without bacterial vaginosis (Gram stain score 7 or higher) was compared. RESULTS: Among 2,888 women without gonorrhea, Chlamydia, or trichomonas, 75% of women with and 82% of women without bacterial vaginosis never noted any vaginal odor in the past 6 months (P < .001). The corresponding values were 63% and 65% for never noting vaginal “wetness” (P = .02); 58% and 57% for vaginal discharge (P = .65); 91% and 86% for irritation (P = .004); 88% and 85% for itching (P = .64); and 96% and 94% for dysuria (P = .002), respectively. Cumulatively, 58% of women with bacterial vaginosis noted odor, discharge, and/or wetness in the past 6 months compared with 57% of women without bacterial vaginosis (P = .70). CONCLUSION: The 2 classic symptoms of bacterial vaginosis discharge and odor are each reported by a minority of women with bacterial vaginosis and are only slightly more prevalent than among women without bacterial vaginosis. LEVEL OF EVIDENCE: II-3

Obstetric determinants of neonatal survival: Influence of willingness to perform cesarean delivery on survival of extremely low-birth-weight infants

OBJECTIVE Our purpose was to evaluate the relationship between the approach to obstetric management and survival of extremely low-birth-weight infants. STUDY DESIGN In this prospective observational study we evaluated 713 singleton births of infants weighing < or = 1000 gm during 1 year at the 11 tertiary perinatal care centers of the National Institutes of Child Health and Human Development network of maternal-fetal medicine units. Major anomalies, extramural delivery, antepartum stillbirth, induced abortion, and gestational age < 21 weeks were excluded. The obstetricians opinion of viability and willingness to perform cesarean delivery in the event of fetal distress were ascertained from the medical record or interview when documentation was unclear. Grade 3 and 4 intraventricular hemorrhage, grade 3 and 4 retinopathy of prematurity, necrotizing enterocolitis requiring surgery, oxygen dependence at discharge or 120 days, and seizures were considered serious morbidity. Survival without serious morbidity was considered intact survival. Logistic regression was used to evaluate the influence of the approach to obstetric management, adjusted for birth weight, growth, gender, presentation, and ethnicity. RESULTS Willingness to perform cesarean delivery was associated with increased likelihood of both survival (adjusted odds ratio 3.7, 95% confidence interval 2.3 to 6.0) and intact survival (adjusted odds ratio 1.8, 95% confidence interval 1.0 to 3.3). Willingness to intervene for fetal indications appeared to virtually eliminate intrapartum stillbirth and to reduce neonatal mortality. Below 800 gm or 26 weeks, however, willingness to perform cesarean delivery was linked to an increased chance of survival with serious morbidity. Although obstetricians were willing to intervene for fetal indications in most cases by 24 weeks, willingness to perform cesarean delivery was associated with twice the risk for serious morbidity at that gestational age. CONCLUSIONS The approach to obstetric management significantly influences the outcome of extremely low-birth-weight infants. Above 800 gm or 26 weeks the obstetrician should usually be willing to perform cesarean delivery for fetal indications. Between 22 and 25 weeks willingness to intervene results in greater likelihood of both intact survival and survival with serious morbidity. In these cases patients and physicians should be aware of the impact of the approach to obstetric management and consider the likelihood of serious morbidity and mortality when formulating plans for delivery.

Estimated effect of 17 alpha-hydroxyprogesterone caproate on preterm birth in the United States

OBJECTIVE: A multicenter, randomized placebo-controlled trial among women with singleton pregnancies and a history of spontaneous preterm birth found that weekly injections of 17 alpha-hydroxyprogesterone caproate (17P), initiated between 16 and 20 weeks of gestation, reduced preterm birth by 33%. The current study estimated both preterm birth recurrence and the potential reduction in the national preterm birth rate. METHODS: Using 2002 national birth certificate data, augmented by vital statistics from 2 states, we estimated the number of singleton births delivered to women eligible for 17P through both a history of spontaneous preterm birth and prenatal care onset within the first 4 months of pregnancy. The number and rate of recurrent spontaneous preterm births were estimated. To predict effect, the reported 33% reduction in spontaneous preterm birth attributed to 17P therapy was applied to these estimates. RESULTS: In 2002, approximately 30,000 recurrent preterm births occurred to women eligible for 17P, having had a recurrent preterm birth rate of 22.5%. If 17P therapy were delivered to these women, nearly 10,000 spontaneous preterm births would have been prevented, thereby reducing the overall United States preterm birth rate by approximately 2%, from 12.1% to 11.8% (P < .001), with higher reductions in targeted groups of eligible pregnant women. CONCLUSION: Use of 17P could reduce preterm birth among eligible women, but would likely have a modest effect on the national preterm birth rate. Additional research is urgently needed to identify other populations who might benefit from 17P, evaluate new methods for early detection of women at risk, and develop additional prevention strategies. LEVEL OF EVIDENCE: III

The risk of childhood cancer after neonatal exposure to vitamin K.

Background Two recent studies have found that infants who received intramuscular vitamin K were at twice the expected risk for cancer during childhood. Since nearly all newborns in the United States receive this drug, the public health implications of this association, if confirmed, would be substantial. Methods We examined the relation between vitamin K and cancer in a nested case-control study that used data from the Collaborative Perinatal Project, a multicenter, prospective study of pregnancy, delivery, and childhood. Among 54,795 children born from 1959 through 1966, 48 cases of cancer were diagnosed after the first day of life and before the eighth birthday. Each case child was matched with five randomly selected controls whose last study visit occurred at or after the age when the case childs cancer was diagnosed. Exposure to vitamin K was determined from study forms and medical records. Results Vitamin K had been administered to 68 percent of the 44 case children and 71 percent of the 226 control...