This study was undertaken to evaluate the association between umbilical cord interleukin-6 (IL-6) levels and neonatal morbidity in infants born at less than 32 weeks' gestation.
Umbilical cord plasma ...IL-6 levels and neonatal outcomes were assessed in 309 infants born between 24 weeks and 0 days' and 31 weeks and 6 days' gestation.
Mean IL-6 levels were higher in spontaneous (n=193, 355 ± 1822 pg/mL) compared with indicated preterm births (n=116, 37 ± 223 pg/mL, P < .0001). Adjusting for gestational age, a progressive relationship was noted between increasing IL-6 levels and increased risk of neonatal systemic inflammatory response syndrome (SIRS). IL-6 levels beyond the 90th percentile (≥516.6 pg/mL) were also significantly associated with periventricular leukomalacia (PVL; odds ratio OR 15, 95% CI 2-149) and necrotizing enterocolitis (NEC; OR 6, 95% CI 1.1-33). In the multivariate analysis, an IL-6 level 107.7 pg/mL or greater (determined by receiver operating curve analysis) remained a significant independent risk factor for PVL (OR 30.3, 95% CI 4.5-203.6).
Umbilical cord IL-6 levels are higher in preterm infants born after spontaneous preterm labor or premature rupture of membranes. Elevated IL-6 levels are associated with an increased risk for SIRS, PVL, and NEC in infants born at less than 32 weeks' gestation.
To prospectively compare digital cervical score with Bishop score as a predictor of spontaneous preterm delivery before 35 weeks of gestation.
Data from a cohort of 2,916 singleton pregnancies ...enrolled in a multicenter preterm prediction study were available. Patients underwent digital cervical examinations at 22-24 and 26-29 weeks of gestation for calculation of Bishop score and cervical score. Relationships between Bishop score, cervical score, and spontaneous preterm delivery were assessed with multivariable logistic regression analysis, McNemar test, and receiver operating characteristic (ROC) curves to identify appropriate diagnostic thresholds and predictive capability.
One hundred twenty-seven of 2,916 patients (4.4%) undergoing cervical examination at 22-24 weeks had a spontaneous preterm delivery before 35 weeks. Eighty-four of the 2,538 (3.3%) reexamined at 26-29 weeks also had spontaneous preterm delivery. Receiver operating characteristic curves indicated that optimal diagnostic thresholds for Bishop score were at least 4 at 22-24 weeks, at least 5 at 26-29 weeks, and less than 1.5 at both examinations for cervical score. At 22-24 weeks, areas under the ROC curve favored Bishop score. At 26-29 weeks, there was no significant difference in areas under the ROC curve; however, a cervical score less than 1.5 (sensitivity 35.7%, false positive rate 4.8%) was superior to a Bishop score of 5 or more (P<.001).
Both cervical evaluations are associated with spontaneous preterm delivery in a singleton population; however, predictive capabilities for spontaneous preterm delivery were modest among women with low event prevalence. Although Bishop score performed better in the mid trimester, by 26-29 weeks a cervical score less than 1.5 was a better predictor of spontaneous preterm delivery before 35 weeks than a Bishop score of at least 5.
To determine the population effectiveness of a city-wide perinatal HIV prevention program.
An anonymous surveillance of newborn cord blood for HIV serology and nevirapine (NVP).
All 10 public-sector ...delivery centers in Lusaka, Zambia participated. All mother-infant pairs delivering during the 12-week surveillance period at the participating centers and who received antenatal care at a public-sector facility in Lusaka were included in the study. The main outcome measure was population NVP coverage, defined as the proportion of HIV-infected women and HIV-exposed infants in the population that ingested NVP.
Of 8787 women in the surveillance population, 7204 (82%) had been offered antenatal HIV testing, of which 5149 (71%) had accepted, and of which 5129 (99%) had received a result. Overall, 2257 of 8787 (26%) were cord seropositive. Of the 1246 (55%) cord blood seropositive women who received an antenatal HIV test result, 1112 (89%) received a positive result; the other 134 comprise seroconverters and clerical errors. Only 751 of 1112 (68%) women who received a positive antenatal test result and a NVP tablet for ingestion at labor onset had NVP detected in the cord blood (i.e., maternal non-adherence rate was 32%). A total of 675 infants born to 751 adherent mothers (90%) received NVP before discharge. Thus, only 675 of 2257 (30%) seropositive mother-infant pairs in the surveillance population received both a maternal and infant dose of NVP.
Successful perinatal HIV prevention requires each mother-infant pair to negotiate a cascade of events that begins with offering HIV testing and continues through adherence to the prescribed regimen. This novel surveillance demonstrates that failures occur at each step, resulting in reduced coverage and diminished program effectiveness.
Objective: We sought to evaluate the association between prior spontaneous preterm delivery and subsequent pregnancy outcome.
Study Design: A total of 1711 multiparous women with singleton gestations ...were prospectively evaluated at 23 to 24 weeks’ gestation. Prior pregnancies were coded for the presence or absence of a prior spontaneous preterm delivery. If a prior spontaneous preterm delivery had occurred, the gestation of the earliest prior delivery (13-22, 23-27, 28-34, and 35-36 weeks’ gestation) was recorded. Current gestations were categorized as spontaneous preterm delivery at <28, <30, <32, <35, or <37 weeks’ gestation. The risk of spontaneous preterm delivery in the current gestation was determined on the basis of the occurrence, gestational age, and cause of the earliest prior spontaneous preterm delivery.
Results: The incidences of spontaneous preterm delivery before 28, 30, 32, 35, and 37 weeks’ gestation were 0.8%, 1.1%, 1.9%, 5.1%, and 11.9%, respectively. Those with a prior spontaneous preterm delivery carried a 2.5-fold increase in the risk of spontaneous preterm delivery in the current gestation over those with no prior spontaneous preterm delivery (21.7% vs 8.8%;
P ≤ .001). Gravid women with an early prior spontaneous preterm delivery (23-27 weeks’ gestation) had a higher risk of recurrent spontaneous preterm delivery (27.1% vs 8.8%;
P ≤ .001). Prior spontaneous preterm delivery was more closely associated with subsequent early spontaneous preterm delivery at <28 weeks’ gestation (relative risk, 10.6) than for spontaneous preterm delivery overall (relative risk, 2.5). An early prior spontaneous preterm delivery (23-27 weeks’ gestation) was most highly associated with early spontaneous preterm delivery (<28 weeks’ gestation) in the current gestation (relative risk, 22.1). The relationship between prior spontaneous preterm delivery and current outcome was not as strong for those with a very early spontaneous preterm delivery (13-22 weeks’ gestation). Prior spontaneous preterm delivery caused by preterm premature rupture of the membranes and preterm labor was significantly associated with similar outcomes in the current gestation (
P < .001).
Conclusion: Prior spontaneous preterm delivery is highly associated with recurrence in the current gestation. An early prior spontaneous preterm delivery is more predictive of recurrence and is most highly associated with subsequent early spontaneous preterm delivery. (Am J Obstet Gynecol 1999;181:1216-21.)
Infants of women with lower education levels are at higher risk for perinatal mortality.
We explored the impact of training birth attendants and pregnant women in the Essential Newborn Care (ENC) ...Program on fresh stillbirths (FSBs) and early (7-day) neonatal deaths (END) by maternal education level in developing countries.
A train-the-trainer model was used with local instructors in rural communities in six countries (Argentina, Democratic Republic of the Congo, Guatemala, India, Pakistan, and Zambia). Data were collected using a pre-/post-active baseline controlled study design.
A total of 57,643 infants/mothers were enrolled. The follow-up rate at 7 days of age was 99.2%. The risk for FSB and END was higher for mothers with 0-7 years of education than for those with ≥8 years of education during both the pre- and post-ENC periods in unadjusted models and in models adjusted for confounding. The effect of ENC differed as a function of maternal education for FSB (interaction p = 0.041) without evidence that the effect of ENC differed as a function of maternal education for END. The model-based estimate of FSB risk was reduced among mothers with 0-7 years of education (19.7/1,000 live births pre-ENC, CI: 16.3, 23.0 vs. 12.2/1,000 live births post-ENC, CI: 16.3, 23.0, p < 0.001), but was not significantly different for mothers with ≥8 years of education, respectively.
A low level of maternal education was associated with higher risk for FSB and END. ENC training was more effective in reducing FSB among mothers with low education levels.
Objective: Our goal was to identify risk factors for the development of preeclampsia in nulliparous women enrolled in a multicenter trial comparing calcium supplementation to a placebo.
Study Design: ...A total of 4589 women from five centers was studied. Analysis of risk factors for preeclampsia was performed in 4314 who carried the pregnancy to >20 weeks. Baseline systolic and diastolic blood pressure, demographic characteristics, and findings after randomization were examined for the prediction of preeclampsia. Preeclampsia was defined as hypertension (diastolic blood pressure ≥90 mm Hg on two occasions 4 hours to 1 week apart) and proteinuria (≥300 mg/24 hours, a protein/creatinine ratio ≥0.35, one dipstick measurement ≥2+ or two dipstick measurements ≥1+ at an interval as specified for diastolic blood pressure).
Results: Preeclampsia developed in 326 women (7.6%). The first analysis treated each risk factor as a categoric variable in a univariate regression. Maternal age, blood group and Rh factor, alcohol use, previous abortion or miscarriage, private insurance, and calcium supplementation were not statistically significant. Risk factors initially found to be significant were body mass index, systolic blood pressure, diastolic blood pressure, non-white race (African-American and other), clinical center, and smoking. Adjusted odds ratios computed with a Iogistic regression model revealed that body mass index (odds ratio 3.22 for ≥35 kg/m
2 vs <19.8 kg/m
2), systolic blood pressure (odds ratio 2.66 for ≥120 vs <101 mm Hg), diastolic blood pressure (odds ratio 1.72 for ≥61 mm Hg vs <60 mm Hg), and clinical center (odds ratio 1.85 for Memphis vs the other clinical centers) were statistically significant predictors of preeclampsia. Results of the final model fit revealed that preeclampsia risk increases significantly (
p < 0.0001) with increased body mass index at randomization, as well as with increased systolic and diastolic blood pressure at randomization. Calcium supplementation had no effect on the risks posed by body mass index and blood pressure. Among risk factors developing after randomization, an abnormal result of a glucose screen (plasma glucose ≥140 mg/dl 1 hour after a 50 gm glucose challenge) was not found to be associated with a significant risk of preeclampsia.
Conclusion: These risk factors should be of value in counseling women regarding preeclampsia and should aid in understanding the pathophysiologic characteristics of this syndrome.
Objective Periodontal disease may increase the risk of adverse birth outcomes; however, results have been mixed. Few studies have examined periodontal disease in developing countries. We describe the ...relationship between periodontal disease and birth outcomes in a community setting in Pakistan. Study Design This was a prospective cohort study. Enrollment occurred at 20-26 weeks of gestation. A study dentist performed the periodontal examination to assess probing depth, clinical attachment level, gingival index, and plaque index. Outcomes included stillbirth, neonatal death, perinatal death, <32 weeks preterm birth, 32-36 weeks preterm birth, and low birthweight and are presented for increasing periodontal disease severity by quartiles. Results Dental examinations and outcome data were completed for 1152 women: 81% of the women were multiparous, with a mean age of 27 years; 33% of the women had no education. Forty-seven percent of the women had dental caries; 27% of the women had missing teeth, and 91% of the women had had no dental care in the last year. Periodontal disease was common: 76% of the women had ≥3 teeth with a probing depth of ≥3 mm; 87% of the women had ≥4 teeth with a clinical attachment level of ≥3 mm; 56% of the women had ≥4 teeth with a plaque index of 3; and 60% of the women had ≥4 teeth with a gingival index of 3. As the measures of periodontal disease increased from the 1st to 4th quartile, stillbirth and neonatal and perinatal death also increased, with relative risks of approximately 1.3. Early preterm birth increased, but the results were not significant. Late preterm birth and low birthweight were not related to measures of periodontal disease. Conclusion Pregnant Pakistani women have high levels of moderate-to-severe dental disease. Stillbirth and neonatal and perinatal deaths increased with the severity of periodontal disease.
Preterm delivery is the primary cause of perinatal mortality in the United States. To date, no effective means of preventing spontaneous preterm delivery has been identified. At least in some cases, ...however, microbial colonization of the fetal membranes or the amniotic fluid, or alterations in the vaginal flora such as are seen in patients with bacterial vaginosis, have been associated with spontaneous labor and preterm delivery.
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We undertook a prospective, double-blind trial to address three questions. First, does antimicrobial therapy reduce the incidence of preterm delivery in women at risk for preterm delivery? Second, does antimicrobial therapy reduce the . . .
Objective: The Preterm Prediction Study evaluated 28 potential biologic markers for spontaneous preterm birth in asymptomatic women at 23 to 24 weeks gestational age. This analysis compares those ...markers individually and in combination for an association with spontaneous preterm birth at <32 and <35 weeks gestational age. Study Design: With the use of a nested case-control design from an original cohort study of 2929 women, results of tests from 50 women with a spontaneous preterm birth at <32 weeks and 127 women with a spontaneous preterm birth at <35 weeks were compared with results from matched-term control subjects. Results: In the univariate analysis, the most potent markers that are associated with spontaneous preterm birth at <32 weeks by odds ratio were a positive cervical-vaginal fetal fibronectin test (odds ratio, 32.7) and <10th percentile cervical length (odds ratio, 5.8), and in serum, >90th percentiles of α-fetoprotein (odds ratio, 8.3) and alkaline phosphatase (odds ratio, 6.8), and >75th percentile of granulocyte colony-stimulating factor (odds ratio, 5.5). Results for spontaneous preterm birth at <35 weeks were generally similar but not as strong. Univariate and multivariate logistic regression analyses demonstrated little interaction among the tests in their association with spontaneous preterm birth. Combinations of the 5 markers were evaluated for their association with <32 weeks spontaneous preterm birth. Ninety-three percent of case patients had at least 1 positive test result versus 34% of control subjects (odds ratio, 24.0; 95% CI, 6.4-93.4). Among the case patients, 59% had ≥2 positive test results versus 2.4% of control subjects (odds ratio, 56.5; 95% CI, 7.1-451.7). If a cutoff of 3 positive test results was used, 20% of case patients and none of the control subjects had positive test results (P <.002). With the use of only the 3 serum tests (alkaline phosphatase, α-fetoprotein, and granulocyte colony-stimulating factor), any positive test identified 81% of cases versus 22% of control subjects (odds ratio, 14.7; 95% CI, 5.0-42.7). For spontaneous preterm birth at <35 weeks gestation, any 2 positive tests identified 43% of cases and 6% of control subjects (odds ratio, 11.2; 95% CI, 4.8-26.2). Conclusion: Overlap among the strongest biologic markers for spontaneous preterm birth is small. This suggests that the use of tests such as maternal serum α-fetoprotein, alkaline phosphatase, and granulocyte colony-stimulating factor as a group or adding their results to fetal fibronectin test and cervical length test results may enhance our ability to predict spontaneous preterm birth and that the development of a multiple-marker test for spontaneous preterm birth is feasible. (Am J Obstet Gynecol 2001;185:643-51.)
There are limited data relating folate nutritional status of mothers during pregnancy to mental and psychomotor development of their offspring. Using an existing data set from a study on the effect ...of prenatal zinc supplementation on child neurodevelopment, we evaluated the association between folate nutritional status of mothers during pregnancy and neurodevelopment of their children.
Maternal blood folate and total homocysteine (tHcy) concentrations were measured at 19, 26, and 37 weeks of gestation. At a mean of 5.3 years of age, 355 black children with low-socioeconomic background were given 6 tests: Differential Ability Scales, Visual and Auditory Sequential Memory, Knox Cube Test, Gross Motor Scale, and Grooved Pegboard. The scores of the tests between the 2 groups of mothers with poor versus adequate folate nutritional status classified by blood folate or tHcy concentrations were compared.
There were no differences in the test scores of neurodevelopment between the 2 groups.
Folate nutritional status of mothers in the later half of pregnancy assessed by plasma and erythrocyte folate and plasma tHcy concentrations had no impact on neurodevelopment of their children at age 5. It is unknown whether our findings in a low-socioeconomic population can be readily extrapolated to other populations.
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