Faculty Bibliography

OBJECTIVE:To examine whether acute and chronic respiratory diseases are associated with an increased risk of spontaneous premature rupture of the membranes (PROM). METHODS:We used the 1993-2004 National Hospital Discharge Survey data of singleton deliveries in the USA (N = 41 250 539). The International Classification of Diseases Ninth Revision was utilized to identify acute (acute upper respiratory diseases, viral/bacterial pneumonia, and acute bronchitis/bronchiolitis) and chronic (chronic bronchitis and asthma) respiratory conditions and spontaneous PROM. All analyses were adjusted for potential confounders. RESULTS:The incidence of PROM was 5%, and rates of acute and chronic respiratory conditions were 2.1 and 9.5 per 1000 pregnancies, respectively. Chronic bronchitis was associated with a reduced risk of PROM (RR 0.39, 95% CI 0.31, 0.48). Asthma was significantly associated with PROM at preterm (RR 1.15, 95% CI 1.14, 1.17) and term (RR 1.27, 95% CI 1.23, 1.30). Stratification by race showed that acute upper respiratory disease was associated with preterm PROM in whites (RR 1.90, 95% CI 1.71, 2.11) and blacks (RR 6.76, 95% CI 5.67, 8.07). Viral/bacterial pneumonia was associated with preterm PROM in blacks and term PROM in both races. Asthma was associated with term PROM in blacks but not whites. CONCLUSIONS:Acute respiratory diseases and asthma during pregnancy are associated with spontaneous PROM, with substantially stronger association among blacks than whites. We speculate that timely diagnosis and treatment, coupled with closely mentoring of pregnant women may help reduce the rate of PROM and associated complications.

OBJECTIVE:Most women in their first pregnancy are at 'unknown' risk for preterm birth. We hypothesized that such women may be at an increased risk for preterm birth in comparison to those with a prior term birth. METHODS:We used Missouri's maternally-linked data (1989-97), comprised of women delivering their first singleton live birth (N = 259 431) and women delivering their first two consecutive singleton live births (N = 154 810). We compared preterm birth (<37 weeks) rates among women with a previous term birth, women with no reproductive history (primiparous women), and in those with a previous preterm birth. Risks of spontaneous and medically indicated preterm birth were also examined after adjustments for confounders through multivariate log-binomial regression models. RESULTS:Preterm birth rates were 8.1%, 9.6%, and 23.3% among women with a previous term birth, among primiparous women, and among those with a previous preterm birth, respectively. In comparison to women with a prior term birth, risks of spontaneous preterm birth among primiparous women and among women with a prior preterm birth were 1.1-fold (95% confidence interval (CI) 1.0, 1.2) and 2.5-fold (95% CI 2.4, 2.6) higher, respectively. These risks were higher for medically indicated preterm birth among both primiparous women (RR 1.3, 95% CI 1.2, 1.4) and those with a prior preterm birth (RR 3.2, 95% CI 3.0, 3.5) than for spontaneous preterm births. CONCLUSIONS:Primiparous women are at increased risk of both medically indicated and spontaneous preterm birth. The findings suggest that studies on preterm birth should consider a risk assignment to include three groups: low-risk (prior term birth), intermediate risk (primiparity), and high-risk (prior preterm birth). This strategy will be informative for the identification of women with impending risk of delivering preterm, and complications associated with prematurity.

OBJECTIVE: To test the hypothesis that the presence of preeclampsia, small for gestational age (SGA)-birth, and placental abruption in the first pregnancy confers increased risk in the second pregnancy. METHODS: A retrospective cohort study entailing a case-crossover analysis was performed based on women who had two consecutive singleton live births (n=154,810) between 1989 and 1997 in Missouri. Small for gestational age was defined as infants with birth weight below the 10th centile for gestational age. Risk and recurrence of ischemic placental disease was assessed from fitting logistic regression models after adjusting for several confounders. RESULTS: Preeclampsia in the first pregnancy was associated with significantly increased risk of preeclampsia (odds ratio 7.03, 95% confidence interval 6.51, 7.59), SGA (odds ratio 1.16, 95% confidence interval 1.06, 1.27), and placental abruption (odds ratio 1.90, 95% confidence interval 1.51, 2.38) in the second pregnancy. Similarly, women with SGA and abruption in the first pregnancy were associated with increased risks of all other conditions in the second pregnancy. CONCLUSION: Women with preeclampsia, SGA, and placental abruption in their first pregnancy--conditions that constitute ischemic placental disease--are at substantially increased risk of recurrence of any or all these conditions in their second pregnancy. Although causes of these conditions remain largely speculative, these entities may manifest through a common pathway of ischemic placental disease with significant risk of recurrence.

PROBLEM/OBJECTIVE:Data regarding cervical interleukin 18 (IL-8) and IL-10 concentrations during pregnancy is limited. METHOD OF STUDY/METHODS:This was a cross sectional study of healthy pregnant women. Specimens were collected from the cervical os secretions. IL-8 and IL-10 levels were measured by using enzyme-linked immunosorbent assay. Median (range) cytokine concentrations were derived for each trimester and compared across trimesters. The relationship between gestational age and cytokine levels was assessed by regression analysis. The mean of the ratios of IL-8 to IL-10 was compared in each trimester using anova. RESULTS:The median (range) IL-8 concentrations in cervical secretions were in pg/mL: 1562 (1210-4100), 2460 (1047-4688), 3660 (1451-4748) (P < 0.0021); the median (range) IL-10 concentrations in cervical secretions were in pg/mL: 38.3 (6.8-227.9), 10.9 (0-263.3), 9.5 (0-35.6); the mean IL10/IL-8 x 100 (+/- standard deviation) concentrations were: 3.33 +/- 0.65, 1.47 +/- 0.41, 0.38 +/- 0.52 (P = 0.0035) during the first, second and third trimesters, respectively. CONCLUSION/CONCLUSIONS:The patterns of cervical IL-8 concentration is inversely related to gestational age, and the ratio of IL-10/IL-8 decreases with advancing gestation.

Preterm birth (<37 weeks) complicates 12.5% of all deliveries in the USA, and remains the leading cause of perinatal mortality and morbidity, accounting for as many as 75% of perinatal deaths. Despite the recent temporal increase in preterm birth, efforts to understand the problem of prematurity have met with little success. This may be attributable to the under-appreciation of the etiologic heterogeneity of preterm birth as well as the heterogeneity in its underlying clinical presentations--spontaneous onset of labor, preterm premature rupture of membranes, and medically indicated preterm birth. In this paper, we review data regarding preterm births with particular focus on its incidence, temporal trends, and recurrence. Studies of births from the USA indicate that the recent temporal increase in the overall preterm birth rate is driven by an impressive concomitant increase in medically indicated preterm birth. However, the largest temporal decline in perinatal mortality has also occurred among medically indicated preterm births (relative to other clinical subtypes), suggesting that these obstetric interventions at preterm gestational ages are associated with a reduction in perinatal mortality. Recent data indicate that spontaneous preterm birth is not only associated with increased recurrence of spontaneous, but also medically indicated, preterm birth, and vice versa. This suggests that the clinical subtypes may share common underlying etiologies. Since medically indicated preterm birth accounts for as many as 40% of all preterm births, efforts to understand the reasons for such interventions and their impact on short- and long-term morbidity in newborns is compelling. Further research is necessary in order to understand the mechanisms and etiology of preterm birth, thus leading to the possibility of effective preventive or therapeutic strategies.

OBJECTIVE: This study was undertaken to determine the accuracy of our previously published and prospectively validated institution-specific singleton transcerebellar diameter (TCD) nomogram in the prediction of gestational age (GA) in twin pregnancies. We further evaluated whether the prediction of GA in twin gestations using the singleton TCD nomogram differs between monochorionic and dichorionic twins. STUDY DESIGN: In our previously published studies, we retrospectively constructed a cross-sectional nomogram using TCD measurements in 24,026 well-dated, singleton fetuses, and prospectively validated the nomogram using 2,597 singleton fetuses. The current study comprised of 1,278 well-dated twins (19.6% monochorionic) seen in our ultrasound unit between August 1994 and May 2003, and the singleton TCD nomogram was validated in these twin gestations. The actual GA was subtracted from the GA predicted by the TCD nomogram and the concordance between actual and predicted GAs was assessed on the basis of the Pearson's correlation coefficient (r). This was performed separately for monochorionic and dichorionic twins. RESULTS: Concordance between the actual and predicted twin TCD measurements based on our previously published singleton TCD nomogram was high (Pearson's correlation, r = 0.95, P < .0001). Between 16 and 23 weeks' gestation, the predicted mean GA was within 6 days of actual GA. Between 24 and 30 weeks, the predicted mean GA was within 3 days, and at 32 weeks or more, the predicted mean GA was within 5 days of the actual GA. Prediction of GA based on the singleton TCD nomogram was equally accurate in both monochorionic and dichorionic twin gestations (P = .686). CONCLUSION: This study demonstrates that our previously validated singleton TCD nomogram is reliable and accurate in twins irrespective of placental chorionicity.

OBJECTIVE:The objective of the study was to evaluate the extent to which maternal and fetal conditions necessitate medically indicated preterm birth. STUDY DESIGN/METHODS:A population-based, retrospective, cohort study of women who delivered a singleton live birth at 20 weeks or longer in Missouri, 1989 to 1997 was performed (n = 684,711). Maternal-fetal conditions that necessitated iatrogenic preterm birth included preeclampsia, small-for-gestational-age birth, fetal distress, placental abruption, placenta previa, unexplained vaginal bleeding, pregestational and gestational diabetes, renal disease, Rh sensitization, and congenital malformations. We examined the association between each of the aforementioned conditions and risk of medically indicated preterm birth at less than 35 weeks. Medically indicated preterm birth was defined as a labor induction or a prelabor cesarean in the absence of premature rupture of membranes at preterm gestations. Adjusted relative risk with 95% confidence interval for preterm birth was derived from multivariable logistic regression models, and population attributable fractions were calculated. RESULTS:The preterm birth rate (less than 35 weeks) was 4.6% (n = 31,238), with 23.5% (n = 7,347) of such births being medically indicated. Preeclampsia, fetal distress, small-for-gestational-age, and placental abruption were the most common indications for a medical intervention resulting in preterm birth, with at least 1 of these conditions present in 53.2% of medically indicated preterm births and in 17.7% of term births (relative risk 4.9, 95% confidence interval 4.7, 5.2). CONCLUSION/CONCLUSIONS:Preeclampsia, fetal distress, small-for-gestational-age, and placental abruption, conditions that are associated with ischemic placental disease, are implicated in well over half of all medically indicated preterm births. Although the etiology of preterm birth is heterogeneous, it is reasonable that ischemic placental disease may serve as an important pathway to preterm birth.

OBJECTIVE:This study was undertaken to examine the associations between maternal respiratory diseases and placental abruption. STUDY DESIGN/METHODS:A population-based, retrospective cohort study was conducted to examine the associations between maternal respiratory diseases and abruption in the United States. Data on women who delivered singleton births (n = 37,314,022) were derived from the National Hospital Discharge Survey for the years 1993 to 2003. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes were used to identify pregnant women hospitalized for acute upper respiratory diseases, viral and bacterial pneumonia, acute bronchitis, and acute bronchiolitis, chronic bronchitis, asthma, and abruption. Relative risk (RR) and 95% CI were derived from multivariable logistic regression models to evaluate the associations after adjusting for maternal age, race, marital status, smoking, cocaine use, adequacy of prenatal care, maternal insurance status, geographic location, and year of birth (although data on smoking and cocaine use are likely underreported). RESULTS:The rate of abruption was 9.7 per 1,000 singleton births. The overall rate for acute respiratory conditions was 2.2 per 1000 pregnancies. Acute upper respiratory diseases (RR 3.2, 95% CI 3.0-3.4) and viral/bacterial pneumonia (RR 2.2, 95% CI 1.9-2.4) were associated with abruption. The rate of chronic respiratory conditions was 9.0 per 1,000 pregnancies. Chronic bronchitis was strongly associated with abruption (RR 31.8, 95% CI 29.6-34.3), but the association between asthma and abruption was modest (RR 1.1, 95% CI 1.0-1.2). Stratified analysis by maternal race showed that asthma was associated with abruption among black women but not white women. CONCLUSION/CONCLUSIONS:Pregnancies complicated by acute and chronic respiratory diseases requiring hospitalization are associated with placental abruption.

OBJECTIVE:Despite the increased tendency of preterm birth to recur, little is known with regard to recurrence risks for spontaneous and medically indicated preterm birth as well as recurrence risks in relation to severity of preterm birth. We examined the recurrence of spontaneous and medically indicated preterm birth. STUDY DESIGN/METHODS:A population-based, retrospective cohort study of births in Missouri (1989 to 1997) was carried out with analyses restricted to women who delivered their first 2 consecutive singleton live births (n = 154,809). Women who experienced spontaneous onset of labor and subsequently delivered preterm (less than 35 weeks) were classified as spontaneous preterm birth. Medically indicated preterm birth included women who delivered preterm through a labor induction or a prelabor cesarean delivery. Risk and odds ratio of preterm birth recurrence were derived from fitting multivariate conditional logistic regression models after adjusting for potential confounders. RESULTS:If the first pregnancy resulted in a spontaneous preterm birth, then affected women were more likely to deliver preterm spontaneously (adjusted odds ratio 3.6, 95% confidence interval 3.2, 4.0) and also as a medically indicated preterm birth (odds ratio 2.5, 95% confidence interval 2.1, 3.0) in the second birth. Similarly, if the first pregnancy resulted in a medically indicated preterm birth, affected women were 10.6-fold (95% confidence interval 10.1, 12.4) more likely to deliver preterm because of medical indications in the second pregnancy as well as preterm spontaneously (odds ratio 1.6, 95% confidence interval 1.3, 2.1). The greatest risk of recurrence of preterm birth in the second pregnancy tended to occur around the same gestational age as preterm birth in the first pregnancy, regardless of the clinical subtype. CONCLUSION/CONCLUSIONS:The observation that spontaneous preterm birth is not only associated with increased recurrence of spontaneous but also medically indicated preterm birth and vice versa, suggests that the 2 clinical subtypes may share common etiologies.

OBJECTIVE:To estimate whether the acid-base status of neonates born to women with meconium-stained amniotic fluid varies across gestation. METHODS:We carried out a retrospective cohort study of all pregnancies that were complicated by meconium-stained amniotic fluid in 2004. Cases were identified from a perinatal pathology database that contained data on all pregnancies complicated by meconium-stained amniotic fluid. Data abstracted from the charts included gestational age at delivery, umbilical arterial pH, birth weight, and the presence or absence of labor. Cases were stratified according to gestational age at delivery. The distribution of meconium-stained amniotic fluid across gestation was computed. The mean umbilical arterial pH values (with 95% confidence intervals) across gestation were assessed by analysis of variance. RESULTS:The mean umbilical arterial pH in women with meconium-stained amniotic fluid did not differ across gestation. The overall incidence of meconium-stained amniotic fluid was 12.0% (766 of 6,403 deliveries). The rates of meconium-stained amniotic fluid increased from 1.2% at 32 weeks to 100% at 42 weeks. CONCLUSION/CONCLUSIONS:The rising incidence of meconium-stained amniotic fluid with gestational age is consistent with the hypothesis that fetal maturation is a major etiologic factor in meconium passage. Also, the lack of variation of mean umbilical arterial pH across gestation suggests that fetal acidemia is not increased when meconium passage occurs earlier in pregnancy rather than at later gestational ages.