Anthony M. Vintzileos

Epidemiology of preterm birth and its clinical subtypes

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.

Trends in preterm birth and perinatal mortality among singletons : United states, 1989 through 2000

OBJECTIVE: Despite the recent increase in preterm birth in the United States, trends in preterm birth subtypes have not been adequately examined. We examined trends in preterm birth among singletons following ruptured membranes, medical indications, and spontaneous preterm birth and evaluated the impact of these trends on perinatal mortality. METHODS: A population-based, retrospective cohort study comprising 46,375,578 women (16% blacks) who delivered singleton births in the United States, 1989 through 2000, was performed. Rates of preterm birth (< 37 weeks), their subtypes, and associated perinatal mortality (stillbirths at ≥ 22 weeks plus neonatal deaths within 28 days), before and after adjustment for potential confounders, were derived from ecological logistic regression models. RESULTS: Preterm birth rates increased by 14% (95% confidence interval 13–15%) among whites from 8.3% to 9.4% and decreased by 15% (95% confidence interval 14–16%) among blacks from 18.5% to 16.2% between 1989 and 2000. Among whites, preterm birth following ruptured membranes declined by 23%, medically indicated preterm birth increased by 55%, and spontaneous preterm birth increased by 3%. Among blacks, preterm birth following ruptured membranes declined by 37%, medically indicated preterm birth increased by 32%, and spontaneous preterm birth decreased by 27%. The largest decline in perinatal mortality among whites was associated with increases in medically indicated preterm birth, whereas the largest decline in perinatal mortality among blacks was associated with declines in preterm birth following ruptured membranes and spontaneous preterm birth. CONCLUSION: Temporal trends in preterm birth varied substantially based on underlying subtype and maternal race. The recent increase in medically indicated preterm birth was associated with a favorable reduction in perinatal mortality. LEVEL OF EVIDENCE: II-2

The association of placenta previa with history of cesarean delivery and abortion: A metaanalysis

OBJECTIVE Our purpose was to determine the incidence of placenta previa based on the available epidemiologic evidence and to quantify the risk of placenta previa based on the presence and number of cesarean deliveries and a history of spontaneous and induced abortion. STUDY DESIGN We reviewed studies on placenta previa published between 1950 and 1996 on the basis of a comprehensive literature search with use of MEDLINE and by identifying studies cited in the references of published reports. Studies were chosen for inclusion in the metaanalysis if the incidence of placenta previa and its cross-classification with either prior cesarean delivery or abortions (both spontaneous and induced) or both were available. We also extracted details about the study design (case-control or cohort study) and place where they were conducted (United States or other countries). Published case reports dealing with placenta previa and studies relating to abruptio placentae were excluded from this review. We also restricted the search to studies published in English. No attempts were made to locate any unpublished studies. Data from studies identified during the literature search were reviewed and abstracted by a single author. In case of discrepancies or when the information presented in a study was unclear, abstraction by a (blinded) second reviewer was sought to resolve the discrepancy. RESULTS Data on the incidence of placenta previa and its associations with previous cesarean delivery and abortions were abstracted. Subgroup analyses were performed to identify potential sources of heterogeneity by study design and place where they were conducted. Statistical methods used for the metaanalysis included the fixed-effects logistic regression model, whereas potential sources of heterogeneity among studies were evaluated by fitting random-effects models. The tabulation of 36 studies identified a total of 3.7 million pregnant women, of whom 13,992 patients were diagnosed with placenta previa. The reported incidence of placenta previa ranged between 0.28% and 2.0%, or approximately 1 in 200 deliveries. Women with at least one prior cesarean delivery were 2.6 (95% confidence interval 2.3 to 3.0) times at greater risk for development of placenta previa in a subsequent pregnancy. The results varied by study design, with case-control studies showing a stronger relative risk (relative risk 3.8, 95% confidence interval 2.3 to 6.4) than cohort studies did (relative risk 2.4, 95% confidence interval 2.1 to 2.8). Four studies, encompassing 170,640 pregnant women, provided data on the number of previous cesarean deliveries. These studies showed a dose-response pattern for the risk of previa on the basis of the number of prior cesarean deliveries. Relative risks were 4.5 (95% confidence interval 3.6 to 5.5) for one, 7.4 (95% confidence interval 7.1 to 7.7) for two, 6.5 (95% confidence interval 3.6 to 11.6) for three, and 44.9 (95% confidence interval 13.5 to 149.5) for four or more prior cesarean deliveries. Women with a history of spontaneous or induced abortion had a relative risk of placenta previa of 1.6 (95% confidence interval 1.0 to 2.6) and 1.7 (95% confidence interval 1.0 to 2.9), respectively. Substantial heterogeneity in the results of the metaanalysis was noted among studies. CONCLUSION There is a strong association between having a previous cesarean delivery, spontaneous or induced abortion, and the subsequent development of placenta previa. The risk increases with number of prior cesarean deliveries. Pregnant women with a history of cesarean delivery or abortion must be regarded as high risk for placenta previa and must be monitored carefully. This study provides yet another reason for reducing the rate of primary cesarean delivery and for advocating vaginal birth for women with prior cesarean delivery.

Incidence of Placental Abruption in Relation to Cigarette Smoking and Hypertensive Disorders During Pregnancy: A Meta-Analysis of Observational Studies

OBJECTIVE To systematically review the literature and summarize the relationship between cigarette smoking and placental abruption, and to evaluate the joint influences of smoking and hypertensive disorders (chronic hypertension and preeclampsia) on the subsequent development of abruption. DATA SOURCES We reviewed studies identified through a MEDLINE literature search between 1966 and 1997 and through studies cited in the references of published reports. METHODS OF STUDY SELECTION A total of 13 observational (seven case-control and six cohort) studies were identified which included a total of 1,358,083 pregnancies. We excluded case reports on placental abruption, and restricted the literature search to studies published in English. A meta-analysis was performed by computing pooled odds ratios based on random-effects models describing the association between placental abruption, smoking, and hypertensive disorders. Potential sources of heterogeneity among these studies were explored in detail. TABULATION, INTEGRATION, AND RESULTS The overall incidence of placental abruption was 0.64% (8724 of 1,358,623). Smoking was associated with a 90% increase in the risk of placental abruption (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.8, 2.0). This pattern was consistent by study design (case-control compared with cohort studies) and smoking prevalence (low compared with high prevalence, defined as less than 30% compared with 30% or more, respectively). However, the association was significantly (p < .001) stronger among the seven studies conducted outside the United States (OR 2.1, 95% CI 2.0, 2.2), compared with the six studies conducted in the United States (OR 1.6, 95% CI 1.5, 1.8). Pooled population attributable risk percentage for each stratum ranged between 15% and 25%, implying that 15-25% of placental abruption episodes are attributable to cigarette smoking. Data on the dose-response relationship between number of cigarettes smoked per day and the risk of abruption indicate that the OR increased with increasing number of cigarettes smoked. Furthermore, a meta-analysis of the joint effects of smoking and hypertension during pregnancy on the development of abruption identified two published studies, including 102,609 pregnancies. In the presence of smoking, the risk of abruption was further increased due to chronic hypertension, mild or severe preeclampsia, or chronic hypertension with superimposed preeclampsia. CONCLUSION Our meta-analyses showed an increased risk for placental abruption in relation to both cigarette smoking and hypertensive disorders during pregnancy. Because cigarette smoking is a modifiable risk factor, and hypertensive disorders are potentially treatable if diagnosed early in pregnancy, patient education, smoking cessation programs, and early prenatal care may be important factors in the prevention of placental abruption.

The Fetal Biophysical Profile and Its Predictive Value

Six fetal biophysical variables--the nonstress test, fetal movements, fetal breathing movements, fetal tone, amniotic fluid volume, and placental grading (biophysical profile)--were assessed in 150 high-risk pregnancies during a 30-minute observation period. The predictive value of the nonstress test alone, biophysical scoring, and contraction stress test alone in the identification of the healthy fetus as well as the fetus in jeopardy are discussed. The relationships between individual variables and combinations of variables to the outcome of pregnancy, as reflected by abnormal intrapartum fetal heart rate patterns, meconium during labor, fetal distress, and perinatal mortality rate were determined. The biophysical profile of all hypoxic fetuses was analyzed. These data suggest that the biophysical profile is more accurate in the identification of the hypoxic fetus than any other single method; therefore, a new protocol including the biophysical profile for antepartum fetal evaluation is presented.

Preterm premature rupture of membranes, intrauterine infection, and oligohydramnios: risk factors for placental abruption.

OBJECTIVE: To examine whether preterm premature rupture of membranes (PROM), intrauterine infection, and oligohydramnios are risk factors for placental abruption. METHODS: Data for this retrospective cohort study were derived from the 1988 National Maternal and Infant Health Survey (N = 11,777). Association between abruption and these clinical risk factors was expressed as relative risk (RR) and 95% confidence interval (CI), with multivariate adjustment for potential confounders. RESULTS: The overall incidence of abruption was 0.87%. The risk of abruption was 3.58-fold higher (95% CI 1.74–7.39) among women with preterm PROM (2.29%) compared with women with intact membranes (0.86%). The rates of abruption among women with and without intrauterine infection were 4.81% and 0.83%, respectively (RR 9.71, 95% CI 3.23–29.17). However, oligohydramnios was not associated with abruption (1.46% compared with 0.87%; RR 2.09, 95% CI 0.92–5.31). Compared with women with intact membranes, the RR for abruption among preterm PROM and whose membranes were ruptured for 24–47 hours and 48 hours or more before delivery, respectively, were 2.37 (95% CI 0.99–9.09), and 9.87 (95% CI 3.57–27.82). When preterm PROM was accompanied by intrauterine infections, the RR for abruption was 9.03 (95% CI 2.80–29.15) compared with women with intact membranes and no infections. Similarly, preterm PROM accompanied by oligohydramnios conferred over a 7.17-fold risk (95% CI 1.35–38.10) for abruption compared with women with neither of these 2 conditions. CONCLUSION: Women presenting with preterm PROM are at increased risk of developing abruption, with the risk being higher either in the presence of intrauterine infections or oligohydramnios. Physicians managing patients with preterm PROM should be aware that these patients are at increased risk of developing abruption after 24 hours following preterm PROM. LEVEL OF EVIDENCE: II-2

Management and outcomes of pregnancies complicated by human B19 parvovirus infection: A prospective study

During a large statewide outbreak of fifth disease in Connecticut in 1988, 39 pregnant women were identified who had serologic evidence of recent human B19 parvovirus infection. The patients were followed up prospectively with targeted fetal ultrasonographic examinations to detect signs of fetal hydrops. Of these 39 pregnant women, 37 had healthy infants and two patients had miscarriages. None of the fetuses developed hydrops. We propose that pregnant women exposed to B19 parvovirus be tested for evidence of IgG and IgM B19-specific antibodies and that targeted fetal ultrasonography be considered when IgM antibodies are found. Percutaneous umbilical blood sampling and intrauterine transfusion can be considered in cases of B19 parvovirus-associated hydrops and anemia. The overall fetal loss rate in this prospective follow-up group was 5%.

Recurrence of Ischemic Placental Disease

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. LEVEL OF EVIDENCE: II

The fetal biophysical profile in patients with premature rupture of the membranes—An early predictor of fetal infection

A modified fetal biophysical profile (nonstress test, fetal movements, fetal breathing movements, fetal tone, amniotic fluid volume, and placental grading) was serially assessed in 73 patients who presented with premature rupture of the membranes and were not in labor. The last study before delivery was compared with the outcome of pregnancy. The relationships between individual variables and combinations of variables (biophysical scoring) and the outcome of pregnancy--as reflected by the development of chorioamnionitis and/or neonatal sepsis--were determined. These data suggest that the fetal biophysical profile is a useful tool for evaluating patients with rupture of the membranes. Rupture of the membranes by itself does not alter the biophysical scoring of the healthy fetus; however, a low biophysical score (less than or equal to 7) was a good predictor of impending fetal infection in patients with premature rupture of the membranes.

Clinical Chorioamnionitis and Histologic Placental Inflammation

OBJECTIVE To estimate the rate of histologic chorioamnionitis in the presence of diagnosed clinical chorioamnionitis and determine whether clinical markers of maternal and neonatal infection are associated with histologic chorioamnionitis. METHODS We identified singleton pregnancies from 1996 in which discharge diagnoses included clinical chorioamnionitis and reviewed maternal and neonatal records for clinical evidence of chorioamnionitis and suspected or confirmed neonatal infections. Placentas were examined for acute histologic chorioamnionitis. RESULTS One hundred thirty-nine pregnancies with the discharge diagnosis of maternal clinical chorioamnionitis were included. Eighty-six (61.9%) had the clinical diagnosis supported by histologic chorioamnionitis. Histologic chorioamnionitis was associated with an earlier gestational age at delivery (35.7+/-6.5 weeks versus 38.6+/-2.9 weeks, P = .002), lower epidural usage (72.1% versus 92.5%, P = .004), less internal monitoring (47.7% versus 75.5%, P = .001), and possible neonatal sepsis (60.5% versus 35.8%, P = .005). For 19 of 71 (26.8%) infants with possible neonatal sepsis, placentas did not show histologic chorioamnionitis. CONCLUSION Clinical chorioamnionitis and possible neonatal infection were not supported by histologic evidence for infection in 38.1% and 26.8% of cases, respectively, suggesting other noninflammatory causes of signs and symptoms.