Cande V. Ananth

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.

Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis.

Objective To estimate the contributions of biological aging, historical trends, and birth cohort effects on trends in pre-eclampsia in the United States. Design Population based retrospective study. Setting National hospital discharge survey datasets, 1980-2010, United States. Participants 120 million women admitted to hospital for delivery. Main outcome measures Temporal changes in rates of mild and severe pre-eclampsia in relation to maternal age, year of delivery, and birth cohorts. Poisson regression as well as multilevel age-period-cohort models with adjustment for obesity and smoking were incorporated. Results The rate of pre-eclampsia was 3.4%. The age-period-cohort analysis showed a strong age effect, with women at the extremes of maternal age having the greatest risk of pre-eclampsia. In comparison with women delivering in 1980, those delivering in 2003 were at 6.7-fold (95% confidence interval 5.6-fold to 8.0-fold) increased risk of severe pre-eclampsia. Period effects declined after 2003. Trends for severe pre-eclampsia also showed a modest birth cohort effect, with women born in the 1970s at increased risk. Compared with women born in 1955, the risk ratio for women born in 1970 was 1.2 (95% confidence interval 1.1 to 1.3). Similar patterns were also evident for mild pre-eclampsia, although attenuated. Changes in the population prevalence of obesity and smoking were associated with period and cohort trends in pre-eclampsia but did not explain the trends. Conclusions Rates of severe pre-eclampsia have been increasing in the United States and age-period-cohort effects all contribute to these trends. Although smoking and obesity have driven these trends, changes in the diagnostic criteria may have also contributed to the age-period-cohort effects. Health consequences of rising obesity rates in the United States underscore that efforts to reduce obesity may be beneficial to maternal and perinatal health.

Gestational diabetes in the United States: temporal trends 1989 through 2004

OBJECTIVE The objective of the study was to characterize trends in gestational diabetes (GDM) by maternal age, race, and geographic region in the United States. STUDY DESIGN The National Hospital Discharge Survey, comprised of births in the United States between 1989 and 2004 (weighted n = 58,922,266), was used to examine trends in GDM, based on an International Classification of Diseases, Ninth Revision, Clinical Modification code of 648.8. We examined temporal trends by comparing GDM rates in the earliest (1989-1990) vs most recent (2003-2004) biennial periods. Relative risks, quantifying racial disparity (black vs white) in GDM, were derived through logistic regression models after adjusting for confounders. These analyses were further stratified by maternal age and geographic region. RESULTS Prevalence rates of GDM increased from 1.9% in 1989-1990 to 4.2% in 2003-2004, a relative increase of 122% (95% confidence interval [CI] 120%, 124%). Among whites, GDM increased from 2.2% in 1989-1990 to 4.2% in 2003-2004 (relative increase of 94% [95% CI 91%, 96%]), and this was largely driven by an increase in the 25-34 year age group. In contrast, the largest relative increase in GDM (260% [95% CI 243%, 279%]) among blacks between 1989-1990 (0.6%) and 2003-2004 (2.1%) occurred to women aged younger than 25 years. The black-white disparity in GDM rates widened markedly among women aged younger than 35 years in the 1997-2004 periods. The largest relative increases were seen in the West (182% [95% CI 177%, 187%]) followed by the South and Northeast. The observed increase in GDM rates in the Northeast, Midwest, and South regions most likely is due to increase in GDM prevalence rates among blacks. CONCLUSION This study shows that the prevalence rate of GDM in the United States has increased dramatically between 1989 and 2004. The temporal increase and the widening black-white disparity in the rate of GDM deserves further investigation.

Previous cesarean delivery and risks of placenta previa and placental abruption.

OBJECTIVE: To examine the association between cesarean delivery and previa and abruption in subsequent pregnancies. METHODS: A retrospective cohort study of first 2 (n = 156,475) and first 3 (n = 31,102) consecutive singleton pregnancies using the 1989–1997 Missouri longitudinally linked data were performed. Relative risk (RR) was used to quantify the associations between cesarean delivery and risks of previa and abruption in subsequent pregnancies, after adjusting for several confounders. RESULTS: Rates of previa and abruption were 4.4 (n = 694) and 7.9 (n = 1,243) per 1,000 births, respectively. The pregnancy after a cesarean delivery was associated with increased risk of previa (0.63%) compared with a vaginal delivery (0.38%, RR 1.5, 95% confidence interval [CI] 1.3–1.8). Cesarean delivery in the first and second births conferred a two-fold increased risk of previa in the third pregnancy (RR 2.0, 95% CI 1.3–3.0) compared with first two vaginal deliveries. Women with a cesarean first birth were more likely to have an abruption in the second pregnancy (0.95%) compared with women who had a vaginal first birth (0.74%, RR 1.3, 95% CI 1.2–1.5). Two consecutive cesarean deliveries were associated with a 30% increased risk of abruption in the third pregnancy (RR 1.3, 95% CI 1.0–1.8). A second pregnancy within a year after a cesarean delivery was associated with increased risks of previa (RR 1.7, 95% CI 0.9–3.1) and abruption (RR 1.5, 95% CI 1.1–2.3). CONCLUSION: A cesarean first birth is associated with increased risks of previa and abruption in the second pregnancy. There is a dose–response pattern in the risk of previa, with increasing number of prior cesarean deliveries. A short interpregnancy interval is associated with increased risks of previa and abruption. LEVEL OF EVIDENCE: II-2

Etiology and risk factors for placenta previa: an overview and meta-analysis of observational studies

Objective: Several clinical and epidemiologic studies have reported disparate data on the prevalence rate as well as risk factors associated with placenta previa - a major cause of third-trimester bleeding. We performed a systematic literature review and identified 58 studies on placenta previa published between 1966 and 2000. Study design: Each study was reviewed independently by the two authors and was scored (on the basis of established criteria) on method of diagnosis of placenta previa and on quality of study design. We extracted data on the prevalence rate of placenta previa, as well as associations with various risk factors from each study. A meta-analysis was then performed to determine the extent to which different risk factors predispose women to placenta previa. Results: Our results showed that the overall prevalence rate of placenta previa was 4.0 per 1000 births, with the rate being higher among cohort studies (4.6 per 1000 births), USA-based studies (4.5 per 1000 births) and hospital-based studies (4.4 per 1000 births) than among case-control studies (3.5 per 1000 births), foreign-based studies (3.7 per 1000 births) and population-based studies (3.7 per 1000 births), respectively. Advancing maternal age, multiparity, previous Cesarean delivery and abortion, smoking and cocaine use during pregnancy, and male fetuses all conferred increased risk for placenta previa. Strong heterogeneity in the associations between risk factors and placenta previa were noted by study design, accuracy in the diagnosis of placenta previa and population-based versus hospital-based studies. Conclusion: Future etiological studies on placenta previa must, at the very least, adjust for potentially confounding effects of maternal age, parity, prior Cesarean delivery and abortions.

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.

Pracental abruption and its association with hypertension and prolonged rupture of membranes: A methodologic review and meta-analysis*

Objective To conduct a meta-analysis of published studies on placental abruption to examine its incidence, recurrence, and association with hypertensive disorders (chronic hyper-tension and preeclampsia) and prolonged rupture of membranes (PROM) in pregnancy. Data Sources We reviewed studies on placental abruption published since 1950, based on a comprehensive literature search using MEDLINE, and by identifying studies cited in the references of published reports. Methods of Study Selection We identified 54 studies, excluding case reports on placental abruption and studies relating to placenta previa and vaginal bleeding of unknown origin. We also restricted the search to articles published in English. Tabulation, Integration, and Results Studies chosen for the meta-analysis were categorized based on their study design (case-control or cohort), where they were conducted (United States or other countries), source of the data (vital records versus other sources), and magnitude of risk (risk of abruption greater or less than 1.0%). We used both fixed- and random-effects analysis to identify sources of heterogeneity in results among studies. There were striking differences in the incidence of placental abruption between cohort (0.69%) and case-control (0.35%) studies. United States-based studies found a somewhat higher incidence both for cohort (0.81%) and case-control (0.37%) studies compared with studies conducted outside the U.S. (0.60% and 0.26%, respectively). Abruption was more than ten times more common in pregnancies preceded by a pregnancy with abruption. Chronically hypertensive patients were more than three times as likely to develop placental abruption (odds ratio [OR] 3.13, 95% confidence interval [CI] 2.04–4.80) as normotensive patients. The OR for placental abruption was 1.73 (95% CI 1.47–2.04) for patients with preeclampsia. Similarly, women with pregnancies complicated by PROM were more than three times as likely to develop placental abruption (OR 3.05, 95% CI 2.16–4.32). United States-based studies, case-control studies, and studies with an incidence of abruption greater than 1% demonstrated stronger associations between abruption and hypertension and PROM. Conclusion Risk of abruption is strongly associated with chronic hypertension, PROM, and especially abruption in a prior pregnancy, and somewhat more modestly with pre-eclampsia. The criteria for the diagnosis of placental abruption, hypertensive disorders, and PROM may have introduced variability among the results of these studies. More standardized definitions of these pregnancy complications would improve the comparability of the study results.

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