Baha M. Sibai

Maternal Morbidity Associated With Multiple Repeat Cesarean Deliveries

OBJECTIVE: Although repeat cesarean deliveries often are associated with serious morbidity, they account for only a portion of abdominal deliveries and are overlooked when evaluating morbidity. Our objective was to estimate the magnitude of increased maternal morbidity associated with increasing number of cesarean deliveries. METHODS: Prospective observational cohort of 30,132 women who had cesarean delivery without labor in 19 academic centers over 4 years (1999–2002). RESULTS: There were 6,201 first (primary), 15,808 second, 6,324 third, 1,452 fourth, 258 fifth, and 89 sixth or more cesarean deliveries. The risks of placenta accreta, cystotomy, bowel injury, ureteral injury, and ileus, the need for postoperative ventilation, intensive care unit admission, hysterectomy, and blood transfusion requiring 4 or more units, and the duration of operative time and hospital stay significantly increased with increasing number of cesarean deliveries. Placenta accreta was present in 15 (0.24%), 49 (0.31%), 36 (0.57%), 31 (2.13%), 6 (2.33%), and 6 (6.74%) women undergoing their first, second, third, fourth, fifth, and sixth or more cesarean deliveries, respectively. Hysterectomy was required in 40 (0.65%) first, 67 (0.42%) second, 57 (0.90%) third, 35 (2.41%) fourth, 9 (3.49%) fifth, and 8 (8.99%) sixth or more cesarean deliveries. In the 723 women with previa, the risk for placenta accreta was 3%, 11%, 40%, 61%, and 67% for first, second, third, fourth, and fifth or more repeat cesarean deliveries, respectively. CONCLUSION: Because serious maternal morbidity increases progressively with increasing number of cesarean deliveries, the number of intended pregnancies should be considered during counseling regarding elective repeat cesarean operation versus a trial of labor and when debating the merits of elective primary cesarean delivery. LEVEL OF EVIDENCE: II-2

Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome)

OBJECTIVE Our purpose was to describe the incidence and effects of serious obstetric complications on maternal outcome in pregnancies complicated by HELLP syndrome. STUDY DESIGN A prospective cohort study was performed on 442 pregnancies with HELLP syndrome managed at this center from August 1977 through July 1992. RESULTS Of 437 women who had 442 pregnancies with HELLP syndrome; 309 (70%) of the cases occurred ante partum and 133 (30%) post partum; 149 (11%) developed at < 27 weeks and 80 (18%) at term. Maternal mortality was 1.1% (five patients). Serious maternal morbidity included disseminated intravascular coagulation (21%), abruptio placentae (16%), acute renal failure (7.7%), pulmonary edema (6%), subcapsular liver hematoma (0.9%), and retinal detachment (0.9%). Fifty-five percent of patients required transfusions with blood or blood products, and 2% required laparotomies for major intraabdominal bleeding. Abruptio placentae was strongly correlated with the development of disseminated intravascular coagulation (p < 0.0001), acute renal failure (p < 0.001), and pulmonary edema (p < 0.01). Moreover, there was a strong association between pulmonary edema and acute renal failure (p < 0.0001). There were no differences in laboratory findings between HELLP syndrome before and after delivery; however, women with postpartum HELLP syndrome had significantly higher incidences of pulmonary edema and renal failure. CONCLUSION HELLP syndrome is associated with serious maternal morbidity, especially when it arises in the postpartum period.

Etiology and pathogenesis of preeclampsia: current concepts.

Abstract The etiology of preeclampsia is unknown. At present, 4 hypotheses are the subject of extensive investigation, as follows: (1) Placental ischemia—Increased trophoblast deportation, as a consequence of ischemia, may inflict endothelial cell dysfunction. (2) Very low-density lipoprotein versus toxicity-preventing activity—In compensation for increased energy demand during pregnancy, nonesterified fatty acids are mobilized. In women with low albumin concentrations, transporting extra nonesterified fatty acids from adipose tissues to the liver is likely to reduce albumin’s antitoxic activity to a point at which very-low density lipoprotein toxicity is expressed. (3) Immune maladaptation—Interaction between decidual leukocytes and invading cytotrophoblast cells is essential for normal trophoblast invasion and development. Immune maladaptation may cause shallow invasion of spiral arteries by endovascular cytotrophoblast cells and endothelial cell dysfunction mediated by an increased decidual release of cytokines, proteolytic enzymes, and free radical species. (4) Genetic imprinting—Development of preeclampsia-eclampsia may be based on a single recessive gene or a dominant gene with incomplete penetrance. Penetrance may be dependent on fetal genotype. The possibility of genetic imprinting should be considered in future genetic investigations of preeclampsia. (Am J Obstet Gynecol 1998;179:1359-75.)

Timing of elective repeat cesarean delivery at term and neonatal outcomes

BACKGROUND Because of increased rates of respiratory complications, elective cesarean delivery is discouraged before 39 weeks of gestation unless there is evidence of fetal lung maturity. We assessed associations between elective cesarean delivery at term (37 weeks of gestation or longer) but before 39 weeks of gestation and neonatal outcomes. METHODS We studied a cohort of consecutive patients undergoing repeat cesarean sections performed at 19 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network from 1999 through 2002. Women with viable singleton pregnancies delivered electively (i.e., before the onset of labor and without any recognized indications for delivery before 39 weeks of gestation) were included. The primary outcome was the composite of neonatal death and any of several adverse events, including respiratory complications, treated hypoglycemia, newborn sepsis, and admission to the neonatal intensive care unit (ICU). RESULTS Of 24,077 repeat cesarean deliveries at term, 13,258 were performed electively; of these, 35.8% were performed before 39 completed weeks of gestation (6.3% at 37 weeks and 29.5% at 38 weeks) and 49.1% at 39 weeks of gestation. One neonatal death occurred. As compared with births at 39 weeks, births at 37 weeks and at 38 weeks were associated with an increased risk of the primary outcome (adjusted odds ratio for births at 37 weeks, 2.1; 95% confidence interval [CI], 1.7 to 2.5; adjusted odds ratio for births at 38 weeks, 1.5; 95% CI, 1.3 to 1.7; P for trend <0.001). The rates of adverse respiratory outcomes, mechanical ventilation, newborn sepsis, hypoglycemia, admission to the neonatal ICU, and hospitalization for 5 days or more were increased by a factor of 1.8 to 4.2 for births at 37 weeks and 1.3 to 2.1 for births at 38 weeks. CONCLUSIONS Elective repeat cesarean delivery before 39 weeks of gestation is common and is associated with respiratory and other adverse neonatal outcomes.

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 associated with preeclampsia in healthy nulliparous women

Abstract 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 2 ), systolic blood pressure (odds ratio 2.66 for ≥120 vs p Conclusion: These risk factors should be of value in counseling women regarding preeclampsia and should aid in understanding the pathophysiologic characteristics of this syndrome.

Diagnosis, Prevention, and Management of Eclampsia

The pathogenesis of eclamptic convulsions remains unknown. Cerebral imaging suggests that cerebral abnormalities in eclampsia (mostly vasogenic edema) are similar to those found in hypertensive encephalopathy. However, cerebral imaging is not necessary for the diagnosis or management of most women with eclampsia. The onset of eclamptic convulsions can be antepartum (38-53%), intrapartum (18-36%), or postpartum (11-44%). Recent data reveal an increase in the proportion of women who develop eclampsia beyond 48 hours after delivery. Other than early detection of preeclampsia, there are no reliable tests or symptoms for predicting the development of eclampsia. In developed countries, the majority of cases reported in recent series are considered unpreventable. Magnesium sulfate is the drug of choice for reducing the rate of eclampsia developing intrapartum and immediately postpartum. There are 4 large randomized trials comparing magnesium sulfate with no treatment or placebo in patients with severe preeclampsia. The rate of eclampsia was significantly lower in those assigned to magnesium sulfate (0.6% versus 2.0%, relative risk 0.39, 95% confidence interval 0.28-0.55). Thus, the number of women needed to treat to prevent one case of eclampsia is 71. Magnesium sulfate is the drug of choice to prevent recurrent convulsions in eclampsia. The development of eclampsia is associated with increased risk of adverse outcome for both mother and fetus, particularly in the developing nations. Pregnancies complicated by eclampsia require a well-formulated management plan. Women with a history of eclampsia are at increased risk of eclampsia (1-2%) and preeclampsia (22-35%) in subsequent pregnancies. Recommendations for diagnosis, prevention, management, and counseling of these women are provided based on results of recent studies and my own clinical experience.

The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP

There has never been a definite consensus on the classification and diagnostic criteria for the hypertensive disorders of pregnancy. This uncertainty is likely to have led to between-centre differences in rates of adverse maternal and foetal outcomes for the various hypertensive disorders in pregnancy, particularly pre-eclampsia. In 2000, the International Society for the Study of Hypertension in Pregnancy (ISSHP) recognised that this lack of consensus was one reason for controversies concerning counselling, management and documentation of immediate and remote pregnancy outcomes. Accordingly, the Society appointed a committee that reviewed available classifications and endorsed and published an international recommendation for how these disorders should be classified and diagnosed in pregnancy [1]. The major stumbling block remained whether or not proteinuria should be retained as a sine qua non for the diagnosis of pre-eclampsia; the Society recommended that a broad definition, at times not including proteinuria, could be applied for the clinical definition of pre-eclampsia whilst the inclusion of proteinuria would ensure more specificity around the diagnosis when reporting clinical criteria for patients enrolled in scientific research. The purpose of this document is to update ISSHP thinking on this subject.

Hypertensive Pregnancy Disorders and Subsequent Cardiovascular Morbidity and Type 2 Diabetes Mellitus in the Mother

Minimal data exist concerning the relationship between hypertensive pregnancy disorders and various subsequent cardiovascular events and the effect of type 2 diabetes mellitus on these. In a registry-based cohort study, we identified women delivering in Denmark from 1978 to 2007 with a first singleton (n=782 287) and 2 first consecutive singleton deliveries (n=536 419). The exposures were gestational hypertension and mild and severe preeclampsia. We adjusted for preterm delivery, small for gestational age, placental abruption, and stillbirth and, in a second model, we also adjusted for the development of type 2 diabetes mellitus. The end points were subsequent hypertension, ischemic heart disease, congestive heart failure, thromboembolic event, stroke, and type 2 diabetes mellitus. The risk of subsequent hypertension was increased 5.31-fold (range: 4.90 to 5.75) after gestational hypertension, 3.61-fold (range: 3.43 to 3.80) after mild preeclampsia, and 6.07-fold (range: 5.45 to 6.77) after severe preeclampsia. The risk of subsequent type 2 diabetes mellitus was increased 3.12-fold (range: 2.63 to 3.70) after gestational hypertension and 3.68-fold (range: 3.04 to 4.46) after severe preeclampsia. Women having 2 pregnancies both complicated by preeclampsia had a 6.00-fold (range: 5.40 to 6.67) increased risk of subsequent hypertension compared with 2.70-fold (range: 2.51 to 2.90) for women having preeclampsia in their first pregnancy only and 4.34-fold (range: 3.98 to 4.74) for women having preeclampsia in their second pregnancy only. The risk of subsequent thromboembolism was 1.03-fold (range: 0.73 to 1.45), 1.53-fold (range: 1.32 to 1.77), and 1.91-fold (range: 1.35 to 2.70) increased after gestational hypertension and mild and severe preeclampsia, respectively. Thus, hypertensive pregnancy disorders are strongly associated with subsequent type 2 diabetes mellitus and hypertension, the latter independent of subsequent type 2 diabetes mellitus. The severity, parity, and recurrence of these hypertensive pregnancy disorders increase the risk of subsequent cardiovascular events.

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...