Objective
To determine maternal and perinatal outcome in women with severe preeclampsia at <26 weeks according to gestational age at the onset of expectant management and the presence of severe fetal growth restriction (<5th percentile).
Study Design
Fifty-one patients (53 fetuses; 2 twins) were retrospectively studied.
Results
Median prolongation was 7 days (2-55). Maternal morbidity rate was 43%. Perinatal survival rate was 42%. Severe fetal growth restriction complicated 17 fetuses (33%). There were no perinatal survivors in those managed at <24 weeks (n = 12). For those at 24-24 6/7 and 25-25 6/7 weeks, the perinatal survival rates were 50% and 57%, respectively, and in the presence of severe fetal growth restriction 0% and 30%, respectively.
Conclusion
Perinatal outcome in severe preeclampsia in the midtrimester is dependent on gestational age and/or the presence of severe fetal growth restriction. Given the high maternal morbidity and the extremely low perinatal survival rates, we do not recommend expectant management before 24 weeks and/or in those with severe fetal growth restriction at any gestational age <26 weeks.
Severe preeclampsia (PE) in the second trimester is becoming an increasing problem because of the high rate of pregnancies obtained by assisted reproductive technologies and increasing rates of preexisting medical conditions (chronic hypertension and renal disease) associated with advanced maternal age at first pregnancy. Severe PE remote from term remains an important challenge in obstetrics as it is associated with an increased risk of adverse maternal and perinatal outcomes. In addition, the onset of severe PE at less than 26 weeks’ gestation is associated with an increased rate of perinatal death and substantial maternal morbidity. Most of the studies addressing this question, however, included a limited number of cases, and the results are not encouraging. Moreover, adverse perinatal outcomes remain high, and it is unclear whether expectant management is safe for the mother when balancing the risk with perinatal outcomes. Also, the benefits of such management in the presence of severe fetal growth restriction (SFGR) at less than 26 weeks’ gestation remains unclear.
The aim of this study was to analyze adverse maternal and perinatal outcomes in women having severe PE diagnosed at less than 26 weeks’ gestation who were expectantly managed, according to gestational age at the onset of expectant management and by the presence of SFGR (<5th percentile).
Patients and Methods
We retrospectively reviewed the medical records of all women with severe PE diagnosed at <26 weeks’ gestation and admitted at 2 perinatal centers (between 2000-2008 at CHI Creteil and between 2005-2008 at AP-HP Cochin Port-Royal). Diagnosis of severe PE was based on the presence of PE and 1 or more of the following criteria: persistent blood pressure of 160 mm Hg systolic or higher or 110 mm Hg diastolic or higher, proteinuria ≥5 g in a 24-hour urine sample, oliguria of less than 500 mL in 24 hours, cerebral or visual disturbances, pulmonary edema, epigastric or right upper-quadrant pain, impaired liver function, thrombocytopenia (<100,000 platelets/μL), or SFGR.
Expectant management was defined as pregnancy prolongation after the first 48 hours. This period was used to identify those women with stable maternal condition and to allow time to accelerate fetal lung maturity with corticosteroids when indicated, at gestational age >24 weeks’ gestation.
Pregnancies with unstable maternal and/or fetal conditions during the first 48 hours after admission were delivered before completion of steroids. Particularly, women with eclampsia, hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome, severe uncontrolled hypertension (defined as difficulties to stabilize systolic blood pressure at <160 mm Hg and diastolic blood pressure at <110 mm Hg), abruptio placentae, and/or abnormal fetal heart rate monitoring were excluded.
Patients were monitored carefully in labor or in high-risk pregnancy unit, depending on severity of clinical or laboratory parameters. A resident, a midwife, a nurse, and a senior obstetrician were dedicated to monitor these patients. Prophylactic magnesium sulfate was used, depending on local protocol. Maternal monitoring included 4 hourly blood pressure measurements, clinical evaluation of symptoms at least twice daily, and analysis of 24-hour urine excretion daily. Antihypertensive drugs were used to keep systolic blood pressure <160 mm Hg and diastolic blood pressure <110 mmHg. Intravenous nicardipine or intravenous labetalol were used as firstline treatment in women with severe hypertension (defined as systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥110 mm Hg). When necessary, these 2 drugs were used together. Blood tests included hemoglobin, platelet count, liver enzymes, serum creatinine, lactate dehydrogenase, fibrinogen, d -dimers, prothrombin, and partial thromboplastin times. These tests were performed daily or every other day, depending on clinical symptoms and laboratory findings. Fetal evaluation included ultrasound evaluation of fetal growth (estimated fetal weight or abdominal circumference), umbilical artery Doppler measurement, and estimation of amniotic fluid volume at entry. Before 24 weeks’ gestation, fetal heart monitoring was not performed. After 24 weeks’ gestation, fetal heart rate monitoring with short-term variability analysis and clinical evaluation of fetal movements were performed twice daily.
Indications for delivery before 24 weeks’ gestation were either for maternal reasons (eclampsia, HELLP syndrome, abruptio placentae, severe uncontrolled hypertension, pulmonary edema, or oliguria) or for fetal reasons (fetal death, SFGR at <5th percentile, severe oligohydramnios identified as the largest vertical pocket <2 cm, or absence or reverse end diastolic [ARED] flow at the umbilical artery Doppler examination).
Maternal indications for delivery after 24 weeks’ gestation were similar to those before 24 weeks. Fetal indications for delivery were abnormal fetal heart rate monitoring (repeated late decelerations or decreased short-term variability analysis). Furthermore, the desire of the parents regarding neonatal resuscitation were considered before any delivery.
The main outcomes of the study were major maternal morbidity and mortality and major perinatal morbidity and mortality. Major maternal complications included maternal death, eclampsia, the new onset of thrombocytopenia, HELLP syndrome, abruptio placentae, disseminated intravascular coagulopathy (DIC), pulmonary edema, and acute renal failure. HELLP syndrome was defined by the presence of all 3 of the following criteria: hemolysis (characteristic peripheral blood smear and serum lactate dehydrogenase [LDH] ≥600 U/L or serum total bilirubin ≥1.2 mg/dL), elevated liver enzymes (serum aspartate aminotransferase [AST] ≥70 U/L), and low platelet counts (<100,000 cells/μL). DIC was defined as the presence of 3 or more of the following criteria: low platelets (<100,000 cells/mL), low fibrinogen (<300 mg/dL), positive d -dimers (≥50 mg/dL), or prolonged prothrombin (≥14 seconds) and partial thromboplastin (≥40 seconds) times. Pulmonary edema was diagnosed on the basis of clinical findings and chest radiography. Acute renal failure was diagnosed in the presence of oligoanuria in association with elevated serum creatinine greater than 120 μmol/L (>1.4 mg/dL). The need for dialysis was considered as severe acute renal failure. Composite morbidity was defined as the occurrence of one of the following maternal complications: death, HELLP syndrome, abruptio placentae, eclampsia, pulmonary edema, renal insufficiency, isolated thrombocytopenia, or DIC.
Major perinatal complications included fetal and neonatal death, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) grade 3 and 4, and necrotizing enterocolitis (NEC). RDS was defined by the presence of characteristic radiographic findings and an oxygen requirement at 24 hours. BPD was defined as an oxygen requirement at 36 weeks’ postmenstrual age. IVH grade 3 was defined as hemorrhage with ventricular dilation, and grade 4 as hemorrhage with parenchymal spread. NEC was defined by characteristic clinical symptoms with radiographic findings of pneumatosis cystoides intestinalis or pneumoperitoneum or portal air.
Gestational age was determined by last menstrual period and/or first trimester ultrasound examination. SFGR was defined as birthweight less than 5th percentile. Pregnancy prolongation and maternal and perinatal outcomes were analyzed according to gestational age at time of admission that was divided into 4 groups: <23 weeks, 23 0/7 -23 6/7 weeks, 24 0/7 -24 6/7 weeks, 25 0/7 -25 6/7 weeks.
Data are presented as median and range or percentage, as appropriate. Categorical variables were compared by χ 2 test or Fisher exact test. Continuous variables were analyzed by Student t test. A P value < .05 was considered significant.
The evaluation of our conservative management did not need approval of our ethical committee, because it was a prospective collection of data in women who received standard management at both hospitals. Therefore, our ethical committee has waved requirement for approval.
Results
During the study period, 56 patients were admitted for severe PE at less than 26 weeks’ gestation. Two of them had twin pregnancies. Among the 56 patients admitted, 51 women were expectantly managed, and 5 had their pregnancy terminated during the first 48 hours. These 5 pregnancies were terminated for fetal death in 2 cases (gestational age: 25 3/7 weeks, weight: 695 g; and gestational age: 25 5/7 weeks, 770 g), for abnormal fetal heart rate monitoring in 1 case (gestational age: 25 6/7 weeks, weight: 660 g, liveborn, discharge alive at 33 5/7 weeks postmenstrual age, without complication), for abnormal fetal heart rate monitoring and RED umbilical flow in 1 case (gestational age: 26 weeks, weight: 630 g, liveborn, discharge alive at 41 weeks postmenstrual age, with bronchopulmonary dysplasia), and for HELLP syndrome associated with severe FGR in 1 case (gestational age: 24 4/7 weeks, weight: 360 g, stillborn).
Demographic and clinical characteristics of patients expectantly managed are shown in Table 1 . Table 2 describes maternal complications according to gestational age at onset of expectant management. Twenty-two (43%) had at least 1 major complication. None of these women died, and none had eclampsia or DIC. It is important to note that HELLP syndrome was the most frequent complication (14 patients, 27%). The rates of maternal complications were similar in those having expectant management at less than 25 weeks, compared with those at 25 weeks and higher (41% and 46%, respectively).
