Brian M. Mercer

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

OBJECTIVEnOur purpose was to describe the incidence and effects of serious obstetric complications on maternal outcome in pregnancies complicated by HELLP syndrome.nnnSTUDY DESIGNnA prospective cohort study was performed on 442 pregnancies with HELLP syndrome managed at this center from August 1977 through July 1992.nnnRESULTSnOf 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.nnnCONCLUSIONnHELLP syndrome is associated with serious maternal morbidity, especially when it arises in the postpartum period.

Preterm premature rupture of the membranes.

Preterm premature rupture of membranes (PROM) affects over 120,000 pregnancies annually in the United States and is associated with significant maternal, fetal, and neonatal risk. Management of PROM requires an accurate diagnosis as well as evaluation of the risks and benefits of continued pregnancy or expeditious delivery. An understanding of gestational age-dependent neonatal morbidity and mortality is important in determining the potential benefits of conservative management of preterm PROM at any gestation. Where possible, the treatment of pregnancies complicated by PROM remote from term should be directed towards conserving the pregnancy and reducing perinatal morbidity due to prematurity while monitoring closely for evidence of infection, placental abruption, labor, or fetal compromise due to umbilical cord compression. Current evidence suggests aggressive adjunctive antibiotic therapy to reduce gestational age-dependent and infectious infant morbidity. Similarly, review of evaluable data indicates that antenatal corticosteroid administration in this setting enhances neonatal outcome without increasing the risk of perinatal infection. It is not clear that tocolysis in the setting of preterm PROM remote from term reduces infant morbidity. When preterm PROM occurs near term, particularly if fetal pulmonary maturity is evident, the patient is generally best served by expeditious delivery.

Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks' gestation: a randomized controlled trial.

OBJECTIVEnOur purpose was to determine whether aggressive or expectant management of severe preeclampsia at 28 to 32 weeks is more beneficial to maternal and neonatal outcome.nnnSTUDY DESIGNnNinety-five eligible patients were randomly assigned to either aggressive (n = 46) or expectant management (n = 49). Aggressive management patients were prepared for delivery, either by cesarean or induction, 48 hours after glucocorticoids were administered. Expectant management patients were managed with bed rest, oral antihypertensives, and intensive antenatal fetal testing.nnnRESULTSnAt the time of randomization there were no differences between the two groups in mean systolic blood pressure (170 +/- 9.7 vs 172 +/- 9.4 mm Hg), diastolic blood pressure (110 +/- 5.4 vs 112 +/- 4.2 mm Hg), proteinuria (3.0 +/- 2.3 vs 3.6 +/- 2.3 gm per 24 hours), and gestational age (30.4 +/- 1.6 vs 30.7 +/- 1.5 weeks) for the aggressive and expectant management groups. The average latency period in the expectant management group was 15.4 days (range 4 to 36), and this period was not affected by the amount of proteinuria at randomization. There was no eclampsia or perinatal death in either group. The two groups had similar incidences of abruptio placentae (4.1% vs 4.3%) and similar days of postpartum hospital stay. The expectant management group had a significantly higher gestational age at delivery (32.9 +/- 1.5 vs 30.8 +/- 1.7 weeks, p < 0.0001), higher birth weight, lower incidence of admission to the neonatal intensive care unit (76% vs 100%, p = 0.002), lower mean days of hospitalization in the intensive care unit (20.2 +/- 14 vs 36.6 +/- 17.4, p < 0.0001), and lower incidence of neonatal complications.nnnCONCLUSIONnExpectant management, with close monitoring of mother and fetus at a perinatal center, reduces neonatal complications and neonatal stay in the newborn intensive care unit.

The preterm prediction study: A clinical risk assessment system ☆ ☆☆ ★ ★★

OBJECTIVEnOur aims were to develop a risk assessment system for the prediction of spontaneous preterm delivery using clinical information available at 23 to 24 weeks gestation and to determine the predictive value of such a system.nnnSTUDY DESIGNnA total of 2929 women were evaluated between 23 and 24 weeks gestation at 10 centers. Demographic factors, socioeconomic status, home and work environment, drug and alcohol use, and medical history were evaluated. Information regarding symptoms, cultures, and treatments in the current pregnancy were ascertained. Anthropomorphic and cervical examinations were performed. Univariate analysis and multivariate logistic regression were performed in a random selection, constituting 85% of the study population. The derived risk assessment system was applied to the remaining 15% of the population to evaluate its validity.nnnRESULTSnA total of 10.4% of women were delivered of preterm infants. The multivariate models for spontaneous preterm delivery were highly associated with spontaneous preterm delivery (p < 0.0001). A low body mass index (<19.8) and increasing Bishop scores were significantly associated with spontaneous preterm delivery in nulliparous and multiparous women. Black race, poor social environment, and work during pregnancy were associated with increased risk for nulliparous women. Prior obstetric outcome overshadowed socioeconomic risk factors in multiparous women with a twofold increase in the odds of spontaneous preterm delivery for each prior spontaneous preterm delivery. Current pregnancy symptoms, including vaginal bleeding, symptomatic contractions within 2 weeks, and acute or chronic lung disease were variably associated with spontaneous preterm delivery in nulliparous and multiparous women. When the system was applied to the remainder of the population, women defined to be at high risk for spontaneous preterm delivery (> or = 20% risk) carried a 3.8-fold (nulliparous women) and 3.3-fold (multiparous women) higher risk of spontaneous preterm delivery than those predicted to be at low risk. However, the risk assessment system identified a minority of women who had spontaneous preterm deliveries. The sensitivities were 24.2% and 18.2% and positive predictive values were 28.6% and 33.3%, respectively, for nulliparous and multiparous women.nnnCONCLUSIONSnAlthough it is possible to develop a graded risk assessment system that includes factors that are highly associated with spontaneous preterm delivery in nulliparous and multiparous women, such a system does not identify most women who subsequently have a spontaneous preterm delivery. This system has investigational value as the basis for evaluating new technologies designed to identify at-risk subpopulations.

Risk Factors and Opportunities for Prevention of Early-onset Neonatal Sepsis: A Multicenter Case-Control Study

Background. Early-onset group B streptococcal (GBS) prevention efforts are based on targeted use of intrapartum antibiotic prophylaxis (IAP); applicability of these prevention efforts to infections caused by other organisms is not clear. Methods. Multicenter surveillance during 1995 to 1996 for culture-confirmed, early-onset sepsis in an aggregate of 52u2009406 births; matched case-control study of risk factors for GBS and other sepsis. Results. Early-onset disease occurred in 188 infants (3.5 cases per 1000 live births). GBS (1.4 cases per 1000 births) andEscherichia coli (0.6 cases per 1000 births) caused most infections. GBS sepsis less often occurred in preterm deliveries compared with other sepsis. Compared with gestation-matched controls without documented sepsis, GBS disease was associated with intrapartum fever (matched OR, 4.1; CI, 1.2–13.4) and frequent vaginal exams (matched OR, 2.9; CI, 1.1–8.0). An obstetric risk factor—preterm delivery, intrapartum fever, or membrane rupture ≥18 hours—was found in 49% of GBS cases and 79% of other sepsis. IAP had an adjusted efficacy of 68.2% against any early-onset sepsis. Ampicillin resistance was evident in 69% of E coliinfections. No deaths occurred among susceptible E coliinfections, whereas 41% of ampicillin-resistant E coliinfections were fatal. Ninety-one percent of infants who developed ampicillin-resistant E coli infections were preterm, and 59% of these infants were born to mothers who had received IAP. Conclusions. Either prenatal GBS screening or a risk-based strategy could potentially prevent a substantial portion of GBS cases. Sepsis caused by other organisms is more often a disease of prematurity. IAP seemed efficacious against early-onset sepsis. However, the severity of ampicillin-resistant E colisepsis and its occurrence after maternal antibiotics suggest caution regarding use of ampicillin instead of penicillin for GBS prophylaxis.

Severe preeclampsia in the second trimester: Recurrence risk and long-term prognosis

A total of 125 women with severe preeclampsia that developed in the second trimester underwent follow-up for an average of 5.4 years. Seventeen women had no further pregnancies and 108 had 169 subsequent pregnancies: 59 (35%) were normotensive and 110 (65%) were complicated by preeclampsia (32% of these developing in the second trimester, 32% at 28 to 36 weeks, and 36% at 37 to 40 weeks). Overall, 21% of subsequent pregnancies were complicated by severe preeclampsia in the second trimester. Forty-four patients (35%) had chronic hypertension, the highest incidence being in those with recurrent severe preeclampsia in the second trimester and the lowest in those with only normotensive subsequent pregnancies (67% vs 4%, p less than 0.0001). Long-term maternal complications included two maternal deaths and two other patients with end-stage renal disease requiring dialysis. We conclude that these women are at increased risk for repeat preeclampsia, particularly in the second trimester, and are at increased risk for chronic hypertension and maternal mortality and morbidity.

Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

CONTEXTnIntrauterine infection is thought to be one cause of preterm premature rupture of the membranes (PPROM). Antibiotic therapy has been shown to prolong pregnancy, but the effect on infant morbidity has been inconsistent.nnnOBJECTIVEnTo determine if antibiotic treatment during expectant management of PPROM will reduce infant morbidity.nnnDESIGNnRandomized, double-blind, placebo-controlled trial.nnnSETTINGnUniversity hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.nnnPATIENTSnA total of 614 of 804 eligible gravidas with PPROM between 24 weeks and 0 days and 32 weeks and 0 days gestation who were considered candidates for pregnancy prolongation and had not received corticosteroids for fetal maturation or antibiotic treatment within 1 week of randomization.nnnINTERVENTIONSnIntravenous ampicillin (2-g dose every 6 hours) and erythromycin (250-mg dose every 6 hours) for 48 hours followed by oral amoxicillin (250-mg dose every 8 hours) and erythromycin base (333-mg dose every 8 hours) for 5 days vs a matching placebo regimen. Group B streptococcus (GBS) carriers were identified and treated. Tocolysis and corticosteroids were prohibited after randomization.nnnMAIN OUTCOME MEASURESnThe composite primary outcome included pregnancies complicated by at least one of the following: fetal or infant death, respiratory distress, severe intraventricular hemorrhage, stage 2 or 3 necrotizing enterocolitis, or sepsis within 72 hours of birth. These perinatal morbidities were also evaluated individually and pregnancy prolongation was assessed.nnnRESULTSnIn the total study population, the primary outcome (44.1 % vs 52.9%; P=.04), respiratory distress (40.5% vs 48.7%; P=.04), and necrotizing enterocolitis (2.3% vs 5.8%; P=.03) were less frequent with antibiotics. In the GBS-negative cohort, the antibiotic group had less frequent primary outcome (44.5% vs 54.5%; P=.03), respiratory distress (40.8% vs 50.6%; P=.03), overall sepsis (8.4% vs 15.6%; P=.01), pneumonia (2.9% vs 7.0%; P=.04), and other morbidities. Among GBS-negative women, significant pregnancy prolongation was seen with antibiotics (P<.001).nnnCONCLUSIONSnWe recommend that women with expectantly managed PPROM remote from term receive antibiotics to reduce infant morbidity.

Maternal plasma level of endothelin is increased in preeclampsia

Endothelin is a potent vasoconstrictor that is reportedly increased in conditions characterized by endothelial damage. Maternal plasma endothelin levels were compared between 27 women with preeclampsia (23 without and 4 with the hemolysis, elevated liver enzymes, and low platelet count syndrome) and 14 women with normotensive pregnancies. The mean +/- SEM plasma endothelin values were significantly higher in patients with preeclampsia uncomplicated by the hemolysis, elevated liver enzymes, and low platelet count syndrome (5.48 +/- 0.30 fmol/ml vs 3.86 +/- 0.28, p less than 0.001). In addition, the preeclamptic group with the hemolysis, elevated liver enzymes, and low platelet count syndrome had significantly higher endothelin levels than those without the syndrome (8.30 +/- 1.62 fmol/ml vs 5.48 +/- 0.30, p less than 0.05). There was no correlation between plasma endothelin values and either systolic or diastolic blood pressure. We conclude that plasma endothelin levels are significantly increased in women with preeclampsia and particularly in those with the hemolysis, elevated liver enzymes, and low platelet count syndrome, suggesting an association with widespread endothelial damage.

Urinary dipstick protein: A poor predictor of absent or severe proteinuria☆☆☆*

OBJECTIVEnOur purpose was to compare urinary protein dipstick values with standard 24-hour urinary protein excretion in women with hypertension in pregnancy.nnnSTUDY DESIGNnUrinary protein dipstick determinations and concurrent 24-hour urinary protein excretion measurements were compared by review of 300 urine samples obtained from women with hypertension in pregnancy.nnnRESULTSnOne hundred twenty-three samples had negative to trace protein on dipstick on two occasions at least 6 hours apart. Eight-one (66%) of these patients had significant proteinuria (> or = 300 mg per 24 hours). Seventy-six samples revealed 3+ to 4+ protein on dipstick in at least two samples. Of these, 27 (36%) had heavy proteinuria (> or = 5 gm per 24 hours), and 42 (55%) had nephrotic range proteinuria of > or = 3.5 gm per 24 hours. One hundred one patients had urine dipstick values of 1+ to 2+, of whom 89 (88%) had significant proteinuria.nnnCONCLUSIONnUrinary protein dipstick values > or = 1+ have a positive predictive value of 92% (162/177) for predicting > or = 300 mg per 24 hours. In contrast, a dipstick of negative to trace should not be used to rule out significant proteinuria because its negative predictive value is only 34% (42/123) in hypertensive patients. Moreover, urine dipstick values of 3+ to 4+ should not be used to diagnose severe preeclampsia because their positive predictive value is only 36% (27/76).

Antimicrobial therapy in expectant management of preterm premature rupture of the membranes

We review the impact of antimicrobial treatment on maternal and fetal outcome during expectant management of preterm premature rupture of the membranes. Relevant studies were retrieved from Medline (1966 to August, 1994) with the search term fetal-membrane-premature-rupture and antibiotics or antimicrobial, Excerpta Medica (1972 to August, 1994) with the search term premature fetus, membrane rupture, and antibiotic or antimicrobial therapy, and the Cochrane database of systemic reviews with the criterion antibiotics and prelabour rupture of membranes. We also obtained unpublished data from a randomised clinical trial of ceftizoxime versus placebo. The selected studies were randomised controlled trials of systemic antimicrobial therapy for prolongation of gestation in non-labouring women after preterm premature rupture of the membranes. Data extraction was done by a single reviewer. Studies were evaluated for post-randomisation exclusion and other confounding variables that might introduce analytical bias. Analysis was done with SAS statistical software by a blinded investigator. Antimicrobial therapy after preterm premature rupture of the membranes is associated with a reduced number of women delivering within 1 week (62 vs 76%; OR 0.51, 95% CI 0.41-0.68), and reduced diagnosis of maternal morbidity including chorioamnionitis (12 vs 23%; 0.45, 0.33-0.60) and postpartum infection (8 vs 12%; 0.63, 0.41-0.97). Fetal morbidity, including confirmed sepsis (5 vs 9%; 0.57, 0.36-0.88), pneumonia (1 vs 3%; 0.32, 0.11-0.96), and intraventricular haemorrhage (9 vs 14%; 0.65, 0.45-0.92) were less often diagnosed after antimicrobial therapy. Separate analysis of the six placebo-controlled trials revealed similar or improved odds of pregnancy prolongation, chorioamnionitis, neonatal sepsis, postpartum infection, positive infant blood cultures, and pneumonia. Antimicrobial therapy, when used in the expectant management of preterm premature rupture of the membranes is associated with prolongation of pregnancy and a reduction in the diagnosis of maternal and infant morbidity. Further study should be directed towards determination of optimal antimicrobial therapy, increasing pregnancy prolongation, and enhancement of corticosteroid therapy for induction of pulmonary maturity after preterm premature rupture of the membranes.