Paul J. Meis

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.

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...

The preterm prediction study: Fetal fibronectin testing and spontaneous preterm birth*

Objective To evaluate the presence of fetal fibronectin in the cervix and vagina as a screening test for spontaneous preterm birth. Methods Two thousand nine hundred twenty-nine women at ten centers were routinely screened every 2 weeks from 22–24 to 30 weeks for cervical and vaginal fetal fibronectin. A positive test was defined as a value equal to or greater than 50 ng/mL. The relation between a positive test at four gestational ages and spotaneous pretern birth at various intervals after the test was determined. Results In each testing period 3–4% of the fetal fibronectin tests were positive. The correlation between cervical and vaginal fetal firbonectin at the same visit was always approximately 0.7 (P < .001), and that between cervical or vaginal fetal fibronectin in consecutive visits was between 0.17 and 0.25 (P < .001). The sensitivity of fetal fibronectin at 22–24 weeks to predict spontaneous preterm birth at less than 28 weeks was 0.63, and the relative risk for a positive versus negative test was 59. The specificity was always 96–98%, whereas the positive predictive value rose from 13% to 36% as the upper limit of the definition of preterm birth was increased from less than 28 to less than 37 weeks. The relative risk for spontaneous preterm birth after a positive fetal fibronectin test compared with a negative fetal fibronectin test varied substantially by testing period and by the definition of spontaneous preterm birth, but always remained greater than 4 and statistically significant. Conclusion A positive cervical or vaginal fetal fibronectin test at 22–24 weeks predicted more than half of the spontaneous preterm births at less than 28 weeks (sensitivity 0.63). As the definition of spontaneous preterm birth was extended to include later gestational ages or when the fetal fibronectin test was performed later in pregnancy, the level of association between a positive fetal fibronectin test and spontaneous preterm birth, while remaining highly significant, tended to decrease. Although fetal fibronectin is an excellent test for predicting spontaneous preterm birth, we present no evidence that the use of this test will result in a reduction in spontaneous preterm birth.

The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus.

Objective: We sought to estimate the frequency of pregnancy-related thromboembolic events among carriers of the factor V Leiden (FVL) mutation without a personal history of thromboembolism, and to evaluate the impact of maternal and fetal FVL mutation carriage or other thrombophilias on the risk of adverse outcomes. Methods: Women with a singleton pregnancy and no history of thromboembolism were recruited at 13 clinical centers before 14 weeks of gestation from April 2000 to August 2001. Each was tested for the FVL mutation, as was the resultant conceptus after delivery or after miscarriage, when available. The incidence of thromboembolism (primary outcome), and of other adverse outcomes, was compared between FVL mutation carriers and noncarriers. We also compared adverse outcomes in a secondary nested carrier-control analysis of FVL mutation and other coagulation abnormalities. In this secondary analysis, we defined carriers as women having one or more of the following traits: carrier for FVL mutation, protein C deficiency, protein S deficiency, antithrombin III deficiency, activated protein C resistance, or lupus anticoagulant-positive, heterozygous for prothrombin G20210A or homozygous for the 5,10 methylenetetrahydrofolate reductase mutations. Carriers of the FVL mutation alone (with or without activated protein C resistance) were compared with those having one or more other coagulation abnormalities and with controls with no coagulation abnormality. Results: One hundred thirty-four FVL mutation carriers were identified among 4,885 gravidas (2.7%), with both FVL mutation status and pregnancy outcomes available. No thromboembolic events occurred among the FVL mutation carriers (0%, 95% confidence interval 0–2.7%). Three pulmonary emboli and one deep venous thrombosis occurred (0.08%, 95% confidence interval 0.02–0.21%), all occurring in FVL mutation noncarriers. In the nested carrier-control analysis (n = 339), no differences in adverse pregnancy outcomes were observed between FVL mutation carriers, carriers of other coagulation disorders, and controls. Maternal FVL mutation carriage was not associated with increased pregnancy loss, preeclampsia, placental abruption, or small for gestational age births. However, fetal FVL mutation carriage was associated with more frequent preeclampsia among African-American (15.0%) and Hispanic (12.5%) women than white women (2.6%, P = .04), adjusted odds ratio 2.4 (95% confidence interval 1.0–5.2, P = .05). Conclusion: Among women with no history of thromboembolism, maternal heterozygous carriage of the FVL mutation is associated with a low risk of venous thromboembolism in pregnancy. Neither universal screening for the FVL mutation, nor treatment of low-risk carriers during pregnancy is indicated. Level of Evidence: II-2

Asthma during pregnancy

OBJECTIVE: To determine neonatal and maternal outcomes stratified by asthma severity during pregnancy by using the 1993 National Asthma Education Program Working Group on Asthma and Pregnancy definitions of asthma severity. The primary hypothesis was that moderate or severe asthmatics would have an increased incidence of delivery at <32 weeks of gestation compared with nonasthmatic controls. METHODS: This was a multicenter, prospective, observational cohort study conducted over 4 years at 16 university hospital centers. Asthma severity was defined according to the National Asthma Education Program Working Group on Asthma and Pregnancy classification and modified to include medication requirements. This study had 80% power to detect a 2- to 3-fold increase in delivery less than 32 weeks of gestation among the cohort with the moderate or severe asthma compared with controls. Secondary outcome measures included obstetrical and neonatal outcomes. RESULTS: The final analysis included 881 nonasthmatic controls, 873 with mild asthma, 814 with moderate, and 52 with severe asthma. There were no significant differences in the rates of preterm delivery less than 32 weeks (moderate or severe 3.0%, mild 3.4%, controls 3.3%; P = .873) or less than 37 weeks of gestation. There were no significant differences for neonatal outcomes except discharge diagnosis of neonatal sepsis among the mild group compared with controls, adjusted odds ratio 2.9, 95% confidence interval 1.2, 6.8. There were no significant differences for maternal complications except for an increase in overall cesarean delivery rate among the moderate-or-severe group compared with controls (adjusted odds ratio 1.4, 95% confidence interval 1.1, 1.8). CONCLUSION: Asthma was not associated with a significant increase in preterm delivery or other adverse perinatal outcomes other than a discharge diagnosis of neonatal sepsis. Cesarean delivery rate was increased among the cohort with moderate or severe asthma. LEVEL OF EVIDENCE: II-2

Factors associated with preterm birth in Cardiff, Wales: II. Indicated and spontaneous preterm birth

OBJECTIVE Our purpose was to examine and contrast associations of risk factors with spontaneous preterm birth and indicated preterm birth. STUDY DESIGN Separate multiple logistic regression analyses were performed of indicated and spontaneous preterm births in a large database of births in Cardiff, Wales. RESULTS Spontaneous preterm births were associated with young maternal age, low maternal weight, low or high parity, previous abortion, smoking, and early pregnancy bleeding. Indicated preterm births were associated with older age, low weight, previous stillbirth, bacteriuria, and early pregnancy bleeding. CONCLUSION Spontaneous and indicated preterm births have different overall profiles of association with pregnancy risk factors.

Factors associated with preterm birth in Cardiff, Wales: I. Univariable and multivariable analysis

OBJECTIVE Our purpose was to examine the associations of demographic, social, and medical factors with risk of preterm birth. STUDY DESIGN By use of the Cardiff Births Survey, a large database of largely homogeneous (white) births in Wales, multivariable analysis by logistic regression examined the relative importance of risk variables associated with preterm birth. RESULTS Significant independent associations with preterm birth were found (in decreasing order of magnitude) for late pregnancy bleeding, preeclampsia-proteinuria, low maternal weight, low maternal age, early pregnancy bleeding, history of previous stillbirth, smoking, high parity, low or high hemoglobin concentration, history of previous abortion, low social class, bacteriuria, and nulliparity. CONCLUSION In this population demographic, social, and medical characteristics of the pregnancies showed significant associations with preterm birth.

Causes of low birth weight births in public and private patients

This examination of the cause of low birth weight births in two model populations, one of public and one of private patients, finds significant differences in the reasons for low birth weight births in the two groups. Idiopathic premature labor was related to 47.1% of private low birth weight births, but only 24.8% of public births; low birth weight term (26.7%) and premature rupture of fetal membranes (33.7%) were more common in public low birth weight births than in private births (13.8% and 23.0%, respectively). Medical problems were related to 16.1% of private and 14.9% of public low birth weight births. Since current prematurity prevention methods are most likely to prevent low birth weight births related to idiopathic premature labor, the relative success of such programs in reducing the rate of low birth weight births is likely to depend on the characteristics of the patient population to which the programs are directed.

Predictors of pre-eclampsia in women at high risk

OBJECTIVE We assessed several variables as predictors for pre-eclampsia risk in a group of women at high risk. STUDY DESIGN We studied 2503 women with either diabetes mellitus, chronic hypertension, multifetal gestation, or pre-eclampsia in a previous pregnancy who participated in a multicenter study comparing aspirin and placebo in preventing pre-eclampsia. We evaluated multiple variables for predicting pre-eclampsia risk with use of univariate and multivariable analysis. RESULTS Parity and mean arterial pressure at randomization were most predictive of pre-eclampsia risk. The risk was 8% with a mean arterial pressure at enrollment of <75 mm Hg versus 27% with a mean arterial pressure >85 mm Hg (relative risk and 95% confidence interval 3.3 [2.4 to 4.4]). The risk of pre-eclampsia was 26% in nulliparous patients versus 17% in parous subjects (relative risk and 95% confidence interval 1.5 [1.3-1.8]). CONCLUSIONS The finding that second-trimester mean arterial pressure affects pre-eclampsia risk suggests that the pathophysiologic process of preeclampsia is initiated before that time.

Blood transfusion and cesarean delivery

OBJECTIVE: To evaluate risks for intraoperative or postoperative packed red blood cell transfusion in women who underwent cesarean delivery. METHODS: This was a 19-university prospective observational study. All primary cesarean deliveries from January 1, 1999, to December 31, 2000, and all repeat cesareans from January 1, 1999, to December 31, 2002, were included. Trained, certified research nurses performed systematic data abstraction. Primary and repeat cesarean deliveries were analyzed separately. Univariable analyses were used to inform multivariable analyses. RESULTS: A total of 23,486 women underwent primary cesarean delivery, of whom 762 (3.2%) were transfused (median 2 units, 25th% to 75th% 2–3 units). A total of 33,683 women underwent primary cesarean delivery, and 735 (2.2%) were transfused (median 2 units, 25th% to 75th% 2–4 units). Among primary cesareans, general anesthesia (odds ratio [OR] 4.2, 95% confidence interval [CI] 3.5–5.0), placenta previa (OR 4.8, CI 3.5–6.5) and severe (hematocrit less than 25%) preoperative anemia (OR 17.0, CI 12.4–23.3) increased the odds of transfusion. Among repeat cesareans, the risk was increased by general anesthesia (OR 7.2, CI 5.9–8.7), a history of five or more prior cesareans (OR 7.6, CI 4.0–14.3), placenta previa (OR 15.9, CI 12.0–21.0), and severe preoperative anemia (OR 19.9, CI 14.5–27.2). CONCLUSION: Overall, the risk of transfusion in association with cesarean is low. However, both severe preoperative maternal anemia and placenta previa are associated with markedly increased risks. The former argues for optimizing maternal antenatal iron status to avoid severe anemia and the latter for careful perioperative planning when previa complicates cesarean. LEVEL OF EVIDENCE: II-2