Mitchell P. Dombrowski

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...

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

Risk Factors and Outcome of Varicella-Zoster Virus Pneumonia in Pregnant Women

To determine the factors associated with an increased risk of developing varicella-zoster virus (VZV) pneumonia during pregnancy, a case-control analysis was done in which 18 pregnant women with VZV pneumonia were compared with 72 matched control subjects. VZV infection was identified clinically, and VZV pneumonia was diagnosed by dyspnea and findings on chest radiographs. Of 347 pregnant women with VZV infection, 18 (5.2%) had pneumonia treated with acyclovir, and none died. Mean gestational age at rash onset was 25.8 plus minus 8.8 weeks for patients with pneumonia and 17.7 +/- 10.3 weeks for control subjects, which was not significant in the multivariable model. Women with VZV pneumonia were significantly more likely to be current smokers (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.6-16.7) and to have > or = 100 skin lesions (OR, 15.9; 95% CI, 1.9-130.2). Pregnant women with VZV infection may be more likely to develop varicella pneumonia if they are smokers or manifest > or = 100 skin lesions.

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.

Frequency of congenital varicella syndrome in a prospective cohort of 347 pregnant women

OBJECTIVE To estimate the rate of congenital varicella zoster virus syndrome in neonates born to women developing varicella zoster virus infections during pregnancy. METHODS Pregnant women with clinical varicella zoster virus infection were enrolled at ten perinatal centers. Maternal and fetal immunoglobulin (Ig) G and IgM by fluorescent antibody confirmed 74.3% of cases. Specialists examined neonates at 0–6 months, 7–18 months, and 19–30 months after delivery to detect abnormalities of their eyes, hearing, and physical and developmental features. A hierarchical set of criteria was used to define congenital varicella syndrome. A jury of four investigators assigned the classification of all findings. RESULTS In 362 women enrolled from 1993 to 1996, 15 had herpes zoster, and 347 had primary varicella zoster virus infection. Varicella zoster virus affected 140 women (38.7%) in the first trimester, 122 (33.7%) in the second trimester, and 100 (27.6%) in the third trimester. Five twin pairs were included. Only one case (0.4%) of definite congenital varicella syndrome was found, a 3360‐g female infant having a left retinal macular lesion with typical skin scars after maternal varicella at 24 weeks. The maternal blood sample at birth was negative for IgG antibodies to toxoplasmosis and cytomegalovirus. Two cases involved fetal death at 20 weeks and fetal hydrops at 17 weeks after maternal varicella at 11 and 5 weeks, respectively. We found no cases of limb hypoplasia, microcephalus, or cataract. CONCLUSION The frequency of congenital varicella syndrome is very low (0.4%) in a prospectively studied cohort. Eye examinations of exposed infants had a low yield.

Predictive value of fetal serum β2-microglobulin for neonatal renal function

Abstract When fetal urinary-tract malformations (UTM) are discovered, management is based on the prediction of postnatal renal function, currently made by fetal urinary biochemistry and sonography. Serum β 2 -microglobulin has been used postnatally to estimate renal function and does not cross the placenta. We investigated the relation between fetal serum β 2 -microglobulin and renal function by comparing 64 unaffected fetuses and 15 fetuses with UTM. A β 2 -microglobulin above a 5·6 mg/L cut-off gave cross-validated sensitivity of 80·0%, specificity of 98·6%, a positive predictive value of 88·9%, and a negative predictive value of 97·1% for our cohort study.

Reduced medicolegal risk by compliance with obstetric clinical pathways: a case–control study☆

OBJECTIVE To estimate whether guideline compliance affected medicolegal risk in obstetrics and whether malpractice claims data can provide useful information on guideline noncompliance by focusing on the claims experience of a large health system delivering approximately 12,000 infants annually. METHODS We retrospectively identified 290 delivery-related (diagnosis-related groups 370–374) malpractice claims and 262 control deliveries at the health system during the period from 1988 to 1998. Clinical pathways for vaginal and cesarean delivery implemented in 1998 were used as a “standard of care.” We compared rates of non-compliance with the pathways in the claims and control groups, calculated an odds ratio for increased risk of being sued given departure from the guideline standards, and calculated the elevated risk of litigation introduced by noncompliance. We also compared the frequencies of different types of departures across claims and control groups. RESULTS Claims closely resembled controls on several descriptive measures (mothers age, location of delivery, type of delivery, and complication rates), but noncompliance with the clinical pathway was significantly more common among claims than controls (43.2% versus 11.7%, P < .001; odds ratio = 5.76, 95% confidence interval 3.59, 9.2). In 81 (79.4%) of the claims involving noncompliance with the pathway, the main allegation in the claim related directly to the departure from the pathway. The excess malpractice risk attributable to noncompliance explained approximately one third (104 of 290) of the claims filed (attributable risk = 82.6%). There were no significant differences in the types of deviation from the guidelines across claims and control groups. CONCLUSION In addition to reducing clinical variation and improving clinical quality of care, adherence to clinical pathways might protect clinicians and institutions against malpractice litigation. Malpractice data might also be a useful resource in understanding breakdowns in processes of care.

Clinical practice. Asthma in pregnancy.

Asthma is themost common respiratory disease that accompanies pregnancy. About 8% of pregnant women have asthma, which puts them at higher risk of known complications of pregnancy even when potential confounding variables are controlled, suggesting that better asthma control might reduce these risks. As most patients have a prior history of asthma, diagnosis of the condition during pregnancy is usually straightforward, but testing can be performed in women with unusual respiratory symptoms who do not have a history of asthma. Testing is similar to that performed in the nonpregnant woman, with demonstration of a reduced force expiratory volume in 1 second and force expiratory volume in 1 second to forced vital capacity ratio which improves 12% or greater with inhaled albuterol administration. Methacholine testing is contraindicated during pregnancy. Adequate asthma control is assessed on the basis of the frequency of symptoms and their severity (well-controlled defined as r2 d/wk of symptoms), the patient’s use of rescue therapy (well-controlled defined as r2 d/wk of use), a history of exacerbations requiring systemic corticosteroid administration (poor control defined as administration Z2 times in past 12mo), and the results of pulmonary function tests (adequate control defined as an force expiratory volume in 1 second Z80% of predicted). A substantial proportion of asthmatic exacerbations during pregnancy have been associated with nonadherence to treatment regimens using inhaled steroids. Therapy involves the long-termuseofmedications that prevent the manifestations of asthma [inhaled corticosteroids, long-acting b-agonists (LABAs), leukotrienemodifiers, cromolyn, and theophylline] and rescue drugs that offer quick symptom relief (short-acting inhaled b-agonists). Inhaled corticosteroids have been considered themost effectivemedication in nonpregnant patients. In studiesonpregnantpatients, inhaledbeclomethasonewasmore effective than theophylline in improving pulmonary function, and inhaledbeclomethasone in addition to b-agonists and oral corticosteroids were found to be more effective than oral corticosteroids or inhaled b-agonists alone when prescribed after a hospitalization for asthma.Most studies have found no increased adverse perinatal risks with the use of inhaled b-agonists or corticosteroids. The benefits of LABAs outweigh the risks as long as they are used concurrently with inhaled corticosteroids. Studies that have suggestedan increased riskof congenital malformations may be confounded by variables that are associatedwithmore severe asthma.Clearly the risks to the fetus whose mother uses asthma medication are lower than the risks associated with uncontrolled maternal asthma. For pregnant patients with well-controlled asthma, medications can be continued, with consideration of a step down in therapy if asthma has been controlled for 3 months or greater. The progression of asthma treatment involves 6 steps: (1) no therapy, (2) low dose inhaled steroid, (3) an increase in inhaled steroid dose, (4) addition of a LABA, (5) an increase in LABA dose, and (6) addition of oral prednisone for refractory cases. For those with treated asthma that is poorly controlled, a 2-step increase in therapy is recommended. Exacerbations of asthma in pregnant women should be managed with inhaled b-agonists, inhaled anticholinergic drugs, and systemic corticosteroids. Arterial oxygen saturation should be kept atZ95%. If the fetus has reached the point of viability, a fetal assessment that includes electronic fetal monitoring, a biophysical profile, or both, should be performed. During labor and delivery, the asthmatic parturient requires adequate hydration and analgesia with care taken that analgesia does not compromise the patient’s respiratory status. Lack of pain control can trigger bronchospasm. Patients who have been receiving systemic corticosteroids during pregnancy should receive intravenous corticosteroids during labor and for 24 hours after delivery to prevent adrenal crisis. Prostaglandins E or E1 can be used for cervical ripening, but carboprost (15-methyl prostaglandin F2q) should be avoided.Magnesium sulfate and terbutaline are preferred for tocolysis. Women with well-controlled asthma during pregnancy usually have good pregnancy outcomes. Education is necessary along with testing for asthma triggers. Treatment with inhaled budesonide is preferred due to more reassuring data in humans compared with other agents. Education on optimal inhaler technique should be given along with a personalized self-treatment action plan, with follow-up monthly throughout the pregnancy.

Incidence of preeclampsia among asthmatic patients lower with theophylline

The incidence of preeclampsia was reduced among asthmatic patients taking theophylline (one of 85) compared to other asthmatic patients (six of 68, p less than 0.05). Other factors did not appear to account for these results. Theophylline, which is known to inhibit platelet aggregation and alter vascular tone, may reduce the incidence of preeclampsia, at least among asthmatic patients.

Proteomic identification of serum peptides predicting subsequent spontaneous preterm birth

OBJECTIVE We sought to identify serum markers of subsequent spontaneous preterm birth (SPTB) in asymptomatic women prior to labor. STUDY DESIGN Serum proteomics was applied to sera from 80 pregnant women sampled at 24 weeks and an additional 80 pregnant women sampled at 28 weeks. Half had uncomplicated pregnancies and half had SPTB. RESULTS Three specific peptides arising from inter-alpha-trypsin inhibitor heavy chain 4 protein were significantly reduced in women at 24 and 28 weeks having subsequent SPTB. The most discriminating peptide had a sensitivity of 65.0% and specificity of 82.5%; odds ratio, 8.8; and 95% confidence interval, 3.1-24.8. A combination of the 3 new biomarkers and 6 previously studied biomarkers increased sensitivity to 86.5%, with a specificity of 80.6% at 28 weeks. CONCLUSION Three novel serum markers of SPTB have been identified using serum proteomics. Using a combination of these new markers with additional markers, women at risk of SPTB can be identified weeks prior to SPTB.