Marshall D. Lindheimer

THE CLASSIFICATION AND DIAGNOSIS OF THE HYPERTENSIVE DISORDERS OF PREGNANCY: STATEMENT FROM THE INTERNATIONAL SOCIETY FOR THE STUDY OF HYPERTENSION IN PREGNANCY (ISSHP)

The literature relating to classification of the hypertensive disorders in pregnancy and diagnostic definitions of each hypertensive category has been and remains confusing to clinicians and investigators (1). One encounters an assortment of terms and schemes, some quite complex and detailed, and on occasion, the same term (e.g., pregnancy-induced hypertension) is used to include different disorders by various authors. This lack of consensus on classification and diagnosis is one reason for controversies in a variety of areas, including counseling, management, and documenting immediate and remote outcomes. Cognizant of these problems, the Council of the ISSHP appointed a committee to consider these issues, adopting many of their recommendations at the 12th World Congress in Paris, France, in July 2000. The following is a summary of the adopted report. The first charge to this committee, formed in October 1998, was to monitor the progress of the two working groups that were in the process of updating previous reports, one for the Australasian Society for the Study of Hypertension in Pregnancy (ASSHP) and the other for the National High Blood Pressure Education Program (NHBPEP) in the United States. These have now been published (2,3) and have been considered along with currently published criteria (e.g., the older ISSHP (4), WHO (3, and Canadian Hypertension Society (6) reports).

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...

Serial Assessment of the Cardiovascular System in Normal Pregnancy Role of Arterial Compliance and Pulsatile Arterial Load

BACKGROUND Temporal changes in systemic arterial compliance and wave propagation properties (pulsatile arterial load) and their role in ventricular-systemic arterial coupling during gestation have not been explored. Noninvasive methods combined with recently developed mathematical modeling techniques were used to characterize vascular and left ventricular (LV) mechanical adaptations during normal gestation. METHODS AND RESULTS Fourteen healthy women were studied at each trimester of pregnancy and again postpartum. Experimental measurements included instantaneous aortic pressure (subclavian pulse tracings) and flow (aortic Doppler velocities) and echocardiographic imaging of the LV. A small increase in LV muscle mass and end-diastolic chamber dimension occurred by late gestation, with no significant alterations in myocardial contractility. Cardiac output increased and the steady component of arterial load (total vascular resistance) decreased during pregnancy. Several changes in pulsatile arterial load were noted: Global arterial compliance increased (approximately 30%) during the first trimester and remained elevated thereafter. The magnitude of peripheral wave reflections at the aorta was reduced. The mathematical model-based analysis revealed that peripheral wave reflections at the aorta were delayed and that both conduit and peripheral vessels contributed to the increased arterial compliance. Finally, coordinated changes in the pulsatile arterial load and LV properties were responsible for maintaining the efficiency of LV-to-arterial system energy transfer. CONCLUSIONS The rapid time course of compliance changes and the involvement of both conduit and peripheral vessels are consistent with reduced vascular tone as being the main underlying mechanism. The pulsatile arterial load alterations during normal pregnancy are adaptive in that they help to accommodate the increased intravascular volume while maintaining the efficiency of ventricular-arterial coupling and diastolic perfusion pressure.

Maternal infection and risk of preeclampsia: Systematic review and metaanalysis

There are lingering questions regarding the association between maternal infection and preeclampsia. Systematic review and metaanalysis was conducted of observational studies that examined the relationship between maternal infection and preeclampsia. Forty-nine studies met the inclusion criteria. The risk of preeclampsia was increased in pregnant women with urinary tract infection (pooled odds ratio, 1.57; 95% CI, 1.45-1.70) and periodontal disease (pooled odds ratio, 1.76; 95% CI, 1.43-2.18). There were no associations between preeclampsia and presence of antibodies to Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus, treated and nontreated HIV infection, and malaria. Individual studies did not find a relationship between herpes simplex virus type 2, bacterial vaginosis, and Mycoplasma hominis and preeclampsia. Urinary tract infection and periodontal disease during pregnancy are associated with an increased risk of preeclampsia. More studies are required to verify this as well as to explore whether or not such relationships are causal and, if so, the mechanisms involved.

A modified definition for peripartum cardiomyopathy and prognosis based on echocardiography.

The diagnosis of peripartum cardiomyopathy is one of exclusion, made after careful search for an underlying cause. Research in this area is compromised by the reliance of some on clinical criteria alone without strict echocardiographic criteria. This article argues for uniform criteria that define peripartum cardiomyopathy, similar to the criteria for idiopathic dilated cardiomyopathy set forth by a National Heart, Lung, and Blood Institute-sponsored workshop and proposes that the new definition include heart failure within the last month of pregnancy or 5 months postpartum; absence of preexisting heart disease; no determinable etiology, the traditional definition; and strict echocardiographic criteria of left ventricular dysfunction: ejection fraction less than 45%, or M-mode fractional shortening less than 30%, or both, and end-diastolic dimension more than 2.7 cm/m2. Mortality from peripartum cardiomyopathy remains high, 25-50%, and a recent review related long-term prognosis to echocardiographic measures of left ventricular chamber dimension and function at diagnosis and recovery. We describe a modified pharmacologic echocardiographic stress test that might be useful in determining left ventricular contractile reserve in women believed to be recovered by routine echocardiographic studies. The test reproduces hemodynamic stress akin to pregnancy, and the data might be useful when counseling women on future childbearing. Women who respond with reduced cardiac reserve might be advised to avoid pregnancy.

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

Summary of the NHLBI Working Group on Research on Hypertension During Pregnancy

A Working Group on Research in Hypertension in Pregnancy was recently convened by the National Heart Lung and Blood Institute to determine the state of knowledge in this area and suggest appropriate directions for research. Hypertensive disorders in pregnancy, especially preeclampsia, are a leading cause of maternal mortality worldwide and even in developed countries increase perinatal mortality five‐fold. Much has been learned about preeclampsia but gaps in the knowledge necessary to direct therapeutic strategies remain. Oxidative stress is a biologically plausible contributor to the disorder that may be amenable to intervention. Hypertension that antedates pregnancy (chronic hypertension) bears many similarities to hypertension in nonpregnant women but the special setting of pregnancy demands information to guide evidence based therapy. The recommendations of the Working Group are to attempt a clinical trial of antioxidant therapy to prevent preeclampsia that is be complemented by mechanistic research to increase understanding of the genetics and pathogenesis of the disorder. For chronic hypertension clinical trials are recommended to direct choice of drugs, evaluate degree of control and assess implications to the mother and fetus. Recommendations to increase participation in this research are also presented.

Mapping the theories of preeclampsia and the role of angiogenic factors : A systematic review

OBJECTIVE: To evaluate claims that elevated soluble fms-like tyrosine kinase-1 receptor (sFlt-1) and decreased placental growth factor predict preeclampsia. DATA SOURCES: MEDLINE (1966–March 2006), EMBASE (1980–June 2006), POPLINE (1980–June 2006), CINAHL (1982–June 2006), and LILACS (1982–June 2006) were searched, and experts contacted. METHODS OF STUDY SELECTION: Studies identified and included were those reporting blood and urine levels of sFlt-1 or placental growth factor obtained before gestational week 30 or overt preeclampsia. TABULATION, INTEGRATION, AND RESULTS: Ten of 184 available studies analyzing sFlt-1 and 14 of 319 studies analyzing placental growth factor were included in this review. There was considerable interreport heterogeneity in methodology and results for sFlt-1 measured before gestational week 25. After week 25 placental growth factor and sFlt-1 levels varied consistently between the normal pregnancy group and women destined to develop preeclampsia, achieving significance in women who developed severe preeclampsia. CONCLUSION: Third-trimester increases in sFlt-1 and decreases in placental growth factor levels are associated with preeclampsia, specifically severe disease, based on retrospective data. The evidence is insufficient to recommend these markers to be used for screening, and prospective studies employing rigorous laboratory and study design criteria are needed to determine the clinical usefulness of these tests.

Thyroid Hormone and the Kidney

Thyroid hormones affect both renal morphology and function. They are required for kidney growth and development, and thyroid deficiency results in decreased renal plasma flow and glomerular filtration rate and in impaired urinary concentration and dilution. Thyroid hormones also influence membrane transport and electrolyte metabolism, and alterations in mineral metabolism in hyperthyroidism frequently cause calcium nephropathy which affects renal function adversely. The kidney plays an important role in the peripheral metabolism of iodine and thyroid hormones, and thyroid function is altered in certain kidney diseases, particularly chronic renal failure. The pathogenesis of these alterations is currently under active investigation.

Preeclampsia selectively impairs endothelium-dependent relaxation and leads to oscillatory activity in small omental arteries.

The vascular pathophysiology of preeclampsia, a hypertensive disorder unique to human pregnancy, has been postulated to be due to endothelial dysfunction, primarily manifest as deficient nitric oxide (NO) synthesis. We evaluated contraction (KCl and arginine vasopressin [AVP]) and dilation (acetylcholine and bradykinin) in small resistance-size omental arteries obtained during surgery from women with preeclampsia, postulating that these vessels would exhibit augmented contraction and diminished endothelium-dependent relaxation, most likely due to decreased NO synthesis. For comparison, vessels were also obtained from normotensive gravidas, pregnant women with chronic hypertension, or with chronic hypertension and superimposed preeclampsia, as well as from premenopausal nonpregnant controls. Vessels of approximately 200 micron in internal diameter were studied in vitro using a Mulvany-Halpern myograph. Maximal contraction due to either KCl or AVP was significantly augmented in vessels from women with preeclampsia; these vessels all exhibited endothelium- and cyclooxygenase-dependent phasic oscillations while vessels from all other groups exhibited only tonic contractions. Acetylcholine and bradykinin both led to dose- and endothelium-dependent relaxation which was unaffected by inhibitors of NO synthesis. Responses to bradykinin were similar in vessels from normal pregnant and preeclamptic women while those to acetylcholine were absent in vessels from women with preeclampsia. These data suggest specific defects in resistance-artery endothelium from women with preeclampsia.