Carole McBride

The effect of maternal hypertension on mortality in infants 22, 29weeks gestation.

OBJECTIVE To evaluate the effect of maternal hypertension on mortality risk prior to discharge, in infants 22+0 to 29+6weeks gestational age. STUDY DESIGN We evaluated 88,275 North American infants whose births were recorded in Vermont Oxford Network centers between 2008 and 2011 Infants born between 22+0 and 29+6weeks gestational age were evaluated in 2-week gestational age cohorts and followed until death or discharge. Logistic regression was used to adjust for birth weight, antenatal steroid exposure, infant sex, maternal race, inborn/outborn, prenatal care and birth year. RESULTS 21,896 infants were born to hypertensive mothers; 13% died prior to Neonatal Intensive Care Unit discharge compared to 20% of the 66,379 infants born to mothers without hypertension. After adjustment, infants had significantly lower mortality compared to preterm infants not born to hypertensive mothers, at all gestational ages examined (22/23: odds ratio (OR)=0.65 (95% Confidence Interval (CI): 0.55, 0.77; 24/25); OR=0.77 (95% CI: 0.71, 0.84); 26/27: OR=0.66 (95% CI: 0.59, 0.74); 28/29: OR=0.58 (95% CI: 0.51, 0.67). Additionally, births associated with maternal hypertension increase dramatically by gestational age, resulting in a larger proportion of births associated with maternal hypertension at later gestational ages. CONCLUSIONS Preterm birth due to any cause carries significant risk of mortality, especially at the earliest of viable gestational ages. Maternal hypertension independently influences mortality, with lower odds of mortality seen in infants born to hypertensive mothers, after adjustment, and should be taken into consideration as an element in counseling parents.

The relationship of a family history for hypertension, myocardial infarction, or stroke with cardiovascular physiology in young women.

Cardiovascular disease (CVD) and preeclampsia share several pathophysiologic risk factors. We examined family history (FH) and physiologic status in 60 healthy, nulliparous women to determine the relationship between FH and known risk factors for CVD. Data are presented as mean ± standard error (SE). Decreased uterine blood flow was observed in women with FH of hypertension (+FH: 21.5 ± 1.7, no FH: 33.3 ± 9.0 mL/min; P = .04). Women reporting an FH of stroke showed increased alpha- and beta-adrenergic response, as measured by Valsalva maneuver (α: FH: 24.7 ± 1.9, −FH: 18.9 ± 1.1 mm Hg, P = .02; β: FH: 22.0 ± 2.1, −FH: 16.9 ± 1.4 mm Hg; P = .04), and increased cardiac output (4.83 ± 0.22 vs 4.31 ± 0.12 L/min; P = .01). We identified no significant physiologic associations linked to an FH of myocardial infarction. Our observations show significant differences in physiologic characteristics in women with specific CVD family histories. These data, coupled with known heritable contributions to CVD and preeclampsia, suggest a distinct physiologic phenotype that may link preeclampsia risk with FH of CVD, independent of pregnancy.

Maternal Hypertension and Mortality in Small for Gestational Age 22- to 29-Week Infants:

Infants born before 30 weeks gestational age (GA) to mothers with hypertension (HTN) experience lower rates of mortality and serious morbidities when corrected for maternal and infant characteristics. Growth restriction and maternal HTN are often associated. We sought to determine if small for gestational age (SGA) infants have similarly decreased mortality risk when born to mothers with HTN. We identified 6897 singleton SGA, 22 + 0 to 29 + 6 weeks GA infants born between 2008 and 2011, cared for at 578 North American centers in the Vermont Oxford Network. Chromosomal abnormalities and birth defects were excluded. Mortality rates prior to discharge were compared between 4317 HTN and 2580 comparison infants. Logistic regression was used to adjust for birth weight, infant sex, maternal race, inborn/outborn, antenatal steroid exposure, prenatal care, and GA. Small for gestational age HTN infants were older (mean: 26.9 [1.9] vs 26.6 [2.2] weeks; P < .001) and larger (HTN = 584 [159] g vs 562 [156] g; P < .001) than comparison infants. Death prior to discharge occurred in 29% of HTN and 43% of comparison infants. Univariate analyses revealed lower mortality for HTN infants (odds ratio [OR] = 0.54, 95% confidence interval [CI]: 0.48-0.60). After adjustment, mortality remained lower when compared to non-HTN infants (OR = 0.60, 95% CI: 0.52-0.69). Extremely preterm SGA infants face high rates of mortality. Although maternal HTN is associated with SGA, SGA infants born to mothers with HTN have decreased risk of mortality compared to non-HTN SGA infants, prior to and after adjustment for antenatal and maternal characteristics. This may reflect detrimental physiologic effects associated with alternative mechanisms for fetal growth restriction and is important for parental counseling.

Adiposity, but not Obesity, Is Associated With Arterial Stiffness in Young Nulliparous Women

Subclinical vascular dysfunction is increasingly recognized as an independent risk factor for cardiovascular events and adverse pregnancy outcomes. The evidence linking indices of obesity and vascular dysfunction is mixed. As an example, some data suggest that adiposity may be a better predictor of endothelial dysfunction than body mass index (BMI). The aim of the current study is to compare the association of obesity, as evaluated by BMI, and a direct measure of body fat to biophysical parameters of vascular function including flow-mediated vasodilation and pulse wave velocity (PWV) in healthy nulliparous reproductive-age women. This is a secondary analysis of data collected as a prospective study of prepregnancy physiology in healthy, nulliparous women. Body mass index was calculated as weight (kg)/height (m2). Total and android body fat were calculated by dual-energy X-ray absorptiometry. Brachial PWV and flow-mediated vasodilation were assessed ultrasonographically. Seventy-nine women were evaluated. Mean BMI was 24.4 (5.4) kg/m2, and 15% of women were obese (BMI ≥ 30 kg/m2). In contrast, 39% were considered to have excess adiposity, with ≥39% android body fat. Brachial PWV was associated with increased adiposity, but not obesity. We found no differences in flow-mediated dilation associated with either BMI or body fat. Adiposity may be superior to BMI in identifying women with vascular dysfunction at increased risk of adverse pregnancy outcome and cardiovascular disease. Proper identification may allow implementation of prevention strategies to improve perinatal outcomes and maternal health.

Differences in cardiovascular function comparing prior preeclamptics with nulliparous controls

OBJECTIVE The objective of the current study was to evaluate cardiovascular function; including blood pressure, cardiac output, pulse wave velocity and vascular compliance in nonpregnant nulliparous women compared to women with a history of preterm preeclampsia. STUDY DESIGN This was a case control study. Blood pressure was measured using the Finapres Pro. Baseline cardiac output was determined by echocardiography. Pulse wave velocity was estimated using simultaneous electrocardiographic tracings and ultrasound determined arterial flow waveforms and calculated as estimated distance divided by the time interval between EKG r-wave peak and ultrasound derived peak popliteal artery flow. During volume challenge, 500mL of lactated Ringers solution was infused through an indwelling antecubital catheter over 10min. Cardiac output and blood pressure during and 15min after the infusion were estimated using the Finapres Pro. MAIN OUTCOME MEASURES Indices of arterial stiffness and vascular compliance. RESULTS Previous preeclamptics exhibited a significant increase in pulse pressure and cardiac output in response to volume challenge when compared with nulliparous controls. Prior preeclamptics had a strong positive correlation between blood pressure indices (r=0.50-0.68, p⩽0.01) and pulse pressure (r=0.58, P=0.008) with pulse wave velocity that was not evident in control women. CONCLUSIONS In women with prior preterm preeclampsia a relationship between blood pressure, intravascular volume and arterial stiffness, is evident in the nonpregnant state and in the absence of hypertension or overt cardiovascular disease. This supports an overarching hypothesis that nonpregnant physiology is an important contributor to pregnancy adaptations.

Contributions of Remodeling and Asymmetrical Growth to Vertebral Wedging in a Scoliosis Model

STUDY DESIGN We performed a laboratory study of rats of 3 different ages with imposed angulation and compressive loading to caudal vertebrae to determine causes of vertebral wedging. OBJECTIVES The purpose was to determine the percentage of total vertebral wedging that was caused by asymmetric growth, vertebral body, and epiphyseal wedging. Approval from the Institutional Animal Care and Use Committee, the University of Vermont, was obtained for the live animal procedures used in this study. BACKGROUND SUMMARY Vertebral wedging from asymmetrical growth (Hueter-Volkmann law) is reported to cause vertebral wedging in scoliosis with little attention to the possible contribution of bony remodeling (Wolffs law). METHODS In our study, an external fixator imposed a 30° lateral curvature and compression of 0.1 megapascal (MPa) in 5- and 14-week-old animals (Groups 1 and 2) and 0.2 MPa in 14- and 32-week-old animals (groups 3 and 4). Total vertebral wedging was measured from micro CT scans. Wedging due to asymmetrical growth and epiphyseal remodeling was calculated from fluorescent labels and the difference was attributed to vertebral body wedging. RESULTS Total vertebral wedging averaged 18°, 6°, 10° and 5° in Groups 1, 2, 3, and 4, respectively. Metaphyseal asymmetrical growth averaged 8°, 1°, 4°, 0° (44%, 17%, 40% and 0% of total). Epiphyseal wedging averaged 9°, 0°, 3°, and -1°. The difference (vertebral body) averaged 1°, 5°, 3°, and 7° (6%, 83%, 30% and 140% of total). The growth of the loaded vertebrae as a percentage of control vertebrae was 56%, 39% and 25% in Groups 1, 2 and 3; negligible in Group 4. Vertebral body cortical remodeling, with increased thickness and increased curvature on the concave side was evident in young animals and 0.2 MPa loaded older animals. CONCLUSIONS We conclude that asymmetrical growth was the largest contributor to vertebral wedging in young animals; vertebral body remodeling was the largest contributor in older animals. If, conversely, vertebral wedging can be corrected by appropriate loading in young and old animals, it has important implications for the nonfusion treatment of scoliosis.