CHANGES IN FETAL AND MATERNAL DOPPLER PARAMETERS OBSERVED DURING ACUTE SEVERE HYPERTENSION TREATMENT WITH HYDRALAZINE OR LABETALOL: A RANDOMIZED CONTROLLED TRIAL

We evaluated 16 pregnant women with gestational age between 20 and 32 weeks in acute severe hypertension which were randomly allocated to receive either hydralazine or labetalol. Blood pressure and Doppler ultrasound parameters from maternal uterine and fetal middle cerebral and umbilical arteries were assessed during acute severe hypertension and after treatment. A significant reduction in systolic and diastolic blood pressure was observed in both groups. A significant change in Doppler parameters was observed only in pregnant women who received hydralazine: an increase in uterine arteries resistance index. We concluded that both drugs were highly effective in reducing blood pressure in these women. Despite the observed increase in resistance index of uterine arteries associated with hydralazine, the use of hydralazine and labetalol were not related to any significant changes in fetal Doppler, which is reassuring about the safety of these drugs when treating acute severe hypertension in pregnancy. (E-mail: wpmartins@gmail.com) (C) 2011 World Federation for Ultrasound in Medicine & Biology.

Doppler Echocardiographic Assessment of Pregnant Women with Chronic Arterial Hypertension

OBJECTIVE: To assess structural and functional cardiac changes in asymptomatic pregnant women with chronic arterial hypertension (CAH). METHODS: One hundred pregnant women with CAH underwent conventional Doppler echocardiography. The Student t test was used to compare them with 29 normotensive pregnant women (NT) in their third gestational trimester. RESULTS: Systolic (SBP; mmHg) and diastolic (DBP; mmHg) blood pressure values were higher (p<0.001) in the CAH pregnant women (SBP: 139±19 and DBP: 92± 18) as compared with those of the NT group (SBP: 112±10 and DBP: 74±9). A significant enlargement of the left atrium (4.10±0.48 cm vs 3.6±0.3 cm; p<0.001) and of the left ventricular normalized mass (59.6±19.7 g/cm2,7 vs 41.9±3.4 g/cm2,7; p<0.001) was observed. Cardiac output (CO, L/min) and systolic volume (SV, mL) were significantly higher in the CAH group (CO: 6.0±1.54 vs 4.9±2.1, p<0.01; SV: 77.3±19.8 vs 56.5±25.8, p<0.001). CONCLUSION: Chronic hypertensive pregnant women have structural and functional cardiac changes that justify routine cardiologic assessment, even in the absence of cardiopulmonary symptoms.

16q24.1 microdeletion in a premature newborn: Usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn.

OBJECTIVE:: Report of a 16q24.1 deletion in a premature newborn, demonstrating the usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn and multiple congenital malformations. DESIGN:: Descriptive case report. SETTING:: Genetic department and neonatal intensive care unit of a tertiary care children's hospital. INTERVENTIONS:: None. PATIENT:: We report the case of a preterm male infant, born at 26 wks of gestation. A cardiac malformation and bilateral hydronephrosis were diagnosed at 19 wks of gestation. Karyotype analysis was normal, and a 22q11.2 microdeletion was excluded by fluorescence in situ hybridization analysis. A cesarean section was performed due to fetal distress. The patient developed persistent pulmonary hypertension unresponsive to mechanical ventilation and nitric oxide treatment and expired at 16 hrs of life. MEASUREMENTS AND MAIN RESULTS:: An autopsy revealed partial atrioventricular canal malformation and showed bilateral dilation of the renal pelvocaliceal system with bilateral ureteral stenosis and annular pancreas. Array-based comparative genomic hybridization analysis (Agilent oligoNT 44K, Agilent Technologies, Santa Clara, CA) showed an interstitial microdeletion encompassing the forkhead box gene cluster in 16q24.1. Review of the pulmonary microscopic examination showed the characteristic features of alveolar capillary dysplasia with misalignment of pulmonary veins. Some features were less prominent due to the gestational age. CONCLUSIONS:: Our review of the literature shows that alveolar capillary dysplasia with misalignment of pulmonary veins is rare but probably underreported. Prematurity is not a usual presentation, and histologic features are difficult to interpret. In our case, array-based comparative genomic hybridization revealed a 16q24.1 deletion, leading to the final diagnosis of alveolar capillary dysplasia with misalignment of pulmonary veins. It emphasizes the usefulness of array-based comparative genomic hybridization analysis as a diagnostic tool with implications for both prognosis and management decisions in newborns with refractory persistent pulmonary hypertension and multiple congenital malformations.

Gestational diabetes mellitus and the risk of metabolic syndrome: a population-based study in Lausanne, Switzerland

RESUME EN FRANÇAIS BUTS. Étudier les relations entre le diabète gestationnel (GDM) et le syndrome métabolique (MS), comme la résistance à l'insuline est une des caractéristiques des 'deux conditions. Analyser le dépistage du diabète dans le post-partum pour identifier les facteurs de risque associés au développement d'un diabète de type 2 ultérieur. MÉTHODES. Étude rétrospective de toutes les grossesses uniques diagnostiquées avec un diabète gestationnel à l'hôpital universitaire de Lausanne, pendant une durée de trois ans. La présence d'une obésité, d'une hypertension ou d'une dyslipidémie avant la grossesse définissent les composants du syndrome métabolique. RÉSULTATS. Sur 5788 grossesses, 159 patientes (2.7%) présentaient un diabète gestationnel. Des composants du syndrome métabolique étaient présents avant la grossesse chez 26% des patientes (n=37/144) : 84% (n=31/37) étaient obèses, 38% (n=14/37) présentaient une hypertension et 22% (n=8/37) une dyslipidémie. Le développement d'une hypertension gravidique était associé à l'obésité (OR=3.2, p=0.02) et à la dyslipidémie (OR=5.4, p=0.002). Septante-quatre patientes (47%) sont revenues pour l'HGPO dans le post-partum. Celle-ci était anormale chez 20 femmes (27%): 11 % (n=8) présentaient un diabète de type 2 et 16% (n=12) avaient une intolérance au glucose. Les facteurs de risque indépendants associés à une anomalie de la tolérance au glucose dans le post-partum étaient d'avoir plus de 2 valeurs anormales au test diagnostique durant la grossesse et présenter des composants du syndrome métabolique (OR=5.2, CI 1.8-23.2 et OR=5.3, CI 1.3-22.2). CONCLUSIONS. Dans un quart des grossesses avec un diabète gestationnel, des anomalies métaboliques précèdent l'apparition de l'intolérance au glucose. Ces patientes présentent un haut risque de développer un syndrome métabolique et un diabète de type 2 ultérieurement. Là où le dépistage du diabète gestationnel n'est pas systématique, les praticiens devraient être avertis de ces risques métaboliques chez les patiente se présentant avec une obésité, une hypertension ou une dyslipidémie, afin de mieux les diagnostiquer et surtout de mieux les suivre et traiter après leur grossesse.

Moderate postnatal hyperoxia accelerates lung growth and attenuates pulmonary hypertension in infant rats after exposure to intra-amniotic endotoxin.

To determine the separate and interactive effects of fetal inflammation and neonatal hyperoxia on the developing lung, we hypothesized that: 1) antenatal endotoxin (ETX) causes sustained abnormalities of infant lung structure; and 2) postnatal hyperoxia augments the adverse effects of antenatal ETX on infant lung growth. Escherichia coli ETX or saline (SA) was injected into amniotic sacs in pregnant Sprague-Dawley rats at 20 days of gestation. Pups were delivered 2 days later and raised in room air (RA) or moderate hyperoxia (O₂, 80% O₂ at Denver's altitude, ∼65% O₂ at sea level) from birth through 14 days of age. Heart and lung tissues were harvested for measurements. Intra-amniotic ETX caused right ventricular hypertrophy (RVH) and decreased lung vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) protein contents at birth. In ETX-exposed rats (ETX-RA), alveolarization and vessel density were decreased, pulmonary vascular wall thickness percentage was increased, and RVH was persistent throughout the study period compared with controls (SA-RA). After antenatal ETX, moderate hyperoxia increased lung VEGF and VEGFR-2 protein contents in ETX-O₂ rats and improved their alveolar and vascular structure and RVH compared with ETX-RA rats. In contrast, severe hyperoxia (≥95% O₂ at Denver's altitude) further reduced lung vessel density after intra-amniotic ETX exposure. We conclude that intra-amniotic ETX induces fetal pulmonary hypertension and causes persistent abnormalities of lung structure with sustained pulmonary hypertension in infant rats. Moreover, moderate postnatal hyperoxia after antenatal ETX restores lung growth and prevents pulmonary hypertension during infancy.

Doppler Echocardiographic Assessment of Pregnant Women with Chronic Arterial Hypertension

OBJECTIVE: To assess structural and functional cardiac changes in asymptomatic pregnant women with chronic arterial hypertension (CAH). METHODS: One hundred pregnant women with CAH underwent conventional Doppler echocardiography. The Student t test was used to compare them with 29 normotensive pregnant women (NT) in their third gestational trimester. RESULTS: Systolic (SBP; mmHg) and diastolic (DBP; mmHg) blood pressure values were higher (p<0.001) in the CAH pregnant women (SBP: 139±19 and DBP: 92± 18) as compared with those of the NT group (SBP: 112±10 and DBP: 74±9). A significant enlargement of the left atrium (4.10±0.48 cm vs 3.6±0.3 cm; p<0.001) and of the left ventricular normalized mass (59.6±19.7 g/cm2,7 vs 41.9±3.4 g/cm2,7; p<0.001) was observed. Cardiac output (CO, L/min) and systolic volume (SV, mL) were significantly higher in the CAH group (CO: 6.0±1.54 vs 4.9±2.1, p<0.01; SV: 77.3±19.8 vs 56.5±25.8, p<0.001). CONCLUSION: Chronic hypertensive pregnant women have structural and functional cardiac changes that justify routine cardiologic assessment, even in the absence of cardiopulmonary symptoms.

The impact of prior preeclampsia on the risk of superimposed preeclampsia and other adverse pregnancy outcomes in patients with chronic hypertension

OBJECTIVE: We sought to compare the rates of superimposed preeclampsia and adverse outcomes in women with chronic hypertension with or without prior preeclampsia.STUDY DESIGN: We conducted secondary analysis of 369 women with chronic hypertension (104 with prior preeclampsia) enrolled at 12-19 weeks as part of a multisite trial of antioxidants to prevent preeclampsia (no reduction was found). Outcome measures were rates of superimposed preeclampsia and other adverse perinatal outcomes.RESULTS: Prepregnancy body mass index, blood pressure, and smoking status at enrollment were similar between groups. The rates of superimposed preeclampsia (17.3% vs 17.7%), abruptio placentae (1.0% vs 3.1%), perinatal death (6.7% vs 8.7%), and small for gestational age (18.4% vs 14.3%) were similar between groups, but preterm delivery <37 weeks was higher in the prior preeclampsia group (36.9% vs 27.1%; adjusted risk ratio, 1.46; 95% confidence interval, 1.05-2.03; P = .032).CONCLUSION: In women with chronic hypertension, a history of preeclampsia does not increase the rate of superimposed preeclampsia, but is associated with an increased rate of delivery at <37 weeks.

Mild gestational hyperglycaemia as a risk factor for metabolic syndrome in pregnancy and adverse perinatal outcomes

Objective The aims of this study were to evaluate the prevalence of metabolic syndrome (MS) in a cohort of pregnant women with a wide range of glucose tolerance, pre-pregnancy risk factors for MS during pregnancy and the effects of MS in the occurrence of adverse perinatal outcomes.Research Design and Methods One hundred and thirty six women with positive screening for gestational diabetes (GDM) were classified by two diagnostic methods: glycaemic profile and 100 g oral glucose tolerance test (OGTT) as normoglycaemic, mild gestational hyperglycaemic, GDM, and overt GDM. Markers of insulin resistance were measured between 24-28 and 36th week of gestation, and 6 weeks after delivery.Results The prevalence of MS was 0; 20.0; 23.5 and 36.4% in normoglycaemic, mild hyperglycaemic, GDM and overt GDM groups, respectively. Previous history of GDM with or without insulin use, body mass index (BMI) >= 25, hypertension, family history of diabetes in first-degree relatives, non-Caucasian ethnicity, history of prematurity and polyhydramnios were statistically significant pre-pregnancy predictors for MS in the index pregnancy, that by its turn increased the occurrence of adverse perinatal outcomes (p = 0.01).Conclusions The prevalence of MS increases with the worsening of glucose tolerance and is an independent predictor of adverse perinatal outcomes; impaired glycaemic profile identifies pregnancies with important metabolic abnormalities that are linked to the occurrence of adverse perinatal outcomes even in the presence of a normal OGTT, in patients that are not currently classified as having GDM. Copyright (C) 2008 John Wiley & Sons, Ltd.

Association Between Insulin Resistance, Glucose Intolerance, and Hypertension in Pregnancy

There is an association between insulin resistance, glucose intolerance, and essential hypertension, but the relation between insulin resistance, glucose intolerance, and hypertension diagnosed during pregnancy is not well understood. Transient hypertension of pregnancy, the new-onset nonproteinuric hypertension of late pregnancy, is associated with a high risk of later essential hypertension and glucose intolerance; thus, these conditions may have a similar pathophysiology. To assess the association between insulin resistance, glucose intolerance, essential hypertension, and subsequent development of proteinuric and nonproteinuric hypertension in pregnancy in women without underlying essential hypertension, we performed a prospective study comparing glucose (fasting, I and 2 hours postglucose load), insulin, glycosylated hemoglobin (HbA1c), high-density lipoprotein cholesterol (HDL-C), and triglycerides levels on routine screening for gestational diabetes mellitus. Women who developed hypertension in pregnancy (n = 37) had higher glycemic levels (fasting, 1 and 2 hours postglucose load) on a 100-gram oral glucose loading test, although only the fasting values showed a statistical significance (p < 0.05), and a significantly higher frequency of abnormal glucose loading tests, two hours after glucose load (>= 140 mg/dL) (p < 0.05) than women who remained normotensive (n = 180). Glucose intolerance was common in women who developed both subtypes of hypertension, particularly preeclampsia. Women who developed hypertension had greater prepregnancy body mass index (p < 0.0001), higher frequency and intensity of acanthosis nigricans (p < 0.0001), and higher baseline systolic and diastolic blood pressures (p <= 0.0001 for both), although all subjects were normotensive at baseline by study design; they also presented lower levels of HDL-C (p < 0.05). However, after adjustment for these and other potential confounders, an abnormal glucose loading test remained a significant predictor of development of hypertension (p < 0.05) and, specifically, preeclampsia (p < 0.01). There was a trend toward higher insulin and homeostasis model assessment-insulin resistance (HOMA-IR) levels in women developing any type of hypertension. When comparing women that remained normotensive to term with those with transient hypertension and preeclampsia, the preeclamptic women were born with lower weight (p < 0.05) and shorter length (p < 0.005); at screening they were older (p < 0.005), showed higher frequency and intensity of acanthosis nigricans (p < 0.0001), had higher prepregnancy BMI (p < 0.0005), as well as higher baseline systolic and diastolic blood pressures (p <= 0.0001 for both). They also showed higher HOMA-IR levels that did not show a statistical significance. When glucose tolerance status was taken in account, an association was found between increasing indexes of hypertension (p < 0.05) and of HOMA-IR (p < 0.05) with the worsening of glucose tolerance. These results suggest that insulin resistance and relative glucose intolerance are associated with an increased risk of new-onset hypertension in pregnancy, particularly preeclampsia, and support the hypothesis that insulin resistance may play a role in the pathogenesis of this disorder.

Oxidative DNA damage in diabetic and mild gestational hyperglycemic pregnant women

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Assessment of structural cardiac abnormalities and diastolic function in women with gestational diabetes mellitus

Background: The main manifestation of hyperglycaemia during pregnancy is gestational diabetes mellitus. It can herald diabetes mellitus type 2 and its deleterious long-term effects, such as hypertension and cardiovascular disease. The aim of this study was to assess diastolic function in women with gestational diabetes mellitus, one of the first signs of future cardiovascular disease.Methods: A total of 21 women with gestational diabetes mellitus and 23 healthy pregnant women (control group) between 34 and 37weeks of gestation underwent echocardiographic assessment. The diagnosis of gestational diabetes mellitus was made in agreement with the American Diabetes Association criteria. Echocardiographic images obtained were analysed according to the criteria of the American Society of Echocardiography. Data were analysed using Pearson correlation coefficient, analysis of variance and Student's t-test.Results: Women with gestational diabetes mellitus had higher posterior wall and interventricular septum thickness, increased left ventricular mass and left ventricular mass index, lower early diastolic annular velocity and early diastolic annular velocity/late diastolic annular velocity ratio. There was a positive correlation between left ventricular mass index and fasting glucose and pregnancy body mass index.Conclusion: Patients with gestational diabetes mellitus seem to have a different diastolic profile as well as a mildly dysfunctional pattern on echocardiogram, which may show a need for greater glycaemic control.

IRS-1 gene polymorphism and DNA damage in pregnant women with diabetes or mild gestational hyperglycemia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Growth of preterm low birth weight infants until 24 months corrected age: effect of maternal hypertension

Objective: To evaluate the growth pattern of low birth weight preterm infants born to hypertensive mothers, the occurrence of growth disorders, and risk factors for inadequate growth at 24 months of corrected age (CA).Methods: Cohort study of preterm low birth weight infants followed until 24 months CA, in a university hospital between January 2009 and December 2010. Inclusion criteria: gestational age < 37 weeks and birth weight of 1,500-2,499g. Exclusion criteria: multiple pregnancies, major congenital anomalies, and loss to follow up in the 2nd year of life. The following were evaluated: weight, length, and BMI. Outcomes: growth failure and risk of overweight at 0, 12, and 24 months CA. Student's t-test, Repeated measures ANOVA (RM-ANOVA), and multiple logistic regression were used.Results: A total of 80 preterm low birth weight infants born to hypertensive mothers and 101 born to normotensive mothers were studied. There was a higher risk of overweight in children of hypertensive mothers at 24 months; however, maternal hypertension was not a risk factor for inadequate growth. Logistic regression showed that being born small for gestational age and inadequate growth in the first 12 months of life were associated with poorer growth at 24 months.Conclusion: Preterm low birth weight born infants to hypertensive mothers have an increased risk of overweight at 24 months CA. Being born small for gestational age and inadequate growth in the 1st year of life are risk factors for growth disorders at 24 months CA. (C) 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Effect of gestational protein restriction on left ventricle hypertrophy and heart angiotensin II signaling pathway in adult offspring rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)