Extremely asynchronic delivery of second and third fetuses in a triple pregnancy.

Report of clinical treatment of a patient with a triple pregnancy after ICSI, who had the abortion of the first fetus at 16 weeks of gestation and the "asynchronic delivery" of the other two, at 28 weeks. A reproductive inflammatory process previously diagnosed in the couple could have been related with the premature rupture of membranes (PROM) occurred at 15.5 weeks of pregnancy. The clinical interventions described, made possible the delayed delivery and the survival of the other two triplets. This case shows us the importance to transfer no more than two embryos during ART, to avoid the catastrophic consequences of a triple pregnancy.

Endothelial dysfunction: a link among preeclampsia, recurrent pregnancy loss, and future cardiovascular events?

We tested the hypothesis that endothelial dysfunction could cause placentation-related defects, persist after the complicated pregnancy, and probably cause cardiovascular disease later in life. Brachial arterial reactivity and factors related to endothelial dysfunction, such as circulating cholesterol, uric acid, nitrites, l-arginine, asymmetrical dimethylarginine, vascular endothelial growth factor, and soluble vascular endothelial growth factor receptor-1, in women with previous healthy pregnancies (n=22), patients with severe preeclampsia (n=25), or patients with recurrent pregnancy loss (n=29), at day 10 of the luteal phase of an ovulatory cycle an average of 11 to 27 months after pregnancy were evaluated. Both groups with placentation defects had a significant decrease in endothelium-dependent dilatation, a higher rate of endothelial dysfunction, lower serum nitrites, and higher cholesterol as compared with control subjects; subjects with previous preeclampsia additionally had higher normal blood pressures and a greater parental prevalence of cardiovascular disease. Patients with recurrent pregnancy loss also demonstrated a significantly lower endothelium-independent vasodilatation. A trend to an inverse correlation was found between serum cholesterol serum and endothelial-mediated vasodilatation in the whole study population. Uric acid, l-arginine, asymmetrical dimethylarginine, vascular endothelial growth factor, and soluble vascular endothelial growth factor receptor-1 were similar in all of the groups. We postulate that endothelial dysfunction may represent a link between preeclampsia and increased cardiovascular disease latter in life and propose that women with unexplained recurrent miscarriages are also at increased cardiovascular risk. The identification and correction of endothelial dysfunction detected during the reproductive stage on obstetric outcome and on cardiovascular diseases needs to be elucidated.

Maternal melatonin stimulates growth and prevents maturation of the capuchin monkey fetal adrenal gland.

The primate fetal adrenal reaches a large size relative to body weight followed by a rapid decrease in size in the postnatal period. We tested the hypothesis that maternal melatonin stimulates growth and prevents maturation of the primate fetal adrenal gland. We suppressed maternal melatonin by exposing eight pregnant capuchin monkeys to constant light (LL) from 63% to 90% gestation (term 155 days). Three of these received daily oral melatonin replacement (LL + Mel). Five mothers remaining in light:dark cycle were used as controls. Fetuses were delivered at 90% gestation. The absence of maternal melatonin selectively decreased fetal adrenal weight (Control: 488.8 +/- 51.5; LL: 363.2 +/- 27.7 and LL + Mel 519 +/- 46 mg; P < 0.05 ANOVA) without effecting fetal weight, placental weight or the weight of other fetal tissues. Changes in fetal adrenal size were accompanied by an increase in the levels of Delta5-3beta-hydroxysteroid dehydrogenase (3beta-HSD) mRNA (Control: 0.8 +/- 0.2; LL: 5.2 +/- 0.6 and LL + Mel 0.8 +/- 0.1; 3beta-HSD/18S-rRNA; P < 0.05 ANOVA). In vitro we found that maternal melatonin suppression increased basal progesterone production to levels similar to those of the adult adrenal gland (Control: 0.36 +/- 0.09; LL 0.99 +/- 0.13; LL + Mel 0.18 +/- 0.06 and adult: 0.88 +/- 0.10 ng/mg of tissue; P < 0.05 ANOVA) but no change in cortisol production. We found an increased production of cortisone (Control: 1.65 +/- 0.60; LL: 5.44 +/- 0.63; LL + Mel: 2.90 +/- 0.38 and adult: 1.70 +/- 0.45 ng/mg of tissue; P < 0.05 ANOVA). Collectively, the effects of maternal melatonin suppression and their reversion by maternal melatonin replacement suggest that maternal melatonin stimulates growth and prevents maturation of the capuchin monkey fetal adrenal gland.

Diet and endothelial function.

Endothelial dysfunction is one of the earliest events in atherogenesis. A consequence of endothelial damage is a lower availability of nitric oxide (NO), the most potent endogenous vasodilator. NO inhibits platelet aggregation, smooth muscle cell proliferation and adhesion of monocytes to endothelial cells. Endothelial dysfunction is present in patients with cardiovascular disease and/or coronary risk factors, such as hypertension, dyslipidemia, diabetes, smoking or hyperhomocysteinemia. At present, soluble markers and high resolution ultrasound of the brachial artery, have provided simple tools for the study of endothelial function and the effects of several interventions. It has been demonstrated that dietary factors may induce significant changes on vascular reactivity. Nutrients, such as fish oil, antioxidants, L-arginine, folic acid and soy protein have shown an improvement in endothelial function that can mediate, at least partially, the cardioprotective effects of these substances. Attention has been focused on dietary patterns in populations with lower prevalence of cardiovascular disease. There is some evidence suggesting that Mediterranean diet characterized by high consumption of vegetables, fish, olive oil and moderate wine consumption may have a positive effect on endothelial function. These results give us evidence on the significant role of diet on endothelial function and its impact on the pathogenesis of atherosclerosis.

[Ultrasound assessment of endothelial function in Chilean children and adults]. / Evaluación ultrasonográfica de la función endotelial en niños y adultos chilenos.

BACKGROUND: Endothelial dysfunction is an important pathogenetic mechanism in the development of atherosclerosis. AIM: To evaluate endothelial function in Chilean children and adult subjects and to provide normal values of flow mediated dilatation (FMD) in the Chilean population. SUBJECTS AND METHODS: Flow mediated dilation of the brachial artery was measured by high resolution ultrasonography in healthy children (n=32) and adults (n=69) of both gender, in a group of 8 healthy women during 4 periods of pregnancy and late postpartum, and in 22 men and women with a history of stroke or coronary heart disease. RESULTS: FMD in boys and girls was 9.9 +/- 3.6 and 10.0 +/- 4.2% respectively (NS). The figures for young women and young men were 11.3 +/- 3.8 and 8.6 +/- 3.9, respectively (p=0.02); for postmenopausal women and older men, 5.5 +/- 6.6 and 7.6 +/- 6.7 respectively (NS). During normal pregnancy and postpartum there were no significant changes in FMD. Patients with cardiovascular disease had a FMD of 0.3 +/- 5.2%, (p <0.001, with other groups). CONCLUSIONS: The present study provides values of FMD in healthy Chilean subjects of different ages, and in patients with coronary heart disease.

Management of Eisenmenger syndrome in pregnancy with sildenafil and L-arginine.

BACKGROUND: Eisenmenger syndrome in pregnancy may be a life-threatening disease despite recent additions to the treatment options. CASE: We present a woman with severe pulmonary hypertension due to Eisenmenger syndrome treated during pregnancy and delivery and postpartum with L-arginine and sildenafil to enhance the nitric oxide pathway. This combination was associated with significant improvement in the mother's clinical and hemodynamic condition and fetal well-being. CONCLUSION: The concomitant use of sildenafil and L-arginine for the management of pulmonary hypertension in pregnancy, combined with multidisciplinary care, permitted a good outcome for the mother and her infant.

Maternal melatonin selectively inhibits cortisol production in the primate fetal adrenal gland.

We tested the hypothesis that in primates, maternal melatonin restrains fetal and newborn adrenal cortisol production. A functional G-protein-coupled MT1 membrane-bound melatonin receptor was detected in 90% gestation capuchin monkey fetal adrenals by (a) 2-[(125)I] iodomelatonin binding (K(d), 75.7 +/- 6.9 pm; B(max), 2.6 +/- 0.4 fmol (mg protein)(-1)), (b) cDNA identification, and (c) melatonin inhibition of adrenocorticotrophic hormone (ACTH)- and corticotrophin-releasing hormone (CRH)-stimulated cortisol but not of dehydroepiandrosterone sulphate (DHAS) production in vitro. Melatonin also inhibited ACTH-induced 3beta-hydroxysteroid dehydrogenase mRNA expression. To assess the physiological relevance of these findings, we next studied the effect of chronic maternal melatonin suppression (induced by exposure to constant light during the last third of gestation) on maternal plasma oestradiol during gestation and on plasma cortisol concentration in the 4- to 6-day-old newborn. Constant light suppressed maternal melatonin without affecting maternal plasma oestradiol concentration, consistent with no effect on fetal DHAS, the precursor of maternal oestradiol. However, newborns from mothers under constant light condition had twice as much plasma cortisol as newborns from mothers maintained under a normal light-dark schedule. Newborns from mothers exposed to chronic constant light and daily melatonin replacement had normal plasma cortisol concentration. Our results support a role of maternal melatonin in fetal and neonatal primate cortisol regulation.

Diet and endothelial function

Endothelial dysfunction is one of the earliest events in atherogenesis. A consequence of endothelial damage is a lower availability of nitric oxide (NO), the most potent endogenous vasodilator. NO inhibits platelet aggregation, smooth muscle cell proliferation and adhesion of monocytes to endothelial cells. Endothelial dysfunction is present in patients with cardiovascular disease and/or coronary risk factors, such as hypertension, dyslipidemia, diabetes, smoking or hyperhomocysteinemia. At present, soluble markers and high resolution ultrasound of the brachial artery, have provided simple tools for the study of endothelial function and the effects of several interventions. It has been demonstrated that dietary factors may induce significant changes on vascular reactivity. Nutrients, such as fish oil, antioxidants, L-arginine, folic acid and soy protein have shown an improvement in endothelial function that can mediate, at least partially, the cardioprotective effects of these substances. Attention has been focused on dietary patterns in populations with lower prevalence of cardiovascular disease. There is some evidence suggesting that Mediterranean diet characterized by high consumption of vegetables, fish, olive oil and moderate wine consumption may have a positive effect on endothelial function. These results give us evidence on the significant role of diet on endothelial function and its impact on the pathogenesis of atherosclerosis.

Bile acids increase response and expression of human myometrial oxytocin receptor.

OBJECTIVE: We tested the hypothesis that during intrahepatic cholestasis of pregnancy bile acids activate the myometrial oxytocin receptor pathway. STUDY DESIGN: Myometrial sensitivity to oxytocin and oxytocin-receptor messenger RNA and protein level was investigated. The ability of cholic acid to mediate such changes was evaluated. RESULTS: Cholestasis patients required lesser oxytocin to elicit four uterine contractions in 10 minutes (1.3+/-0.6 vs 3.6+/-0.8 U, P<.05, n=7) and had lower in vitro ED(50) (1.6 x 10(-10) mol/L vs 1.0 x 10(-8) mol/L, P<.05, n=7) than controls. The 24-hour incubation of control myometrial strips (n=7) with cholic acid (20 micromol/L) increased oxytocin sensitivity. Incubation of cultured myometrial cells (n=5) with cholic acid increased oxytocin-receptor expression (messenger RNA and protein). CONCLUSION: We demonstrate that during intrahepatic cholestasis of pregnancy, an activation of the oxytocin receptor pathway occurs. This event seems to be the result of a cholic acid-mediated increase in oxytocin-receptor expression.

[Pulmonary hypertension and pregnancy]. / Hipertensión pulmonar y embarazo.

A 36 year old woman, with an 18 year history of syncope, became pregnant shortly after a cardiac catheterization demonstrated a high pulmonary arterial pressure and resistance and a low cardiac output. During pregnancy she remained stable at NYHA FC III, on nifedipine, apresoline, isosorbide, aspirin and bed rest. At 28 weeks, catheterization showed a decreased pulmonary pressure and an increased cardiac output. At 38 weeks, she was submitted to an elective caesarean section, and delivered a healthy newborn of 2820 g. After 5 months, her catheterization showed a pulmonary artery pressure similar to the pre-pregnancy study. Her condition deteriorated, leading to death 10 months later. Urinary 6-keto-PGF1[symbol: see text], nitrates/nitrites, kallikrein and angiotensin-(1-7) were increased from 13 to 33 weeks, to drop in week 35 of pregnancy. The safe maternal and fetal outcome, and the intragestational hemodynamic improvement are attributed to a close multidisciplinary surveillance, and to the effects of the endogenous vasodilators of pregnancy on the reversible component of the pulmonary hypertension. Reports in the literature show a decrease in maternal mortality rate, from 56% for the period previous to 1963, to 34 and 30% for those spanning between 1978-1996 y 1997-2001 respectively.

Intrahepatic cholestasis of pregnancy: an intriguing pregnancy-specific disorder.

OBJECTIVE: To review animal and human data available regarding the etiology, maternal and fetal impact, and treatment of intrahepatic cholestasis of pregnancy (ICP). METHODS: Pertinent studies on human and animal models of ICP were selected through a MEDLINE database search, focusing on etiology and clinical impact of the disease. Analytic and descriptive studies were included, and the data were analyzed looking for crude numbers. RESULTS: Intrahepatic cholestasis of pregnancy is a pregnancy-specific disorder. Its prevalence is higher in Chile and Sweden compared with any other population. Its etiology is largely unknown, although endocrine, genetic, and environmental factors have been postulated as responsible for the appearance of the disease. Maternal effects of ICP are mild; however, there is a clear association between ICP and poor perinatal outcome, including a higher frequency of fetal distress, preterm labor and delivery, and unexplained fetal death. The treatment is mainly symptomatic. Recent data suggest that oral use of ursodeoxycholic acid improves maternal condition and might prevent the fetal complications of ICP. CONCLUSIONS: Intrahepatic cholestasis of pregnancy should be considered a high-risk condition, and careful fetal assessment and appropriate medical intervention might improve perinatal outcome.

[Primary aldosteronism and pregnancy: report of 2 cases]. / Hiperaldosteronismo primario y embarazo: lecciones obtenidas de 2 casos clínicos.

Based on two patients, we discuss the difficulties in diagnosing and managing primary aldosteronism in pregnancy, which derive from changes of the renin-angiotensin-aldosterone axis, from the uncertainty regarding blood pressure control along gestation and postpartum, and from the contraindication to the use of spironolactone. The first case is a 27 years old woman with a long standing refractory hypertension, a hemorrhagic stroke with left brachial hemiplegia and crural hemiparesia, two miscarriages, one stillbirth and one offspring with intrauterine growth retardation. Due to hypokalemia, a plasma aldosterone/renin activity ratio of 91, and a negative genetic screening for glucocorticoid remediable aldosteronism (GRA), a primary hyperaldosteronism with normal adrenals in CT scan was diagnosed, and good blood pressure control was attained with spironolactone. After two and a half years of normotension, a fifth pregnancy, managed with methyldopa evolved with satisfactory blood pressures, plasma potassium, fetal growth, uterine and umbilical arterial resistance indexes, and maternal endothelial function. At 37 1/2 weeks of pregnancy the patient delivered a healthy newborn weighing 2,960 g. Blood pressure rose during the 48 hours of postpartum in the absence of proteinuria and required i.v. hydralazine. The second patient is a 37 years old woman, with known refractory hypertension for 7 years, hypokalemia, plasma aldosterone/renin activity ratio greater than 40, normal adrenals in the CAT scan, and a negative genetic screening for GRA. She had normotensive pregnancies 5 and 3 years prior to the detection of hypertension, with hypertensive crisis in both postpartum periods, retrospectively considered as expressions of primary hyperaldosteronism.