Hypertensive Disorders of Pregnancy and Future Cardiovascular Health.

Hypertensive disorders of pregnancy (HDP) occur in almost 10% of gestations. These women are known to have higher cardiovascular morbidity and mortality later in life in comparison with parous controls who had normotensive pregnancies. Several studies have demonstrated that women with preeclampsia present in a state of segmental impaired myocardial function, biventricular chamber dysfunction, adverse biventricular remodeling, and hypertrophy, a compromised hemodynamic state and indirect echocardiographic signs of localized myocardial ischemia and fibrosis. These cardiac functional and geometric changes are known to have strong predictive value for cardiovascular disease in non-pregnant subjects. A "dose effect" response seems to regulate this relationship with severe HDP, early-onset HDP, coexistence of fetal growth disorders, and recurrence of HDP resulting in poorer cardiovascular measures. The mechanism underlying the relationship between HDP in younger women and cardiovascular disease later in life is unclear but could be explained by sharing of pre-pregnancy cardiovascular risk factors or due to a direct impact of HDP on the maternal cardiovascular system conferring a state of increased susceptibility to future metabolic or hemodynamic insults. If so, the prevention of HDP itself would become all the more urgent. Shortly after delivery, women who experienced HDP express an increased risk of classic cardiovascular risk factors such as essential hypertension, renal disease, abnormal lipid profile, and diabetes with higher frequency than controls. Within one or two decades after delivery, this group of women are more likely to experience premature cardiovascular events, such as symptomatic heart failure, myocardial ischemia, and cerebral vascular disease. Although there is general agreement that women who suffered from HDP should undertake early screening for cardiovascular risk factors in order to allow for appropriate prevention, the exact timing and modality of screening has not been standardized yet. Our findings suggest that prevention should start as early as possible after delivery by making the women aware of their increased cardiovascular risk and encouraging weight control, stop smoking, healthy diet, and daily exercise which are well-established and cost-effective prevention strategies.

Intrahepatic cholestasis of pregnancy: new insights into its pathogenesis.

AIM: To search a specific gene expression profile in women with intrahepatic cholestasis of pregnancy (ICP) and to evaluate the maternal and foetal outcome. METHODS: We consecutively enrolled 12 women with ICP and 12 healthy pregnant controls. The gene expression profile was assayed with the microarray technique including a panel of 5541 human genes. Microarray data were validated by real-time PCR technique. RESULTS: Caesarean delivery was performed in eight patients with ICP versus three controls (p = 0.05). ICP women delivered at earlier gestational age than control (p < 0.001). Foetal distress was recorded in two babies, but we failed to find any correlation between bile salt concentration and foetal distress. Twenty genes potentially correlated with ICP were found differentially expressed (p < 0.05). Among these, three belong to genetic classes involved in pathogenic mechanisms of ICP: (1) pathophysiology of pruritus (GABRA2, cases versus controls = 2, upregulated gene); (2) lipid metabolism and bile composition (HLPT, cases versus controls = 0.6, down-regulated gene) and (3) protein trafficking and cytoskeleton arrangement (KIFC3, cases versus controls = 0.5, down-regulated gene). CONCLUSIONS: Different gene expression may contribute to the complex pathogenesis of ICP. An upregulation of GABRA2 receptor may indicate that GABA may play a role in the pathogenesis of pruritus in this condition.

Effects of female sex hormones and contraceptive pill on the diagnostic work-up for primary aldosteronism.

OBJECTIVES: Due to the widespread use of the aldosterone to renin ratio (ARR), primary aldosteronism is currently recognized as a frequent cause of secondary hypertension. After a positive screening, primary aldosteronism diagnosis needs confirmation by an inhibitory test such as intravenous saline load (ivSLT). The aim of the present study was to investigate the role of female hormones in primary aldosteronism diagnosis, by evaluating possible differences by sex on ARR screening, on the rate of ivSLT response and analyzing the influence of free and oral contraceptive-induced menstrual cycle on ARR. METHODS: We examined ARR in 103 healthy normotensive volunteers, 81 hypertensive patients who underwent ivSLT, 33 healthy women during free menstrual cycle and after oral contraceptive therapy. RESULTS: A significantly higher proportion of normotensive women than men had an elevated ARR (13.6 versus 2.3%, P < 0.05). In 44 out of 81 hypertensive patients, diagnosis of primary aldosteronism was confirmed by ivSLT. Patients with positive and negative ivSLT differed only for sex distribution: 85.2% of men had the primary aldosteronism diagnosis confirmed, compared with 38.9% of women. In healthy women, renin and aldosterone concentrations increased from the follicular to luteal phase of menstrual period, with unchanged ARR. By contrast, renin nearly halved, aldosterone slightly decreased and ARR doubled after oral contraceptive therapy. CONCLUSION: ARR screening fails to predict positive ivSLT in most (60.2%) hypertensive women as compared with 14.8% of hypertensive men. ARR is more often increased in normotensive women than men. Oral contraceptive may affect ARR contributing to the diagnostic inaccuracy in women.

Therapy of inflammatory bowel diseases in pregnancy and lactation.

Inflammatory bowel diseases (IBDs) are a group of disorders characterised by chronic or relapsing inflammation within the gastrointestinal tract of variable severity. A chronic medication is often needed and management of fertile women is a crucial point because of the possible adverse effects associated with the administered drugs and the disease itself. The risk of pregnancy-related complications and the disease behaviour during pregnancy depends mainly on disease activity at time of conception. So, it is very important to plan the pregnancy and reach and maintain a clinical remission of the disease before conception. Drugs usually used in IBD treatment include 5- aminosalicylic acid compounds, corticosteroids, azathioprine and 6-mercaptopurine, cyclosporine A, mesalazine, and antibiotics such as metronidazole and ciprofloxacin. Management of IBD in pregnancy at present is not standardised or supported by strong evidence. In this report, we summarise the available data, mainly derived from retrospective and case-control studies, about IBD management in pregnancy, focusing mostly on the safety of drugs during gestation and peripartum.

Ballantyne syndrome: a case report.

Ballantyne syndrome (also called mirror syndrome or triple edema) describes the unusual association of fetal and placental hydrops with maternal preeclampsia. This is a case report illustrating a 37-year-old patient who was referred to our clinics at 28 weeks of gestation (wg) because of fetal hydrothorax. On examination, the woman did not show signs of preeclampsia. The fetal ultrasound examination revealed bulky hydrothorax, generalized subcutaneous edema, placental edema, and polyhydramnios. It was not possible to find the cause of the fetal hydrops. At 29 weeks and 4 days of gestation, the fetal hydrothorax was removed by two pleuro-amniotic shunts, but at the moment of our intervention anasarca was already present. In the following 3 days, despite observing bed rest, the mother developed edema of hands and face, while blood pressure remained normal. At 30 wg the patient underwent cesarean section because fetal movements ceased and the fetal heart rate monitoring showed loss of variability and decelerations. Before dying, the neonate lived for 20 days in a state of deep hypotension.