Effect of Docosahexaenoic Acid on Apoptosis and Proliferation in the Placenta: Preliminary Report.

INTRODUCTION: Observational studies confirm a higher incidence of preeclampsia in patients with low erythrocyte concentrations of omega-3 fatty acids. Observations point to an association of disorders of pregnancy, such as intrauterine growth restriction (IUGR) and preeclampsia, with excessive apoptosis. One potential mechanism of action of docosahexaenoic acid (DHA) promoting a reduction in the risk of pathological pregnancy may be by influencing these processes in the placenta. MATERIALS AND METHODS: We investigated 28 pregnant women supplemented with a fish oil product containing 300 mg DHA starting from pregnancy week 20 until delivery (DHA group). The control group consisted of 50 women who did not receive such supplementation (control group). We determined the expression of Ki-67 and p21 as markers of proliferation and caspase 3 activity as a marker of apoptosis and DHA levels in umbilical cord blood. RESULTS: Caspase 3 activity was significantly lower in the DHA group in comparison to the control group. Umbilical cord blood DHA concentration was higher in the DHA group. The expression of the proteins p21 and Ki-67 did not differ significantly between the groups. CONCLUSIONS: We observed an association between DHA supplementation and inhibition of placental apoptosis. We did not find an association between DHA and proliferation process in the placenta.

Late prematurity in twins: a Polish multicenter study.

The study aimed at investigating the impact of late prematurity (LPT) on neonatal outcome in twins and neonatal morbidity and mortality within LPT with regard to the completed weeks of gestation. The study was conducted in six tertiary obstetric departments from different provinces of Poland (Warsaw, Lublin, Poznan, Wroclaw, Bytom). It included 465 twin deliveries in the above centers in 2012. A comparative analysis of maternal factors, the course of pregnancy and delivery and neonatal outcome between LPT (34 + 0-36 + 6 weeks of gestation) and term groups (completed 37 weeks) was performed. The neonatal outcome included short-term morbidities. The analysis of neonatal complication rates according to completed gestational weeks was carried out. Out of 465 twin deliveries 213 (44.8%) were LPT and 156 (33.55%) were term. There were no neonatal deaths among LPT and term twins. One-third of LPT newborns suffered from respiratory disorders or required antibiotics, 40% had jaundice requiring phototherapy, and 30% were admitted to NICU. The analysis of neonatal morbidity with regard to each gestational week at delivery showed that most analyzed complications occurred less frequently with the advancing gestational age, especially respiratory disorders and NICU admissions. The only two factors with significant influence on neonatal morbidity rate were neonatal birth weight (OR = 0.43, 95% CI = 0.2-0.9, p = .02) and gestational age at delivery (OR = 0.62, 95% CI = 0.5-0.8, p < .01). LPT have a higher risk of neonatal morbidity than term twins. Gestational age and neonatal birth weight seem to play a crucial role in neonatal outcome in twins.

Polyunsaturated fatty acids in pregnancy and metabolic syndrome: a review.

This review presents available evidence for possible application of n-3 long chain polyunsaturated fatty acids (PUFAs) in pregnant obese women with metabolic syndrome (MS) and focuses on prophylaxis of pregnancy complications associated with MS such as gestational hypertension, preeclampsia and gestational diabetes. Dietary supplementation with n-3 PUFAs has recently become popular and their adequate intake during pregnancy and early childhood is of clinical importance. The results of experimental and epidemiological investigations reveal that n-3 PUFAs, especially α- linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), may decrease the risk of cardiovascular diseases. It is believed that n-3 PUFAs affect a multitude of molecular pathways, involving regulation of gene expression, alteration of physical and chemical properties of cellular membranes and modulation of membrane channels and proteins. A large body of evidence focuses on anti-inflammatory properties of PUFAs which seem to be fundamental in prevention and reversing of insulin resistance, atherogenic dyslipidemia, hypertension, thromboembolism and in improving vascular function. Despite the potential PUFAs benefits of decreasing insulin resistance, their application in order to prevent preeclampsia, gestational hypertension and gestational diabetes mellitus in pregnant women with MS has not yet been established. Numerous reports have revealed that appropriate fetal development, including neuronal, retinal and immune function depends on EPA and DHA which are crucial also for prevention of preterm birth. Thus the supplementation with EPA and DHA is highly recommended during pregnancy although the optimal dosing and treatment strategies still need to be determined.

[Clinical practice guidelines of the Team of Experts of the Polish Gynecological Society: management of the intrahepatic cholestasis of pregnancy]. / Rekomendacje Zespolu Ekspertów Polskiego Towarzystwa Ginekologicznego dotyczace postepowania w wewnatrzwatrobowej cholestazie ciezarnych.

Intrahepatic Cholestasis of Pregnancy (ICP) constitutes the most common, reversible liver disease closely connected with pregnancy and spontaneously resolving in puerperium. ICP usually reoccurs in consecutive pregnancies (45-90%), often in a more intensified form. Many compounds (hormones, cytokines, medicines, endotoxins) can impair transport in the hepatocyte, disturb the intracellular transport and increase the permeability of the intercellular connections. As a result, the elements of bile may appear in the peripheral blood. Gestational cholestasis constitutes a classic example of intrahepatic cholestasis. The etiology of ICP is multifactorial with hormonal, genetic and environmental factors participating in the process. The diagnosis is based on the presence of pruritus, elevated values of bile acids in the blood serum and of aminotransferases (aspartic, aminopropionic and gamma-glutamylotranspeptydase (AspAt, AlAt, GGTP)), as well as spontaneous remission in the second or third week after childbirth, of lack of other illnesses causing pruritus and icterus. Clinical and biochemical symptoms of ICP include: pruritus without skin rash (usually after 30 weeks of gestation), mild icterus, steatorrhea etc. Abnormalities in the laboratory tests of the LFT (liver function tests) encompass: an increase in the serum concentration of fatty acids (BA) which can be the first and only laboratory abnormality. Concentrations surpassing 10 micromol/l are considered to be abnormal. Concentration of BA higher than 40 micromol/l allows to recognize a case of severe ICP, connected with the risk of premature delivery presence of the meconium liquor, surgical means of delivery and low APGAR score of the newborn (< 7 pt). In about 80% of pregnant women with ICP, the BA concentration ranges between 10-40 micromol/l, but perinatal results are comparable with uncomplicated pregnancies. Some authors are of the opinion that abnormal AlAt value is the most sensitive test, other authors consider the abnormal values of alkaline phosphatase and bilirubin to be the most pathognomonic factors. Other abnormal tests include: higher activity of alpha-hydroxybutyric dehydrogenase correlated with an increase of the alkaline phosphatase and bilirubin; mild metabolic acidosis; dyslipidemia with elevated concentrations of the total lipids, total cholesterol and free LDL cholesterol and apolipoprotein; abnormal glucose tolerance test. ICP constitutes a medical problem that carries a considerable risk for the fetus, resulting from an increased flow of bile acids to the fetal blood circulation (elevated level in the amniotic fluid, in the umbilical blood serum and meconium). The risk of adverse effects for the fetus correlates with the rise of BA concentration in maternal blood serum. Cholestasis increases the risk of premature labor, presence of meconium in the amniotic fluid, fetal bradycardia, intrauterine asphyxia and stillbirth, particularly when the concentration of serum bile acids on an empty stomach is above 40 micromol/l. However, maternal clinical signs and symptoms do not correlate with the fetal outcome. Aspiration of bile acids or their accumulation in the fetal blood circulation are responsible for the increased frequency of RDS appearing in ICP. The aim of the obstetric management of ICP is to reduce maternal symptoms and biochemical disorders and to minimize the risk of premature delivery fetal distress and sudden death. ICP management should include: bed regime, light, low-fat diet, no stress, upper abdomen ultrasound examination, LFT tests and thrombotic tests once a week, monitoring of the fetal well-being with the available biophysical methods, pharmacotherapy and therapeutic termination of pregnancy in case of serious illness and/or the fetal distress. Ursodeoxycholic acid (UDCA) is the basis of the pharmacological treatment of pregnant women and currently constitutes the most promising treatment option of ICP. UDCA is administered orally in the dosage of 10-16 mg/kg/24, what in practice means 250-300 mg/2-3 times a day.

[Obesity among women. Pregnancy after bariatric surgery: a qualitative review]. / Otylosc u kobiet. Ciaza p operacji bariatrycznej--przeglad jakosciowy.

Bariatric surgery is a safe and most effective method of achieving substantial long-term weight loss. Surgery should be considered in case of all patients with a BMI of more than 40 kg/m2 and for those with a BMI of over 35 kg/m2 with obesity-related co-morbidities, after conventional treatment failure. The most frequently used procedures in surgical treatment of obesity performed mostly laparoscopically are restrictive operations limiting energy intake by reducing gastric capacity (vertical banded gastroplasty adjustable gastric band, sleeve gastrectomy) and restrictive/ malabsorptive surgeries also inducing decreased absorption of nutrients by shortening the functional length of the small intestine (Roux-en-Y gastric bypass). Frequent complications following surgery may include hyperemesis, intragastric band migration, gastric perforation, nutritional deficiencies, anastomotic leak, bleeding, anastomotic stricture, internal hernia, wound infection. It is generally recommended for women after bariatric surgery to wait approximately at least 12 months before becoming pregnant. There exists considerable threat that rapid weight loss (relative starvation phase) may be unhealthy for a mother and a baby. Pregnancy after weight loss surgery is not only safe for the mother and the baby but may also be less risky than pregnancy in morbidly obese patients. Postoperative nutrient supplementation and close supervision before, during, and after pregnancy adjusted to individual requirements of a woman can help to prevent nutrition-related complications such as deficiencies in iron, vitamin A, vitamin B12, vitamin K, folate and calcium, and improve maternal and fetal health.

[Tocolytic therapy in threatened preterm labor]. / Leczenie tokolityczne w zagrazajacym porodzie przedwczesnym.

The most important benefit of tocolysis is a 48-hour prolongation of gestational age in order to administer corticosteroids to reduce perinatal mortality and morbidity as well as, if necessary to gain time for "in utero" transfer to a tertiary centre with neonatal facilities. The tocolytic agents used in clinical practice can be grouped into six classes, namely: calcium channel blockers, betamimetics, magnesium sulfate, cyclooxygenase inhibitors, oxytocin receptor antagonists and nitric oxide donors. The use of them should be individualized and based on tocolytic effectiveness, safety gestational age as well as maternal, fetal and neonatal outcomes. Data from clinical trials suggests that nifedipine appears to be the drug of first choice in the management of preterm labor.

Glyburide for the treatment of gestational diabetes mellitus.

Insulin is the traditional treatment for gestational diabetes mellitus (GDM) unresponsive to dietary interventions. Until recently, oral hypoglycemic drugs had been contraindicated due to concerns regarding teratogenicity and the possibility of neonatal hypoglycemia. In contrast to other sulfonylurea drugs, in vitro and in vivo investigations have demonstrated very low transplacental transport of glyburide to the fetal circulation. The mechanisms preventing glyburide from crossing the human placenta are not completely understood. A combination of extremely high protein binding and a relatively short elimination half-life might partially explain it. It has also been demonstrated that glyburide is effluxed from the fetal to the maternal circulation by the breast cancer resistance protein (BRCP) and the human multidrug resistance protein 3 (MRP3). Since 2000, several studies have reported an 80-85% success rate of glyburide treatment. However, some authors have noticed glyburide-related increased risk of preeclampsia, macrosomia, neonatal hypoglycemia, admission to a neonatal intensive care unit and need for phototherapy. These possible maternal as well as neonatal adverse outcomes warrant further investigations. Until that time, the use of glyburide should remain inadvisable in pregnancy.

[Efficacy and safety of Black cohosh (Actaea/Cimicifuga racemosa) in the treatment of vasomotor symptoms--review of clinical trials]. / Skutecznosc i bezpieczenstwo stosowania Pluskwicy groniastej (Actaea/Cimicifuga racemosa) w leczeniu objawów naczynioruchowych--przeglad badan klinicznych.

The occurrence of vasomotor symptoms in women is directly related to deficiency of estrogen, which occurs as a result of natural or surgical menopause. Hot flushes may also be a major problem for patients with a history of breast cancer, as they may result directly from cancer treatment (oophorectomy, chemotherapy-induced ovarian failure or adjuvant tamoxifen citrate therapy). Despite the lack of reliable data regarding their efficacy and safety, in recent years the usage of herbs among menopausal women has increased dynamically all over the world. The following paper reviews professional literature about Black Cohosh (Actaea/Cimicifuga racemosa), either used alone or in combination with other medicinal herbs administered in management of vasomotor symptoms. Extracts of the rootstock of Black cohosh contain such potentially biologically active constituents as triterpene glycosides (actein, cimicifugoside, deoxyacetein), isoferulic acid and alkaloids (n-methylcytisine). The mechanism of its action remains unclear. Some authors suggest that Black Cohosh contains substances with selective estrogen receptor modulator (SERM) activity. Recent data has demonstrated that Black Cohosh may have an effect on dopaminergic and serotoninergic systems. Thirty-two papers formed the basis for this review. Open-label, noncomparative studies, as well as treatment-controlled, randomized, open trials, have proven that Black Cohosh significantly reduced frequency or severity of hot flashes. The results of randomized, placebo-controlled, double-blind clinical trials were contradictory. Adverse symptoms have been rare (5,4%), mild and reversible. Most of them included gastrointestinal upsets, rashes, headaches, dizziness and mastalgia. Nevertheless, single cases of serious adverse events, including acute hepatocellular damage, have been reported, but without a clear causality relationship.