Vaginal micronised progesterone for the prevention of hypertensive disorders of pregnancy: A systematic review and meta-analysis.

BACKGROUND: Treatment with vaginal progesterone reduces the risk of miscarriage and preterm birth in selected high-risk women. The hypothesis that vaginal progesterone can reduce the risk of hypertensive disorders of pregnancy (HDP) is unexplored. OBJECTIVES: To summarise the evidence on the effectiveness of vaginal progesterone to reduce the risk of HDP. SEARCH STRATEGY: We searched Embase (OVID), MEDLINE (OVID), PubMed, CENTRAL and clinicaltrials.gov from inception until 20 June 2023. SELECTION CRITERIA: We included placebo-controlled randomised trials (RCTs) of vaginal progesterone for the prevention or treatment of any pregnancy complications. DATA COLLECTION AND ANALYSIS: We extracted absolute event numbers for HDP and pre-eclampsia in women receiving vaginal progesterone or placebo, and meta-analysed the data with a random effects model. We appraised the certainty of the evidence using GRADE methodology. MAIN RESULTS: The quantitative synthesis included 11 RCTs, of which three initiated vaginal progesterone in the first trimester, and eight in the second or third trimesters. Vaginal progesterone started in the first trimester of pregnancy lowered the risk of any HDP (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53-0.93, 2 RCTs, n = 4431 women, I2 = 0%; moderate-certainty evidence) and pre-eclampsia (RR 0.61, 95% CI 0.41-0.92, 3 RCTs, n = 5267 women, I2 = 0%; moderate-certainty evidence) when compared with placebo. Vaginal progesterone started in the second or third trimesters was not associated with a reduction in HDP (RR 1.19, 95% CI 0.67-2.12, 3 RCTs, n = 1602 women, I2 = 9%; low-certainty evidence) or pre-eclampsia (RR 0.97, 95% CI 0.71-1.31, 5 RCTs, n = 4274 women, I2 = 0%; low-certainty evidence). CONCLUSIONS: Our systematic review found first-trimester initiated vaginal micronised progesterone may reduce the risk of HDP and pre-eclampsia.

Hipotiroidismo subclínico y pérdida de embarazo: una revisión de la literatura / Subclinical Hypothyroidism and Pregnancy Loss: A Literature Review

Existe una alta prevalencia de hipotiroidismo subclínico (SCH) en el embarazo. Está vinculado a una importante morbilidad y mortalidad materna y fetal. Los efectos de SCH sobre el embarazo incluyen mayores riesgos de hipertensión gestacional y ruptura prematura de membranas (PROM). Sus fetos y bebés tenían más probabilidades de sufrir de bajo peso al nacer (LBW) y retraso del crecimiento intrauterino (IUGR). El riesgo de aborto espontáneo se informa alto en varios estudios para SCH no tratado. SCH se asocia directamente con una mayor presencia de anti -cuerpos anti TPO en suero materno. La detección temprana y el tratamiento de SCH han sido testigos de mejores resultados en términos de resultado del embarazo. Esta revisión se centra para establecer la relación de una mayor prevalencia de SCH en los países en desarrollo, así como su asociación con el aumento de los cuerpos anti TPO en suero materna y sacar una conclusión que puede ayudar a reducir las razones y proporcionar una solución. Este estudio concluyó que SCH es más frecuente en los países en desarrollo, ya sea debido a la deficiencia de yodo, una disminución de la conciencia sobre este problema o menos acceso a las instalaciones médicas. Por lo tanto, se sugiere que las hembras con antecedentes de partos prematuros, IUGR anteriores o abortos involuntarios deben someterse a una detección de hipotiroidismo subclínico y niveles de anticuerpos anti TPO durante sus visitas prenatales

There is a high prevalence of subclinical hypothyroidism (SCH) in pregnancy. It is linked to significant maternal and fetal morbidity and mortality. SCH's effects on pregnancy include increased risks of gestational hypertension and premature rupture of membranes (PROM). Their fetuses and infants had been more likely to suffer from low birth weight (LBW) and intrauterine growth retardation (IUGR). The risk of miscarriage is reported high in various studies for untreated SCH. SCH is directly associated with increased presence of anti TPO anti bodies in maternal serum. Early detection and treatment of SCH have witnessed better results in terms of pregnancy outcome. This review focuses to establish the relationship of increased prevalence of SCH in the developing countries as well as its association with increased anti TPO anti bodies in maternal serum and draw a conclusion which can help narrow down the reasons and provide solution. This study concluded that SCH is more prevalent in developing countries, either due to iodine deficiency, decreased awareness about this problem or less access to medical facilities. Therefore, it is suggested that females with history of preterm deliveries, previous IUGRs, or miscarriages should undergo screening for subclinical hypothyroidism and Anti TPO antibody levels during their antenatal visits.

A Comparison of the Cost-Effectiveness of Lifestyle Interventions in Pregnancy.

OBJECTIVES: Lifestyle interventions during pregnancy improve maternal and infant outcomes. We aimed to compare the cost-effectiveness of 4 antenatal lifestyle intervention types with standard care. METHODS: A decision tree model was constructed to compare lifestyle intervention effects from a novel meta-analysis. The target population was women with singleton pregnancies and births at more than 20 weeks' gestation. Interventions were categorized as diet, diet with physical activity, physical activity, and mixed (lacking structured diet and, or, physical activity components). The outcome of interest was cost per case prevented (gestational diabetes, hypertensive disorders in pregnancy, cesarean birth) expressed as an incremental cost-effectiveness ratio (ICER) from the Australian public healthcare perspective. Scenario analyses were included for all structured interventions combined and by adding neonatal intensive care unit costs. Costs were estimated from published data and consultations with experts and updated to 2019 values. Discounting was not applied owing to the short time horizon. RESULTS: Physical activity interventions reduced adverse maternal events by 4.2% in the intervention group compared with standard care and could be cost saving. Diet and diet with physical activity interventions reduced events by 3.5% (ICER = A$4882) and 2.9% (ICER = A$2020), respectively. Mixed interventions did not reduce events and were dominated by standard care. In scenario analysis, all structured interventions combined and all interventions when including neonatal intensive care unit costs (except mixed) may be cost saving. Probabilistic sensitivity analysis showed that for physical activity and all structured interventions combined, the probability of being cost saving was 58% and 41%, respectively. CONCLUSIONS: Governments can expect a good return on investment and cost savings when implementing effective lifestyle interventions population-wide.

Loss of the Protective Effect of Estrogen Contributes to Maternal Gestational Hypertension-Induced Hypertensive Response Sensitization Elicited by Postweaning High-Fat Diet in Female Offspring.

Background A recent study conducted in male offspring demonstrated that maternal gestational hypertension (MHT) induces hypertensive response sensitization (HTRS) elicited by postweaning high-fat diet (HFD). In this study, we investigated the sensitizing effect of MHT on postweaning HFD-induced hypertensive response in female rat offspring and assessed the protective role of estrogen in HTRS. Methods and Results The results showed that MHT also induced a sensitized HFD-elicited hypertensive response in intact female offspring. However, compared with male offspring, this MHT-induced HTRS was sex specific in that intact female offspring exhibited an attenuated increase in blood pressure. Ovariectomy significantly enhanced the HFD-induced increase in blood pressure and the pressor response to centrally administered angiotensin II or tumor necrosis factor-α in offspring of normotensive dams, which was accompanied by elevated centrally driven sympathetic activity, upregulated mRNA expression of prohypertensive components, and downregulated expression of antihypertensive components in the hypothalamic paraventricular nucleus. However, when compared with HFD-fed ovariectomized offspring of normotensive dams, the MHT-induced HTRS and pressor responses to centrally administered angiotensin II or tumor necrosis factor-α in HFD-fed intact offspring of MHT dams were not potentiated by ovariectomy, but the blood pressure and elicited pressor responses as well as central sympathetic tone remained higher. Conclusions The results indicate that in adult female offspring MHT induced HTRS elicited by HFD. Estrogen normally plays a protective role in antagonizing HFD prohypertensive effects, and MHT compromises this normal protective action of estrogen by augmenting brain reactivity and centrally driven sympathetic activity.

Naringenin prevents pregnancy-induced hypertension via suppression of JAK/STAT3 signalling pathway in mice.

BACKGROUND: Pregnancy-induced hypertension (PIH) is characterized by high blood pressure during pregnancy, which causes perinatal and maternal mortality. Inflammation, oxidative stress and the JAK2/STAT3 signalling pathway have been reported to play critical roles in the pathogenies of PIH. Due to the safety and side effects of current treatments for PIH, searching for new therapeutic agents is urgently needed. Naringenin is a flavonoid with anti-inflammation and anti-oxidation activities. In the current study, the effects of naringenin on PIH were investigated. METHODS: We established the PIH mouse model and administrated naringenin to these mice. The blood pressure, total urine protein, plasma levels of vasodilation converting enzyme (VCE), α-1A adrenergic receptor (α-ADR) and angiotensin, inflammatory cytokines, oxidative stress markers were measured. The protein levels of reactive oxygen species proto-oncogene 1 (ROS1), superoxide dismutase 2 (SOD2), signal transducer and activator of transcription 3 (STAT3), phospho-STAT3, Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1), Janus kinase 2 (JAK2) and phospho-JAK2, in vascular endothelium cells were detected by western blot. RESULTS: Administration of naringenin significantly decreased blood pressure, total urine protein level, plasma levels of VCE, α-ADR and angiotensin in PIH mice. Naringenin decreased serum levels of pro-inflammatory cytokines interleukin (IL)-2, IL-6 and tumour necrosis factor alpha (TNF-α), while increased IL-10. Naringenin decreased serum levels of ROS, endothelin while increased SOD and nitric oxide levels. Western blot analysis showed that naringenin inhibited ROS expression, while increased SOD expression in vascular endothelial cells of mice. In addition, western blot also showed that naringenin inhibited JAK2/STAT3 signalling by suppressing SHP-1 expression in vascular endothelial cells of mice. CONCLUSION: Naringenin suppressed the activation of JAK2/STAT3 signalling pathway and promoted SHP-1 expression, leading to ameliorated hypertension in pregnancy.

Melatonin attenuates hypertension and oxidative stress in a rat model of L-NAME-induced gestational hypertension.

Preeclampsia is a life-threatening multiorgan systemic disease with manifestations including gestational hypertension, oxidative stress, and vascular dysfunction. We aimed to evaluate the therapeutic effects of melatonin on an L-NAME (NLG-nitro-l-arginine methyl ester)-induced rat preeclampsia model. During gestation, L-NAME was added to drinking water at 50 mg/kg/day from gestation day (GD) 8. Rats received the combination of L-NAME with melatonin (10 mg/kg/day), or aspirin (1.5 mg/kg/day), and rats that received only L-NAME or no treatments were used as controls. Aspirin was mixed with rodent chow and melatonin was administered intraperitoneally. Blood pressure and urine protein content were monitored every 3 days. On GD19, blood samples were collected for biochemical analysis. Compared to untreated L-NAME rats, melatonin led to markedly lowered blood pressure and urine protein content, and recovery in the fetus alive ratio, fetal weight, and the fetal weight/placental weight ratio. Compared to untreated L-NAME rats, plasma antioxidant capacity and plasma malondialdehyde were increased and decreased by melatonin, respectively, in L-NAME rats. Melatonin treatment also reduced sFlt-1, increased PlGF, and decreased the sFlt-1/PlGF ratio. In the placenta, melatonin also reduced sFlt-1 levels and increased Nrf2, PlGF, and HO-1 levels. We have demonstrated in a rat model of preeclampsia that melatonin exerts significant protective effects through lowering blood pressure and reducing oxidative stress.

Cardiac remodeling in morbidly obese women and its association with adverse perinatal outcomes.

OBJECTIVES: To determine the association of cardiac remodeling in early pregnancy and adverse perinatal outcomes among women with BMI ≥ 40 kg/m2. STUDY DESIGN: We performed a retrospective cohort study including women with BMI ≥ 40 kg/m2 without known cardiac disease. Women who underwent screening transthoracic echocardiography prior to gestational age 24 weeks were included. Women were analyzed by group with normal or abnormal geometry, including concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. Multivariable logistic regression was used to assess the association of abnormal geometry with perinatal outcomes. We had 80% power with alpha 0.05 to detect a 3.0-fold increase in the primary outcome among women with abnormal geometry. MAIN OUTCOME MEASURES: Our primary outcome was a composite of adverse perinatal outcomes including any 1 of the following: preterm birth (<37 weeks), low birth weight (<2500 g), or hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and chronic hypertension with superimposed preeclampsia. RESULTS: Of 140 women, 53 (37.9%) had abnormal geometry. The average BMI was similar between those with normal and abnormal geometry (44.7 vs. 44.2 kg/m2, p = 0.53). The primary outcome occurred in 20.7% with normal geometry and 30.2% with abnormal geometry (p = 0.20). After adjustment for parity, chronic hypertension, and tobacco use, abnormal cardiac geometry was not associated with the composite primary outcome (adjusted OR 2.01 [95% CI 0.84-4.78]) but was associated with hypertensive disorders of pregnancy (adjusted OR 2.82 [95% CI 1.03-7.78]). CONCLUSIONS: Cardiac remodeling early in pregnancy is associated with hypertensive disorders of pregnancy.

Views and preferences of medical professionals and pregnant women about a novel primary prevention intervention for hypertensive disorders of pregnancy: a qualitative study.

BACKGROUND: Calcium and low-dose aspirin are two potential approaches for primary prevention of hypertensive disorders of pregnancy (HDP). This study aimed to explore the acceptability, views and preferences of pregnant women and primary healthcare providers for a fixed-dose combined preparation of aspirin and calcium (a polypill) as primary prevention of HDP in an unselected pregnant population. METHODS: In this qualitative study eight in-depth semi-structured interviews were conducted with Dutch primary care midwives and general practitioners. Seven focus group discussions were organised with women with low-risk pregnancies. Topics discussed were: perceptions of preeclampsia; information provision about preeclampsia and a polypill; views on the polypill concept; preferences and needs regarding implementation of a polypill. Thematic analysis of the data transcripts was carried out to identify emerging themes. RESULTS: Two major themes shaped medical professionals' and women's views on the polypill concept: 'Informed Choice' and 'Medicalisation'. Both could be divided into subthemes related to information provision, personal choice and discussions with regard to the balance between 'unnecessary medicalisation' and 'scientific progress'. CONCLUSIONS: In general, women and healthcare practitioners expressed a positive attitude towards a polypill intervention as primary prevention strategy with aspirin and calcium, providing some conditions are met. The most important conditions for implementation of such a strategy were safety, effectiveness and the possibility to make a well-informed autonomous decision.

Outcomes of singleton small for gestational age preterm infants exposed to maternal hypertension: a retrospective cohort study.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a major cause of small for gestational age (SGA). Preterm SGA infants have higher rates of adverse outcomes than appropriate for gestational age infants. However, the outcomes are not well established in the setting of HDP. METHODS: Retrospective population-based study using the Canadian Neonatal Network database from January 1, 2010 to December 31, 2016 of SGA infants <33 weeks gestation. Using multivariable models, we determined the adjusted odds ratios (AORs) with 95% confidence intervals (CI) for mortality, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH), severe retinopathy of prematurity, necrotizing enterocolitis, late-onset sepsis, and patent ductus arteriosus (PDA) in infants of HDP mothers and compared them to infants of non-HDP mothers. RESULTS: Of the 2081 eligible SGA infants, 1317 (63%) were born to HDP mothers and had lower odds of mortality (AOR 0.57, 95% CI 0.39-0.83) and BPD (AOR 0.69, 95% CI 0.53-0.90). Sub-group analysis demonstrated decreased mortality in 26-28 and 29-32 weeks gestation groups, decreased BPD in 29-32 weeks gestation group, and decreased PDA in <26 weeks gestation group. CONCLUSION: Preterm SGA infants of HDP mothers have lower odds of mortality and BPD compared to infants of non-HDP mothers.

Morbilidad materna extrema en pacientes de un Hospital Materno Infantil en República Dominicana / Severe Maternal Morbidity in Patients of a Maternal and Child Hospital in the Dominican Republic

Introducción: La morbilidad materna extrema se define como una complicación grave que ocurre durante el embarazo, parto y puerperio que pone en riesgo la vida de la mujer o requiere de una atención inmediata con el fin de evitar la muerte; el cual constituye un problema de salud pública y factor responsable para la mortalidad materna. Objetivo: Caracterizar los casos de morbilidad materna extrema en las pacientes de un Hospital Materno Infantil en el período enero- diciembre 2016. Métodos: Se realizó el estudio en base de 221 casos de Morbilidad Materna Extrema, donde 113 de estos casos cumplieron con los criterios de MME establecidos por el SINAVE del 2016. La recolección de la información fue por medio indirecto con la utilización de expedientes clínicos y base de datos obtenida del Instituto Nacional de Epidemiologia (INE), con llenado de ficha complementaria. Se analizó diferentes caracteres y variables obstétricas que conllevaron a los casos de MME. Resultados: Según nuestra muestra, a Morbilidad Materna Extrema (MME) afectó a un total de 113 pacientes, con índice de mortalidad (MM) de 0.097 y relación MME/MM de 10.27. Estuvo relacionada con pacientes de 21-35 años de edad, nivel educativo medio, multiparidad, mínima cantidad de controles prenatales, gestaciones mayormente del tercer trimestre, la mayoría terminando en desembarazo por vía cesárea e ingreso a UCI. La causa principal de los casos de MME fue por trastornos hipertensivos durante el embarazo (76.11 por ciento). Conclusiones: La causa principal de los casos de MME son los trastornos hipertensivos durante la gestación, teniendo el mayor porcentaje antecedentes de hipertensión arterial antes del embarazo(AU)

Severe maternal morbidity is as a serious complication that occurs during pregnancy, childbirth and puerperium that puts the woman's life at risk or requires immediate attention in order to avoid death. This entity represents a public health problem and responsible factor for maternal mortality. We conducted a cross-section descriptive study from retrospective and indirect information compilation from San Lorenzo de Los Mina Hospital, Santo Domingo, Dominican Republic with the purpose of interpreting risk factors that lead to maternal near miss event (NME) cases from January to December 2016 according to sociodemographic and gynecological characteristics. The study population consisted of 221 pregnant women of whom only 113 met the specific inclusion criteria used in this study. The main cause of severe maternal morbidity in this study were hypertensive disorders. The majority of cases had pre-eclampsia, eclampsia was in second place and HELLP Syndrome in third place. The average age of the patients was 26.64 years and median age 27 years. The age group over 35 years had the highest incidence. The highest percentage of complications occurred during the third trimester of pregnancy with cesarean section completion with 71 cases. There were 11 deaths (9.73 percent) of the cases of severe maternal morbidity(AU)

Prenatal care and hypertensive gestational syndromes: A systematic review / Atenção pré-natal e síndromes gestacionais hipertensivas: uma revisão sistemática

Abstract Objective Evaluate the influence of prenatal care on the occurrence of gestational hypertension. Methods The Web of Science, Scopus, Pubmed, Cochrane and ClinicalTrials electronic databases were searched for articles published between January 1st, 2012 and December 31st, 2016. No language restrictions were imposed. The following keywords were used: prenatal care, medical assistance, prenatal education, pregnancy-induced hypertension. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist was employed. Two hundred and forty articles were identified during the initial search, but only seven met the inclusion criteria. This systematic review is registered with the international prospective register of systematic reviews (PROSPERO; #CRD42017064103). Results The seven studies hada lowriskof bias,withmethodological quality scores ranging fromsix to eight points. Five studies found a positive relationship between prenatal care and pregnancy-induced hypertension, whereas two studies found no significant association between the two variables. The divergence among the studies may have been due to the type of healthcare service at which the study was conducted and the sample size. Conclusion Although the studies analyzed differed with regard to methodological aspects, the findings demonstrate the importance of prenatal care during the gestational period as a prevention and health promotion measure.

Resumo Objetivo Avaliar a influência da assistência pré-natal no acometimento de síndromes hipertensivas gestacionais. Métodos A revisão buscou artigos publicados nas plataformas eletrônicas de pesquisa Web of Science, Scopus, Pubmed, Cochrane e Clinical Trials, sem restrições de linguagem e com os artigos publicados entre 01/01/2012 e 31/12/2016. Os descritores utilizados foram: assistência pré-natal, assistência médica, educação pré-natal, hipertensão induzida pela gravidez, gestação. Foi utilizado o checklist preferred reporting items for systematic reviews and meta-analyses PRISMA. A busca na literatura, de acordo com a estratégia adotada, identificou 240 artigos. Contudo, somente 7 artigos foram selecionados de acordo com os critérios de inclusão. A revisão sistemática foi incluída no registro prospectivo internacional de revisões sistemáticas (PROSPERO, na sigla em inglês; #CRD42017064103). Resultados Cinco estudos encontraram relação positiva entre a assistência pré-Natal e síndromes hipertensivas gestacionais. Dois estudos não encontraram uma associação estatística significativa entre estas duas variáveis. Os sete estudos apresentam um baixo risco de viés, com as pontuações na análise de qualidade variando entre seis e oito. As possíveis diferenças entre os achados podem ser devidas ao momento do diagnóstico das síndromes hipertensiva gestacionais, tipo de serviço onde foi realizada a pesquisa e o tamanho amostral. Conclusão Embora os estudos apresentem diferentes aspectos metodológicos, observou-se a importância da implementação da Assistência Pré-Natal durante o período gestacional, o que atuará como medida de promoção e prevenção em saúde.

Calcium supplementation commencing before or early in pregnancy, or food fortification with calcium, for preventing hypertensive disorders of pregnancy.

BACKGROUND: Pre-eclampsia is considerably more prevalent in low- than high-income countries. One possible explanation for this discrepancy is dietary differences, particularly calcium deficiency. Calcium supplementation in the second half of pregnancy reduces the serious consequences of pre-eclampsia and is recommended by the World Health Organization (WHO) for women with low dietary calcium intake, but has limited effect on the overall risk of pre-eclampsia. It is important to establish whether calcium supplementation before and in early pregnancy has added benefit. Such evidence would be justification for population-level fortification of staple foods with calcium. OBJECTIVES: To determine the effect of calcium supplementation or food fortification with calcium, commenced before or early in pregnancy and continued at least until mid-pregnancy, on pre-eclampsia and other hypertensive disorders, maternal morbidity and mortality, as well as fetal and neonatal outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Trials Register (10 August 2017), PubMed (29 June 2017), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (10 August 2017) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials of calcium supplementation or food fortification which include women of child bearing age not yet pregnant, or in early pregnancy. Cluster-RCTs, quasi-RCTs and trials published in abstract form only would have been eligible for inclusion in this review but none were identified. Cross-over designs are not appropriate for this intervention.The scope of this review is to consider interventions including calcium supplementation with or without additional supplements or treatments, compared with placebo or no intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: This review is based on one RCT (involving 60 women) which looked at calcium plus additional supplements versus control. The women (who had low antioxidant status) were in the early stages of pregnancy. We did not identify any studies where supplementation commenced pre-pregnancy. Another RCT comparing calcium versus placebo is ongoing but not yet complete. We did not identify any studies looking at any of our other planned comparisons. Calcium plus antioxidants and other supplements versus placeboWe included one small study (involving 60 women with low antioxidant levels) which was conducted in an academic hospital in Indondesia. The study was at low risk of bias for all domains with the exception of selective reporting, for which it was unclear. Women in the intervention group received calcium (800 mg) plus N-acetylcysteine (200 mg), Cu (2 mg), Zn (15 mg), Mn (0.5 mg) and selenium (100 mcg) and vitamins A (1000 IU), B6 (2.2 mg), B12 (2.2 mcg), C (200 mg), and E (400 IU) versus the placebo control group of women who received similar looking tablets containing iron and folic acid. Both groups received iron (30 mg) and folic acid (400 mcg). Tablets were taken twice daily from eight to 12 weeks of gestation and then throughout pregnancy.The included study found that calcium supplementation plus antioxidants and other supplements may slightly reduce pre-eclampsia (gestational hypertension and proteinuria) (risk ratio (RR) 0.24, 95% confidence interval (CI) 0.06 to 1.01; low-quality evidence), but this is uncertain due to wide confidence intervals just crossing the line of no effect, and small sample size. It appears that earlypregnancy loss before 20 weeks' gestation (RR 0.06, 95% CI 0.00 to 1.04; moderate-quality evidence) may be slightly reduced by calcium plus antioxidants and other supplements, but this outcome also has wide confidence intervals, which just cross the line of no effect. Very few events were reported under the composite outcome, severe maternal morbidity and mortality index and no clear difference was seen between groups (RR 0.36, 95% CI 0.04 to 3.23; low-quality evidence). However, the included study observed a reduction in the composite outcome pre-eclampsia and/or pregnancy loss at any gestational age (RR 0.13, 95% CI 0.03 to 0.50; moderate-quality evidence), and pregnancy loss/stillbirth at any gestational age (RR 0.06, 95% CI 0.00 to 0.92; moderate-quality evidence) in the calcium plus antioxidant/supplement group.Other outcomes reported (placental abruption, severe pre-eclampsia and preterm birth (less than 37 weeks' gestation)) were too infrequent for meaningful analysis. No data were reported for the outcomes caesarean section, birthweight < 2500 g, Apgar score less than seven at five minutes, death or admission to neonatal intensive care unit (ICU), or pregnancy loss, stillbirth or neonatal death before discharge from hospital. AUTHORS' CONCLUSIONS: The results of this review are based on one small study in which the calcium intervention group also received antioxidants and other supplements. Therefore, we are uncertain whether any of the effects observed in the study were due to calcium supplementation or not. The evidence in this review was graded low to moderate due to imprecision. There is insufficient evidence on the effectiveness or otherwise of pre- or early-pregnancy calcium supplementation, or food fortification for preventing hypertensive disorders of pregnancy.Further research is needed to determine whether pre- or early-pregnancy supplementation, or food fortification with calcium is associated with a reduction in adverse pregnancy outcomes such as pre-eclampsia and pregnancy loss. Such studies should be adequately powered, limited to calcium supplementation, placebo-controlled, and include relevant outcomes such as those chosen for this review.There is one ongoing study of calcium supplementation alone versus placebo and this may provide additional evidence in future updates.

Antithrombin improves the maternal and neonatal outcomes but not the angiogenic factors in extremely growth-restricted fetuses at <28 weeks of gestation.

AIMS: Severe preterm fetal growth restriction (FGR) remote from term is problematic. We aimed to investigate the effect of maternally-administered antithrombin on maternal and neonatal outcomes. A prospective, one-arm, pilot study was performed in 14 women with severe FGR (≤5th centile) at <28 weeks of gestation, without hypertensive disorders. Maternal plasma concentrations of soluble Feline McDonough Sarcoma (FMS)-like trypsin kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured and categorized into three groups: group 1; low sFlt-1 and high PlGF, group 2; moderate sFlt-1 and low PlGF, and group 3; high sFlt-1 and low PlGF. Antithrombin was administered for 3 days. The incidence of perinatal mortality, infant morbidity, and the period of pregnancy prolongation were compared. RESULTS: In group 1 (n=4), their pregnancies were extended for longer periods and the maternal and infant outcomes were good. The prolongation periods were shorter in groups 2 (n=3) and 3 (n=7), which resulted in poor maternal [severe preeclampsia or hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome] and infant outcomes. CONCLUSIONS: The evaluation of the maternal sFlt-1 and PlGF at 21-27 weeks of gestation is useful in the managements of severe FGR. Antithrombin treatment could prolong the pregnancies with low sFlt-1 and high PlGF without negatively affecting maternal or fetal health.

Sodium hydrosulfide prevents hypertension and increases in vascular endothelial growth factor and soluble fms-like tyrosine kinase-1 in hypertensive pregnant rats.

Sodium hydrosulfide (NaHS) has presented antihypertensive and antioxidant effects and may reduce circulating soluble fms-like tyrosine kinase-1 (sFlt-1). We examined whether NaHS prevents maternal and fetal detrimental changes in a model of hypertension in pregnancy induced by N(G)-nitro-L-arginine methyl ester (L-NAME). Forty pregnant rats were divided into four groups (n = 10 per group): Norm-Preg, Preg + NaHS, HTN-Preg, or HTN-Preg + NaHS. Systolic blood pressure (SBP), number of viable fetuses, litter size, pups, and placentae weights were recorded. Circulating plasma sFlt-1, vascular endothelial growth factor (VEGF), myeloperoxidase (MPO), trolox equivalent antioxidant capacity (TEAC) levels, and biochemical determinants of nitric oxide (NO) formation were assessed. SBP values were elevated in the HTN-Preg group on gestational days 16, 18, and 20. However, HTN-Preg + NaHS group presented lower SBP values on days 18 and 20. Lower number of viable fetuses and litter size were found only in HTN-Preg group compared to other. Reductions in placental weight were found in HTN-Preg and HTN-Preg + NaHS groups. Increases in fetal weight were found only in Preg + NaHS group. Increases in circulating sFlt-1 and VEGF levels were observed only in HTN-Preg group compared to other. Higher MPO and lower TEAC plasma levels were found in HTN-Preg + NaHS and HTN-Preg groups. NO was diminished in HTN-Preg animals, and NaHS treatment increased NO levels only in hypertensive pregnant animals. Treatment with NaHS prevents hypertension in pregnancy and concomitantly reduces circulating plasma sFlt-1 and VEGF levels; this correlates with improved litter size with more viable fetuses and increase in NO levels. However, these beneficial effects presented no relation with oxidative stress.

Preventing deaths due to the hypertensive disorders of pregnancy.

In this chapter, taking a life cycle and both civil society and medically oriented approach, we will discuss the contribution of the hypertensive disorders of pregnancy (HDPs) to maternal, perinatal and newborn mortality and morbidity. Here we review various interventions and approaches to preventing deaths due to HDPs and discuss effectiveness, resource needs and long-term sustainability of the different approaches. Societal approaches, addressing sustainable development goals (SDGs) 2.2 (malnutrition), 3.7 (access to sexual and reproductive care), 3.8 (universal health coverage) and 3c (health workforce strengthening), are required to achieve SDGs 3.1 (maternal survival), 3.2 (perinatal survival) and 3.4 (reduced impact of non-communicable diseases (NCDs)). Medical solutions require greater clarity around the classification of the HDPs, increased frequency of effective antenatal visits, mandatory responses to the HDPs when encountered, prompt provision of life-saving interventions and sustained surveillance for NCD risk for women with a history of the HDPs.

Dimethylesculetin ameliorates maternal glucose intolerance and fetal overgrowth in high-fat diet-fed pregnant mice via constitutive androstane receptor.

The constitutive androstane receptor (CAR) has been reported to decrease insulin resistance along with obesity. 6,7-dimethylesculetin (DE) is an active component of Yin Zhi Huang which is a traditional Asian medicine used to treat neonatal jaundice via CAR. In this study, we examined whether DE could affect the expression of gluconeogenic and lipogenic genes via human CAR pathway using human HepG2 cells in vitro. We also studied whether DE treatment during pregnancy could prevent maternal hypertension, glucose intolerance and hyperlipidemia, and fetal overgrowth in high-fat diet (HFD)-induced obese pregnant mice. Dimethylesculetin suppressed the mRNA expression of gluconeogenic genes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, and lipogenic genes, sterol regulatory element-binding protein 1 and stearoyl-CoA desaturase 1, and enhanced CAR-mediated transcription. Blocking the CAR-mediated pathway abolished the effect of DE in vitro. DE treatment during pregnancy could prevent maternal hypertension, glucose intolerance and hyperlipidemia, and fetal overgrowth in HFD-induced obese pregnant mice in vivo. Our data indicate that DE might be a potential therapeutic agent for obese pregnant patients with insulin resistance through CAR to prevent the perinatal outcomes such as preeclampsia, gestational diabetes, and macrosomia. Further analysis of possible complications and side effects using animal models is required.

Resultados perinatales en gestantes con trastornos hipertensivos del embarazo, Hospital Regional Santa Teresa, 2015 / Perinatal Outcome in Pregnant Women with Hypertensive Disorders of Pregnancy, Regional Hospital Santa Teresa, 2015

Antecedente. Las enfermedades hipertensivas del embarazo representan una alta incidencia de morbimortalidad materna y perinatal, por lo que es necesario conocer las características de los recién nacidos de madres con trastornos hipertensivos para intervenir de forma precoz y oportuna. Objetivo. Describir las características clínicas y epidemiológicas de los recién nacidos de madres con trastornos hipertensivos del embarazo de la sala de labor y parto del Hospital Regional Santa Teresa, Comayagua, durante el año 2015. Métodos. Estudio observacional descriptivo. En este período ingresaron 6,090 gestantes, de las cuales 361 (5.9%) presentaron enfermedad hipertensiva del embarazo. Se estimó un tamaño de muestra de 186 (51.5%, IC95%). Las variables estudiadas fueron: datos maternos, datos clínicos y del nacimiento, complicaciones perinatales. La información recolectada fue ingresada en Epiinfo versión 7.1.5 (CDC, Atlanta). Los resultados se presentan como frecuencias y porcentajes. La información personal de los casos se manejó confidencialmente. Resultados. El 58.6%(109) eran gestantes entre 19-35 años, 73.1%(136) procedentes de área rural, 65.1%(121) con más de cinco consultas prenatales. La vía de parto más frecuente vaginal en 63.4%(118) y el trastorno hipertensivo más frecuente fue preeclampsia-eclampsia con 65.1%(121). El 53.2%(99) de los recién nacidos fueron del género masculino, 94.1%(175) presentaron puntaje de Apgar normal, 84.4(157) peso al nacer entre 2500 ­ 3999 gr. La complicación materna y perinatal más frecuente fue el síndrome de Hellp con 3.8%(7) y síndrome de distress respiratorio 10.2%(19). Discusión. El 58.1% de los recién nacidos presentó alguna complicación al momento del nacimiento...(AU)

Sodium nitrite attenuates hypertension-in-pregnancy and blunts increases in soluble fms-like tyrosine kinase-1 and in vascular endothelial growth factor.

Preeclampsia is a pregnancy-associated disorder characterized by hypertension with uncertain pathogenesis. Increases in antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and reductions in nitric oxide (NO) bioavailability have been observed in preeclamptic women. However, the specific mechanisms linking these detrimental changes to the hypertension-in-pregnancy are not clearly understood. In this regard, while recent findings have suggested that nitrite-derived NO formation exerts antihypertensive and antioxidant effects, no previous study has examined these responses to orally administered nitrite in hypertension-in-pregnancy. We then hypothesized restoring NO bioavailability with sodium nitrite in pregnant rats upon NO synthesis inhibition with N(omega)-nitro-l-arginine methyl ester (L-NAME) attenuates hypertension and high circulating levels of sFlt-1. Number and weight of pups and placentae were recorded to assess maternal-fetal interface. Plasma sFlt-1, vascular endothelial growth factor (VEGF) and biochemical determinants of NO formation and of antioxidant function were measured. We found that sodium nitrite blunts the hypertension-in-pregnancy and restores the NO bioavailability, and concomitantly prevents the L-NAME-induced high circulating sFlt-1 and VEGF levels. Also, our results suggest that nitrite-derived NO protected against reductions in litter size and placental weight caused by L-NAME, improving number of viable and resorbed fetuses and antioxidant function. Therefore, the present findings are consistent with the hypothesis that nitrite-derived NO may possibly be the driving force behind the maternal and fetal beneficial effects observed with sodium nitrite during hypertension-in-pregnancy. Certainly further investigations are required in preeclampsia, since counteracting the damages to the mother and fetal sides resulting from hypertension and elevated sFlt-1 levels may provide a great benefit in this gestational hypertensive disease.

Systematic review of antenatal dietary and lifestyle interventions in women with a normal body mass index.

INTRODUCTION: Women who commence pregnancy with a normal body mass index (BMI) are at the greatest risk of excessive gestational weight gain, impacting on infant birthweight, pregnancy-related complications and postpartum weight retention. Our aim was to review systematically the effect of antenatal dietary and lifestyle interventions in pregnant women with a normal BMI on maternal and infant outcomes. MATERIAL AND METHODS: We searched the Cochrane Controlled Trials Register, PubMed, Medline, and the Australian and International Clinical Trials Registry with the date of the last search in July 2015. We included all published, unpublished and ongoing randomized trials recruiting women of a normal BMI, comparing dietary and/or lifestyle interventions with standard antenatal care. RESULTS: Twelve randomized controlled trials were identified, involving a total of 2713 pregnant women, with five studies reporting clinical data for 714 women with a normal BMI. Women who received a dietary and lifestyle intervention were less likely to experience gestational weight gain [four studies, 446 women; mean difference -1.25 kg; 95% confidence interval (CI) -2.39 to -0.11], weight gain above the Institute of Medicine guidelines (four studies, 446 women; risk ratio 0.66; 95% CI 0.53-0.83) and hypertension (two studies; 243 women; risk ratio 0.34; 95% CI 0.13-0.91). There were no statistically significant differences in the occurrence of gestational diabetes, cesarean section or birthweight greater than 4 kg. CONCLUSIONS: While providing an antenatal dietary and lifestyle intervention for pregnant women of normal BMI appears to reduce gestational weight gain, the review was limited by the relatively small available sample size. Further well-designed randomized controlled trials are required.