Major Complication Of Pregnancy Research Articles

A double blind, randomised, placebo-controlled trial to evaluate the efficacy of metformin to treat preterm pre-eclampsia (PI2 Trial): study protocol

IntroductionPre-eclampsia is a major complication of pregnancy, globally responsible for 60 000 maternal deaths per year, and far more fetal losses. There is no definitive treatment other than delivery. A...

Sulfasalazine reduces placental secretion of antiangiogenic factors, up-regulates the secretion of placental growth factor and rescues endothelial dysfunction.

BackgroundPreeclampsia is a major complication of pregnancy with no medical treatment. It is associated with placental oxidative stress, hypoxia and inflammation leading to soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sENG) secretion and reduced placental growth factor (PlGF). This results in widespread endothelial dysfunction causing hypertension and multisystem organ injury. Sulfasalazine is an anti-inflammatory and antioxidant medication used to treat autoimmune disease. Importantly, it is safe in pregnancy. We examined the potential of sulfasalazine to quench antiangiogenic factors and endothelial dysfunction and increase angiogenic factor secretion.MethodsWe performed functional experiments using primary human pregnancy tissues to examine the effects of sulfasalazine on sFlt-1, sENG and PlGF secretion. Sulfasalazine is known to inhibit nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) and upregulate heme-oxygenase 1 (HO-1) thus we explored the effect of these transcription factors on sFlt-1 secretion from human cytotrophoblasts. We examined the ability of sulfasalazine to reduce key markers of endothelial dysfunction and dilate whole blood vessels.FindingsWe demonstrate sulfasalazine administration reduces sFlt-1 and sENG and upregulates PlGF secretion from human placental tissues. Furthermore sulfasalazine mitigates endothelial dysfunction in several in vitro/ex vivo assays. It enhanced endothelial cell migration and proliferation, promoted blood vessel dilation (vessels obtained from women at caesarean section) and angiogenic sprouting from whole blood vessel rings. The effect of sulfasalazine on the secretion of sFlt-1 was not mediated through either the NFkB or HO-1 pathways.InterpretationWe conclude that sulfasalazine reduces sFlt-1 and sENG secretion and endothelial dysfunction and upregulates PlGF. Sulfasalazine has potential to treat or prevent preeclampsia and warrants investigation in clinical trials.FundingThis work was funded by The National Health and Medical Research Council of Australia (NHMRC; #1048707, #1046484. #1101871, #1064845), an Arthur Wilson RANZCOG scholarship and a Norman Beischer Medical Research Foundation grant. FB was supported by a NHMRC Early Career Fellowship (NHMRC #1142636). NJH was supported by a CR Roper Research Fellowship. The NHMRC provided salary support (#1136418 to ST #1062418 to TKL, #1064845 to SS). The funders had no role in study design, data collection, analysis, decision to publish or the preparation of the manuscript.

Down-regulated expressed protein HMGB3 inhibits proliferation and migration, promotes apoptosis in the placentas of fetal growth restriction.

Fetal growth restriction (FGR) is one of the major complications of pregnancy, which can lead to serious short-term and long-term diseases. High-mobility group box 3 (HMGB3) has been found to contribute to the development of many cancers. However, the role of HMGB3 in the pathogenesis of FGR is blank. Here, we measured the expression level of HMGB3 in the placenta tissues of six normal pregnancies and five FGR patients by western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). CCK8 assay, transwell assay and flow cytometry were used to detect the functional effects of overexpression and silencing of HMGB3 on the HTR8/SVneo trophoblast cell line. The results showed that the protein levels of HMGB3 were significantly decreased in FGR placentas compared to normal controls, while mRNA levels of HMGB3 were not significantly altered. Furthermore, when overexpressed of protein HMGB3 of the trophoblast cells, the proliferation and migration abilities were significantly promoted, and the apoptosis abilities of these cells were statistically inhibited. Cell functional experiments showed the opposite results when the expression of HMGB3 was silent. And the expression of cell function-related genes PCNA, Ki67, Tp53, Bax, MMP-2 and E-cadherin was observed to show corresponding changes by qRT-PCR. The results of mass spectrometry showed that HMGB3 may directly or indirectly interact with 71 proteins. In summary, our results indicated that HMGB3 might be of very great significance to the pathogenesis of FGR and might play the role by leading the dysfunction of placental villous trophoblast cells and through the interaction with some other proteins.

Clinical and Ultrasound Predictors of Placenta Accreta in Pregnant Women with Antepartum Diagnosis of Placenta Previa: A Multicenter Study

Background/Aims: Abnormally invasive placenta (AIP) includes placenta accreta, increta, and percreta and represents major complications of pregnancy. This study was designed to assess the role of ultrasonography in the identification of AIP among pregnant women with antepartum diagnosis of placenta previa. Methods: A cross-sectional study was performed between May 2015 and April 2016 in 11 centers, including 242 women with antepartum diagnosis of placenta previa. Results: Ninety-eight out of 242 (40.49%) women had a histological diagnosis of placenta accreta. A higher number of caesarean deliveries (p = 0.001) and curettages (p = 0.027) and older age of the woman at the delivery (p = 0.031) were identified as risk factors for placenta accreta. The presence of irregularly shaped placental lacunae (vascular spaces) within the placenta (p = 0.008), protrusion of the placenta into the bladder (p < 0.0001), and turbulent blood flow through the lacunae on Doppler ultrasonography (p = 0.008) were predictors of placenta accreta. Conclusions: Women with a prior delivery by caesarean section have a high incidence of placenta accreta among women with antepartum diagnosis of placenta previa.

HYDROGEN PEROXIDE LEVELS CORRELATE WITH SUPEROXIDE DISMUTASE IN IRAQI WOMEN WITH PREGNANCY-INDUCED HYPERTENSION

Objective: Pregnancy-induced hypertension (PIH) is a major pregnancy complication that leads to maternal mortality. Here, we have scrutinized the correlation between serum levels of hydrogen peroxide (H2O2) and superoxide dismutase (SOD) in PIH.Methods: Serum samples were collected from 80 Iraqi women (40 women with PIH as patients group, 20 normotensive pregnant women as a positive control, and 20 normotensive non-pregnant women as a negative control) all groups were diagnosed clinically.Results: Serum of H2O2 and SOD levels was measured for all studied groups. Results showed that there were no significant variances in age and gestational age distribution between all studied groups. Furthermore, result showed that the serum level of SOD was a highly significant decrease in PIH in compared to control groups while H2O2 was a highly significant increase in PIH in compared with control groups. The obtained results also indicated that there was a negative correlation between SOD and H2O2 PIH women while no correlation in other control groups.Conclusion: Our study showed that there was a correlation between H2O2 levels and SOD in PIH. These imbalance lead to generate oxidative stress that could be responsible for starting and progression of pathological processes related to PIH and may be a critical determinant of diseases. Testing for SOD and H2O2 level can be a monitoring instrument for oxidative stress in early pregnancy, and they could help in the detection and consequently prevent future hypertension in pregnancy.

Study the correlation between Human Chorionic Gonadotropin Hormone and Some Biochemical Parameters in Iraqi Women with Pregnancy-Induced Hypertension

Pregnancy-induced hypertension (PIH) is a major pregnancy complication that causes pregnant women mortality. Here, we had scrutinized the correlation between serum levels of ?-hCG and biochemical parameters in PIH. Serum samples were collected from eighty Iraqi women (forty women with pregnancy-induced hypertension as patients group, twenty normotensive pregnant women as a positive control, and twenty normotensive non-pregnant women as a negative control) all groups were diagnosed clinically. All ?-hCG hormone level was measured for all studied groups, also serum uric acid, albumin, and total protein levels were measured as biochemical parameters. Data analysis showed that serum level of ?-hCG hormone was significant increase (p?0.05) in PIH in compared to control groups. Also Uric acid level was increased significantly in PIH group in compared with control groups. While Albumin show there was no significant difference in PIH group. Total serum protein level was measured by Bradford total Protein assay all results was in normal value and showed a significant difference in PIH group in comparison to control groups. Our study shows that there is correlation between ?-hCG with uric acid and albumin levels in PIH. Serial estimation of serum ?-hCG, uric acid, and albumin can be important to use as a marker of disease and also can be used in better early management of established cases that lead to preeclampsia and eclampsia.

Mitochondrial and glycolysis-regulatory gene expression profiles are associated with intrauterine growth restriction

Introduction: Intrauterine growth restriction (IUGR) is a major pregnancy complication with significant postnatal implications. IUGR is characterized by high placental oxidative stress (OS) and increased mitochondrial DNA (mtDNA) abundance that altogether alter the placental metabolism. Such alterations may be captured by changes in the expression of mitochondrial-encoded oxidative phosphorylation genes and glycolysis-regulatory genes.Study design: We aimed here to determine the association between the placental expression of all 13 protein-coding mitochondrial-encoded genes and seven key nuclear glycolysis-regulatory genes, PDK1, PDK2, PDK3, PDK4, PKLR, PKM, OGT, with IUGR, within a case-control study including 50 IUGR and 100 control pregnancies. We additionally assessed placental mtDNA abundance and OS.Results: Three mitochondrial genes, MT-ND5, MT-ND6, and MT-ATP6 were found negatively associated with IUGR, while one glycolysis-regulatory gene, PDK1 was positively associated with IUGR. mtDNA abundance and OS were positively associated with IUGR. Our study confirmed the existing data on IUGR inducing increased placental OS and mtDNA abundance. Further, our data highlighted the significant involvement of mitochondria and glucose metabolism in the OS-challenged IUGR placentas, which might modulate the placental expression of genes affecting the OXPHOS and promoting glycolysis.Brief rationale: By using banked placenta samples available at Icahn School of Medicine at Mount Sinai, this study aims at laying the foundation for the characterization of the role of mitochondria epi/genetics in IUGR. IUGR is a highly prevalent pregnancy outcome with long-term effects on the progeny that, at present, has limited tools that can be used for its diagnosis and characterization, thus limiting the efficacy of both clinical and public health interventions. The alterations of mitochondrial copy number, OS and mitochondrial and glycolysis-regulatory gene expression that we detected, together, provide the first evidence that these phenomena are playing an important role in the pathophysiology of IUGR. These findings suggest possible new research paths for the full characterization of mitochondrial biomarkers of IUGR.

Maternal mortality due to hemorrhage: population-based study in Turkey

Objective: The aim of this study was to determine the epidemiological characteristics of maternal mortality due to postpartum hemorrhage, and to investigate whether national preventative measures of the Maternal Mortality Program have been successful in Turkey.Design: A population-based cohort study.Setting: Turkish National Maternal Mortality Data collected by the Turkish Ministry of Health.Participants: Women who died due to hemorrhage during pregnancy or after delivery within the initial 42 days, from 2012 to 2015, throughout Turkey (N = 812/146).Main outcome measures: The preventability and problems in each maternal death due to hemorrhage.Results: A total of 779 maternal deaths were identified during the study period. Our estimate of the Maternal Mortality Ratio (MMR) in the 3-year period was 19.7 per 100,000 live births. Of the 779 deaths, the report listed 411 as direct and 285 as indirect deaths. Direct obstetric complications were the leading causes of maternal deaths, the most common of which was maternal cardiovascular diseases (21%) and obstetric hemorrhage (20.6%).Conclusion: Improving data surveillance and implementing national guidelines for the prevention and management of major complications of pregnancy, childbirth, and puerperium is necessary to reduce MMR. The healthcare authorities of Turkey should continue to set a sustainable development goal of ≤70 maternal deaths per 100,000 live births by 2030. We believe our results may provide useful information for other developing countries that are aiming to reduce maternal mortality, as well as mobilize global efforts to improve women’s health.

Magnesium sulfate versus esomeprazole impact on the neonates of preeclamptic rats

ObjectivePreeclampsia represents a major complication of pregnancy, associated with greater maternal and fetal complications. We compared the effects of esomeprazole (a proton pump inhibitor) and magnesium sulfate (MgSO4) on the deleterious effects observed on the mother and neonates in experimentally induced preeclampsia in rats. Study designPreeclampsia was induced in pregnant rats with NG-nitro-l-arginine methyl ester (L-NAME) starting from day 10-till end of pregnancy. Pregnant rats were divided into four groups: control pregnant; untreated preeclampsia; preeclamptic rats treated with MgSO4 and preeclamptic treated with esomeprazole. Treatment was started on day 14 and continued until end of pregnancy. Systolic blood pressure, gestation duration, the total number of pups/fetal resorption, pups birth weight, and histopathology examination of the pup’s organs were recorded. ResultsIn comparison with the L-NAME group, the MgSO4 and esomeprazole treatment reduced the values of systolic blood pressure; MgSO4 normalized gestational duration while esomeprazole prolonged it (post-term pregnancy); both restored number of delivered pups; with no statistical differences between the numbers of died pups between the four groups studied while with esomeprazole, out of 10 pregnant females, 2 of them had complete intrauterine fetal resorption; esomeprazole normalized birth weight and histological structure of fetal liver, kidney, and brain. On the other side, MgSO4 treatment gave rise to lower than normal birth weight and minimal tissue damage. ConclusionEsomeprazole and MgSO4 improved systolic blood pressure, prevented preterm labor and restored numbers of pups delivered and fetal weight. Esomeprazole prolonged gestational period post-term with subsequent improving reproductive outcome.

Innate immune cells in the placental bed in healthy pregnancy and preeclampsia

Immune cells in the placental bed are important for adequate development of the placental bed. The most prominent immune cells in the placental bed early in pregnancy are uterine natural killer cells (uNK) cells and macrophages. Also dendritic cells and mast cells can be found in the early placental bed. These cells not only have an immune regulatory function, but are also involved in the regulation of trophoblast invasion, angiogenesis and spiral artery remodeling. In preeclampsia, one of the major complications of pregnancy, decreased trophoblast invasion and spiral artery remodeling has been found. This is associated with decreased numbers of uNK cells, increased numbers of macrophages around the spiral arteries and similar or increased numbers of dendritic cells in the placental bed. In this review, we discuss the current insights in the functions of uNK cells, macrophages, dendritic cells and mast cells in the placental bed in humans during healthy pregnancy and during preeclampsia. As animal models are instrumental in understanding the role of immune cells in the placental bed, we also review studies on the function and phenotype of these innate immune cells in experimental preeclampsia. A better understanding of the dynamics and functional changes of these immune cells in the placental bed may eventually lead to new therapeutic targets for preeclampsia.

Aspirin for Evidence-Based Preeclampsia Prevention trial: effect of aspirin on length of stay in the neonatal intensive care unit

Preeclampsia is a major pregnancy complication with adverse short- and long-term implications for both the mother and baby. Screening for preeclampsia at 11-13 weeks' gestation by a combination of maternal demographic characteristics and medical history with measurements of biomarkers can identify about 75% of women who develop preterm preeclampsia with delivery at <37 weeks' gestation and 90% of those with early preeclampsia at <32 weeks, at a screen-positive rate of 10%. A recent trial (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention) has reported that in women identified by first-trimester screening as being at high risk for preeclampsia, use of aspirin (150 mg/d from the first to the third trimester), compared to placebo, reduced the incidence of preterm preeclampsia, which was the primary outcome, by 62% (95% confidence interval, 26-80%) and the incidence of early preeclampsia by 89% (95% confidence interval, 53-97%). The surprising finding of the trial was that despite the reduction in preeclampsia the incidence of admission to the neonatal intensive care unit, which was one of the secondary outcomes, was not significantly affected (odds ratio, 0.93; 95% confidence interval, 0.62-1.40). We sought to examine the effect of prophylactic use of aspirin during pregnancy in women at high risk of preeclampsia on length of stay in the neonatal intensive care unit. This was a secondary analysis of data from the Aspirin for Evidence-Based Preeclampsia Prevention trial to assess evidence of differences in the effect of aspirin on length of stay in neonatal intensive care. Bootstrapping was used for the comparison of mean length of stay between the aspirin and placebo groups. Logistic regression was used to assess treatment effects on stay in the neonatal intensive care unit. In the trial there were 1620 participants and 1571 neonates were liveborn. The total length of stay in neonatal intensive care was substantially longer in the placebo than aspirin group (1696 vs 531 days). This is a reflection of significantly shorter mean lengths of stay in babies admitted to the neonatal intensive care unit from the aspirin than the placebo group (11.1 vs 31.4 days), a reduction of 20.3 days (95% confidence interval, 7.0-38.6; P= .008). Neonatal intensive care of babies born at <32 weeks' gestation contributed 1856 (83.3%) of the total of 2227 days in intensive care across both treatment arms. These occurred in 9 (1.2%) of the 777 livebirths in the aspirin group and in 23 (2.9%) of 794 in the placebo group (odds ratio, 0.42; 95% confidence interval, 0.19-0.93; P= .033). Overall, in the whole population, including 0 lengths of stay for those not admitted to the neonatal intensive care unit, the mean length of stay was longer in the placebo than aspirin group (2.06 vs 0.66 days; reduction of 1.4 days; 95% confidence interval, 0.45-2.81; P= .014). This corresponds to a reduction in length of stay of 68% (95% confidence interval, 20-86%). In pregnancies at high risk of preeclampsia administration of aspirin reduces the length of stay in the neonatal intensive care unit by about 70%. This reduction could essentially be attributed to a decrease in the rate of births at <32 weeks' gestation, mainly because of prevention of early preeclampsia. The findings have implications for both short- and long-term health care costs as well as infant survival and handicap.

Microdissection testicular sperm extraction in Finland - results of the first 100 patients.

Testicular microdissection sperm extraction (MD-TESE) combined with intracytoplasmic sperm injection (ICSI) has made biological fatherhood possible for many men with the most severe form of male infertility, non-obstructive azoospermia. MD-TESE was introduced in Turku in 2008, and by 2015, 100 Finnish men with non-obstructive azoospermia have been operated on. The average age of the men was 33years at the time of surgery. Forty-eight had a needle biopsy previously and 56% had a testicular size <15mL. The most common diagnoses were idiopathic (n=65), Klinefelter syndrome (n=15), operated cryptorchidism or torsion (n=10), and Y chromosome microdeletion (n=7). The pregnancy outcomes were followed. The sperm recovery rate (SRR) overall was 42%: 31% for idiopathic non-obstructive azoospermia, 40% for Klinefelter syndrome, 57% for Y chromosome microdeletion AZFc, 90% for previous testicular surgery (mostly for cryptorchidism; n=10) and 67% for previous cytotoxic treatment (n=3). SRR with histopathologic diagnosis Sertoli-cell-only was 29%, and 44% for spermatogenic arrest. Age did not affect the outcome of the surgery. Small testicular size seemed to predict a higher SRR. A previous needle biopsy did not predict a lower SRR. Surgical complications were rare. Of couples, 32 had at least one ICSI attempt, and 22 at least one live birth, giving a cumulative live birth rate of 69%. No major pregnancy complications occurred. Our SRR is comparable with international results, and the cumulative live birth rate similar to other ICSI indications in Finland. Physicians and specialists need to be made aware of new treatment options to enable biological fatherhood for men with non-obstructive azoospermia.

A population‐based study of the effect of pregnancy history on risk of stillbirth

To examine the effect of pregnancy history on the risk of stillbirth. In a population-based cross-sectional study, data were reviewed from all women aged at least 20years with singleton pregnancies in Finland between 2000 and 2010. The primary outcome-stillbirth-was defined as fetal death after 22 gestational weeks or death of a fetus weighing at least 500g. Among 604047 singleton pregnancies, the prevalence of stillbirth was 3.17 per 1000 deliveries. Prevalence was lowest for multiparous women without previous pregnancy loss after adjusting for major pregnancy complications associated with stillbirth (placenta previa, placental abruption, and pre-eclampsia) and other confounders. Relative to these women, stillbirth prevalence was higher among multiparous women with previous spontaneous abortion and/or stillbirth (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.05-1.36), nulliparous women with no previous pregnancy loss (aOR 1.23, 95% CI 1.10-1.38), and nulliparous women with prior spontaneous abortion (aOR 1.43, 95% CI 1.18-1.74). Previous pregnancy loss was found to be an independent risk factor for stillbirth, irrespective of the number of prior deliveries.

SERUM VASPIN LEVELS IN NORMAL PREGNANT AND GESTATIONAL DIABETIC ALBINO RAT MODEL

Background:Gestational diabetes mellitus (GDM) is a major pregnancy complication with increased blood glucose levels and insulin resistance. Vaspin is a visceral adipokine that is synthesized and secreted by abdominal fat tissue and one of the superfamily of serine protease inhibitors. Data proposed vaspin levels in normal pregnancy and GDM are still controversial. Objective : To assess serum vaspin levels in both of late pregnancy and experimentally-induced GDM in relation to certain metabolic parameters in albino rats. Material and methods: Thirty six virgin female albino rats of a local strain weighing 100-150 g were divided randomly into three equals groups. Group I (Control); virgin rats were fed normal diet. Group II (normal pregnant); rats were fed normal diet for five weeks before induction of pregnancy. Group III (experimentally-induced GDM); rats were fed fatty-sucrose diet (FSD) for five weeks before induction of pregnancy, then injected intraperitoneally with streptozotocin (25 mg/kg) on the 7th day of gestation. In all groups, serum vaspin, body mass index (BMI), serum estradiol, progesterone, total triglycerides (TG), total cholesterol (TC), low density lipoproteins-cholesterol (LDL-c), high density lipoproteins-cholesterol (HDL-c), glucose, insulin levels and calculated homeostatic model assessment of insulin resistance index (HOMA-IR) were estimated. Results: Normal pregnant rats showed a significant increase in BMI, serum vaspin, TG, TC, LDL-c, insulin levels and HOMA-IR compared to controls. Additionally, serum vaspin levels were significantly and positively correlated with BMI, serum glucose, TG levels and HOMA-IR. GDM-induced rats had significantly increased levels of serum vaspin, TC, TG, LDL-c, glucose, BMI and HOMA-IR, while decreased insulin and HDL-c levels compared to normal pregnant and control rats. Moreover, serum vaspin levels showed significant positive correlations with BMI, HOMA-IR, glucose, TG, TC levels, and an inverse correlation with HDL-c levels in GDM-induced group. Conclusion: Serum vaspin levels increased in both of late pregnancy and experimentally-induced GDM, but more in the later possibly for compensating GDM-induced insulin resistance and dyslipidemia.

Activating Transcription Factor 3 Is Reduced in Preeclamptic Placentas and Negatively Regulates sFlt-1 (Soluble fms-Like Tyrosine Kinase 1), Soluble Endoglin, and Proinflammatory Cytokines in Placenta.

Preeclampsia is a major pregnancy complication associated with poor placental perfusion and placental hypoxia. Systemic and placental inflammation and elevated placental secretion of the antiangiogenic factors sFlt-1 (soluble fms-like tyrosine kinase 1) and sEng (soluble endoglin) are hallmarks of preeclampsia, causing endothelial dysfunction and multiorgan injury. A molecule that links placental hypoxia, inflammation, and antiangiogenic factor release has not been described. ATF3 (activating transcription factor 3) is highly expressed in placenta. We assessed whether placental ATF3 is dysregulated in preterm preeclampsia, is altered by hypoxia, and regulates proinflammatory cytokine and antiangiogenic factor production. ATF3 mRNA and protein expression was significantly reduced in preterm preeclamptic placentas compared with gestation-matched controls. Hypoxia reduced ATF3 expression in primary cytotrophoblast and placental explants. Silencing ATF3 in primary cytotrophoblast increased proinflammatory cytokine (IL-6 [interleukin 6], TNF-α [tumor necrosis factor α]) and NF-κB (nuclear factor κB) expression. In silico analysis identified an ATF3-binding site in the promoter of Flt-1 (the transcript from which sFlt-1 is produced). Silencing ATF3 increased sFlt-1 and sEng secretion from primary cytotrophoblast possibly by increasing Rab11a and Arf1, cargo proteins that facilitate exosomal release of sFlt-1. ATF3 knockout mice did not have a preeclampsia phenotype, suggesting that these pathways may be specific to humans (preeclampsia is a uniquely human condition). To conclude, we have shown that ATF3 is decreased in preeclamptic placentas and that this decrease is likely to occur after prolonged hypoxia. We show that ATF3 is a regulator of placental proinflammatory cytokines and antiangiogenic factors sFlt-1 and sEng. Therefore, reduced ATF3 may be centrally involved in the pathology of preeclampsia.

Maternal mortality audit in Suriname between 2010 and 2014, a reproductive age mortality survey

BackgroundThe fifth Millennium Development Goal (MDG-5) aimed to improve maternal health, targeting a maternal mortality ratio (MMR) reduction of 75% between 1990 and 2015. The objective of this study was to identify all maternal deaths in Suriname, determine the extent of underreporting, estimate the reduction, audit the maternal deaths and assess underlying causes and substandard care factors.MethodsA reproductive age mortality survey was conducted in Suriname (South-American upper-middle income country) between 2010 and 2014 to identify all maternal deaths in the country. MMR was compared to vital statistics and a previous confidential enquiry from 1991 to 1993 with a MMR 226. A maternal mortality committee audited the maternal deaths and identified underlying causes and substandard care factors.ResultsIn the study period 65 maternal deaths were identified in 50,051 live births, indicating a MMR of 130 per 100.000 live births and implicating a 42% reduction of maternal deaths in the past 25 years. Vital registration indicated a MMR of 96, which marks underreporting of 26%. Maternal deaths mostly occurred in the urban hospitals (84%) and the causes were classified as direct (63%), indirect (32%) or unspecified (5%). Major underlying causes were obstetric and non-obstetric sepsis (27%) and haemorrhage (20%). Substandard care factors (95%) were mostly health professional related (80%) due to delay in diagnosis (59%), delay or wrong treatment (78%) or inadequate monitoring (59%). Substandard care factors most likely led to death in 47% of the cases.ConclusionDespite the reduction in maternal mortality, Suriname did not reach MDG-5 in 2015. Steps to reach the Sustainable Development Goal in 2030 (MMR ≤ 70 per 100.000 live births) and eliminate preventable deaths include improving data surveillance, installing a maternal death review committee, and implementing national guidelines for prevention and management of major complications of pregnancy, childbirth and puerperium.

Principles of first trimester screening in the age of non-invasive prenatal diagnosis: screening for other major defects and pregnancy complications.

First trimester risk assessment plays a major role in the contemporary pregnancy care. It has evolved significantly since its introduction in the 1990s when it essentially consisted of just the nuchal translucency measurement. Today, it involves the measurement of several biophysical and biochemical markers and can assess the risk for a wide array of major chromosomal and non-chromosomal defects as well as other pregnancy-related complications. A search of the Medline and Embase databases was done looking for articles about first trimester screening. We performed a detailed review of the literature to evaluate the screening tests currently available and their respective test performance. The detailed ultrasound examination results in the detection of about half of major structural defects, determination of a very accurate gestational age, and identification of multiple pregnancies as well as their chorionicity. In addition, risk assessment for preeclampsia and early IUGR can be established at this stage. In case of an increased risk, the daily use of low-dose aspirin can be offered at a point in pregnancy when it still can have a positive impact. Additional screening tests for gestational diabetes and macrosomia are available. Contemporary first trimester screening is essential to establish an individual risk profile and can be used to tailor the pregnancy care.

Description of a method for inducing fetal growth restriction in the spiny mouse.

Intrauterine or fetal growth restriction (IUGR) is a major complication of pregnancy and leads to significant perinatal morbidities and mortality. Typically, induction of IUGR in animals involves the complete occlusion or ablation of vessels to the uterus or placenta, acutely impairing blood flow and fetal growth, usually with high fetal loss. We aimed to produce a model of reduced fetal growth in the spiny mouse with minimal fetal loss. At 27 days gestational age (term is 38-39 days), a piece of silastic tubing was placed around the left uterine artery to prevent the further increase of uterine blood flow with advancing gestation to induce IUGR (occluded). Controls were generated from sham surgeries without placement of the tubing. Dams were humanely euthanized at 37 days gestational age and all fetuses and placentas were weighed and collected. Of the 17 dams that underwent surgery, 15 carried their pregnancies to 37 days gestational age and 95% of fetuses survived to this time. The difference in fetal body weight between occluded and control was ~21% for fetuses in the left uterus side: there were no differences for fetuses in the right uterus side. Offspring from the occluded group had significantly lower brain, liver, lung, kidney and carcass weights compared with shams. Preventing the gestation-related increase of uterine blood flow induced significant growth restriction in the fetal spiny mouse, with minimal fetal loss. This technique could be readily adapted for other small animal.

The Global Burden of Obesity on Pregnancy Outcomes in the Developed World [17Q

INTRODUCTION: Essentially all major complications of pregnancy are more likely to occur in the obese gravida when compared to women with normal body mass indices. The purpose of this study was to estimate as accurately as possible, the quantitative burden of obesity on pregnancy outcomes in the developed world. METHODS: Pooled odds ratios for outcomes of interest related to maternal overweight and obesity were extracted from previously published meta-analyses. Rates of overweight and obesity in adult women in the Group of Eight countries were corrected for the decreased incidence in women prior pregnancy. The prevalence of each adverse outcome was extracted from published literature. Together this information was used to calculate the population attributable fraction that can be attributed to overweight and obesity each year for each outcome. RESULTS: Each year an estimated 3,168 stillbirths, 3,610 infant deaths, 570,449 cesarean deliveries, 1,105 neural tube defects, 780 cases of congenital heart defects, and 135,258 cases of preeclampsia can be attributed to maternal obesity in the Group of Eight countries. Calculations were also performed for maternal overweight. CONCLUSION: While the negative impact of maternal overweight and obesity is well known, it becomes easy to lose sight of the human cost of these increased odds ratios. By estimating the number of attributable cases this study humanizes the burden of overweight and obesity in the perinatal setting. Furthermore, this detailed estimate assists in the prioritization of public health efforts in the treatment and prevention of obesity and research into its proper management in pregnancy.

Human endometrial stromal cell plasticity: Reversible sFlt1 expression negatively coincides with decidualization

ABSTRACTPreeclampsia (PE) is a major complication of pregnancy in which the placenta is known to have shallow implantation into the uterine decidua. Studies have implicated soluble fms-like tyrosine kinase-1 (sFlt1), a soluble vascular endothelial growth factor (VEGF) receptor protein, in the pathogenesis of PE. sFlt1 has the ability to bind to and neutralize the angiogenic functions of VEGF and placental growth factor (PlGF). The presence of sFlt1 and its action in the endometrium is yet to be determined. We hypothesize that endometrial stromal cells (ESC) at the maternal–fetal interface may play a role in sFlt-1 regulation during pregnancy. In this study, we seek to understand the dynamic regulation of sFlt1 production in primary human ESC as a result of hormone stimulation and withdrawal. To mimic a biphasic menstrual cycle, ESC were treated with cAMP to induce endometrial decidualization that occurs during the luteal secretory phase, followed by cAMP withdrawal reflecting the follicular proliferative phase. Here, we present data to show that (1) ESC produce detectable amounts of sFlt1, (2) sFlt1 expression is turned off during decidualization at both the protein and RNA level (3) ESC decidualization and resulting sFlt1 expression are reversible phenomenon, and (4) Decidualization markers prolactin (PRL) and VEGF expressions in ESC are negatively correlated with sFlt1. These findings may have important implications in diseases such as PE that involve abnormal decidualization, implantation and angiogenesis at the maternal-fetal interface.