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In the near future, stem cell research may lead to several major therapeutic innovations in medical practice. Secretome, a "by-product" of stem cell line cultures, has many advantages. Its easiness of storage, usage, and fast direct effect are some of those to consider. Fetal growth restriction (FGR) remains one of the significant challenges in maternal-fetal and neonatal medicine. Placentation failure is one of the most profound causal and is often related to increasing sFlt-1 in early pregnancy. This study aimed to investigate hUC-MSC secretome in ameliorating sFlt-1 and how to improve outcomes in preventing FGR in an animal model. Pristane-induced systemic lupus erythematosus (SLE) in a mouse model was used to represent placentation failure and its consequences. Twenty-one mice were randomized into three groups: (I) normal pregnancy, (II) SLE, and (III) SLE with secretome treatment. Pristane was administered in all Groups four weeks prior mating period. Secretome was derived from human umbilical cord mesenchymal stem cells (hUC-MSC) conditioned medium on the 3rd and 4th passage, around day-21 until day-28 from the start of culturing process. Mesenchymal stem cell was characterized using flow cytometry for CD105+, CD90+, and CD73+ surface antigen markers. Immunohistochemistry anlysis by using Remmele's Immunoreactive Score (IRS) was used to quantify the placental sFlt-1 expression in each group. Birth weight and length were analyzed as the secondary outcome. The number of fetuses obtained was also calculated for pregnancy loss comparison between Groups. The administration of secretome of hUC-MSC was found to lower the expression of the placental sFlt-1 significantly in the pristane SLE animal model (10.30 ± 1.40 vs. 4.98 ± 2.57; p < 0.001) to a level seen in normal mouse pregnancies in Group I (3.88 ± 0.49; p = 0.159). Secretome also had a significant effect on preventing fetal growth restriction in the pristane SLE mouse model (birth weight: 354.29 ± 80.76 mg vs. 550 ± 64.03 mg; p < 0.001 and birth length: 14.43 ± 1.27 mm vs. 19.00 ± 1.41 mm), comparable to the birth weight and length of the normal pregnancy in Group I (540.29 ± 75.47 mg and 18.14 ± 1.34 mm, p = 0.808 and = 0.719). Secretome administration also showed a potential action to prevent high number of pregnancy loss as the number of fetuses obtained could be similar to those of mice in the normal pregnant Group (7.71 ± 1.11 vs. 7.86 ± 1.06; p = 0.794). Administration of secretome lowers sFlt-1 expression in placenta, improves fetal growth, and prevents pregnancy loss in a mouse SLE model. [ABSTRACT FROM AUTHOR]

Introduction The Indonesian INOVASIA study is an ongoing multicentre randomized, open controlled trial of pravastatin for the prevention of preeclampsia in patients deemed to be high risk. Here we evaluate the effects of pravastatin on circulating inflammatory and endothelial markers, i.e. Vascular Endothelial Growth Factor (VEGF), Interleukin-6 (IL-6), Endothelin-1 (ET-1), and Nitric Oxide (NO). Methods Pregnant women deemed to be at a high risk of developing preeclampsia women were recruited based on the Fetal Medicine Foundation preeclampsia screening test or a history of preterm preeclampsia, or clinical risk factors in combination with an abnormal uterine artery Doppler flow pattern at 11–20 week's gestation. This is a nested cohort study within the larger trial (INOVASIA); 38 patients were consecutively recruited and assigned to the pravastatin group and the control group. Participants in the pravastatin group received pravastatin (2 × 20 mg p.o) in addition to a standard regimen of aspirin (80 mg p.o) and calcium (1 g p.o), from 14 to 20 weeks until delivery. Blood samples to measure the various biomarkers were obtained in consecutive patients before starting the research medication and just before delivery (pre and post-test examination). Result The number of samples on the 2 time points for the various biomarkers was: VEGF: 38, IL-6: 30, ET-1: 38, and NO: 35. IL-6 levels decreased significantly in the pravastatin group (mean ± SD): (191.87 ± 82.99 vs. 151.85 + 48.46, p = .013), while levels in the control group did not change significantly (median (interquartile range)) (144.17 (53.91) vs. 140.82 (16.18), p = .177). ET-1 levels decreased significantly in the pravastatin group (3.64 ± 0.85 vs. 3.01 ± 0.74, p = .006) while the control group had more or less stable levels (3.57 ± 1.12 vs. 3.78 ± 0.73 p = .594). NO was the only serum marker that showed significant changes in both groups. NO levels increased in pravastatin group (11.30 (17.43) vs. 41.90 (53.18), p = .044) and decreased in control group (38.70 (34.80) vs. 10.03 (26.96), p = .002). VEGF levels appeared to follow opposite trends in the 2 groups (NS) (Pravastatin: 3.22 (0.62) vs. 3.28 (0.75), p = .402. Control: 3.38 (0.83) vs. 3.06 (0.74), p = .287). Conclusion Administration of 40 mg pravastatin resulted in an improvement in NO levels, and a decrease in IL-6 and endothelin (ET-1) levels. The direction of the effect of pravastatin on these biomarkers appears to underpin the potential for a beneficial effect of pravastatin in the prevention of preeclampsia. [ABSTRACT FROM AUTHOR]

To present a comprehensive overview of different risk factors for early onset preeclampsia (<34 weeks gestation, EOP) vs. late onset (LOP). South-Reunion University's maternity (Reunion Island, Indian Ocean). 18.5 year-observational population-based cohort study (2001–2019). Epidemiological perinatal database with information on obstetrical and neonatal risk factors. All consecutive singleton pregnancies (>21 weeks) compared with all preeclamptic pregnancies delivered in the south of Reunion island. Comparing risk factors between EOP and LOP. Among 1814 singleton preeclamptic pregnancies (600 EOP and 1214 LOP), EOP women were older than LOP 29.5 vs. 28.6 years, p =.009, primigravidas (OR 0.78 [0.63–0.96], p =.02) were prone to LOP. History of preeclampsia (PE) (aOR 12.8 vs. 7.1), chronic hypertension (aOR 6.5 vs. 4.5) had much higher adjusted odds ratios for EOP than for LOP, p <.001. Specific to EOP: coagulopathies (aOR 2.95, p =.04), stimulated pregnancies (aOR 3.9, p =.02). Specific to LOP: renal diseases (aOR 2.0, p =.05) and protective effect for smoking (aOR 0.75, p =.008). EOP women were prone to have a lower BMI. "Placental preeclampsia" (defective placentation) being linked to early onset PE (<34 weeks gestation) while "maternal preeclampsia" (maternal cardiovascular predisposition) being typically manifesting as the late form of the disease LOP is not systematically verified. Future researches are needed to propose a more adapted paradigm. Risk factors for different preeclampsia phenotypes (early/late); challenging proposed models [ABSTRACT FROM AUTHOR]

Prevention of neurologic disability associated with preterm birth is one of the major challenges in current perinatal medicine. Magnesium sulfate (MgSO4), the focus of this review has been proposed as major step forward for that matter. MgSO4 is easily accessible, cheap, and has been proposed as a mandatory part of the management of inevitable preterm birth. The results of the various RCT's on the use of MgSO4 for neuroprotection has been the subject of many systematic reviews, other studies focused on dosing schedules, side effects and only a few focused on exploring magnesium's mechanism of action. Meanwhile, many guidelines worldwide have plugged MgSO4 as an essential ingredient of daily best practice when managing inevitable preterm birth because it has been shown to reduce the risk of severe neurologic deficit, in particular, cerebral palsy in appropriately selected patients. The more premature, the greater benefit associated with the use of antenatal MgSO4. The dose of 4 g given intravenously 15 min continued by 1 g/h until maximum 24 h and minimum for 4 h is the standard regiment proposed in most guidelines. It should be noted, however, that a recent study found that a total dose of 64 g was associated with the maximum protective effect. Only the protocol used by the largest RCT, the BEAM trial, with a loading dose of 6 g initially followed by a 2-g/h maintenance dose, if continued for 24 h would give a total dose over 50 g. Other studies report on an increased risk of neonatal death with these high doses. Several studies expressed concerns about the risk of serious side effects for both mother and neonate. The results from the systematic review showed that the most commonly used dosage, 4 g bolus continued by 1 g/h maintenance, did not increase neonatal mortality and other suspected neonatal complication such as neonatal asphyxia, spontaneous intestinal perforation, necrotizing enterocolitis, and feeding intolerance. Giving a single bolus injection of 4 g MgSO4 for stimulating BDNF production in highly "suspicious" preterm labor, and 4 g again when preterm birth become inevitable may be best from a safety perspective and also appears to have a stronger rationale. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the maternal-neonatal outcome in magnesium (Mg)-intoxicated women with preeclampsia with severe features (PESF) treated with magnesium sulfate (MgSO4).Methods: A total of 19 Mg intoxicated PESF women (cases) were compared with 166 PESF women without signs of intoxication (controls).Results: Mg serum levels of cases was higher compared to control group (12.36 ± 3.54 mg/dl versus 2.69 ± 0.83 mg/dl). 3 women died and 3 had major maternal morbidity in cases group compared with zero in the control group (P = 0.009). Mg intoxication was also significantly associated with perinatal deaths and low Apgar scores at 1 and 5 minutes.Conclusion: Mg intoxication is associated with a increased risk of maternal and perinatal mortality and morbidity. [ABSTRACT FROM AUTHOR]

This study questioned whether raised pre-pregnancy two-hour (2 h) insulin levels, measured in recurrent embryonic miscarriage (RM) patients via a 75 g Oral Glucose Tolerance Test (OGTT), are associated with an increased risk of gestational diabetes mellitus (GDM) in a subsequent pregnancy. Patients had a 75 g OGTT and insulin levels evaluated (n = 170). 54.1% had normal glucose and insulin levels, 45.9% had levels indicating hyperinsulinism (HI). In the 98 patients who achieved a pregnancy, the prevalence of GDM was 3.7% in those without HI, and 35.7% in the patients who only had raised 2 h insulin levels. While HI has been described as a risk factor for miscarriages only in relation to raised fasting (basal) insulin levels, this study demonstrated that raised 2 h insulin levels predict an increased risk of GDM in a subsequent pregnancy. Thus raised 2 h insulin levels likely confer a similar risk to raised fasting insulin levels in RM patients.Impact statementWhat is already known on this subject? Fasting hyperinsulinism is known to be associated with an increased risk of gestational diabetes mellitus (GDM) in pregnancy. Hyperinsulinism, as reflected by the fasting (basal) insulin levels >20mU/L, has been recognized as a risk factor for recurrent miscarriages, particularly in patients with polycystic ovarian syndrome (PCOS), in the World literature. Raised two-hour insulin levels have not been considered as a risk factor in the literature before.What do the results of the study add? We have demonstrated a 10-fold increase in the development of GDM in patients with fasting insulin resistance, and/or raised 2h insulin levels, and an almost 10-fold increase in patients with only raised 2h levels. 58.8% of the patients who subsequently developed GDM only had raised 2h levels and would have been missed with routine testing.What are the implications of these findings for clinical practice and/or further research? Our study has demonstrated that GDM was three times more prevalent in the patients with only raised 2h levels, than in those only with raised fasting levels, reflecting insulin resistance/hyperinsulinism. Insulin studies including 2h insulin levels are therefore an important factor to consider when working up these patients. Insulin studies pre-pregnancy may be useful in identifying women at risk of suffering miscarriages or of developing GDM in a subsequent pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between parental MTHFR 677C > T (RS1801133) and 1298A > C (RS1801131), and fetal loss (FL).Design: Case-control study.Setting: Department of Obstetrics and Gynecology, Lyell McEwin Hospital (LMH), and the Women's and Children's Hospital (WCH) in Adelaide, Australia.Patients: A total of 222 couples with FL and 988 couples with uncomplicated pregnancies.Measurements: The main outcomes were FL and hyperhomocysteinemia (HHcy). All couples were tested for MTHFR 677C > T and 1298A > C. Fasting homocysteine was measured in the women with FL.Results: The main finding was a significant difference between the FL group and controls in couples with ≥4 abnormal alleles compared to <4 [p=.0232, OR 1.9 (95% CI 1.1-3.3)]. None of the couples with FL had zero abnormal alleles (both parents 677CC/1298 AA). However, this was also rare amongst the controls. Maternal carriage of both 677C > T and the 1298A > C polymorphisms was similar between the FL group and controls. The prevalence of paternal 677TT/1298AA and 677CC/1298AC was significantly higher in the FL group compared with controls. HHcy was significantly more common in the FL group compared with controls.Conclusion: The presence of parental MTHFR 677C > T and 1298A > C is associated with FL. The association between maternal MTHFR genotypes with FL is less pronounced than in previously published articles investigating first trimester miscarriages. Maternal HHcy is a significant risk factor for FL. [ABSTRACT FROM AUTHOR]

Aims: Some studies have suggested that vitamin D deficiency is associated with an increased risk of first trimester miscarriages, others have suggested that it is associated with an increased risk of hyperinsulinism/insulin resistance and the development of gestational diabetes. Hyperinsulinism is also thought to increase miscarriages. We investigated the association between vitamin D levels and hyperinsulinism in a cohort of recurrent miscarriage patients. Methods: Patients undergoing miscarriage investigations had insulin and vitamin D levels tested. Vitamin D levels were classified as: sufficient (≥75 nmol/L), insufficient (50-74.9 nmol/L) or deficient (<50 nmol/L). Hyperinsulinism was assessed via a 75 g oral glucose tolerance test (OGTT) with insulin studies. Results: One hundred and fifty-five patients underwent the testing. Hyperinsulinism was detected in 58.3% of the vitamin D deficient group, 38.7% of the insufficient group, and 33.3% of the sufficient group (chi-square p = .034). There were no significant associations between BMI and vitamin D levels, or BMI and hyperinsulinism. Caucasians comprised 82% of the clinic, and 67% of these women had vitamin D insufficiency/deficiency. Noncaucasians comprised 18% of the clinic but 89% of these patients had vitamin D insufficiency/deficiency. Discussion: We found that insufficient or deficient vitamin D levels were significantly associated with hyperinsulinism in these patients. Vitamin D deficiency is also thought to contribute to an increased risk of adverse pregnancy outcomes including preeclampsia, preterm birth, small-for-gestational-age gestational diabetes mellitus, and miscarriages. Larger level one trials are needed to establish if increasing serum vitamin D levels prior to conception or in early pregnancy improves adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

This prospective cohort study measured anti-Müllerian hormone (AMH) levels in recurrent miscarriage (RM) patients, compared them to a normal population, and assessed the pregnancy outcomes. The RM patients demonstrated AMH levels that were significantly lower than the normal population, both in women aged ≤35 years, and those aged >35 years. AMH percentiles were found to be significantly lower in the study group of RM patients ≤35 years (p< .004) in the 5th and 50th percentiles, and in all percentiles in women >35 years (p< .03), were compared to women from a normal population. Serum AMH levels may reflect quality, and quantity of the remaining oocytes in these patients, and RM patients may have a low ovarian reserve, and a potentially poor oocyte quality, as shown by low circulating AMH. The evaluation of AMH levels in a RM work up may allow realistic counselling and possible ART referral in RM patients. Impact statement What is already known on this subject? There is some evidence to show that low AMH levels are associated with recurrent miscarriages and this is thought to be due to a decreased oocyte quality. The AMH levels are lower in the patients with endometriosis, and are often significantly higher in the patients with polycystic ovarian syndrome. Both conditions are independently associated with miscarriages. What the results of this study add? Anti-Müllerian hormone (AMH) levels were found to be significantly lower in recurrent miscarriage patients, compared to a normal population. This may be another factor contributing to miscarriages. The spontaneous pregnancy rates in the miscarriage group significantly improved with increasing AMH levels. This may confirm that patients with low AMH levels have poorer quality oocytes, and thus may be considered 'sub-fertile'. It was also found that the utilisation of assisted reproductive technologies (ART) to achieve a pregnancy was significantly reduced in the groups with a higher serum AMH. What the implications are of these findings for clinical practice and/or further research? Serum AMH levels should be offered to all patients as part of a recurrent miscarriage work up. Detecting the low AMH levels and counselling the patients on these findings may allow them the option of accessing ART. ART may have the ability to expedite conception rates, and with pre-implantation genetic analyses, could possibly select the embryos with the greatest chance of survival. Further research is needed to establish how the decreased AMH levels contribute to recurrent miscarriages. [ABSTRACT FROM AUTHOR]

Prevention of neurologic disability associated with preterm birth is one of the major challenges in current perinatal medicine. Magnesium sulfate (MgSO4), the focus of this review has been proposed as major step forward for that matter. MgSO4 is easily accessible, cheap, and has been proposed as a mandatory part of the management of inevitable preterm birth. The results of the various RCT's on the use of MgSO4 for neuroprotection has been the subject of many systematic reviews, other studies focused on dosing schedules, side effects and only a few focused on exploring magnesium's mechanism of action. Meanwhile, many guidelines worldwide have plugged MgSO4 as an essential ingredient of daily best practice when managing inevitable preterm birth because it has been shown to reduce the risk of severe neurologic deficit, in particular, cerebral palsy in appropriately selected patients. The more premature, the greater benefit associated with the use of antenatal MgSO4. The dose of 4 g given intravenously 15 min continued by 1 g/h until maximum 24 h and minimum for 4 h is the standard regiment proposed in most guidelines. It should be noted, however, that a recent study found that a total dose of 64 g was associated with the maximum protective effect. Only the protocol used by the largest RCT, the BEAM trial, with a loading dose of 6 g initially followed by a 2-g/h maintenance dose, if continued for 24 h would give a total dose over 50 g. Other studies report on an increased risk of neonatal death with these high doses. Several studies expressed concerns about the risk of serious side effects for both mother and neonate. The results from the systematic review showed that the most commonly used dosage, 4 g bolus continued by 1 g/h maintenance, did not increase neonatal mortality and other suspected neonatal complication such as neonatal asphyxia, spontaneous intestinal perforation, necrotizing enterocolitis, and feeding intolerance. Giving a single bolus injection of 4 g MgSO4 for stimulating BDNF production in highly "suspicious" preterm labor, and 4 g again when preterm birth become inevitable may be best from a safety perspective and also appears to have a stronger rationale. [ABSTRACT FROM AUTHOR]

Acute fatty liver of pregnancy (AFLP) is a rare, often autosomal recessive disorder with a major risk for maternal and perinatal mortality and morbidity. In order to achieve a more favorable outcome, awareness of its clinical signs and symptoms and early recognition are of pivotal importance. Over a 5-year period, 18 patients were diagnosed with AFLP (one twin, 19 babies). The most common sign and symptoms were jaundice, hypoglycemia, nausea and vomiting, encephalopathy, and hypertension. Abnormal laboratory test results included elevated total/conjugated (direct) bilirubin, AST, ALT, PT, APTT, creatinine, leukocyte count, and hypoalbuminemia. Maternal and fetal mortality rate was high: 66.7% resulted in a maternal death and 57.9% in an intrauterine fetal demise (IUFD). The number of complications was found to correlate with maternal death (p = .042). Surviving AFLP patients had ≤3 complications, while patients with >3 complications on presentation had a high risk of maternal death (OR = 5.0; 95% CI: 0.55-45.4). The presence of hypertension significantly increased the risk of maternal death (OR: 24.5; 95% CI: 1.1-542.8; p = .01). The risk of IUFD was primarily related to gestational age at delivery and birth weight. The high rate of jaundice as presenting symptom of AFLP suggests that Indonesian primary maternity care providers may often miss its important earlier signs and symptoms, in particular de novo onset of nausea and vomiting in late pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To compare the level of serum heme oxygenase 1 (HO-1), soluble FMS like tyrosine kinase (sFlt-1), and neonatal outcome in early onset preeclampsia (EO-PE), late onset preeclampsia (LO-PE), and normal pregnancy (NP).Methods: In this prospective observational case control study, HO-1 and sFlt-1 levels were measured in blood samples within 24 h of hospital admission. Preeclampsia cases were divided into two groups based on gestational age at delivery: EO-PE (<34 weeks) and LO-PE (≥34 weeks). A total of 45 patients were involved in this study.Result: Maternal serum level of sFlt-1 was higher in EO-PE than LO-PE and NP groups (mean ± SD; 14.50 ± 17.12 ng/ml vs 5.20 ± 6.69 ng/ml vs 2.72 ± 1.2 ng/ml [p = 0.020]. Maternal serum level of HO-1 was not different between EO-PE, LO-PE, and NP groups (p = 0.681). Birthweights were significantly lower in the EO-PE group compared with the LO-PE and NP groups (1580 ± 536 g vs 2635 ± 578 g vs 3010 ± 371 g [p = 0.000]). The rate of small for gestational age infant (26.7% vs 6.7% vs 0%; p = 0.046) and perinatal death (20% vs 0 vs 0; p = 0.037) was also significantly higher in EO-PE compared to LO-PE and NP. The maternal sFlt-1 level was negatively correlated with birthweight (p = 0.006; CC = -0.445).Conclusion: This study did not find a correlation between maternal HO-1 levels and sFlt-1 levels. Maternal serum sFLt-1 levels in preeclampsia were higher in EO-PE and were associated with a worse perinatal outcome. [ABSTRACT FROM AUTHOR]

Objectives: We sought to investigate the potential association between maternal age and the need for active obstetrical intervention intrapartum in primiparas.Study Design: Observational study over 14 years (2001-2014) of all consecutive primiparous singleton births having delivered at the Centre Hospitalier Universitaire Hospitalier Sud Reunion's maternity (French overseas department, Indian Ocean).Results: Of the 21,235 singleton primiparous births, there were three significant linear associations between maternal age from 12 years of age to 42 + (all χ2 for linear trend, p < .0001) (a) vaginal deliveries without any medical intervention, (b) rate of cesarean sections, and (c) rate of operative vaginal procedures. These three linear associations persisted when controlling for maternal obesity (±30 kg/m2), "heavy babies" (>3.5 kg), and ethnicity. Using maternal age remained significantly an independent risk factor (p < .0001), after controlling for the major confounders: maternal BMI, maternal height, birthweight ≥3500 g, p < .0001.Conclusions: Increasing maternal age has a linear association with vaginal deliveries without any medical intervention, rate of cesarean sections, and rate of operative vaginal procedures. These associations are independent of maternal BMI and maternal height. We currently do not have a specific explanation why younger women appear to be protected from requiring intrapartum obstetric intervention. Nevertheless, these strong facts deserve acknowledgement and further research. [ABSTRACT FROM AUTHOR]

Objective:To analyze risk factors, obstetric outcome and the need for mechanical ventilation in preeclampsia complicated by pulmonary edema. Materials and methods:Case–control study using medical record on preeclampsia complicated by pulmonary edema patients in East Java tertiary referral hospital over 2 years. A simple scoring system was developed to predict the need for mechanical ventilation, using logistic regression. Results:1106 cases of preeclampsia were admitted, with 62 cases (5.6%) had pulmonary edema. Postpartum (p < .001) and cesarean delivery (p = .001) proportions were higher in the preeclampsia with pulmonary edema group. Of the 62 cases with pulmonary edema, 81% required intensive care admission and 60% needed mechanical ventilation support. Mechanical ventilation used was associated with eclampsia (p = .04), hypertensive crisis (p = .02), lower serum albumin (p = .05) and higher creatinine (p = .01). A simple scoring model developed could predict a 46%–99% probability of need for mechanical ventilation (AUC (ROC): 0.856, 95%CI 0.763–0.95). Conclusions:Pulmonary edema is a common complication of preeclampsia in Indonesian referral hospitals. This severe complication increased maternal and perinatal morbidity and mortality. The developed scoring model in this study can be used as a triage tool to predict the probability of mechanical ventilation use due to this complication. [ABSTRACT FROM PUBLISHER]

Purpose: To investigate the association between maternal age and spontaneous breech presentation.Material and Methods: Fifteen-year observational study over (2001-2015). All consecutive singleton births delivered at the Centre Hospitalier Universitaire Sud Reunion's maternity. The only single exclusion criterion was uterine malformations (N = 123) women.Results: Of the 60,963 singleton births, there was a linear association (χ2 for linear trend, p< 0.0001) between maternal age and spontaneous breech presentation. Overall rate of breech presentation was 2.7% in deliveries over 32 weeks gestation, while it was 1.9% in women aged 15 to 19 years and 4.0% in women aged 45+, with a linear progression for each 5-year age category. This linearity remained significant controlling for early prematurity (<33 weeks) and severe fetal malformations (χ2 for linear trend = 64, p < 0.0001). Controlling in a multiple logistic regression model for other major risk factors gestational age, female sex, primiparity, maternal age remained significantly an independent risk factor, p < 0.0001.Conclusion: Maternal age (x) is an independent factor for breech presentation in singleton pregnancies after 32 weeks gestation with a linear association that may be approximated at y = 0.1x. (y: incidence, percent). [ABSTRACT FROM AUTHOR]

Introduction: The aim of this paper was to provide an in-depth analysis of all stillbirth causation over a period of 10 years in a busy maternity unit located in a socioeconomically disadvantaged urban area, with an emphasis on overlapping pathology.Materials and Methods: A retrospective analysis of all structurally normal stillbirths in singleton pregnancies born during 2002-2012. The PSANZ stillbirth classification was used; per stillbirth subgroup main risk factors were evaluated.Results: Out of 130 cases, 43% showed overlapping pathologies. In the remaining 74 (56%) cases, the following single pathologies were found: IUGR 20 (15%), infection 12 (9%), abruption 8 (6%), placental thrombotic pathology 8 (6%), miscellaneous 6 stillbirths (5%), and 20 cases (15%) unexplained. Smoking was a risk factor for stillbirth associated with abruption (OR 3.639), infection (OR 2.271), and thrombotic pathology (OR 2.168). Drug use had an association with (placental) infection (OR 3.598). Obesity showed a significant association with IUGR (OR 3.782) and abruption (OR 9.040). Thrombophilia risk analysis for the overall group of stillbirths showed significant results for Protein S (OR 8.889) and homocysteine >90th centile (OR 2.087).Conclusions: Overlapping pathology was identified in 43% of stillbirths. Infection, IUGR, and abruption were the most important single cause of stillbirth. [ABSTRACT FROM AUTHOR]

Objective: To determine the impact of self-reported maternal depression/anxiety on asthma control during pregnancy.Method: Pregnant women with a doctor diagnosis of asthma (n = 189) were prospectively recruited at their antenatal booking visit, and the presence of maternal depression and anxiety was identified using self-report and routine questionnaire assessments. Data on exacerbations and asthma control were collected during gestation. Asthma control was assessed using the Juniper Asthma Control Questionnaire (ACQ) and women were classified as having recurrent uncontrolled asthma if their ACQ score was >1.5 during two or more consecutive study visits. Exacerbations were defined as events that led to increased treatment requirements, and doctor or hospital visits.Results: There were 85 women with self-reported depression/anxiety and 104 women without self-reported depression/anxiety. The presence of depression/anxiety was associated with an increased likelihood (adjusted hazard ratio (HR) 1.67: 95% confidence interval (CI) 1.03–2.72) and incidence (adjusted incidence rate ratio (IRR) 1.71: 95% CI 1.13–2.58) of uncontrolled asthma during pregnancy, as well as an increased risk of recurrent uncontrolled asthma during 2 or more study visits (adjusted relative risk (RR) 1.98: 95% CI 1.00–3.91). No impact of depression/anxiety was observed with respect to the likelihood (adjusted HR 0.70: 95% CI 0.35–1.41) or incidence of exacerbations during pregnancy (adjusted IRR 0.66: 95% CI 0.35–1.26).Conclusions: This study provides evidence that the presence of maternal depression/anxiety is associated with an increased likelihood and incidence of uncontrolled asthma during pregnancy. Given the high prevalence of co-morbid depression/anxiety among asthmatics, further research investigating such associations is urgently required. [ABSTRACT FROM PUBLISHER]

Objective: To analyze risk factors, obstetric outcome and the need for mechanical ventilation in preeclampsia complicated by pulmonary edema.Materials and Methods: Case-control study using medical record on preeclampsia complicated by pulmonary edema patients in East Java tertiary referral hospital over 2 years. A simple scoring system was developed to predict the need for mechanical ventilation, using logistic regression.Results: 1106 cases of preeclampsia were admitted, with 62 cases (5.6%) had pulmonary edema. Postpartum (p < .001) and cesarean delivery (p = .001) proportions were higher in the preeclampsia with pulmonary edema group. Of the 62 cases with pulmonary edema, 81% required intensive care admission and 60% needed mechanical ventilation support. Mechanical ventilation used was associated with eclampsia (p = .04), hypertensive crisis (p = .02), lower serum albumin (p = .05) and higher creatinine (p = .01). A simple scoring model developed could predict a 46%-99% probability of need for mechanical ventilation (AUC (ROC): 0.856, 95%CI 0.763-0.95).Conclusions: Pulmonary edema is a common complication of preeclampsia in Indonesian referral hospitals. This severe complication increased maternal and perinatal morbidity and mortality. The developed scoring model in this study can be used as a triage tool to predict the probability of mechanical ventilation use due to this complication. [ABSTRACT FROM AUTHOR]

Objective: Elevated pro-inflammatory cytokines play an important role in the pathogenesis of preeclampsia. We investigated the prevalence of functional polymorphisms in genes regulating inflammation in preeclamptic women. Methods: One hundred seventy-five nulliparous Sinhalese women with preeclampsia (cases) and 171 normotensive women matched for age, ethnicity, parity and body mass index (BMI) (controls) were recruited. Preeclampsia was diagnosed using international guidelines. Genotyping was performed on DNA extracted from peripheral blood using the Sequenom MassARRAY system. Results: The prevalence of the CT genotype ofIL1Ars17561 polymorphism was increased in preeclamptic women compared with controls {p = 0.04, odds ratio (OR) [95% class interval (CI)] = 1.6 (1.0–2.5)}. The prevalence of the CT genotype [p = 0.01, OR (95% CI) = 1.8 (1.1–2.8)] and the dominant model (CT + TT) [p = 0.03, OR (95% CI) = 1.6 (1.1–2.5)] of theIL1Ars1800587 polymorphism were increased in preeclamptic women compared with controls. The prevalence of the GA genotype [p = 0.04, OR (95% CI) = 0.6 (0.4–0.9)] and the dominant model (GA + AA) [p = 0.03, OR (95% CI) = 0.6 (0.4–0.9)] of theMBL1rs1800450 polymorphism were reduced in preeclamptic women compared to controls. Conclusion: Genotypes conferring a pro-inflammatory phenotype are increased in preeclamptic women. [ABSTRACT FROM PUBLISHER]

Objective: To compare oral iron to intravenous iron administration to women in late pregnancy and/or after labor to correct iron deficiency. Methods: 271 anemic women (148 pregnant women and 123 women post lower segment caesarean section) with hemoglobin (Hb) levels below 110 g/L were enrolled over a two-year period and randomized to receive either two tablets FGF (ferrous sulfate with folic acid) or 400 mg of intravenous iron sucrose plus folic acid 600 µg. Treatment effectiveness was assessed by measuring Hb and ferritin postpartum on day 1, day 14 and day 42. Transfusions of red blood cells and adverse drug reactions were recorded. Results: Data of 214 women were available for analysis. Both forms of iron replacement therapy led to increased hemoglobin and ferritin levels over the testing period. Ferritin was significantly higher in the i.v. iron treatment group compared to the oral iron treatment group ( p = 0.004) two weeks after delivery, while Hb values did not differ between the groups. No serious adverse drug reactions were observed. Red blood cell transfusion rate was low (1.9%), with equal rates observed in both treatment groups. Conclusion: Intravenous and oral irons were both effective in correcting peripartum anemia, although intravenous iron restored stores faster than oral iron. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association of polymorphisms in the vascular endothelial growth factor (VEGF) family genes ( VEGFA rs699947, VEGFA rs3025039, PGF rs1042886, KDR rs2071559 and KDR rs2305948) with preeclampsia in Sinhalese women in Sri-Lanka. Methods: We conducted a case-control study where 175 nulliparous Sinhalese women with preeclampsia and 171 normotensive women matched for age, ethnicity, parity and BMI were recruited in tertiary care maternity hospitals in Sri-Lanka. Preeclampsia was diagnosed using international guidelines. DNA extracted from peripheral venous blood and was genotyped using the Sequenom MassARRAY system. χ2-test was used to compare the distribution of allele and genotype frequencies between the cases and the control subjects. Results: The frequency of PGF rs1042886 variant allele (odds ratio (OR) 1.5, 95% confidence interval (CI) 1.1-2.1) and dominant genotype model (aOR 1.6, 95% CI 1.0-2.4) were increased in preeclamptic women compared to controls. VEGFA rs699947, VEGFA rs3025039, KDR rs2071559, and KDR rs2305948 polymorphisms were not associated with preeclampsia. Conclusion: Maternal PGF rs1042886 polymorphism is associated with preeclampsia in Sinhalese women in Sri-Lanka. [ABSTRACT FROM AUTHOR]

Objective: Intrauterine infection is a risk factor for cerebral palsy. Previous work reported a high frequency of viral DNA in newborn screening cards from cerebral palsy cases and controls possibly due to contamination. Methods: Retrospective case-control study using improved methodologies to minimize contamination during PCR-based detection of viral DNA sequences. Newborn screening cards of 339 Caucasian children with cerebral palsy and 594 controls were examined. Viruses tested were herpes simplex viruses 1 and 2 (HSV1 and 2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpes viruses 6, 7 and 8 (HHV6, HHV7 and HHV8), and parvovirus B19. Genotyping was performed on DNA extracted from dried blood spots. Results: CMV and EBV were detected in 5 (1.5%) and 3 (0.9%) of 339 cases, respectively, but not in controls ( p = 0.047 and 0.006). Frequencies of detection of the other viruses examined were similar for cases and controls. DNA from at least one of the nine viruses tested was found in 4.4% of cases and 3.1% of controls [OR 1.4 95% CI (0.71-2.76)]. Conclusion: Evidence of congenital viral infection was uncommon in cases of cerebral palsy and controls. However, CMV and EBV were significantly associated with cerebral palsy. [ABSTRACT FROM AUTHOR]

Objective: To determine if maternal circulating red blood cell (RBC) folate concentration in early pregnancy is associated with late gestation pregnancy complications including small for gestational age (SGA) infants, preeclampsia and preterm birth (PTB) in a socioeconomically disadvantaged population. Method: This was a retrospective case control study, conducted at Lyell McEwin Health Service, South Australia, including 400 primiparous women. RBC folate and demographic data were collected at 10-12 weeks gestation. Pregnancy outcome data were obtained from patient case notes. Results: Patients who were folate deficient were more likely to develop pregnancy complications, specifically SGA (OR 6.9, 95% CI 2-24.3) and PTB (OR 5.4 95% CI 1.4-21.2). Those who were folate insufficient were also at increased risk of SGA (OR 3.0, 95% CI 1.3-7.7). No association between folate and preeclampsia was found. Women who were supplementing with folic acid delivered infants who were 179 g heavier (5.5% increased birth weight, P = 0.003) and 4.5 days later, compared to those who did not supplement. Furthermore, low RBC folate was associated with cigarette smoking ( P < 0.001). Conclusions: Maternal RBC folate concentration in early pregnancy is associated with SGA and PTB, but not with preeclampsia. [ABSTRACT FROM AUTHOR]

Objective. The purpose of this study was to compare population and customized-based birth weight centiles in their association with perinatal outcome and maternal risk factors, in nulliparous Caucasian women in a socio-economic disadvantaged region. Methods. We analyzed perinatal outcomes in births of 302 Caucasian women of which 155 were small for gestational age (SGA) and 147 were appropriate for gestational age (AGA). Out of the overall study group, two cohort studies were designed. One was classified by population centiles as either SGA ( n== 133) or AGA ( n == 169) and the other was classified by customized centiles as either SGA ( n == 131) or AGA ( n == 172). Maternal risk factors and operative delivery rates for fetal distress, Apgar scores, need for resuscitation and neonatal nursery care given, were determined for both customized and population-based SGA babies. Results. The customized SGA only group showed more mental health problems and special nursery in comparison with the AGA group. The population SGA only group had more smoking and mental health problems than the AGA group, but no differences on neonatal outcome measures. Conclusion. Use of customized centiles does identify an additional group neonates with a significantly higher need for special nursery admission in a homogeneous ethnic Caucasian group. [ABSTRACT FROM AUTHOR]

Objective. To investigate the roles of inherited polymorphisms in the MBL2 gene and exposure to viral infection in the development of a range of adverse pregnancy outcomes, including birthweight <10th percentile (small-for-gestational age, SGA), antepartum hemorrhage (APH), pregnancy-induced hypertensive disorders (PIHD), and preterm birth (PTB). Methods. This was a case--control study using DNA from newborn screening cards of 717 cases (babies with at least one of the adverse pregnancy outcomes listed above) and 609 controls, to screen for six polymorphisms within the MBL2 gene. These combine to create haplotypes with high (HYPA), intermediate (LYQA, LYPA), low (LXPA), and defective (HYPD, LYQC, LYPB) circulating MBL2 levels. Results. Significant associations were found between variant MBL2 haplotypes and SGA (LYPA <32 weeks OR 5.37, 95%% CI 1.50--17.27), antepartum hemorrhage (LYPA <37 weeks OR 2.29, 95%% CI 1.25--4.18), and PIHD (LYQC <32 weeks (OR 17.89, 95%% CI 2.20--139.57). Evidence of exposure to infection increased the effect of these associations, (SGA OR 17.00, 95%% CI 1.03--252.48; APH OR 5.67, 95%% CI 1.73--18.84; PIHD OR 23.80, 95%% CI 1.08--1414.76), while no evidence of exposure to infection demonstrated no associations. PTB was significantly associated with the defective HYPD haplotype with evidence of exposure to infection (OR 6.14, 95%% CI 1.21--29.89). Conclusions. This research suggests that the combination of fetal MBL2 haplotypes and exposure to in utero viral infection increases the risk of adverse pregnancy outcomes, including PTB, antepartum hemorrhage, small-for-gestational age and PIHD. [ABSTRACT FROM AUTHOR]

Objective: Circulating angiogenic growth factors (such as vascular endothelial growth factor [VEGF] and placental growth factor [PlGF]) and their interaction may be associated with vascular remodeling of spiral arteries in normal pregnancy. Soluble Flt-1, an antagonist of both VEGF and PlGF, has been shown to be increased, while PlGF is decreased in women prior to the onset of preeclampsia. The purpose of this study was to compare maternal soluble Flt-1 and PlGF levels in the second trimester with a marker of abnormal placentation, abnormal uterine artery Doppler (UAD). Method: A prospective cohort of women, 16 to 24 weeks estimated gestational age (EGA), with singleton pregnancies, underwent UAD and phlebotomy. Maternal soluble Flt-1 and free PlGF were measured by ELISA in samples from women with abnormal UAD with a group, controlled for EGA, with normal UAD. Mann-Whitney Rank-Sum test was used to compare maternal serum levels of both soluble Flt-1 and PlGF between women with abnormal uterine artery Doppler versus women with normal uterine artery Doppler. Results: Of the 222 study subjects enrolled, 34 (15%) had abnormal UAD. The mean EGA at enrollment of subjects in each group was 18 weeks. There was no difference in PlGF between subjects with abnormal UAD (median, 191 pg/mL; range, 187 to 337 pg/mL) versus controls (median, 171 pg/mL; range, 169 to 289 pg/mL) (p = 0.59) or soluble Flt-1 (median, 780 pg/mL; range, 280 to 3200 pg/mL) or between subjects with abnormal UAD versus controls (median, 720 pg/mL; range, 220 to 1980 pg/mL) (p = 0.36). Conclusion: Concentrations of maternal soluble Flt-1 and free PlGF in the second trimester do not appear to be altered in women with abnormal UAD. This suggests that these biochemical markers are independent of the increased placental resistance seen with abnormal uterine artery Doppler. [ABSTRACT FROM AUTHOR]

Introduction . To determine whether the risk of preeclampsia in multiparous women with a previous normal pregnancy is related to changing paternity or to prolonged birth interval, a retrospective study was conducted at the Lyell McEwin Health Service (University of Adelaide). Methods . The study included all multiparous women known to the hospital because of their preceding 1st delivery in the same hospital followed by their 2nd and/or 3rd ongoing pregnancy resulting in a delivery in the period 2001 – 2003. Case records were analyzed for birth interval, pregnancy interval, paternity and recognized risk factors such as booking weight and smoking. For the analysis both the International Society for the Study of Hypertension in Pregnancy (ISSHP) definition and the more recently introduced classification by the Australian Society for the Study of Hypertension in Pregnancy (ASSHP) were used. Results . In the 656 women in this study cohort, 148 (26.2%) women had a different partner in their 2nd and/or 3rd ongoing pregnancy. Using the ISSHP definition for preeclampsia, changing partners had an odds ratio (OR) of 1.304 (95% CI 0.43 – 3.99); using ASSHP criteria an OR of 1.556 (95% CI 0.6506 – 3721); and looking at the combined group of pregnancy-induced hypertensive disorders an OR of 1.99 (95% CI 1.01 – 3.89). A longer birth interval if anything was associated with a lower risk of preeclampsia (non-significant), whatever definition was used. Also the inter-pregnancy interval did not show a consistent relation with the risk for developing a hypertensive complication. Conclusions . The results of this study on risk factors for preeclampsia in multiparous women appear to be in line with the primipaternity hypothesis, but are in direct contrast with the so-called birth interval hypothesis. [ABSTRACT FROM AUTHOR]

Objective . Tumor necrosis factor-alpha (TNF-α) is thought to play a role in immune activation in preeclampsia. The objective of this study was to establish if soluble TNF-receptor I (sTNF-rI) levels relate to the onset and severity of preeclampsia. Methods . Maternal plasma sTNF-rI levels were studied throughout pregnancy in 68 women with a history of severe preeclampsia or intra-uterine growth restriction (IUGR), and primigravidas with chronic hypertension. Data are presented as mean (SD) in ng/ml. Results . In the second trimester there was a significant difference in sTNF-rI levels between preeclamptic pregnancies with and without IUGR (means 1.33 (0.20) and 1.11 (0.15) respectively, p < 0.005). In severe preeclampsia with delivery before 34 weeks of gestation, sTNF-rI levels were higher than in mild preeclampsia in the second and third trimesters (means 1.40 (0.16) vs. 1.16 (0.19), p < 0.02 and 1.82 (0.47) vs. 1.42 (0.22), p < 0.05, respectively). Conclusion . sTNF-rI levels were higher in preeclampsia with fetal involvement, suggesting that increased TNF-α production in preeclampsia is related to impaired placentation rather than to the maternal syndrome. [ABSTRACT FROM AUTHOR]

Presents the case of three women with a hepatic rupture in combination with preeclampsia, as encountered since 1990 in the Vrije Medical Center. Case histories; Diagnosis of multiple pulmonary embolisms; Postpartum testing for protein C and S deficiency; Complication of pregnancy with a high maternal and fetal mortality.

Objective: To establish if agreement exists between central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP) measurements in severe hypertension in pregnancy as analyzed by tests of bias, precision, and 95% limits of agreement.Methods: In a prospective study, CVP and PCWP data in 30 patients were collected by means of a pulmonary artery catheter from initiation of therapy until delivery. Patients with a diastolic blood pressure of more than 110 mm Hg were included. Correlation and agreement between CVP and PCWP before and after treatment were evaluated.Results: The correlation coefficient (r) for CVP-PCWP data in 30 untreated patients was r = 0.64 (p = 0.0002) and for 256 pairs of posttreatment data, it was r = 0.53 (p < 0.0001). Linear regression and correlation for each individual patient in 29 patients with more than 3 measurements showed a significant correlation (p < 0.05) in 19 patients (66%). Correlation was poor (p > 0.05) in 10 patients (34%). The mean difference between PCWP and CVP was 3.5 +/- 2.6 mm Hg (limits of agreement: -1.6 to 8.7) in untreated patients. The mean difference between PCWP and CVP for 256 pairs of data derived posttreatment was 4.9 +/- 3.8 mm Hg (limits of agreement: -2.7 to 12. 5).Conclusion: Invasive measurements of CVP and PCWP were found to agree poorly. Until a reliable noninvasive method is available to measure left ventricular preload, PCWP is the measurement of choice when invasive hemodynamic monitoring is necessary in patients with severe preeclampsia. [ABSTRACT FROM AUTHOR]

Focuses on a study which investigated the relationship between smoking behavior of pregnant nulliparous women and self-reported daily stressors, as well as psychological and somatic well-being. Methodology; Results and discussion on the findings of the study.