Polycystic ovary syndrome and low-grade inflammation with special reference to YKL-40

Objective: To evaluate the plasma level of YKL-40 in a Danish polycystic ovary syndrome (PCOS) population and to investigate whether YKL-40 is associated with CVD risk factors such as waist circumference, body mass index (BMI), insulin resistance (IR), fasting glucose, fasting insulin, blood lipids and CRP.

Design: Cross-sectional study.

Setting: Gynecological clinics at three Danish University Hospitals.

Patients: One hundred seventy-one premenopausal women with PCOS recruited consecutively from April 2010 to February 2012. PCOS was diagnosed according to the Rotterdam criteria.

Main outcome measures: Plasma level of YKL-40 in four phenotypes of PCOS defined by BMI and IR.

Results: No statistically significant difference was observed in the plasma level of YKL-40 across the four BMI/IR-phenotypes. Positive associations were observed between YKL-40 and BMI, total and free testosterone, triglycerides, and CRP. Total and free testosterone were independent predictors of YKL-40.

Conclusion: YKL-40, the marker of low-grade inflammation is not increased in women with PCOS.     

Does preeclampsia involve the pancreas? A report of original research

Objective: To analyze the effect, if any, of pregnancy-related hypertension on the pancreas.

Methods: A database of pregnant women with hyperbilirubinemia was reviewed for cases with serum amylase values. These cases were linked to a computerized obstetric database, and women were analyzed according to the diagnosis of preeclampsia.

Results: A total of 292 consecutive women with hyperbilirubinemia during pregnancy delivered at our institution between 2005 and 2011. Of these, 52 (18%) were diagnosed with preeclampsia, and in only nine was serum amylase abnormally elevated.

Conclusion: Using serum analytes as surrogates for organ injury, it appears preeclampsia infrequently affects the pancreas.     

Anti-Mullerian hormone and insulin resistance in polycystic ovary syndrome

Introduction: Polycystic ovary syndrome (PCOS) is a prevalent disease affecting women of reproductive age. It may be associated with metabolic disorders such as insulin resistance (IR) and obesity. The anti-Mullerian hormone (AMH) levels seem to be higher in patients with PCOS.

Objective: The present study was designed to evaluate the association between AMH and insulin in women with PCOS with and without IR.

Methods: Cross-sectional study, including 86 patients, selected and divided into three groups: Group A: 26 women with PCOS and IR; Group B: 30 women with PCOS and without IR; and Group C: 30 controls without PCOS.

Results: We found significant difference between serum AMH levels in the group of women with PCOS and without IR when compared to the control group, thus showing that PCOS and IR play an important role in elevating the levels of this hormone. When the groups were compared with each other following adjustment for BMI, serum AMH levels were significantly higher in the group of women with PCOS and IR.

Conclusion: AMH levels are significantly higher in patients with PCOS, particularly in those women with PCOS and IR. Nevertheless, larger samples are required to confirm these findings.     

The influence of psychological factors on postpartum weight retention 12 months post-birth

Background

During the first postpartum year 20% of women retain excessive weight from pregnancy (postpartum weight retention; PPWR), which predicts long-term overweight/obesity.

Objective

The aim of this study was to explore the associations between psychological factors (depression, anxiety and stress symptoms and body attitudes) in late gestation and at 12-months postpartum with PPWR one-year post-birth.

Methods

Pregnant women (N = 176) completed questionnaires in early–mid pregnancy (Time 1; mean (SD) = 16.97 (1.35) weeks), late pregnancy (Time 2; mean (SD) = 33.33 (2.05) weeks), and one year postpartum (Time 3; mean (SD) = 53.12 (3.34) weeks). Women provided demographic characteristics, height and pre-pregnancy weight at Time 1. At Times 2 and 3, weight, depressive, anxiety and stress symptoms and body attitudes (salience of weight and shape, attractiveness, feeling fat, and strength and fitness) were assessed in addition to physiological, socio-contextual and lifestyle factors. Gestational weight gain and PPWR were calculated. Hierarchical linear regression models were conducted to explore variance in 12-month PPWR.

Results

Overall, models explained 26–39% variance in PPWR. Gestational weight gain in late pregnancy and low attractiveness at 12 months postpartum were the only variables associated significantly with 12-month PPWR.

Conclusion

While psychological factors did not appear to be important direct contributors to PPWR at 12 months, the overall contribution of all variables suggests that such factors may be implicated in a small and incremental way. Exploration of the interactions between variables will help unpack potential mechanisms of the development of PPWR at 12 months post-birth.     

D2-Thr92Ala,thyroid hormone levels and biochemical hypothyroidism in preeclampsia

Aim: To identify if there is a relationship between the deiodinase D2-Thr92Ala genetic variant, thyroid hormone levels and biochemical hypothyroidism in preeclampsia.

Materials and methods: We genotyped 125 women with preeclampsia and 131 normal pregnant women using PCR-RFLP. Serum thyroid hormone levels were determined using ELISA.

Results: Our study showed higher TSH and FT4 levels and lower FT3 levels in women with preeclampsia compared to normal pregnant women, with statistical significance for women with mild and severe preeclampsia. The risk to develop pregnancy-induced hypertension (PIH), mild or severe preeclampsia was increased in carriers of at least one D2-Ala92 allele. TSH and FT4 levels were significantly higher and FT3 levels were significantly lower in preeclamptic women with severe preeclampsia if they carried the D2-Ala92 allele compared to non-carriers. Pregnant women with PIH and mild preeclampsia, carriers of at least one D2-Ala92 allele, delivered at lower gestational age neonates with a lower birth weight compared to non-carriers, but the results were statistically significant only in severe preeclampsia.

Conclusion: The D2-Thr92Ala genetic variant is associated with the severity and the obstetric outcome of preeclampsia, and it also influences thyroid hormone levels. The study demonstrates non-thyroidal biochemical hypothyroidism – as a result of deiodination effects due to D2 genotypes.     

Transcervical Foley’s catheter versus Cook balloon for cervical ripening in stillbirth with a scarred uterus: a randomized controlled trial

Objective: To compare the efficacy and safety of the use of transcervical Foley’s catheter versus Cook cervical ripening balloon in pregnant women with stillbirth, unfavorable cervix and scarred uterus.

Design: Randomized controlled study.

Setting: El Minia University Hospital, El Minia, Egypt.

Patients and methods: Two-hundred pregnant women with stillbirth, unfavorable cervix and scarred uterus were recruited into this study. They were randomized into two groups. In group I (n?=?100), cervical ripening was done using Foley’s catheter. In group II (n?=?100), cervical ripening was done using Cook cervical ripening balloon.

Main outcome measures: Balloon insertion to delivery interval, successful ripening rate, cesarean delivery rate, maternal adverse events and maternal satisfaction.

Results: Time from balloon insertion to expulsion and from balloon insertion to delivery was significantly shorter in Foley’s catheter group. However, the difference between the two groups regarding time from balloon insertion to active labor, time from balloon expulsion to delivery, cervical ripening, cesarean section, instrumental delivery, pain score, need for analgesia, hospital stay and maternal satisfaction was not statistically significant.

Conclusions: Foley’s catheter and Cook cervical ripening balloon are comparable regarding efficacy and safety profile when used to ripen the cervix in pregnant women with stillbirth, unfavorable cervix and scarred uterus. However, Foley’s catheter has a shorter induction to delivery interval and is relatively cheaper device.     

Maternal venous hemodynamics assessment for prediction of preeclampsia should be longitudinal

Objective: To address the question whether maternal venous abnormalities exist at the onset of, or develop during the course of pregnancy.

Methods: We present five case reports of patients with early onset preeclampsia (EPE), late onset preeclampsia (LPE), gestational hypertension (GH), essential hypertension (EH) and an uncomplicated pregnancy (UP). Maternal renal and hepatic vein Doppler waves and maternal venous pulse transit times (VPTT) were assessed in early pregnancy and again shortly before delivery.

Results: In all cases, maternal VPTT were normal in early pregnancy and changed to abnormal values in EPE and LPE, which was not true for UP and GH or EH.

Conclusion: These observations support the view that venous hemodynamic dysfunction of preeclampsia (PE) develops during the course of pregnancy. Therefore, assessment of an individual's venous function for prediction of PE should be serial and longitudinal.     

Blood-based biomarkers of adverse perinatal outcomes in maternal obesity

Objective: Increasing maternal weight has been shown to predict adverse perinatal outcome, including increases in the relative risk of fetal death, stillbirth, neonatal death, perinatal death and infant death. In order to better understand the pathophysiological factors associated with obesity during pregnancy, the role of biomarkers associated with adverse outcomes in obese pregnant women is under investigation. The purpose of this review study was to examine potential biomarkers that could serve as effective screening strategies in obese pregnant women to reduce fetal and neonatal morbidity, as well as maternal morbidity.

Methods: Electronic databases (Pubmed, Embase) were searched for previously published research studies that investigated biomarkers associated with perinatal outcomes in obese pregnant women and the putative mechanisms underlying biomarker effects on pregnancy outcomes.

Results: It is evident that while several biomarkers predict perinatal complications in obese pregnant women, none fulfilled the criteria to be considered clinically useful.

Conclusion: There is a critical need for reliable blood-based biomarkers associated with an increased risk of adverse perinatal outcomes in obese pregnant women.     

ß-hCG and prediction of therapeutic success in ectopic pregnancies treated with methotrexate,results from a prospective observational study

Objective: To evaluate the diagnostic accuracy of different beta-human chorionic gonadotrophin (ß-hCG) levels measurement, for predicting success of medical treatment in cases diagnosed as tubal ectopic pregnancy (TEP).

Design: Five-year prospective observational study.

Setting: Prenatal Diagnosis Unit, Vall d'Hebron University Hospital – Barcelona.

Patients: TEP cases fulfilling criteria for medical treatment with Methotrexate.

Interventions: ß-hCG levels were measured on d 0, 4 and 7 of treatment. Results were compared by non-parametrical tests. A ROC curve was plotted to define cut-off points. Diagnostic accuracy of the different measurements was evaluated.

Main outcome measure: Failure of treatment defined as need for surgical treatment or persistence of high ß-HCG levels despite treatment.

Results: 126 women were diagnosed as TEP, eligible for medical treatment. There were no differences in parity, age, previous TEP, or adnexal mass size. Success rate was 88%. ß-HCG decreased significantly more, between days 0–7 and 4–7, in the successful cases. LR for success prediction was 6.2 and 7.8 for ß-HCG levels at days 4 and 7 respectively, 4.02 and 2.47 for decrement between days 0–7 (25%) and 4–7 (20%), respectively.

Conclusion: ß-hCG cutoff values have a potential for predicting a successful medical treatment of TEP.     

Quantitative assessment of hepatic blood flow in the diagnosis and management of necrotizing enterocolitis

Background: Necrotizing enterocolitis (NEC) is the most important gastrointestinal emergency in the neonatal period and early detection is very important for its management. Bowel ischemia-hypoperfusion is one of the main etiological factors. In the literature, a few studies have focused on arterial Doppler ultrasonography (DUS) features of splanchnic arteries; however, their clinical implications are not clear.

Objective: In this study, we aimed to quantitatively evaluate the blood flow features in the hepatic portal vein (PV) and hepatic veins (HVs) by using DUS in newborns with NEC.

Patient-Method: Enrolled subjects were divided into two groups as patient (suspected/confirmed NEC, n?=?24), and control group (n?=?25). Daily serial DUS examinations were performed after the onset of the suspicion of NEC and continued until the initial day of the enteral feeding. Portal blood flow (PBF) and “hepatic blood flow ratio” (RHBF) were calculated manually by using DUS findings. Two groups were compared with respect to their PBF and RoHBF values.

Results: PBF and RHBF levels were significantly lower in patient group than those in control group. Clinical improvement in patients with NEC was associated with improvement in the PBF and RHBF. Cut-off level of the RHBF for the diagnosis of NEC was 0.66.

Conclusion: DUS seems to be useful for the diagnosis and follow-up of NEC by providing quantitative information on liver blood flow. Daily measurements of the PBF and RoHBF in newborns with NEC may be beneficial to make the decision of starting enteral feeding.     

Neonatal morbidities among full-term infants born to obese mothers

Introduction: Impact of maternal obesity on full-term neonates is not known.

Objective: We hypothesized increased incidence of neonatal morbidities requiring NICU admission in full-term neonates of obese women compared to neonates of normal-weight women.

Methods: Data from full-term pregnancies collected in the Consortium of Safe Labor study were analyzed. Maternal BMI was classified using the WHO criteria. Incidence of neonatal outcomes including sepsis, PDA, NEC, respiratory distress, or their combination were compared between newborns of obese and normal-weight women.

Results: Of the 109?488 women included in the study, 17.7% were obese. Maternal co-morbidities (diabetes, gestational diabetes, hypertension, and preeclampsia) increased with increasing maternal BMI. Both maternal obesity and its related co-morbidities were associated with higher incidence of neonatal morbidities. After adjusting for maternal comorbidities, there was a higher incidence of sepsis (AOR 1.91(1.45–2.50)), and combination of any of the neonatal outcomes (AOR 1.66(1.32–2.09)) among newborns of obese women than those of normal-weight women, along with an increased trend for incidence of PDA (Cochran-Armitage Test (CA)?=?23.1, p?<?0.0001) and NEC (CA?=?7.2, p?=?0.007).

Conclusion: Maternal obesity is independently associated with increased incidence of neonatal sepsis and a combination of neonatal morbidities in full-term newborns with an increased trend for PDA and NEC.     

A novel marker in pregnant with preeclampsia: renalase

Background: Preeclampsia is characterized by an increase in high blood pressure and decrease in GFR and proteinuria, however, the underlying mechanisms are still unclear. Renalase is a recently discovered protein implicated in regulation of blood pressure in humans.

Materials and methods: Plasma concentrations of serum renalase were measured in healthy controls, healthy pregnant and pregnant with preeclampsia matched for age, gestational age, in the third trimester of pregnancy. Serum renalase levels were compared in pregnant with and without preeclampsia and non-pregnant controls. Factors associated with serum renalase levels in pregnancies were also evaluated.

Results: In healthy pregnant serum renalase levels were significantly higher than in controls. However, pregnant with preeclampsia had lower renalase levels than healthy controls. Serum renalase levels were inversely associated with blood pressure levels and positively correlated with glomerular filtration rate.

Conclusion: The results indicated that the development of preeclampsia in pregnant is accompanied by altered serum renalase levels. High blood pressure and kidney damage that characterize this disorder are mediated at least in part by low renalase levels.     

Early pregnancy protein multiplex screening reflects circulating and urinary divergences associated with the development of preeclampsia

Background: Preeclampsia, a pregnancy disorder characterized by hypertension and proteinuria, represents the leading cause of fetal and maternal morbidity and mortality in developing countries. The identification of novel and accurate biomarkers that are predictive of preeclampsia is necessary to improve the prognosis of patients with preeclampsia.

Objective: To evaluate the preeclampsia predictive value of 34 angiogenic-related proteins.

Methods: We performed a nested cohort case-control study of pregnant women. The profile of the 34 proteins was evaluated at 12, 16, and 20 gestational weeks (GWs), using urine/plasma from 16 women who developed preeclampsia and 20 normotensive pregnant controls by Bio-Plex Pro^TM Human Cancer Biomarker Panels 1 and 2.

Results: The urine concentration of soluble epidermal growth factor receptor (sEGFR), hepatocyte growth factor (HGF), angiopoietin-2 (ANG-2), endoglin (ENG), soluble fas ligand (sFASL), interleukin 6 (IL-6), placental growth factor (PLGF), and vascular endothelial growth factor A (VEGF-A) at 12 GW, prolactin (PRL), ANG-2, transforming growth factor alpha (TGF-α), and VEGF-A at 16 GW, and soluble IL-6 receptor alpha (sIL-6Rα), ANG-2 and sFASL at 20 GW, were different between groups (p < 0.05). The concentration cut-off values calculated in this study for the mentioned proteins, predicted an increased risk to developing preeclampsia in a range of 3.8–29.8 times in the study population.

Conclusion: The proteins sEGFR, HGF, ANG-2, sFASL, IL-6, PLGF, VEGF-A, PRL, TGF-α FGF-b, sHER2/Neu sIL-6Rα, ENG, uPA, and insulin-like growth factor binding protein 1 (IGFBP-1), were predictive of the development of preeclampsia and their use as markers for this disease should be considered.     

Early pregnancy angiogenic proteins levels and pregnancy related hypertensive disorders

Introduction: Normal placental vascular development depends on multiple interactions of many regulatory molecules including pro and antiangiogenic proteins. It is considered that these vascular modulators might be one of the factors responsible for development hypertensive disorders in pregnancy.

Objective: To evaluate and compare the early pregnancy (11–14 week of gestation) serum level of angiogenic proteins sFlt1, VEGF i PIGF between different types of pregnancy related hypertensive disorders.

Materials and methods: The study included 177 pregnant women between 11 and 14 weeks of gestation, divided into four study subgroups (preeclampsia group-41, gestational hypertension group-31, chronic hypertension group-32 and miscarriage group-19) and control group-54. Blood samples (serum) were taken for measuring sFlt1, VEGF i PIGF by a quantitative ELISA technique and measuring other biochemical and hematological parameters.

Results: Significantly higher levels of sFlt1 were in the subgroups with preeclampsia and miscarriages, significantly lower level of VEGF in the all study subgroups and lover level of PIGF were in miscarriage group. In the groups with chronic and gestational hypertension there were higher level of sFlt1 and lover level of VEGF than in the control group, but the differences did not reach statistical significance.

Conclusion: Early pregnancy imbalance between antiangiogenic protein sFlt1 and proangiogenic molecules VEGF and PIGF could have impact on pathophysiology of placental disorders which leads to development of pregnancy related hypertensive disorders.     

Is preeclampsia associated with fetal malformation? A review and report of original research

Objective: To examine fetal malformations in mother–infant pairs with and without pregnancy-related hypertension.

Methods: This was an observational, population-based study of women delivering a singleton at our hospital. Specific fetal malformations identified in women with gestational hypertension or preeclampsia were compared to those without pregnancy-related hypertension. Women with chronic hypertension, superimposed preeclampsia on chronic hypertension and pregestational diabetes were excluded.

Results: Between March 2002 and December 2012, a total of 151 997 women delivered, and 10?492 (7%) had preeclampsia, 4282 (3%) had gestational hypertension and 137?223 (90%) were referent normotensive controls. Women with preeclampsia were significantly more likely to deliver infants with malformations when compared to normotensive controls (2.5% versus 1.6%, p?<?0.001), whereas women with gestational hypertension were not (1.9% versus 1.6%, p?=?0.16). The overall risk for fetal malformation associated with preeclampsia remained significant following logistic regression for age, race, parity and maternal body-habitus (adjusted OR 1.5; 95% CI: 1.3–1.7). Only single-organ system malformations – microcephaly and hypospadias – remained associated with preeclampsia (p?<?0.001), and fetal growth restriction was a co-factor for both.

Conclusions: Preeclampsia was associated with increased rates of fetal malformations when compared to normotensive women – specifically microcephaly and hypospadias. These associations appear predominantly as a consequence of impaired fetal growth.     

Maternal outcomes according to mode of delivery in women with severe preeclampsia: a cohort study

Objective: To determine the association between mode of delivery and maternal complications in patients with severe preeclampsia.

Methods: A prospective cohort study was conducted with 500 pregnant women with severe preeclampsia. The mode of delivery, vaginal or caesarean section, was considered the exposure, while the postpartum maternal complications and severe maternal morbidity were the outcomes. Logistic regression analysis was performed to determine the adjusted risk and 95% confidence intervals (95% CI) of maternal morbidity.

Results: Labour was spontaneous in 22.0% and induced in 28.2%, while 49.8% had an elective caesarean section. Ninety-five (67.4%) of the patients in whom labour was induced delivered vaginally. Total Caesarean rate was 68.2%. The risk of severe maternal morbidity was significantly greater in patients submitted to Caesarean section (54.0% versus 32.7%) irrespective of the presence of labour. Factors that remained associated with severe maternal morbidity following multivariate analysis were a diagnosis of HELLP syndrome after delivery (OR?=?3.73; 95% CI: 1.55–9.88) and having a caesarean (OR?=?1.91; 95% CI: 1.52–4.57).

Conclusions: Caesareans are often performed in patients with severe preeclampsia and are associated with significant postpartum maternal morbidity. Induction of labour should be considered a feasible option in these patients.     

Prediction of preeclampsia in type 1 diabetes in early pregnancy by clinical predictors: a systematic review

Purpose: The purpose of this study is to evaluate the prevalence and possible clinical predictors of preeclampsia present in early pregnancy among women with type 1 diabetes.

Methods: A systematic search of PubMed was conducted in April 2017. Inclusion criteria were largely unselected cohort, including at least 100 women with type 1 diabetes, dealing with either the prevalence of preeclampsia or possible clinical predictors of preeclampsia identified in early pregnancy.

Results: Based on 11,518 pregnancies in 11 articles, the prevalence of preeclampsia in women with type 1 diabetes was 17%, five to six times more than in the background population. In early pregnancy, the following clinical predictors were associated with increased prevalence of preeclampsia: diabetic nephropathy (OR 3.7–23.5), microalbuminuria (OR 3.8–11.7), diabetic retinopathy (OR 1.9–2.9) and pre-existing hypertension (OR 3.8–17.1) as well as high blood pressure within the normotensive range. HbA1C, body mass index and nulliparity were positively associated with preeclampsia, but not consistently.

Conclusion: The prevalence of preeclampsia in women with type 1 diabetes was 17%. In early pregnancy pre-existing hypertension and high blood pressure within the normotensive range as well as presence of microangiopathy were predictors of preeclampsia. Poor glycaemic control, obesity and nulliparity probably also contribute to the increased risk.     

The role of narrative medicine in pregnancy after liver transplantation

Narrative medicine allows professionals from all fields of medical sciences to understand the patient’s total experience of illness, and meet his/her needs in an empathetic environment. Narrative medicine helps spread holistic knowledge of a multitude of complex clinical conditions, including transplantation.

Objective: To underline the role of narrative medicine in women who become pregnant after a liver transplant by using their narrations of this very special experience.

Methods: We describe our study with narration and listening to the stories of three women expecting their first child after a liver transplant, by analysing the structure and role of narration in the context of relationships between patients and caregivers. The narrations were transcribed verbatim with the main plot analysed in order to address all the aspects of this rare clinical condition and the transition to parenthood.

Results: The women narrated this experience in three phases: transplantation, pregnancy and delivery, and post-partum. They described all phases of pregnancy as stressful but satisfying, whereas the fact of becoming a mother was perceived as a victory both as a woman and as a transplant patient.

Conclusions: Our results suggest that narrative medicine represents a significant professional tool for caring for transplant patients during pregnancy.     

Preeclampsia enhances neuroglial marker expression in umbilical cord Wharton's jelly-derived mesenchymal stem cells

Objective: The aim of the study was to compare the neuroglial phenotype of Wharton's jelly-derived mesenchymal stem cells (WJ-MSC) from pregnancies complicated with preeclampsia and gestational age (GA)-matched controls.

Methods: WJ-MSC were isolated from umbilical cords from both groups and analyzed for the cell surface expression of MSC markers and the gene and protein expression of neuroglial markers.

Results: All WJ cells were highly positive for the MSC markers CD105, CD90 and CD73, but negative for markers specific for hematopoietic (CD34) and immunological cells (CD45, CD14, CD19 and HLA-DR). WJ-MSC from both groups expressed neuroglial markers (MAP-2, GFAP, MBP, Musashi-1 and Nestin) at the mRNA and protein level. The protein expressions of neuronal (MAP-2) and oligodendrocytic (MBP) markers were significantly increased in WJ-MSC from preeclampsia versus GA-matched controls.

Conclusions: WJ-MSC from preeclamptic patients are possibly more committed to neuroglial differentiation through the activation of pathways involved both in the pathophysiology of the disease and in neurogenesis.