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.     

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.     

Increasing maternal percentage body fat in early second trimester: a risk factor for preeclampsia

Objective: To determine if maternal percentage body fat (PBF) or fat free mass (FFM) in the early second trimester of pregnancy influenced the development of preeclampsia.

Methods: A matched nested case-control study was conducted from a cohort study of 1668 women at Gansu provincial maternal and child care hospital from July 2007 to August 2011 in China. Maternal PBF and FFM were assessed by bioelectrical impedance analysis during 12th–16th gestational week. The demographic characteristics were all chart abstracted. After childbirth, 70 cases of preeclampsia were matched by race/age with 140 uncomplicated pregnancies women. Multivariate logistic regression analysis was performed to determine the associated risk factors.

Results: Pre-pregnancy body mass index were higher in women who subsequently developed preeclampsia compared with controls (p?<?0.001). During 12th–16th gestational week, there were nearly 7-fold increase in the odds of preeclampsia (adjusted OR: 6.84, 95% CI: 4.15–41.60) among women with PBF?≥?40% versus women with PBF?<?40%. But FFM were not at further increased risk of the development of preeclampsia (adjusted OR, 1.02; 95% CI, 0.6–3.6).

Conclusion: Maternal PBF but not FFM is a predictor of preeclampsia in the early second trimester. Excessive adipose tissue possibly played an important role in developing of preeclampsia.     

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.     

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.     

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 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.     

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.     

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.     

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.     

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.     

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.     

Differential oxidative stress levels in mothers with preeclampsia delivering male and female babies

Objectives: Increased oxidative stress is known to be associated with pregnancy complications like preeclampsia (PE). We hypothesize that increased maternal oxidative stress may differentially affect/program the pregnancy outcome during early postnatal periods in male and female babies.

Materials and methods: One-hundred three healthy pregnant women (gestation ≥37 weeks) were recruited for the normotensive control (NC) group and 57 women with term-preeclampsia (T-PE; gestation ≥37 weeks) and 28 women with preterm-preeclampsia (PT-PE; gestation <37 weeks) were also recruited. All infants were followed for anthropometric measurements until six months of age.

Results: Higher maternal plasma malondialdehyde (MDA) and erythrocyte superoxide dismutase and glutathione peroxidase (GPx) levels were observed in both T-PE and PT-PE groups. Higher maternal levels of MDA and GPx were seen in mothers delivering male babies in T-PE and PT-PE groups, respectively, as compared to mothers delivering female babies. Babies born to mothers with PT-PE showed poor growth and development on all the anthropometric parameters compared to those born to mothers with T-PE and NC.

Conclusion: The altered levels of oxidative stress and antioxidant enzymes in mothers with PE delivering male babies suggest that they may be at higher risk for developing metabolic and neurodevelopmental disorders than female babies.     

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.     

Mode of delivery changes oxidative and antioxidative properties of human milk: a prospective controlled clinical investigation

Objective: To evaluate the influence of delivery mode on oxidative stress in human breast milk.

Methods: Thirty-three women who delivered by vaginal birth and 55 women who underwent cesarean section (CS) were included in this study. Colostral samples were collected on the second day after delivery. Total antioxidative status (TAS), total oxidative status (TOS), oxidative stress index (OSI), malonyldialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were determined and compared.

Results: Colostrum TAS was significantly higher in women of vaginal birth, than in women with CS (p?<?0.001). Milk TOS and OSI were found to be significantly increased in women with CS under general anesthesia. A marked increase in colostral GSH-Px levels after vaginal delivery was also noticed (p?<?0.001).

Conclusion: This study revealed that vaginal birth is associated with decreased oxidative stress in colostrum than CS, which suggest that mode of delivery plays an important role in the antioxidative production of breast milk.     

Little beneficial effect of maternal vitamin supplement on metabolic disturbances in the offspring from the obese mother mice

Objective: To examine whether vitamin supplement before and during pregnancy alters the detrimental effect of maternal obesity on the offspring.

Methods: Obese C57BL/6 female mice were randomly divided into four groups and fed with the control, vitamin D, folic acid or multivitamin supplement diet before and during pregnancy. Physiologic and biochemical variables were obtained.

Results: No significant differences were observed in glucose and lipid variables among offspring from each maternal obese group.

Conclusions: Overall, vitamin D, folic acid or multivitamin supplement cannot ameliorate the detrimental effect of maternal obesity on the metabolic disturbances in the offspring.     

Maternal and umbilical cord copeptin levels in pregnancies complicated by fetal growth restriction

Objective: The aim of this study was to compare maternal and fetal serum copeptin concentrations in pregnancies complicated by isolated fetal growth restriction (FGR), and uncomplicated pregnancies, and to investigate relationships between copeptin levels and clinical parameters.

Methods: Maternal and fetal serum copeptin levels were measured in 21 women with pregnancies complicated by isolated FGR and 20 women with normal pregnancies (control group). Doppler assessment of the uterine and umbilical arteries was performed in each patient.

Results: Maternal serum copeptin levels were significantly higher in women with isolated FGR compared to controls (p?=?0.042). In addition, maternal copeptin levels were inversely correlated with the uterine artery pulsatility and resistance indices and positively correlated with neonatal birth weight. Umbilical vein copeptin levels were significantly increased in neonates with adverse outcomes (p?=?0.001).

Conclusions: Increased maternal copeptin concentration may reflect a response to stress, thus serving as a compensatory mechanism in pregnancies complicated by FGR.     

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.