Interleukin-10: a novel metabolic inducer of macrophage differentiation and subsequently contributing to improved pregnancy outcomes of mice by orchestrating oxidative phosphorylation metabolism.

Metabolism regulates the phenotype and function of macrophages. After recruitment to local tissues, monocytes are influenced by the local microenvironment and differentiate into various macrophages depending on different metabolic pathways. However, the metabolic mechanisms underlying decidual macrophage differentiation remain unknown. Interleukin-10 (IL-10) is an important decidual macrophage inducer and promotes oxidative phosphorylation (OXPHOS) of bone marrow-derived macrophages. In this study, we mainly investigate the metabolic changes involved in IL-10 generated macrophages from monocytes using in vitro models. We demonstrate that exposure of monocytes (either peripheral or THP-1) to IL-10 altered the phenotype and function of resultant macrophages that is linked with OXPHOS changes. IL-10 enhanced the mitochondrial complex I and III activity of THP-1 cell-differentiated macrophages and increased the mitochondrial membrane potential, intracellular adenosine triphosphate, and reactive oxygen species levels. OXPHOS blockage with oligomycin changed the cell morphology of IL-10-generated macrophages and the expression levels of cytokines, such as transforming growth factor beta, tumor necrosis factor-alpha, interferon gamma, and IL-10, apart from changes in the expression level of the surface markers CD206, CD209, and CD163. Moreover, in vivo IL-10 administration reduced the lipopolysaccharide (LPS)-induced embryo resorption rate, and this effect was diminished when OXPHOS was inhibited, demonstrating that OXPHOS is important for the improved pregnancy outcomes of IL-10 in LPS-induced abortion-prone mice. Our findings provide deep insights into the roles of IL-10 in macrophage biology and pregnancy maintenance. Nevertheless, the direct evidence that OXPHOS is involved in decidual macrophage differentiation or not needs further investigations.

Sonographic Evaluation of Maternal Renal Echogenicity in Healthy Pregnant Women in the Niger Delta Region of Nigeria.

Background: Increased renal echogenicity is a nonspecific ultrasound finding. It may be a normal variation or suggestive of various underlying conditions like renal amyloidosis, chronic kidney disease, sickle cell disease and HIV associated nephropathy (HIVAN). Objective: To study maternal renal echogenicity in normal pregnancy, and explore its relationship with maternal baseline characteristics in our subregion. Methods: This descriptive, cross-sectional study was conducted in the Obstetrics and Radiology Units of the two tertiary health facilities, one secondary facility and one radio-diagnostic facility, all in Bayelsa State, South-South Nigeria, between March-August 2022. The relationships between maternal renal echogenicity and age, parity and gestational age were explored using Chi-square test of proportion, while with an analysis of variance (ANOVA), the mean difference of age, weight and height between the grades of renal echogenicity was investigated. Kruskal Wallis test was deployed to examine parity in the grades of renal echogenicity. The level of significance was set at p<0.05. Results: The study participants that had Grade 0, 1 and 2 renal echogenicity were 160 (39.7%), 403 (58.3%) and 8 (2.0%), respectively. There were statistically significant relationships between maternal renal echogenicity and maternal age (χ2=36.94; p=0.001), parity (χ2=64.29; p=0.001), gestational age (χ2=16.03; p=0.003) and body mass index (BMI) (χ2 = 45.15; p - 0.001). Conclusion: Our study revealed a significant relationship between maternal renal echogenicity in normal pregnancy and maternal baseline characteristics (age, parity, gestational age and weight).

Pigment Epithelium-Derived Factor, a Novel Adipokine, Contributes to Gestational Diabetes Mellitus.

CONTEXT: Excessive insulin resistance, inadequate insulin compensation, or both could result in gestational diabetes mellitus (GDM). Levels of pigment epithelium-derived factor (PEDF), a novel adipokine that could induce insulin resistance, are high in patients with obesity and diabetes. However, the impact of PEDF in pregnancy remains unknown. OBJECTIVE: This study aimed to elucidate the role of PEDF on insulin resistance and compensatory elevation of insulin levels during normal pregnancy and in patients with GDM. METHODS: In this population-based and cohort study, logistic regression analysis was performed to determine the association of PEDF/adiponectin/leptin levels with the risk of developing GDM and to predict postpartum prediabetes. PEDF protein, PEDF transgenic mice, PEDF knockout mice, and PEDF-neutralized antibodies were used to observe changes in insulin resistance and insulin levels with pregnancy. RESULTS: Plasma PEDF levels were increased in normal pregnancy and higher in GDM women. Higher PEDF levels were associated with the increased risk of developing GDM and emerged as a significant independent determinant of postpartum prediabetes in GDM women. Mechanistically, in vivo and in vitro experiments revealed that PEDF induced insulin resistance by inhibiting the insulin signaling pathway. CONCLUSION: In addition to insulin resistance and upregulated insulin levels in normal pregnancy and GDM, aberrant PEDF levels can serve as a "fingerprint" of metabolic abnormalities during pregnancy. Thus, PEDF is a valuable biomarker but could interfere with the time course for early diagnosis and prognosis of GDM.

Gestational age-related changes in cervical gland length in normal singleton pregnancies from 17 to 36 weeks of gestation.

AIM: To determine the gestational age-related changes in cervical gland length in relation to cervical length (CL) in normal singleton pregnancies. METHODS: We studied 363 women with an uncomplicated singleton pregnancy (188 nulliparous and 175 multiparous women with one or more previous transvaginal deliveries). A total of 1138 cervical gland and CLs were measured longitudinally at 17-36 weeks of gestation using transvaginal ultrasonography along the curvature from the external os to the lower uterine segment and the internal end of the cervical gland area (CGA), respectively. Gestational age-related changes in cervical gland and CLs and their relationships were analyzed using a linear mixed model. RESULTS: Cervical gland and CLs decreased in different ways with advancing gestation depending on parity, and their changes were related to each other. The CGAs in nulliparous women were longer than those in multiparous women at 17-25 weeks of gestation (p < 0.05), but with no differences thereafter. CLs in multiparous women were different from those in nulliparous women at 17-23 and 35-36 weeks (p < 0.05), but there were no differences at 24-34 weeks. The cervix did not shorten compared with the CGA throughout the observational periods in nulliparous and multiparous women. CONCLUSIONS: Shortening of the cervix indicates changes to the lower uterine segment in normal pregnancies. The cervical gland region can be a useful marker representing the true cervix beyond 25 weeks of gestation, irrespective of parity.

Ultrasound Measurement of Foetal Kidney Length during Healthy Pregnancy: Relationship with Gestational Age.

Background: Foetal kidney length (FKL) measurements and comparisons to normal charts can be used to assess the development of the foetal kidneys throughout the entire course of pregnancy. This study was designed to assess FKL between 20 - 40 weeks' gestation, establish reference ranges for FKL and determine the relationship between FKL and gestational age (GA) in normal pregnancy. Methods: This descriptive, cross-sectional study was conducted between March-August 2022, at the Obstetric Units and Radiology Departments of the two tertiary health facilities, one secondary facility and one radio-diagnostic facility in Bayelsa State, Southern Nigeria. Transabdominal ultrasound scan was used to evaluate the foetal kidneys. The relationship between foetal kidney dimensions and GA was explored using Pearson's correlation analysis. Linear regression analysis was done to define the relationship between GA and mean kidney length (MKL). A nomogram predicting GA from MKL was constructed. Level of significance was set at p<0.05. Results: There was a very strong significant correlation between foetal renal dimensions and GA. The correlation coefficient between GA and mean FKL, width and anteroposterior diameter were 0.89 (p=0.001), 0.87 (p=0.001) and 0.82 (p=0.001), respectively. A unit change in mean FKL corresponded to a 79% change in GA (ɼ2), showing a very strong association between mean FKL and GA. The regression equation: GA = 9.87 + 5.91 x MKL, was derived for estimation of GA for a given MKL. Conclusions: Our study revealed a significant relationship between FKL and GA. The FKL can therefore be reliably used to estimate GA.

Acute pyelonephritis in pregnancy and plasma syndecan-1: evidence of glycocalyx involvement.

BACKGROUND: Acute pyelonephritis, a risk factor for maternal sepsis, adult respiratory distress syndrome, and preterm labor, is a frequent cause of hospitalization. This condition is characterized by excessive intravascular inflammation and endothelial cell activation and dysfunction. Syndecan-1, a major component of the glycocalyx, is a gel-like layer that covers the luminal surface of healthy endothelial cells, preserving and mediating many endothelial functions. During pregnancy, there is an additional potential source of syndecan-1, the "syncytiotrophoblast glycocalyx," which lines the intervillous space. Insults that damage the glycocalyx lead to a shedding of syndecan-1 into the circulation. Hence, syndecan-1 has been proposed as a marker of endothelial injury in conditions such as sepsis, trauma, cardiovascular disease, and diabetes mellitus. OBJECTIVE: The objective of this study was to determine whether the plasma syndecan-1 concentration changes in women with acute pyelonephritis in the presence or absence of bacteremia. STUDY DESIGN: This cross-sectional study included three groups: (1) non-pregnant women (n = 25); (2) women with an uncomplicated pregnancy from whom samples were collected preterm (n = 61) or at term (n = 69); and (3) pregnant women diagnosed with acute pyelonephritis from whom samples were collected at the time of diagnosis during the second and third trimesters (n = 33). The diagnosis of acute pyelonephritis was based on clinical findings and a positive urine culture for bacteria. Blood culture results were available in 85% (28/33) of women with acute pyelonephritis. Plasma concentrations of syndecan-1 were determined by a validated immunoassay. RESULTS: (1) Women with an uncomplicated pregnancy had a higher plasma concentration of syndecan-1 than non-pregnant women. The geometric mean (95% confidence interval [CI]) of syndecan-1 concentration was 51.0 (12.1-216.1) ng/mL in non-pregnant controls; 1280 (365-4487) ng/mL in normal preterm gestations; and 1786 (546-5834) ng/mL in normal term gestations (adjusted p < .005 for all three between group comparisons); (2) plasma syndecan-1 concentrations increased with gestational age among women with a normal pregnancy (p < .001, R2 = 0.27); (3) syndecan-1 multiple of the mean (MoM) values in pregnant patients with acute pyelonephritis were higher than those in normal pregnant women based on second- and third-trimester samples (p = .048, 1.26-fold change). The increase was driven primarily by cases with a positive blood culture (p = .009, 1.74-fold change); (4) when data from third-trimester samples were compared, overall differences in syndecan-1 MoM values between cases and controls were slightly larger (p = .03, 1.36- fold change), which were especially contributed to by cases with a positive blood culture (p = .023, fold change 1.79-fold change). CONCLUSIONS: Plasma syndecan-1 concentration is higher in pregnant women and increases as a function of gestational age. Patients with acute pyelonephritis have a higher plasma concentration of syndecan-1, and this is particularly the case in the presence of bacteremia.

Quantification of Myocardial Work by 2-D Echocardiography during a Normal Pregnancy: A Preliminary Study.

This study was aimed at investigating the adaptive changes in myocardial work (MyW) during normal pregnancy. Sequential 2D standard and speckle-tracking echocardiography was performed on 41 pregnant women in each gestational trimester and 4 to 11 mo after delivery. Thirty-eight age-matched, healthy, non-pregnant women served as controls. Four components of MyW-global myocardial work index (GWI), constructive work (GCW), wasted work (GWW) and work efficiency (GWE)-were calculated. GWI began to decline early in the first trimester and remained at a low level until delivery; GCW gradually decreased with gestational progression and reached its lowest level in the third trimester. When compared with the values for non-pregnant women and those postpartum, GWE and GWW remained unchanged in gestation. This study provides normal ranges of MyW during pregnancy. Despite the adapted decrease in GWI and GCW, the myocardium manages to work efficiently in the healthy pregnancy with drastic hemodynamic alternations.

Unfolding the role of placental-derived Extracellular Vesicles in Pregnancy: From homeostasis to pathophysiology.

The human placenta is a critical structure with multiple roles in pregnancy, including fetal nutrition and support, immunological, mechanical and chemical barrier as well as an endocrine activity. Besides, a growing body of evidence highlight the relevance of this organ on the maternofetal wellbeing not only during gestation, but also from birth onwards. Extracellular vesicles (EVs) are complex macromolecular structures of different size and content, acting as carriers of a diverse set of molecules and information from donor to recipient cells. Since its early development, the production and function of placental-derived EVs are essential to ensure an adequate progress of pregnancy. In turn, the fetus receives and produce their own EVs, highlighting the importance of these components in the maternofetal communication. Moreover, several studies have shown the clinical relevance of EVs in different obstetric pathologies such as preeclampsia, infectious diseases or gestational diabetes, among others, suggesting that they could be used as pathophysiological biomarkers of these diseases. Overall, the aim of this article is to present an updated review of the published basic and translational knowledge focusing on the role of placental-derived EVs in normal and pathological pregnancies. We suggest as well future lines of research to take in this novel and promising field.

Expression of Matrix Metalloproteinase-2,-7,-9 in Serum during Pregnancy in Patients with Pre-Eclampsia: A Prospective Study.

BACKGROUND: Matrix Metalloproteinases (MMPs) have been found to have important roles in vascular pathology and may be involved in the occurrence of pre-eclampsia. In this study, the serum levels of MMP-2, -7, -9 in normal pregnant women and pre-eclampsia patients were analyzed to assess their predictive value. METHODS: A total of 1563 pregnant women from Peking University Third Hospital, from February 2021 to October 2021, were enrolled. Serum samples were collected from patients one to three times, during the different trimesters. Among the 102 singleton pre-eclampsia patients, we collected samples from 33 patients in the first trimester (6-13 GW), 33 in the second trimester (14-28 GW), 41 in the third trimester (29-41 GW) and 28 after onset of pre-eclampsia. Samples from each trimester were collected before the onset of pre-eclampsia. Then we selected 35, 37, 43 and 25 samples from 124 healthy pregnant women by matching their age, BMI and gestational weeks, using these as the control groups. Serum levels of MMP-2, -7, -9 were detected by ELISA. The receiver operating characteristic (ROC) curve was used to evaluate their predictive value. RESULTS: Except for the first trimester, MMP-2 and MMP-7 were significantly higher in the pre-eclampsia group (p < 0.5). Additionally, in the pre-eclampsia group, MMP-9 increased significantly in the first trimester and after the onset of pre-eclampsia but decreased significantly in the second and third trimesters (p < 0.5). The ROC curve indicated that MMP-9, MMP-2 and MMP-7 were the best indicators for predicting pre-eclampsia in the first, second and third trimesters, respectively. CONCLUSION: Increased MMP-2 and MMP-7 levels and a decreased MMP-9 level seem to be related to the pathogenesis of pre-eclampsia and are expected to be potential predictors of pre-eclampsia.

Relationship of serum lipid profiles in preeclampsia and normal pregnancy, Bangladesh.

Objective: The purpose of this present study to investigate the lipid profile levels and basal body mass index in preeclampsia and normal pregnancy in Bangladeshi women. Material and methods: This case-control study was conducted at Sheba Hospital Kaligonj Bangladesh with 70 participants among 35 normal pregnancy (control) and 35 preeclampsia women (case) were enrolled from August 2018 to July 2019. Blood samples were obtained for analysis of total cholesterol, triglyceride and high-density lipoprotein by enzymatic assays and low-density lipoprotein by using Fried Ewald's formula in between 22-36 weeks of gestation. Results: This study found the mean age of preeclampsia and normal pregnancy women were 24.71±2.56 and 23.09±2.1 respectively with significant (P= 0.005). Basal body mass index, total cholesterol, triglyceride and low-density lipoprotein significantly higher (P=0.002), (P= 0.000), (P= 0.022) and (P=0.000) in preeclampsia compared to normal pregnancy respectively. While high-density lipoprotein comparatively lower in preeclampsia than normal pregnancy and consider significant as (P=0.037). Conclusion: Abnormal lipid profile and increased body mass index is contributed to the development of preeclampsia. The frequent antenatal monitoring of lipid profiles provides the status which helps to require management and reduces the preeclampsia which enhances maternal and fetal wellbeing and fetal outcome.

Decorin promotes decidual M1-like macrophage polarization via mitochondrial dysfunction resulting in recurrent pregnancy loss.

Rationale: Recurrent pregnancy loss (RPL) is a distressing disorder that seriously affects the physical and psychological health of women. RPL is also a sentinel risk marker for future obstetric complications and warrants in-depth investigation. Abnormal polarization and functions of decidual macrophages are associated with RPL; however, the underlying mechanisms remain poorly understood. Methods: Decorin expression, localization, and content in the decidua of women with normal pregnancy (NP) and those with RPL were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, immunofluorescence, and enzyme-linked immunosorbent assay. The profiles of decidual macrophage subsets were determined using flow cytometry and immunofluorescence in both groups. The correlation between decorin content and the proportion of decidual macrophage subsets in the decidua of early NP women was determined using Pearson analysis. The effects of decorin on the polarization and functions of macrophages were assessed in an in-vitro model of Raw264.7 cells via flow cytometry, western blotting, and RT-qPCR. Moreover, the mitochondrial metabolism in Raw264.7 cells under decorin administration was measured via flow cytometry, western blotting, and immunofluorescence. Thirty-three pregnant mice were included in the in vivo model and underwent different treatments. The embryo abortion rate, macrophage phenotype in the spleen and uteri, and placental development were evaluated using flow cytometry and hematoxylin-eosin staining. Results: Decorin, derived from decidual stromal cells, was highly expressed in the decidua of women with RPL. A positive correlation between decorin content and the proportion of M1-like macrophages was also observed in the decidua of early NP women. In vitro studies showed that decorin treatment inhibited macrophage polarization to M2-like subsets and boosted the inflammatory response, which was related to enhanced anaerobic glycolysis, increased mitochondrial membrane potential and intracellular reactive oxygen species levels, reduced mitochondrial mass, and activation of the myeloid differentiation primary response 88-nuclear factor-κB signaling pathway. Adoptive transfer of decorin-treated bone marrow-derived macrophages in pregnant C57BL/6 mice increased the embryo absorption, accompanied by impaired fetal vascularization. Conclusions: Decidual stromal cell-derived decorin can polarize decidual macrophages toward the M1 phenotype by regulating mitochondrial metabolism, resulting in the occurrence of RPL.

Platelet aggregation in normal pregnancy.

It was recently shown that abnormal platelet aggregation (PA) had played a critical role in some adverse pregnancies. Till now reference range for PA in normal pregnancy has not been determined. Furthermore, few study has been conducted to explore the factors related to PA. Our study was performed to assess the reference range of PA in normal pregnancy (150 participants in the second trimester), and to determine whether it differs from that of the controls (38 nonpregnant participants). In addition, this study explored the factors related to PA. The results showed that PA was significantly higher in normal pregnancy than that in the controls (84.40% vs. 80.7%, respectively, P = 0.013). The reference interval for PA in normal pregnancy was 74.75%-94.77%. Hemoglobin (Hb), platelet counts (PLT) and albumin (Alb) were significant lower in normal pregnancy than those in the control group. Moreover, it was found that PA was positively correlated with PLT (r = 0.263, P < 0.001), and negatively correlated with platelet distribution width (PDW) (r = -0.342, P < 0.001) and mean platelet volume (r = -0.296, P < 0.001). Linear correlations between PA and Alb, PDW were proved by linear regression model (LRM). In conclusion, PA was enhanced in normal pregnancy, and Alb and PDW might be the possible contributing factors to PA.

Electrocardiographic findings in pregnant women in Angola.

BACKGROUND: Studies on the electrocardiogram findings in African pregnant women are limited. There is no information available in the literature on the electrocardiographic parameters of pregnant Angolan women. OBJECTIVES: The aim of this study was to describe electrocardiographic findings in women with normal pregnancies in Bengo Province, Angola. METHODS: This is a community-based study with a cross-sectional design conducted between September 2013 and March 2014 in Bengo. The study involved 114 black pregnant women, compared with a paired control group comprising of 120 black non-pregnant women, aged 15 to 42 years. A 12-lead electrocardiogram and a rhythm strip were recorded for all participants. RESULTS: In this study, the mean age was 26.2 ± 7.3 years. Comparing pregnant women vs. non-pregnant, we found the following mean values: Heart rate (83 bpm vs. 74 bpm, p < .001), PR interval (146 ms vs. 151 ms, p = .034), QT interval (360 ms vs. 378 ms, p < .001), QTIc Fridericia (398 ms vs. 403, p = .017), QTIc Framingham (399 ms vs. 404 ms, p = .013) and T-wave axis (340 vs. 410 , p = .001).The main electrocardiographic changes found were: Sinus tachycardia (4.4% vs. 2.5%), T-wave inversion (14.9% vs. 1.7%), Minor ST segment depression (4.5% vs. 0%) and left ventricular hypertrophy (11.4% vs. 11.7%, p = .726). CONCLUSIONS: Pregnant Angolan women compared with controls, had several significantly higher values for heart rate, and significantly lower values of systolic blood pressure and diastolic blood pressure, PR interval, QT interval, QTc interval by Fridericia and Framingham and T-wave axis. Sinus tachycardia, T-wave inversion, and left ventricular hypertrophy, were the main electrocardiographic changes found.

"I would never be able to forgive myself if it ended up having consequences for the child": A qualitative study of perceptions of stress and worries among healthy first-time pregnant Danish women.

BACKGROUND: Becoming a mother is one of the most transitional experiences in life. It requires psychological, physical, and social adjustment and adaptation in various areas and can be conceived as both a stressful and joyful experience by many women. Especially, first-time pregnancies are recognised as a period of emotional sensitivity. Moreover, stress is a well-established risk factor for premature birth and low birth weight and might affect the health of the offspring. Thus, this study explores the perception of stress and worries in healthy Danish pregnant nulliparous women. METHODS: We used a qualitative, inductive, exploratory design. Three focus group interviews were conducted with 16 healthy pregnant nulliparous women. Data from the focus group interviews were analysed using content analysis according to Graneheim and Lundman. FINDINGS: Three main categories contributed to the core theme "Identity Limbo". The categories were: (1) The great responsibility, (2) Imagining picture-perfect, and (3) Two-in-one body. The participants expressed that holding on to their current identity was extremely important. They simultaneously tried to incorporate their new identity as mothers, which imposed sadness about saying goodbye to their old life, leaving them in an identity limbo. These women did not experience classic stressors such as bereavement, poverty, or trauma. Still, the great responsibility for the child's future, changes to their work and career, and saying goodbye to their pre-pregnancy identity were all essential contributors to feelings of stress in the women's current pregnancy and life. CONCLUSION: Our findings suggest that the identity limbo triggered by pregnancy can make the transition to motherhood stressful for some women. Therefore, with the potentially severe consequences of stress in mind, developing tools that can help women and midwives focus on the mental transition of pregnancy is needed.

Comparison of hemodynamic changes and fetal outcome between normotensive and preeclamptic parturient undergoing elective cesarean section under spinal anesthesia: A prospective observational cohort study.

Background: Maternal hypotension is a common problem during spinal anesthesia resulting in adverse maternal and fetal outcomes. According to theoretical knowledge, it is more common in severe preeclamptic parturients undergoing cesarean section with spinal anesthesia. Objective: To compare fetomother outcome in normotensive and severe preeclamptic parturients undergoing elective cesarean section under spinal anesthesia. Methodology: A prospective cohort study was conducted from Novembers to May 30, 2019 on 84 ASA II and III pregnant mothers. After preloading with 500 ml-1000ml crystalloids, a 0.5%isobaric bupivacaine of 10 mg-12.5 mg was administered for spinal anesthesia.Vital signs (SBP, DBP, MAP and HR) were recorded every 3 min till 30 min, every 5 min then after. Neonatal Apgar scores at one and 5 min after birth and intraoperative fluids consumption were recorded. Data distribution was checked by Shapiro walk's test. Chi-square test was used to calculate the incidence of hypotension between groups; both paired and unpaired t-tests were also used to calculate the percent fall in blood pressure and heart rate from baselines of each group and intergroup respectively, and P-value less than 0.05 were considered statistical significance. Results: The incidence of hypotension (over a period of 30 min after spinal anesthesia) in the preeclamptic patients (31%) was less than that of the healthy parturients (59.5%). There was no statistically significant difference in heart rate of both groups before and after induction of spinal anesthesia. The 5th minute Apgar score recordings were also comparable between the groups. Conclusion: This study showed that the incidence and magnitude of spinal anesthesia-induced hypotension was less in severely preeclamptic parturient than healthy parturient who underwent elective cesarean delivery under spinal anesthesia and fetal outcome was comparable.

Differential effects of delayed cord clamping on bilirubin levels in normal and diabetic pregnancies.

The purpose of the study is to investigate the effects of delayed cord clamping on bilirubin levels and phototherapy rates in neonates of diabetic mothers. This was a prospective study that enrolled pregnant women without pregnancy complications and those with diabetes. Their neonates were randomized in a 1:1 ratio to delayed cord clamping. The main outcomes were the neonatal transcutaneous bilirubin values on 2-4 days postpartum and the rate of requiring phototherapy in infants. A total of 261 pregnant women were included in the final analysis (132 women with diabetic pregnancies and 129 women with normal pregnancies). In diabetic pregnancies, neonatal bilirubin levels on the 2-4 days postpartum and phototherapy rates were significantly higher in the delayed cord clamping group than in the immediate cord clamping group (7.65 ± 1.83 vs 8.25 ± 1.96, P = 0.039; 10.35 ± 2.23 vs 11.54 ± 2.56, P = 0.002; 11.54 ± 2.94 vs 12.83 ± 3.07 P = 0.024, 18.2% vs 6.3%, P = 0.042), while in normal pregnancies, there was no statistical difference in bilirubin values and phototherapy rates between the delayed cord clamping group and the immediate cord clamping group (P > 0.05). After receiving delayed cord clamping, bilirubin levels on the third postnatal day and the rate of requiring phototherapy in infants were higher in the diabetic pregnancy group than in the normal pregnancy group (10.35 ± 2.23 vs 11.54 ± 2.56, P = 0.013). CONCLUSION: Delayed cord clamping increased the risk of jaundice in newborns born to diabetic mothers, but had no effect in newborns from mothers with normal pregnancies. DCC may be a risk factor for increased bilirubin in infants of diabetic mothers. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04369313; date of registration: April 27, 2020 (retrospectively registered). WHAT IS KNOWN: • Delayed cord clamping had significant benefits for newborns by increasing neonatal hemoglobin levels and reducing the risk of neonatal anemia, etc. • Delayed cord clamping may lead to neonatal hyperemia, erythrocytosis, and hyperbilirubinemia, which increases the risk of neonatal jaundice. WHAT IS NEW: • Our trial focused on the differential effects of delayed cord clamping on jaundice in full-term newborns between diabetic pregnancies and normal pregnancies. And newborns of diabetic mothers who received delayed cord clamping had a significantly increased risk of jaundice compared to newborns with normal pregnancy. • Delayed cord clamping may be a risk factor for increased bilirubin levels in neonates of diabetic mothers.

Arachidonic acid-induced platelet aggregation and acetylsalicylic acid treatment during pregnancy in women with recurrent miscarriage, a post hoc study.

In this post hoc study, arachidonic acid (AA)-induced platelet aggregation during pregnancy with and without acetylsalicylic acid (ASA) treatment was studied in 323 women with unexplained recurrent first-trimester miscarriage and in 59 healthy women with normal pregnancies. All women had normal AA-induced platelet aggregation in the non-pregnant state. Women with recurrent miscarriage were treated with 75 mg ASA or placebo daily. AA-induced platelet aggregation was measured with multiple electrode impedance aggregometry and presented in units (U), where 1 U = 10 aggregation units x minutes. There were no significant differences in platelet aggregation between placebo-treated women with recurrent miscarriage and healthy women. The mean differences were-0.7 (95%CI; -7.0; 5.6) U in the non-pregnant state, 3.8 (95%CI; -4.6; 12.2) U during the late first trimester and 1.7 (95%CI; -6.7; 10.3) U and 4.1 (95%CI; -3.9; 12.0) U during the early and late third trimester, respectively. ASA reduced platelet aggregation by median -84.0% (Q1; Q3; -89.8; -76.3), -79.9% (-84.7; -69.2) and -75.7% (-83.5; -49.5), respectively, during pregnancy. The degree of inhibition by ASA decreased during the third trimester (p < .0001). There were two (1.9%) complete non-responders to ASA and 32.1% with a partial response. The rate of subsequent miscarriage was not affected by ASA, which did not seem to influence the rate of early miscarriage if treatment was initiated when a viable pregnancy was detectable by ultrasound.

Índice neutrófilo-linfocito, relación plaquetas-linfocito y distribución de la anchura del eritrocito en pacientes con preeclampsia / Neutrophil-to-lymphocyte ratio, plateletto- lymphocyte ratio, and erythrocyte width distribution. and erythrocyte width distribution in patients with preeclampsia

Resumen OBJETIVO: Comparar el índice neutrófilo-linfocito, la relación plaquetas-linfocito y la distribución de la anchura del eritrocito de mujeres con preeclampsia con o sin criterios de severidad y los de mujeres sin ésta. MATERIALES Y MÉTODOS: Estudio retrospectivo, de casos y controles, efectuado en mujeres con y sin preeclampsia atendidas entre enero y diciembre de 2019. RESULTADOS: Se estudiaron 70 mujeres con preeclampsia y 70 con embarazo sin esta complicación. El índice neutrófilo-linfocito fue significativamente mayor en las mujeres con preeclampsia (4.11 ± 2.76; IC95%: 3.47-4.75) que en las mujeres sin esta complicación (2.99 ± 1.6; IC95%: 2.62-3.36; p = 0.004), similar a la relación plaquetas-linfocitos (117.61 ± 47.53; IC95%:106.48-128.24 vs 97.64 ± 43.67; IC95%: 87.41-107.87; p = 0.006) y para la distribución de la anchura del eritrocito (14.46 ± 1.9; IC95%: 14.02-14.9 vs 13.56 ± 1.38; IC95%: 13-13.72; p = 0.0002). Ninguno de estos parámetros logró discriminar entre las pacientes con preeclampsia con o sin criterios de severidad. CONCLUSIÓN: Un índice neutrófilo-linfocito ≥ 5.1 y una relación plaquetas-linfocito ≥ 113.1 son capaces de discriminar de manera adecuada entre preeclampsia con o sin criterios de severidad.

Abstract OBJECTIVE: To compare the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and erythrocyte width distribution, of women with preeclampsia with or without severity criteria and those of women without. MATERIALS AND METHODS: Retrospective case-control study in 70 women with preeclampsia and 70 with normal pregnancy between January and December 2019. RESULTS: Seventy women with preeclampsia and 70 with pregnancy without this complication were studied. The neutrophil-lymphocyte ratio was significantly higher in women with preeclampsia (4.11 ± 2.76; 95%CI: 3.47-4.75), than in women with normal pregnancies (2.99 ± 1.6; 95%CI: 2.62-3.36; p = 0.004); which is similar for the platelet-lymphocyte ratio (117.61 ± 47.53, 95%CI: 106.48-128.24 vs 97.64 ± 43.67; 95%CI: 87.41-107.87; p = 0.006) and for the distribution of the width of the erythrocyte; (14.46 ± 1.9, CI95%: 14.02-14.9 vs 13.56 ± 1.38; CI95%: 13-13.72; p = 0.0002). None of these parameters was able to discriminate between patients with preeclampsia with or without severity criteria. A neutrophil-lymphocyte ratio ≥ 5.1 discriminates between women with a normal pregnancy and those with preeclampsia with or without severity criteria [area under the curve of 0.746, (95%CI: 0.664-0.827)], sensitivity 42%, specificity 91%, positive predictive value 82%, negative predictive value 60% and Odds Ratio 7.1 (95%CI: 2.7-18.6, p = 0.001). The platelet-lymphocyte ratio ≥ 113.4 can discriminate between women with a normal pregnancy and preeclampsia with or without severity criteria, with an area under the curve of 0.617 (95% CI 0.525-0.709). CONCLUSION: A neutrophil-lymphocyte ratio ≥ 5.1, and a platelet-lymphocyte ratio ≥ 113.1 are able to adequately discriminate between patients with normal pregnancy and those with preeclampsia with or without severity criteria.

Assessment of adherence to medication during chronic illnesses in pregnancy.

PURPOSE/AIM: To evaluate adherence to medication in chronic illnesses during pregnancy and to identify factors responsible for non-adherence. METHODS: This was a prospective, cross-sectional, questionnaire based study initiated after approval of the institutional ethics committee. Pregnant women suffering from any chronic illness (except HIV) were questioned to evaluate adherence to medication in chronic illnesses during pregnancy and to detect factors responsible for non-adherence using a semi-structured, open-ended questionnaire. Adherence to medication was also assessed using 4-item Morisky's medication adherence scale. RESULTS: Rate of high adherence was significantly more (58.77%) with medications for chronic illness compared to medications for normal pregnancy (15.78%). Majority of women were more concerned about the chronic illness and believed that keeping the chronic illness under control is more important for normal growth of the baby. Unawareness about usefulness of each medicine and forgetfulness were the most common reasons for non-adherence to medications. Not taking prescribed dose was the most common type of non-adherence. Level of adherence positively correlated with level of education while it was inversely related to number of tablets per day. CONCLUSION: Higher adherence to medications for chronic illnesses during pregnancy is an encouraging finding but at the same time poor adherence to medications for normal pregnancy is a matter of concern. Most of the issues responsible for non-adherence to medication as reported in this study can be resolved to a significant extent by planning and implementing interventions aimed at improving adherence to treatment during pregnancy in which health professionals play a major role.

The metabolic landscape of decidua in recurrent pregnancy loss using a global metabolomics approach.

INTRODUCTION: Maternal metabolism undergoes dynamic changes during pregnancy. A deviation from this physiological metabolic status might be involved in the pathogenesis of pregnancy complications, such as recurrent pregnancy loss (RPL). Decidua is an important uterine tissue, which provides immunological protection as well as nutritional support to the developing embryo during early pregnancy. Previous studies have shown that aberrant metabolism of the decidua is related to the etiology of RPL. However, the metabolic profile of the decidua in RPL has not yet been fully elucidated. METHODS: In the current study, decidual samples from RPL patients (n = 23) and normal pregnancy (NP) women (n = 30) were collected, and hydrophilic and hydrophobic metabolites were extracted and measured using a liquid chromatography electrospray ionization tandem mass spectrometry system. Besides, the mRNA expression of several critical enzymes involved in sphingolipid metabolism and glycerophospholipid metabolism was detected. RESULTS: The OSC-PLS-DA scores plot illustrates that metabolic differences are present in the decidual tissue of RPL patients compared with that of NP women. Combining multivariate analysis with univariate statistical analysis, a total of 62 metabolites related to RPL were selected, including carnitine, glycerophospholipids, sphingomyelin (SM), ceramide, organic acids and their derivatives, and amino acid metabolomics. KEGG analysis showed that abnormalities in multiple metabolic pathways occurred in RPL decidua, including vitamin digestion and absorption, tryptophan metabolism, citrate cycle, arginine biosynthesis, glycerophospholipid metabolism, sphingolipid metabolism, and sphingolipid signaling pathway. Increased SM synthase and decreased Phospholipase A2 Group IIE mRNA levels were detected in RPL compared with NP group. DISCUSSION: Disruption of decidual metabolism, especially glycerophospholipid metabolism and sphingolipid metabolism, might be involved in the occurrence of RPL.