Prediction of neonatal respiratory morbidity by quantitative ultrasound lung texture analysis: a multicenter study.

BACKGROUND: Prediction of neonatal respiratory morbidity may be useful to plan delivery in complicated pregnancies. The limited predictive performance of the current diagnostic tests together with the risks of an invasive procedure restricts the use of fetal lung maturity assessment. OBJECTIVE: The objective of the study was to evaluate the performance of quantitative ultrasound texture analysis of the fetal lung (quantusFLM) to predict neonatal respiratory morbidity in preterm and early-term (<39.0 weeks) deliveries. STUDY DESIGN: This was a prospective multicenter study conducted in 20 centers worldwide. Fetal lung ultrasound images were obtained at 25.0-38.6 weeks of gestation within 48 hours of delivery, stored in Digital Imaging and Communication in Medicine format, and analyzed with quantusFLM. Physicians were blinded to the analysis. At delivery, perinatal outcomes and the occurrence of neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, were registered. The performance of the ultrasound texture analysis test to predict neonatal respiratory morbidity was evaluated. RESULTS: A total of 883 images were collected, but 17.3% were discarded because of poor image quality or exclusion criteria, leaving 730 observations for the final analysis. The prevalence of neonatal respiratory morbidity was 13.8% (101 of 730). The quantusFLM predicted neonatal respiratory morbidity with a sensitivity, specificity, positive and negative predictive values of 74.3% (75 of 101), 88.6% (557 of 629), 51.0% (75 of 147), and 95.5% (557 of 583), respectively. Accuracy was 86.5% (632 of 730) and positive and negative likelihood ratios were 6.5 and 0.3, respectively. CONCLUSION: The quantusFLM predicted neonatal respiratory morbidity with an accuracy similar to that previously reported for other tests with the advantage of being a noninvasive technique.

Prepregnancy body mass index influences lipid oxidation rate during pregnancy.

INTRODUCTION: The influence of maternal body mass index (BMI) on respiratory quotient during pregnancy is not clear. We aim to evaluate longitudinal changes in energy expenditure, respiratory quotient, and substrate oxidation rates in normal and overweight women with uncomplicated pregnancies. We hypothesized that the threshold period in switching from a predominantly carbohydrate to a predominantly lipid metabolism may be different in normal and overweight women. MATERIAL AND METHODS: Forty healthy pregnant women were recruited for a prospective cohort study. They were divided into two groups, normal and overweight (BMI <25 kg/m2 or ≥25 kg/m2 ). Comparisons of indirect calorimetry data were performed monthly throughout pregnancy. The relationships between energy and substrate metabolism variables and maternal BMI were also analyzed. RESULTS: There was a significant increase in oxygen consumption (Vo2 ), carbon dioxide production (Vco2 ) and resting energy expenditure during pregnancy in both normal and overweight women. In the normal weight group, respiratory quotient decreased during the second trimester and increased in the last trimester. Respiratory quotient was lower in the overweight group in the second trimester and decreased in the last trimester; between-group differences being significant at 20 and 36 weeks (0.85 ± 0.06 vs. 0.81 ± 0.01, p = 0.009; 0.87 ± 0.05 vs. 0.80 ± 0.03, p = 0.01, respectively). Lipid oxidation was significantly higher in overweight women at both 20 and 36 weeks (36.8 ± 19.7% vs. 55.2 ± 5.6%, p = 0.003 and 33.6 ± 18.2% vs. 59.6 ± 12.7%, p = 0.007, for normal and overweight group, respectively). CONCLUSION: Prepregnancy maternal BMI influences lipid oxidation rate and respiratory quotient during pregnancy.

Tissue specific expression of human fatty acid oxidation enzyme genes in late pregnancy.

BACKGROUND: Abnormal fatty acid oxidation (FAO) is associated with maternal and fetal complications during pregnancy. The contribution of maternal and fetal tissues to FAO capacity during late pregnancy is important to understand the pathophysiology of pregnancy-associated complications. The aim of this study was to determine the expression levels of mitochondrial FAO enzymes in maternal and fetal tissues during late normal pregnancy. METHODS: We have measured by Real-time PCR the levels of long- and medium -chain acyl-CoA dehydrogenase (LCHAD and MCAD), two acyl-CoA dehydrogenases that catalyze the initial step in the mitochondrial FAO spiral. RESULTS: LCHAD and MCAD were expressed in maternal skeletal muscle, subcutaneous adipose tissue, placenta, and maternal and fetal blood cells. LCHAD gene expression was four- to 16-fold higher than MCAD gene expression in placenta, adipose tissue and skeletal muscle. In contrast, MCAD gene expression was ~5-fold higher in fetal blood than maternal blood (p = 0.02), whereas LCHAD gene expression was similar between fetal blood and maternal blood (p =0.91). CONCLUSIONS: LCHAD and MCAD are differentially expressed in maternal and fetal tissues during normal late pregnancy, which may represent a metabolic adaptation in response to physiological maternal dyslipidemia during late pregnancy.

High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta.

Placentas of women with gestational diabetes mellitus (GDM) exhibit an altered lipid metabolism. The mechanism by which GDM is linked to alterations in placental lipid metabolism remains obscure. We hypothesized that high glucose levels reduce mitochondrial fatty acid oxidation (FAO) and increase triglyceride accumulation in human placenta. To test this hypothesis, we measured FAO, fatty acid esterification, de novo fatty acid synthesis, triglyceride levels, and carnitine palmitoyltransferase activities (CPT) in placental explants of women with GDM or no pregnancy complication. In women with GDM, FAO was reduced by ~30% without change in mitochondrial content, and triglyceride content was threefold higher than in the control group. Likewise, in placental explants of women with no complications, high glucose levels reduced FAO by ~20%, and esterification increased linearly with increasing fatty acid concentrations. However, de novo fatty acid synthesis remained unchanged between high and low glucose levels. In addition, high glucose levels increased triglyceride content approximately twofold compared with low glucose levels. Furthermore, etomoxir-mediated inhibition of FAO enhanced esterification capacity by ~40% and elevated triglyceride content 1.5-fold in placental explants of women, with no complications. Finally, high glucose levels reduced CPT I activity by ~70% and phosphorylation levels of acetyl-CoA carboxylase by ~25% in placental explants of women, with no complications. We reveal an unrecognized regulatory mechanism on placental fatty acid metabolism by which high glucose levels reduce mitochondrial FAO through inhibition of CPT I, shifting flux of fatty acids away from oxidation toward the esterification pathway, leading to accumulation of placental triglycerides.

The NDDG criteria versus the IADPSG or the ADA criteria for diagnosing early-onset gestational diabetes mellitus or abnormal glucose tolerance.

OBJECTIVE: To analyze the effects of substituting the National Diabetes Data Group (NDDG) criteria with the International Association of Diabetes and Pregnancy Study Groups (IADPSG) or American Diabetes Association (ADA) criteria for the diagnosis of early-onset gestational diabetes mellitus (Early-GDM) or first trimester abnormal glucose tolerance (1 t-AGT). METHODS: A retrospective cohort study was conducted of 3200 women: 400 with Early-GDM, 800 with GDM, and 2000 with Non-GDM, according to the NDDG criteria. Rates of women with missed and new Early-GDM according to the IADPSG or ADA criteria were calculated. Multivariate logistic regression analysis was used to compare perinatal outcomes between groups. RESULTS: Using the IADPSG criteria, 61.6% of women with Early-GDM according to the NDDG were undiagnosed (Missed-Early-GDM group), and 25.9% of women with GDM and 15.7% of women with Non-GDM were diagnosed with Early-GDM (New-Early-GDM groups). Perinatal outcomes were worse in Missed-Early-GDM than in Non-GDM and better in New-Early-GDM groups than in the Early-GDM group. According to the ADA recommendations, only 11.8% of women with Early-GDM according to the NDDG criteria were diagnosed. CONCLUSION: Replacing the NDDG recommendations for the diagnosis of Early-GDM with the IADPSG or ADA criteria would mean depriving a large number of women with AGT and higher risk of adverse perinatal outcomes from early treatment and treating others with lower risk.

Maternal elevated inflammation impairs placental fatty acids ß-oxidation in women with gestational diabetes mellitus.

Introduction: An adverse proinflammatory milieu contributes to abnormal cellular energy metabolism response. Gestational diabetes mellitus (GDM) is closely related to an altered maternal inflammatory status. However, its role on lipid metabolism regulation in human placenta has not yet been assessed. The aim of this study was to examine the impact of maternal circulating inflammatory mediators ([TNF]-α, [IL]-6, and Leptin) on placental fatty acid metabolism in GDM pregnancies. Methods: Fasting maternal blood and placental tissues were collected at term deliveries from 37 pregnant women (17 control and 20 GDM). Molecular approach techniques as radiolabeled lipid tracers, ELISAs, immunohistochemistry and multianalyte immunoassay quantitative analysis, were used to quantify serum inflammatory factors' levels, to measure lipid metabolic parameters in placental villous samples (mitochondrial fatty acid oxidation [FAO] rate and lipid content [Triglycerides]), and to analyze their possible relationships. The effect of potential candidate cytokines on fatty acid metabolism in ex vivo placental explants culture following C-section a term was also examined. Results: Maternal serum IL-6, TNF-α and leptin levels were significantly increased in GDM patients compared with control pregnant women (9,9±4,5 vs. 3,00±1,7; 4,5±2,8 vs. 2,1±1,3; and 10026,7±5628,8 vs. 5360,2±2499,9 pg/ml, respectively). Placental FAO capacity was significantly diminished (~30%; p<0.01), whereas triglyceride levels were three-fold higher (p<0.01) in full-term GDM placentas. Uniquely the maternal IL-6 levels showed an inverse and positive correlation with the ability to oxidize fatty acids and triglyceride amount in placenta, respectively (r= -0,602, p=0.005; r= 0,707, p=0.001). Additionally, an inverse correlation between placental FAO and triglycerides was also found (r=-0.683; p=0.001). Interestingly, we ex vivo demonstrated by using placental explant cultures that a prolonged exposure with IL-6 (10 ng/mL) resulted in a decline in the fatty acid oxidation rate (~25%; p=0.001), along to acute increase (2-fold times) in triglycerides accumulation (p=0.001), and in lipid neutral and lipid droplets deposits. Conclusions: Enhanced maternal proinflammatory cytokines levels (essentially IL-6) is closely associated with an altered placental fatty acid metabolism in pregnancies with GDM, which may interfere with adequate delivery of maternal fat across the placenta to the fetus.

First Trimester Evaluation of Maternal Visceral Fat and Its Relationship with Adverse Pregnancy Outcomes.

Obese women are more likely to experience pregnancy complications. The distribution of fat, and more particularly the rise in visceral fat, is well established to be more closely linked to the onset of cardiovascular disease and metabolic syndrome than obesity itself. We aim to examine the relationship between maternal visceral fat assessment in the first trimester and the appearance of adverse pregnancy outcomes. A prospective cohort study including 416 pregnant women was conducted. During the first trimester scan (11-13 + 6 weeks), all individuals had their visceral fat and subcutaneous thicknesses measured by ultrasonography. Blood samples were obtained, and maternal demographics and clinical information were documented. After delivery, the obstetric outcomes were evaluated. We contrasted two groups: one with healthy pregnancies and the other with adverse pregnancy outcomes (APO), defined as the development of at least one of the following complications: gestational diabetes mellitus, hypertensive disorders of pregnancy, abnormal fetal growth, preterm delivery or preterm premature rupture of membranes. Median maternal age was 33 and 34 years old for the uncomplicated and adverse pregnancy outcomes groups, respectively. We found that women with adverse pregnancy outcomes had higher VFT (median 30 vs. 26.5 mm, p = 0.001) and SFT (median 18.9 vs. 17.1 mm, p = 0.03). However, the visceral/subcutaneous fat ratio was not statistically different between groups. Finally, we performed a subanalysis for metabolic and placental vascular dysfunction complications. After performing a multivariate logistic regression analysis adjusted for maternal age, smoking, and mean arterial pressure, both the VFT (aOR 1.03, p < 0.001) and the ratio of visceral/subcutaneous fat (aOR 1.37, p = 0.04) were significantly associated with the development of adverse pregnancy outcomes; however, the associations of VFT and the VFT-to-SFT ratio were higher for the occurrence of gestational diabetes (aOR 1.07, p < 0.001; aOR 2.09, p = 0.001; respectively) and showed no relationships with placental complications. When conducting a first-trimester ultrasound assessment, sonographers may measure VFT without additional time or cost involved. Identification of pregnant women with increased VFT (>37 mm) may benefit from a close follow-up, especially for the development of gestational diabetes, independent of BMI.

Fetal cerebral three-dimensional power Doppler vascularization indices and their relationships with maternal glucose levels in pregnancies complicated with gestational diabetes.

OBJECTIVES: We aimed to evaluate fetal cerebral circulation using three-dimensional power Doppler (3DPD) vascular indices and to study their relationships with maternal lipid and glycaemic profiles. METHODS: Case-control study in women with and without gestational diabetes mellitus (GDM) at 28-32 weeks in which feto-maternal Doppler study and 3DPD cerebral vascularization indices (FI, VI and VFI) were determined. Maternal lipid and glycaemic profiles were also analysed. Both groups were compared and the correlations of the 3DPD indices with studied variables were analysed. RESULTS: There were significant differences between groups in cerebral FI (p= 0.02), mean maternal Uterine artery PI (p= 0.009) and glucose levels (p= 0.001), being higher in the GDM group. Significant negative correlations were found in GDM group between VFI and MCA PI (p = 0.02) and between VI and MCA PI (p= 0.01). In the GDM group we found a negative significant correlation between FI, VI, VFI and maternal glucose (r= -0.52, p<0.001; r= -0.32, p=0.03 and r= -0.36, p= 0.01, respectively). CONCLUSIONS: Fetal cerebral FI values were higher in GDM pregnancies. All 3DPD vascular indices showed an inverse correlation with maternal glucose levels. These findings support the view that GDM may also represent a fetal vascular disorder influencing fetal neurodevelopment.

Blood Pressure Monitoring and Perinatal Outcomes in Normotensive Women with Gestational Diabetes Mellitus.

Alterations in ambulatory blood pressure detected by monitoring (ABPM) have been associated with perinatal complications in hypertensive pregnant women. AIM: To establish the relationships between the blood pressure (BP) profiles detected by ABPM and adverse perinatal outcomes in normotensive women with gestational diabetes mellitus (GDM). METHODS: A prospective study of normotensive women in whom 24 h ABPM was performed at 28-32 weeks of pregnancy. The obstetric and perinatal outcomes were evaluated. RESULTS: Two hundred patients were included. Thirty-seven women with GDM and obesity had significantly higher mean systolic BP (SBP) and nocturnal SBP and diastolic BP (DBP) compared to women with only GDM (n = 86). Nocturnal SBP (OR = 1.077; p = 0.015) and obesity (OR = 1.131; p = 0.035) were risk factors for the development of hypertensive disorders of pregnancy (HDPs). Mothers of newborns with neonatal complications (n = 27) had higher nocturnal SBP (103.8 vs. 100 mmHg; p = 0.047) and DBP (62.7 vs. 59.4; p = 0.016). Women who delivered preterm (n = 10) had higher BP and a non-dipper pattern (p = 0.005). CONCLUSIONS: Nocturnal SBP was a predictor of HDPs in normotensive women with obesity or GDM. Alterations in ABPM in these patients were associated with poor obstetric and perinatal outcomes.

Fasting Glucose for the Diagnosis of Gestational Diabetes Mellitus (GDM) during the COVID-19 Pandemic.

Background: During the COVID-19 pandemic, different non-validated tests were proposed to simplify the diagnosis of gestational diabetes (GDM). Aim: To analyse the effects of replacing the two-step approach for Early-GDM and GDM diagnosis, with a fasting plasma glucose test. Material and Methods: This is a cohort study consisting of 3200 pregnant women: 400 with Early-GDM, 800 with GDM and 2000 with Non-GDM diagnosed using the two-step approach. Using fasting plasma glucose for Early-GDM and GDM diagnosis, according to the recommendations of Spain, Australia, Italy and the UK during the pandemic, the rates of missed and new Early-GDM and GDM were calculated and perinatal outcomes were analysed. Results: Using fasting plasma glucose in the first trimester >100 mg/dL for Early-GDM diagnosis, the rates of post-COVID missed and new Early-GDM were 79.5% and 3.2%, respectively. Using fasting plasma glucose at 24−28 weeks <84 or >92, 95 or 100 mg/dL for GDM diagnosis, the rates of missed GDM were 50.4%, 78%, 82.6% and 92.4%, respectively, and 8.6%, 5.6% and 2.3% women with Non-GDM were diagnosed with new GDM. Conclusion: Fasting plasma glucose is not a good test for the diagnosis of GDM either in the first trimester or at 24−28 weeks.

Angiogenic Imbalance and Inflammatory Biomarkers in the Prediction of Hypertension as Well as Obstetric and Perinatal Complications in Women with Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) increases the risk of hypertensive disorders of pregnancy (HDP). We aimed to analyze the altered inflammatory markers and angiogenic factors among women with GDM to identify pregnant women at higher risk of developing HDP. Methods: This was a prospective study of 149 women without hypertension diagnosed in the third trimester with GDM. Inflammatory markers and angiogenic factors were measured at 28−32 weeks of pregnancy. Obstetric and perinatal outcomes were evaluated. Results: More than eight percent of the women developed HDP. Higher levels of the soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PIGF) ratio (4.9 ± 2.6 versus 2.3 ± 1.3, respectively; p < 0.001) and leptin (10.9 ± 0.8 versus 10.08 ± 1.1, respectively; p = 0.038), as well as lower levels of adiponectin (10.5 ± 1.3 versus 12.9 ± 2.7, respectively; p = 0.031), were seen in women who developed HDP versus normotensive women with GDM. A multivariable logistic regression analysis showed that adiponectin had a protective effect with 0.45-fold odds (0.23−0.83; p = 0.012), and that the sFlt-1/PIGF ratio was associated with 2.70-fold odds of developing HDP (CI 95%: 1.24−5.86; p = 0.012). Conclusion: An increase in angiogenic imbalance in the sFlt-1/PIGF ratio in women with GDM was detected and may be an indicator of developing HDP in addition to any subsequent obstetric and perinatal complications.

Assessment of an intervention to optimise antenatal management of women admitted with preterm labour and intact membranes using amniocentesis-based predictive risk models: study protocol for a randomised controlled trial (OPTIM-PTL Study).

INTRODUCTION: The majority of women admitted with threatened preterm labour (PTL) do not delivery prematurely. While those with microbial invasion of the amniotic cavity (MIAC) represent the highest risk group, this is a condition that is not routinely ruled out since it requires amniocentesis. Identification of low-risk or high-risk cases might allow individualisation of care, that is, reducing overtreatment with corticosteroids and shorten hospital stay in low-risk women, while allowing early antibiotic therapy in those with MIAC. Benefits versus risks of amniocentesis-based predictor models of spontaneous delivery within 7 days and/or MIAC have not been evaluated. METHODS AND ANALYSIS: This will be a Spanish randomised, multicentre clinical trial in singleton pregnancies (23.0-34.6 weeks) with PTL, conducted in 13 tertiary centres. The intervention arm will consist in the use of amniocentesis-based predictor models: if low risk, hospital discharge within 24 hours of results with no further medication will be recommended. If high risk, antibiotics will be added to standard management. The control group will be managed according to standard institutional protocols, without performing amniocentesis for this indication. The primary outcome will be total antenatal doses of corticosteroids, and secondary outcomes will be days of maternal stay and the occurrence of clinical chorioamnionitis. A cost analysis will be undertaken. To observe a reduction from 90% to 70% in corticosteroid doses, a reduction in 1 day of hospital stay (SD of 2) and a reduction from 24% to 12% of clinical chorioamnionitis, a total of 340 eligible patients randomised 1 to 1 to each study arm is required (power of 80%, with type I error α=0.05 and two-sided test, considering a dropout rate of 20%). Randomisation will be stratified by gestational age and centre. ETHICS AND DISSEMINATION: Prior to receiving approval from the Ethics Committee (HCB/2020/1356) and the Spanish Agency of Medicines and Medical Devices (AEMPS) (identification number: 2020-005-202-26), the trial was registered in the European Union Drug Regulating Authorities Clinical Trials database (2020-005202-26). AEMPS approved the trial as a low-intervention trial. All participants will be required to provide written informed consent. Findings will be disseminated through workshops, peer-reviewed publications and national/international conferences. PROTOCOL VERSION: V.4 10 May 2021. TRIAL REGISTRATION NUMBERS: NCT04831086 and Eudract number 2020-005202-26.

Heterotopic triplets: tubal ectopic and twin intrauterine pregnancy. A review of obstetric outcomes with a case report.

INTRODUCTION: Heterotopic triplets hardly take place, but nowadays the extended use of assisted reproductive technologies is increasing the ectopic pregnancies rate and subsequently the heterotopic pregnancies, leading to a potentially dangerous condition for the woman and the intrauterine pregnancy. MATERIAL AND METHODS: Fourteen cases previously reported in the literature of patients presenting an intrauterine twin pregnancy which became complicated by a tubal ectopic pregnancy have been reviewed. The case of a patient following a homologous intrauterine insemination treatment, resulting in live birth of both twins, is also described. CONCLUSION: Although the diagnosis of heterotopic triplets with tubal ectopic is challenging, a timely surgical treatment will preserve intrauterine gestation with a great chance of a successful obstetric outcome for both twins.

Placental Adaptive Changes to Protect Function and Decrease Oxidative Damage in Metabolically Healthy Maternal Obesity.

Pregnancy-related disorders, including preeclampsia and gestational diabetes, are characterized by the presence of an adverse intrauterine milieu that may ultimately result in oxidative and nitrosative stress. This scenario may trigger uncontrolled production of reactive oxygen species (ROS) such as superoxide anion (O●-) and reactive nitrogen species (RNS) such as nitric oxide (NO), along with an inactivation of antioxidant systems, which are associated with the occurrence of relevant changes in placental function through recognized redox post-translational modifications in key proteins. The general objective of this study was to assess the impact of a maternal obesogenic enviroment on the regulation of the placental nitroso-redox balance at the end of pregnancy. We measured oxidative damage markers-thiobarbituric acid-reacting substances (TBARS) and carbonyl groups (C=O) levels; nitrosative stress markers-inducible nitric oxide synthase, nitrosothiol groups, and nitrotyrosine residues levels; and the antioxidant biomarkers-catalase and superoxide dismutase (SOD) activity and expression, and total antioxidant capacity (TAC), in full-term placental villous from both pre-pregnancy normal weight and obese women, and with absence of metabolic complications throughout gestation. The results showed a decrease in C=O and TBARS levels in obese pregnancies. Although total SOD and catalase concentrations were shown to be increased, both activities were significantly downregulated in obese pregnancies, along with total antioxidant capacity. Inducible nitric oxide sintase levels were increased in the obese group compared to the lean group, accompanied by an increase in nitrotyrosine residues levels and lower levels of nitrosothiol groups in proteins such as ERK1/2. These findings reveal a reduction in oxidative damage, accompanied by a decline in antioxidant response, and an increase via NO-mediated nitrative stress in placental tissue from metabolically healthy pregnancies with obesity. All this plausibly points to a placental adaptation of the affected antioxidant response towards a NO-induced alternative pathway, through changes in the ROS/RNS balance, in order to reduce oxidative damage and preserve placental function in pregnancy.

Transformed alpha-fetoprotein (t-AFP) levels in women with threatened preterm labor.

BACKGROUND/AIMS: To evaluate maternal serum transformed alpha-fetoprotein (MSt-AFP) levels, a new molecular conformation of AFP was used in cases of threatened preterm labor (TPL). METHODS: Prospective case-control study. Maternal serum levels of classical AFP and transformed AFP (t-AFP) were compared between 2 groups matched by gestational age: 25 women with TPL and 25 healthy pregnant women as controls. RESULTS: There was no significant difference in classical maternal serum AFP (MSAFP) levels between the 2 groups. In contrast, MSt-AFP levels were significantly lower in cases of TPL than in the control group [7.64 (1.78-29.06) vs. 33.38 (13.80-190.50) ng/ml; p = 0.006]. Similarly, the t-AFP:AFP ratio was also decreased in the TPL group [0.04 (0.004-0.12) vs. 0.16 (0.05-0.80); p = 0.008]. There was no significant correlation between MSAFP and MSt-AFP levels. CONCLUSIONS: MSt-AFP levels are decreased in women with TPL.

Effect of Different Insulin Therapies on Obstetric-Fetal Outcomes.

To evaluate the effectiveness of the different insulin therapies on obstetrics-fetal outcomes in women with pregestational diabetes mellitus. We enrolled 147 pregnant women with pre-existing type 1 or 2 diabetes mellitus. Clinical and biochemical parameters were analysed in relation to obstetric and fetal outcomes. 14.2% received treatment with Neutral Protamine Hagedorn insulin and short-acting insulin analogues; 19% with premixed human insulin; 40.1% with insulin glargine and lispro, 6.2% with detemir and aspart and 20% with continuous subcutaneous insulin infusion. All 5 types of treatment achieved a reduction of the mean HbA1c during pregnancy (p = 0.01). Pre-pregnancy care was carried out for 48% of patients. We found no statistically significant differences between the different insulin therapies and the obstetric-fetal outcomes. In conclusión, the different insulin therapies used in patients with pregestational diabetes mellitus does not seem to affect obstetric-fetal outcomes.

Metabolic syndrome in normal and complicated pregnancies.

OBJECTIVE: To evaluate the prevalence of metabolic syndrome and its components in normal and complicated pregnancies. SETTING: university hospital, tertiary referral centre. SUBJECTS: 90 pregnant women in four groups: 20 women with preeclampsia, 20 women with gestational hypertension, 30 women with late-onset gestational diabetes and 20 healthy pregnant women as a control group. INTERVENTION: peripheral insulin resistance was measured by using the insulin tolerance test. Glucose, triglycerides, high-density lipoprotein cholesterol, blood pressure and body mass index were analysed. Comparisons were done by Chi-squared test, one-way analysis of variance and the Bonferroni's test. Prevalence of the metabolic syndrome was calculated by adapting both the WHO and the NCEP definitions of the metabolic syndrome to pregnancy. RESULTS: There were no cases of metabolic syndrome in the control group according to any of the adapted definitions. The prevalence of this syndrome was 3.3% and 10% in the late-onset gestational diabetes group, 35% and 20% in the gestational hypertension group and 30% and 30% in the preeclampsia group for the WHO and the NCEP definitions, respectively. CONCLUSIONS: Metabolic syndrome is present in about one-third of women with pregnancy-induced hypertension but only in 10% of women with late-onset gestational diabetes.

Effects of antenatal betamethasone on human fetal branch pulmonary artery flow velocity waveforms.

OBJECTIVE: To evaluate the effect of antenatal betamethasone on fetal branch pulmonary artery flow velocity waveforms. METHODS: Betamethasone 12 mg i.m. in 2 injections 24 h apart was given to 25 pregnant women at risk of preterm delivery. Pulsatility (PI) and resistance (RI) indexes were measured at the proximal, middle and distal segments of the fetal pulmonary artery before and repeatedly 1, 2 and 7 days after the first dose. ANOVA for repeated measures and the general linear model were used to statistically analyze the results. RESULTS: Blood flow resistance decreased after betamethasone treatment at both the middle (p = 0.001 and p = 0.02 for RI and PI, respectively) and the proximal (p = 0.03 for RI) segments returning to basal values after 7 days. CONCLUSIONS: Antenatal betamethasone decreases fetal branch pulmonary artery vascular resistance.

The Influence of Lipid and Proinflammatory Status on Maternal Uterine Blood Flow in Women With Late Onset Gestational Diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with increased proinflammatory cytokines and is also associated with adverse cardiovascular disease (CVD) outcomes later in life. We aim to evaluate the relationships between uterine arteries vascularization and endothelial dysfunction markers, proinflammatory cytokines, and glycemic and lipid profile in women with GDM. METHODS: Fifty pregnant women were recruited at the third trimester of pregnancy for a prospective cohort study. They were classified into 2 groups: control and GDM. Comparisons of maternal plasma concentrations of endothelial dysfunction markers (vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and plasminogen activator inhibitor 1), proinflammatory cytokines and mediators (interleukin 6 [IL-6], tumor necrosis factor α, vascular endothelial growth factor, placental growth factor, leptin, leukocyte count, and C-reactive protein), lipid profile, glucose, and glycosylated hemoglobin levels were performed. Mean uterine arteries Doppler pulsatility index (PI) was calculated and the relationships between the variables and PI were also analyzed. RESULTS: Women with GDM showed higher proinflammatory cytokines, however, endothelial dysfunction markers were similar in both groups. In the diabetic group, significant correlations were found between the mean uterine arteries PI and maternal IL-6 ( r = .56, P = .01), triglycerides ( r = .49; P = .03), total cholesterol/high-density lipoprotein cholesterol (HDL-c) ratio ( r = .61; P = .006), glucose (r = .62, P = .005), and glycosylated hemoglobin ( r = .48; P = .03). A negative significant correlation between mean uterine arteries PI and HDLc ( r = -.58; P = .02) was also found. CONCLUSION: The proinflammatory status, hyperlipidemia, and metabolic control correlate with uterine blood flow velocity waveforms in women with gestational diabetes.

Maternal serum transformed alpha-fetoprotein levels in women with intrauterine growth retardation.

OBJECTIVE: To evaluate maternal serum transformed alpha-fetoprotein (t-AFP) levels in women with intrauterine growth retardation (IUGR). METHODS: 60 pregnant women in two groups were studied: 30 with IUGR and 30 healthy pregnant women as a control group. t-AFP concentrations were determined by ELISA assay. RESULTS: Maternal serum t-AFP levels were higher in women with IUGR than in the control group: 15.39 (10.81-24.01) ng/ml vs. 8.66 (6.22-13.45) ng/ml (p = 0.003). t-AFP levels were even higher in those with fetal hemodynamic redistribution 21.08 (16.02-40.85) ng/ml than in those without 12.15 (10.48-17.45) ng/ml (p = 0.03). CONCLUSIONS: Maternal serum t-AFP is increased in women with IUGR and this elevation is marked in those with fetal hemodynamic redistribution.