The Use of Atomic Force Microscopy in Comprehensive Assessment of the "Mother-Placenta-Fetus" System in Obstetric and Endocrine Pathology during Pregnancy.

Atomic force microscopy is not very popular in practical health care, therefore, its potential is not studied enough, for example, in obstetrics when studying the "mother-placenta-fetus" system. Our study summarizes the possibilities of using atomic force microscopy for detection of various circulatory disorders and vascular changes at the microscopic level in the uterus (endometrium and myometrium), placenta, and umbilical cord in the main variants of obstetric and endocrine pathology. For instance, in the case of endocrine pathologies, changes in the form of stasis, sludge, diapedesis, ischemia, destruction and separation of endotheliocytes in villous blood vessels were found in the mother. The oxygen content in erythrocytes also naturally decreased in pathologies; poikilo- and anisocytosis were observed.

Assessment of the effect of pregnancy planning in women with type 1 diabetes treated by insulin pump.

BACKGROUND: Pregnant women with type 1 diabetes (T1D) have high risk of complications despite improved care based on technology advancements. OBJECTIVE: To assess the effects of pregnancy planning on fetal and maternal outcomes in T1D women treated with continuous subcutaneous insulin infusion (CSII). STUDY DESIGN: We retrospectively assessed maternal and neonatal outcomes in T1D women using CSII who had planned or unplanned pregnancies between 2002 and 2018. The study was done in two European countries with similar sustained programs for pregnancy planning over the study period. RESULTS: Data from 107 pregnancies and newborn babies were collected. Seventy-nine pregnancies (73.8%) had been planned. HbA1c was lower in planned versus unplanned pregnancy before and during all three trimesters of pregnancy (p < 0.0001). Pregnancy planning was associated with a reduction in the occurrence of iatrogenic preterm delivery (RR 0.44, 95% CI 0.23-0.95; p = 0.01). Risk reduction persisted after adjustments for mother's age above 40 years and preeclampsia. High HbA1c before or during pregnancy was associated with an increased risk of iatrogenic preterm delivery (RR 3.05, 95% CI 1.78-5.22, p < 0.0001). Premature newborns needed intensive care more often than those at term (RR 3.10, 95% CI 1.53-4.31; p = 0.002). CONCLUSIONS: Pregnancy planning in T1D women using CSII was associated with better glucose control and decreased risk of iatrogenic preterm delivery. Hence preconception care also improves pregnancy outcome in patients using an advanced mode of insulin delivery. Planned pregnancies could further benefit from the use of new metrics of glucose control.

Improving systems of care during and after a pregnancy complicated by hyperglycaemia: A protocol for a complex health systems intervention.

BACKGROUND: Many women with hyperglycaemia in pregnancy do not receive care during and after pregnancy according to standards recommended in international guidelines. The burden of hyperglycaemia in pregnancy falls disproportionately upon Indigenous peoples worldwide, including Aboriginal and Torres Strait Islander women in Australia. The remote and regional Australian context poses additional barriers to delivering healthcare, including high staff turnover and a socially disadvantaged population with a high prevalence of diabetes. METHODS: A complex health systems intervention to improve care for women during and after a pregnancy complicated by hyperglycaemia will be implemented in remote and regional Australia (the Northern Territory and Far North Queensland). The Theoretical Domains Framework was used during formative work with stakeholders to identify intervention components: (1) increasing workforce capacity, skills and knowledge and improving health literacy of health professionals and women; (2) improving access to healthcare through culturally and clinically appropriate pathways; (3) improving information management and communication; (4) enhancing policies and guidelines; (5) embedding use of a clinical register as a quality improvement tool. The intervention will be evaluated utilising the RE-AIM framework at two timepoints: firstly, a qualitative interim evaluation involving interviews with stakeholders (health professionals, champions and project implementers); and subsequently a mixed-methods final evaluation of outcomes and processes: interviews with stakeholders; survey of health professionals; an audit of electronic health records and clinical register; and a review of operational documents. Outcome measures include changes between pre- and post-intervention in: proportion of high risk women receiving recommended glucose screening in early pregnancy; diabetes-related birth outcomes; proportion of women receiving recommended postpartum care including glucose testing; health practitioner confidence in providing care, knowledge and use of relevant guidelines and referral pathways, and perception of care coordination and communication systems; changes to health systems including referral pathways and clinical guidelines. DISCUSSION: This study will provide insights into the impact of health systems changes in improving care for women with hyperglycaemia during and after pregnancy in a challenging setting. It will also provide detailed information on process measures in the implementation of such health system changes.

Awareness about diabetes and pregnancy among diabetes specialists and fellows: The YoSID diabetes and pregnancy project.

BACKGROUND AND AIMS: Despite evidence that pregnancy planning improves outcomes, in Italy, as in many other countries worldwide, <50% of women with diabetes prepare their pregnancy. The aim of this study was to document training and knowledge on diabetes and pregnancy (D&P) among diabetes professionals. METHODS AND RESULTS: We administered an anonymous online questionnaire, focused on diabetes and pregnancy planning, to diabetes team members. Between Nov-2017 and Jul-2018, n = 395 professionals (60% diabetes/endocrinology/internal medicine specialists, 28% fellows) completed the survey. Fifty-nine percent of the specialists, mainly (78%) those completing their fellowship after 2006, reported having received training on D&P during fellowship. Considering specialists reporting training, 43% correctly identified fetal risks of inadequate preconceptional glucose control and 55% maternal risks, 38% identified risks associated with overweight/obesity, and 39% would prescribe hormonal contraception to women with diabetes only if glucose control is good. CONCLUSIONS: The results of our survey suggest the need to improve training and awareness of professionals in the area of diabetes and pregnancy.

The association between novel glucose indices in parturients with type 1 diabetes mellitus and clinically significant neonatal hypoglycemia.

The aim of this study was to determine the association between glucose control indices of parturient with type 1 diabetes (T1DM), treated with an insulin pump and utilizing continuous glucose monitoring (CGM), and clinically significant neonatal hypoglycemia. This was a retrospective cohort study which included 37 pregnant women with T1DM. All women were followed at a single tertiary center and had available CGM data. The association between maternal glucose indices before delivery and the risk for neonatal hypoglycemia requiring IV glucose (clinically significant hypoglycemia) was assessed using logistic regression. Mothers to neonates that experienced clinically significant hypoglycemia had a higher glucose standard deviation (SD) before delivery than did mothers to neonates who did not (25.5 ± 13 mg/dL vs. 14.7 ± 6.7 mg/dl respectively; p = .008). This association persisted after adjustment for maternal age, maternal pregestational body mass index (BMI), gestational age at delivery, neonatal birth weight, large for gestational age (LGA) and gender. This study demonstrates an association between high maternal glucose standard deviation before delivery and the risk for clinically significant neonatal hypoglycemia. Larger studies are needed to confirm these results and further explore the role of intrapartum glucose variability in the prediction and prevention of significant neonatal hypoglycemia.

Diabetes care in remote Australia: the antenatal, postpartum and inter-pregnancy period.

BACKGROUND: Aboriginal and Torres Strait Islander women experience high rates of diabetes in pregnancy (DIP), contributing to health risks for mother and infant, and the intergenerational cycle of diabetes. By enhancing diabetes management during pregnancy, postpartum and the interval between pregnancies, the DIP Partnership aims to improve health outcomes and reduce risks early in the life-course. We describe a mixed methods formative study of health professional's perspectives of antenatal and post-partum diabetes screening and management, including enablers and barriers to care. METHODS: Health professionals involved in providing diabetes care in pregnancy, from a range of health services across the Northern Territory, completed the survey (n = 82) and/or took part in interviews and/or focus groups (n = 62). RESULTS: Qualitative findings highlighted factors influencing the delivery of care as reported by health professionals, including: whose responsibility it is, access to care, the baby is the focus and pre-conception care. The main challenges were related to: disjointed systems and confusion around whose role it is to provide follow-up care beyond six weeks post-partum. Quantitative findings indicated that the majority of health professionals reported confidence in their own skills to manage women in the antenatal period (62%, 40/79) and slightly lower rates of confidence in the postpartum interval (57%, 33/58). CONCLUSION: These findings regarding whose role it is to provide postpartum care, along with opportunities to improve communication pathways and follow up care have informed the design of a complex health intervention to improve health systems and the provision of DIP related care.

Application of customized birth weight curves in the assessment of perinatal outcomes in infants of diabetic mothers.

OBJECTIVE: To determine whether the use of customized curves (CC) allows better detection of large- (LGA) or small-for-gestational age (SGA) infants at risk of adverse perinatal morbidity than non-CC in women with diabetes mellitus (DM). MATERIAL AND METHODS: A model of CC was applied to all infants of diabetic mothers (IDM) who attended the Hospital Universitario Materno Infantil de Canarias between 2008 and 2011. We compared perinatal outcomes of IDM classified as LGA or SGA by non-CC versus CC. RESULTS: One of 4 LGA was appropriate for gestational age (AGA) by CC (false-positive rate: 25%) and 30% of SGA by CC were not identified by non-CC (false-negative rate). False-positive LGA and SGA showed similar perinatal outcomes to AGA infants. The rates of cesarean section, cephalopelvic disproportion, total fetal distress and shoulder dystocia were significantly higher in false-negative LGA than in AGA by CC (p < 0.004, p < 0.02, p < 0.04 and p < 0.04, respectively). Fetal distress was higher in false-negative SGA than in AGA by CC (p < 0.03). DISCUSSION: In pregnancies complicated by DM, the use of CC allowed more accurate identification of LGA and SGA infants at high risk of perinatal morbidity than non-CC.

Diabetes and pregnancy: perspectives from Asia.

There has been a marked increase in the prevalence of diabetes in Asia over recent years. Diabetes complicating pregnancy, in particular gestational diabetes, has also increased markedly in the region. Multi-ethnic studies have highlighted the increased risk of gestational diabetes mellitus among the different Asian populations. Prevalence of gestational diabetes in Asian countries varies substantially according to the screening strategy and diagnostic criteria applied, and ranges from 1% to 20%, with evidence of an increasing trend over recent years. The International Association for Diabetes in Pregnancy Study group criteria have been adopted by some Asian countries, although they present significant challenges in implementation, especially in low-resource settings. Studies on offspring of mothers with gestational diabetes have reported adverse cardiometabolic profiles and increased risk of diabetes and obesity. Gestational diabetes is likely to be a significant factor contributing to the epidemic of diabetes and other non-communicable diseases in the Asian region. In recognition of this, several large-scale prevention and intervention programmes are currently being implemented in different Asian countries in order to improve glucose control during pregnancy, as well as overall maternal health. Lessons emerging from gestational diabetes studies in Asia may help inform and provide insights on the overall burden and treatment strategies to target gestational diabetes, with the ultimate aim to reduce its adverse short- and long-term consequences.

The efficacy and effectiveness of continuous glucose monitoring during pregnancy: a systematic review.

OBJECTIVE: Diabetic pregnancies carry a high risk for both mother and child, especially when glycemic control is poor. A novel technique that aims to improve glycemic control is the continuous glucose monitor (CGM). This tool is already in use to improve pregnancy outcome. This review presents the available evidence on the efficacy of CGM use in pregnancy and the effectiveness on pregnancy outcome. METHODS: A systematic search was conducted using PubMed, EMBASE, and the Cochrane Libraries for articles on CGM in pregnancy. We evaluated the selected articles with particular attention for clinical and cost-effectiveness of CGM to improve pregnancy outcome. RESULTS: We retrieved 5032 articles, 11 of which remained as relevant after selection according to predefined criteria. Most studies were limited to the evaluation of the role of CGM on clinical decision making. Only 2 studies were randomized controlled trials (RCTs) evaluating the effect on pregnancy outcome. One small RCT on retrospective CGM showed a significant reduction in third-trimester HbA1c and a significant reduction in neonatal macrosomia. A second RCT on real-time CGM did not show any effect on either glycemic control or on pregnancy outcome. CONCLUSIONS: Current evidence on the efficacy of CGM on improving glycemic control during pregnancy as well as on the effectiveness on pregnancy outcome is limited to 2 RCTs with contradicting results. Evidence on the cost-effectiveness is lacking. Further proper RCTs on the effectiveness and cost-effectiveness of CGM in pregnancy are required before wide implementation in practice.

Gestational diabetes guidelines in a HAPO world.

The impact of gestational diabetes on maternal and fetal health has been increasingly recognized. However, universal consensus on the diagnostic methods and thresholds has long been lacking. Published guidelines from major societies differ considerably from one another, ranging in recommendations from aggressive screening to no routine screening at all. As a result, real-world practice is equally varied. The recently published Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study, and two randomized controlled trials evaluating treatment of mild maternal hyperglycemia, have served to confirm the findings of smaller, nonrandomized studies solidifying the link between maternal hyperglycemia and adverse perinatal outcomes. In response to these studies, the International Association of Diabetes and Pregnancy Study Groups (IADPSG) has formulated new guidelines for screening and diagnosis of diabetes in pregnancy. Key components of the IADPSG guidelines include the recommendation to screen high-risk women at the first encounter for pre-gestational diabetes, to screen universally at 24-28 weeks' gestation, and to screen with use of the 75-g oral glucose tolerance test interpreting abnormal fasting, 1-h, and 2-h plasma glucose concentrations as individually sufficient for the diagnosis of gestational diabetes. Furthermore, to translate the continuous association between maternal glucose and adverse outcomes demonstrated in the HAPO cohort, they recommend thresholds for positive screening tests at which the odds of elevated birth weight, cord C-peptide, and fetal percent body fat are 1.75 relative to odds of those outcomes at mean glucose values. Opponents to the IADPSG recommendations will likely be those who favor risk-based screening in addition to those who endorse the 50-g glucose challenge test followed by the 100-g oral glucose tolerance test as a more cost-effective, familiar, and possibly, well-validated screening tool. Others may argue that the diagnostic thresholds chosen by the IADPSG are arbitrary and will continue to miss many cases of abnormal glucose metabolism and therefore leave open the possibility of adverse perinatal outcomes due to untreated gestational diabetes. Finally, the potential economic impact of the IADPSG guidelines are unknown, and with minimal long-term data yet available on the offspring of the HAPO cohort, a true cost-effectiveness analysis will be difficult to perform accurately. Given these potential points of contention, the responses of professional and international groups to the IADPSG guidelines are difficult to gauge. Regardless, these guidelines serve to advance the discussion on appropriate screening and diagnosis of diabetes in pregnancy.

Definition, size of the problem, screening and diagnostic criteria: who should be screened, cost-effectiveness, and feasibility of screening.

The epidemic of obesity and increased prevalence of diabetes necessitates reconsideration of its definition and screening by separating type 2 diabetic women from women with gestational diabetes to provide a better model of care. The unique problems concerning an undiagnosed type 2 diabetic woman are not major issues in the gestational diabetic woman. This review underscores the need for a unique diagnosis for women with moderate to severe hyperglycemia and/or other evidence of long-standing diabetes complications, and the urgent need for more intensive surveillance and treatment than is otherwise available for gestational diabetic women.

[Value of fetal lung maturity assessment in maternal diabetes]. / Wert der fetalen Lungenreifebestimmung bei mütterlichem Diabetes.

OBJECTIVE: Results of antepartal fetal lung maturity (FLM) testing in diabetics were compared to control patients. We analysed 274 patients by phospholipid profile and 219 by phosphatidylglycerol (PG), consisting of 73, respectively 54 diabetic and 201, resp. 165 normal control subjects. MATERIAL AND METHODS: Phospholipid concentration increased exponentially with gestational age (rreg = 0.44 for diabetic and 0.57 for normal control patients). There was no significant difference between both groups. Measurement of PG showed a trend towards lung immaturity in diabetic infants for preterm and term gestations, which did not reach significance (chi-square [chi 2] test 0.07, resp. 0.06). RESULTS: Diabetic and non-diabetic pregnancies did not differ significantly in FLM and RDS frequency. Both methods show a high rate of falsely immature results. Antepartal FLM testing by measurement of phospholipids and PG does not play a role in clinical management of diabetic patients.

Variability of adjustments to indices in determining patient risk in biochemical screening.

It has long been appreciated that the measurement of biochemical parameters for prenatal screening for neural tube defects, and later aneuploidy, is not as simple as measuring hemoglobin or hematocrit. Early in the game, it was recognized that there are gestational age curves, and that since alpha-fetoprotein (AFP), for example, is a fetal product, its distribution varies as a function of maternal plasma volume, and therefore the weight of the mother. A number of different adjustment factors have been used for AFP and other parameters for years, with varying degrees of consistency and reliability. Here we review a number of adjustments that have been used, and try to give priority to those that have been most effective. Furthermore, laboratories and programs need to be cognizant that with newer parameters being added, the specifics of requirements will vary on a case-by-case parameter basis, and optimal screening can only be achieved with the appropriate adjustments.

Selective screening for gestational diabetes mellitus in adolescent pregnancies.

OBJECTIVE: It is unclear whether it is cost-effective to universally screen adolescent gravidas for gestational diabetes mellitus (GDM). Our objective was to identify the prevalence of gestational diabetes in our adolescent population and to review risk factors that would most easily identify a subset of adolescent patients at greatest risk for the development of gestational diabetes. METHODS: Six hundred thirty-two adolescents were identified from 11,486 deliveries in our institution through International Classification of Diseases (9th edition) codes. Eleven of those adolescents had GDM. Their charts and those of a representative group of nondiabetic adolescent gravidas were analyzed for GDM risk factors, including race/ethnicity, body mass index (BMI), family history of diabetes, other medical disorders, and previous history of GDM, macrosomia, stillbirths, or anomalous fetus. Statistical analyses used chi2 and Student t tests as appropriate. RESULTS: The prevalence of GDM among adolescent gravidas was 1.7%. No difference was identified between the adolescent pregnancies with GDM and the comparison group for race/ethnicity, family history, or presence of medical disorders. Risk factors requiring a previous obstetric history could not be evaluated adequately because of the high prevalence of nulliparas. There was a higher prevalence of BMI over 27 in adolescents with GDM (P < .001). CONCLUSION: Body mass index is an important risk factor for the development of gestational diabetes in adolescent gravidas. We recommend that selective screening for GDM of adolescent gravidas be performed on the basis of BMI.

[Insulinemic response to oral glucose loading tests in screening for diabetes in pregnancy]. / Risposta insulinemica al carico orale di glucosio nei test di screening del diabete gestazionale.

BACKGROUND AND AIMS: Given that an increased peripheral insensitivity to insulin represents the primum movens of gestational diabetes, it is reasonable to suppose that the determination and evaluation of the insulinemic response to an oral glucose loading test may represent a simple, effective and low cost screenign test. A method was devised which consisted in performing two assays of insulin and glycemia in venous blood; the first while fasting, the second one hour after the ingestion per os of 50 g glucose. METHODS: A group of 79 pregnant women, aged between 20 and 41 years old (mean age 30.5), was tested in around the 23rd week of gestation. All women were attending the Obstetric and Gynecological Clinic at Trieste University. RESULTS: Based on the results obtained, insulinemic parameters appear to be significantly correlated with data for the short glycemic curve according to O'Sullivan-Mahan. CONCLUSIONS: This study appears to confirm the need to include insulinemic tests as part of the new and more efficacious glucose tolerance tests and to perform prospective studies in order to identify the most reliable screening method in terms of sensitivity and specificity, also in relation to the cost-benefit ratio.

[Determination of postpartum fructosamine for assessment of gestational diabetes--a suitable method?]. / Postpartale Fruktosamin-Bestimmung zur Erfassung des Risikofaktors Gestationsdiabetes--eine geeignete Methode?

Postpartal screening of undetected gestational diabetes has proven to be difficult. Rapid decrease in diabetogenic hormones and normalisation of the former delayed insulin-response make it difficult to detect disturbed glucose tolerance in the puerperium. Therefore, glycolysated serum proteins offer the opportunity for retrospective diagnosis. They allow an evaluation of the patient's carbohydrate metabolism, retrospectively over several weeks. In this context, we were most interested in the significance of fructosamine. In a prospective study covering 12 months, 123 patients with several risk factors for gestational diabetes underwent a 100 g glucose tolerance test in the puerperium. Furthermore, we measured fructosamine and glycolysated hemoglobin. A carbohydrate intolerance could be detected by the oral glucose tolerance test in 22.7%. In 12.2% of the cases, glycolysated hemoglobin was found to be higher than 5.5%. Fructosamine levels were normal for all patients, with a mean value of 1.84 mmol/l. Even though fructosamine concentration was significantly higher (p < 0.05) in patients with a pathologic glucose tolerance, our study showed the oral glucose tolerance test to be better to detect unknown gestational diabetes than measurement of serum fructosamine.

Assessment and management of pregnancies complicated by pregestational and gestational diabetes mellitus.

Diabetes mellitus is a commonly encountered medical complication of pregnancy that affects more than 100,000 pregnancies annually. The discovery of insulin and numerous scientific advances, including both fetal heart rate and glucose monitoring, dramatically improved the outlook for women with diabetes and their offspring. However, despite these recent advances, women with diabetes and their infants still remain at higher risk for a number of complications. Pregnancy has frequently been characterized as having a diabetogenic effect on normal carbohydrate metabolism, as evidenced by hyperglycemia and hyperinsulinemia in response to feeding. This leads to gestational diabetes in 2% to 3% of women and a worsened metabolic state in women with insulin-dependent diabetes mellitus. Since the availability of nutrients for the fetus is primarily dependent on the maternal metabolic state, these aberrations in fuel metabolism are believed to result in a host of perinatal complications, including diabetic embryopathy. In fact, the frequency of congenital anomalies is increased among infants of women with diabetes; they are responsible for approximately 40% of all perinatal deaths. Recent evidence suggests that normalization of blood glucose levels coupled with contemporary management strategies can reduce the frequency of congenital anomalies as well as improve maternal and neonatal outcomes. However, to impact on the congenital anomalies, euglycemia must begin in the preconceptual period and continue throughout organogenesis. Preconception counseling and intensive therapy regimens remain the focus of management programs targeted at women with diabetes.

Screening recommendations for gestational diabetes mellitus.

As a result of extensive experiences in multiple centers and a review of the current literature, we conclude that a plasma glucose level obtained 1 hour after a 50 gm oral glucose challenge is the "best" gestational diabetes mellitus screening test. This universal screening is performed at least once during pregnancy. The screening threshold should be no higher than 140 mg/dl, or an unacceptable loss in sensitivity occurs. Universal screening for gestational diabetes mellitus is justified by morbidity reduction, cost, and protocol simplicity and ease.