MicroRNA-322 overexpression reduces neural tube defects in diabetic pregnancies.

BACKGROUND: Hyperglycemia from pregestational diabetes mellitus induces neural tube defects in the developing fetus. Folate supplementation is the only effective way to prevent neural tube defects; however, some cases of neural tube defects are resistant to folate. Excess folate has been linked to higher maternal cancer risk and infant allergy. Therefore, additional interventions are needed. Understanding the mechanisms underlying maternal diabetes mellitus-induced neural tube defects can identify potential targets for preventing such defects. Despite not yet being in clinical use, growing evidence suggests that microRNAs are important intermediates in embryonic development and can serve as both biomarkers and drug targets for disease intervention. Our previous studies showed that maternal diabetes mellitus in vivo activates the inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) in the developing embryo and that a high glucose condition in vitro reduces microRNA-322 (miR-322) levels. IRE1α is an RNA endonuclease; however, it is unknown whether IRE1α targets and degrades miR-322 specifically or whether miR-322 degradation leads to neural tube defects via apoptosis. We hypothesize that IRE1α can inhibit miR-322 in maternal diabetes mellitus-induced neural tube defects and that restoring miR-322 expression in developing neuroepithelium ameliorates neural tube defects. OBJECTIVE: This study aimed to identify potential targets for preventing maternal diabetes mellitus-induced neural tube defects and to investigate the roles and relationship of a microRNA and an RNA endonuclease in mouse embryos exposed to maternal diabetes mellitus. STUDY DESIGN: To determine whether miR-322 reduction is necessary for neural tube defect formation in pregnancies complicated by diabetes mellitus, male mice carrying a transgene expressing miR-322 were mated with nondiabetic or diabetic wide-type female mice to generate embryos with or without miR-322 overexpression. At embryonic day 8.5 when the neural tube is not yet closed, embryos were harvested for the assessment of 3 miR-322 transcripts (primary, precursor, and mature miR-322), tumor necrosis factor receptor-associated factor 3 (TRAF3), and neuroepithelium cell survival. Neural tube defect incidences were determined in embryonic day 10.5 embryos when the neural tube should be closed if there is no neural tube defect formation. To identify which miR-322 transcript is affected by maternal diabetes mellitus and high glucose conditions, 3 miR-322 transcripts were assessed in embryos from dams with or without diabetes mellitus and in C17.2 mouse neural stem cells treated with different concentrations of glucose and at different time points. To determine whether the endonuclease IRE1α targets miR-322, small interfering RNA knockdown of IRE1α or overexpression of inositol-requiring transmembrane kinase/endoribonuclease 1α by DNA plasmid transfection was used to determine the effect of IRE1α deficiency or overexpression on miR-322 expression. RNA immunoprecipitation was performed to reveal the direct targets of inositol-requiring transmembrane kinase/endoribonuclease 1α. RESULTS: Maternal diabetes mellitus suppressed miR-322 expression in the developing neuroepithelium. Restoring miR-322 expression in the neuroepithelium blocked maternal diabetes mellitus-induced caspase-3 and caspase-8 cleavage and cell apoptosis, leading to a neural tube defect reduction. Reversal of maternal diabetes mellitus-inhibited miR-322 via transgenic overexpression prevented TRAF3 up-regulation in embryos exposed to maternal diabetes mellitus. Activated IRE1α acted as an endonuclease and degraded precursor miR-322, resulting in mature miR-322 reduction. CONCLUSION: This study supports the crucial role of the IRE1α-microRNA-TRAF3 circuit in the induction of neuroepithelial cell apoptosis and neural tube defect formation in pregnancies complicated by diabetes mellitus and identifies IRE1α and miR-322 as potential targets for preventing maternal diabetes mellitus-induced neural tube defects.

Glycemic control and neonatal outcomes in twin pregnancies with gestational diabetes mellitus.

BACKGROUND: Preliminary data suggest that strict glycemic control in twin pregnancies with gestational diabetes mellitus may not improve outcomes but might increase the risk of fetal growth restriction. OBJECTIVE: This study aimed to investigate the association of maternal glycemic control with the risk of gestational diabetes mellitus-related complications and small for gestational age in twin pregnancies complicated by gestational diabetes mellitus. STUDY DESIGN: This was a retrospective cohort study of all patients with a twin pregnancy complicated by gestational diabetes mellitus in a single tertiary center between 2011 and 2020, and a matched control group of patients with a twin pregnancy without gestational diabetes mellitus in a 1:3 ratio. The exposure was the level of glycemic control, described as the proportion of fasting, postprandial, and overall glucose values within target. Good glycemic control was defined as a proportion of values within target above the 50th percentile. The first coprimary outcome was a composite variable of neonatal morbidity, defined as at least 1 of the following: birthweight >90th centile for gestational age, hypoglycemia requiring treatment, jaundice requiring phototherapy, birth trauma, or admission to the neonatal intensive care unit at term. A second coprimary outcome was small for gestational age, defined as birthweight <10th centile or <3rd centile for gestational age. Associations between the level of glycemic control and the study outcomes were estimated using logistic regression analysis and were expressed as adjusted odds ratio with 95% confidence interval. RESULTS: A total of 105 patients with gestational diabetes mellitus in a twin pregnancy met the study criteria. The overall rate of the primary outcome was 32.4% (34/105), and the overall proportion of pregnancies with a small for gestational age newborn at birth was 43.8% (46/105). Good glycemic control was not associated with a reduction in the risk of composite neonatal morbidity when compared with suboptimal glycemic control (32.1% vs 32.7%; adjusted odds ratio, 2.06 [95% confidence interval, 0.77-5.49]). However, good glycemic control was associated with higher odds of small for gestational age compared with nongestational diabetes mellitus pregnancies, especially in the subgroup of diet-treated gestational diabetes mellitus (65.5% vs 34.0%, respectively; adjusted odds ratio, 4.17 [95% confidence interval, 1.74-10.01] for small for gestational age <10th centile; and 24.1% vs 7.0%, respectively; adjusted odds ratio, 3.97 [95% confidence interval, 1.42-11.10] for small for gestational age <3rd centile). In contrast, the rate of small for gestational age in gestational diabetes mellitus pregnancies with suboptimal control was not considerably different when compared with non-gestational diabetes mellitus pregnancies. In addition, in cases of diet-treated gestational diabetes mellitus, good glycemic control was associated with a left-shift of the distribution of birthweight centiles, whereas the distribution of birthweight centiles among gestational diabetes mellitus pregnancies with suboptimal control was similar to that of nongestational diabetes mellitus pregnancies. CONCLUSION: In patients with gestational diabetes mellitus in a twin pregnancy, good glycemic control is not associated with a reduction in the risk of gestational diabetes mellitus-related complications but may increase the risk of a small for gestational age newborn in the subgroup of patients with mild (diet-treated) gestational diabetes mellitus. These findings further question whether the gestational diabetes mellitus glycemic targets used in singleton pregnancies also apply to twin pregnancies and support the concern that applying the same diagnostic criteria and glycemic targets in twin pregnancies may result in overdiagnosis and overtreatment of gestational diabetes mellitus and potential neonatal harm.

Diabetic ketoacidosis in pregnancy.

The clinical presentation of diabetic ketoacidosis (DKA) includes nausea, vomiting, thirst, polyuria, polydipsia, abdominal pain, tachypnoea, and change in mental status in cases of severe DKA. DKA is similar in pregnant and non-pregnant women, but in pregnant women it can be seen at lower serum glucose levels and symptoms may develop more rapidly. Most, but not all, cases occur in the second or third trimester.DKA results in reduction in uteroplacental blood flow due to osmotic diuresis, and also in metabolic abnormalities (maternal acidosis, hyperglycaemia, electrolyte imbalance), resulting in fetal hypoxaemia and acidosis. In fetuses with mature cardiac activity, the fetal heart rate may show minimal or absent variability, repetitive deceleration and absence of acceleration. These abnormalities in heart rate usually resolve with resolution of the DKA, which may last for several hours before normalisation.For the patient reported on here, immediate delivery based on pathological fetal heart rate would have resulted in preterm delivery and jeopardised the maternal clinical condition. However, a holistic clinical approach by the multidisciplinary team to management of the patient led to normal term delivery 5 weeks after presentation with DKA; fetal and maternal outcome were good.

Maternal obesity, diabetes, preeclampsia, and asthma during pregnancy and likelihood of autism spectrum disorder with gastrointestinal disturbances in offspring.

LAY ABSTRACT: Autism spectrum disorder is heterogeneous and often accompanied by co-occurring conditions. Previous studies have shown that maternal health conditions during pregnancy including obesity, diabetes, preeclampsia, and asthma were associated with increased likelihood of autism. However, little has been done examining the likelihood associated with autism with co-occurring conditions. This study assessed these maternal health conditions in relationship to autism and gastrointestinal disturbances, a common co-occurring condition in children diagnosed with autism. Data included 308,536 mother-child pairs from one integrated health care system with comprehensive electronic medical records. Among the study cohort, 5,131 (1.7%) children had a diagnosis of autism by age 5. Gastrointestinal disturbances were present in 35.4% of children diagnosed with autism and 25.1% of children without autism diagnoses. Our results showed that each of the four maternal health conditions during pregnancy was associated with increased likelihood of gastrointestinal disturbances, autism without gastrointestinal disturbances, and autism with gastrointestinal disturbances. For all four maternal health conditions, the association was greatest for likelihood of autism with gastrointestinal disturbances. Given that children diagnosed with autism are more likely to have gastrointestinal disturbances and over 80% of gastrointestinal disturbances in this cohort were diagnosed prior to autism diagnosis, this study suggests that there may be common biological pathways between autism and gastrointestinal disturbances impacted by these maternal exposures. Future studies are warranted to assess associations between different exposures and autism with other co-occurring conditions to increase our understanding of autism heterogeneity.

Characteristics of pregnant women with diabetes using injectable glucose-lowering drugs in the EVOLVE study.

AIMS: To examine clinical parameters, glycemic control, folic acid supplementation, and the presence of other chronic diseases during early pregnancy in the EVOLVE study population (women with pre-existing diabetes treated with injectable glucose-lowering drugs). METHODS: Cross-sectional baseline evaluation of EVOLVE: an international, multicenter, non-interventional study investigating the safety of injectable glucose-lowering drugs in pregnant women with pre-existing type 1 (T1D) or type 2 diabetes (T2D). Data were collected at enrollment visit interviews before gestational week 16. RESULTS: In total, 2383 women from 17 mainly European countries were enrolled in the study: 2122 with T1D and 261 with T2D; mean age was 31 and 33 years, and duration of diabetes was 15 and 6 years, respectively. For women with T1D or T2D, 63% and 75%, respectively, received basal and rapid-acting insulin, 36% and 3% rapid-acting insulin only, 0.7% and 14.0% basal insulin only, 0.2% and 5.4% premix insulin, 0.0% and 1.2% injectable glucagon-like peptide-1 receptor agonist treatment without insulin. In women with T1D or T2D, respectively, during early pregnancy, 59% and 62% had HbA1c <7.0% (53 mmol/mol); 16% and 36% reported not taking folic acid before or during early pregnancy. Overall, >40% of women had ≥1 chronic concomitant condition (predominantly thyroid disease or hypertension). Retinopathy was the most commonly reported diabetic complication. The most commonly reported previous pregnancy complication was miscarriage. CONCLUSIONS: Baseline data from this large multinational population of women with pre-existing diabetes indicate that sub-optimal glycemic control, poor pregnancy planning, and chronic concomitant conditions were common in early pregnancy.

Interaction between Metformin, Folate and Vitamin B12 and the Potential Impact on Fetal Growth and Long-Term Metabolic Health in Diabetic Pregnancies.

Metformin is the first-line treatment for many people with type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to maintain glycaemic control. Recent evidence suggests metformin can cross the placenta during pregnancy, thereby exposing the fetus to high concentrations of metformin and potentially restricting placental and fetal growth. Offspring exposed to metformin during gestation are at increased risk of being born small for gestational age (SGA) and show signs of 'catch up' growth and obesity during childhood which increases their risk of future cardiometabolic diseases. The mechanisms by which metformin impacts on the fetal growth and long-term health of the offspring remain to be established. Metformin is associated with maternal vitamin B12 deficiency and antifolate like activity. Vitamin B12 and folate balance is vital for one carbon metabolism, which is essential for DNA methylation and purine/pyrimidine synthesis of nucleic acids. Folate:vitamin B12 imbalance induced by metformin may lead to genomic instability and aberrant gene expression, thus promoting fetal programming. Mitochondrial aerobic respiration may also be affected, thereby inhibiting placental and fetal growth, and suppressing mammalian target of rapamycin (mTOR) activity for cellular nutrient transport. Vitamin supplementation, before or during metformin treatment in pregnancy, could be a promising strategy to improve maternal vitamin B12 and folate levels and reduce the incidence of SGA births and childhood obesity. Heterogeneous diagnostic and screening criteria for GDM and the transient nature of nutrient biomarkers have led to inconsistencies in clinical study designs to investigate the effects of metformin on folate:vitamin B12 balance and child development. As rates of diabetes in pregnancy continue to escalate, more women are likely to be prescribed metformin; thus, it is of paramount importance to improve our understanding of metformin's transgenerational effects to develop prophylactic strategies for the prevention of adverse fetal outcomes.

Detemir vs neutral protamine Hagedorn insulin for diabetes mellitus in pregnancy: a comparative effectiveness, randomized controlled trial.

BACKGROUND: Insulin detemir, being used increasingly during pregnancy, may have pharmacologic benefits compared with neutral protamine Hagedorn. OBJECTIVE: We evaluated the probability that compared with treatment with neutral protamine Hagedorn, treatment with insulin detemir reduces the risk for adverse neonatal outcome among individuals with type 2 or overt type 2 diabetes mellitus (gestational diabetes mellitus diagnosed at <20 weeks' gestation). STUDY DESIGN: We performed a multiclinic randomized controlled trial (September 2018 to January 2020), which included women with singleton gestation with type 2 or overt type 2 diabetes mellitus who sought obstetrical care at ≤21 weeks' gestation. Participants were randomized to receive either insulin detemir or neutral protamine Hagedorn by a clinic-stratified scheme. The primary outcome was a composite of adverse neonatal outcomes, including shoulder dystocia, large for gestational age, neonatal intensive care unit admission, respiratory distress (defined as the need of at least 4 hours of respiratory support with supplemental oxygen, continuous positive airway pressure or ventilation at the first 24 hours of life), or hypoglycemia. The secondary neonatal outcomes included gestational age at delivery, small for gestational age, 5-minute Apgar score of <7, lowest glucose level, need for intravenous glucose, respiratory distress syndrome, need for mechanical ventilation or continuous positive airway pressure, neonatal jaundice requiring therapy, brachial plexus injury, and hospital length of stay. The secondary maternal outcomes included hypoglycemic events, hospital admission for glucose control, hypertensive disorder of pregnancy, maternal weight gain, cesarean delivery, and postpartum complications. We used the Bayesian statistics to estimate a sample size of 108 to have >75% probability of any reduction in the primary outcome, assuming 80% power and a hypothesized effect of 33% reduction with insulin detemir. All analyses were intent to treat under a Bayesian framework with neutral priors (a priori assumed a 50:50 likelihood of either intervention being better; National Clinical Trial identifier 03620890). RESULTS: There were 108 women randomized in this trial (57 in insulin detemir and 51 in neutral protamine Hagedorn), and 103 women were available for analysis of the primary outcome (n=5 for pregnancy loss before 24 weeks' gestation). Bayesian analysis indicated an 87% posterior probability of reduced primary outcome with insulin detemir compared with neutral protamine Hagedorn (posterior adjusted relative risk, 0.88; 95% credible interval, 0.61-1.12). Bayesian analyses for secondary outcomes showed consistent findings of lower adverse maternal outcomes with the use of insulin detemir vs neutral protamine Hagedorn: for example, maternal hypoglycemic events (97% probability of benefit; posterior adjusted relative risk, 0.59; 95% credible interval, 0.29-1.08) and hypertensive disorders (88% probability of benefit; posterior adjusted relative risk, 0.81; 95% credible interval, 0.54-1.16). CONCLUSION: In our comparative effectiveness trial involving individuals with type 2 or overt type 2 diabetes mellitus, use of insulin detemir resulted in lower rates of adverse neonatal and maternal outcomes compared with neutral protamine Hagedorn.

Is the erythropoietin-erythroferrone-hepcidin axis intact in human neonates?

In a two-part process, we assessed elements of the principal hormonal pathway regulating iron homeostasis in human neonates. Part 1: Quantifying erythropoietin (Epo), erythroferrone (ERFE), hepcidin, and relevant serum and erythrocytic iron-related metrics in umbilical cord blood from term (n = 13) and preterm (n = 10) neonates, and from neonates born to mothers with diabetes and obesity (n = 13); Part 2: Quantifying serum Epo, ERFE, and hepcidin before and following darbepoetin administration. Part 1: We measured Epo, ERFE and hepcidin in all cord blood samples. Epo and ERFE levels did not differ between the three groups. Preterm neonates had the lowest hepcidin levels, while neonates born to diabetic women with a very high BMI had the lowest ferritin and RET-He levels. Part 2: Following darbepoetin dosing, ERFE levels generally increased (p < 0.05) and hepcidin levels generally fell (p < 0.05). Our observations suggest that the Epo/ERFE/hepcidin axis is intact in the newborn period.

Evaluation of the Effects of Delayed Cord Clamping in Infants of Diabetic Mothers.

OBJECTIVE: This study aimed to investigate the effect of delayed cord clamping (DCC) in infants of diabetic mothers. STUDY DESIGN: Women who had diabetes throughout their pregnancy and gave birth at 37 weeks of gestation or later were included in the study along with their babies. Early cord clamping was performed as soon as possible after birth, while DCC was performed by clamping 60 second after birth. The two groups were compared in terms of venous hematocrit (htc) levels and rates of hypoglycemia, jaundice requiring phototherapy, and respiratory distress. RESULTS: Venous htc levels at postnatal 6 and 24 hours were significantly higher in the DCC group (p = 0.0001). Polycythemia rates were higher in the DCC group at both 6 and 24 hours, but partial exchange transfusion (PET) was not needed in either group. There were no differences between the groups with regard to the rates of hypoglycemia or jaundice requiring phototherapy. Rate of admission to the neonatal intensive care unit (NICU) was lower in the DCC group. CONCLUSION: Although DCC increased the rate of polycythemia, it did not result in PET requirement. Moreover, DCC reduced the severity of respiratory distress and the rate of admission to NICU due to respiratory distress.

In vivo: maternal betaine supplementation normalized fetal growth in diabetic pregnancy.

PURPOSE: Diabetes alters maternal metabolism and can lead to aberrant fetal growth. In addition to insulin treatment, nutritional diet interventions are recommended for promoting fetal health against diabetes-induced adverse effects. Therefore, we conducted an in vivo study to investigate betaine efficacy on fetal development against maternal diabetes. METHODS: Thirty-two dams were divided into four equal groups: control (C), betaine supplementation (BS), diabetic pregnancy (DP) and diabetic pregnancy plus betaine supplementation (DP + BS). Fasting blood sugar (FBS) and body weight (BW) were monitored during pregnancy. After physiological delivery, dams glycated hemoglobin (HbA1c) concentrations were measured, followed by fetal development indices including litter size (LS), neonatal weight (NW) and crown-rump (CR). Also, maternal oxidative status was assessed by evaluating glutathione (GSH) content, glutathione peroxidase (GSH-Px) and catalase (CAT) activities, and malondialdehyde (MDA) concentration in the erythrocytes. RESULTS: Betaine supplementation significantly alleviated FBS and tended to recover BW loss. It also significantly decreased HbA1c values in dams of DP + BS compared to DP group. Normalized fetal indices such as LS, NW and CR under betaine supplementation were associated with a significant increase in GSH content and GSH-Px activity, as well as decreased MDA concentrations in erythrocytes of dams in the DP + BS versus the DP group, indicating improved redox balance in the dams. CONCLUSION: We indicated for the first time that betaine supplementation improved the maternal glucose metabolism and redox balance associated with normalized fetal growth. Nevertheless, further studies are required to investigate the mechanisms through which betaine protects fetal growth in diabetic pregnancy.

An overview of the management of diabetes from pre-conception, during pregnancy and in the postnatal period.

Diabetes is one of the most common medical conditions complicating pregnancy. Both pre-existing diabetes and gestational diabetes are associated with increased risks to the mother and fetus. These risks can be reduced by improving pre-conception and antenatal care. Pre-conception planning and care is important to ensure women are taking high dose folic acid, to optimise glucose control, to review medications and to screen for and manage any complications. All women with either pre-existing diabetes or gestational diabetes should be reviewed by the antenatal team every 1-2 weeks throughout pregnancy. This is to optimise glucose control and to monitor fetal growth and development. Women with diabetes in pregnancy should receive an individualised care plan for delivery. The exact timing of delivery will depend on maternal glucose control, fetal growth and any other complications. Women diagnosed with gestational diabetes in pregnancy are at high risk of developing both gestational diabetes and type 2 diabetes in the future. After delivery, they should be offered a fasting plasma glucose at 6 weeks or a glycated haemoglobin (HbA1c) at 13 weeks to ensure that the gestational diabetes has resolved and an annual HbA1c.

Progress in Development of Interventions to Prevent Birth Defects in Diabetic Pregnancies.

Diabetic embryopathy is a diabetic complication, in which maternal hyperglycemia in early pregnancy causes birth defects in newborn infants. Under maternal diabetic conditions, hyperglycemia disturbs intracellular molecular activities and organelles functions. These include protein misfolding in the endoplasmic reticulum (ER), overproduction of reactive oxygen species (ROS) in mitochondria, and high levels of nitric oxide (NO). The resultant ER, oxidative, and nitrosative stresses activate apoptotic machinery to cause cell death in the embryo, ultimately resulting in developmental malformations. Based on the basic research data, efforts have been made to develop interventional strategies to alleviate the stress conditions and to reduce embryonic malformations. One of the challenges in birth defect prevention is to identify effective and safe agents to be used in pregnancy. One approach is to search and characterize naturally occurring phytochemicals, including flavonoids, curcuminoids and stilbenoids, for use in prevention of diabetic embryopathy.

In-hospital formula supplementation and breastfeeding initiation in infants born to women with pregestational diabetes mellitus.

OBJECTIVE: To ascertain the rate of in-hospital supplementation as it relates to early breastfeeding (BF) and early formula feeding (FF) and its effects on BF (exclusive and partial) at the time of discharge for infants born to women with pregestational diabetes mellitus (PGDM). METHODS: Retrospective cohort investigation of 282 women with PGDM who intended to BF and their asymptomatic infants admitted to the newborn nursery for blood glucose monitoring and routine care. Early feeding was defined by the initial feeding if given within four hours of birth. RESULTS: Of the 282 mother-infant dyads, for 134 (48%) early feeding was BF and for 148 (52%) early feeding was FF. Times from birth to BF and FF (median 1 hr, 0.3-6) were similar, while the time to first BF for those who FF and supplemented was longer (median 6 hr., 1-24). Ninety-seven infants (72%) who first BF also supplemented. Of these, 22 (23%) BF exclusively, 67 (69%) BF partially and 8 (8%) FF at discharge. One hundred seventeen (79%) who first FF also supplemented. Of these, 21 (18%) BF exclusively, 76 (65%) BF partially and 20 (17%) FF at discharge. CONCLUSION: Regardless of the type of first feeding, the majority of infants born to women with PGDM require supplementation. Even when medically indicated, in-hospital supplementation is an obstacle, albeit not absolute, to exclusive BF at discharge. Parents should be reminded that occasional supplementation should not deter resumption and continuation of BF.

The effects of expressing antenatal colostrum in women with diabetes in pregnancy: A retrospective cohort study.

BACKGROUND: Some women with diabetes in pregnancy express and store colostrum in the antenatal period for the purposes of preventing and treating neonatal hypoglycaemia. AIMS: Our primary aim was to compare rates of neonatal hypoglycaemia in babies born to mothers who express and store antenatal colostrum to babies born to mothers who do not. MATERIALS AND METHODS: Retrospective cohort study involving 357 women with diabetes in pregnancy, who had live, singleton births delivered after 36 weeks gestation, in a regional hospital in North Queensland (2014-2015). Multivariable binary logistic regression modelling identified independent characteristics associated with primary outcomes. RESULTS: Eighty women (23%) expressed antenatal colostrum and 223 (62%) did not. One hundred and thirty-one babies (37%) were diagnosed with hypoglycaemia. Aboriginal and Torres Strait Islander women were less likely to express than Caucasian women (odds ratio (OR) 0.10, 95% confidence interval (CI) 0.01-0.77). There were no significant differences in the rates of hypoglycaemia, or median blood glucose levels in babies born to mothers who expressed antenatal colostrum compared to babies born to mothers who did not express. Babies born to mothers who expressed were significantly less likely to receive formula in hospital compared to babies born to mothers who did not (OR 0.12, 95% CI 0.05-0.32). CONCLUSIONS: We found no independent association of expressing antenatal colostrum on rates of neonatal hypoglycaemia or median blood glucose levels. Expressing antenatal colostrum may have some benefits to the newborn such as reduced formula consumption in hospital. Further research into other methods of reducing neonatal hypoglycaemia appears warranted.

Comparing outcomes of nutrition therapy, insulin and oral anti-diabetics in managing diabetes mellitus in Pregnancy: Retrospective study and review of current guidelines.

AIMS: This study aims to evaluate the glycemic profile and outcomes of Indonesian diabetic pregnant mothers based on their methods of therapy and review current international as well as national guidelines on management of diabetes in pregnancy. MATERIALS AND METHODS: Data was obtained from medical records of Hermina-Podomoro Hospital. Subjects were grouped based on therapy - nutrition therapy only, insulin and oral anti-diabetics group. RESULTS: Forty-five subjects were obtained with an average age of 31-years. Around thirty-five percent of patients were given nutrition therapy only, 55.6% were using insulin and 8.8% were using oral anti-diabetics. Oral anti-diabetics users showed worse glycemic profile among the three groups. Six-patients suffered from IUFD with the highest proportion found in oral anti-diabetics users. CONCLUSION: The above results show the negative impacts of DM on pregnant mothers and the unborn. Caution is advised on the use of oral anti-diabetics as it may increase the risk of infant mortality. Increased monitoring and prenatal services for DM patients are essential in achieving blood glucose targets.

Perspectives and experiences of collecting antenatal colostrum in women who have had diabetes during pregnancy: a North Queensland semistructured interview study.

OBJECTIVES: To explore and describe the experiences and perspectives of collecting and storing colostrum in the antenatal period in women who have had diabetes in pregnancy. DESIGN: Face-to-face, semistructured interviews analysed with purposive sampling and thematic analysis. SETTING: A regional hospital in North Queensland with a high prevalence of diabetes in pregnancy. PARTICIPANTS: Six women with a previous pregnancy complicated by diabetes who were advised to collect and store colostrum in pregnancy. RESULTS: Six themes were identified: wariness of medicalisation (adjusting to an 'abnormal' pregnancy, seeking continuity of care, determination to reduce formula, fear of invasive intervention); underlying altruism (providing the best for baby, preparing for complications, eager for milk donation); internal pressure to succeed (coping with confronting information, disheartened by failures, constant fear of insufficient supply, overwhelming guilt, concern for future breastfeeding success); self-management and ownership (adapting to awkwardness, developing strategies for success, actively seeking education, gaining confidence to request help, accepting personal limitations); frustrated by waste (encroaching on time, squandering a precious resource, ambiguous about necessity) and building fortitude for motherhood (physically preparing for breast feeding, symbolic of the imminent infant, establishing early relationships with supports, approaching challenges with realistic optimism). CONCLUSION: Women with diabetes in pregnancy experience guilt and stress about the added risk of hypoglycaemia to their babies and strive to provide the best for their babies by collecting and storing colostrum, even if this leads to distress to themselves. It is crucial that these women be provided accurate, realistic advice about the benefits and disadvantages of collecting colostrum in the antenatal period.

A aceitação da medicina alternativa complementar por gestantes com diabetes / Acceptance of additional alternative medicine by pregnant diabetics

Objetivo: avaliar como as mulheres grávidas com diabetes compreendem e aceitam o uso de práticas integrativas e complementares na saúde, especialmente o Reiki, durante o atendimento pré-natal. Método: trata-se de um estudo qualitativo, descritivo, exploratório, de gestantes diabéticas atendidas num Centro de Investigação do Diabetes Perinatal em um centro terciário, por meio de entrevistas semiestruturadas com 12 gestantes. Audiogravaram-se e transcreveram-se as entrevistas para posterior análise cujos dados foram submetidos à técnica de Análise de Conteúdo. Resultados: demonstrou-se, pela maioria das mulheres gestantes diagnosticadas com diabetes, o conhecimento de algumas práticas integrativas e complementares na saúde. Receber-se-iam, além disso, por um grande número de entrevistadas, tais terapias se essas fossem disponíveis no Sistema Único de Saúde (SUS), porém, a terapia Reiki mostrou ser desconhecida entre as pacientes. Conclusão: serve-se este estudo como ponto de partida para profissionais de saúde introduzirem as terapias integrativas e complementares na saúde pública brasileira. Tornam-se necessários estudos adicionais em outras populações para obter uma visão mais profunda e detalhada do perfil das pacientes em diferentes regiões.(AU)

Objective: to evaluate how pregnant women with diabetes understand and accept the use of integrative and complementary health practices, especially Reiki, during prenatal care. Method: this is a qualitative, descriptive, exploratory study of diabetic pregnant women seen at a Perinatal Diabetes Research Center in a tertiary center, through semi-structured interviews with 12 pregnant women. The interviews were audio recorded and transcribed for later analysis whose data were submitted to the Content Analysis technique. Results: it was demonstrated, by most pregnant women diagnosed with diabetes, the knowledge of some integrative and complementary practices in health. In addition, a large number of respondents would receive such therapies if they were available in the Unified Health System (UHS), but Reiki therapy was unknown to patients. Conclusion: this study serves as a starting point for health professionals to introduce integrative and complementary therapies in Brazilian public health. Further studies in other populations are needed to gain a deeper and more detailed view of patients' profiles in different regions.(AU)

Objetivo: evaluar cómo las mujeres embarazadas con diabetes entienden y aceptan el uso de prácticas de salud integradoras y complementarias en salud, especialmente el Reiki, durante la atención prenatal. Método: este es un estudio cualitativo, descriptivo, exploratorio de mujeres embarazadas diabéticas atendidas en un Centro de Investigación de Diabetes Perinatal en un centro terciario, a través de entrevistas semiestructuradas con 12 mujeres embarazadas. Las entrevistas se grabaron en audio y se transcribieron para un análisis posterior cuyos datos fueron sometidos a la técnica de Análisis de Contenido. Resultados: la mayoría de las mujeres embarazadas diagnosticadas con diabetes demostraron el conocimiento de algunas prácticas integradoras y complementarias en salud. Además, un gran número de encuestados recibiría tales terapias si estuvieran disponibles en el Sistema Único de Salud (SUS), pero la terapia de Reiki era desconocida para los pacientes. Conclusión: este estudio sirve como punto de partida para que los profesionales de la salud introduzcan terapias integradoras y complementarias en la salud pública brasileña. Se necesitan más estudios en otras poblaciones para obtener una visión más profunda y detallada de los perfiles de los pacientes en diferentes regiones.(AU)

Dietary vitamin and mineral intakes in a sample of pregnant women with either gestational diabetes or type 1 diabetes mellitus, assessed in comparison with Polish nutritional guidelines.

OBJECTIVES: Maintaining proper nutrition during pregnancy is crucial for pregnant women and especially for who have been diagnosed with type 1 diabetes mellitus (T1DM) or who develop gestational diabetes mellitus (GDM). MATERIAL AND METHODS: To measure differences in vitamin and mineral intakes among women with normal pregnancies, pregnant women with GDM, and pregnant women with pre-gestational T1DM; and to assess the women's dietary intakes in comparison with Polish nutritional guidelines. The analysis was conducted among 83 pregnant women (29 GDM patients, 26 T1DM patients and 28 normal pregnancy participants) from whom we collected seven-day 24-hour dietary records during the second part of their pregnancies. RESULTS: There were no statistically significant differences observed for most of the vitamin and mineral intakes across the three groups. However, we did observe a significant difference in the vitamin C and calcium intakes between groups. The mean vitamin C and calcium intakes were significantly higher in the control group than among the diabetic patients. Insufficient dietary calcium intakes were found among 52.3% of the GDM patients and 61.6% of the T1DM participants, while only 28.6% of the normal pregnancy patients experienced a calcium deficiency. The highest incidence of inadequate intake in each of the GDM, T1DM and control groups was observed for vitamin D (100%, 100%, 100%), folate (97.7%, 100%, 100%), iron (97.7%, 100%, 100%), and iodine (97.7%, 92.4%, 85.7%), respectively. CONCLUSIONS: Diet alone may not be enough to provide adequate levels of vitamins and minerals for most micronutrients. Supplement use reduces the risk of inadequate intake for many micronutrients, but diet-related issues during pregnancy and pregnancy diagnosed with diabetes remain, and they deserve to be addressed during public health interventions.

The effect of different forms of dysglycemia during pregnancy on maternal and fetal outcomes in treated women and comparison with large cohort studies.

AIMS OF THE STUDY: We describe the impact of different forms of dysglycemia on maternal and neonatal health. This research is a part of the PEARL-Peristat Maternal and newborn registry, funded by Qatar National Research Fund (QNRF) Doha, Qatar. METHODS: A population-based retrospective data analysis of 12,255 women with singleton pregnancies screened during the year 2016-2017, of which 3,027 women were identified with gestation diabetes mellitus (GDM) during pregnancy and 233 were diabetic before pregnancy. Data on maternal outcome was collected from the PEARL-Peristat Maternal and newborn registry. RESULTS: The prevalence of GDM and diabetes mellitus (DM) was 24.7 % and 1.9%, respectively. 55% of DM, 38% of GDM and 25.6% of controls were obese (p<0.001). 71% of pregnant women with DM and 57.8% of those with GDM were older than 30 years versus 44.2% of controls. Pregnant women with DM or GDM had higher prevalence of hypertension versus normal controls (9.9%, 5.5% and 3.5%, respectively; p<0.001). Among women with vaginal deliveries, the proportion of women with induction of labor was significantly higher in the DM and GDM compared to control subjects (33.9%, 26.5% and 12.4%, respectively; p<0.001). The number of women who underwent Cesarean section was significantly higher in the DM and GDM groups versus normal controls (51.9%, 36.8%, and 28.5%, respectively; p<0.001).  Preterm delivery was significantly higher in women with DM and GDM (13.7% and 9%, respectively versus normal women (6.4%); p<0.001). Babies of DM and GDM had significantly higher occurrence of respiratory distress (RDS) or transient tachypnea (TTS): 9% and 5.8 % versus normal controls (4.8%). Macrosomia was more prevalent in babies of DM (6.4%) and GDM (6.8%) compared to controls (5%) (p: <0.001). Significant hypoglycemic episodes occurred more frequently in babies of DM and GDM women (11.2% and 3%, respectively) versus controls (0.6%) (p: <0.001. Infants of DM and GDM mothers required more treatments of phototherapy (9.4% and 8.9%, respectively) versus those born to normal women (7.2%) (p: 0.006). The prevalence of congenital anomalies and neonatal death did not differ between the groups. CONCLUSIONS: Despite the improvement in the prenatal diagnosis and management of dysglycemia, there is still a higher prevalence of prematurity, macrosomia, and hypoglycemia in infants of mothers with DM and GDM. Measurements to reduce obesity and control dysglycemia in women during the childbearing period are highly required to prevent the still higher morbidity during pregnancy.

Is post exposure prevention of teratogenic damage possible: Studies on diabetes, valproic acid, alcohol and anti folates in pregnancy: Animal studies with reflection to human.

We discuss the possibilities to prevent the post-exposure teratogenic effects of several teratogens: valproic acid (VPA), diabetes and alcohol. Co-administration of folic acid with VPA reduced the rate of Neural Tube Defects (NTD) and other anomalies in rodents, but apparently not in pregnant women. Antioxidants or the methyl donor S-adenosyl methionine prevented Autism Spectrum Disorder (ASD) like behavior in mice and rats. In vivo and in vitro studies demonstrated that antioxidants, arachidonic acid, myoinositol and nutritional agents may prevent diabetes-embryopathy. Prevention of alcohol-induced embryonic and fetal injuries and neurodevelopmental deficits was achieved by supplementation of zinc, choline, vasoactive intestinal proteins (VIP related peptides), antioxidants and folic acid. While the animal research described in this review is indicative of possible preventions of the different teratogenic effects, this is not yet the focus in human research. Future research should promote further knowledge where our current understanding is the vaguest, human prevention.