Diabetes mellitus e saúde materna durante a pandemia de covid-19 no Brasil / Diabetes mellitus and maternal health during the COVID-19 pandemic in Brazil / Diabetes mellitus y salud materna durante la pandemia de la COVID-19 en Brasil

A pandemia do novo coronavírus (covid-19) é um grave problema de saúde pública. Adicionalmente, a hiperglicemia na gestação (diabetes preexistente, diabetes diagnosticado pela primeira vez na gestação e diabetes mellitus gestacional) é uma das complicações maternas mais frequentes na população obstétrica. A sobreposição desses problemas pode refletir na saúde materna e fetal. Desse modo, o objetivo deste estudo é reunir evidências acerca da saúde materna de mulheres com hiperglicemia na gestação durante a pandemia de covid-19 no Brasil. Trata-se de uma revisão narrativa, em que a fonte de dados compreendeu artigos publicados até maio de 2023 nas bases de dados Medline, via PubMed, Lilacs e WHO COVID-19 Research Database. Foram listados 167 artigos e, após a aplicação dos critérios de elegibilidade, cinco estudos foram incluídos, compreendendo 1.469 gestantes e puérperas com diabetes mellitus gestacional ou diabetes preexistente. Quanto à saúde materna, os principais desfechos foram relacionados à infecção por covid-19, como gravidade da doença e risco de morte. Além disso, foi observada maior prevalência de transtornos mentais comuns, como ansiedade e depressão. Portanto, a saúde materna de mulheres com hiperglicemia na gestação foi impactada negativamente durante a pandemia de covid-19 no país.

The new coronavirus (COVID-19) pandemic is a major public health issue. Hyperglycemia during pregnancy (pre-existing diabetes, diabetes first diagnosed in pregnancy and gestational diabetes mellitus) is a frequent maternal complication in the obstetric population. Their overlap may impact maternal and fetal health. Thus, this narrative review gathered evidence on the maternal health of women with gestational hyperglycemia during the COVID-19 pandemic in Brazil. Articles published until May 2023 in the Medline (via PubMed), Lilacs and WHO COVID-19 Research Database online databases were eligible. Bibliographic search retrieved a total of 167 articles, of which five remained after applying the inclusion criteria, resulting in a sample of 1,469 pregnant and postpartum women with gestational diabetes or pre-existing diabetes. Regarding maternal health, the main outcomes were related to COVID-19 infection, such as disease severity and risk of death. Additionally, results showed a higher prevalence of common mental disorders such as anxiety and depression. In conclusion, the maternal health of women with gestational hyperglycemia was negatively impacted during the COVID-19 pandemic.

La pandemia del nuevo coronavirus (COVID-19) es un grave problema de salud pública. Además, la hiperglucemia durante el embarazo (diabetes preexistente, diabetes diagnosticada por primera vez durante el embarazo y diabetes mellitus gestacional) es una de las complicaciones maternas más frecuentes en la población obstétrica. La superposición de estos problemas puede afectar la salud materna y fetal. Por lo tanto, el objetivo de este estudio es recopilar evidencia sobre la salud materna de las mujeres con hiperglucemia en el embarazo durante la pandemia de la COVID-19 en Brasil. Se trata de una revisión narrativa, y la fuente de datos comprendió artículos publicados hasta mayo de 2023 en las bases de datos MEDLINE vía PubMed, LILACS y WHO COVID-19 Research Database. Se enumeró un total de 167 artículos y, después de aplicar los criterios de elegibilidad, se incluyeron cinco estudios con 1.469 mujeres embarazadas y puérperas con diabetes gestacional o diabetes preexistente. En cuanto a la salud materna, los principales resultados se relacionaron con el contagio por COVID-19, como la gravedad de la enfermedad y el riesgo de muerte. Además, se observó una mayor prevalencia de trastornos mentales comunes, como la ansiedad y la depresión. Por lo tanto, la salud materna de las mujeres con hiperglucemia durante el embarazo se ha visto afectada negativamente durante la pandemia de la COVID-19 en Brasil.

The presence of polycystic ovary syndrome increases the risk of maternal but not neonatal complications in women with type 2 diabetes in pregnancy.

AIMS: Our aims were, in the setting of type 2 diabetes mellitus (T2DM) in pregnancy, to investigate the association of polycystic ovary syndrome (PCOS) with perinatal outcomes and to examine whether treatment with metformin had a differential effect in those with and without PCOS. MATERIALS AND METHODS: We performed a retrospective cohort study using the metformin in women with type 2 diabetes in pregnancy (MiTy) trial data. We examined differences in maternal and neonatal outcomes among MiTy participants with and without PCOS using linear and logistic regression to adjust for potential confounders. We additionally examined the relative difference in the effect of metformin treatment on pregnancy outcomes among MiTy participants with PCOS versus those without PCOS. RESULTS: Among women with T2DM in pregnancy, PCOS was significantly associated with higher excess gestational weight gain (unadjusted 12.0 vs. 11.4 kg, adjusted mean difference 2.1 kg [0.3, 3.9], p = 0.021) and higher total insulin dose at 34-36 weeks (unadjusted 172 vs. 124 units per day, adjusted mean difference 44 units [15, 73], p = 0.004), but no difference was seen in neonatal outcomes. Unlike the non-PCOS subgroup, metformin treatment versus placebo in the PCOS subgroup was associated with an increase in extremely large-for-gestational-age infants (28.6 vs. 14.0%, p = 0.008 for interaction) and an increase in worsened pre-existing maternal hypertension (16.7 vs. 4.5%, p = 0.046 for interaction). CONCLUSIONS: Clinicians should be alerted to the potential for high insulin requirements and excess weight gain in pregnant patients with T2DM and comorbid PCOS. Moreover, metformin may not be as beneficial in this population as previously understood.

The Benefits Of Continuous Glucose Monitoring In Pregnancy.

Previous studies have consistently demonstrated the positive effects of continuous glucose monitoring (CGM) on glycemic outcomes and complications of diabetes in people with type 1 diabetes. Guidelines now consider CGM to be an essential and cost-effective device for managing type 1 diabetes. As a result, insurance coverage for it is available. Evidence supporting CGM continues to grow and expand to broader populations, such as pregnant people with type 1 diabetes, people with type 2 diabetes treated only with basal insulin therapy, and even type 2 diabetes that does not require insulin treatment. However, despite the significant risk of hyperglycemia in pregnancy, which leads to complications in more than half of affected newborns, CGM indications and insurance coverage for those patients are unresolved. In this review article, we discuss the latest evidence for using CGM to offer glycemic control and reduce perinatal complications, along with its cost-effectiveness in pregestational type 1 and type 2 diabetes and gestational diabetes mellitus. In addition, we discuss future prospects for CGM coverage and indications based on this evidence.

Call for a More Specific Diagnosis of Infant of a Diabetic Mother to Optimize Neonatal Care.

Hyperglycemia is the diagnostic feature of diabetes mellitus (DM), and during pregnancy, hyperglycemia has numerous serious implications for organogenesis and fetal growth. Each type of DM has different neonatal implications based on pathogenesis, length of disease, and comorbidities. Currently, limited attention is given to the woman's type of DM when evaluating risks for neonates. The diagnosis of infant of a diabetic mother is not sufficient because of the varying pathophysiology of diabetes classifications and associated neonatal outcomes. By expanding the diagnosis to include the woman's classification and glucose control, maternity and neonatal care providers could develop plans of care based on potential neonatal outcomes, including anticipatory guidance for families. In this commentary, we propose a more specific diagnosis, rather than infant of a diabetic mother, to better serve these infants.

Maternal-fetal outcomes of pregnant women with type 1 diabetes treated with continuous subcutaneous insulin infusion or multiple daily injections during pregnancy - A Brazilian health care referral center cohort study.

Objective: Pregnant women with type 1 diabetes (T1D) have an increased risk of maternal-fetal complications. Regarding treatment, continuous subcutaneous insulin infusion (CSII) has advantages compared to multiple daily injections (MDI), but data about the best option during pregnancy are limited. This study's aim was to compare maternal-fetal outcomes among T1D patients treated with CSII or MDI during pregnancy. Subjects and methods: This study evaluated 174 pregnancies of T1D patients. Variables of interest were compared between the groups (CSII versus MDI), and logistic regression analysis was performed (p < 0.05). Results: Of the 174 included pregnancies, CSII was used in 21.3% (37) and MDI were used in 78.7% (137). HbA1c values improved throughout gestation in both groups, with no difference in the first and third trimesters. The frequency of cesarean section was significantly higher in the CSII group [94.1 vs. 75.4%, p = 0.017], but there was no significant difference in the frequency of other complications, such as miscarriage, premature delivery and preeclampsia. The mean birth weight and occurrence of neonatal complications were also similar, except for the proportion of congenital malformations, which was significantly lower in the CSII group [2.9 vs. 15.6%, p = 0.048]. In regression analysis, the association of CSII with cesarean section and malformations lost significance after adjusting for HbA1c and other covariates of interest. Conclusion: In this study, we observed a higher frequency of cesarean section and a lower occurrence of congenital malformations in the CSII group, but the adjusted results might indicate that these associations are influenced by glycemic control.

Understanding the self-management experiences and support needs during pregnancy among women with pre-existing diabetes: a qualitative descriptive study.

BACKGROUND: With the increasing prevalence of pre-existing type 1 and type 2 diabetes in pregnancy and their associated perinatal risks, there is a need to focus on interventions to achieve optimal maternal glycemia to improve pregnancy outcomes. One strategy focuses on improving diabetes self-management education and support for expectant mothers with diabetes. This study's objective is to describe the experience of managing diabetes during pregnancy and identify the diabetes self-management education and support needs during pregnancy among women with type 1 and type 2 diabetes. METHODS: Using a qualitative descriptive study design, we conducted semi-structured interviews with 12 women with pre-existing type 1 or 2 diabetes in pregnancy (type 1 diabetes, n = 6; type 2 diabetes, n = 6). We employed conventional content analyses to derive codes and categories directly from the data. RESULTS: Four themes were identified that related to the experiences of managing pre-existing diabetes in pregnancy; four others were related to the self-management support needs in this population. Women with diabetes described their experiences of pregnancy as terrifying, isolating, mentally exhausting and accompanied by a loss of control. Self-management support needs reported included healthcare that is individualized, inclusive of mental health support and support from peers and the healthcare team. CONCLUSIONS: Women with diabetes in pregnancy experience feelings of fear, isolation and a loss of control, which may be improved through personalized management protocols that avoid "painting everybody with the same brush" as well as peer support. Further examination of these simple interventions may yield important impacts on women's experience and sense of connection.

Maternal-fetal outcomes of pregnant women with type 1 diabetes treated with continuous subcutaneous insulin infusion or multiple daily injections during pregnancy - A Brazilian health care referral center cohort study

ABSTRACT Objective: Pregnant women with type 1 diabetes (T1D) have an increased risk of maternal-fetal complications. Regarding treatment, continuous subcutaneous insulin infusion (CSII) has advantages compared to multiple daily injections (MDI), but data about the best option during pregnancy are limited. This study's aim was to compare maternal-fetal outcomes among T1D patients treated with CSII or MDI during pregnancy. Subjects and methods: This study evaluated 174 pregnancies of T1D patients. Variables of interest were compared between the groups (CSII versus MDI), and logistic regression analysis was performed (p < 0.05). Results: Of the 174 included pregnancies, CSII was used in 21.3% (37) and MDI were used in 78.7% (137). HbA1c values improved throughout gestation in both groups, with no difference in the first and third trimesters. The frequency of cesarean section was significantly higher in the CSII group [94.1 vs. 75.4%, p = 0.017], but there was no significant difference in the frequency of other complications, such as miscarriage, premature delivery and preeclampsia. The mean birth weight and occurrence of neonatal complications were also similar, except for the proportion of congenital malformations, which was significantly lower in the CSII group [2.9 vs. 15.6%, p = 0.048]. In regression analysis, the association of CSII with cesarean section and malformations lost significance after adjusting for HbA1c and other covariates of interest. Conclusion: In this study, we observed a higher frequency of cesarean section and a lower occurrence of congenital malformations in the CSII group, but the adjusted results might indicate that these associations are influenced by glycemic control.

Diabetes materna y deficiencia de zinc: riesgos para la descendencia / Maternal diabetes and zinc deficiency, risks for the offspring

Resumen ANTECEDENTES: Cuando la mujer embarazada tiene déficit de zinc, esta carencia puede ser un factor que contribuya a la aparición de alteraciones en el feto, como las malformaciones congénitas y otros trastornos del desarrollo. OBJETIVO: Identificar los aspectos relevantes del estado actual del conocimiento de las complicaciones de la diabetes en la mujer embarazada y el déficit de zinc en el feto. Además, explicar cuál es la posible consecuencia de la deficiencia del micronutriente, entre otras causas moleculares subyacentes. METODOLOGÍA: Revisión bibliográfica efectuada en las bases de datos de Google, PubMed-Medline y SciELO de artículos publicados en inglés o español del año 2012 al 2022, con los MeSH: Maternal diabetes; Hyperglycemia; Zinc deficiency; Congenital malformations; Epigenetics; con su correspondiente traducción al español. Criterios de selección: artículos originales, estudios prospectivos, de revisión bibliográfica, metanálisis, capítulos de libro y reportes de la Asociación Americana de Diabetes (ADA) y la Asociación Latinoamericana de Diabetes (ALAD). RESULTADOS: Se localizaron 187 artículos de los que se excluyeron 126 no adecuados para el tema de la revisión, duplicados o en idioma diferente al inglés y español. CONCLUSIONES: El análisis bibliográfico evidenció que los trastornos metabólicos provocados por la hiperglucemia de la madre, el déficit de zinc, la alteración de su homeostasis y su interacción con el desequilibrio redox, la inflamación de bajo grado, la activación apoptósica y las modificaciones epigenéticas producen un ambiente intrauterino adverso que condiciona la aparición de malformaciones y otros trastornos del desarrollo en la descendencia.

Abstract BACKGROUND: When pregnant women are deficient in zinc, this deficiency may be a contributing factor to foetal disorders, such as congenital malformations and other developmental disorders. OBJECTIVE: To identify the relevant aspects of the current state of knowledge of the complications of diabetes in pregnant women and zinc deficiency in the foetus. In addition, to explain the possible consequences of micronutrient deficiency, among other underlying molecular causes. METHODOLOGY: Bibliographic review carried out in Google, PubMed-Medline and SciELO databases of articles published in English or Spanish from 2012 to 2022, with the MeSH: Maternal diabetes; Hyperglycemia; Zinc deficiency; Congenital malformations; Epigenetics; with their corresponding translation into Spanish. Selection criteria: original articles, prospective studies, literature reviews, meta-analyses, book chapters and reports of the American Diabetes Association (ADA) and the Latin American Diabetes Association (ALAD). RESULTS: 187 articles were located of which 126 unsuitable for the review topic, duplicates or in language other than English and Spanish were excluded. CONCLUSIONS: The literature review evidenced that metabolic disorders caused by maternal hyperglycemia, zinc deficiency, alteration of its homeostasis and its interaction with redox imbalance, low-grade inflammation, apoptotic activation and epigenetic modifications produce an adverse intrauterine environment that conditions the appearance of malformations and other developmental disorders in the offspring.

Hyperglycemia affects neuronal differentiation and Nestin, FOXO1, and LMO3 mRNA expression of human Wharton's jelly mesenchymal stem cells of children from diabetic mothers.

Pregestational Diabetes Mellitus (PDM) during pregnancy constitutes an unfavorable embryonic and fetal development environment, with a high incidence of congenital malformations (CM). Neural tube defects are the second most common type of CM in children of diabetic mothers (CDM), who also have an elevated risk of developing neurodevelopmental disorders. The mechanisms that lead to these neuronal disorders in CDM are not yet fully understood. The present study aimed to know the effect of hyperglycemia on proliferation, neuronal differentiation percentage, and expression of neuronal differentiation mRNA markers in human umbilical cord Wharton's jelly mesenchymal stem cells (hUCWJMSC) of children from normoglycemic pregnancies (NGP) and PDM. We isolated and characterized hUCWJMSC by flow cytometry, immunofluorescence, RT-PCR and were induced to differentiate into adipocytes, osteocytes, and neurons. Proliferation assays were performed to determine the doubling time, and Nestin, TUBB3, FOXO1, KCNK2, LMO3, and MAP2 mRNA gene expression was assessed by semiquantitative RT-PCR. Hyperglycemia significantly decreased proliferation and neuronal differentiation percentage in NGP and PDM cells treated with 40 mM d-glucose. Nestin mRNA expression decreased under control glycemic conditions, while FOXO1, KCNK2, LMO3, and MAP2 mRNA expression increased during neuronal differentiation in both NGP and PDM cells. On the other hand, under hyperglycemic conditions, Nestin was significantly decreased in cells from NGP but not in cells from PDM, while mRNA expression of FOXO1 and LMO3 was significantly increased in cells from NGP, but not in cells from PDM. We found evidence that maternal PDM, with hyperglycemia in culture, affects the biological properties of fetal cells. All these results could be part of fetal programming.

Monitoreo continuo de glucosa durante la gestación en pacientes con diabetes mellitus tipo 2 pregestacional

La diabetes pregestacional requiere un control glicémico estricto durante el embarazo. Los dispositivos de monitoreo continuo de glucosa (MCG) miden niveles de glucosa intersticial sin necesidad de punción capilar. Se estudió 4 gestantes con diabetes mellitus tipo 2 pregestacional con la ayuda del MCG durante 2 semanas de su gestación. Ellas tuvieron sesiones nutricionales semanales y controles médicos con un endocrinólogo. El promedio de nivel de glucosa osciló entre 82 y 171 mg/dL. El MCG permitió cambios tempranos en el tratamiento de una paciente con hipoglicemia. Todas las pacientes manifestaron que el MCG les ayudó en la selección de sus alimentos. En conclusión, el MCG ayudó en el reconocimiento de carbohidratos y en el reajuste del tratamiento. El MCG tuvo buena aceptación de su uso.

Pregestational diabetes requires strict glycemic control during pregnancy. Continuous glucose monitoring (CGM) devices measure interstitial glucose levels without the need for capillary puncture. Four pregnant women with pregestational type 2 diabetes mellitus were studied with the aid of CGM during 2 weeks of their gestation. They had weekly nutritional sessions and medical controls with an endocrinologist. The average glucose level ranged from 82 to 171 mg/dL. The CGM allowed early changes in the treatment of one patient with hypoglycemia. All patients stated that the GCM helped them in their food selection. In conclusion, the GCM helped in carbohydrate recognition and treatment readjustment. The CGM was well accepted for use.

Gestational weight gain in women with type 2 diabetes and perinatal outcomes: A secondary analysis of the metformin in women with type 2 diabetes in pregnancy (MiTy) trial.

AIMS: Our study assesses perinatal outcomes among women with type 2 diabetes, with gestational weight gain (GWG) within and outside of US Institute of Medicine (IOM) guidelines, by conducting a secondary analysis of the Metformin in Type 2 Diabetes in Pregnancy (MiTy) trial. METHODS: 460 participants were classified into three cohorts by total and weekly GWG (excessive, appropriate vs. restricted according to IOM). The primary outcome was birthweight z score, and secondary outcomes included both maternal and fetal outcomes. RESULTS: Women with restricted (total and weekly) GWG had lower birthweight z score, lower fetal birthweight, and lower neonatal body fat mass. Women with restricted weekly GWG had fewer LGA, extreme LGA, and lower neonatal body fat mass infants, but more SGA and preterm births. Women with excessive (total and weekly) GWG had higher maternal total insulin doses in the third trimester. Women with excessive weekly GWG had more preeclampsia and higher SGA. CONCLUSIONS: Restricted GWG among women with type 2 diabetes is associated with both benefits and harms. Both must be considered when counseling patients.

Pregnancy outcomes in women with type 1 diabetes in China during 2004 to 2014: A retrospective study (the CARNATION Study).

BACKGROUND: We aimed to report pregnancy outcomes of women with type 1 diabetes (T1D) in China, on which data were sparse. METHODS: This is a nationwide retrospective study conducted in 11 general medical centers in 8 cities across China. We investigated the clinical data of all women who attended these centers with a singleton pregnancy and whose pregnancy ended between 1 January 2004 and 31 December 2014. Pregnancies of women with pregestational T1D were ascertained and compared with those of women without T1D. RESULTS: From over 300 000 pregnancies over the 11-year study period, we identified 265 singleton pregnancies of women with T1D. One maternal death was documented among 265 (0.37%) women with T1D and 83 among 318 486 (0.03%) women without T1D. Women with T1D suffered from higher rates of pregnancy loss (13.21% vs 2.92%, crude risk ratio [cRR] 5.08 [95% CI, 3.56-7.26]) and preeclampsia (17.74% vs 4.20%, cRR 4.94 [95% CI, 3.60-6.77]) compared with those without T1D. Infants of these women with T1D had elevated rates of neonatal death (5.65% vs 0.16%, cRR 37.36 [95% CI, 21.21-65.82]) and congenital malformation(s) (8.26% vs 3.53%, cRR 2.46 [95% CI, 1.54-3.93]) compared with those of women without T1D. No significant improvement in pregnancy outcomes in women with T1D was observed over the period 2004 to 2014. CONCLUSIONS: Pregnancy outcomes were persistently poor in women with T1D during 2004 to 2014 in China. Pregnancy care needs to be improved to reduce adverse pregnancy outcomes among Chinese women with T1D.

The use of glucose-lowering medications for the treatment of type 2 diabetes mellitus during pregnancy in the United States.

INTRODUCTION: Some guidelines allow for the use of either insulin or noninsulin antidiabetic agents for gestational diabetes, but only insulin is recommended for pregnant women with preexisting type 2 diabetes mellitus (T2DM). We aimed to document treatment patterns in routine care for women with preexisting T2DM. METHODS: We identified pregnancy cohorts within 2 US claims databases for publicly and privately insured individuals: the Medicaid Analytical eXtract (2000-2014) and OptumClinformatics (2004-2014). T2DM was classified with a validated algorithm using ICD-9-CM and CPT codes. We assessed medication usage over the years of the study, and changes in medication use before and after the beginning of pregnancy, using prescription fills as a proxy for the use of insulin, metformin, sulphonylureas and other noninsulin antidiabetic agents before pregnancy and during each trimester. RESULTS: Among 12,631 women with T2DM, insulin use in pregnancy was stable over the study years (55%-60% in the 2nd trimester), but 2nd trimester use of metformin increased from <5% to 20%. Over the study period, 41% of women filled a prescription for metformin before pregnancy, 37% in the 1st trimester and 17% in the 2nd trimester. By the 2nd trimester, few women used sulphonylureas (11%) or other noninsulin antidiabetic agents (1%). Of the women on metformin only before pregnancy, 36% switched to insulin only by 2nd trimester, 11% added insulin and 16% continued on metformin only. Of the women on metformin and insulin before pregnancy, 61% switched to insulin only by 2nd trimester, 22% continued with metformin and insulin and <5% used only metformin. CONCLUSION: The use of insulin-metformin combinations and other noninsulin antidiabetic drugs during pregnancy has increased. Safety studies for these medication regimens are needed.

The Clinical Characteristics of Gestational Diabetes Mellitus in Korea: A National Health Information Database Study.

BACKGROUND: To investigate the clinical characteristics of gestational diabetes mellitus (GDM) in Korea, using a nationwide database. METHODS: We analyzed 417,139 women who gave birth between 2011 and 2015 using the Korean National Health Information Database. They underwent the Korean National Health Screening Program within one year before pregnancy and were not prescribed drugs for diabetes nor diagnosed with diabetes mellitus before 280 days antepartum. Patients with GDM were defined as those who visited the outpatient clinic more than twice with GDM codes. RESULTS: The prevalence of GDM was 12.70% and increased with increasing maternal age, prepregnancy body mass index (BMI), waist circumference (WC), and fasting plasma glucose (FPG) (P for trend <0.05). As compared with those aged <25 years, the odds ratio for women with GDM aged ≥40 years were 4.804 (95% confidence interval [CI], 4.436 to 5.203) after adjustment for covariates. Women with prepregnancy BMI ≥30 kg/m2 were at 1.898 times (95% CI, 1.736 to 2.075) greater risk for GDM than those with prepregnancy BMI <18.5 kg/m2. Women with WC of ≥95 cm were at 1.158 times (95% CI, 1.029 to 1.191) greater risk for GDM than women with WC of less than 65 cm. High FPG, high income, smoking, and drinking were associated with an elevated risk of GDM. CONCLUSION: The prevalence of GDM in Korean women increased up to 12.70% during 2011 to 2015. These data suggest the importance of GDM screening and prevention in high-risk groups in Korea.

Can placental growth factors explain birthweight variation in offspring of women with type 1 diabetes?

AIMS/HYPOTHESIS: Maternal hyperglycaemia alone does not explain the incidence of large offspring amongst women with type 1 diabetes. The objective of the study was to determine if there is an association between placental function, as measured by angiogenic factors, and offspring birthweight z score in women with type 1 diabetes. METHODS: This cohort study included samples from 157 Continuous Glucose Monitoring in Pregnant Women with Type 1 Diabetes (CONCEPTT) trial participants. Correlations were estimated between birthweight z score and placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) levels measured at baseline and at 24 and 34 weeks of gestation. Linear regression was used to assess the relationship between birthweight z score and placental health, as measured by PlGF and sFlt-1/PlGF ratio, stratified by glycaemic status (continuous glucose monitoring and HbA1c measures) and adjusted for potential confounders of maternal BMI, smoking and weight gain. Higher PlGF levels and lower sFlt-1/PlGF ratios represent healthy placentas, while lower PlGF levels and higher sFlt-1/PlGF ratios represent unhealthy placentas. RESULTS: Among CONCEPTT participants, the slopes relating PlGF levels to birthweight z scores differed according to maternal glycaemia at 34 weeks of gestation (p = 0.003). With optimal maternal glycaemia (HbA1c < 48 mmol/mol [6.5%]/ or continuous glucose monitoring time above range ≤ 30%), birthweight z scores were reduced towards zero (normal weight) with increasing PlGF values (representing a healthy placenta), and increased with decreasing PlGF values. With suboptimal glycaemic status (HbA1c ≥ 48 mmol/mol [6.5%] or time above range > 30%), increasing PlGF values were associated with heavier infants. Those with a healthy placenta (PlGF > 100) and suboptimal glycaemic control had a higher mean z score (2.45) than those with an unhealthy placenta (mean z score = 1.86). Similar relationships were seen when using sFlt-1/PlGF ratio as a marker for a healthy vs unhealthy placenta. CONCLUSIONS/INTERPRETATION: In women with type 1 diabetes, infant birthweight is influenced by both glycaemic status and placental function. In women with suboptimal glycaemia, infant birthweight was heavier when placentas were healthy. Suboptimal placental function should be considered in the setting of suboptimal glycaemia and apparently 'normal' birthweight.

Obstetric and perinatal outcomes for women with pre-existing diabetes in rural compared to metropolitan settings in Victoria, Australia.

BACKGROUND: Pre-existing diabetes in pregnancy is associated with an increased risk of complications. Likewise, living in rural, regional and remote Victoria, Australia, is also associated with poorer health outcomes. There is a gap in the literature with regard to whether Victorian women with pre-existing diabetes experience a greater risk of adverse pregnancy outcomes compared to their metropolitan counterparts. AIM: Our objective is to compare obstetric and perinatal outcomes for women with pre-existing diabetes delivering in rural vs metropolitan hospitals in Victoria, Australia. MATERIALS AND METHODS: Retrospective population-based study using routinely collected state-based data of singleton births to women with type 1 and type 2 diabetes who delivered in metropolitan (n = 3233) and rural hospitals (n = 693) in Victoria, Australia, between 2006-2015. Pearson's χ2 test, Fisher's exact test and MannWhitney U-test were used to compare obstetric and perinatal outcomes between metropolitan and rural locations. RESULTS: Delivery in a rural hospital was associated with higher rates of stillbirth (2.3% vs 1.1%, P = 0.027), macrosomia (25.9% vs 16.9%, P < 0.001), shoulder dystocia (8.4% vs 3.5%, P < 0.001) and admission to the neonatal intensive care unit/special care nursery (73.2% vs 59.3%, P < 0.001). Smoking (18.0% vs 8.9%, P < 0.001), overweight/obesity (P = 0.047) and socioeconomic disadvantage (P < 0.001) were more common in rural women. CONCLUSIONS: Women with pre-existing diabetes who deliver in rural hospitals experience a greater risk of adverse perinatal outcomes and present with increased maternal risk factors. These results suggest a need to improve care for women with pre-existing diabetes in rural Victoria.

Rethinking third trimester ultrasound measurements and risk of adverse neonatal outcomes in pregnancies complicated by hyperglycaemia: A retrospective study.

BACKGROUND: Antenatal ultrasound is used frequently in pregnancies complicated by hyperglycaemia; however, it is unclear which measurements have the greatest association with adverse neonatal outcomes. AIM: To assess the association between third trimester ultrasound parameters with adverse neonatal outcomes in pregnancies complicated by hyperglycaemia. METHOD: All pregnant women with gestational or type 2 diabetes who birthed in a regional hospital over 12 months were included. A composite adverse neonatal outcome was defined by one or more: admission to special care nursery, acidosis, hypoglycaemia, jaundice, shoulder dystocia, respiratory distress syndrome or 5-minute Apgar score < 5. Logistic regression was used to determine odds ratios (OR) for an adverse neonatal outcome, according to pre-specified cut points in both lower and upper percentiles of abdominal circumference (AC) and estimated fetal weight (EFW). RESULTS: Of 275 births an adverse outcome occurred in 122 (44%). Unadjusted OR (95% CI) for AC ≤30th was 3.2 (1.1-8.8) and >95th percentile was 3.1 (1.5-6.0) compared with the reference group of 31-70th percentile. Unadjusted OR for EFW ≤30th was 1.5 (0.7-3.1) and >95th percentile was 3.0 (1.4-6.3). After adjusting for maternal age, body mass index, diabetes type, ethnicity, gravidity, mode of delivery and gestation at birth the OR (95% CI) were as follows: AC ≤30th percentile, 3.7 (1.1-12.4); AC >95th , 2.2 (1.1-4.8); EFW ≤30th , 2.6 (1.1-6.1); EFW >95th , 2.5 (1.1-6.1). CONCLUSION: An AC and EFW up to the 30th percentile may pose just as great a risk to the fetus as an AC or EFW >95th percentile in pregnancies complicated by hyperglycaemia.

Hyperglycemia in pregnancy: sleep alterations, comorbidities and pharmacotherapy

SUMMARY OBJECTIVE: To investigate sleep alterations and associated factors in pregnant diabetic women (n=141). METHODS: Sleep profile, sociodemographics and clinical information were collected. Poor sleep quality (Pittsburgh Sleep Quality Index >5) and excessive daytime sleepiness (Epworth Sleepiness Scale ≥10), sleep duration (h), sleep latency (min), frequent sleep interruption and short sleep (≤6 h) were assessed in type 1 diabetes mellitus (16.3%), type 2 diabetes mellitus (25.5%) and gestational diabetes mellitus (58.2%). RESULTS: Poor sleep quality was found in 58.8% of patients and daytime sleepiness in 25.7%, regardless of hyperglycemia etiology. No correlation existed between daytime sleepiness and poor sleep quality (Pearson correlation r=0.02, p=0.84). Short sleep duration occurred in 1/3 of patients (31.2%). Sleep interruptions due to frequent urination affected 72% of all and sleep interruptions due to any cause 71.2%. Metformin was used by 65.7% of type 2 diabetes mellitus and 28.7% of gestational diabetes mellitus. In gestational diabetes mellitus, parity number was independently associated with poor sleep quality (p=0.02; OR=1.90; 95%CI 1.07-3.36) and metformin use was also independently associated with poor sleep quality (p=0.03; OR=2.36; 95%CI 1.05-5.29). CONCLUSIONS: Our study originally shows that poor sleep quality and excessive daytime sleepiness are frequent in diabetic pregnancy due to different etiologies. Interestingly, only in gestational diabetes mellitus, metformin therapy and higher parity were associated with poor sleep quality.