Talk:Abnormal Development - Maternal Diabetes

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On this website the Discussion Tab or "talk pages" for a topic has been used for several purposes: References - recent and historic that relates to the topic Additional topic information - currently prepared in draft format Links - to related webpages Topic page - an edit history as used on other Wiki sites Lecture/Practical - student feedback Student Projects - online project discussions. Links: Pubmed Most Recent | Reference Tutorial | Journal Searches Glossary Links Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link Cite this page: Hill, M.A. (2024, April 23) Embryology Abnormal Development - Maternal Diabetes. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Abnormal_Development_-_Maternal_Diabetes

2020

D'Ambrosi F, Rossi G, Soldavini CM, Di Maso M, Carbone IF, Cetera GE, Colosi E & Ferrazzi E. (2020). Ultrasound assessment of maternal adipose tissue during 1st trimester screening for aneuploidies and risk of developing gestational diabetes. Acta Obstet Gynecol Scand , 99, 644-650. PMID: 31898313 DOI.

Ultrasound assessment of maternal adipose tissue during 1st trimester screening for aneuploidies and risk of developing gestational diabetes

INTRODUCTION: The objective of the present study is to compare the sonographic measurement of subcutaneous adipose thickness and visceral adipose thickness during 1st trimester screening for aneuploidies between non-diabetic pregnant women and patients who develop 1st trimester or 2nd trimester gestational diabetes mellitus (GDM). MATERIAL AND METHODS: Adipose thickness was measured by transabdominal ultrasound imaging in pregnant women attending our clinic for screening for fetal aneuploidies between 11 and 13 weeks of gestation. During the 1st trimester all patients were evaluated for fasting glycemia in accordance with the International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations. Patients with confirmed fasting glycemia (FPG) ≥92 mg/dL were diagnosed as 1st trimester GDM. Patients with FPG <92 mg/dL underwent a 75-g oral glucose tolerance test between 24 and 28 weeks. RESULTS: The study population included 238 non-diabetic women, 29 women with 1st trimester GDM and 28 women with 2nd trimester GDM. Mean subcutaneous adipose thickness and visceral adipose thickness values in non-diabetic women were 9.8 mm (standard deviation [SD = 4.9) and 7.2 mm (SD = 3.5), respectively. Values in women with 1st trimester GDM were 12.8 mm (SD = 6.5) and 9.9 mm (SD = 4.4). In the 2nd trimester GDM group, the mean subcutaneous adipose thickness was 11.1 mm (SD = 4.6) and the mean visceral adipose thickness 10.5 mm (SD = 5.3). Multiple logistic regression analysis showed that visceral adipose thickness, but not subcutaneous adipose thickness, was significantly and independently associated with both 1st trimester GDM (OR 1.15, 95% CI 1.02-1.29) and 2nd trimester GDM (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.05-1.34). CONCLUSIONS: Sonographic thickness of maternal visceral adipose tissue was greater in women with GDM than in non-diabetic patients, independently of other known risk factors associated with GDM in the 1st and in the 2nd trimester of pregnancy. Thus, this measurement may be considered of clinical use in 1st trimester screening. © 2020 Nordic Federation of Societies of Obstetrics and Gynecology. KEYWORDS: 1st trimester screening; International Association of Diabetes and Pregnancy Study Groups; adipose tissue; gestational diabetes; glycemia; subcutaneous adipose thickness DOI: 10.1111/aogs.13800

Lyu Y, Jia S, Wang S, Wang T, Tian W & Chen G. (2020). Gestational diabetes mellitus affects odontoblastic differentiation of dental papilla cells via Toll-like receptor 4 signaling in offspring. J. Cell. Physiol. , 235, 3519-3528. PMID: 31595494 DOI.

Gestational diabetes mellitus affects odontoblastic differentiation of dental papilla cells via Toll-like receptor 4 signaling in offspring

Abstract Gestational diabetes mellitus (GDM) is an important factor involved in the pathogenesis of organ development in the offspring. Here, we analyzed the effects of GDM on odontoblastic differentiation of dental papilla cells (DPCs) and dentin formation in offspring and investigated their underlying mechanisms. A GDM rat model was induced by intraperitoneal injection of streptozotocin and offspring were collected. The results showed that GDM significantly affected odontoblast differentiation and dentin formation in offspring tooth. GDM activated the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-ĸB) signaling pathway and inhibited SMAD1/5/9 signaling to modulate the odontoblastic differentiation of DPCs in offspring. Inhibition of TLR4 signaling by treated with TAK-242 significantly reverses the suppression of odonto-differentiation of DPCs in diabetic offspring. Taken together, these data indicate GDM activated the offspring DPCs TLR4/NF-ĸB signaling, which suppressed the SMAD1/5/9 phosphorylation and then inhibited odontoblasts differentiation and dentin formation. © 2019 Wiley Periodicals, Inc.

KEYWORDS: TLR4/NF-ĸB signaling; dental papilla cells; gestational diabetes mellitus; odontoblast PMID: 31595494 DOI: 10.1002/jcp.29240

2019

Yu Y, Arah OA, Liew Z, Cnattingius S, Olsen J, Sørensen HT, Qin G & Li J. (2019). Maternal diabetes during pregnancy and early onset of cardiovascular disease in offspring: population based cohort study with 40 years of follow-up. BMJ , 367, l6398. PMID: 31801789 DOI.

Maternal diabetes during pregnancy and early onset of cardiovascular disease in offspring: population based cohort study with 40 years of follow-up.

Abstract OBJECTIVE: To evaluate the associations between maternal diabetes diagnosed before or during pregnancy and early onset cardiovascular disease (CVD) in offspring during their first four decades of life. DESIGN: Population based cohort study. SETTING: Danish national health registries. PARTICIPANTS: All 2 432 000 liveborn children without congenital heart disease in Denmark during 1977-2016. Follow-up began at birth and continued until first time diagnosis of CVD, death, emigration, or 31 December 2016, whichever came first. EXPOSURES FOR OBSERVATIONAL STUDIES: Pregestational diabetes, including type 1 diabetes (n=22 055) and type 2 diabetes (n=6537), and gestational diabetes (n=26 272). MAIN OUTCOME MEASURES: The primary outcome was early onset CVD (excluding congenital heart diseases) defined by hospital diagnosis. Associations between maternal diabetes and risks of early onset CVD in offspring were studied. Cox regression was used to assess whether a maternal history of CVD or maternal diabetic complications affected these associations. Adjustments were made for calendar year, sex, singleton status, maternal factors (parity, age, smoking, education, cohabitation, residence at childbirth, history of CVD before childbirth), and paternal history of CVD before childbirth. The cumulative incidence was averaged across all individuals, and factors were adjusted while treating deaths from causes other than CVD as competing events. RESULTS: During up to 40 years of follow-up, 1153 offspring of mothers with diabetes and 91 311 offspring of mothers who did not have diabetes were diagnosed with CVD. Offspring of mothers with diabetes had a 29% increased overall rate of early onset CVD (hazard ratio 1.29 (95% confidence interval 1.21 to 1.37); cumulative incidence among offspring unexposed to maternal diabetes at 40 years of age 13.07% (12.92% to 13.21%), difference in cumulative incidence between exposed and unexposed offspring 4.72% (2.37% to 7.06%)). The sibship design yielded results similar to those of the unpaired design based on the whole cohort. Both pregestational diabetes (1.34 (1.25 to 1.43)) and gestational diabetes (1.19 (1.07 to 1.32)) were associated with increased rates of CVD in offspring. We also observed varied increased rates of specific early onset CVDs, particularly heart failure (1.45 (0.89 to 2.35)), hypertensive disease (1.78 (1.50 to 2.11)), deep vein thrombosis (1.82 (1.38 to 2.41)), and pulmonary embolism (1.91 (1.31 to 2.80)). Increased rates of CVD were seen in different age groups from childhood to early adulthood until age 40 years. The increased rates were more pronounced among offspring of mothers with diabetic complications (1.60 (1.25 to 2.05)). A higher incidence of early onset CVD in offspring of mothers with diabetes and comorbid CVD (1.73 (1.36 to 2.20)) was associated with the added influence of comorbid CVD but not due to the interaction between diabetes and CVD on the multiplicative scale (P value for interaction 0.94). CONCLUSIONS: Children of mothers with diabetes, especially those mothers with a history of CVD or diabetic complications, have increased rates of early onset CVD from childhood to early adulthood. If maternal diabetes does have a causal association with increased CVD rate in offspring, the prevention, screening, and treatment of diabetes in women of childbearing age could help to reduce the risk of CVD in the next generation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

DOI: 10.1136/bmj.l6398

Blotsky AL, Rahme E, Dahhou M, Nakhla M & Dasgupta K. (2019). Gestational diabetes associated with incident diabetes in childhood and youth: a retrospective cohort study. CMAJ , 191, E410-E417. PMID: 30988041 DOI.

Gestational diabetes associated with incident diabetes in childhood and youth: a retrospective cohort study.

Abstract BACKGROUND: Indicators of childhood- and youth-onset diabetes may be useful for early detection of diabetes; there is a known association between composite exposure of parental type 2 diabetes and gestational diabetes mellitus with childhood- and youth-onset diabetes. We examined associations between gestational diabetes mellitus and incidence of childhood- and youth-onset diabetes in offspring. METHODS: Using public health insurance administrative databases from Quebec, Canada, we randomly selected singleton live births with maternal gestational diabetes mellitus (1990-2007) and matched them 1:1 with singleton live births without gestational diabetes mellitus. Follow-up was to Mar. 31, 2012. We examined associations of diabetes in offspring with maternal gestational diabetes mellitus through unadjusted and adjusted Cox proportional hazards models. In secondary analyses, we separately considered age groups ranging from birth to age 12 years, and age 12 to 22 years. RESULTS: Incidence of pediatric diabetes (per 10 000 person-years) was higher in offspring born to mothers with gestational diabetes mellitus (4.52, 95% confidence interval [CI] 4.47-4.57) than in mothers without gestational diabetes mellitus (2.4, 95% CI 2.37-2.46). In an adjusted Cox proportional hazards model, maternal gestational diabetes mellitus was associated with development of pediatric diabetes overall (birth to age 22 yr: hazard ratio [HR] 1.77, 95% CI 1.41-2.22), during childhood (birth to age 12 yr: HR 1.43, 95% CI 1.09-1.89), and in youth (age 12 to 22 yr: HR 2.53, 95% CI 1.67-3.85). INTERPRETATION: Gestational diabetes mellitus is associated with incident diabetes in offspring during childhood and adolescence. Future studies are needed to examine longer-term outcomes in patients with pediatric diabetes with a maternal history of gestational diabetes mellitus, to ascertain how they compare with other patients with childhood- or youth-onset diabetes, in terms of disease severity and outcomes. © 2019 Joule Inc. or its licensors. PMID: Blotsky AL, Rahme E, Dahhou M, Nakhla M & Dasgupta K. (2019). Gestational diabetes associated with incident diabetes in childhood and youth: a retrospective cohort study. CMAJ , 191, E410-E417. PMID: 30988041 DOI. PMCID: PMC6464886 DOI: 10.1503/cmaj.181001

Wang X, Lu J, Xie W, Lu X, Liang Y, Li M, Wang Z, Huang X, Tang M, Pfaff DW, Tang YP & Yao P. (2019). Maternal diabetes induces autism-like behavior by hyperglycemia-mediated persistent oxidative stress and suppression of superoxide dismutase 2. Proc. Natl. Acad. Sci. U.S.A. , , . PMID: 31685635 DOI.

Epidemiological studies show that maternal diabetes is associated with an increased risk of autism spectrum disorders (ASDs), although the detailed mechanisms remain unclear. The present study aims to investigate the potential effect of maternal diabetes on autism-like behavior in offspring. The results of in vitro study showed that transient hyperglycemia induces persistent reactive oxygen species (ROS) generation with suppressed superoxide dismutase 2 (SOD2) expression. Additionally, we found that SOD2 suppression is due to oxidative stress-mediated histone methylation and the subsequent dissociation of early growth response 1 (Egr1) on the SOD2 promoter. Furthermore, in vivo rat experiments showed that maternal diabetes induces SOD2 suppression in the amygdala, resulting in autism-like behavior in offspring. SOD2 overexpression restores, while SOD2 knockdown mimics, this effect, indicating that oxidative stress and SOD2 expression play important roles in maternal diabetes-induced autism-like behavior in offspring, while prenatal and postnatal treatment using antioxidants permeable to the blood-brain barrier partly ameliorated this effect. We conclude that maternal diabetes induces autism-like behavior through hyperglycemia-mediated persistent oxidative stress and SOD2 suppression. Here we report a potential mechanism for maternal diabetes-induced ASD. Copyright © 2019 the Author(s). Published by PNAS. KEYWORDS: SOD2; autism spectrum disorders; epigenetics; maternal diabetes; oxidative stress PMID: 31685635 DOI: 10.1073/pnas.1912625116 Free full text

2018

Comparative proteomic analysis of maternal peripheral plasma and umbilical venous plasma from normal and gestational diabetes mellitus pregnancies

Liao Y, Xu GF, Jiang Y, Zhu H, Sun LJ, Peng R & Luo Q. (2018). Comparative proteomic analysis of maternal peripheral plasma and umbilical venous plasma from normal and gestational diabetes mellitus pregnancies. Medicine (Baltimore) , 97, e12232. PMID: 30200149 DOI.

Liao Y1, Xu GF, Jiang Y, Zhu H, Sun LJ, Peng R, Luo Q. Author information Abstract Gestational diabetes mellitus (GDM) increases many health risks in offspring. The study aims to investigate the underlying mechanism in fetal risk of GDM.We collected maternal peripheral plasma and umbilical venous plasma samples from 4 GDM and 4 control patients during their delivery at a university-based women's hospital. An isobaric tag for relative and absolute quantitation-labeled proteomics analysis was performed. The enzyme-linked immunosorbent assay was used to confirm the change of cholesteryl ester transfer protein (CETP). Bioinformatic analysis was performed with Ingenuity Pathway Analysis (IPA) software package.We identified 19 up-regulated proteins and 15 down-regulated proteins in GDM peripheral plasma, 29 up-regulated proteins and 69 down-regulated proteins in GDM umbilical venous plasma. CETP concentration was significantly lower in both GDM peripheral plasma and umbilical venous plasma. Upstream regulator analysis predicted follicle-stimulating hormone (FSH) as the activated regulator of differentially expressed proteins.The protein profiles in both GDM peripheral plasma and umbilical venous plasma between normal and GDM patients were significantly different. The results indicated that CETP and FSH might associates with health problem of GDM offspring. PMID: 30200149 PMCID: PMC6133416 DOI: 10.1097/MD.0000000000012232

Increased risk of cardiovascular disease in women with prior gestational diabetes: A systematic review and meta-analysis

Diabetes Res Clin Pract. 2018 Apr 12. pii: S0168-8227(17)31153-1. doi: 10.1016/j.diabres.2018.03.054. [Epub ahead of print]

Li J1, Song C2, Li C1, Liu P3, Sun Z1, Yang X4.

Abstract

This study aims to investigate the effect of gestational diabetes mellitus (GDM) on the long-term risk of cardiovascular disease (CVD). PubMed and other databases were searched up to August 31, 2017. Cohort studies evaluating risk of CVD postpartum in women with and without prior GDM were included. Random-effect model was used to estimate the pooled relative risk of CVD. Sensitivity and subgroup analyses were performed to check the consistency of the effect size and to explore sources of heterogeneity. Multivariable logistic regression was used to control for high heterogeneity. Seven cohort studies with 3,417,020 pregnant women including 14,146 incident CVD events were retrieved. In the pooled analysis, women with previous GDM had a higher risk of CVD than those without (RR: 1.74, 95%CI: 1.28-2.35, I2=95.7%). Four studies reported the event of coronary artery disease (CAD) and two studies reported stroke. The overall RR for CAD was 2.09 (95% CI: 1.56-2.80, I2=91.2%) and that for stroke was 1.25 (95% CI: 1.07-1.48). In view of the high level of heterogeneity, adjustments were made for this, with the resulting adjusted OR for CVD and CAD being 1.95 (95%CI: 1.83-2.08) and 1.59 (95%CI: 1.30-1.94). Women with prior GDM have increased risk of CVD. KEYWORDS: Cardiovascular disease; Gestational diabetes mellitus; Meta-analysis; Pregnancy; Systematic review PMID: 29655653 DOI: 10.1016/j.diabres.2018.03.054

Neonatal outcomes of live-born term singletons in vertex presentation born to mothers with diabetes during pregnancy by mode of birth: a New South Wales population-based retrospective cohort study

BMJ Paediatr Open. 2018 Jan 30;2(1):e000224. doi: 10.1136/bmjpo-2017-000224. eCollection 2018.

Zeki R1, Wang AY1, Lui K2, Li Z1, Oats JJN3, Homer CSE4, Sullivan EA1. Author information Abstract OBJECTIVES: To investigate the association between the mode of birth and adverse neonatal outcomes of macrosomic (birth weight ≥4000 g) and non-macrosomic (birth weight <4000 g) live-born term singletons in vertex presentation (TSV) born to mothers with diabetes (pre-existing and gestational diabetes mellitus (GDM)). DESIGN: A population-based retrospective cohort study. SETTING: New South Wales, Australia. PATIENTS: All live-born TSV born to mothers with diabetes from 2002 to 2012. INTERVENTION: Comparison of neonatal outcomes by mode of birth (prelabour caesarean section (CS) and planned vaginal birth resulted in intrapartum CS, non-instrumental or instrumental vaginal birth). MAIN OUTCOME MEASURES: Five-minute Apgar score <7, admission to neonatal intensive care unit (NICU) or special care nursery (SCN) and the need for resuscitation. RESULTS: Among the 48 882 TSV born to mothers with diabetes, prelabour CS was associated with a significant increase in the rate of admission to NICU/SCN compared with planned vaginal birth.For TSV born to mothers with pre-existing diabetes, compared with non-instrumental vaginal birth, instrumental vaginal birth was associated with increased odds of the need for resuscitation in macrosomic (adjusted ORs (AOR) 2.6; 95% CI (1.2 to 7.5)) and non-macrosomic TSV (AOR 3.3; 95% CI (2.2 to 5.0)).For TSV born to mothers with GDM, intrapartum CS was associated with increased odds of the need for resuscitation compared with non-instrumental vaginal birth in non-macrosomic TSV (AOR 2.3; 95% CI (2.1 to 2.7)). Instrumental vaginal birth was associated with increased likelihood of requiring resuscitation compared with non-instrumental vaginal birth for both macrosomic (AOR 2.3; 95% CI (1.7 to 3.1)) and non-macrosomic (AOR 2.5; 95% CI (2.2 to 2.9)) TSV. CONCLUSION: Pregnant women with diabetes, particularly those with suspected fetal macrosomia, need to be aware of the increased likelihood of adverse neonatal outcomes following instrumental vaginal birth and intrapartum CS when planning mode of birth. KEYWORDS: diabetes; intensive care; outcomes research; resuscitation PMID: 29637191 PMCID: PMC5843011 DOI: 10.1136/bmjpo-2017-000224

2017

Maternal diabetes causes developmental delay and death in early-somite mouse embryos

Sci Rep. 2017 Sep 15;7(1):11714. doi: 10.1038/s41598-017-11696-x.

Zhao J1, Hakvoort TBM1, Ruijter JM2, Jongejan A3, Koster J4, Swagemakers SMA5, Sokolovic A1, Lamers WH6.

Abstract

Maternal diabetes causes congenital malformations and delays embryonic growth in the offspring. We investigated effects of maternal diabetes on mouse embryos during gastrulation and early organogenesis (ED7.5-11.5). Female mice were made diabetic with streptozotocin, treated with controlled-release insulin implants, and mated. Maternal blood glucose concentrations increased up to embryonic day (ED) 8.5. Maternal hyperglycemia induced severe growth retardation (approx.1 day) in 53% of the embryos on ED8.5, death in most of these embryos on ED9.5, and the termination of pregnancy on ED10.5 in litters with >20% dead embryos. Due to this selection, developmental delays and reduction in litter size were no longer observed thereafter in diabetic pregnancies. Male and female embryos were equally sensitive. High-throughput mRNA sequencing and pathway analysis of differentially expressed genes showed that retarded embryos failed to mount the adaptive suppression of gene expression that characterized non-retarded embryos (cell proliferation, cytoskeletal remodeling, oxidative phosphorylation). We conclude that failure of perigastrulation embryos of diabetic mothers to grow and survive is associated with their failure to shut down pathways that are strongly down-regulated in otherwise similar non-retarded embryos. Embryos that survive the early and generalized adverse effect of maternal diabetes, therefore, appear the subset in which malformations become manifest. PMID: 28916763 PMCID: PMC5601907 DOI: 10.1038/s41598-017-11696-x

Incidence of insulin-treated diabetes in Australia, 2015

This fact sheet provides the latest available national data on new cases of insulin-treated diabetes in Australia. It shows that in 2015 there were 28,775 people who began using insulin to treat their diabetes in Australia

• 63% had type 2 diabetes
• 26% (18,142) had gestational diabetes
• 9% had type 1 diabetes
• 2% had other forms of diabetes or their diabetes status was unknown.

AIHW catalogue number CVD 78

AIHW 2017. Incidence of insulin-treated diabetes in Australia, 2015. Diabetes series no. 27. Cat. no. CVD 78. Canberra: AIHW. Viewed 20 February 2017 http://www.aihw.gov.au/publication-detail/?id=60129558632.

Maternal and neonatal outcomes in Korean women with type 2 diabetes

Korean J Intern Med. 2017 Jan 26. doi: 10.3904/kjim.2016.105. [Epub ahead of print]

Jang HJ1, Kim HS2, Kim SH3.

Abstract

BACKGROUND/AIMS: The purpose of this study was to compare maternal and neonatal outcomes in Korean women with type 2 diabetes and nondiabetic controls.

METHODS: We performed a retrospective survey of 200 pregnancies in women with type 2 diabetes (n = 100) and nondiabetic controls (n = 100) who delivered from 2003 to 2010 at Cheil General Hospital & Women's Healthcare Center, Korea. We compared maternal characteristics as well as maternal and neonatal outcomes between groups matched by age, pre-pregnancy weight, body mass index, parity, and gestational age at delivery.

RESULTS: The number of infants that were small for gestational age and the rate of major congenital malformations were not significantly different. However, women with type 2 diabetes showed a slightly higher risk for primary caesarean section (35.0% vs. 18.0%, p = 0.006) as well as pre-eclampsia (10.0% vs. 2.0%, p = 0.017), infections during pregnancy (26.0% vs. 2.0%, p < 0.001), neonatal weight (3,370 ± 552.0 vs. 3,196 ± 543.3, p = 0.025), large for gestational age (22.0% vs. 9.0%, p = 0.011), and macrosomia (15.0% vs. 5.0%, p = 0.018) compared to nondiabetic controls.

CONCLUSIONS: Maternal and neonatal outcomes for women with type 2 diabetes were worse than those for nondiabetic controls. Diabetic women have a higher risk for primary caesarean section, pre-eclampsia, infections during pregnancy, large neonatal birth weight, large for gestational age, and macrosomia.

KEYWORDS: Diabetes mellitus, type 2; Pregnancy outcome

PMID 28122420 DOI: 10.3904/kjim.2016.105

2014

Gestational diabetes in a rural, regional centre in south Western Australia: predictors of risk

Rural Remote Health. 2014 Jul-Sep;14(3):2667. Epub 2014 Aug 29.

Kirke AB1, Evans SF2, Walters BN3.

Abstract

INTRODUCTION: Gestational diabetes mellitus (GDM) is the most common antenatal complication in Western Australia. Rural areas may be at greater risk due to poorer socioeconomic status, reduced healthcare access, increased obesity and greater Aboriginal population. This paper reviews the prevalence and risk factors of GDM and outcomes for pregnancies in a regional rural centre, with a view to predicting the risk of GDM in this population, given factors identified early in the pregnancy. METHODS: Retrospective logistic regression analysis of all deliveries at Bunbury Regional Hospital (BRH) from February 2009 to March 2011 was used to produce a risk score for development of GDM. RESULTS: Of 1645 women delivered at BRH in the study period, nine had pre-existing diabetes and were excluded. A further 73 (4.46%) developed GDM in the current pregnancy. Logistic regression showed GDM to be strongly associated with maternal obesity (adjusted odds ratio 2.48; 95% CI 1.62-3.82), age (2.21; 1.57-3.09) lowest socioeconomic quintile (2.34; 1.23-4.22) and Asian ethnicity (3.47; 1.25-8.26). A cut-off value of 0.4 for the scoring system predicted the absence of GDM in 97.75% of women with a sensitivity of 69.9% and a predicted risk of 20.7% for GDM. Maternal outcomes showed that GDM was associated with an increased caesarean section rate (48.0% vs 30.8%; p=0.0066), lower spontaneous vaginal birth rate (37.7% vs 56.6%; p=0.048), postpartum haemorrhage (28.8% vs 17.7%; p=0.028) and longer median hospital stay (3 vs 2 days; p=0.0001). Neonatal outcomes showed a threefold increase in shoulder dystocia (10.5% vs 3.5%; p=0.025). CONCLUSIONS: These results confirm the known association of GDM with age; obesity, lower socioeconomic quintile and Asian ethnicity are also present in the rural population. The absence of association with Aboriginal ethnicity was not expected and is discussed. KEYWORDS: Australia/Pacific; Diabetes; Endocrinology; Epidemiology; Maternal and Child Health; Medical; Obstetrics; Public Health

PMID 25171091

Prevalence Estimates of Gestational Diabetes Mellitus in the United States, Pregnancy Risk Assessment Monitoring System (PRAMS), 2007-2010

Prev Chronic Dis. 2014 Jun 19;11. doi: 10.5888/pcd11.130415. DeSisto CL1, Kim SY2, Sharma AJ2.

Abstract

INTRODUCTION: The true prevalence of gestational diabetes mellitus (GDM) is unknown. The objective of this study was 1) to provide the most current GDM prevalence reported on the birth certificate and the Pregnancy Risk Assessment Monitoring System (PRAMS) questionnaire and 2) to compare GDM prevalence from PRAMS across 2007-2008 and 2009-2010. METHODS: We examined 2010 GDM prevalence reported on birth certificate or PRAMS questionnaire and concordance between the sources. We included 16 states that adopted the 2003 revised birth certificate. We also examined trends from 2007 through 2010 and included 21 states that participated in PRAMS for all 4 years. We combined GDM prevalence across 2-year intervals and conducted t tests to examine differences. Data were weighted to represent all women delivering live births in each state. RESULTS: GDM prevalence in 2010 was 4.6% as reported on the birth certificate, 8.7% as reported on the PRAMS questionnaire, and 9.2% as reported on either the birth certificate or questionnaire. The agreement between sources was 94.1% (percent positive agreement = 3.7%, percent negative agreement = 90.4%). There was no significant difference in GDM prevalence between 2007-2008 (8.1%) and 2009-2010 (8.5%, P = .15). CONCLUSION: Our results indicate that GDM prevalence is as high as 9.2% and is more likely to be reported on the PRAMS questionnaire than the birth certificate. We found no statistical difference in GDM prevalence between the 2 phases. Further studies are needed to understand discrepancies in reporting GDM by data source.

PMID 24945238

http://www.cdc.gov/pcd/issues/2014/13_0415.htm

Effect of treatment of gestational diabetes mellitus: a systematic review and meta-analysis

PLoS One. 2014 Mar 21;9(3):e92485. doi: 10.1371/journal.pone.0092485. eCollection 2014.

Poolsup N1, Suksomboon N2, Amin M2. Author information

Abstract OBJECTIVE: To assess the efficacy and safety of treating pregnant women with gestational diabetes mellitus in comparison to usual antenatal care. METHODS: A systematic review and meta-analysis was conducted by including randomized controlled trials comparing any form of therapeutic intervention in comparison to usual antenatal care. A literature search was conducted using electronic databases together with a hand search of relevant journals and conference proceedings. RESULTS: Ten studies involving 3,881 patients contributed to meta-analysis. Our results indicated that gestational diabetes mellitus treatment significantly reduced the risk for macrosomia (RR, 0.47; 95% CI, 0.38-0.57), large for gestational age births (RR, 0.55; 95% CI, 0.45-0.67), shoulder dystocia (RR, 0.42; 95% CI, 0.23-0.77) and gestational hypertension (RR, 0.68; 95% CI, 0.53-0.87) without causing any significant increase in the risk for small for gestational age babies. However, no significant difference was observed between the two groups regarding perinatal/neonatal mortality, neonatal hypoglycemia, birth trauma, preterm births, pre-eclampsia, caesarean section and labor induction. CONCLUSION: Treating GDM reduces risk for many important adverse pregnancy outcomes and its association with any harm seems unlikely.

PMID 24658089

The Relation of a Woman's Impaired in Utero Growth and Association of Diabetes During Pregnancy

Matern Child Health J. 2014 Feb 21. [Epub ahead of print]

Chawla R1, Rankin KM, Collins JW Jr. Author information

Abstract

Small for gestational age (weight for gestational age <10th percentile, SGA) birth status and adulthood susceptibility to diabetes is well established, but the relationship to diabetes during pregnancy is incompletely understood. The authors investigated the association between women's impaired fetal growth (as measured by SGA status) and diabetes mellitus (DM) during pregnancy. Stratified and multivariable binomial regression analyses were performed on the Illinois transgenerational dataset. Former SGA (n = 13,934) mothers had a greater prevalence of DM during pregnancy than former appropriate for gestational age (AGA) mothers (n = 116,683): 2.7 versus 1.9 %, relative prevalence (RP) equaled 1.4 [95 % confidence interval (CI)1.3, 1.6]. In a multivariable binomial regression model, the adjusted RP (95 %CI) (controlling for maternal age, education, parity, plurality, marital status, and race/ethnicity) for DM during pregnancy for former SGA (compared to AGA) mothers equaled 1.5 (1.3, 1.6). When stratified by race/ethnicity, the adjusted RP (95 % CI) of DM during pregnancy for former SGA (compared to AGA), non-Latina White, African-American, and Mexican-American mothers was 1.4 (1.3, 1.6), 1.6 (1.2, 2.1), and 2.3 (1.1, 4.7), respectively. The authors conclude that impaired fetal growth (as measured by SGA status) is a risk factor for DM during pregnancy among the leading racial/ethnic groups in the United States.

PMID 24557833

2013

• NIH Consensus Development Conference: Diagnosing Gestational Diabetes Mellitus Bethesda, Maryland March 4–6, 2013.
• Diagnostic and Prognostic Performances Over 9 Years of a Selective Screening Strategy for Gestational Diabetes Mellitus "We aimed to evaluate a selective screening strategy for gestational diabetes mellitus (GDM) based on the presence of risk factors: BMI ≥25 kg/m(2), age ≥35 years, family history of diabetes, personal history of GDM, or birth of a child with macrosomia. ...The presence of risk factors increased during the last decade. This condition is predictive of GDM and GDM-related events. However, a selective screening would lead to missing one-third of the women with GDM who, even without risk factors, had more events than women without GDM. Therefore, these data stand against the present selective screening currently proposed in the French guidelines."
• Pre-pregnancy body mass index and the risk of adverse outcome in type 1 diabetic pregnancies: a population-based cohort study To assess the risk of perinatal complications in overweight and obese women with and without type 1 diabetes (T1DM) based on data from the Swedish Medical Birth Registry from 1998 to 2007 (3457 T1DM and 764 498 non-diabetic pregnancies). ...High pre-pregnancy BMI is an important risk factor for adverse outcome in type 1 diabetic pregnancies. The combined effect of both T1DM and overweight or obesity constitutes the greatest risk. It seems prudent to strive towards normal pre-pregnancy BMI in women with T1DM.
• The branching pattern of villous capillaries and structural changes of placental terminal villi in type 1 diabetes mellitus "Formalin fixed and paraffin embedded specimens of 14 normal and 17 Type 1 diabetic term placentas. Hypervascular as well as hypovascular villi of diabetic placenta displayed changed structure of villous stroma, i.e. the collagen envelope around capillaries looked thinner and the network of collagen fibers seemed less dense. ...The quantitative assessment of capillary branching has shown that villous capillaries are more branched in diabetic placentas. It is concluded that type 1 maternal diabetes enhances the surface area of the capillary wall by elongation, enlargement of diameter and higher branching of villous capillaries and disrupts the stromal structure of terminal villi."
• Diabetes in pregnancy: its impact on Australian women and their babies 2010 "Diabetes in pregnancy is common, affecting about 1 in 20 pregnancies. Pre-existing diabetes in pregnancy affected less than 1% of pregnancies, and gestational diabetes mellitus (GDM) affected about 5% in 2005–07. Among Aboriginal and Torres Strait Islander mothers, pre-existing diabetes affecting pregnancy was 3 to 4 times as common, and GDM twice as common, as in non-Indigenous mothers. The rate of Type 2 diabetes in Indigenous mothers was 10 times as high. Mothers with pre-existing diabetes were more likely to have pre-term birth, pre-term induced labour, caesarean section, hypertension and longer stay in hospital than mothers with GDM or without diabetes in pregnancy. Babies of mothers with pre-existing diabetes had higher rates of stillbirth, pre-term birth, high birthweight, low Apgar score, high-level resuscitation, admission to special care nursery/neonatal intensive care unit, and longer stay in hospital than babies of mothers with GDM or without diabetes in pregnancy.
• Fetoplacental vascular endothelial dysfunction as an early phenomenon in the programming of human adult diseases in subjects born from gestational diabetes mellitus or obesity in pregnancy "Gestational diabetes mellitus (GDM) and obesity in pregnancy (OP) are pathological conditions associated with placenta vascular dysfunction coursing with metabolic changes at the fetoplacental microvascular and macrovascular endothelium. These alterations are seen as abnormal expression and activity of the cationic amino acid transporters and endothelial nitric oxide synthase isoform, that is, the "endothelial L-arginine/nitric oxide signalling pathway." Several studies suggest that the endogenous nucleoside adenosine along with insulin, and potentially arginases, are factors involved in GDM-, but much less information regards their role in OP-associated placental vascular alterations. There is convincing evidence that GDM and OP prone placental endothelium to an "altered metabolic state" leading to fetal programming evidenced at birth, a phenomenon associated with future development of chronic diseases. In this paper it is suggested that this pathological state could be considered as a metabolic marker that could predict occurrence of diseases in adulthood, such as cardiovascular disease, obesity, diabetes mellitus (including gestational diabetes), and metabolic syndrome."

Metformin vs Insulin in the Management of Gestational Diabetes: A Meta-Analysis

PLoS One. 2013 May 27;8(5):e64585. doi: 10.1371/journal.pone.0064585. Print 2013.

Gui J, Liu Q, Feng L. Source Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Abstract

BACKGROUND: Nowadays, there have been increasing studies comparing metformin with insulin. But the use of metformin in pregnant women is still controversial, therefore, we aim to examine the efficiency and safety of metformin by conducting a meta-analysis of randomized controlled trials (RCTs) comparing the effects of metformin with insulin on glycemic control, maternal and neonatal outcomes in gestational diabetes mellitus (GDM). METHODS: We used the key words "gestational diabetes" in combination with "metformin" and searched the databases including Pubmed, the Cochrane Library, Web of knowledge, and Clinical Trial Registries. A random-effects model was used to compute the summary risk estimates. RESULTS: Meta-analysis of 5 RCTs involving 1270 participants detected that average weight gains after enrollment were much lower in the metformin group (n = 1006, P = 0.003, SMD = -0.47, 95%CI [-0.77 to -0.16]); average gestational ages at delivery were significantly lower in the metformin group (n = 1270, P = 0.02, SMD = -0.14, 95%CI [-0.25 to -0.03]); incidence of preterm birth was significantly more in metformin group (n = 1110, P = 0.01, OR = 1.74, 95%CI [1.13 to 2.68]); the incidence of pregnancy induced hypertension was significantly less in the metformin group (n = 1110, P = 0.02, OR = 0.52, 95%CI [0.30 to 0.90]). The fasting blood sugar levels of OGTT were significantly lower in the metformin only group than in the supplemental insulin group (n = 478, P = 0.0006, SMD = -0.83, 95%CI [-1.31 to -0.36]). CONCLUSIONS: Metformin is comparable with insulin in glycemic control and neonatal outcomes. It might be more suitable for women with mild GDM. This meta-analysis also provides some significant benefits and risks of the use of metformin in GDM and help to inform further development of management guidelines.

PMID 23724063

MedlinePlus - Metformin

New guidelines for diagnosis of gestational diabetes: pathology-based impact assessment

N Am J Med Sci. 2013 Mar;5(3):191-4. doi: 10.4103/1947-2714.109184.

Nwose EU, Richards RS, Bwititi PT, Butkowski EG. Source Charles Darwin University, NT Australia ; NSW Health Pathology, NSW Australia. Abstract BACKGROUND: A recent study indicated an average of 19.5% abnormal oral glucose tolerance in antenatal clients per year. AIM: The purpose of this study was to determine the impact on gestational diabetes cases due to new guidelines for diagnosis and classification of hyperglycaemia in pregnancy. MATERIALS AND METHODS: This study reviewed the archived clinical pathology data on oral glucose tolerance tests performed between January 1999 and December 2008 on antenatal clients (N = 615). The cases were reviewed to determine changes if any in percentage of gestational diabetes due to new guidelines. RESULTS: Over the 10 years period, a yearly average of additional 10.8% antenatal cases suggestive of gestational diabetes was observed due to the new recommended thresholds. Further, the average yearly incidence would have increased from 8.8 cases to 16.2 cases, which translates to almost 46% increase in the prospective numbers of gestational diabetes. CONCLUSIONS: This report presents the extent of how the new recommended guidelines for diagnosis and classification of hyperglycaemia in pregnancy could increase the prevalence of gestational diabetes. It also provides pathology-based evidence for the epidemiology of gestational diabetes mellitus and allows for planning the costs that would be attendant to the full implementation of the new guidelines. KEYWORDS: Gestational diabetes, Impact evaluation, New guidelines, Oral glucose tolerance test, Pathology-based evidence

PMID 23626954

First-trimester detection of fetal anomalies in pregestational diabetes using nuchal translucency, ductus venosus Doppler, and maternal glycosylated hemoglobin

Am J Obstet Gynecol. 2013 Jan 24. pii: S0002-9378(13)00088-4. doi: 10.1016/j.ajog.2013.01.041. [Epub ahead of print]

Miller JL, de Veciana M, Turan S, Kush M, Manogura A, Harman CR, Baschat AA. Source Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD; Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA.

Abstract

OBJECTIVE: The frequency of fetal anomalies in women with pregestational diabetes correlates with their glycemic control. This study aimed to assess the predictive performance of first-trimester fetal nuchal translucency (NT), ductus venosus (DV) Doppler, and hemoglobin A1c (HbA1c) to predict fetal anomalies in women with pregestational diabetes. STUDY DESIGN: This was a prospective observational study of patients undergoing first-trimester NT with DV Doppler. Screening performance was tested for first-trimester parameters to detect fetal anomalies. RESULTS: Of 293 patients, 17 had fetal anomalies (11 cardiac, 7 major, 3 multisystem). All anomalous fetuses were suspected prenatally. One had NT >95th centile, 2 had reversed DV a-wave, and 13 had HbA1c >7.0%. The HbA1c was the primary determinant of anomalies (r(2), 0.15; P < .001) and >8.35% was the optimal cutoff for prediction of anomalies with an area under the curve of 0.72 (95% confidence interval, 0.57-0.88). Therefore, first-trimester prediction of anomalies was best in women with increased NT or HbA1c >8.3% (sensitivity 70.6%, specificity 77.4%, positive predictive value 16.2%, negative predictive value 97.7%, P < .001). CONCLUSION: In women with pregestational diabetes and poor glycemic control an increased NT increases risks for major fetal anomalies. Second-trimester follow-up is required to achieve accurate prenatal diagnosis. Copyright © 2013 Mosby, Inc. All rights reserved.

PMID 23353022

2012

Transfer of maternal immunity to newborns of diabetic mothers

Clin Dev Immunol. 2012;2012:928187. Epub 2012 Sep 9.

França EL, Calderon Ide M, Vieira EL, Morceli G, Honorio-França AC. Source Institute of Biological and Health Science, Federal University of Mato Grosso, 78600-000 Barra do Garças, MT, Brazil.

Abstract

This study was carried out with hyperglycemic pregnant women to investigate the transfer of antibody classes to newborns across the placenta or by colostrum and the functional activity of phagocytes in maternal blood, cord blood, and colostrum from diabetes mothers. Samples from maternal blood, cord blood, and colostrum were collected from 20 normoglycemic and 20 hyperglycemic pregnant women. We determined antibodies levels, superoxide release, phagocytosis and bactericidal activity of phagocytes. We demonstrated that IgG levels in cord blood were higher in the hyperglycemic group. IgA and IgM levels were higher in maternal than in cord blood samples. Plasma antibody levels were lower in hyper- than in normoglycemic women. The colostrum of diabetic mothers had lower IgA and IgG levels. Colostrum and maternal blood phagocytes when exposed to EPEC increased the superoxide release. Cord blood phagocytes of hyperglycemic group, independently of bacteria, had higher superoxide release. Colostrum and blood phagocytes from diabetic group exhibited some phagocytic and microbicidal activity in response to EPEC. Mononuclear phagocytes from cord blood had the lowest phagocytosis, and bactericidal activity for EPEC, regardless of glycemic status. These data showed that hyperglycemia altered IgG transfer across the placenta and decreases immunoglobulin levels in maternal blood and colostrum.

PMID 22991568

http://www.hindawi.com/journals/cdi/2012/928187

Diagnostic and Prognostic Performances Over 9 Years of a Selective Screening Strategy for Gestational Diabetes Mellitus in a Cohort of 18,775 Subjects

Diabetes Care. 2012 Nov 12. [Epub ahead of print]

Cosson E, Benbara A, Pharisien I, Nguyen MT, Revaux A, Lormeau B, Sandre-Banon D, Assad N, Pillegand C, Valensi P, Carbillon L. Source Centre de Recherche en Nutrition Humaine d'Ile-de-France, Department of Endocrinology-Diabetology-Nutrition, Jean Verdier Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne Paris Cité, Paris 13 University, Bondy, France. Abstract OBJECTIVEWe aimed to evaluate a selective screening strategy for gestational diabetes mellitus (GDM) based on the presence of risk factors: BMI ≥25 kg/m(2), age ≥35 years, family history of diabetes, personal history of GDM, or birth of a child with macrosomia.RESEARCH DESIGN AND METHODSOf 20,630 deliveries between 2002 and 2010, we selected 18,775 deliveries in women with no known diabetes and for whom all risk factors were known. GDM was universally screened and defined as fasting plasma glucose level ≥5.3 mmol/L and/or 2-h postload (75 g) glucose level ≥7.8 mmol/L.RESULTSThe prevalence of at least one risk factor has increased since 2002 (P < 0.001) from 51.7 to 61.5%, with no change in the GDM prevalence (mean 14.4%, intention to screen). At least one risk factor was present in 58.5% of women who represented 65.3% of all those with GDM. The presence of risk factors was significantly associated with GDM (odds ratio 1.4 [95% CI 1.3-1.5], P < 0.001) and with GDM-related events (preeclampsia/large for gestational age/dystocia) (P < 0.001) with the following incidences: no GDM/no risk factor 8.8%, no GDM/risk factor 11.1%, GDM/no risk factor 16.7%, and GDM/risk factor 18.2%.CONCLUSIONSThe presence of risk factors increased during the last decade. This condition is predictive of GDM and GDM-related events. However, a selective screening would lead to missing one-third of the women with GDM who, even without risk factors, had more events than women without GDM. Therefore, these data stand against the present selective screening currently proposed in the French guidelines.

PMID 23150287

Adverse pregnancy outcomes in women with diabetes

Diabetol Metab Syndr. 2012 Sep 11;4(1):41. [Epub ahead of print]

Negrato CA, Mattar R, Gomes MB.

Abstract

ABSTRACT: Pregnancy affects both the maternal and fetal metabolism and even in nondiabetic women exerts a diabetogenic effect. Among pregnant women, 2 to 17.8% develop gestational diabetes. Pregnancy can also occur in women with preexisting diabetes, that can predispose the fetus to many alterations in organogenesis, growth restriction and the mother to some diabetes-related complications like retinopathy and nephropathy or accelerate the course of these complications if they are already present. Women with gestational diabetes generally start their treatment with diet and lifestyle modification; when these changes fail in keeping an optimal glycemic control, then insulin therapy must be considered. Women with type 2 diabetes in use of oral hypoglycemic agents are advised to change to insulin therapy. Those with preexisting type 1 diabetes must start an intensive glycemic control, preferably before conception. All these procedures are performed aiming to keep glycemic levels normal or near-normal as possible to avoid the occurrence of adverse perinatal outcomes to the mother and to the fetus. The aim of this review is to reinforce the need to improve the knowledge on reproductive health of women with diabetes during gestation and to understand what are the reasons for them failing to attend for prepregnancy care programs, and to understand the underlying mechanisms of adverse fetal and maternal outcomes, which in turn may lead to strategies for its prevention.

PMID 22964143

http://www.dmsjournal.com/content/pdf/1758-5996-4-41.pdf

Metabolic manifestations of insulin deficiency do not occur without glucagon action

Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):14972-6. Epub 2012 Aug 13.

Lee Y, Berglund ED, Wang MY, Fu X, Yu X, Charron MJ, Burgess SC, Unger RH. Source Touchstone Center for Diabetes Research, Hypothalamic Research Center, Department of Internal Medicine, and Advanced Imaging Research Center, Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390.

Abstract

To determine unambiguously if suppression of glucagon action will eliminate manifestations of diabetes, we expressed glucagon receptors in livers of glucagon receptor-null (GcgR(-/-)) mice before and after β-cell destruction by high-dose streptozotocin. Wild type (WT) mice developed fatal diabetic ketoacidosis after streptozotocin, whereas GcgR(-/-) mice with similar β-cell destruction remained clinically normal without hyperglycemia, impaired glucose tolerance, or hepatic glycogen depletion. Restoration of receptor expression using adenovirus containing the GcgR cDNA restored hepatic GcgR, phospho-cAMP response element binding protein (P-CREB), and phosphoenol pyruvate carboxykinase, markers of glucagon action, rose dramatically and severe hyperglycemia appeared. When GcgR mRNA spontaneously disappeared 7 d later, P-CREB declined and hyperglycemia disappeared. In conclusion, the metabolic manifestations of diabetes cannot occur without glucagon action and, once present, disappear promptly when glucagon action is abolished. Glucagon suppression should be a major therapeutic goal in diabetes.

PMID 22891336

Pre-pregnancy body mass index and the risk of adverse outcome in type 1 diabetic pregnancies: a population-based cohort study

BMJ Open. 2012 Feb 14;2(1):e000601. Print 2012.

Persson M, Pasupathy D, Hanson U, Westgren M, Norman M. Source Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden.

Abstract

OBJECTIVE: To assess the risk of perinatal complications in overweight and obese women with and without type 1 diabetes (T1DM). DESIGN: Prospective population-based cohort study. SETTING: This study was based on data from the Swedish Medical Birth Registry from 1998 to 2007. PARTICIPANTS: 3457 T1DM and 764 498 non-diabetic pregnancies were included. T1DM was identified based on ICD code O24.0. Mothers were categorised according to pre-pregnancy body mass index (BMI: weight in kilograms per height in square metres) as normal weight (BMI 18.5-24.9), overweight (BMI 25-29.9) or obese (BMI ≥30). Only women with singleton pregnancies and with data on BMI were included. PRIMARY/SECONDARY OUTCOMES: The primary outcome was large for gestational age (LGA: birth weight >90th percentile) infants. Secondary outcomes were major malformations, pre-eclampsia (PE), preterm delivery, perinatal mortality, delivery by Caesarean section and neonatal overweight. Logistic regression analysis was performed with normal weight non-diabetic women as the reference category and also within the diabetic cohort with normal weight type 1 diabetic women as the reference. The ORs were adjusted for ethnicity, maternal age, height, parity, smoking and chronic hypertension. RESULTS: 35% of women with T1DM were overweight and 18% were obese, as compared with 26% and 11%, respectively, in non-diabetic pregnancies. The incidences of adverse outcome increased with greater BMI category. As compared with non-diabetic normal weight women, the adjusted OR for obese T1DM for LGA was 13.26 (95% CI 11.27 to 15.59), major malformations 4.11 (95% CI 2.99 to 5.65) and PE 14.19 (95% CI 11.50 to 17.50). T1DM was a significant effect modifier of the association between BMI and LGA, major malformations and PE (p<0.001). CONCLUSION: High pre-pregnancy BMI is an important risk factor for adverse outcome in type 1 diabetic pregnancies. The combined effect of both T1DM and overweight or obesity constitutes the greatest risk. It seems prudent to strive towards normal pre-pregnancy BMI in women with T1DM.

PMID 22334581

http://bmjopen.bmj.com/content/2/1/e000601

Body Mass Index	18.5 - 24.9	25 - 29.9	≥30	p Value
Large for Gestational Age
Type 1 diabetes	778 (47)	603 (50)	313 (51)	0.170
Non-diabetic	39 265 (8.2)	26 828 (13)	15 049 (18)	<0.001
Major malformations
Type 1 diabetes	65 (4.0)	44 (3.7)	41 (6.6)	0.008
Non-diabetic	8186 (1.7)	3736 (1.9)	1610 (2.0)	<0.001
Pre-eclampsia
Type 1 diabetes	222 (14)	185 (15)	114 (18)	0.012
Non-diabetic	9872 (2.1)	6529 (3.3)	4810 (5.8)	<0.001
Preterm delivery
Type 1 diabetes	322 (20)	275 (23)	144 (23)	0.041
Non-diabetic	21 714 (4.5)	9464 (4.7)	4700 (5.7)	<0.001
Perinatal mortality
Type 1 diabetes	14 (0.85)	15 (1.3)	6 (0.97)	0.566
Non-diabetic	1554 (0.32)	948 (0.47)	593 (0.72)	<0.001
Caesarean section
Type 1 diabetes	748 (46)	639 (53)	362 (59)	<0.001
Non-diabetic	64 131 (13)	34 081 (17)	18 166 (22)	<0.001
Neonatal overweight
Type 1 diabetes	351 (21)	288 (24)	166 (27)	0.016
Non-diabetic	15 359 (3)	10 430 (5)	6466 (8)	<0.001
Table Data are presented as numbers (percentages). p Value = χ2 test, Kruskal–Wallis test, χ2 test for trends.

The branching pattern of villous capillaries and structural changes of placental terminal villi in type 1 diabetes mellitus

Placenta. 2012 Feb 6. [Epub ahead of print]

Jirkovská M, Kučera T, Kaláb J, Jadrníček M, Niedobová V, Janáček J, Kubínová L, Moravcová M, Zižka Z, Krejčí V. Source Institute of Histology and Embryology, First Faculty of Medicine, Charles University in Prague, Albertov 4, CZ-12801 Prague 2, Czech Republic.

Abstract

Maternal diabetes is associated with changes of the placental structure. These changes include great variability of vascularity manifested by strikingly hypovascular as well as hypervascular terminal villi. In this paper, normal placental terminal villi and pathological villi of type 1 diabetic placentas were compared concerning the structure of villous stroma, spatial arrangement of villous capillary bed and quantitative assessment of capillary branching pattern. Formalin fixed and paraffin embedded specimens of 14 normal and 17 Type 1 diabetic term placentas were used for picrosirius staining, vimentin and desmin immunohistochemistry and confocal microscopy. 3D models of villi and villous capillaries were constructed from stacks of confocal optical sections. Hypervascular as well as hypovascular villi of diabetic placenta displayed changed structure of villous stroma, i.e. the collagen envelope around capillaries looked thinner and the network of collagen fibers seemed less dense. The desmin immunocytochemistry has shown that stromal cells of hypervascular as well as hypovascular villi appeared nearly or completely void of desmin filaments. In comparison with normal villi, capillaries of hypovascular villi had a smaller diameter and displayed a markedly wavy course whereas in hypervascular villi numerous capillaries occurred in reduced stroma and often had a large diameter. The quantitative assessment of capillary branching has shown that villous capillaries are more branched in diabetic placentas. It is concluded that type 1 maternal diabetes enhances the surface area of the capillary wall by elongation, enlargement of diameter and higher branching of villous capillaries and disrupts the stromal structure of terminal villi. Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID 22317894

2011

Diabetes in pregnancy among indigenous women in Australia, Canada, New Zealand, and the United States: a method for systematic review of studies with different designs

BMC Pregnancy Childbirth. 2011 Dec 23;11:104.

Chamberlain C, Yore D, Li H, Williams E, Oldenburg B, Oats J, McNamara B, Eades S. Source International Public Health Unit Department of Epidemiology and Preventive Medicine School of Medicine, Nursing and Health Sciences Monash University, Victoria, Australia. Catherine.chamberlain@monash.edu Abstract BACKGROUND: Diabetes in pregnancy, which includes gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM), is associated with poor outcomes for both mother and infant during pregnancy, at birth and in the longer term. Recent international guidelines recommend changes to the current GDM screening criteria. While some controversy remains, there appears to be consensus that women at high risk of T2DM, including indigenous women, should be offered screening for GDM early in pregnancy, rather than waiting until 24-28 weeks as is current practice. A range of criteria should be considered before changing screening practice in a population sub-group, including: prevalence, current practice, acceptability and whether adequate treatment pathways and follow-up systems are available. There are also specific issues related to screening in pregnancy and indigenous populations. The evidence that these criteria are met for indigenous populations is yet to be reported. A range of study designs can be considered to generate relevant evidence for these issues, including epidemiological, observational, qualitative, and intervention studies, which are not usually included within a single systematic review. The aim of this paper is to describe the methods we used to systematically review studies of different designs and present the evidence in a pragmatic format for policy discussion. METHODS/DESIGN: The inclusion criteria will be broad to ensure inclusion of the critical perspectives of indigenous women. Abstracts of the search results will be reviewed by two persons; the full texts of all potentially eligible papers will be reviewed by one person, and 10% will be checked by a second person for validation. Data extraction will be standardised, using existing tools to identify risks for bias in intervention, measurement, qualitative studies and reviews; and adapting criteria for appraising risk for bias in descriptive studies. External validity (generalisability) will also be appraised. The main findings will be synthesised according to the criteria for population-based screening and summarised in an adapted "GRADE" tool. DISCUSSION: This will be the first systematic review of all the published literature on diabetes in pregnancy among indigenous women. The method provides a pragmatic approach for synthesizing relevant evidence from a range of study designs to inform the current policy discussion.

PMID 22196083

Lesser than diabetes hyperglycemia in pregnancy is related to perinatal mortality: a cohort study in Brazil

BMC Pregnancy Childbirth. 2011 Nov 11;11:92.

Wendland EM, Duncan BB, Mengue SS, Schmidt MI. Source Post-Graduate Program in Epidemiology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. elianawend@gmail.com

Abstract

BACKGROUND: Gestational diabetes related morbidity increases along the continuum of the glycemic spectrum. Perinatal mortality, as a complication of gestational diabetes, has been little investigated. In early studies, an association was found, but in more recent ones it has not been confirmed. The Brazilian Study of Gestational Diabetes, a cohort of untreated pregnant women enrolled in the early 1990's, offers a unique opportunity to investigate this question. Thus, our objective is to evaluate whether perinatal mortality increases in a continuum across the maternal glycemic spectrum. METHODS: We prospectively enrolled and followed 4401 pregnant women attending general prenatal care clinics in six Brazilian state capitals, without history of diabetes outside of pregnancy, through to birth, and their offspring through the early neonatal period. Women answered a structured questionnaire and underwent a standardized 2-hour 75-g oral glucose tolerance test (OGTT). Obstetric care was maintained according to local protocols. We obtained antenatal, delivery and neonatal data from hospital records. Odds ratios (OR) were estimated using logistic regression. RESULTS: We ascertained 97 perinatal deaths (67 fetal and 31 early neonatal). Odds of dying increased according to glucose levels, statistically significantly so only for women delivering at gestational age ≥34 weeks (p < 0.05 for glycemia-gestational age interaction). ORs for a 1 standard deviation difference in glucose, when analyzed continuously, were for fasting 1.47 (95% CI 1.12, 1.92); 1-h 1.55 (95% CI 1.15, 2.07); and 2-h 1.53 (95% CI 1.15, 2.02). The adjusted OR for IADPSG criteria gestational diabetes was 2.21 (95% CI 1.15, 4.27); and for WHO criteria gestational diabetes, 3.10 (95% CI 1.39, 6.88). CONCLUSIONS: In settings of limited detection and treatment of gestational diabetes mellitus, women across a spectrum of lesser than diabetes hyperglycemia, experienced a continuous rise in perinatal death with increasing levels of glycemia after 34 weeks of pregnancy. Current GDM diagnostic criteria identified this increased risk of mortality.

PMID 22078268

Importance of early complex evaluation in high-risk pregnancy associated to diabetes mellitus. Case presentation and review of the literature

Rom J Morphol Embryol. 2011;52(3 Suppl):1127-32.

Gheorman L, Iliescu D, Ceauşu I, Paulescu D, Pleşea IE, Gheorman V. Source Department of Obstetrics and Gynecology, University of Medicine and Pharmacy of Craiova, Romania. Abstract We report and analyze a case of pregnancy associated with pre-existent diabetes mellitus and fetal congenital anomalies involving neural tube defect (NTD) and congenital heart defect (CHD). We discuss the early antenatal management of such high-risk pregnancies. The clinical course, maternal paraclinic profile and morpho-sonographic investigation of the fetus are described. A 28-year-old pregnant woman with pre-existing diabetes and a pre-pregnancy BMI 31 kg/m², without preconception counseling for optimization of glycemic control was evaluated in our center for first trimester genetic screening at 12 weeks of gestation. Considering a high-risk pregnancy, careful fetal morphological assessment by ultrasound was performed; the extensive examination using high-resolution probes, both by transabdominal and transvaginal approach, found hypoplastic left heart syndrome (HLHS) and open spina bifida (OSB). Both anomalies present important difficulties regarding first trimester diagnostic. The couple was informed and chose termination of pregnancy (TOP). We consider that an anomaly scan at 12-13 + 6 gestational weeks by expert operators should be offered to high-risk pregnancies, because it provides the chance to detect the majority of fetal anomalies. This offer for couples the option of an early decision about the management of pregnancy in cases of severe fetal anomalies; postnatal treatment could be discussed as well as TOP and if the latter is chosen, the maternal risk and the potential psychological burden are lowered, as compared with TOP performed in the mid-second trimester.

PMID 22119836

Fetoplacental vascular endothelial dysfunction as an early phenomenon in the programming of human adult diseases in subjects born from gestational diabetes mellitus or obesity in pregnancy

Exp Diabetes Res. 2011;2011:349286. Epub 2011 Nov 24. Leiva A, Pardo F, Ramírez MA, Farías M, Casanello P, Sobrevia L.

Source Cellular and Molecular Physiology Laboratory (CMPL) and Perinatology Research Laboratory (PRL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Catolica de Chile, P.O. Box 114-D, Santiago, Chile.

Abstract

Gestational diabetes mellitus (GDM) and obesity in pregnancy (OP) are pathological conditions associated with placenta vascular dysfunction coursing with metabolic changes at the fetoplacental microvascular and macrovascular endothelium. These alterations are seen as abnormal expression and activity of the cationic amino acid transporters and endothelial nitric oxide synthase isoform, that is, the "endothelial L-arginine/nitric oxide signalling pathway." Several studies suggest that the endogenous nucleoside adenosine along with insulin, and potentially arginases, are factors involved in GDM-, but much less information regards their role in OP-associated placental vascular alterations. There is convincing evidence that GDM and OP prone placental endothelium to an "altered metabolic state" leading to fetal programming evidenced at birth, a phenomenon associated with future development of chronic diseases. In this paper it is suggested that this pathological state could be considered as a metabolic marker that could predict occurrence of diseases in adulthood, such as cardiovascular disease, obesity, diabetes mellitus (including gestational diabetes), and metabolic syndrome.

PMID 22144986

Morphometric characteristics of placental villi in pregnant women with diabetes

Bull Exp Biol Med. 2011 Sep;151(5):650-4.

[Article in English, Russian] Dubova EA, Pavlov KA, Yesayan RM, Nagovitsyna MN, Tkacheva ON, Shestakova MV, Shchegolev AI. Source V. I. Kulakov Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russian Federation; Institute of Diabetes, Endocrinology Research Center, Ministry of Health and Social Development of Russian Federation, Moscow, Russia. dubovaea@gmail.com. Abstract We conducted a comparative morphological study of placentas from women with gestational diabetes and diabetes mellitus. Morphometry of histological preparations revealed similar type of changes in the studied parameters of placental villi in diabetes mellitus and gestational diabetes. The maximum deviation of the studied parameters from the control was noted in type 1 diabetes mellitus.

PMID 22462069

Breast milk hormones and regulation of glucose homeostasis

Int J Pediatr. 2011;2011:803985. Epub 2011 May 5.

Savino F, Liguori SA, Sorrenti M, Fissore MF, Oggero R. Source Department of Pediatrics, Regina Margherita Children's Hospital, University of Turin, 10126 Turin, Italy.

Abstract

Growing evidence suggests that a complex relationship exists between the central nervous system and peripheral organs involved in energy homeostasis. It consists in the balance between food intake and energy expenditure and includes the regulation of nutrient levels in storage organs, as well as in blood, in particular blood glucose. Therefore, food intake, energy expenditure, and glucose homeostasis are strictly connected to each other. Several hormones, such as leptin, adiponectin, resistin, and ghrelin, are involved in this complex regulation. These hormones play a role in the regulation of glucose metabolism and are involved in the development of obesity, diabetes, and metabolic syndrome. Recently, their presence in breast milk has been detected, suggesting that they may be involved in the regulation of growth in early infancy and could influence the programming of energy balance later in life. This paper focuses on hormones present in breast milk and their role in glucose homeostasis.

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PMID 21760816

2010

Pictorial Essay: Infants of diabetic mothers

Alorainy IA, Barlas NB, Al-Boukai AA.

Indian J Radiol Imaging. 2010 Aug;20(3):174-81.

About 3 to 10% of pregnancies are complicated by glycemic control abnormalities. Maternal diabetes results in significantly greater risk for antenatal, perinatal, and neonatal morbidity and mortality, as well as congenital malformations. The number of diabetic mothers is expected to rise, as more and more of the obese pediatric female population in developed and some developing countries progresses to childbearing age. Radiologists, being part of the teams managing such pregnancies, should be well aware of the findings that may be encountered in infants of diabetic mothers. Timely, accurate, and proper radiological evaluation can reduce morbidity and mortality in these infants. The purpose of this essay is to illustrate the imaging findings in the various pathological conditions involving the major body systems in the offspring of women with diabetes.

PMID: 21042439 http://www.ncbi.nlm.nih.gov/pubmed/21042439

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963757

The possible role of epigenetics in gestational diabetes: cause, consequence, or both

Obstet Gynecol Int. 2010;2010:605163. Epub 2010 Oct 31.

Fernández-Morera JL, Rodríguez-Rodero S, Menéndez-Torre E, Fraga MF.

Endocrinology and Nutrition Service, Hospital Universitario Central de Asturias, Av. Julian Clavería s/n, 33006 Oviedo, Spain. Abstract Gestational diabetes mellitus (GDM) is defined as the glucose intolerance that is not present or recognized prior to pregnancy. Several risk factors of GDM depend on environmental factors that are thought to regulate the genome through epigenetic mechanisms. Thus, epigenetic regulation could be involved in the development of GDM. In addition, the adverse intrauterine environment in patients with GDM could also have a negative impact on the establishment of the epigenomes of the offspring.

PMID: 21052542 http://www.ncbi.nlm.nih.gov/pubmed/21052542

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2968420

Elevated glucose induces congenital heart defects by altering the expression of tbx5, tbx20, and has2 in developing zebrafish embryos

Liang J, Gui Y, Wang W, Gao S, Li J, Song H. Birth Defects Res A Clin Mol Teratol. 2010 Jun;88(6):480-6.

BACKGROUND: Maternal diabetes increases the risk of congenital heart defects in infants, and hyperglycemia acts as a major teratogen. Multiple steps of cardiac development, including endocardial cushion morphogenesis and development of neural crest cells, are challenged under elevated glucose conditions. However, the direct effect of hyperglycemia on embryo heart organogenesis remains to be investigated.

METHODS: Zebrafish embryos in different stages were exposed to D-glucose for 12 or 24 hr to determine the sensitive window during early heart development. In the subsequent study, 6 hr post-fertilization embryos were treated with either 25 mmol/liter D-glucose or L-glucose for 24 hr. The expression of genes was analyzed by whole-mount in situ hybridization.

RESULTS: The highest incidence of cardiac malformations was found during 6-30 hpf exposure periods. After 24 hr exposure, D-glucose-treated embryos exhibited significant developmental delay and diverse cardiac malformations, but embryos exposed to L-glucose showed no apparent phenotype. Further investigation of the origin of heart defects showed that cardiac looping was affected earliest, while the specification of cardiac progenitors and heart tube assembly were complete. Moreover, the expression patterns of tbx5, tbx20, and has2 were altered in the defective hearts.

CONCLUSIONS: Our data demonstrate that elevated glucose alone induces cardiac defects in zebrafish embryos by altering the expression pattern of tbx5, tbx20, and has2 in the heart. We also show the first evidence that cardiac looping is affected earliest during heart organogenesis. These research results are important for devising preventive and therapeutic strategies aimed at reducing the occurrence of congenital heart defects in diabetic pregnancy.

PMID: 20306498 http://www.ncbi.nlm.nih.gov/pubmed/20306498

The impact of gestational diabetes mellitus on pregnancy outcome comparing different cut-off criteria for abnormal glucose tolerance

Acta Obstet Gynecol Scand. 2010 Nov 5. [Epub ahead of print]

Anderberg E, Källén K, Berntorp K.

Department of Obstetrics and Gynecology in Lund, Skåne University Hospital, Lund University, Sweden.

Abstract Objective. To examine pregnancy outcomes in relation to different categories of glucose tolerance during pregnancy. Design. Prospective observational cohort study. Setting. Patient recruitment and data collection were performed in four delivery departments in southern Sweden. Population. Women delivering during 2003-2005; 306 with gestational diabetes mellitus, 744 with gestational impaired glucose tolerance and 329 randomly selected controls. Methods. All women were offered a 75 g oral glucose tolerance test during pregnancy. On the basis of their capillary 2-hour plasma glucose concentrations, three groups were identified: gestational diabetes mellitus (>10.0 mmol/l), gestational impaired glucose tolerance (8.6-9.9 mmol/l) and controls (<8.6 mmol/l). Data for the groups were compared using a population-based database. Main outcome measures. Maternal and fetal outcomes. Results. For the gestational diabetes mellitus group, adjusted odds ratios (95% confidence intervals) for hypertensive disorders during pregnancy and induction of labor and emergency cesarean section were 2.7 (1.3-5.8), 3.1 (1.8-5.2) and 2.5 (1.5-4.4), respectively; and for Apgar score <7 at 5 minutes, need for neonatal intensive care >1 day and large-for-gestational age infant were 9.6 (1.2-78.0), 5.2 (2.8-9.6) and 2.5 (1.3-5.1), respectively. The increases in odds ratios for the gestational impaired glucose tolerance group were less pronounced but still significant for hypertension during pregnancy, induction of labor, large-for-gestational age infant and use of neonatal intensive care >1 day, with odds ratios (95% confidence interval) 2.0 (1.0-4.1), 1.8 (1.1-3.0), 2.1 (1.1-3.9) and 2.1 (1.1-3.8), respectively. Conclusions. These data indicate that even limited degrees of maternal hyperglycemia may affect the outcome of pregnancy.

PMID: 21050147 http://www.ncbi.nlm.nih.gov/pubmed/21050147

Sonographic Evaluation and the Pregnancy Complicated by Diabetes

Curr Diab Rep. 2010 Nov 3. [Epub ahead of print]

McNamara JM, Odibo AO.

Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Washington University School of Medicine, 4911 Barnes-Jewish Plaza, 5th Floor Maternity Building, Campus Box 8064, Saint Louis, MO, 63110, USA, mcnamaraj@wudosis.wustl.edu. Abstract Sonography is a fundamental tool in the management of pregnancies affected by maternal diabetes. Purposeful use of ultrasound in each trimester provides an invaluable amount of information about the developing fetus including gestational age and growth patterns, anatomical structure and function, assessment of fetal well-being, and prediction of adverse outcome. There are great ongoing research efforts in this field of prenatal diagnosis and management, yet even more are needed.

PMID: 21046292 http://www.ncbi.nlm.nih.gov/pubmed/21046292

Recommended changes to diagnostic criteria for gestational diabetes: Impact on workload

Aust N Z J Obstet Gynaecol. 2010 Oct;50(5):439-43. doi: 10.1111/j.1479-828X.2010.01218.x. Epub 2010 Sep 1.

Flack JR, Ross GP, Ho S, McElduff A.

Diabetes Centre, Bankstown-Lidcombe Hospital Department of Medicine, University of NSW, Bankstown Department of Endocrinology, Royal North Shore Hospital Discipline of Medicine, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, Australia. Abstract Background:  Gestational diabetes mellitus (GDM) is recognised as a significant problem in pregnancy. Changes to GDM diagnostic criteria have been proposed following analysis of data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. We sought to assess the impact on the workload for GDM management in Australia that would occur if these changes were adopted. Aim:  To assess the impact on health professional workload, specifically management of the number of additional women who would be diagnosed with GDM, should the newly recommended diagnostic criteria be adopted in Australia. Methods:  We analysed oral glucose tolerance test results undertaken in pregnant women at two large pathology services in South West and Northern Sydney. We calculated GDM rates using current Australasian Diabetes in Pregnancy Society (ADIPS) Australian Criteria and the rates using the proposed new criteria. Results:  These workload data compare ADIPS and proposed International Association of Diabetes and Pregnancy Study Groups Criteria. In a high-risk population examined in two time periods, the estimated increase in workload was 29.0% (based on November 2005 to August 2007 data) and 31.9% (based on September 2007 to August 2009 data). Data from Northern Sydney indicated a 21.7% increased workload (based on September 1998 to July 2009 data). Conclusions:  If the newly recommended changes to the diagnostic criteria for GDM are implemented in Australia, we may need to change the way we currently structure our services to manage GDM, to cope with the workload impact of the significantly increased number of women who would require management. In some units this change will be substantial.

© 2010 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology © 2010 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. PMID: 21039377

Gestational diabetes mellitus: why screen and how to diagnose

Karagiannis T, Bekiari E, Manolopoulos K, Paletas K, Tsapas A. Hippokratia. 2010 Jul;14(3):151-4. PMID: 20981162

Maternal nutrition and perinatal outcomes

J Midwifery Womens Health. 2010 Nov-Dec;55(6):502-11.

Barger MK.

Department of Family Health Care Nursing, University of California San Francisco School of Nursing, San Francisco, CA 94143-0606, USA. Mary.Barger@nursing.ucsf.edu

Abstract Diet and patterns of eating during pregnancy can affect perinatal outcomes through direct physiologic effects or by stressing the fetus in ways that permanently affect phenotype. Supplements are not a magic nutritional remedy, and evidence of profound benefit for most supplements remains inconclusive. However, research supports calcium supplements to decrease preeclampsia. Following a low glycemic, Mediterranean-type diet appears to improve ovulatory infertility, decrease preterm birth, and decrease the risk of gestational diabetes. Although women in the United States have adequate levels of most nutrients, subpopulations are low in vitamin D, folate, and iodine. Vitamin D has increasingly been shown to be important not only for bone health, but also for glucose regulation, immune function, and good uterine contractility in labor. To ensure adequate vitamin and micronutrient intake, especially of folate before conception, all reproductive age women should take a multivitamin daily. In pregnancy, health care providers need to assess women's diets, give them weight gain recommendations based on their body mass index measurement, and advise them to eat a Mediterranean diet rich in omega-3 fatty acids (ingested as low-mercury risk fatty fish or supplements), ingest adequate calcium, and achieve adequate vitamin D levels through sun exposure or supplements. Health care providers should continue to spend time on nutrition assessment and counseling.

Copyright © 2010 American College of Nurse-Midwives. Published by Elsevier Inc. All rights reserved. PMID: 20974412

Maternal diabetes induces congenital heart defects in mice by altering the expression of genes involved in cardiovascular development

Kumar SD, Dheen ST, Tay SS. Cardiovasc Diabetol. 2007 Oct 30;6:34. PMID: 17967198

On awakening	not above 95
1 hour after a meal	not above 140
2 hours after a meal	not above 120