Which growth standards should be used to identify large- and small-for-gestational age infants of mothers with type 1 diabetes? A pre-specified analysis of the CONCEPTT trial

Abstract: Background: Offspring of women with type 1 diabetes are at increased risk of fetal growth patterns which are associated with perinatal morbidity. Our aim was to compare rates of large- and small-for-gestational age (LGA; SGA) defined according to different criteria, using data from the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT). Methods: This was a pre-specified analysis of CONCEPTT involving 225 pregnant women and liveborn infants from 31 international centres (ClinicalTrials.gov NCT01788527; registered 11/2/2013). Infants were weighed immediately at birth and GROW, INTERGROWTH and WHO centiles were calculated. Relative risk ratios, sensitivity and specificity were used to assess the different growth standards with respect to perinatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, respiratory distress, neonatal intensive care unit (NICU) admission and a composite neonatal outcome. Results: Accelerated fetal growth was common, with mean birthweight percentiles of 82.1, 85.7 and 63.9 and LGA rates of 62, 67 and 30% using GROW, INTERGROWTH and WHO standards respectively. Corresponding rates of SGA were 2.2, 1.3 and 8.9% respectively. LGA defined according to GROW centiles showed stronger associations with preterm delivery, neonatal hypoglycaemia, hyperbilirubinaemia and NICU admission. Infants born > 97.7th centile were at highest risk of complications. SGA defined according to INTERGROWTH centiles showed slightly stronger associations with perinatal outcomes. Conclusions: GROW and INTERGROWTH standards performed similarly and identified similar numbers of neonates with LGA and SGA. GROW-defined LGA and INTERGROWTH-defined SGA had slightly stronger associations with neonatal complications. WHO standards underestimated size in preterm infants and are less applicable for use in type 1 diabetes. Trial registration: This trial is registered with ClinicalTrials.gov. number NCT01788527. Trial registered 11/2/2013

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial.

BACKGROUND: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING: Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research

Counterpoint: Establishing consensus in the diagnosis of GDM following the HAPO study

The International Association of Diabetes in Pregnancy Study Groups (IADPSG) recommended a new protocol of 1-step testing with a 75 g oral glucose tolerance test for gestational diabetes in 2010. Since that time, these recommendations have been carefully scrutinized and accepted by a variety of organizations, but challenged or rejected by others. In the current review, we present more details regarding the background to the development of the IADPSG recommendations and seek to place them in context with the available epidemiologic and randomized controlled trial data. In this "counterpoint," we also provide specific rebuttal for errors of fact and disputed contentions provided by Long and Cundy in their 2013 article in Current Diabetes Reports

Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study:associations of maternal A1C and glucose with pregnancy outcomes

OBJECTIVE-To compare associations of maternal glucose and MC with adverse outcomes in the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and determine, based on those comparisons, if A1C measurement can provide an alternative to an oral glucose tolerance test (OGTT) in pregnant women

Hyperglycemia and adverse pregnancy outcome study:Neonatal glycemia

OBJECTIVE: The goal was to describe the temporal pattern of neonatal plasma glucose levels and associations with maternal glucose levels, cord serum C-peptide levels, and neonatal size and adiposity

Strategies for implementing the WHO diagnostic criteria and classification of hyperglycaemia first detected in pregnancy

The World Health Organization (WHO) has recently released updated recommendations on Diagnostic Criteria and Classification of Hyperglycaemia First Detected in Pregnancy which are likely to increase the prevalence of gestational diabetes mellitus (GDM). Any increase in the number of women with GDM has implications for health services since these women will require treatment and regular surveillance during the pregnancy. Some health services throughout the world may have difficulty meeting these demands since country resources for addressing the diabetes burden are finite and resource allocation must be prioritised by balancing the need to improve care of people with diabetes and finding those with undiagnosed diabetes, including GDM. Consequently each health service will need to assess their burden of hyperglycaemia in pregnancy and decide if and how it will implement programmes to test for and treat such women. This paper discusses some considerations and options to assist countries, health services and health professionals in these deliberations. (C) 2014 Elsevier Ireland Ltd. All rights reserved.World Diabetes Foundation for a study on the screening for gestational diabetes in Tamil NaduUniv Sydney, Boden Inst Obes Nutr & Exercise, Sydney, NSW 2006, AustraliaUniv Fed Rio Grande do Sul, Post Grad Program Epidemiol, Porto Alegre, RS, BrazilUAE Univ, Fac Med, Al Ain, U Arab EmiratesUniv Geneva, Fac Med, Serv Obstet Matern HUG, Geneva, SwitzerlandUniv Cape Town, Groote Schuur Hosp, Dept Obstet & Gynaecol, ZA-7925 Cape Town, South AfricaTel Aviv Univ, Sackler Fac Med, Rabin Med Ctr, Helen Schneider Hosp Women, IL-69978 Tel Aviv, IsraelMcGill Univ, Dept Med, Montreal, PQ, CanadaMcGill Univ, Dept Obstet & Gynaecol, Montreal, PQ, CanadaNorthwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USATokyo Womens Med Univ, Ctr Diabet, Ebina Gen Hosp, Tokyo, JapanRiga Stradins Univ, Riga East Clin Univ Hosp, Riga, LatviaDr Balaji Diabet Care Ctr, Diabet Res Inst, Chennai, Tamil Nadu, IndiaNatl Hlth Serv Fdn Trust, Cambridge Univ Hosp, Inst Metab Sci, Cambridge, EnglandUniv Yaounde I, Fac Med & Biomed Sci, Yaounde, CameroonNewcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne, Tyne & Wear, EnglandUniversidade Federal de São Paulo, Dept Obstet, São Paulo, BrazilPeking Univ, Hosp 1, Beijing 100871, Peoples R ChinaUniversidade Federal de São Paulo, Dept Obstet, São Paulo, BrazilWeb of Scienc

Nutritional interventions to ameliorate the effect of endocrine disruptors on human reproductive health: A semi-structured review from FIGO.

BackgroundEndocrine disrupting chemicals have harmful effects on reproductive, perinatal, and obstetric outcomes.ObjectiveTo analyze the evidence on nutritional interventions to reduce the negative effects of endocrine disruptors on reproductive, perinatal, and obstetric outcomes.Search strategyA search of MEDLINE (PubMed), Allied Health Literature (CINAHL), EMBASE, Web of Science, and the Cochrane Database was conducted from inception to May 2021.Selection criteriaExperimental studies on human populations.Data collection and analysisData were collected from eligible studies. Risk of bias assessment was completed using the Cochrane risk of bias tool and the ROBINS-I Tool.ResultsDatabase searches yielded 15 362 articles. Removing 11 181 duplicates, 4181 articles underwent abstract screening, 26 articles were eligible for full manuscript review, and 16 met full inclusion criteria. Several interventions were found to be effective in reducing exposure to endocrine disruptors: avoidance of plastic containers, bottles, and packaging; avoidance of canned food/beverages; consumption of fresh and organic food; avoidance of fast/processed foods; and supplementation with vitamin C, iodine, and folic acid. There were some interventional studies examining therapies to improve clinical outcomes related to endocrine disruptors.ConclusionDietary alterations can reduce exposure to endocrine disruptors, with limited data on interventions to improve endocrine-disruptor-related clinical outcomes. This review provides useful instruction to women, their families, healthcare providers, and regulatory bodies

Nutritional interventions to ameliorate the effect of endocrine disruptors on human reproductive health: A semi-structured review from FIGO

Background: Endocrine disrupting chemicals have harmful effects on reproductive, perinatal, and obstetric outcomes. Objective: To analyze the evidence on nutritional interventions to reduce the negative effects of endocrine disruptors on reproductive, perinatal, and obstetric outcomes. Search strategy: A search of MEDLINE (PubMed), Allied Health Literature (CINAHL), EMBASE, Web of Science, and the Cochrane Database was conducted from inception to May 2021. Selection criteria: Experimental studies on human populations. Data collection and analysis: Data were collected from eligible studies. Risk of bias assessment was completed using the Cochrane risk of bias tool and the ROBINS-I Tool. Results: Database searches yielded 15 362 articles. Removing 11 181 duplicates, 4181 articles underwent abstract screening, 26 articles were eligible for full manuscript review, and 16 met full inclusion criteria. Several Interventions were found to be effective in reducing exposure to endocrine disruptors: avoidance of plastic containers, bottles, and packaging; avoidance of canned food/beverages; consumption of fresh and organic food; avoidance of fast/processed foods; and supplementation with vitamin C, iodine, and folic acid. There were some interventional studies examining therapies to improve clinical outcomes related to endocrine disruptors. Conclusion: Dietary alterations can reduce exposure to endocrine disruptors, with limited data on interventions to improve endocrine-disruptor–related clinical outcomes. This review provides useful instruction to women, their families, healthcare providers, and regulatory bodie