Technology and Pregnancy

Abstract

Diabetes Technology & TherapeuticsVol. 16, No. S1 Original ArticlesFree AccessTechnology and PregnancyAdrian Cotarelo, Homaira T. Zaman, Lois Jovanovič, and Moshe HodAdrian CotareloSansum Diabetes Research Institute, Santa Barbara, CA.Search for more papers by this author, Homaira T. ZamanSansum Diabetes Research Institute, Santa Barbara, CA.Search for more papers by this author, Lois JovanovičSansum Diabetes Research Institute, Santa Barbara, CA.Search for more papers by this author, and Moshe HodHelen Schneider Hospital for Women, Rabin Medical Center, Petah Tikva, Israel.Search for more papers by this authorPublished Online:30 Jan 2014https://doi.org/10.1089/dia.2014.1508AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail IntroductionIn part because of the global obesity epidemic, pregnancies complicated by diabetes have grown into a widespread issue throughout all parts of the world. There are over 25 million people affected by diabetes in the United States alone, with 12.6 million diabetic women aged 20 and over (1). Maternal hyperglycemia can have devastating effects on pregnancy when uncontrolled, including above-average birth weight, macrosomia, birth defects, and an increased risk for obesity and diabetes in the future. This year, we reviewed 1,299 articles and came to a final listing of 81 possible articles to analyze. We selected 15 studies that we felt were representative of the research conducted in the field of technology, treatment, and pregnancy over the course of the past year. A large proportion of these original articles related to diagnostic methods for determining gestational diabetes mellitus (GDM). While this topic comprised much of the literature over the past year, we chose to address this topic by citing the National Institutes of Health (NIH) consensus article on the matter. Studies were reviewed systematically and evaluated for sample size, implications on diabetes care, and the validity of their findings.Gestational diabetes, pre-pregnancy obesity and pregnancy weight gain in relation to excess fetal growth: variations by race/ethnicityBowers K1,2, Laughon SK1, Kiely M1, Brite J3, Chen Z4, Zhang C11Epidemiology Branch and 4Biostatistics Branch, Division of Epidemiology, Statistics, and Preventive Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD; 2Present address: Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; and 3CUNY Institute of Demographic Research and CUNY School of Public Health at Hunter College City University of New York, New York, NYDiabetologia 2013;56: 1263–71ObjectiveThe incidence of pediatric obesity and diabetes is increasing throughout the world, with children of ethnic backgrounds being impacted more severely. This study observed the effects of prepregnancy adiposity, weight gain during the pregnancy, and GDM on excess fetal growth to evaluate the susceptibility of various ethnic populations to adverse effects of hyperglycemia.MethodsA retrospective observational study was formed from a cohort of 228,562 births between 2002 and 2008 across 19 hospitals spread throughout the United States. Ethnicities and races observed included non-Hispanic white, non-Hispanic black, Hispanic, and Asian/Pacific Islander. Data were abstracted from electronic medical records. Exclusion criteria included multiple gestation pregnancies, and limited available data on relevant statistics such as GDM, prepregnancy body–mass index (BMI), and birth weight. The final cohort consisted of 105,985 pregnancies. High pregnancy weight gain was defined as that which was greater than the median weight gain observed in the cohort. Each of three factors (prepregnancy adiposity, weight gain during the pregnancy, and GDM) were evaluated independently for association with large-for-gestational-age (LGA) and macrosomic infants. Each was then weighed together in order to observe the joint effects between the presence of one, two, or all three factors.ResultsAll three factors were found to be independently associated with an increased risk for LGA births. This was true for all races with the exception of non-Hispanic white women, who did not observe an increase in LGA births from GDM alone. 10,689 neonates were LGA, and 8,682 were macrosomic. In general, LGA and macrosomic infants were more likely to be born to women with GDM, as well as those who had a previous macrosomic infant. Birth weight was linearly associated with prepregnancy BMI, with the highest proportion of LGA and macrosomic infants born to mothers with a prepregnancy BMI over 30 kg/m2. Asian and Pacific Islander (PI) women had the highest percentage of LGA infants and GDM, while white non-Hispanic women had the lowest. Asian and PI women were also less likely to be overweight or obese before the pregnancy. A significant interaction was observed between race, BMI, and GDM incidence. With the exception of non-Hispanic white women with GDM, the presence of any of the observed factors was significantly associated with LGA infants. The presence of two factors increased the risk further across all races. The presence of all three did not increase the risk by a significant amount further in Asian women, while they nearly doubled the risk for Hispanic and non-Hispanic white women compared with being exposed to only two factors.ConclusionsGDM, prepregnancy adiposity, and pregnancy weight gain were each associated with an increased birth weight, while combinations of these factors increased the risk for LGA and macrosomia even further. The degree to which these combinations of factors affected the risk for LGA and macrosomic births depended on race. This may be a genetic difference or due to physiological differences in fat storage or glucose metabolism between races. Due to differences in body size between races and genders, it is not appropriate in a clinical setting to identify a general cut-off weight for LGA and macrosomia. Race must also be considered due to these differences in genetics and physiology. GDM was greatly associated with an increased risk of an LGA or macrosomic birth, including those who were underweight and of normal weight. This increase in risk varied by race, prepregnancy BMI, and pregnancy weight gain, with an increased joint effect that varied by race. A woman's race should be considered when evaluating the prevention strategy for excess fetal growth in a pregnancy complicated by GDM.CommentThis study had an impressively large and varied sample size from throughout the United States, granting their result's generalizability. One limitation addressed in the article is the combination of Asian and Pacific Islander races. These were factored in together because of the organization of the Consortium of Safe Labor database, which provided the patient data for the study. Differences in risk for LGA and macrosomia have been noted between Asian and Pacific Islander women, and this may have affected the findings relating to this group. However, the study makes a strong case for a further consideration of race among women with GDM. The observation of a synergistic effect of the three additional factors evaluated by the study allows for a more aggressive treatment plan for women presenting with the relevant risk factors for their race and should be considered in future GDM care.Association between serum 25-hydroxyvitamin D in early pregnancy and risk of gestational diabetes mellitusParlea L1, Bromberg IL2,3, Feig DS3–5, Vieth R2,3,6, Merman E1, Lipscombe LL4,71Faculty of Medicine; 2Department of Laboratory Medicine and Pathobiology, Faculty of Medicine; 4Department of Medicine; and 6Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada; Departments of 3Pathology and Laboratory Medicine and 5Medicine, Mount Sinai Hospital, New York, NY; and 7Department of Medicine, Women's College Research Institute, Women's College Hospital, Toronto, Ontario, CanadaDiabet. Med. 2012;29: e25–e32Vitamin D deficiency in pregnancy and gestational diabetes mellitusBurris HH1,2, Rifas-Shiman SL7, Kleinman K7, Litonjua AA4,5, Huh SY3, Rich-Edwards JW6,8, Camargo CA Jr.4,10, Gillman MW7,91Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA; Divisions of 2Newborn Medicine and 3Gastroenterology and Nutrition, Department of Pediatrics, Children's Hospital Boston, Boston, MA; 4Channing Laboratory, 5Division of Pulmonary and Critical Care, and 6Division of Women's Health, Department of Medicine, Brigham & Women's Hospital, Boston, MA; 7Obesity Prevention Program, Department of Population Medicine, Harvard Medical School, and Harvard Pilgrim Health Care Institute, Boston, MA; Departments of 8Epidemiology and 9Nutrition, Harvard School of Public Health, Boston, MA; and 10Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MAAm J Obstet Gynecol 2012;207: 182.e1–8.ObjectiveBoth of the above studies aimed to evaluate whether or not low levels of 25-hydroxyvitamin D in pregnancy were associated with an increased risk of developing GDM. The Parlea study measured vitamin D levels in the first trimester between weeks 15 and 18, while the Burris study tested for vitamin D levels during the second trimester between weeks 26 and 28.MethodsThe Parlea study was a nested case–control study that gathered data from March 1, 2008, to December 31, 2009, and 116 cases of women with GDM were compared with 219 control subjects. 25-Hydroxyvitamin D levels were obtained from antenatal blood samples. The Burris study was a prospective cohort of 1,314 women enrolled into the study before the 22nd week of their pregnancy. 25-Hydroxyvitamin D levels were measured during a GDM screening involving a 1-hour 50 g glucose challenge test.ResultsIn the Parlea study, GDM patients had significantly lower 25-hydroxyvitamin D levels in the first trimester than control subjects. Vitamin D levels below the top quartile (<73.5 nmol/L) were associated with a doubled likelihood of developing GDM. During the Burris study, patients with a vitamin D level below 25 nmol/L were associated with an increased risk for GDM. Both studies resulted in an odds ratio of 2.2 for increased risk of GDM when 25-hydroxyvitamin D levels were low.ConclusionsBoth studies arrived at the conclusion that low 25-hydroxyvitamin D levels resulted in a significantly increased risk for GDM. While they tested for vitamin D levels at different points in the pregnancy, the association with GDM was the same. As vitamin D may affect glucose tolerance, future treatment of GDM patients should monitor vitamin D levels in order to better care for pregnant patients.CommentThe Burris study had a large sample size, adding to the validity of its results. While the Parlea study was smaller by almost 10-fold, both analyses came to the same conclusions. As vitamin D levels appear to have a significant impact on the incidence of GDM, it may be worthwhile for providers to consider the findings of these studies for future care of pregnant patients already at risk for developing GDM.National institutes of health consensus development conference statement: diagnosing gestational diabetes mellitus, March 4–6, 2013Consensus Development Panel: VanDorsten1 et al.1Division of Maternal–Fetal Medicine, Medical University of South Carolina, Charleston, SCObstet Gynecol 2013;122: 358–69ObjectiveAt the present, the standard screening for GDM recommended by the American College of Obstetricians and Gynecologists involves first performing a glucose challenge test in which serum glucose is measured 1 hour after a woman drinks a 50 g glucose solution. If these results are abnormal, an oral glucose tolerance test (OGTT) is then performed. The OGTT requires that a woman's blood is drawn four times over 3 hours as she drinks a 100 g glucose solution. The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) has proposed a one-step approach for GDM diagnosis involving a 2-hour OGTT with three blood sugar measurements: one fasting blood glucose, and one at the 1-hour and 2-hour marks. If any of the three are abnormal, GDM is diagnosed. This proposed method is estimated to at least double the number of GDM diagnoses in the United States. The purpose of this statement is to determine if, at this point in time, the NIH can recommend that the United States begin to adopt the one-step approach to diagnosing GDM.MethodsThe Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Nursing Research, Office of Research on Women's Health, Centers for Disease Control and Prevention, and the NIH Office of Disease Prevention convened to review the available scientific evidence in order to assess the official stance on GDM diagnoses. The panel included experts in many fields including, but not limited to, maternal and fetal medicine, healthcare economics, and obstetrics and gynecology. A planning committee developed seven questions to be addressed by the Consensus Development Panel.ConsiderationsThe panel evaluated current screening and diagnostic methods for GDM, the thresholds for these approaches, and how these thresholds were chosen. The impact of a one-step diagnostic tool for GDM on the U.S. healthcare system, as well as the health outcomes of undiagnosed women and their children, were assessed. Finally, the panel considered which diagnostic approach for GDM should be recommended, as well as any research gaps in the approach to GDM diagnosis.ConclusionsThe one-step approach offers some advantages over the current method, primarily used in the United States alone. There is value in adopting the international standard for GDM diagnosis in terms of both future research and outcome comparison between nations. Additionally, it would allow the diagnosis of GDM to be completed in one visit rather than two. There are concerns involving the large increase in the number of GDM diagnoses if the one-step method were implemented. There is also a lack of research to determine whether these additional GDM women would gain benefit from the treatment, and if it is worth the additional cost toward healthcare. The panel does not believe that there is sufficient evidence to adopt the one-step approach recommended by the IADPSG. Additional research is needed before the one-step approach can be recommended.CommentWhile the panel considered many effects that the conversion to the one-step approach will have on the United States, we feel that the one-step approach is entirely appropriate and should be adopted in the United States. While the one-step would increase the number of GDM diagnoses, and the associated costs involved with diagnosis and treatment, the United States is among the few that are not yet on board with this diagnostic method, calling into question the conclusion that further research is necessary.Maternal smoking during pregnancy and daughters' risk of gestational diabetes and obesityMattsson K1, Källén K1, Longnecker MP2, Rignell-Hydbom A1, Rylander L11Division of Occupational and Environmental Medicine, Institute of Laboratory Medicine, Lund University, Lund, Sweden; and 2Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NCDiabetologia 2013;56: 1689–95ObjectiveThis study aimed to examine the risk of developing GDM after being exposed to tobacco smoke in utero. Patients were also assessed for an increased risk of obesity or type 1 or type 2 diabetes mellitus.MethodsData from 80,189 pregnancies were collected from the Medical Birth Register of Sweden. In utero tobacco exposure was classified as nonsmoker, moderate exposure (1–9 cigarettes/day), and heavy exposure (10 cigarettes/day or more). Maternal smoking habits during the pregnancy were obtained via self-report by trained midwives during their first antenatal visit. Data were collected for pregnancies that occurred from 1982 to 2010. These mothers were flagged as generation 1 (G1), and their children as generation 2 (G2). G2 women were observed for outcomes of GDM, nongestational diabetes, and obesity.ResultsThe adjusted odds ratio for gestational diabetes and obesity was increased in those women who had been exposed both moderately and severely to in utero tobacco smoke. Women exposed to heavy tobacco smoke had a decreased adjusted odds ratio for nongestational diabetes. Obesity appeared to have a dose–response association with in utero tobacco exposure, with heavily exposed women having an increased risk over moderately exposed women.ConclusionsWomen who were exposed to tobacco smoke in utero are at a higher risk for developing gestational diabetes and obesity later in life. A decreased risk of nongestational diabetes was observed for women exposed heavily to tobacco in utero. This association remained even after adjusting for age, parity, BMI, gestational age, mode of delivery, birth weight, and age of the mother. While the majority of nongestational diabetes cases observed in the study were type 1, this is similar to the prevalence of type 1 diabetes throughout Sweden.CommentFew studies are available on the effects of in utero tobacco exposure later in life. The information on smoking was obtained via self-report, which could contain a large source of error. People may not report honestly, particularly on a subject that may be taboo such as smoking habits during a pregnancy. The Sweden Medical Birth Register (MBR) has very high levels of completion to its data; however, the MBR does not record what week of gestation the first antenatal visit occurs. Therefore, it is not possible to tell if the meeting influenced smoking status for later parts of the pregnancy. The study concludes that heavy smoking during pregnancy decreases type 1 and type 2 diabetes later in life, while at the same time increasing the risk for obesity.Decreased concentrations of the lipoprotein lipase inhibitor angiopoietin-like protein 4 and increased serum triacylglycerol are associated with increased neonatal fat mass in pregnant women with gestational diabetes mellitusOrtega-Senovilla H1, Schaefer-Graf U2, Meitzner K2, Abou-Dakn M2, Herrera E11Faculties of Pharmacy and Medicine, University CEU San Pablo, Madrid, Spain; and 2Department of Obstetrics and Gynecology, Center for Diabetes in Pregnancy, St. Joseph's Hospital, Berlin, GermanyJ Clin Endocrinol Metab: DOI: 10.1210/jc.2013-1614ObjectiveAngiopoietin-like protein 4 (ANGPTL4) is an inhibitor of lipoprotein lipase (LPL) activity. Past studies have suggested that changes in LPL activity affect the transfer of fatty acids to the fetus and affect growth. This study aimed to evaluate the impact on neonatal fat mass (FM) by concentrations of ANGPTL4 and triacylglycerols (TAG) in maternal blood samples and umbilical cord blood of pregnant women with GDM.MethodsFasting maternal blood samples were drawn during pregnancy no longer than 1 week before delivery, and umbilical cord blood was taken after the vaginal delivery during 80 pregnancies complicated by GDM and 90 controls without GDM. All neonates were grouped based on FM for the 25th percentile or lower, 25th to 75th percentile, or 75th to 100th percentiles. Controls matched for age and pregestational BMI.ResultsThe highest concentrations of TAG and nonesterified fatty acids (NEFA) were found in the maternal blood samples of women with GDM whose infants were born with the highest FM. These women also showed the lowest levels of ANGPTL4. Lower levels of ANGPTL4 were observed in both GDM cases and controls among infants born with the highest FM. Glucose and insulin concentrations were independent of any change to FM. Umbilical cord blood of infants born with the highest FM of women with GDM had higher concentrations of insulin and lower TAG levels than those with lower FM. There was no appreciable difference in NEFA or ANGPTL4 levels between GDM cases and controls.ConclusionsLow levels of ANGPTL4 were associated with an increased placental transfer of lipids. This observation was found in both control cases and women with well-controlled GDM. Higher neonatal FM and TAG levels, along with a decreased ANGPTL4, were observed in pregnancies with well-controlled GDM. Increased maternal TAG was associated with a decreased TAG level in the umbilical cord blood. An increased transfer of lipids across the placenta would contribute to higher fetal FM. GDM pregnancies tended to have higher levels of insulin, and the effect of LPL may have been impacted by the hyperinsulinemia.CommentBecause of the apparent effect of ANGPTL4 levels on neonatal birth weight, it may be worth considering this laboratory value in a clinical setting when assessing GDM patients. However, it is important to consider the relatively small sample size of this study. There may have been a trend simply among the group of patients, as all cases came from the same institution. Despite the sample size, the findings of the study appear valid and should be considered in future clinical care of GDM patients.1,5-Anhydroglucitol as a marker of maternal glycaemic control and predictor of neonatal birthweight in pregnancies complicated by type 1 diabetes mellitusNowak N1, Skupien J1,2, Cyganek K3, Matejko B1, Malecki MT1,31Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland; 2Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, MA; and 3Department of Metabolic Diseases, University Hospital, Krakow, PolandDiabetologia 2013;56: 709–13ObjectiveDespite reaching HbA1c goals, women with diabetes are still faced with an increased risk of macrosomic infants. This study aimed to measure the use of 1,5-anhydroglucitol (1,5-AG) in monitoring glycemic control in pregnant women compared with the standard observation of HbA1c levels.MethodsEighty-two pregnant type 1 diabetic women were observed over the course of 4 years. Every trimester, their 1,5-AG as well as HbA1c levels were monitored, and 58 of these women also had continuous glucose monitoring system (CGMS) data that were analyzed over a 7-day period before 1,5-AG and HbA1c values were collected. CGMS data and birth weight were then analyzed against 1,5-AG and HbA1c levels using linear and logistic regression models, and receiver operating characteristic (ROC) analysis was used to model the association between third-trimester 1,5-AG levels and macrosomia. Macrosomia was defined as a birth weight over the 90th percentile.ResultsThroughout the trial, the women met HbA1c targets and maintained good glycemic control. HbA1c levels were not correlated with 1,5-AG levels; however, 1,5-AG levels were strongly correlated with CGMS mean glucose levels. 1,5-AG levels correlated with hyperglycemia, but not with hypoglycemia. About 80% of macro soma cases occurred in women with HbA1c levels <6.0%. However, the average 1,5-AG levels in the second and third trimester were significantly lower in women with macrosomic infants, with third-trimester 1,5-AG levels as the stronger indicator of macrosomia. In the ROC analysis, the area under the curve resulted in a significantly better model for predicting birth weight when HbA1c and 1,5-AG levels were considered in tandem.ConclusionsThis study indicates that 1,5-AG is a more valuable marker than HbA1c for observing episodes of hyperglycemia in pregnant women with type 1 diabetes. These values were strongly correlated to the CGMS data and were a stronger predictor of macrosomia than HbA1c alone. Because 1,5-AG levels change rapidly with glucose levels, they may improve treatment and dosage modifications in pregnant type 1 diabetic patients. Third-trimester 1,5-AG levels were strongly associated with infant birth weights, and an even stronger model for predicting macrosomia resulted from a combined analysis of both the HbA1c and 1,5-AG levels.CommentPrevalence of macrosomia may be because of the HbA1c target itself (6.0%) being too high and not attributed to the HbA1c readings themselves. 1,5-AG appears to be a valid, useful marker of recent hyperglycemic levels. However, point-of-care HbA1c is more practical in a primary care setting as it can be measured more immediately. Additionally, if 1,5-AG is not associated with hypoglycemia, it may be dangerous to observe this value alone. In the future it may be valid to consider both HbA1c and 1,5-AG levels in the second and third trimesters in order to predict macrosomia in the babies of type 1 diabetic women.A randomized trial comparing perinatal outcomes using insulin detemir or neutral protamine Hagedorn in type 1 diabetesHod M1, Mathiesen ER2–4, Jovanovič L5, McCance DR6, Ivanisevic M7, Durán-Garcia S8, Brøndsted L9, Nazeri A9, Damm P2,4,101Helen Schneider Women's Hospital, Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 2Center for Pregnant Women with Diabetes, Rigshospitalet, 3Department of Endocrinology, and 4Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; 5Sansum Diabetes Research Institute, Santa Barbara, CA; 6Metabolic Unit, Royal Victoria Hospital, Belfast, United Kingdom; 7Department of Obstetrics and Gynecology, University Hospital of Zagreb, Zagreb, Croatia; 8Catedra de Endocrinologia, Unidad de Diabetes y Embarazo, Hospital Universitario de Valme, Seville, Spain; 9Novo Nordisk A/S, Søborg, Denmark; and 10Department of Obstetrics, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkJ Matern Fetal Neonatal Med 2013 June 5: [Epub ahead of print]Maternal efficacy and safety outcomes in a randomized, controlled trial comparing insulin detemir with NPH insulin in 310 pregnant women with type 1 diabetesMathiesen ER1–3, Hod M4, Ivanisevic M5, Duran Garcia S6, Brøndsted L7, Jovanovic L8, Damm P1,3,9, McCance DR10; on behalf of the Detemir in Pregnancy Study Group1Center for Pregnant Women with Diabetes, Rigshospitalet, 2Department of Endocrinology, and 3Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; 4Helen Schneider Women's Hospital, Rabin Medical Centre, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 5Department of Obstetrics and Gynecology, University Hospital of Zagreb, Zagreb, Croatia; 6Catedra de Endocrinologia, Unidad de Diabetes y Embarazo, Hospital Universitario de Valme, Seville, Spain; 7Novo Nordisk A/S, Søborg, Denmark; 8Sansum Diabetes Research Institute, Santa Barbara, CA; 9Department of Obstetrics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; and 10Metabolic Unit, Royal Victoria Hospital, Belfast, United KingdomDiabetes Care 2012;35: 2012–17ObjectiveIn nonpregnant diabetic patients, short- and long-acting insulin analogs have been shown to be more effective than human insulins at facilitating healthy glycemic control; however, few studies have tested the use of long-acting insulin analogs in pregnant women with type 1 diabetes. This is the first clinical trial to compare the safety and efficacy of the basal insulin analog, detemir (IDet), with human neutral protamine Hagedorn (NPH), both in combination with rapid-acting insulin aspart (IAsp), in pregnant women with type 1 diabetes. The publication by Hod et al. reports the perinatal and obstetric outcomes, while a separate article by Mathiesen et al. reports the maternal outcomes of the pregnant women in the same trial.MethodsThis was a randomized, controlled noninferiority trial involving 310 women with type 1 diabetes conducted at 79 sites in 17 countries. The women were either randomized to IDet (49.0%) or to NPH (51.0%). The primary endpoint analyzed was HbA1c at 36 gestational weeks as an indicator of glycemic control. Perinatal outcomes across the two treatment arms, reported in Hod et al., were analyzed in terms of three main categories: fetal death, termination of pregnancy, and live birth. The composite pregnancy outcome was defined as the incidence of at least one of the following secondary outcomes: small/large (<10th or >90th percentile) for gestational age, early fetal death, perinatal or neonatal mortality, congenital malformations, and/or preterm delivery. Maternal efficacy endpoints, as described in Mathiesen et al., included HbA1c values at 8–12, 14, and 24 gestational weeks, fasting plasma glucose (FPG) levels, number of hypoglycemic episodes, insulin dose, and weight gain during pregnancy.ResultsThe primary endpoint, estimated mean HbA1c at 36 gestational weeks, did not statistically differ across the IDet and NPH treatment arms. The composite pregnancy outcomes detailed in Hod et al. were comparable between the two groups. Gestational age at delivery was significantly greater for the offspring of women treated with IDet compared with those of women treated with NPH. No other statistically significant differences in perinatal outcomes were found between the two treatment groups. As described in Mathiesen et al., estimated mean FPG levels were significantly lower in IDet patients compared with NPH patients at both 24 and 36 gestational weeks. No statistically significant differences were observed with regard to weight gain, insulin dose, or number of hypoglycemic episodes between the two groups.ConclusionsThis study demonstrates that the use of IDet during pregnancy is safe and effective with respect to both maternal and perinatal/obstetric outcomes, and is noninferior to NPH for glycemic control in type 1 diabetic mothers. Additionally, maternal FPG levels are significantly lower in IDet-treated subjects compared with NPH-treated subjects, without an accompanying increase in the number of hypoglycemic episodes. A larger sample size is required to analyze the occurrence of uncommon perinatal outcomes with st