Diabetes and Pregnancy

Abstract

Key MessagesPre-Existing DiabetesPreconception and During Pregnancy•All women with pre-existing type 1 or type 2 diabetes should receive preconception care to optimize glycemic control, assess for complications, review medications and begin folic acid supplementation.•Effective contraception should be provided until the woman is ready for pregnancy.•Care by an interprofessional diabetes health-care team composed of a diabetes nurse educator, dietitian, obstetrician and endocrinologist/internist with expertise in diabetes, both prior to conception and during pregnancy, has been shown to minimize maternal and fetal risks in women with pre-existing type 1 and type 2 diabetes.•Women should aim for a glycated hemoglobin (A1C) of ≤7.0% (ideally ≤6.5% if possible) when planning pregnancy, or ≤6.5% (ideally ≤6.1% if possible) during pregnancy.•Women should consider the use of the continuous glucose monitor during pregnancy to improve glycemic control and neonatal outcomes.Postpartum•All women should be given information regarding the benefits of breastfeeding, effective birth control and the importance of planning another pregnancy.Gestational Diabetes MellitusDuring Pregnancy•Untreated gestational diabetes leads to increased maternal and perinatal morbidity. Treatment reduces these adverse pregnancy outcomes.•In women at high risk of undiagnosed type 2 diabetes, early screening (<20 weeks) with an A1C should be done to identify women with potentially overt diabetes to guide fetal surveillance and early maternal treatment, including self-monitoring of blood glucose, interventions that promote healthy behaviours and healthy weight gain.•The diagnostic criteria for gestational diabetes (GDM) remain controversial; however, these guidelines identify a “preferred” and an “alternate” screening approach. The preferred approach is an initial 50 g glucose challenge test, followed, if abnormal, with a 75 g oral glucose tolerance test. A diagnosis of GDM is made if one plasma glucose value is abnormal (i.e. fasting ≥5.3 mmol/L, 1 hour ≥10.6 mmol/L, 2 hours ≥9.0 mmol/L). The alternate approach is a 1-step approach of a 75 g oral glucose tolerance test. A diagnosis of GDM is made if one plasma glucose value is abnormal (i.e. fasting ≥5.1 mmol/L, 1 hour ≥10.0 mmol/L, 2 hours ≥8.5 mmol/L).•First-line therapy consists of diet and physical activity. If glycemic targets are not met, insulin or metformin can then be used.Postpartum•Women with gestational diabetes should be encouraged to breastfeed immediately after birth and for a minimum of 4 months to prevent neonatal hypoglycemia, childhood obesity, and diabetes for both the mother and child.•Women should be screened for diabetes between 6 weeks and 6 months postpartum, with a 75 g oral glucose tolerance test and be given ongoing education regarding strategies to reduce the risk of developing type 2 diabetes.Key Messages for Women with Diabetes Who are Pregnant or Planning a PregnancyPre-Existing Diabetes•The key to a healthy pregnancy for a woman with diabetes is keeping blood glucose levels in the target range—both before she is pregnant and during her pregnancy.•Poorly controlled diabetes in a pregnant woman with type 1 or type 2 diabetes increases her risk of miscarrying, having a baby born with a malformation and having a stillborn.•Women with type 1 or type 2 diabetes should discuss pregnancy plans with their diabetes health-care team to:◦Review blood glucose targets◦Assess general health and status of any diabetes-related complications◦Aim for optimal weight and, if overweight, start weight loss before pregnancy with healthy eating◦Review medications◦Start folic acid supplementation (1.0 mg daily)◦Ensure appropriate vaccinations have occurred.Gestational Diabetes•Between 3% to 20% of pregnant women develop gestational diabetes, depending on their risk factors•Risk Factors include:◦Being:■35 years of age or older■from a high-risk group (African, Arab, Asian, Hispanic, Indigenous, or South Asian)◦Using:■Corticosteroid medication◦Having:■Obesity (a body mass index greater than or equal to 30 kg/m2)■Prediabetes■Gestational diabetes in a previous pregnancy■Given birth to a baby that weighed more than 4 kg■A parent, brother or sister with type 2 diabetes■Polycystic ovary syndrome or acanthosis nigricans (darkened patches of skin).•All pregnant women without known pre-existing diabetes should be screened for gestational diabetes between 24 to 28 weeks of pregnancy•If you were diagnosed with gestational diabetes during your pregnancy, it is important to:◦Breastfeed immediately after birth and for a minimum of 4 months in order to prevent hypoglycemia in your newborn, obesity in childhood, and diabetes for both you and your child◦Reduce your weight, targeting a normal body mass index in order to reduce your risk of gestational diabetes in the next pregnancy and developing type 2 diabetes◦Be screened for type 2 diabetes after your pregnancy:■within 6 weeks to 6 months of giving birth■before planning another pregnancy■every 3 years (or more often depending on your risk factors). Pre-Existing Diabetes Preconception and During Pregnancy•All women with pre-existing type 1 or type 2 diabetes should receive preconception care to optimize glycemic control, assess for complications, review medications and begin folic acid supplementation.•Effective contraception should be provided until the woman is ready for pregnancy.•Care by an interprofessional diabetes health-care team composed of a diabetes nurse educator, dietitian, obstetrician and endocrinologist/internist with expertise in diabetes, both prior to conception and during pregnancy, has been shown to minimize maternal and fetal risks in women with pre-existing type 1 and type 2 diabetes.•Women should aim for a glycated hemoglobin (A1C) of ≤7.0% (ideally ≤6.5% if possible) when planning pregnancy, or ≤6.5% (ideally ≤6.1% if possible) during pregnancy.•Women should consider the use of the continuous glucose monitor during pregnancy to improve glycemic control and neonatal outcomes. Postpartum•All women should be given information regarding the benefits of breastfeeding, effective birth control and the importance of planning another pregnancy. Gestational Diabetes Mellitus During Pregnancy•Untreated gestational diabetes leads to increased maternal and perinatal morbidity. Treatment reduces these adverse pregnancy outcomes.•In women at high risk of undiagnosed type 2 diabetes, early screening (<20 weeks) with an A1C should be done to identify women with potentially overt diabetes to guide fetal surveillance and early maternal treatment, including self-monitoring of blood glucose, interventions that promote healthy behaviours and healthy weight gain.•The diagnostic criteria for gestational diabetes (GDM) remain controversial; however, these guidelines identify a “preferred” and an “alternate” screening approach. The preferred approach is an initial 50 g glucose challenge test, followed, if abnormal, with a 75 g oral glucose tolerance test. A diagnosis of GDM is made if one plasma glucose value is abnormal (i.e. fasting ≥5.3 mmol/L, 1 hour ≥10.6 mmol/L, 2 hours ≥9.0 mmol/L). The alternate approach is a 1-step approach of a 75 g oral glucose tolerance test. A diagnosis of GDM is made if one plasma glucose value is abnormal (i.e. fasting ≥5.1 mmol/L, 1 hour ≥10.0 mmol/L, 2 hours ≥8.5 mmol/L).•First-line therapy consists of diet and physical activity. If glycemic targets are not met, insulin or metformin can then be used. Postpartum•Women with gestational diabetes should be encouraged to breastfeed immediately after birth and for a minimum of 4 months to prevent neonatal hypoglycemia, childhood obesity, and diabetes for both the mother and child.•Women should be screened for diabetes between 6 weeks and 6 months postpartum, with a 75 g oral glucose tolerance test and be given ongoing education regarding strategies to reduce the risk of developing type 2 diabetes. Pre-Existing Diabetes•The key to a healthy pregnancy for a woman with diabetes is keeping blood glucose levels in the target range—both before she is pregnant and during her pregnancy.•Poorly controlled diabetes in a pregnant woman with type 1 or type 2 diabetes increases her risk of miscarrying, having a baby born with a malformation and having a stillborn.•Women with type 1 or type 2 diabetes should discuss pregnancy plans with their diabetes health-care team to:◦Review blood glucose targets◦Assess general health and status of any diabetes-related complications◦Aim for optimal weight and, if overweight, start weight loss before pregnancy with healthy eating◦Review medications◦Start folic acid supplementation (1.0 mg daily)◦Ensure appropriate vaccinations have occurred. Gestational Diabetes•Between 3% to 20% of pregnant women develop gestational diabetes, depending on their risk factors•Risk Factors include:◦Being:■35 years of age or older■from a high-risk group (African, Arab, Asian, Hispanic, Indigenous, or South Asian)◦Using:■Corticosteroid medication◦Having:■Obesity (a body mass index greater than or equal to 30 kg/m2)■Prediabetes■Gestational diabetes in a previous pregnancy■Given birth to a baby that weighed more than 4 kg■A parent, brother or sister with type 2 diabetes■Polycystic ovary syndrome or acanthosis nigricans (darkened patches of skin).•All pregnant women without known pre-existing diabetes should be screened for gestational diabetes between 24 to 28 weeks of pregnancy•If you were diagnosed with gestational diabetes during your pregnancy, it is important to:◦Breastfeed immediately after birth and for a minimum of 4 months in order to prevent hypoglycemia in your newborn, obesity in childhood, and diabetes for both you and your child◦Reduce your weight, targeting a normal body mass index in order to reduce your risk of gestational diabetes in the next pregnancy and developing type 2 diabetes◦Be screened for type 2 diabetes after your pregnancy:■within 6 weeks to 6 months of giving birth■before planning another pregnancy■every 3 years (or more often depending on your risk factors). This chapter discusses pregnancy in both pre-existing diabetes (type 1 and type 2 diabetes diagnosed prior to pregnancy), overt diabetes diagnosed early in pregnancy and gestational diabetes (GDM or glucose intolerance first recognized in pregnancy). Some management principles are common to all types of diabetes. The term “pre-existing diabetes in pregnancy” refers to diabetes diagnosed before pregnancy. The prevalence of pre-existing diabetes has increased in the past decade (1Feig D.S. Hwee J. Shah B.R. et al.Trends in incidence of diabetes in pregnancy and serious perinatal outcomes: A large, population-based study in Ontario, Canada, 1996–2010.Diabetes Care. 2014; 37: 1590-1596Crossref PubMed Scopus (66) Google Scholar) primarily as a result of the increase in type 2 diabetes (2Bell R. Bailey K. Cresswell T. et al.Trends in prevalence and outcomes of pregnancy in women with pre-existing type I and type II diabetes.BJOG. 2008; 115: 445-452Crossref PubMed Scopus (118) Google Scholar). Studies of women with pre-existing diabetes show higher rates of complications compared to the general population, including perinatal mortality, congenital malformations, hypertension, preterm delivery, large-for-gestational-age (LGA) infants, caesarean delivery and other neonatal morbidities (1Feig D.S. Hwee J. Shah B.R. et al.Trends in incidence of diabetes in pregnancy and serious perinatal outcomes: A large, population-based study in Ontario, Canada, 1996–2010.Diabetes Care. 2014; 37: 1590-1596Crossref PubMed Scopus (66) Google Scholar, 3CEMACH Pregnancy in women with type 1 and type 2 diabetes in 2002-03, England, Wales and Northern Ireland. Confidential Enquiry into Maternal and Child Health (CEMACH), London, UK2005http://www.bathdiabetes.org/resources/254.pdfGoogle Scholar, 4Feig D.S. Razzaq A. Sykora K. et al.Trends in deliveries, prenatal care, and obstetrical complications in women with pregestational diabetes: A population-based study in Ontario, Canada, 1996–2001.Diabetes Care. 2006; 29: 232-235Crossref PubMed Google Scholar, 5Macintosh M.C. Fleming K.M. Bailey J.A. et al.Perinatal mortality and congenital anomalies in babies of women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland: Population based study.BMJ. 2006; 333: 177Crossref PubMed Scopus (339) Google Scholar). Preconception care improves maternal and fetal outcomes in women with pre-existing diabetes. This involves educating women about the importance of optimal glycemic control prior to pregnancy, discontinuing potentially harmful medications and achieving a health body weight. Hyperglycemia is teratogenic and if glycemic control is poor in the first few weeks of conception, the risk of congenital anomalies is increased. Women with diabetes should be helped to achieve optimal glycemic control preconception as this is associated with a reduction of congenital anomalies by 70% (6Wahabi H.A. Alzeidan R.A. Bawazeer G.A. et al.Preconception care for diabetic women for improving maternal and fetal outcomes: A systematic review and meta-analysis.BMC Pregnancy Childbirth. 2010; 10: 63Crossref PubMed Scopus (84) Google Scholar, 7Murphy H.R. Roland J.M. Skinner T.C. et al.Effectiveness of a regional prepregnancy care program in women with type 1 and type 2 diabetes: Benefits beyond glycemic control.Diabetes Care. 2010; 33: 2514-2520Crossref PubMed Scopus (77) Google Scholar, 8Lassi Z.S. Imam A.M. Dean S.V. et al.Preconception care: Screening and management of chronic disease and promoting psychological health.Reprod Health. 2014; 11: S5PubMed Google Scholar, 9Owens L.A. Egan A.M. Carmody L. et al.Ten years of optimizing outcomes for women with type 1 and type 2 diabetes in pregnancy-The Atlantic DIP Experience.J Clin Endocrinol Metab. 2016; 101: 1598-1605Crossref PubMed Scopus (7) Google Scholar). However, even women who achieve a glycated hemoglobin (A1C) ≤7.0% preconception have an increased risk of complications compared to the general population. This may be caused, in part, by maternal obesity, especially in women with type 2 diabetes (10Evers I.M. de Valk H.W. Visser G.H. Risk of complications of pregnancy in women with type 1 diabetes: Nationwide prospective study in the Netherlands.BMJ. 2004; 328: 915Crossref PubMed Google Scholar, 11Handisurya A. Bancher-Todesca D. Schober E. et al.Risk factor profile and pregnancy outcome in women with type 1 and type 2 diabetes mellitus.J Womens Health (Larchmt). 2011; 20: 263-271Crossref PubMed Scopus (0) Google Scholar, 12Persson M. Cnattingius S. Wikstrom A.K. et al.Maternal overweight and obesity and risk of pre-eclampsia in women with type 1 diabetes or type 2 diabetes.Diabetologia. 2016; 59: 2099-2105Crossref PubMed Scopus (10) Google Scholar, 13Abell S.K. Boyle J.A. de Courten B. et al.Contemporary type 1 diabetes pregnancy outcomes: Impact of obesity and glycaemic control.Med J Aust. 2016; 205: 162-167Crossref PubMed Scopus (3) Google Scholar). Preconception care should also include advice regarding folic acid supplementation. In 1 case-control study in the United States, women with diabetes who did not take folic acid containing vitamins were at a 3-fold higher rate of congenital anomalies compared to women with diabetes who did (14Correa A. Gilboa S.M. Botto L.D. et al.Lack of periconceptional vitamins or supplements that contain folic acid and diabetes mellitus-associated birth defects.Am J Obstet Gynecol. 2012; 206 (e1-13): 218Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar). There are no intervention trials to support folic acid doses greater than 1 mg for women with diabetes. Obesity, which is more common in women with type 2 diabetes, is associated with lower serum folate levels for the same intake, lower intake of folate rich foods and increased risk of neural tube defects independent of glycemic control (15Laraia B.A. Bodnar L.M. Siega-Riz A.M. Pregravid body mass index is negatively associated with diet quality during pregnancy.Public Health Nutr. 2007; 10: 920-926Crossref PubMed Scopus (0) Google Scholar, 16Mojtabai R. Body mass index and serum folate in childbearing age women.Eur J Epidemiol. 2004; 19: 1029-1036Crossref PubMed Scopus (126) Google Scholar, 17Watkins M.L. Rasmussen S.A. Honein M.A. et al.Maternal obesity and risk for birth defects.Pediatrics. 2003; 111: 1152-1158Crossref PubMed Google Scholar). A higher dose of folic acid may be considered in women with obesity, although there is no clinical evidence that this higher dose reduces congenital anomalies. Measurement of red blood cell (RBC) folate may also be useful to guide adjustment of folic acid dosage in women with obesity or women who have had bariatric surgery. A multifaceted preconception program that included patient information specialized clinics, electronic health records, online resources and local guidelines, increased folic acid use by 26%, improved glycemic control and decreased the risk of congenital malformations from 5% to 1.8% (9Owens L.A. Egan A.M. Carmody L. et al.Ten years of optimizing outcomes for women with type 1 and type 2 diabetes in pregnancy-The Atlantic DIP Experience.J Clin Endocrinol Metab. 2016; 101: 1598-1605Crossref PubMed Scopus (7) Google Scholar). Although receiving care at an interprofessional preconception clinic has been shown to be associated with improved pregnancy outcomes, approximately 50% of women do not receive such care (18Kachoria R. Oza-Frank R. Receipt of preconception care among women with prepregnancy and gestational diabetes.Diabet Med. 2014; 31: 1690-1695Crossref PubMed Scopus (2) Google Scholar, 19Lipscombe L.L. McLaughlin H.M. Wu W. et al.Pregnancy planning in women with pregestational diabetes.J Matern Fetal Neonatal Med. 2011; 24: 1095-1101Crossref PubMed Scopus (0) Google Scholar). The following factors are associated with women with pre-existing diabetes being less likely to receive preconception care: overweight; younger age; smoking history; lower socioeconomic status; lower health literacy and/or poor relationship with their health-care provider (7Murphy H.R. Roland J.M. Skinner T.C. et al.Effectiveness of a regional prepregnancy care program in women with type 1 and type 2 diabetes: Benefits beyond glycemic control.Diabetes Care. 2010; 33: 2514-2520Crossref PubMed Scopus (77) Google Scholar, 20Endres L.K. Sharp L.K. Haney E. et al.Health literacy and pregnancy preparedness in pregestational diabetes.Diabetes Care. 2004; 27: 331-334Crossref PubMed Scopus (52) Google Scholar, 21Holing E.V. Beyer C.S. Brown Z.A. et al.Why don't women with diabetes plan their pregnancies?.Diabetes Care. 1998; 21: 889-895Crossref PubMed Scopus (0) Google Scholar, 22Tripathi A. Rankin J. Aarvold J. et al.Preconception counseling in women with diabetes: A population-based study in the north of England.Diabetes Care. 2010; 33: 586-588Crossref PubMed Scopus (0) Google Scholar). Additionally, some studies have shown that women with type 2 diabetes are less likely to receive preconception care compared to women with type 1 diabetes (19Lipscombe L.L. McLaughlin H.M. Wu W. et al.Pregnancy planning in women with pregestational diabetes.J Matern Fetal Neonatal Med. 2011; 24: 1095-1101Crossref PubMed Scopus (0) Google Scholar, 23Kallas-Koeman M. Khandwala F. Donovan L.E. Rate of preconception care in women with type 2 diabetes still lags behind that of women with type 1 diabetes.Can J Diabetes. 2012; 36: 170-174Abstract Full Text Full Text PDF Google Scholar). Women with type 1 (24Klein B.E. Moss S.E. Klein R. Effect of pregnancy on progression of diabetic retinopathy.Diabetes Care. 1990; 13: 34-40Crossref PubMed Google Scholar, 25Diabetes Control and Complications Trial Research GroupThe Diabetes Control and Complications Trial Research GroupEffect of pregnancy on microvascular complications in the diabetes control and complications trial.Diabetes Care. 2000; 23: 1084-1091Crossref PubMed Google Scholar) and type 2 diabetes (26Omori Y. Minei S. Testuo T. et al.Current status of pregnancy in diabetic women. A comparison of pregnancy in IDDM and NIDDM mothers.Diabetes Res Clin Pract. 1994; 24: S273-S278Abstract Full Text PDF PubMed Scopus (0) Google Scholar) should ideally have ophthalmological assessments before conception, during the first trimester, as needed during pregnancy, and within the first year postpartum (27Chew E.Y. Mills J.L. Metzger B.E. et al.Metabolic control and progression of retinopathy. The Diabetes in Early Pregnancy Study. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study.Diabetes Care. 1995; 18: 631-637Crossref PubMed Google Scholar, 28Rasmussen K.L. Laugesen C.S. Ringholm L. et al.Progression of diabetic retinopathy during pregnancy in women with type 2 diabetes.Diabetologia. 2010; 53: 1076-1083Crossref PubMed Scopus (0) Google Scholar). The risk of progression of retinopathy is increased with poor glycemic control during pregnancy, and progression may occur for up to 1 year postpartum (25Diabetes Control and Complications Trial Research GroupThe Diabetes Control and Complications Trial Research GroupEffect of pregnancy on microvascular complications in the diabetes control and complications trial.Diabetes Care. 2000; 23: 1084-1091Crossref PubMed Google Scholar, 27Chew E.Y. Mills J.L. Metzger B.E. et al.Metabolic control and progression of retinopathy. The Diabetes in Early Pregnancy Study. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study.Diabetes Care. 1995; 18: 631-637Crossref PubMed Google Scholar). Additional risk factors for retinopathy progression include: chronic and pregnancy-induced hypertension, preeclampsia, more severe pre-existing diabetic retinopathy (24Klein B.E. Moss S.E. Klein R. Effect of pregnancy on progression of diabetic retinopathy.Diabetes Care. 1990; 13: 34-40Crossref PubMed Google Scholar, 29Lovestam-Adrian M. Agardh C.D. Aberg A. et al.Pre-eclampsia is a potent risk factor for deterioration of retinopathy during pregnancy in Type 1 diabetic patients.Diabet Med. 1997; 14: 1059-1065Crossref PubMed Scopus (0) Google Scholar, 30Rosenn B. Miodovnik M. Kranias G. et al.Progression of diabetic retinopathy in pregnancy: Association with hypertension in pregnancy.Am J Obstet Gynecol. 1992; 166: 1214-1218Abstract Full Text PDF PubMed Google Scholar, 31Cundy T. Slee F. Gamble G. et al.Hypertensive disorders of pregnancy in women with Type 1 and Type 2 diabetes.Diabet Med. 2002; 19: 482-489Crossref PubMed Scopus (0) Google Scholar), and a greater decrease in A1C between the first and third trimester of pregnancy (32Tulek F. Kahraman A. Taskin S. et al.The effects of isolated single umbilical artery on first and second trimester aneuploidy screening test parameters.J Matern Fetal Neonatal Med. 2015; 28: 690-694Crossref PubMed Scopus (2) Google Scholar). Closer retinal surveillance is recommended for women with more severe pre-existing retinopathy, those with poor glycemic control or women with greater reductions in A1C during pregnancy (27Chew E.Y. Mills J.L. Metzger B.E. et al.Metabolic control and progression of retinopathy. The Diabetes in Early Pregnancy Study. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study.Diabetes Care. 1995; 18: 631-637Crossref PubMed Google Scholar, 33Egan A.M. McVicker L. Heerey A. et al.Diabetic retinopathy in pregnancy: A population-based study of women with pregestational diabetes.J Diabetes Res. 2015; 2015: 7Crossref Scopus (6) Google Scholar). Laser photocoagulation for severe nonproliferative or proliferative retinopathy prior to pregnancy reduces the risk of visual impairment in pregnancy (34Rahman W. Rahman F.Z. Yassin S. et al.Progression of retinopathy during pregnancy in type 1 diabetes mellitus.Clin Exp Ophthalmol. 2007; 35: 231-236Crossref PubMed Scopus (0) Google Scholar); if not performed prior to pregnancy, it is still considered safe to receive during pregnancy. There is insufficient evidence to confirm safety or harm from the use of intravitreal antivascular endothelial growth factor (anti-VEGF) injections for diabetic macular edema or proliferative diabetic retinopathy during pregnancy (35Polizzi S. Mahajan V.B. Intravitreal anti-VEGF injections in pregnancy: Case series and review of literature.J Ocul Pharmacol Ther. 2015; 31: 605-610Crossref PubMed Scopus (7) Google Scholar). Potential side effects include hypertension, proteinuria, defective embryogenesis and fetal loss (36Almawi W.Y. Saldanha F.L. Mahmood N.A. et al.Relationship between VEGFA polymorphisms and serum VEGF protein levels and recurrent spontaneous miscarriage.Hum Reprod. 2013; 28: 2628-2635Crossref PubMed Google Scholar, 37Galazios G. Papazoglou D. Tsikouras P. et al.Vascular endothelial growth factor gene polymorphisms and pregnancy.J Matern Fetal Neonatal Med. 2009; 22: 371-378Crossref PubMed Scopus (0) Google Scholar). It is not known if these medications cross the placenta or if they are secreted in breastmilk. Gestational timing of exposure needs to be considered in situations where potential benefit to the woman justifies the potential fetal risk. Until more safety information is available, we support the recommendations of others: a) to ensure a negative pregnancy test and contraception use during intravitreal anti-VEGF therapy, and b) to consider delaying conception for 3 months after the last intravitreal injection (38Peracha Z.H. Rosenfeld P.J. Anti-vascular endothelial growth factor therapy in pregnancy: What we know, what we don't know, and what we don't know we don't know.Retina. 2016; 36: 1413-1417Crossref PubMed Scopus (1) Google Scholar, 39Safety labeling changes approved by FDA Center for Drug Evaluation and Research (CDER). U.S. Food and Drug Administration, Silver Spring2015https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/Date accessed: January , 2017Google Scholar). Intravitreal anti-VEGF therapy in pregnancy should be avoided especially in the first trimester. Second and third trimester use should occur only if absolutely necessary after discussion of the potential risks and benefits. Diabetic macular edema may often regress after pregnancy without specific therapy. Data are lacking to guide treatment recommendations for diabetic macular edema during pregnancy. One retrospective study of 193 women with type 1 diabetes, 63 with an active second-stage delivery (3 with proliferative diabetic retinopathy) found no impact of expulsive efforts in the active second stage of labour on retinopathy progression in women with stable retinopathy (40Feghali M. Khoury J.C. Shveiky D. et al.Association of vaginal delivery efforts with retinal disease in women with type I diabetes.J Matern Fetal Neonatal Med. 2012; 25: 27-31Crossref PubMed Scopus (3) Google Scholar). Data from the Diabetes Control and Complications Trial (DCCT) has suggested that pregnancy does not affect the long-term outcome of mild-to-moderate retinopathy (27Chew E.Y. Mills J.L. Metzger B.E. et al.Metabolic control and progression of retinopathy. The Diabetes in Early Pregnancy Study. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study.Diabetes Care. 1995; 18: 631-637Crossref PubMed Google Scholar). More recently, preeclampsia and pregnancy-induced hypertension in women with type 1 diabetes has been shown to be associated with an increased risk of severe diabetic retinopathy later in life (41Gordin D. Kaaja R. Forsblom C. et al.Pre-eclampsia and pregnancy-induced hypertension are associated with severe diabetic retinopathy in type 1 diabetes later in life.Acta Diabetol. 2013; 50: 781-787Crossref PubMed Scopus (12) Google Scholar). Women may have pre-existing hypertension or develop hypertension/preeclampsia during pregnancy. Women with type 1 and type 2 diabetes have a 40% to 45% incidence of hypertension complicating pregnancy (31Cundy T. Slee F. Gamble G. et al.Hypertensive disorders of pregnancy in women with Type 1 and Type 2 diabetes.Diabet Med. 2002; 19: 482-489Crossref PubMed Scopus (0) Google Scholar). A systematic review of risk factors for preeclampsia demonstrated a 3.7 risk (relative risk [RR] 3.1 to 4.3) for the development of preeclampsia in women with pre-existing diabetes (42Bartsch E. Medcalf K.E. Park A.L. et al.Clinical risk factors for pre-eclampsia determined in early pregnancy: Systematic review and meta-analysis of large cohort studies.BMJ. 2016; 353Google Scholar). Type 1 diabetes is more often associated with preeclampsia whereas type 2 diabetes is more often associated with chronic hypertension. In the general population, the risk of preeclampsia is highest in nulliparous women and lower in multiparous women. However, in women with type 1 diabetes, the risk of preeclampsia is similar in nulliparous and multiparous women (43Castiglioni M.T. Valsecchi L. Cavoretto P. et al.The risk of preeclampsia beyond the first pregnancy among women with type 1 diabetes parity and preeclampsia in type 1 diabetes.Pregnancy Hypertens. 2014; 4: 34-40Crossref PubMed Scopus (3) Google Scholar). Other risk factors for hypertension, such as poor glycemic control in early pregnancy, are potentially modifiable. Some studies (44Sibai B.M. Caritis S. Hauth J. et al.Risks of preeclampsia and adverse neonatal outcomes among women with pregestational diabetes mellitus. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.Am J Obstet Gynecol. 2000; 182: 364-369Abstract Full Text Full Text PDF PubMed Google Scholar, 45Schröder W. Heyl W. Hill-Grasshoff B. et al.Clinical value of detecting microalbuminuria as a risk factor for pregnancy-induced hypertension in insulin-treated diabetic pregnancies.Eur J Obstet Gynecol Reprod Biol. 2000; 91: 155-158Abstract Full Text Full Text PDF PubMed Scopus (0) Google