<scp>FIGO</scp> (International Federation of Gynecology and Obstetrics) Postpregnancy Initiative: Long‐term Maternal Implications of Pregnancy Complications—Follow‐up Considerations

International Journal of Gynecology & ObstetricsVolume 147, Issue S1 p. 1-31 SUPPLEMENT ARTICLEFree Access FIGO (International Federation of Gynecology and Obstetrics) Postpregnancy Initiative: Long-term Maternal Implications of Pregnancy Complications—Follow-up Considerations Eyal Sheiner, Eyal Sheiner Department of Obstetrics and Gynecology B, Soroka University Medical Center, Ben-Gurion University of the Negev, Beersheba, IsraelSearch for more papers by this authorAnil Kapur, Anil Kapur World Diabetes Foundation, Bagsværd, DenmarkSearch for more papers by this authorRavi Retnakaran, Ravi Retnakaran Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, CanadaSearch for more papers by this authorEran Hadar, Eran Hadar Helen Schneider Hospital for Women, Rabin Medical Center, Petach Tikva, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelSearch for more papers by this authorLiona C. Poon, Liona C. Poon Department of Obstetrics and Gynecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SARSearch for more papers by this authorH. David McIntyre, H. David McIntyre University of Queensland Mater Clinical School, Brisbane, Qld, AustraliaSearch for more papers by this authorHema Divakar, Hema Divakar Divakar's Speciality Hospital, Bengaluru, Karnataka, IndiaSearch for more papers by this authorAnne Cathrine Staff, Anne Cathrine Staff Faculty of Medicine, University of Oslo, Oslo, Norway Division of Obstetrics and Gynecology, Oslo University Hospital, Oslo, NorwaySearch for more papers by this authorJagat Narula, Jagat Narula Icahn School of Medicine at Mount Sinai, New York, NY, USA Department of Cardiology, Mount Sinai St Luke's Hospital, New York, NY, USASearch for more papers by this authorAnne B. Kihara, Anne B. Kihara African Federation of Obstetricians and Gynaecologists, Khartoum, SudanSearch for more papers by this authorMoshe Hod, Corresponding Author Moshe Hod hodroyal@inter.net.il Helen Schneider Hospital for Women, Rabin Medical Center, Petach Tikva, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Correspondence Moshe Hod, Helen Schneider Hospital for Women, Rabin Medical Center, Petah Tikva, Israel. Email: hodroyal@inter.net.ilSearch for more papers by this author Eyal Sheiner, Eyal Sheiner Department of Obstetrics and Gynecology B, Soroka University Medical Center, Ben-Gurion University of the Negev, Beersheba, IsraelSearch for more papers by this authorAnil Kapur, Anil Kapur World Diabetes Foundation, Bagsværd, DenmarkSearch for more papers by this authorRavi Retnakaran, Ravi Retnakaran Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, CanadaSearch for more papers by this authorEran Hadar, Eran Hadar Helen Schneider Hospital for Women, Rabin Medical Center, Petach Tikva, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelSearch for more papers by this authorLiona C. Poon, Liona C. Poon Department of Obstetrics and Gynecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SARSearch for more papers by this authorH. David McIntyre, H. David McIntyre University of Queensland Mater Clinical School, Brisbane, Qld, AustraliaSearch for more papers by this authorHema Divakar, Hema Divakar Divakar's Speciality Hospital, Bengaluru, Karnataka, IndiaSearch for more papers by this authorAnne Cathrine Staff, Anne Cathrine Staff Faculty of Medicine, University of Oslo, Oslo, Norway Division of Obstetrics and Gynecology, Oslo University Hospital, Oslo, NorwaySearch for more papers by this authorJagat Narula, Jagat Narula Icahn School of Medicine at Mount Sinai, New York, NY, USA Department of Cardiology, Mount Sinai St Luke's Hospital, New York, NY, USASearch for more papers by this authorAnne B. Kihara, Anne B. Kihara African Federation of Obstetricians and Gynaecologists, Khartoum, SudanSearch for more papers by this authorMoshe Hod, Corresponding Author Moshe Hod hodroyal@inter.net.il Helen Schneider Hospital for Women, Rabin Medical Center, Petach Tikva, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Correspondence Moshe Hod, Helen Schneider Hospital for Women, Rabin Medical Center, Petah Tikva, Israel. Email: hodroyal@inter.net.ilSearch for more papers by this author First published: 27 September 2019 https://doi.org/10.1002/ijgo.12926Citations: 17AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Contents 1. Executive summary 2. The significance of gestational diabetes mellitus and placental-associated pregnancy complications for long-term maternal health 2.1. Introduction 2.2. Target audience of the FIGO postpregnancy initiative 2.3. Assessment of quality of evidence and grading of recommendations 3. Hyperglycemia in pregnancy 3.1. Insulin resistance, gestational diabetes mellitus, and metabolic syndrome 3.2. Immediate and short-term consequences of gestational diabetes mellitus 3.3. Long-term consequences of gestational diabetes mellitus 4. Placental syndromes 4.1. Hypertensive disorders in pregnancy, pre-eclampsia, and other placental syndromes 4.2. Immediate, short-term, and long-term consequences of hypertensive disorders in pregnancy 4.3. Risk stratification for the long-term consequences of hypertensive disorders in pregnancy 4.4. Long-term consequences of other placental syndromes 5. Long-term follow-up of increased maternal cardiovascular risk after pregnancy complications 5.1. Identifying young women at increased risk of future cardiovascular disease 5.2. Female cardiovascular disease differs from male cardiovascular disease 5.3. Follow-up of cardiovascular disease after pregnancy complications 6. Management of maternal history of gestational diabetes mellitus 6.1. Screening for altered carbohydrate metabolism and type 2 diabetes 7. The health economic argument for focusing on postpregnancy care 7.1. Overweight and obesity 7.2. Hypertensive disorders in pregnancy 7.3. Hyperglycemia in pregnancy 8. Addressing the determinants of and barriers to implementing postpregnancy follow-up and preventive care 9. Summary 10. References 1 EXECUTIVE SUMMARY Pregnancy poses extreme—albeit normal and adaptive—transformations to maternal physiology. The expectant mother needs to swiftly adapt to her new status to provide appropriately for the developing fetus and its immediate postpartum requirements. All aspects of this challenge are a biological “stress test” for the mother's various organ systems, most predominantly the metabolic and cardiovascular systems. It is unclear whether common predisposing factors are implicated during pregnancy complications and postpartum morbidities, or whether the chronic morbidity is the consequence of gestational adverse events. Whatever the reason may be, pregnancy can and should be viewed as a window offering a glimpse of forthcoming adverse maternal health conditions. This may allow for heightened awareness, a priori prediction, early detection, and most importantly, an opportunity to implement appropriate preventive interventions. This Supplement reviews current data regarding the consequences for future maternal health following a complicated pregnancy, with possible implications for surveillance and interventions. The most predominant consequences are myriad noncommunicable diseases (NCDs) implicating mostly cardiovascular and metabolic health. Data regarding the immediate pregnancy complications of gestational diabetes mellitus (GDM) are strong: (1) there is a clear and substantial risk of pregnancy complications associated with GDM; (2) these complications are reduced by detection and treatment of GDM; and (3) treatment of GDM is cost-effective in terms of reduction in pregnancy complications. An important clinical consideration in women with a history of GDM is the recognition and management of their future risk of cardiometabolic disease; most notably, women with previous GDM have a markedly elevated lifetime risk of developing future diabetes. In addition to type 2 diabetes, it should also be recognized that women who are diagnosed with GDM have elevated future risks of other major medical conditions, most importantly cardiovascular disease (CVD) with various metabolic syndrome components (obesity, hypertension, dyslipidemia), but also advanced liver disease, chronic kidney disease, ophthalmic morbidity, and even female malignancies. Placentation is a highly complex vascular event, requiring multiple changes to allow appropriate blood flow to the baby via the evolving and rooted placenta. Defective placentation is a key insult in pre-eclampsia and is associated with other, and nearly all, the great obstetric syndromes: hypertensive disorders in pregnancy, fetal growth restriction, stillbirth or intrauterine fetal death, preterm birth, and recurrent pregnancy loss. Hypertension (systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg) is a common problem, complicating almost 10% of pregnancies. Women with hypertensive disorders in pregnancy are at an increased risk of long-term morbidity, including cardiovascular disease and its subsets (hypertension, cerebrovascular accidents, coronary artery disease), type 2 diabetes, as well as renal and ophthalmic disease. Placental syndromes other than hypertensive disorders in pregnancy—fetal growth restriction, preterm birth, recurrent pregnancy loss, and placental abruption—are also associated with similar long-term maternal morbidity. CVD is the leading cause of death for both men and women worldwide—even more so for women than for men. CVD accounts for 31.5% of all deaths, which is more than twice that caused by cancer. Over the last decade, pregnancy has been acknowledged increasingly as an early life “stress test” for several NCDs in women, including CVD, type 2 diabetes, metabolic syndrome, and renal, ophthalmic, and cognitive morbidities. However, pregnancy outcome has hitherto been underused as a stratification tool for targeting women at increased risk for various NCDs. Such targeting of young women would enable intensified preventive strategies early in life, when interventions are likely to be most efficient, as well as providing optimal clinical follow-up to reduce the severity of the clinical disease. We suggest that the following pregnancy-related risk factors should be acknowledged as predictors of long-term cardiovascular morbidity: hypertensive disorders in pregnancy and gestational diabetes mellitus. The following pregnancy-related risk factors should also be acknowledged as predictors of long-term cardiovascular morbidity: fetal growth restriction, preterm birth, recurrent pregnancy loss, and placental abruption. Pre-eclampsia: long-term follow-up We recommend that the following measures are implemented at 6–12 weeks after birth, and periodically thereafter, following a pregnancy complicated by hypertensive disorders: History and physical examination Blood pressure measurements Consider screening for other cardiovascular risk factors. We suggest that once acknowledged, risk-reducing measures are implemented, including lifestyle modifications (nutrition and physical activity, treating obesity and overweight, controlling hypertension, smoking cessation). Gestational diabetes mellitus: long-term follow-up We recommend that the following measures are implemented at 6–12 weeks after birth, and periodically thereafter, in a pregnancy complicated by gestational diabetes, regardless of the criteria used to diagnose GDM: History and physical examination Blood pressure measurements Screening for diabetes by either an oral glucose tolerance test (OGTT—the most recommended test), fasting glucose, or glycated hemoglobin (HbA1C, less suitable for the first months after birth). Postpartum screening using a 75 g OGTT is recommended over measurement of HbA1c for two reasons: first, in the early postpartum period, HbA1c might not accurately reflect glycemic exposure owing to the impact of either increased red blood cell turnover in pregnancy or blood loss at delivery (both of which will promote reticulocytosis and thereby lower HbA1c by virtue of less time for exposure to glycemia); second, the OGTT provides greater sensitivity for detecting pre-diabetes, particularly impaired glucose tolerance. Other “placental” complications—great obstetric syndromes (fetal growth restriction, stillbirth or intrauterine fetal death, preterm birth, placental abruption, and recurrent pregnancy loss: long-term follow-up We suggest that the following measures are considered at 6–12 weeks after birth, and periodically thereafter, following other placental-associated pregnancy complications, including fetal growth restriction, preterm birth, recurrent pregnancy loss, intrauterine fetal death, and placental abruption: History and physical examination Blood pressure measurements Consider screening for other cardiovascular risk factors. We suggest that once acknowledged, risk-reducing measures are implemented, including lifestyle modifications (nutrition and physical activity, treating obesity and overweight, controlling hypertension, and smoking cessation). 2 THE SIGNIFICANCE OF GESTATIONAL DIABETES MELLITUS AND PLACENTAL-ASSOCIATED PREGNANCY COMPLICATIONS FOR LONG-TERM MATERNAL HEALTH 2.1 Introduction Pregnancy poses extreme—albeit normal and adaptive—transformations to maternal physiology. The expectant mother needs to swiftly adapt to her new status to provide appropriately for the developing fetus and its immediate postpartum requirements. All aspects of this challenge are a biological “stress test” for the mother's various organ systems, most predominantly the metabolic and cardiovascular systems. Presumably, maternal physiology returns to the prepregnancy state, starting immediately after birth and up to the end of the puerperium. However, growing evidence suggests that pregnancy complications are the seeds of maladaptive maternal physiology. Pregnancy comorbidities such as GDM and hypertensive disorders of pregnancy not only have an immediate impact on maternal and neonatal health, but also bear short- and long-term health consequences years and possibly decades after delivery, such as type 2 diabetes, CVD, and many other implications. In addition, and although not the scope of this Supplement, it also incurs long-term impacts on the well-being of the offspring and on maternal mental health, social conditions, quality of life, sexual satisfaction, and functioning/disability, among others.1-4 It is unclear whether and how much of the chronic morbidity is the direct consequence of the gestational adverse event, and what role is played by the common predisposing factors both during and after pregnancy. Whatever the reason may be, pregnancy can and should be viewed as a window offering a glimpse of forthcoming adverse maternal health conditions. This may allow for heightened awareness, a priori prediction, early detection, and most importantly, an opportunity to implement appropriate preventive interventions. This Supplement reviews current data regarding the consequences for future maternal health following a complicated gestation, with possible implications for surveillance and interventions. The most predominant consequences are myriad NCDs, implicating mostly cardiovascular and metabolic health. FIGO acknowledges that various complications during pregnancy have implications for future maternal health, which may justify postpartum surveillance. Level of evidence: Low (⊕⊕OO) 2.2 Target audience of the FIGO postpregnancy initiative This Supplement is directed at multiple stakeholders with the intention of bringing attention to the important postpartum period, as a possible window of opportunity for prevention of NCDs and their long-term consequences for maternal health. The intended target audience includes: Healthcare providers: All those qualified to care for pregnant women, in particular those responsible for prenatal and postnatal follow-up (general practitioners/family physicians, midwives, community health workers, nurses, obstetricians, maternal–fetal medicine specialists, internists, pediatricians, nutritionists, pharmacists, etc.). Healthcare delivery organizations and providers: governments, federal and state legislators, healthcare management organizations, health insurance organizations, international development agencies, and nongovernmental organizations. Professional organizations: international, regional, and national professional organizations of obstetricians and gynecologists, internists, pediatricians, family practitioners, and worldwide national organizations dedicated to the care of pregnant women and children. 2.3 Assessment of quality of evidence and grading of recommendations In assessing the quality of evidence and grading of strength of the recommendations, this Supplement follows the terminology proposed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) working group.5 We used consistent language and graphical descriptions for the strength and quality of the evidence and recommendations based on them. Strong recommendations are numbered as 1 and conditional (weak) recommendations are numbered as 2. For the quality of evidence, cross-filled circles are used: ⊕OOO denotes very low-quality evidence; ⊕⊕OO low quality; ⊕⊕⊕O moderate quality; and ⊕⊕⊕⊕ high quality of evidence (Tables 1 and 2). Table 1. Interpretation of strong and conditional (weak) recommendations according to GRADE.aa Reprinted with permission of the American Thoracic Society. © 2019 American Thoracic Society. Schunemann HJ, Jaeschke R, Cook DJ, et al. An official ATS statement: grading the quality of evidence and strength of recommendations in ATS guidelines and recommendations. Am J Respir Crit Care Med 2006;174:605–614. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society. Implications 1 = Strong recommendation phrased as “we recommend” 2 = Conditional (weak) recommendation phrased as “we suggest” For patients Nearly all patients in this situation would accept the recommended course of action. Formal decision aids are not needed to help patients make decisions consistent with their values and preferences Most patients in this situation would accept the suggested course of action For clinicians According to the guidelines performance of the recommended action could be used as a quality criterion or performance indicator, unless the patient refuses Decision aids may help patients make management decisions consistent with their values and preferences For policy makers The recommendation can be adapted as policy in most situations Stakeholders need to discuss the suggestion a Reprinted with permission of the American Thoracic Society. © 2019 American Thoracic Society. Schunemann HJ, Jaeschke R, Cook DJ, et al. An official ATS statement: grading the quality of evidence and strength of recommendations in ATS guidelines and recommendations. Am J Respir Crit Care Med 2006;174:605–614. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society. Table 2. Interpretation of quality of evidence levels according to GRADE.aa Adapted with permission from Balshem et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol 2011;64:401–6. © 2011, with permission from Elsevier. Level of evidence Definition High⊕⊕⊕⊕ We are very confident that the true effect corresponds to that of the estimated effect Moderate⊕⊕⊕O We are moderately confident in the estimated effect. The true effect is generally close to the estimated effect, but it may be slightly different Low⊕⊕OO Our confidence in the estimated effect is limited. The true effect could be substantially different from the estimated effect Very low⊕OOO We have very little confidence in the estimated effect. The true effect is likely to be substantially different from the estimated effect a Adapted with permission from Balshem et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol 2011;64:401–6. © 2011, with permission from Elsevier. Both caregivers and care recipients need to be involved in the decision-making process before adopting recommendations. 3 HYPERGLYCEMIA IN PREGNANCY 3.1 Insulin resistance, gestational diabetes mellitus, and metabolic syndrome Hyperglycemia in pregnancy is a broad term that encompasses various forms of glucose dysregulation seen during pregnancy. It includes diabetes in pregnancy as well as GDM. Diabetes in pregnancy may be either pre-existing diabetes (type 1 or type 2) predating pregnancy, or overt diabetes first diagnosed during pregnancy. When hyperglycemia—first detected at routine testing anytime during the course of pregnancy in women with no previous history of known diabetes—meets the criteria for the diagnosis of diabetes in the nonpregnant state (fasting plasma glucose ≥7.0 mmol/L or 126 mg/dL and/or 2-hour 75 g OGTT value ≥11.0 mmol/L or 200 mg/dL or random plasma glucose ≥11.0 mmol/L or 200 mg/dL associated with signs and symptoms of diabetes), the condition is called diabetes in pregnancy. Hyperglycemia first detected in pregnancy during routine testing (often between 24 and 28 weeks) that does not meet the criteria for overt diabetes is called GDM. Various diagnostic criteria and glucose cut-off values have been proposed by various organizations and professional groups to diagnose GDM. Globally, there is increasing evidence that metabolic events occurring in the earliest stages of human development influence the mother's and offspring's short- and long-term health. The two most obvious and prevalent influences—maternal overweight/obesity and maternal hyperglycemia/insulin resistance—are both core components of what is commonly termed metabolic syndrome outside of pregnancy. The other major components of metabolic syndrome across various competing definitions are hypertension and dyslipidemia. Obesity, insulin resistance, and diabetes are all major risk factors for pre-eclampsia and other pregnancy complications.6 In the following section we explore their relationship to future postpartum maternal health. Hyperglycemia in pregnancy currently affects around 16.8% of pregnancies worldwide, amounting to 21.4 million births per year, of which over 90% occur in low- and middle-income countries.7 Recent predictions suggest that, by 2025, more than 21% of women globally will be obese.7 Although there are wide variations across countries, the trends toward increasing obesity and hyperglycemia are uniform.8, 9 They pose major health challenges for the future, both in terms of immediate pregnancy complications (such as excess fetal growth, hypertensive disorders in pregnancy, preterm birth) and short- and long-term complications, as discussed in the following sections. Furthermore, in many countries, prediabetes is very common in young women, with estimates of around 14% in the USA even in adolescence,10 and over 30% in the US population aged 20–49 years.11 A similar trend of rising rates of overweight and obesity, and prediabetes and diabetes among young reproductive-aged women, is also emerging in low-resource countries. In the of prepregnancy these are and to the high of GDM when testing is in pregnancy. syndrome is more common in women who have been diagnosed with but of prepregnancy of key such as and in many it more to whether a diagnosis of metabolic syndrome risk with the of its components in terms of immediate pregnancy The in insulin that during pregnancy pre-existing insulin resistance, maternal hyperglycemia and reduced the first pregnancy also changes in of which are those seen in metabolic Pregnancy is associated with levels of and as well as which with the lower levels seen in metabolic changes are as more in pregnancies complicated by Gestational may maternal metabolic and to in the postpartum to a of metabolic syndrome risks in the Immediate and short-term consequences of gestational diabetes mellitus definitions of GDM to of first in but more definitions those women with hyperglycemia to be termed outside pregnancy. of their risk status and possible pre-existing these very women are as or diabetes in They immediate medical attention as are likely to rates of pregnancy complications, even when appropriate treatment is early in in current the term GDM is for those with lower glucose generally in the considered outside pregnancy. Although there is regarding the glucose levels recommended to currently the recommendations of the International of Diabetes in Pregnancy which have been by the World and the International Diabetes Federation criteria are based on the risk of pregnancy complications, excess fetal and neonatal all of which are of the fetal consequences of maternal The International Federation of Gynecology and Obstetrics has the of guidelines for GDM adapted to the healthcare and of hyperglycemia in or recommendations are in Table 3. Table 3. for the diagnosis of gestational diabetes mellitus based on from Hod et to test and when test as per guidelines unless All women at or to diabetes in pregnancy 75 g OGTT at high women are at high risk of hyperglycemia during pregnancy, which may diabetes. The of diabetes is in the particularly among In and HbA1c have much lower sensitivity to diagnose diabetes than the In a of more than of the In a in of the with diabetes of the men and of the increased plasma glucose levels after an the need to hyperglycemia in All women at 75 g OGTT to diabetes in pregnancy 75 g OGTT particularly to low-resource at risk All women between 24 and 28 75 g OGTT strategies as currently used in to low-resource at high risk All women at to diabetes in pregnancy mmol/L or values between and mmol/L as 75 g OGTT reduce the of in women with values between mmol/L and