Open access Original research Trends in prevalence of pre-­existing diabetes and perinatal outcomes: a large, population-­based study in Catalonia, Spain, 2006–2015 Lucia Gortazar,1,2 Albert Goday,1,2,3 Juana Antonia Flores-­Le Roux ‍ ‍,1,2,3 Eugènia Sarsanedas,4 Antonio Payà,5 Laura Mañé,1,2 Juan Pedro-­Botet,1,2,3 David Benaiges1,2,3,6 To cite: Gortazar L, Goday A, ABSTRACT Flores-­Le Roux JA, et al. Introduction This study aims to assess trends in the Significance of this study Trends in prevalence of prevalence of pre-­existing diabetes and whether the risk of pre-­existing diabetes and adverse perinatal outcomes decreased in women between What is already known about this subject? perinatal outcomes: a large, ►► The prevalence of pre-­existing diabetes in pregnan- 2006 and 2015 in Catalonia, Spain. population-­based study in cy is increasing in Europe and worldwide. Catalonia, Spain, 2006–2015. Research design and methods A population-­based study of 743 762 singleton deliveries between 2006 and ►► Women with pre-­existing diabetes have poorer peri- BMJ Open Diab Res Care 2015 in Catalonia, Spain, was conducted using data natal outcomes than women without diabetes. 2020;8:e001254. doi:10.1136/ from the Spanish Minimum Basic Data Set. Cases of ►► Few studies have evaluated trends in perinatal out- bmjdrc-2020-001254 type 1 diabetes (T1DM) and ‘type 2 diabetes and other comes in women with pre-­existing diabetes with pre-­existing diabetes’ (‘T2DM and other PGD’) were different findings. Received 5 February 2020 identified using International Classification of Diseases, Revised 17 June 2020 What are the new findings? Ninth Revision, Clinical Modification codes. Crude and ►► The prevalence of pre-­existing diabetes (type 1 di- Accepted 13 July 2020 age-­adjusted annual prevalences were calculated. Poisson abetes and ‘type 2 diabetes and other pre-­existing regression model was used to assess trends in prevalence diabetes’) has steadily increased between 2006 and and perinatal outcomes during the study period. 2015 in Catalonia. Results Overall prevalences of pre-­existing diabetes, ►► The risk of adverse perinatal outcomes in women T1DM and ‘T2DM and other PGD’ were 0.52% (95% with pre-­existing diabetes remains significantly high © Author(s) (or their CI 0.51 to 0.54), 0.17% (95% CI 0.17 to 0.18) and employer(s)) 2020. Re-­use compared with women without diabetes. 0.35% (95% CI 0.33 to 0.36), respectively. From 2006 permitted under CC BY-­NC. No ►► An increasing trend in pre-­eclampsia, a stable trend to 2015, rates increased for pre-­existing diabetes commercial re-­use. See rights in cesarean rates, prematurity and small for gesta- (from 0.43 (95% CI 0.39 to 0.48) to 0.56% (0.50 to and permissions. Published tional age, and a downward trend in macrosomia by BMJ. 0.62), p<0.001), T1DM (from 0.14 (0.11 to 0.17) to and large for gestational age have been detected in 1 0.20% (0.17 to 0.23), p<0.001) and ‘T2DM and other Department of Endocrinology PGD’ (from 0.29 (0.25 to 0.33) to 0.36% (0.31 to women with pre-­existing diabetes. and Nutrition, Hospital del Mar, Barcelona, Spain 0.40), p<0.001). Pre-­eclampsia rose in women with How might these results change the focus of 2 Department of Medicine, pre-­existing diabetes (from 4.38% to 8.97%, adjusted research or clinical practice? Universitat Autònoma de p<0.001), T1DM (from 3.85% to 12.88%, p=0.005) ►► As pre-­ existing diabetes in pregnancy becomes Barcelona, Barcelona, Spain and ‘T2DM and other PGD’ (from 4.63% to 6.78%, more common, there is an urgent need for preven- 3 Institut Hospital del Mar adjusted p=0.01). Prevalence of prematurity, cesarean tion strategies, early diagnosis and improvement in d'Investigacions Mèdiques section and small for gestational age remained stable maternal clinical care in order to improve perinatal (IMIM), Barcelona, Spain in all diabetes groups. However, the prevalence of 4 Health Information outcomes. macrosomia fell in women with pre-­existing diabetes Management Department, (from 18.18% to 11.9%, adjusted p=0.011) and ‘T2DM Hospital del Mar, Barcelona, and other PGD’ (from 14.71% to 11.06%, non-­adjusted Spain p=0.022, adjusted p=0.305) and large for gestational INTRODUCTION 5 Department of Gynaecology Diabetes among women of childbearing age age decreased in all diabetes groups (from 39.73% to and Obstetrics, Hospital del 30.25% in pre-­existing diabetes, adjusted p=0.004). is a growing concern worldwide1–5 and carries Mar, Barcelona, Spain 6 Consorci Sanitari de l'Alt Conclusions The prevalence of pre-­existing diabetes an increased risk of pregnancy complications Penedès Garraf, Vilafranca del increased significantly in Catalonia between 2006 and and adverse perinatal outcomes.1 6–8 In the Penedès, Spain 2015. Despite improvements in outcomes related to St Vincent Declaration in 1989, the WHO excessive birth weight, pre-­eclampsia rates are rising and the International Diabetes Federation Correspondence to and overall perinatal outcomes in women with pre-­ Dr Juana Antonia Flores-­Le declared, as a 5-­year goal, that ‘the outcome existing diabetes continue to be markedly worse than in Roux; the population without diabetes. of diabetic pregnancy should approxi- ​94066@​parcdesalutmar.​cat mate that of the non-­ diabetic pregnancy’. BMJ Open Diab Res Care 2020;8:e001254. doi:10.1136/bmjdrc-2020-001254 1 Clinical care/Education/Nutrition Preconception counseling with optimization of glycemic weeks of gestation through 40 6/7 weeks of gestation), control and appropriate management of associated late term (41 0/7 weeks of gestation through 41 6/7 comorbidities has proved to lower adverse perinatal weeks of gestation), and post-­ term (42 0/7 weeks of outcome rates in women with pre-­existing diabetes.9 10 gestation and beyond).12 The birthweight percentiles However, despite promising improvements in specialized for gestational age (30‐44 weeks) were established using units, population-­based studies reported that women with non-­customized percentiles, with data obtained from the pre-­existing diabetes continue to have poorer outcomes birth weight by the gestational age population reference than those without diabetes and trends in perinatal curves of Catalonia. A newborn was considered to be outcomes are not improving.1 4 6 7 11 No population-­based large for gestational age (LGA) if the birth weight was data from Southern European countries are currently above the estimated 90th percentile for the baby’s sex available. Thus, the aim of the present study was to assess and gestational age and small for gestational age (SGA) trends in the prevalence of pre-­existing diabetes mellitus if the birth weight was below the 10th percentile. in pregnancy between 2006 and 2015 in Catalonia, Spain, Data from all delivery reports were anonymized. and whether adverse perinatal outcomes in these women improved over the study period. Statistical analysis Prevalence was calculated by dividing the cases of pre-­ existing diabetes, T1DM and ‘T2DM and other PGD’ by PATIENTS AND METHODS the total number of deliveries during each period. Crude Hospital delivery discharges were collected from the and age-­ adjusted annual prevalences were calculated Minimum Basic Data Set for Hospital Discharge (CMBD-­ using direct standardization to the maternal age struc- AH), which is a database that includes all hospital admis- ture of the whole study population. Maternal characteris- sion reports from both public and private hospitals in tics and perinatal outcomes of women with diabetes were Catalonia, the second largest autonomous community in compared using multivariate logistic regression models, Spain in terms of population (7.5 million inhabitants). adjusted for maternal age and smoking status. Time All hospital discharge reports for singleton births in trends in crude and adjusted prevalences of diabetes women aged 15–45 years with diagnostic-­related group and perinatal outcomes were estimated using a Poisson codes 370‐375 (cesarean and vaginal deliveries) from regression model. All statistical analyses were two-­tailed, January 2006 to December 2015 were analyzed. Diabetes with p<0.05 considered significant. All analyses were cases were identified for each hospital delivery discharge made with the statistical software package IBM SPSS report using International Classification of Diseases, Statistics V.25.0. Ninth Revision, Clinical Modificacion (ICD-9-­ CM) codes. Patients diagnosed with ‘gestational diabetes’ (GDM) (codes 648.8x) were excluded. Type 1 diabetes RESULTS (T1DM) was identified by ICD-9-­CM codes 250.x1 or 250. From January 2006 to December 2015, 743 762 hospital x3. The ‘type 2 and other pre-­existing diabetes’ group deliveries were recorded in Catalonia. Data on global (‘T2DM and other PGD’) was defined as women with trends in annual deliveries, mean maternal age in the pre-­existing diabetes who did not have ICD-9-­CM codes population of individuals without diabetes, prevalence of for T1DM, and included women with type 2 diabetes GDM, and trends in perinatal outcomes in women with (T2DM) diagnosis codes 250.x0 or 250.x2) and ‘diabetes GDM and women without diabetes have been published mellitus, pre-­pregnancy’ codes 648.0x) listed anywhere elsewhere.13 on their discharge report. The overall pre-­ existing Of all hospital deliveries, 3882 were identified as having diabetes group comprised all women with diabetes prior pre-­ existing diabetes mellitus (0.52%, 95% CI 0.51 to to pregnancy and included the T1DM and ‘T2DM and 0.54). Of these, 1299 (33.5%) were classified as T1DM other PGD’ groups. Data on maternal characteristics and 2583 (66.5%) as ‘T2DM and other PGD’. As shown included age, hypertension (ICD-9 codes 642.0‐642.2 or in table 1, women with pre-­existing diabetes were older 401‐405), dyslipidemia (ICD-9 code 272), and smoking and had higher hypertension and dyslipidemia rates than status (ICD-9 code 649.0 or 305.1). Regarding obstetric those without diabetes. Women with ‘T2DM and other complications, pre-­eclampsia was defined as ICD-9 codes PGD’ were older than those with T1DM. No differences 642.4‐642.6 and cesarean section by ICD-9 codes 74.0, in the prevalence of hypertension or dyslipidemia were 74.4, 74.9, 74.91, 74.99, 669.7, and 669.71 listed anywhere observed between women with ‘T2DM and other PGD’ on the discharge report. and T1DM; however, smoking was more frequent in Macrosomia was defined according to the American women with T1DM. College of Obstetricians and Gynecologists (ACOG) as Trends in crude and age-­adjusted prevalences of pre-­ birth weight ≥4000 g. Preterm delivery included birth existing diabetes in pregnancy, T1DM and ‘T2DM and before 37 weeks’ gestation according to the WHO and other PGD’ are shown in figure 1. Rates of pre-­existing the ACOG. Term deliveries were categorized according diabetes rose from 0.43% (95% CI 0.39 to 0.48) in 2006 to the ACOG as early term (37 0/7 weeks of gestation to 0.56% (95% CI 0.50 to 0.62) in 2015. The prevalence through 38 6/7 weeks of gestation), full term (39 0/7 of T1DM increased from 0.14% (95% CI 0.11 to 0.17) 2 BMJ Open Diab Res Care 2020;8:e001254. doi:10.1136/bmjdrc-2020-001254 Table 1 Maternal characteristics, obstetric and neonatal outcomes in women with pre-­existing diabetes in pregnancy and those without diabetes ‘T2DM and OR, ‘T2DM and Normoglycemia PGD OR, PGD vs T1DM OR, T1DM vs other PGD’ other PGD’ vs OR, T1DM vs ‘T2DM n=704 148 n=3882 normoglycemia n=1299 normoglycemia n=2583 normoglycemia and other PGD’ Prevalence, % 0.52 – 0.17 – 0.35 – – Age (years) 31.3 33.1 † 32.2 † 33.6 † † Hypertension, % 0.5 4.9 8.3 (7.2 to 9.7)† 3.8 7.0 (5.2 to 9.3)† 5.5 9.0 (7.5 to 10.7)† 0.8 (0.6 to 1.1), p=0.216 Dyslipidemia, % 0.1 1.1 8.2 (6.0 to 11.2)† 1.0 7.8 (4.5 to 13.6)† 1.2 8.4 (5.8 to 12.1)† 1.1 (0.6 to 2.1), p=0.817 BMJ Open Diab Res Care 2020;8:e001254. doi:10.1136/bmjdrc-2020-001254 Smoking, % 5.5 5.8 1.1 (1.0 to 1.3), 7.3 1.4 (1.1 to 1.7)† 5.0 1.0 (0.8 to 1.2), 1.4 (1.1 to 1.9)* p=0.074 p=0.910 Pre-­eclampsia, % 1.4 6.0 4.4 (3.8 to 5.0)† 8.1 6.0 (4.9 to 7.4)† 5.0 3.6 (3.0 to 4.3)† 1.7 (1.3 to 2.3)† Preterm birth, % 6.0 17.6 3.4 (3.1 to 3.7)† 21.9 4.4 (3.9 to 5.1)† 15.5 2.9 (2.6 to 3.2)† 1.5 (1.3 to 1.8)† Early term birth, % 22.4 42.9 2.5 (2.4 to 2.7)† 56.0 4.3 (3.9 to 4.9)† 36.4 1.9 (1.7 to 2.1)† 2.3 (2.0 to 2.6)† Full-­term birth, % 54.3 34.4 0.5 (0.4 to 0.5)† 21.1 0.2 (0.2 to 0.3)† 41.4 0.6 (0.6 to 0.6)† 0.4 (0.3 to 0.5)† Late and post term birth, % 17.3 5.0 0.3 (0.2 to 0.3)† 0.9 0.04 (0.02 to 0.07)† 7.1 0.4 (0.3 to 0.4)† 0.11 (0.06 to 0.20)† Cesarean section, % 25.7 45.9 2.3 (2.1 to 2.4)† 55.7 3.6 (3.2 to 4.0)† 41 1.8 (1.7 to 1.9)† 1.9 (1.7 to 2.2)† Macrosomia, % 6.1 14.6 2.7 (2.4 to 2.9)† 17.2 3.3 (2.8 to 3.8)† 13.1 2.4 (2.1 to 2.7)† 1.3 (1.1 to 1.6)* LGA, % 13.1 35.6 3.7 (3.4 to 3.9)† 44.0 5.3 (4.8 to 5.9)† 31.4 3.0 (2.8 to 3.3)† 1.7 (1.5 to 2.0) † SGA, % 9.0 5.6 0.6 (0.5 to 0.7)† 3.2 0.3 (0.2 to 0.5)† 6.8 0.7 (0.6 to 0.8)† 0.5 (0.3 to 0.7)† OR and p value were adjusted for maternal age and smoking status. *Adjusted p<0.05. †Adjusted p<0.001. LGA, large for gestational age; PGD, pre-­existing diabetes; SGA, small for gestational age; T1DM, type 1 diabetes; T2DM and other PGD, type 2 diabetes and other pre-­existing diabetes. Clinical care/Education/Nutrition 3 Clinical care/Education/Nutrition Similarly, increases in age-­adjusted trends were observed in women with pre-­existing diabetes (from 0.45% (95% CI 0.40 to 0.50) to 0.54% (95% CI 0.49 to 0.60)), T1DM (from 0.14% (95% CI 0.11 to 0.17) to 0.20% (95% CI 0.16 to 0.23)) and ‘T2DM and other PGD’ (from 0.31% (95% CI 0.27 to 0.35) to 0.35% (95% CI 0.30 to 0.39)). Regarding perinatal outcomes, women with pre-­existing diabetes had higher rates of adverse perinatal outcomes, except for SGA, than women without diabetes (table 1). Similarly, with the exception of SGA, the risks for all adverse perinatal outcomes considered were significantly Figure 1 Trends in prevalence of pre-­existing diabetes in greater in women with T1DM compared with those with pregnancy between 2006 and 2015 in Catalonia. P value was ‘T2DM and other PGD’. Trends in pre-­eclampsia, prema- adjusted for maternal age. Note that the y axis is truncated. turity, term deliveries, cesarean deliveries, macrosomia, T1DM, type 1 diabetes; T2DM and other PGD, type 2 LGA and SGA are shown figures 2 and 3. A growing diabetes and other pre-­existing diabetes. trend in crude and adjusted rates of pre-­eclampsia was observed in women with pre-­existing diabetes, T1DM and to 0.20% (95% CI 0.17 to 0.23) and the prevalence of ‘T2DM and other PGD’ between 2006 and 2015 (from ‘T2DM and other PGD’ from 0.29% (95% CI 0.25 to 0.33) 4.38% to 8.96% in pre-­existing diabetes, from 3.85% to to 0.36% (95% CI 0.31 to 0.40) during the study period. 12.88% in T1DM, and from 4.63% to 6.78% in ‘T2DM Figure 2 Trends in perinatal outcomes in women with pre-­existing diabetes in pregnancy between 2006 and 2015. (A) Pre-­ eclampsia, (B) cesarean section, (C) macrosomia, (D) LGA and (E) SGA; *p<0.05, **p<0.001, †adjusted p<0.05, ††adjusted p<0.001. Note that in A–E, the y axis is truncated. LGA, large for gestational age; SGA, small for gestational age; T1DM, type 1 diabetes; T2DM and other PGD, type 2 diabetes and other pre-­existing diabetes. 4 BMJ Open Diab Res Care 2020;8:e001254. doi:10.1136/bmjdrc-2020-001254 Clinical care/Education/Nutrition DISCUSSION This large, population-­based study showed that the prev- alence of overall pre-­existing diabetes in pregnancy rose steadily in Catalonia, Spain between 2006 and 2015, with a 30% overall increase. A more pronounced increase was observed in women with T1DM (43%), whereas the prevalence of ‘T2DM and other PGD’ showed a 24% rise. The frequency of adverse perinatal outcomes in women with pre-­existing diabetes remained substantially high compared with women without diabetes. Regarding trends in perinatal outcomes, an increasing trend in pre-­ eclampsia, a stable trend in cesarean rates, prematurity and SGA, and a downward trend in macrosomia and LGA in women with pre-­existing diabetes were noted. The overall prevalence of pre-­ existing diabetes was 0.52%, consistent with that described in other Euro- pean population-­based studies.1 6 11 14 However, studies conducted in the USA and Canada showed higher prev- alences of pre-­existing diabetes, ranging from 0.8% to 1.3%.2 3 5 Conversely, the only population-­based study in Spain analyzed data from 2001 to 2008 and found a much lower prevalence of pre-­existing diabetes, at 0.2%.15 In that study, the same CMBD database and ICD-9-­CM clas- sification were used as in the present study. However, the diagnosis of pre-­existing diabetes was established using​ Figure 3 Trends in preterm and term deliveries in women 250.​xx codes, whereas 648.0x codes were not included. with pre-­existing diabetes in pregnancy between 2006 and In our registry, 1688 women were found to have 648.0x 2015. †Adjusted p<0.05, ††adjusted p<0.001. T1DM, type 1 code (‘diabetes mellitus pre-­ pregnancy, excluding diabetes; T2DM and other PGD, type 2 diabetes and other GDM’), with none of these women having GDM or T1DM pre-­existing diabetes. ICD-9-­CM codes. These 1688 cases represented almost half (43%) the total pre-­ existing diabetes cases and were therefore considered unrealistic to be excluded. If and other PGD’). Prematurity and cesarean section we had ignored those diagnostic codes, the prevalence rates remained stable for pre-­existing diabetes, T1DM would have been 0.29%, certainly underestimating the and ‘T2DM and other PGD’ during the study period. real figure of pre-­existing diabetes. Previous population-­ However, when analyzing trends on term deliveries, we based studies similarly included 648.0x ICD-9-­CM codes observed an increasing trend in ‘early term birth’ in pre-­ in their analysis of pre-­ existing diabetes prevalence. existing diabetes and in ‘T2DM and other PGD’, whereas Bardenheier et al16 evaluated the prevalence of pre-­ ‘late and post term birth’ decreased in women with pre-­ existing diabetes by considering both ​250.​xx and 648.0x existing diabetes (figure 3). ICD-9-­CM codes and found an 0.8% prevalence in 19 US With respect to fetal growth outcomes, macrosomia states between 2000 and 2010. Moreover, Albrecht et al17 rates showed a diminishing trend in women with pre-­ reported a 0.16% prevalence of ‘unspecified diabetes’, existing diabetes (from 18.2% to 12%, adjusted p=0.011) which included women with ICD-9-­CM codes 648.0x, and and those with ‘T2DM and other PGD’ (from 14.7% to an overall prevalence of pre-­existing diabetes of 0.66%. 11.1%, non-­ adjusted p=0.022); however, the decrease The ‘unspecified diabetes’ group accounted for 24% was not statistically significant in the latter group when of all pre-­existing diabetes cases, thus largely contrib- adjusted for age and smoking status (adjusted p=0.305). uting to the described figure of pre-­existing diabetes.17 Conversely, other studies conducted in the USA using The prevalence of macrosomia remained stable during ICD-9-­CM codes analyzed only ​250.​xx codes, excluding the study period in women with T1DM (adjusted 648.0x ; however, those studies also identified diabetes p=0.119) (figure 2C). LGA rates dropped significantly cases through insulin prescription and glycated hemo- in women with pre-­ existing diabetes (from 39.7% globin levels to avoid underestimation of the prevalence. to 30.2%, adjusted p=0.004), T1DM (from 52.7% to The observed prevalences were 0.8% from 1996 to 2014 35.6%, adjusted p=0.025) and ‘T2DM and other PGD’ in Northern California5 and 1.3% from 1995 to 2005 in (from 33.8% to 27.2%, adjusted p=0.033) between 2006 Southern California.3 and 2015 (figure 2D). Finally, the prevalence of SGA The growing trend in the number of pregnancies remained stable in all diabetes groups during the study complicated by pre-­existing diabetes was also consistent period (figure 2E). with other studies in Europe1 6 14 15 18 and the USA.3 16 17 BMJ Open Diab Res Care 2020;8:e001254. doi:10.1136/bmjdrc-2020-001254 5 Clinical care/Education/Nutrition The rise in diabetes prevalence during pregnancy reflects with 25.7% in women with normoglycemia). Although background trends in T2DM in the general population these rates are similar to those reported in other popu- and in particular in young adults and adolescents.19 20 In lations,6 7 29 a twofold increase in the risk of cesarean this regard, a female preponderance has been described section in women with pre-­existing diabetes remains high. in young-­onset T2DM.19 Obesity, inadequate diet, lack of In this respect, recommendations for cesarean section physical activity, socioeconomic factors, changes in migra- in women with diabetes in Spain are no different from tion patterns and increasing maternal age might be some those for women with normoglycemia, except for esti- of the key factors involved in the rise of T2DM during mated birth weight >4500 kg or prior shoulder dystocia.30 pregnancy. Moreover, as screening for unrecognized pre-­ According to the Spanish Group of Diabetes and Preg- existing diabetes at the first antenatal visit is encouraged nancy (GEDE), induced labor might be considered for by various societies,21 22 a greater number of T2DM cases women with diabetes from 38 weeks of gestation, and might be diagnosed. For many years, GDM was defined from 37 weeks if adequate obstetric and glycemic control as any degree of glucose intolerance with onset or first cannot be assured. In this context, we could speculate recognition during pregnancy.21 Nevertheless, as the that labor induction might increase the risk of cesarean prevalence of undiagnosed T2DM cases in women of section. Previous evidence on the effect of induction of childbearing age continued to increase, the term ‘overt labor on cesarean section rates (compared with expectant diabetes’ was coined by the International Association of management) has provided conflicting results. Results Diabetes and Pregnancy Study Groups (IADPSG) in 2010 from observational studies have generally reported an as pregnant women who meet the criteria for diabetes increase in the rate of cesarean section,31 32 whereas in the non-­pregnant state but were not previously diag- evidence from randomized controlled trials and meta-­ nosed with diabetes.23 Therefore, since 2010, the Amer- analysis shows no difference or a reduction in risk.33–35 ican Diabetes Association (ADA) has endorsed testing for Taking this into consideration, and given that increased overt diabetes24 or pre-­existing pregestational diabetes21 birth weight does not fully explain the increased risk of at the first antenatal visit in women at high risk for T2DM, cesarean section in women with diabetes during preg- and since 2013 the Endocrine Society has recommended nancy, other factors such as practice patterns or physi- universal first-­trimester screening for overt diabetes.22 cian referrals to high-­risk care have been suggested to As the nomenclature and diagnostic criteria of overt contribute to high rates of cesarean delivery in these diabetes changed over the study period, and given there women.36 is no specific ICD-9-­CM code for overt diabetes, we could One of the most alarming results regarding trends in speculate that some of these overt diabetes cases might adverse perinatal outcomes was the rise in pre-­eclampsia have been identified with 648.0* code (‘diabetes mellitus, rates in women from all diabetes groups. In this respect, pre-­pregnancy’). Bardenheier et al16 found that the proportion of pre-­ The increasing prevalence of T1DM in pregnant existing diabetes in deliveries complicated with pre-­ women found in the present study is in line with previous eclampsia significantly increased from 2000 to 2010. reports on a worldwide rising prevalence of T1DM which This rise was also noticed in our cohort of pregnant remains unexplained.20 25 26 We could also speculate that women without diabetes13 and in other previous studies improvements in prepregnancy counseling, with opti- conducted in women with normoglycemia,37 38 and may mization of glycemic control and appropriate manage- account for population-­level changes in prepregnancy ment of related comorbidities, as well as greater access body mass index (BMI), parity, smoking and pre-­existing to assisted reproductive technology might have helped maternal conditions.39 40 women with diabetes to conceive and ultimately give Although no drop in cesarean deliveries and prema- birth to a live infant, thereby increasing the rates of both turity rates in women with pre-­ existing diabetes was T1DM and T2DM in pregnancy. observed, it must be pointed out that these outcomes The present study showed that women with pre-­existing increased in women without diabetes in our cohort over diabetes had higher rates of cardiovascular risk factors the study period.13 Stable rates were also observed in and worse perinatal outcomes than women without women with pre-­existing diabetes by Bell et al11 in the diabetes. North of England between 1996 and 2004 and by Khal- In particular, women with T1DM had an increased risk ifeh et al40 in Dublin between 1999 and 2008. However, of pre-­eclampsia, prematurity, cesarean section, macro- mixed results were found in other surveys analyzing somia and LGA than women with ‘T2DM and other trends in prematurity and cesarean deliveries in women PGD’. These findings concur with those of some previous with pre-­existing diabetes.1 6 16 population-­based studies.6 7 27 However, the meta-­analysis Regarding trends in birthweight outcomes, we detected of Balsells et al28 showed a higher risk of cesarean deliv- a falling trend for LGA in all diabetes groups and for eries in women with T1DM but no statistically signifi- macrosomia in the overall pre-­existing diabetes group. cant differences in pre-­eclampsia, macrosomia and LGA Considering that outcomes related to excessive fetal compared with T2DM. growth are the most likely to be influenced by glycemic Rates of cesarean deliveries were 55.7% for women with control, the decreasing rates of LGA/macrosomia might T1DM and 41% for ‘T2DM and other PGD’ (compared suggest a certain degree of improvement in metabolic 6 BMJ Open Diab Res Care 2020;8:e001254. doi:10.1136/bmjdrc-2020-001254 Clinical care/Education/Nutrition control and diabetic care in women with pre-­ existing Southern Europe. The CMBD database covers all hospital diabetes. Moreover, this downward trend contrasts with admissions in Catalonia and the ICD-9-­CM remained the the increasing rate of LGA observed in women without coding system from 1981 to the end of our study period. diabetes in our database. Varied evidence has been Furthermore, we were not only able to analyze the epide- published in this respect.1 6 miology of pre-­ existing diabetes overall, but also to With reference to diabetes care in pregnancy in Catal- identify the type of pre-­existing diabetes using specific onia, management is based on recommendations of the ICD-9-­CM codes. GEDE, which is composed of members of the Spanish Some limitations must also be considered. Our results Society of Obstetrics and Gynecology, the Spanish Paedi- are based on the retrospective analysis of an administra- atrics Association, and the Spanish Diabetes Society. tive database and diagnoses were established according The GEDE’s management guidelines and recommenda- to ICD-9-­CM codes, without knowledge of the criteria tions are common to all pre-­existing diabetes (including used to make the diagnoses; therefore, issues related to T1DM and T2DM).41 Nevertheless, previous evidence the validity and reliability of coding may arise. Codifica- has shown that women with T2DM have lower rates of tion of diabetes subtypes and perinatal outcomes might, prepregnancy care than women with T1DM.27 28 Further- in some cases, have been unreliable and the ICD-9-­CM more, greater use of technology and the complexity of codes could not be crosschecked with other clinical data- insulin adjustment in women with T1DM might lead to bases. Unfortunately, we were unable to obtain data on a closer follow-­up during pregnancy. Although clinical major perinatal outcomes such as stillbirth, neonatal and guidelines and recommendations made by the GEDE perinatal mortality, congenital anomalies, and newborn are widely followed across maternity hospitals, a study neonatal intensive care unit admission since linked published in 2015 by this group revealed an unequal access to preconception clinic, to new therapies such as maternal and neonatal data were not available. Further- continuous subcutaneous insulin infusion and to nurse more, data on maternal weight, BMI and ethnicity, and all support among maternity hospitals in Spain.42 The relevant conditions that may affect pregnancy outcomes GEDE’s clinical guidelines were revised in 200641 and were not recorded. subsequently updated in 2015.30 Therefore, no major In conclusion, the number of women with pre-­existing changes in management recommendations of diabetes diabetes in pregnancy, both T1DM and ‘T2DM and other in pregnancy were made during the study period. PGD’, has increased in Catalonia over the last 10 years. However, a generalization in the use of insulin analogs Although some improvements in macrosomia and LGA and the increasing access to technology (in particular in rates were detected in these women, their overall risk for women with T1DM) were observed in clinical practice adverse perinatal outcomes remained significantly high over the study period. Furthermore, as a result of ADA, compared with non-­ diabetic pregnancies. The results IADPSG and WHO’s 2010 recommendations to test for highlight the need for effective diabetes prevention and overt diabetes, more women might have been diagnosed control strategies for women of childbearing age which of pre-­existing diabetes in early pregnancy in the second may help protect their health and that of their newborns. half of the study period, therefore affecting the subse- quent management and care of these patients. Acknowledgements We thank Miss Christine O'Hara for review of the English version of the manuscript, Montse Clèries from Unitat d'Informació i Coneixement, An increasing trend of pre-­existing diabetes in preg- Servei Català de la Salut (CatSalut), Marta Albacar from Divisió d'anàlisi de la nancy was found in our study, and as the incidence of demanda i l'activitat, Servei Català de la Salut (CatSalut), and Conxa Castell from diabetes continues to rise in the general population, Servei de Promoció de Vida Saludable i Prevenció de Malalties Cròniques no especially in young age groups, this upward trend is Transmissibles, Agència de Salut Pública de Catalunya, Departament de Salut, Generalitat de Catalunya. unfortunately expected to continue. Furthermore, despite advances in clinical care, overall results show Contributors All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; drafted the article or that the goals stated in the St Vincent Declaration are revised it critically for important intellectual content; gave final approval of the far from being achieved. Increasing efforts are needed to version to be published; and agreed to be accountable for all aspects of the work in curb the upward trend of T2DM prevalence and reduce ensuring that questions related to the accuracy or integrity of any part of the work the rates of adverse perinatal outcomes in women with are appropriately investigated and resolved. Study concept and design: AG, DB, ES, JAF-­LR and LG. Acquisition of data: AG and ES. Analysis and interpretation of data: pre-­existing diabetes. In this respect, diabetes prevention AG, DB, ES, JAF-­LR and LG. Drafting of the manuscript: LG. Critical revision of the and early identification of unknown diabetes in women manuscript for important intellectual content: AG, AP, DB, ES, JAF-­LR, JP-­B, LG and of childbearing age are crucial. Efforts should be made to LM. Statistical analysis: DB, ES and LG. improve both preconception and perinatal healthcare by Funding The authors have not declared a specific grant for this research from any ensuring glycemic optimization and correct assessment funding agency in the public, commercial or not-­for-­profit sectors. of maternal comorbidities. Competing interests None declared. The main strength of the present study lies in the Patient consent for publication Not required. population-­ based data on >700 000 deliveries over a Ethics approval The study was conducted according to the principles of the 10-­year period, providing valuable epidemiological Declaration of Helsinki and approved by the clinical research ethics committee of evidence. Moreover, to our knowledge, this is the only our institution (CEIC-­Parc de Salut MAR, number 2017/7209/I). recent study to analyze trends in pre-­existing diabetes in Provenance and peer review Not commissioned; externally peer reviewed. BMJ Open Diab Res Care 2020;8:e001254. doi:10.1136/bmjdrc-2020-001254 7 Clinical care/Education/Nutrition Data availability statement Data are available upon request from the authors. 20 Dabelea D, Mayer-­Davis EJ, Saydah S, et al. Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to Open access This is an open access article distributed in accordance with the 2009. JAMA 2014;311:1778–86. Creative Commons Attribution Non Commercial (CC BY-­NC 4.0) license, which 21 American Diabetes Association. 2. Classification and diagnosis of permits others to distribute, remix, adapt, build upon this work non-­commercially, diabetes: Standards of Medical Care in Diabetes-2019. 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