Discussion
This large, population-based study showed that the prevalence 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 European population-based studies.1 6 11 14 However, studies conducted in the USA and Canada showed higher prevalences 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 classification were used as in the present study. However, the diagnosis of pre-existing diabetes was established using 250.xx codes, whereas 648.0x codes were not included. In our registry, 1688 women were found to have 648.0x code (‘diabetes mellitus pre-pregnancy, excluding GDM’), with none of these women having GDM or T1DM 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 we had ignored those diagnostic codes, the prevalence would have been 0.29%, certainly underestimating the real figure of pre-existing diabetes. Previous population-based studies similarly included 648.0x ICD-9-CM codes in their analysis of pre-existing diabetes prevalence. Bardenheier et al16 evaluated the prevalence of pre-existing diabetes by considering both 250.xx and 648.0x ICD-9-CM codes and found an 0.8% prevalence in 19 US states between 2000 and 2010. Moreover, Albrecht et al17 reported a 0.16% prevalence of ‘unspecified diabetes’, which included women with ICD-9-CM codes 648.0x, and an overall prevalence of pre-existing diabetes of 0.66%. The ‘unspecified diabetes’ group accounted for 24% of all pre-existing diabetes cases, thus largely contributing to the described figure of pre-existing diabetes.17 Conversely, other studies conducted in the USA using ICD-9-CM codes analyzed only 250.xx codes, excluding 648.0x ; however, those studies also identified diabetes cases through insulin prescription and glycated hemoglobin levels to avoid underestimation of the prevalence. The observed prevalences were 0.8% from 1996 to 2014 in Northern California5 and 1.3% from 1995 to 2005 in Southern California.3
The growing trend in the number of pregnancies complicated by pre-existing diabetes was also consistent with other studies in Europe1 6 14 15 18 and the USA.3 16 17 The rise in diabetes prevalence during pregnancy reflects background trends in T2DM in the general population and in particular in young adults and adolescents.19 20 In this regard, a female preponderance has been described in young-onset T2DM.19 Obesity, inadequate diet, lack of physical activity, socioeconomic factors, changes in migration patterns and increasing maternal age might be some of the key factors involved in the rise of T2DM during pregnancy. Moreover, as screening for unrecognized pre-existing diabetes at the first antenatal visit is encouraged by various societies,21 22 a greater number of T2DM cases might be diagnosed. For many years, GDM was defined as any degree of glucose intolerance with onset or first recognition during pregnancy.21 Nevertheless, as the prevalence of undiagnosed T2DM cases in women of childbearing age continued to increase, the term ‘overt diabetes’ was coined by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) in 2010 as pregnant women who meet the criteria for diabetes in the non-pregnant state but were not previously diagnosed with diabetes.23 Therefore, since 2010, the American Diabetes Association (ADA) has endorsed testing for overt diabetes24 or pre-existing pregestational diabetes21 at the first antenatal visit in women at high risk for T2DM, and since 2013 the Endocrine Society has recommended universal first-trimester screening for overt diabetes.22 As the nomenclature and diagnostic criteria of overt diabetes changed over the study period, and given there is no specific ICD-9-CM code for overt diabetes, we could speculate that some of these overt diabetes cases might have been identified with 648.0* code (‘diabetes mellitus, pre-pregnancy’).
The increasing prevalence of T1DM in pregnant women found in the present study is in line with previous reports on a worldwide rising prevalence of T1DM which remains unexplained.20 25 26 We could also speculate that improvements in prepregnancy counseling, with optimization of glycemic control and appropriate management of related comorbidities, as well as greater access to assisted reproductive technology might have helped women with diabetes to conceive and ultimately give birth to a live infant, thereby increasing the rates of both T1DM and T2DM in pregnancy.
The present study showed that women with pre-existing diabetes had higher rates of cardiovascular risk factors and worse perinatal outcomes than women without diabetes.
In particular, women with T1DM had an increased risk of pre-eclampsia, prematurity, cesarean section, macrosomia and LGA than women with ‘T2DM and other PGD’. These findings concur with those of some previous population-based studies.6 7 27 However, the meta-analysis of Balsells et al28 showed a higher risk of cesarean deliveries in women with T1DM but no statistically significant differences in pre-eclampsia, macrosomia and LGA compared with T2DM.
Rates of cesarean deliveries were 55.7% for women with T1DM and 41% for ‘T2DM and other PGD’ (compared with 25.7% in women with normoglycemia). Although these rates are similar to those reported in other populations,6 7 29 a twofold increase in the risk of cesarean section in women with pre-existing diabetes remains high. In this respect, recommendations for cesarean section in women with diabetes in Spain are no different from those for women with normoglycemia, except for estimated birth weight >4500 kg or prior shoulder dystocia.30 According to the Spanish Group of Diabetes and Pregnancy (GEDE), induced labor might be considered for women with diabetes from 38 weeks of gestation, and from 37 weeks if adequate obstetric and glycemic control cannot be assured. In this context, we could speculate that labor induction might increase the risk of cesarean section. Previous evidence on the effect of induction of labor on cesarean section rates (compared with expectant management) has provided conflicting results. Results from observational studies have generally reported an increase in the rate of cesarean section,31 32 whereas evidence from randomized controlled trials and meta-analysis shows no difference or a reduction in risk.33–35 Taking this into consideration, and given that increased birth weight does not fully explain the increased risk of cesarean section in women with diabetes during pregnancy, other factors such as practice patterns or physician referrals to high-risk care have been suggested to contribute to high rates of cesarean delivery in these women.36
One of the most alarming results regarding trends in adverse perinatal outcomes was the rise in pre-eclampsia rates in women from all diabetes groups. In this respect, Bardenheier et al16 found that the proportion of pre-existing diabetes in deliveries complicated with pre-eclampsia significantly increased from 2000 to 2010. This rise was also noticed in our cohort of pregnant women without diabetes13 and in other previous studies conducted in women with normoglycemia,37 38 and may account for population-level changes in prepregnancy body mass index (BMI), parity, smoking and pre-existing maternal conditions.39 40
Although no drop in cesarean deliveries and prematurity rates in women with pre-existing diabetes was observed, it must be pointed out that these outcomes increased in women without diabetes in our cohort over the study period.13 Stable rates were also observed in women with pre-existing diabetes by Bell et al11 in the North of England between 1996 and 2004 and by Khalifeh et al40 in Dublin between 1999 and 2008. However, mixed results were found in other surveys analyzing trends in prematurity and cesarean deliveries in women with pre-existing diabetes.1 6 16
Regarding trends in birthweight outcomes, we detected a falling trend for LGA in all diabetes groups and for macrosomia in the overall pre-existing diabetes group. Considering that outcomes related to excessive fetal growth are the most likely to be influenced by glycemic control, the decreasing rates of LGA/macrosomia might suggest a certain degree of improvement in metabolic control and diabetic care in women with pre-existing diabetes. Moreover, this downward trend contrasts with the increasing rate of LGA observed in women without diabetes in our database. Varied evidence has been published in this respect.1 6
With reference to diabetes care in pregnancy in Catalonia, management is based on recommendations of the GEDE, which is composed of members of the Spanish Society of Obstetrics and Gynecology, the Spanish Paediatrics Association, and the Spanish Diabetes Society. The GEDE’s management guidelines and recommendations are common to all pre-existing diabetes (including T1DM and T2DM).41 Nevertheless, previous evidence has shown that women with T2DM have lower rates of prepregnancy care than women with T1DM.27 28 Furthermore, greater use of technology and the complexity of insulin adjustment in women with T1DM might lead to a closer follow-up during pregnancy. Although clinical guidelines and recommendations made by the GEDE are widely followed across maternity hospitals, a study published in 2015 by this group revealed an unequal access to preconception clinic, to new therapies such as continuous subcutaneous insulin infusion and to nurse support among maternity hospitals in Spain.42 The GEDE’s clinical guidelines were revised in 200641 and subsequently updated in 2015.30 Therefore, no major changes in management recommendations of diabetes in pregnancy were made during the study period. However, a generalization in the use of insulin analogs and the increasing access to technology (in particular in women with T1DM) were observed in clinical practice over the study period. Furthermore, as a result of ADA, IADPSG and WHO’s 2010 recommendations to test for overt diabetes, more women might have been diagnosed of pre-existing diabetes in early pregnancy in the second half of the study period, therefore affecting the subsequent management and care of these patients.
An increasing trend of pre-existing diabetes in pregnancy was found in our study, and as the incidence of diabetes continues to rise in the general population, especially in young age groups, this upward trend is unfortunately expected to continue. Furthermore, despite advances in clinical care, overall results show that the goals stated in the St Vincent Declaration are far from being achieved. Increasing efforts are needed to curb the upward trend of T2DM prevalence and reduce the rates of adverse perinatal outcomes in women with pre-existing diabetes. In this respect, diabetes prevention and early identification of unknown diabetes in women of childbearing age are crucial. Efforts should be made to improve both preconception and perinatal healthcare by ensuring glycemic optimization and correct assessment of maternal comorbidities.
The main strength of the present study lies in the population-based data on >700 000 deliveries over a 10-year period, providing valuable epidemiological evidence. Moreover, to our knowledge, this is the only recent study to analyze trends in pre-existing diabetes in Southern Europe. The CMBD database covers all hospital admissions in Catalonia and the ICD-9-CM remained the coding system from 1981 to the end of our study period. Furthermore, we were not only able to analyze the epidemiology of pre-existing diabetes overall, but also to identify the type of pre-existing diabetes using specific ICD-9-CM codes.
Some limitations must also be considered. Our results are based on the retrospective analysis of an administrative database and diagnoses were established according to ICD-9-CM codes, without knowledge of the criteria used to make the diagnoses; therefore, issues related to the validity and reliability of coding may arise. Codification of diabetes subtypes and perinatal outcomes might, in some cases, have been unreliable and the ICD-9-CM codes could not be crosschecked with other clinical databases. Unfortunately, we were unable to obtain data on major perinatal outcomes such as stillbirth, neonatal and perinatal mortality, congenital anomalies, and newborn neonatal intensive care unit admission since linked maternal and neonatal data were not available. Furthermore, data on maternal weight, BMI and ethnicity, and all relevant conditions that may affect pregnancy outcomes were not recorded.
In conclusion, the number of women with pre-existing diabetes in pregnancy, both T1DM and ‘T2DM and other PGD’, has increased in Catalonia over the last 10 years. Although some improvements in macrosomia and LGA rates were detected in these women, their overall risk for adverse perinatal outcomes remained significantly high compared with non-diabetic pregnancies. The results highlight the need for effective diabetes prevention and control strategies for women of childbearing age which may help protect their health and that of their newborns.