Background
Diabetes during pregnancy is a high risk situation for both mother and the child. Optimising glycaemic control is a key feature of prenatal care for diabetic women [
1]. Since the 1960s, there has been a reduction in perinatal morbidity and mortality [
2,
3]. However, even if pregnant women with diabetes are monitored according to current guidelines, they do much worse than their normoglycaemic counterparts. In a nationwide study in 2000 on the outcome of 323 women with a pregnancy complicated by type 1 diabetes we found a high prevalence of maternal, perinatal and neonatal complications [
4]. These complications occurred despite good pre-pregnancy care, as 84% of these pregnancies were planned and 70% used adequate folic acid supplementation. Overall, glycaemic control during these pregnancies was acceptable, as average HbA1c value was 44 mmol/mol. Nevertheless, these pregnancies showed high complications rates that require improvement.
The continuous glucose monitoring system (CGMS) is a new technique that retrospectively provides detailed information regarding glucose fluctuations during the day. The CGMS has been studied in non-pregnant patients where it has demonstrated clinical usefulness by enhancing decision-making through detecting previously unrecognised postprandial hyperglycaemia and nocturnal hyper-and hypoglycemia [
5]. Scientific evidence on a HbA1c-reducing effect of CGMS use is limited [
6,
7]. Although some studies do evaluate the effect of CGMS use on biochemical endpoints, such as HbA1c levels, data on clinical endpoints like diabetic complications, are lacking. The usefulness of CGMS use during pregnancy has hardly been evaluated up to now [
7]. A recent RCT showed that intermittent CGMS use during pregnancy in 71 women with pre-existing diabetes resulted in a significant reduction in HbA1c at 32–36 weeks gestation. Furthermore, the odds ratio for reduced risk of macrosomia was 0.36 (95% CI 0.13-0.98, p = 0.05) [
8]. However, this study was hampered by small sample size and both study groups differed in composition (e.g. 5 set of twins in the intervention group as opposed to none in the control group). Furthermore 11 (4%) of the children in the intervention group were small for gestational age (≤10 centile) as opposed to none in the control group. This difference did not reach statistical significance either but may point to an adverse effect of CGMS. Another recent RCT by Secher et al. investigated the effect of intermittent real time CGMS use during pregnancy in 154 women with pre-existing diabetes on pregnancy outcome [
9]. The rate of macrosomia was not significantly different between the intervention group (43%) and the control group (30%) (p = 0.09). Also, HbA1c levels were similar in both groups. The investigators concluded that intermittent CGMS use did not improve glycaemic control in pregnancy nor did it improve pregnancy outcome. Thus, further evaluation in larger studies is urgently needed before wide implementation of CGMS during pregnancy.
Relevance
Despite improvements in blood glucose monitoring technology, and obstetric and neonatal care over the last decades, maternal and fetal complications occur much more frequent in diabetic women than in non-diabetic women [
4]. Our Dutch nationwide study of type 1 diabetes mellitus in pregnancy showed high complication rates in diabetes pregnancies. Maternal complications were episodes of severe hypoglycemia (40%), pre-eclampsia (13%) and caesarean section (44%). Perinatal and neonatal complications included congenital malformations (9%), prematurity (32%), perinatal mortality (3%), macrosomia (45%) and neonatal morbidity such as shoulder dystocia (14%), all remarkably higher rates than those in non-diabetic pregnancies [
4]. Similar rates of complications have recently been found in other nationwide studies in Denmark, the United Kingdom and Sweden [
10‐
12]. In the Dutch study 45% of the newborns were macrosomic and 24% were extremely macrosomic (>p97.7). Recent data from Denmark show that 56% of the newborns of type 2 diabetic women were macrosomic [
11].
The prevalence of gestational diabetes is increasing and comprises approximately 5% of the pregnant women. Given the worldwide rising incidence of diabetes, as a consequence of changed life style and consequent obesity, improvement of obstetric care for diabetic patients is essential [
13,
14]. Moreover, it has been shown that children born macrosomic are at risk for developing obesity and diabetes mellitus type 2 at a young age [
15‐
17]. Reduction of macrosomia will not only reduce the risk of perinatal complications but may also prevent these future health problems.
Acknowledgements
This study is funded by ZonMw, a Dutch organisation for Health Research and Development. Project number 80-82310-97-11157. All researchers involved in this study: M. Kok, Department of Obstetrics and Gynaecology, Academic Medical Centre Amsterdam, Amsterdam M.C.J. Schreuder, Department of Endocrinology , Academic Medical Centre Amsterdam, Amsterdam D.J. Bekedam, Department of Obstetrics and Gynaecology, Onze Lieve Vrouwen gasthuis, Amsterdam C.B. Brouwer, Department of Endocrinology, Onze Lieve Vrouwen gasthuis, Amsterdam B.F. Fong, Department of Obstetrics and Gynaecology, Zaans Medical Centre, Zaandam A. Binnerts, Department of Endocrinology, Zaans Medical Centre, Zaandam M.H.B. Heres, Department of Obstetrics and Gynaecology, Sint Lucas Andreas Hospital, Amsterdam R. Maas, Department of Obstetrics and Gynaecology, Sint Lucas Andreas Hospital, Amsterdam B.J. Potter van Loon, Department of Endocrinology, Sint Lucas Andreas Hospital, Amsterdam J. Lenglet, Department of Obstetrics and Gynaecology, Flevo hospital, Almere N. Smit, Department of Endocrinology, Flevo hospital, Almere B.A. Braams-Lisman, Department of Obstetrics and Gynaecology, Tergooi Hospital, Hilversum E. Seebus, Department of Endocrinology, Tergooi Hospital, Hilversum E. van Beek, Department of Obstetrics and Gynaecology, Sint Antonuis Hospital, Nieuwegein I.M.M.J. Wakelkamp, Department of Endocrinology, Sint Antonuis Hospital, Nieuwegein M.A. Oudijk, Department of Obstetrics and Gynaecology, University Medical Centre, Utrecht H.W. de Valk, Department of Endocrinology, University Medical Centre, Utrecht T.E. Vogelvang, Department of Obstetrics and Gynaecology, Diakonessenhuis, Utrecht A.F. Muller, Department of Endocrinology, Diakonessenhuis, Utrecht M.E. Sanson, Department of Endocrinology, Meander Medical Centre, Amersfoort K.W. Bloemenkamp, Department of Obstetrics and Gynaecology, Leids University Medical Centre, Leiden E.J.P. de Koning, Department of Endocrinology, Leids University Medical Centre, Leiden R.P.L.M. Hoogma, Department of Endocrinology, Groene Hart Hospital, Gouda C.A. van Meir, Department of Obstetrics and Gynaecology, Groene Hart Hospital, Gouda A.H. Feitsma, Department of Obstetrics and Gynaecology, Haga Hospital, Den Haag H. van Houten, Department of Endocrinology, Haga Hospital, Den Haag M.M. Porath, Department of Obstetrics and Gynaecology, Maxima Medical Centre, Veldhoven R.J. Erdtsieck, Department of Endocrinology, Maxima Medical Centre, Veldhoven C.M. Oirschot, Department of Obstetrics and Gynaecology, Sint Elisabeth Hospital, Tilburg W.A.C.M. Nieuwlaat, Department of Endocrinology, Sint Elisabeth Hospital, Tilburg R.J.P. Rijnders, Department of Obstetrics and Gynaecology, Jeroen Bosch Hospital, Den Bosch I.P.M. Gaugler, Department of Obstetrics and Gynaecology, Jeroen Bosch Hospital, Den Bosch H. Janssen, Department of Endocrinology, Jeroen Bosch Hospital, Den Bosch J. langenveld, Department of Obstetrics and Gynaecology, Atrium Medical Centre, Heerlen R. Bianchi, Department of Endocrinology, Atrium Medical Centre, Heerlen A.J. van Loon, Department of Obstetrics and Gynaecology, Martini Hospital, Groningen K. Hoogenberg, Department of Endocrinology, Martini Hospital, Groningen B. Nij Bijvank, Department of Obstetrics and Gynaecology, Isala Hospital, Zwolle H.J.G. Bilo, Department of Endocrinology, Isala Hospital, Zwolle G.C.H. Metz, Department of Obstetrics and Gynaecology, Ikazia Hospital, Rotterdam M.G.A. Baggen, Department of Endocrinology, Ikazia Hospital, Rotterdam B.M.C. Akerboom, Department of Obstetrics and Gynaecology, Albert Schweitzer Hospital, Dordrecht R.M. Rosalie Kiewiet – kemper, Department of Endocrinology, Albert Schweitzer Hospital, Dordrecht M.D. Woiski, Department of Obstetrics and Gynaecology, University Medical Centre Sint Radboud, Nijmegen L.D. Elving, Department of Endocrinology, University Medical Centre Sint Radboud, Nijmegen R.H. Stigter, Department of Obstetrics and Gynaecology, Deventer Hospital, Deventer M.N. Gerding, Department of Endocrinology, Deventer Hospital, Deventer M.J.M. Diekman, Department of Endocrinology, Deventer Hospital, Deventer.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
IME, AF and BWM were involved in conception and design of the study. JHD has made substantial contributions to the design and conduction of the study. DNV, JHD, AF, BWM and IE drafted the manuscript. All authors mentioned in the manuscript are members of the GlucoMOMS-trial study group. All authors read, edited and approved the final manuscript.