In addition to documenting a three to four times increased risk of stillbirth and perinatal death among women with type 1 diabetes compared with the background population, the novel findings in this study were a significantly higher risk of death during the first year of life, and that the increased risk of adverse outcome was limited to term births.
Strengths and limitations of the study
Our study population consists of births at any hospital throughout Norway during 1985–2004. Linkage to the nationwide type 1 diabetes registry secured a valid diagnosis of type 1 diabetes. Thus the results are not influenced by incorrect or unspecific coding of diabetes, nor by selection bias due to selective participation to studies or difference in hospital profiles. The design of the study resulted in a relatively low median age at diagnosis and thereby a relatively long median duration of diabetes at delivery, although all age groups were represented. However, as we found no association between adverse outcome and duration of diabetes within our population, we believe the relatively long median duration has not caused any major bias. Our data did not include clinically relevant data such as glycated haemoglobin and microalbuminuria. We could not, therefore, explore the correlation between birth outcomes and these factors in our population. The large sample allowed for the study of rare outcomes such as infant death, and for exploring the risk of death in subgroups such as term and preterm births.
Comparison with other studies
The three- to fourfold increased risk of stillbirth and perinatal death for women with type 1 diabetes observed in our study is comparable with the better results from population-based studies in other countries [7]. Intensive neonatal care has continuously improved over the past years, making the chance of surviving the first days of life better. We therefore aimed to include death during the whole first year of life (infant death) in the outcomes studied, thus going beyond the focus of most studies in the field. We found a doubled risk of infant death in women with diabetes compared with the background population, and a tripled risk of stillbirth or infant death. The current study is, as far as we know, the first to show a statistically significant excess risk of infant death in women with type 1 diabetes. The magnitude of this result is in accordance with estimates from Great Britain and Sweden, which indicated a doubled or tripled risk of infant death without reaching statistical significance [13–16].
The current study was, to our knowledge, the first since a study in the mid-1980s [14] to present data on mortality for term and preterm deliveries separately. This Swedish study of 914 births examined both late fetal death and infant death in subgroups of preterm and term births, but found no significant differences between women with diabetes and controls in either of the groups. No data on gestational age within the term group were presented, and we find it difficult to speculate on reasons for the apparent conflict with our results.
Our finding of 19% risk of pre-eclampsia was similar to the reported risk of pre-eclampsia among Danish women with type 1 diabetes in the 1990s (18%) [3], but was higher than results from Sweden [1] and the Netherlands [4]. Diagnostic criteria for pre-eclampsia diagnosis are, however, not necessarily alike between countries and studies [17], and while the Swedish study seemed to use similar criteria to ours and allowed 1+ for proteinuria if a dipstick was used, the Danish study required 2+, and the Dutch study was based on 24 h values only. To what extent such differences influence the results is unknown. Our finding that one third of the women with diabetes delivering preterm had a diagnosis of pre-eclampsia was in accordance with results from two single-centre studies from Israel (using similar criteria as in the current study) and the USA, the latter from the 1980s [18, 19].
Considerations and implications
The preterm birth rate in the diabetes group was 26%, much higher than in the background population (7%). Generally, preterm delivery is emphasised to be the most important single factor in perinatal mortality [20], and mild and moderate preterm births (32–36 weeks of gestation) are alone responsible for an important fraction of infant deaths in general populations [21]. Based on these factors, an excess risk of perinatal and infant death in women with diabetes could theoretically be due to a higher proportion of preterm births, which are at higher risk than births to term. If the risks within each stratum of preterm and term births were similar for women with and without diabetes, there would still be a higher risk in the total group of women with diabetes, if the rate of preterm births was higher among them than in the background population. Our finding of an increased risk in women with diabetes delivering to term shows that a higher proportion of preterm births in the diabetes group is not the whole explanation of the total excess risk. It seems that late stillbirth, also after 37 weeks of gestation, still plays a role in the persistent higher risk of adverse pregnancy outcome in women with type 1 diabetes.
The observed lack of excess risk in women with diabetes among preterm births may indicate that clinicians most often succeed in their care for women with type 1 diabetes delivering early, and for their preterm born babies. Yet, stratified analyses like the current one should be interpreted with caution because the interpretation depends on the true causal structure among many related variables [22]. The high proportion of pre-eclampsia occurring preterm in women with diabetes is in itself a challenge [23]. However, this might partly explain the relatively low mortality risk in preterm diabetes deliveries compared with the background population, in which a higher proportion of preterm births might be due to serious conditions less easily detected or intervened in.
While there were 15 cases of death in the term diabetes group (10 of them stillbirths), the expected number would be four if the risk equalled that of the background population. Six of these 15 had a gestational age (LMP-based) of 40 weeks or more. A Danish study exploring 25 cases of stillbirth in women with type 1 diabetes in the 1990s found no explanation, or suboptimal glycaemic control as the only explanation, in four out of six stillbirths to term [24]. Decisions by clinicians regarding whether and when to initiate delivery in women with type 1 diabetes are crucial and will always be a central part of the important care along these pregnancies. The National Institute for Health and Clinical Excellence (NICE) guidance recommends that all women with diabetes are offered elective birth after 38 completed weeks (induction of labour or, if indicated, elective Caesarean section) [25]. The ADA states that: ‘an emerging consensus suggests that well-monitored diabetic women achieving excellent glycaemic control without obstetrical complications can await spontaneous labour up to 39–40 weeks gestation’ [26]. In Norway, the national guidelines from 2008 recommend induction of women with pregestational diabetes around 40 weeks if no circumstances indicate earlier delivery or Caesarean section [27]. The current practice is that women with pregestational diabetes are offered labour induction between 38 and 40 completed weeks of pregnancy (T. Henriksen and S. Vangen, personal communication). Our findings support the need for thorough consideration regarding women with type 1 diabetes approaching term, hinting also towards the need to consider both LMP and ultrasound-based term, in women with a discrepancy between the two term dates. We are worried that the pendulum has gone too far in allowing women with type 1 diabetes with otherwise uncomplicated pregnancy to deliver at a high gestational age.
Conclusions
In conclusion, the three- to fourfold increased risk of stillbirth and perinatal death in women with type 1 diabetes represents a major challenge. Our novel finding that the excess risk was confined to term births is noteworthy. We believe there is a potential for better outcome by further improvement of care and optimised metabolic control for these women.