Gestational diabetes mellitus is a condition specific to pregnancy with known short- and long-term risks to mother and fetus. In this analysis, contrary to other recent studies, we showed that women with gestational diabetes were more likely than women without diabetes to experience a stillbirth after 35 weeks. This increased risk persisted at all gestational ages except at 42 weeks, likely because few women with GDM receiving prenatal care in California remained undelivered at 42 weeks gestational age. This study is the first to examine the incidence rate of stillbirth by gestational age in women diagnosed with GDM, and such stratification by GA may explain the difference in our findings from other recent studies. Since many women with GDM are delivered by 39 weeks, the overall magnitude of difference in the incidence rate of stillbirth between women with and without GDM may be diminished or even reversed because of prevention of stillbirths that are overall more likely to occur at 40 and 41 weeks gestation. Another important difference between this study and others in the literature with different findings is the baseline characteristics of the study population. Due to the rarity of the adverse events of stillbirth and infant death, it is difficult to design and power a study to show a difference compared with non-diabetic controls or with women receiving treatment compared with those poorly controlled. Our findings could be explained by the increased prevalence of GDM in our population as well as the possibility of more severe or undertreated disease. The prevalence of GDM is much higher our dataset (4.6%) than in Sweden or Italy, (0.8% and 0.9%, respectively).8,9
Also, the Israeli study included only women with diet controlled GDM while this study did not differentiate between those who were only diet controlled and those who required medical therapy; thus, it is likely that our study population could have more severe disease, representing a population at higher risk of stillbirth.7
Although we know that infants born to mothers with gestational diabetes are more likely to be macrosomic, to experience shoulder dystocia, and to have short-term metabolic derangements such as hypoglycemia, hyperbilirubinemia, and polycythemia, our analysis does not demonstrate that these morbidities contribute to an excess risk of infant or neonatal mortality. In fact, in this analysis, it appears that these infants overall are at a lower risk of infant death when compared with babies born to women without GDM. An explanation for this finding may be that more women with GDM were delivered by 40 weeks such that there were fewer babies born to mothers with GDM who were born at 41 and 42 weeks, when infant mortality rates are higher.14,16
It may also be that because the infants born to mothers with known GDM are at higher risk of the short term morbidities listed above that these babies are more likely to undergo more screening and treatment compared to the general population that may experience unexpected neonatal morbidities. However, this analysis was restricted to mortality comparisons only and thus can only hypothesize about the effects on neonatal morbidity seen in these populations.
We cannot exclude the fact that confounding may play a role in the elevated risk estimates for stillbirth seen in the women with GDM. From our dataset, we are only able to examine maternal age and race, which have been previously demonstrated to be associated with GDM as well as increased stillbirth risk.3, 14, 17
As expected, women with GDM are more likely to be older and of Latino or Asian descent. Also as expected, the highest rate of stillbirth was seen in the African-American population, which is less likely to have GDM compared with the other ethnic groups. (data not shown). Due to the limitations of the dataset and the rarity of the outcomes, we are unable to quantify the magnitude of these potential confounders, which should be a focus of future research.
There is substantial controversy in the literature and in clinical practice regarding the optimal time to deliver a woman with GDM to minimize the risks to her fetus. The American Diabetes Association recommends delivery at 38 weeks while the American College of Obstetricians and Gynecologists does not recommend routine delivery before 40 weeks.3,18
Multiple observational studies and a single randomized controlled trial did show decreased macrosomia and shoulder dystocia with delivery at 38 weeks, but none of these studies were powered to examine stillbirth or infant death.19,20
There has been increasing concern about the excess morbidities seen in neonates delivered electively before 39 weeks,21,22
and these results have been extrapolated to include women with GDM. The limitation of the studies that focus on neonatal morbidities by GA at delivery is that they do not take into consideration the risks faced by the fetus while still in utero. However, at least one recent study has suggested that the policy of limiting pre-39 week non-indicated labor induction was associated with an increased rate of stillbirth in the 37th
week of gestation.23
Our methodology, which compares expectant management with planned delivery is useful as it more closely approximates the decision faced by a woman with GDM and her provider, in simultaneously weighing the various risks to the baby whether in utero or after birth. Another strength of our study is the heterogeneous study population in California, which is racially/ethnically and socioeconomically diverse; our study findings can be more validly applied to a broad range of populations.
When we examined the population of women with GDM, the risk of expectant management carried a higher risk of mortality than the risk of delivery at 39 and 40 weeks. The absolute risk between expectant management and delivery is low, however, and based on these figures, the “number needed to deliver” to prevent one excess death at 39 or 40 weeks of gestation is 1500 and 1300, respectively. Although our data do show a potential mortality benefit at 38 weeks, this difference is not statistically significant, and the “number needed to deliver” at this gestational age is much higher, 4435. The widespread current obstetrical practice of inducing labor at 39-40 weeks for women with gestational diabetes is designed to lower the risk of macrosomia and shoulder dystocia along with decreasing stillbirth. Our analysis would suggest that 39 weeks may be the most appropriate GA at which to plan delivery in order to decrease infant mortality.
While the current study is novel in its examination of both stillbirth and infant death risks, it is not without limitations. One of our study limitations is that we do not have access to the medical records of these women and thus cannot comment on the degree to which poor gylcemic control due to late diagnosis or suboptimal treatment contributes to these risk estimates, or the extent to which other comorbidities are present and may play a role. As previous research has demonstrated that perinatal mortality rates decrease with improved glycemic control, perhaps the optimal time for delivery for women with poor glycemic control is actually earlier, while those with excellent control could be managed expectantly beyond 39 weeks of gestation.24, 25
We also cannot rule out significant selection bias where the women who had more severe GDM were also those most likely to have early iatrogenic deliveries, avoiding stillbirth as an outcome but inflating the infant death rate due to prematurity. This may play a role in the elevated infant death risk seen in the population of infants delivered at 36 weeks who may have had more severe co-morbidities that necessitated a late preterm delivery. We note, however, that the infant death rates at all gestational ages are higher in the non-diabetic group compared with the gestational diabetics and that the stillbirth rate increases with gestational age in both groups. This suggests that early delivery does not account for a substantial decrease in the stillbirth rate and that had these women not been delivered earlier, the difference in mortality at later gestational ages might be even more pronounced.
Another limitation is that our dataset determines gestational age by LMP alone. Studies show that pregnancies that are dated based on LMP alone rather than clinical judgment or ultrasound have less accurate gestational age assignations, and these pregnancies are more likely to be classified as “post-term.”26-29
Women with gestational diabetes are more likely to be obese and to be of lower socioeconomic status, factors associated with incorrectly recalled LMPs and more specifically, of cycles longer than 28 days.30
This bias, while more prevalent in the GDM group compared with the non-GDM group, should otherwise be distributed evenly among the stillbirth and infant death populations. This misclassification would bias the result towards the null since many “term” infants (at 37-40 wks) would be classified instead as “postterm” (41 and 42 wks) making the pregnancies at these different gestational ages seem more similar than they actually are. Thus, if such misclassification was occurring, our threshold designation of the gestational age at which the GDM patients were having higher risk of the combined fetal and infant death outcome would only be earlier.
Our study suggests that there exists a mortality benefit in delivering women with gestational diabetes at 39 weeks instead of continuing with expectant management. We are cautious when making clinical recommendations from this type of observational data alone, and we acknowledge the absence of neonatal and maternal morbidity in these calculations. We cannot comment on the impact on short-term neonatal outcomes, cesarean delivery rate, maternal complications, and cost to the health care system that a policy of inducing women with GDM at 39 weeks compared with 40 weeks would incur and further research should explore these potential repercussions. Because the absolute risks of stillbirth and infant death are so low, an increase in short-term neonatal morbidities such as NICU admissions associated with a policy of early delivery may have a public health ramification that overshadows any small mortality benefit. Specifically, randomized clinical trials need to be considered in order to determine the best management of term pregnancy for women with GDM that consider both morbidity and mortality as outcomes. Until prospective studies can be performed, this type of risk assessment demonstrated in our study may prove to be very useful in helping women with GDM and their care providers determine the optimal gestational age for delivery.