We sought to compare the different mortality risks between delivery and expectant management in women with gestational diabetes mellitus (GDM).
This is a retrospective cohort study that included singleton pregnancies of women diagnosed with GDM delivering at 36-42 weeks’ gestational age in California from 1997 through 2006. A composite mortality rate was developed to estimate the risk of expectant management at each gestational age incorporating the stillbirth risk during the week of continuing pregnancy plus the infant mortality risk at the gestational age 1 week hence.
In women with GDM, the risk of expectant management is lower than the risk of delivery at 36 weeks (17.4 vs 19.3/10,000), but at 39 weeks, the risk of expectant management exceeds that of delivery (relative risk, 1.8; 95% confidence interval, 1.2–2.6).
In women with GDM, infant mortality rates at 39 weeks are lower than the overall mortality risk of expectant management for 1 week; absolute risks of stillbirth and infant death are low.
Gestational diabetes mellitus (GDM) affects 5-7% of pregnancies in the United States, and in 2005 was diagnosed in 5.3% of all California pregnancies. This condition is characterized by newly recognized hyperglycemia occurring in pregnancy, and is associated with an elevated risk of macrosomia, shoulder dystocia, hypoglycemia, cesarean delivery, and future maternal type 2 diabetes, among other maternal and neonatal morbidities. When O’Sullivan et al first recognized this condition in the 1960s, they observed an increased incidence of stillbirth among women with GDM who were undiagnosed or suboptimally treated. Subsequent early studies and those in the developing world have also demonstrated an increased risk of stillbirth associated with GDM. As screening, diagnosis, and treatment of GDM have become more widespread, however, the association between GDM and perinatal mortality has become less clear. More recent studies in Italy, Israel, and Sweden report a lack of association. Due to this conflicting evidence, there is continuing controversy about the optimal timing of delivery for women with GDM.
When considering the optimal time for delivery to improve perinatal outcomes, the risk of stillbirth must be weighed against the risk of neonatal and infant morbidity and mortality. While GDM has been shown to be associated with macrosomia and neonatal hypoglycemia, this has not consistently been shown to contribute to higher neonatal and infant death rates. Although some studies find that macrosomia is independently associated with increased mortality, other data suggest that neonates born large for gestational age actually have a lower postneonatal death rate when compared with neonates who were average for gestational age or small for gestational age. Thus, examining only short-term morbidities may not fully account for the true mortality risk associated with GDM.
We have previously demonstrated in a large dataset of California births that using a novel composite mortality calculation to estimate the risk of expectant management at term can be useful in quantifying the risks faced by a pregnant woman and her care provider when trying to determine the optimal time of delivery. In this study, we apply this novel methodology to the specific subpopulation of women with GDM to determine their optimal delivery time from a mortality perspective.
Materials and Methods
We designed a retrospective cohort study of singleton births to women diagnosed with GDM identified through the California Vital Statistics Birth Certificate Data linked with the California Patient Discharge Data as well as Vital Statistics Death Certificate Data and Vital Statistics Fetal Death File from 1997 through 2006. Linkage of data was performed by the California Office of Statewide Health Planning and Development Healthcare Information Resource Center under the State of California Health and Human Services Agency. The resultant linked datasets include maternal antepartum and postpartum hospital records for the 9 months prior to delivery and 1 year postdelivery as well as birth records and all infant admission and readmissions occurring within the first year of life. Linkage for the mother/baby pair was achieved using the “record linkage number,” an alphanumeric encrypted code unique to the mother and the baby. Institutional review board approval was obtained from the Committee on Human Research at the University of California, San Francisco; the institutional review board at Oregon Health and Science University; and the California Office of Statewide Health Planning and Development and the Committee for the Protection of Human Subjects. The reporting of births and deaths in California is nearly 100% complete and the California Health and Human Services Agency performs rigorous statistical quality checks. Since the linked dataset did not contain potential patient privacy and identification information, informed consent was exempted.
Women with a diagnosis of GDM were identified using the International Classification of Diseases, Ninth Revision ( ICD-9 ) codes. ICD-9 codes used for the identification of GDM include: 648.8, 648.80, 648.81, 648.82, 648.83, and 648.84. We excluded women with a diagnosis of prepregnancy diabetes mellitus using ICD-9 codes: 648.0, 648.01, 648.02, 648.03, and 648.04. These ICD-9 codes were taken from maternal medical records but do not specify how or when the diagnosis of GDM was made. The California Diabetes and Pregnancy Program, administered by the California Department of Health, oversees the diagnosis and management of most pregnant women with diabetes in the state. During the time frame that these patients were cared for, they recommended, at a minimum, universal screening of GDM with a 1-hour 50-g glucose challenge test, followed by a 3-hour 100-g glucose tolerance test if the screening value was >140 mg/dL. Other exclusion criteria were multiple gestations and births with congenital anomalies as determined by diagnosis codes on the birth certificate and the infant’s medical record ( ICD-9 codes Q00-Q99).
In this database, length of gestation in days was calculated by subtracting the date of last normal menstrual period (LMP) from the date of birth of the linked infant. If a negative value was obtained, 1 year was subtracted from the date of LMP and the interval was recomputed. Gestational age was then converted into weeks and treated as an ordered categorical variable. If date of LMP was missing or was nonsensical, the mother/infant pair was excluded from analysis. For this study, we included births between 36-42 completed weeks; 36 weeks’ gestational age included births ranging from 36 weeks and 0 days to 36 weeks and 6 days; and 42 weeks’ gestational age included births from 42 weeks 0 days to 42 weeks 6 days.
The purpose of this study was to compare the mortality risks (including both stillbirth and infant death) associated with delivery at a given week of gestation, as compared to expectant management (ie, continuing the pregnancy for another week and then delivering 1 week later). More specifically, the mortality risk of delivery at a given week was defined as the rate among those infants born at that week of gestation. The mortality risk of a week of expectant management was defined as the risk of stillbirth over that week plus the mortality risk experienced by infants born in the subsequent week of gestation. This comparison was made at varying gestational ages among women with GDM. Neonatal death (death within 28 days of birth) has typically been the metric included in estimates of perinatal death rates, but recent data demonstrate that term infants who die within the first year of life are more likely to do so in the postneonatal (age 29-365 days of life) period than in the neonatal period. Infant mortality has also been shown to vary with gestational age at term and share many of the same risk factors as stillbirth. Thus, infant death was examined because of its significant magnitude and persistent association with gestational age at delivery.
The incidence of stillbirth at a given gestational age was calculated as the number of stillbirths at that gestational age per 10,000 ongoing pregnancies. Infant mortality at each gestational age was calculated as the number of infants born at this gestational age who die within 1 year of life per 10,000 live births at that same gestational age. The composite risk of expectant management for 1 week represents the sum of the probabilities of stillbirth during a given week of gestation plus the probability of infant death when birth occurs the following week. This composite risk of expectant management was then compared to the risk of infant death in the prior week of gestation to compare risk of delivery vs expectant management.
Our calculations rely on the following assumptions:
The risk of infant death has a uniform distribution throughout the week of gestation.
When estimating the risk of delivering at a particular gestational age, the fetus is not at risk for stillbirth beyond that gestational age, therefore mortality risk in that week is equal only to the risk of infant death.
The composite risk associated with expectant management is the sum of the risk of stillbirth during the week of gestation plus the risk of infant death in the following week of gestation.
Statistical calculations were performed with Excel (version 14.1.4; Microsoft Corporation, Redmond, WA) and Stata (version 12; StataCorp, College Station, TX), including simple proportions, relative risks (RRs), and 95% confidence intervals (CIs). We assumed that the binomial probability distributions of both mortality risks approximated the normal distribution and derived the CI of the composite risk using the sum of the variances of the estimates of infant death and stillbirth. The χ 2 test was performed to compare proportions, 2-tailed t tests were performed to compare means, and a P value < .05 was considered statistically significant.