To investigate whether different degrees of maternal glucose intolerance were associated with the risk of spontaneous preterm birth.

• Pregnancies between January 1, 1996 - July 31, 1998.
• Screened by a 50-g, 1 hour oral glucose tolerance test between 24 to 28 gestation weeks at the Northern California Kaiser Permanente Medical Care program.
• Spontaneous birth - defined as an infant born at less than 37 gestation weeks with at least 1 of the following: spontaneous labor, preterm rupture of membranes, or incompetent cervix.
• The study was approved by the Human Subjects Committee of the Kaiser Foundation Research Institute

• The Kaiser Permanente Diabetes Registry of Northern California was searched to identity and exclude pregnancies with recognized chronic (i.e., nongestational) diabetes before the index pregnancy.
• The Diabetes Registry is a longitudinal surveillance and systematically excludes women with GDM.
• Women were considered to have diabetes before the index pregnancy if they were identified by the Diabetes Registry at least 9 months before the delivery date.
• Pregnancies ending in indicated preterm birth were excluded from the analyses.

Recruitment Method was not detailed

Design : Historical cohort

Blinding used:  not applicable 

Intervention:  not applicable

Statistical Analysis

• X ² tests were used to compare differences in the distribution of age and race-ethnicity groups by glucose tolerance status categories and all characteristics by spontaneous preterm birth.
• Age-adjusted comparisons of characteristics by glucose tolerance status were performed by the Mantel-Haenszel method.
• The age-adjusted spontaneous preterm birth incidence and 95% confidence intervals (CIS) were calculated by the direct method with the age distribution of the entire population used as the standard.
• Relative risks (RRs) were estimated by odds ratios in multiple logistic regression to assess the association of spontaneous preterm birth with glucose tolerance status.
• The association between level of pregnancy glycemia and spontaneous preterm birth was assessed with a test for trend for the ordered variable (glucose tolerance category) using the logistic analogue to the Mantel extension test (i.e., a test based on the significance of a single trend variable coded as the category of exposure).
• A test for interaction in the logistic regression model was performed to assess whether the association between preterm birth and glucose category differed by preeclampsia, largeness for gestational age, smallness for gestational age, or polyhydramnios.
• Statistical significance was defined as a P value less than .05.
• SAS 6.11(SAS Institute Inc., Cary, NC) was used for all analyses.

Timing of Measurements

Dependent Variables

Diagnostic criteria

• The laboratory database, a clinical database that captures all laboratory tests and results performed at the Kaiser Permanente Medical Care Program of Northern California regional laboratory, was searched to obtain screening plasma glucose results of the 50-g, 1-hour oral glucose tolerance test and the 100-g, 3-hour oral glucose tolerance diagnostic test for GDM as well as the dates on which these test were performed.
• Gestational age at screening was calculated by the difference between the infant’s gestational age at birth and the date when the mother performed the screening test       

Glucose tolerance status was categorized as:

• Spontaneous preterm birth-an infant born at least 37 gestation weeks with at least one of the following: (1) spontaneous labor; (2) preterm premature rupture of membranes, or (3) incompetent cervix

Independent Variables

• Age-<25;25-34; > 35
• Race-ethnicity-White, Hispanic, Asian, Black, other/unknown
• Pregnancy-induced hypertension
• Preeclampsia or eclampsia
• Chronic hypertension
• Placenta privia
• Abruptio placentae
• Oligohydramnios
• Polyhydramnios
• Infection of the amniotic cavity
• Fetal growth restriction
• Small for gestational age
• Large for gestational age
• Macrosomia (birth weight > 4000g)
• Cesarean delivery
• Induced labor

Control Variables

Initial N: 46,230 pregnancies

Attrition (final N):  46,230 pregnancies

Age: See Table 1

Ethnicity: See Table 1

Other relevant demographics:

Anthropometrics

Location: Division of Research at Kaiser Permanente, Oakland; and Department of Obstetrics and Gynecology, Kaiser Foundation Hospital, Bellflower, California.

Women with pregnancies with normal screening were younger and more likely to be white than women with pregnancies with higher degrees of glycemia (Table 1).

Table 1. Characteristics of the 46,230 Pregnancies by Glucose Tolerance Status, The Kaiser Permanente Northern California Gestational Diabetes Registry, 1996-1998.

Women with pregnancies with spontaneous preterm birth were significantly more likely to be of nonwhite race and to have pregnancy-induced hypertension, preeclampsia-eclampsia, chronic hypertension, placenta previa, abruption placentae, oligohydramnios, polyhydraminos, infection of amniotic cavity, or fetal growth restriction and less likely to have large for gestational age and macrosomic infants (Table 2). 

Table 2. Characteristics of the 46,230 Pregnancies by Spontaneous Preterm Birth Status. The Kaiser Permanente Northern California Gestational Diabetes Registry, 1996-1998. 

In a model adjusted for age and ethnicity the risk of spontaneous preterm births increased with increasing degrees of maternal glycemia and was 28% higher in abnormal screening pregnancies, 70% higher in Carpenter-Coustan pregnancies, and 61 % higher in GDM pregnancies relative to pregnancies with normal screenings (Table 3). 

Table 3. Association of Maternal Glucose Tolerance Status With Spontaneous Preterm Delivery Among the 46,230 Pregnancies, The Kaiser Permanente Northern California Gestational Diabetes Registry, 1996-1998 

Other Findings

Conclusion:

• The risk of spontaneous preterm birth increased with increasing levels of pregnancy glycemia. This association was independent of perinatal complications that could have triggered early delivery.  
• The association between maternal glycemia and spontaneous preterm birth was not explained by an infant’s birth weight due to maternal glycemia because the association did not vary by birth weight by birth weight for gestational age and the association persisted after adjusting for an infant’s weight.  
• Although maternal conditions such as preeclampsia, pregnancy-induced hypertension, chronic hypertension, and polyhydramnios were significantly associated with both maternal glycemia and spontaneous preterm birth, the direct association between maternal glycemia and spontaneous preterm birth was only slightly attenuated and remained statistically significant after adjusting for these conditions. 

 Limitations:

• This study was limited to recorded data, and therefore we were unable to control for other potential confounding variables of the association between preterm birth and maternal glycemia such as prepregnancy weight and parity which have previously been reported to be associated with both preterm birth and GDM.
• The Kaiser Permanente Medical Care program of Northern California membership represents approximately 30% of the surrounding population and is representative of the population living in the same geographical area demographically, ethnically, and socioeconomically, except the membership under-represents the very poor and the very wealthy.

In a historical cohort study, data on exposure and occurrence of disease are collected after the events have taken place—the cohorts of exposed and non-exposed subjects are assembled from existing records, or health care registries. Studies of this kind provide a better opportunity than one time cross sectional studies to examine whether certain behaviors do in fact lead to (or cause) the disease.

The limitations and critique of the study, as stated by the authors appear to be very appropriate.