| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
ORIGINAL RESEARCH |
From the Division of Research at Kaiser Permanente, Oakland; andDepartment of Obstetrics and Gynecology, Kaiser Foundation Hospital, Bellflower, California.
Address reprint requests to: Monique Hedderson, Division of Research, The Permanent Medical Group, 2000 Broadway, Oakland, CA 94612-2304; E-mail: mmh{at}dor.kaiser.org.
 |
ABSTRACT |
|---|
TOP
 ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
METHODS: We performed a cohort study of 46,230 pregnancies screened by a 50-g, 1-hour oral glucose tolerance test between 24 and 28 gestation weeks at the Northern California Kaiser Permanente Medical Care Program. Spontaneous preterm birth was defined as an infant born at less than 37 gestation weeks with at least one of the following: spontaneous labor, preterm premature rupture of membranes, or incompetent cervix. Glucose tolerance status was categorized as normal screening (1-hour plasma glucose less than 140 mg/dL), abnormal screening (1-hour plasma glucose of at least 140 mg/dL with a normal diagnostic 100-g, 3-hour oral glucose tolerance test result), Carpenter–Coustan (plasma glucose measurements during the diagnostic oral glucose tolerance test met the thresholds but were lower than the National Diabetes Data Group thresholds), and gestational diabetes mellitus (GDM) by the National Diabetes Data Group criteria.
RESULTS: One thousand nine hundred fifty-six spontaneous preterm births occurred. Age-adjusted incidences of spontaneous preterm birth were 4.0% in normal screening, 5.0% in abnormal screening, 6.7% in Carpenter–Coustan, and 6.7% in GDM. In a logistic regression model adjusted for age, race–ethnicity, preeclampsia–eclampsia–pregnancy-induced hypertension, chronic hypertension, polyhydramnios, and birth weight for gestational age, pregnancies with abnormal screening, Carpenter–Coustan, and GDM had a significantly higher risk of spontaneous pre-term birth than pregnancies with normal screening (relative risk [95% confidence interval]: 1.23 [1.08, 1.41], 1.53 [1.16, 2.03], and 1.42 [1.15–1.77], respectively).
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.
Preterm birth (birth at less than 37 completed gestation weeks) complicated 11.6% of all deliveries in the United States1 in 2001 and remains the single most important cause of perinatal mortality and infant morbidity.2 Despite extensive research, established risk factors such as nonwhite race, low socioeconomic status, and single marital status only account for 25–30% of preterm births in developed countries.3 Gestational diabetes mellitus (GDM) and lesser degrees of glucose intolerance have been associated with several perinatal complications that are more common among preterm infants such as respiratory distress syndrome, hypocalcemia, hypoglycemia, and preeclampsia.4 Four studies5–8 have examined the relationship between pregnancy hyperglycemia and pre-term birth; however, results have been inconsistent.
Recently, it has been suggested that preterm births be classified into separate etiologic pathways to create more homogeneous categories.2,9 The American College of Obstetricians and Gynecologists recently defined spontaneous preterm birth as spontaneous preterm labor, preterm premature rupture of membranes (PROM), and/or cervical incompetence resulting in delivery before the completion of 37 gestation weeks. Indicated preterm birth was defined as that which follows medical complications that place the mother or fetus at risk.10 The aim of this study was to determine whether different degrees of maternal glucose intolerance are associated with the risk of spontaneous preterm birth. The study was conducted using data from the 46,230 births that occurred at the Kaiser Permanente Medical Care Program of Northern California between January 1996 and June 1998.
|
MATERIALS AND METHODS |
|---|
|
TOP
ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
To identify pregnancies between January 1, 1996, and July 31, 1998, we searched the health plan’s hospitalization database for admission and or discharge diagnoses related to third-trimester pregnancy conditions, delivery, or stillborn fetus according to the International Classification of Diseases, Ninth Revision (ICD-9). The ICD-9 codes searched for mothers and newborns were V27.x (outcomes of delivery); V30–V39 (live-born infants according to type of birth); 72.x–73.x, 74.0–74.2, and 74.4 (delivery procedures); 644.x (early or threatened labor after 22 weeks); 645.x (prolonged pregnancy); 650 (normal delivery); 658.1–658.3 (delayed delivery after spontaneous or artificial rupture of membranes); 760.x–763.x (maternal causes of perinatal morbidity and mortality); and 764.x–779.x (condition originating in the perinatal period).
Each woman’s demographic information such as age and race–ethnicity was obtained from the computerized hospitalization record, which includes seven race–ethnicity categories: white, black, Hispanic, Asian, Native American, other, and unknown. Because of the small number of Native American and unknown women in our population, they were classified with the other women and race–ethnicity was categorized into five race–ethnicity groups. We have previously shown that the agreement between race–ethnicity recorded in the computerized record and the self-reported race–ethnicity recorded in the medical chart was 93%.12 Infant gestational age at birth was ascertained from the computerized medical record at birth. We were able to validate our electronic data for 498 pregnancies for which we had medical chart review data on a fetal ultrasound performed before 24 weeks’ gestational age. Among these 498 there were 17 infants who had gestational age less than 37 weeks according to electronic databases. Fifteen of these 17 were confirmed by calculations based on gestational age information obtained from an ultrasonographic examination. Of the 481 whose gestational age was at least 37 weeks according to electronic data, 474 (98.5%) were confirmed by ultra-sonographic data.
According to the gestational age–specific weight distribution of the study population, infants were considered large for gestational age (LGA) if their birth weight exceeded the 90th percentile or small for gestational age (SGA) if their birth weight was below the 10th. Macrosomia was defined as birth weight greater than 4000 g.
Information about selected pregnancy complications was obtained from the hospitalization database as follows (according to ICD-9 codes): placenta previa (641.0, 641.1, 762.0), abruptio placenta (641.2, 762.1), chronic hypertension (642.0–642.1), pregnancy-induced hypertension (642.3), preeclampsia–eclampsia (642.4–642.7), fetal growth restriction (656.5, 764.9), oligohydramnios (658.0, 761.2), polyhydramnios (657.0, 761.3), and infection of the amniotic cavity including chorioamnionitis, amnionitis, inflammation of membranes, and placentitis (658.4, 762.7).
Spontaneous preterm birth was defined as occurring at less than 37 gestation weeks and with at least one of the following hospital discharge diagnoses: early spontaneous onset of delivery (ICD-9 code 644.2), PROM (658.1, 761.0), and cervical incompetence (654.5, 761.0). We reviewed medical records of a random sample of 18 pregnancies we defined as ending in spontaneous pre-term birth according to our electronic databases. Of these, only one did not meet our criteria for spontaneous preterm birth because of gestational age greater than 37 weeks based on ultrasonographic data performed before 24 gestational weeks.
Indicated preterm birth was defined as involving an infant born at less than 37 weeks’ gestation who did not have any indication of spontaneous preterm birth (ie, preterm PROM, early spontaneous onset of delivery, or incompetent cervix) and did have a hospital discharge diagnosis or a procedure for induced labor (ICD-9 code V73.4) or cesarean delivery (V74.0, 669.7, or 763.4). Pregnancies ending in indicated preterm birth were excluded from the analyses.
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 tests were performed. All plasma glucose measurements were performed using the hexokinase method at the Kaiser Permanente Medical Care Program of Northern California regional laboratory, which participates in the College of American Pathologists’ accreditation and monitoring program. 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.
Women were classified into four mutually exclusive glucose tolerance categories: normal screening (1-hour plasma glucose after 50-g oral glucose tolerance test less than 140 mg/dL), abnormal screening (1-hour plasma glucose after 50-g oral glucose tolerance test of at least 140 mg/dL with normal 100-g, 3-hour oral glucose tolerance test), Carpenter–Coustan (at least two plasma glucose levels at or higher than the following cutoffs during a 100-g, 3-hour oral glucose tolerance test: fasting, 95 mg/dL; 1 hour, 180 mg/dL; 2 hour, 155 mg/dL; 3 hour, 140 mg/dL13),14 but not meeting the National Diabetes Data Group thresholds and GDM (at least two plasma glucose values during a 100-g, 3-hour oral glucose tolerance test at or higher than the National Diabetes Data Group plasma glucose thresholds: fasting, 105 mg/dL; 1 hour, 190 mg/dL; 2 hour, 165 mg/dL; 3 hour, 145 mg/dL).
The Kaiser Permanente Diabetes Registry of Northern California15 was searched to identify and exclude pregnancies with recognized chronic (ie, 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.
We identified 76,088 pregnancies occurring between January 1996 and July 1998 among members of the Kaiser Permanente Medical Care Program of Northern California who delivered live infant(s) or had stillborn fetus(es). We then excluded the following: 418 pregnancies that occurred in women who had recognized diabetes before the index pregnancy, 5177 pregnancies that were not screened for GDM, 22,268 that were screened before 24 weeks’ or after 28 weeks’ gestation, two pregnancies with singleton stillborn fetuses (V27.1), 699 pregnancies with multiple gestation (651.0–651.9,
761.5, V27.2–V27.7, V31–V37), and 389 pregnancies in which no diagnostic test was performed after an abnormal screening test. Among the remaining 46,865 pregnancies there were 2591 preterm births (5.5%) (less than 37 gestational weeks). Of these, 267 were indicated preterm births and 368 were nonclassifiable (less than 37 weeks but not meeting the spontaneous preterm birth or indicated criteria) and were therefore excluded, leaving 46,230 pregnancies for our analysis.
We used 
2 tests to compare differences in the distributions 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.16 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 study population used as the standard. Relative risks (RRs) are 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 regression analogue to the Mantel extension test (ie, 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 preformed 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)17 was used for all analyses.
This study was approved by the Human Subjects Committee of the Kaiser Foundation Research Institute.
|
RESULTS |
|---|
|
TOP
ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Table 1
compares demographic characteristics and the distribution of selected perinatal complications of the 46,230 mother–infant pairs by maternal glucose tolerance status. Women with pregnancies with normal screening were younger and more likely to be white than women with pregnancies with higher degrees of glycemia. Proportions of pregnancies complicated by preeclampsia–eclampsia, pregnancy-induced hypertension, chronic hypertension, polyhydramnios, large for gestational age, and macrosomia (birth weight greater than 4000 g) significantly increased with increasing degree of maternal glycemia. The proportion of pregnancies that required a cesarean delivery also increased significantly with increasing degree of glycemia. The proportion of pregnancies with SGA infants was significantly higher in pregnancies with normal screening. Abruptio placentae, placenta previa, oligohydramnios, infection of the amniotic cavity, and fetal growth restriction did not vary significantly by glucose tolerance status. Spontaneous preterm birth increased steadily with increasing degrees of maternal glycemia (P for linear trend <.001), and the age-adjusted incidence of spontaneous preterm birth was 4.0% (95% CI 3.8, 4.2) in normal screening, 5.0% (95% CI 4.4, 5.6) in abnormal screening, 6.7% (95% CI 4.7, 8.7) in Carpenter–Coustan, and 6.7% (95% CI 4.9, 8.5) in GDM.
|
shows the clinical characteristics by spontaneous preterm birth status. 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, abruptio placentae, oligohydramnios, polyhydramnios, infection of amniotic cavity, or fetal growth restriction and less likely to have large for gestational age and macrosomic infants. Age and smallness for gestational age were not significantly associated with spontaneous preterm birth (Table 2).
|
Table 3 shows the multivariate-adjusted RR estimates and 95% CIs for spontaneous preterm birth from logistic regression models for maternal glucose tolerance status. In a model adjusted for age and ethnicity the risk of spontaneous preterm birth 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 screening. Age less than 25 was not significantly associated with an increased risk of spontaneous preterm birth (RR 1.00; 95% CI 0.90, 1.12) compared with older groups. Compared with pregnancies that occurred in white women, pregnancies that occurred in ethnic minorities were also at increased risk of spontaneous preterm birth (RR 1.15; 95% CI 1.08, 1.26). When preeclampsia–eclampsia–pregnancy-induced hypertension, chronic hypertension, birth weight for gestational age, and polyhydramnios were added to the model, although all were associated with risk of spontaneous preterm births, the direct association between spontaneous preterm birth and maternal glycemia remained statistically significant (Table 3).
|
|
DISCUSSION |
|---|
|
TOP
ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Our results are consistent with the results of a study5 including a small number (n = 404) of pregnant women in China with 12 preterm births (less than 37 weeks’ gestational age). In this study the 102 women with impaired glucose tolerance according to the World Health Organization criteria were at increased risk of preterm birth.5
Our results are inconsistent with three previous reports that found no association between glucose tolerance and preterm birth. In a study of 2019 randomly selected women in a health maintenance organization, Magee et al6 found no differences in the proportion of pregnancies complicated by prematurity between the 96 women with GDM and women without GDM. Tallarigo et al7 conducted a study of 249 Italian women without GDM according to the National Diabetes Data Group criteria and found no association with prematurity across different maternal 2-hour plasma glucose concentrations. In a study of 811 pregnancies among Pima Indians,8 women were grouped according to 2-hour plasma glucose levels obtained after a 75-g oral glucose tolerance test, and no association between pregnancy glycemia and preterm birth (less than 37 weeks) was found. However, all of these studies suffered from small sample sizes with few preterm infants (no more than 32). In none of these previous studies was a distinction drawn between indicated preterm birth and spontaneous preterm birth. Neither were the data limited to women who were screened at 24–28 weeks of gestation to reduce the variability of glucose tolerance test results related to increasing gestational age.18
The major strengths of our study are our large sample size and our ability to distinguish between indicated and spontaneous preterm births. This distinction is extremely important, as Naylor et al19 have shown that physician intervention (such as induced labor or cesarean delivery) is more common in women who meet the National Diabetes Data Group or Carpenter–Coustan criteria for GDM. Although we also observed that cesarean delivery and induced labor were more common in pregnancies with GDM by Carpenter–Coustan or National Diabetes Data Group criteria, the observed association between maternal glycemia and spontaneous pre-term birth remained significant after exclusion of the 793 spontaneous preterm births that ultimately resulted in cesarean delivery or induced labor.
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 for gestational age and the association persisted after adjusting for an infant’s weight. Finally, 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.
It must be acknowledged, however, that 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.220 Our findings demonstrate that GDM defined by the National Diabetes Data Group criteria as well as lesser degrees of maternal hyperglycemia are independently associated with spontaneous preterm birth. Spontaneous preterm birth is a multifactorial disease with multiple clinical presentations including preterm labor, preterm PROM, and premature cervical effacement–dilation or "competence." The details of the biologic mechanisms behind how glucose intolerance increases the risk of spontaneous preterm birth remain to be elucidated.
|
Footnotes |
|---|
Two abstracts on portions of these data were published in the abstract book of the 59th Annual Scientific Sessions of the American Diabetes Association ( Diabetes 2002;51 Suppl 2) and in the abstract book of the 2001 Congress of Epidemiology ( Am J Epidemiol 2001;153 Suppl).
doi:10.1016/S0029-7844(03)00661-6
Received March 3, 2003. Received in revised form June 2, 2003. Accepted June 5, 2003.
|
REFERENCES |
|---|
|
TOP
ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
2. Berkowitz GS, Papiernik E. Epidemiology of preterm birth. Epidemiol Rev 1993;15:414–43.
3. Kramer MS. Determinants of low birth weight: Methodological assessment and meta-analysis. Bull World Health Organ 1987;65:663–737.[Medline]
4. Coustan DR. Gestational diabetes. In: Harris MI, ed. Diabetes in America. Bethesda, Maryland: National Institutes of Health, 1995:703–16.
5. Yang X, Hsu-Hage B, Zhang H, Zhang C, Zhang Y. Women with impaired glucose tolerance during pregnancy have significantly poor pregnancy outcomes. Diabetes Care 2002;25:1619–24.
6. Magee MS, Walden CE, Benedetti TJ, Knopp RH. Influence of diagnostic criteria on the incidence of gestational diabetes and perinatal morbidity. JAMA 1993;269: 609–15.[Abstract]
7. Tallarigo L, Giampietro O, Penno G, Miccoli R, Gregori G, Navalesi R. Relation of glucose tolerance to complications of pregnancy in nondiabetic women. N Engl J Med 1986;315:989–92.[Abstract]
8. Pettitt DJ, Knowler WC, Baird HR, Bennett PH. Gestational diabetes: Infant and maternal complications of pregnancy in relation to third-trimester glucose tolerance in the Pima Indians. Diabetes Care 1980;3:458–64.[Abstract]
9. Savitz DA, Blackmore CA, Thorp JM. Epidemiologic characteristics of preterm delivery: Etiologic heterogeneity. Am J Obstet Gynecol 1991;164:467–71.[Medline]
10. American College of Obstetricians and Gynecologists Committee on Practice Bulletins—Obstetrics. Perinatal care at the threshold of viability. ACOG practice bulletin no. 38. Obstet Gynecol 2002;100:617–24.[Medline]
11. Krieger N. Overcoming the absence of socioeconomic data in medical records: Validation and application of a census-based methodology. Am J Public Health 1992;82:703–10.
12. Ferrara A, Hedderson MM, Quesenberry CP, Selby JV. Prevalence of gestational diabetes mellitus detected by the National Diabetes Data Group or the Carpenter and Coustan plasma glucose thresholds. Diabetes Care 2002;25: 1625–30.
13. Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 1982;144: 768–73.[Medline]
14. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. National Diabetes Data Group. Diabetes 1979;28:1039–57.[Medline]
15. Selby JV, Ray GT, Zhang D, Colby CJ. Excess costs of medical care for patients with diabetes in a managed care population. Diabetes Care 1997;20:1396–402.[Abstract]
16. Breslow NE, Day NE. Statistical methods in cancer research. Volume 2: The design and analysis of cohort studies. IARC Sci Publ 1987;82:1–406.
17. SAS Institute. SAS/STAT software: Changes and enhancements through release 6.11. Cary, North Carolina: SAS Institute Inc., 1998.
18. Merkatz IR, Duchon MA, Yamashita TS, Houser HB. A pilot community-based screening program for gestational diabetes. Diabetes Care 1980;3:453–7.[Abstract]
19. Naylor CD, Sermer M, Chen E, Sykora K. Cesarean delivery in relation to birth weight and gestational glucose tolerance: Pathophysiology or practice style? Toronto Tri-hospital Gestational Diabetes Investigators. JAMA 1996; 275:1165–70.[Abstract]
20. Berkowitz GS, Lapinski RH, Wein R, Lee D. Race/ethnicity and other risk factors for gestational diabetes. Am J Epidemiol 1992;135:965–73.
This article has been cited by other articles:
|
|
 |
|
  D. B. Carr, K. M. Newton, K. M. Utzschneider, J. Tong, F. Gerchman, S. E. Kahn, and S. R. Heckbert Modestly Elevated Glucose Levels During Pregnancy Are Associated With a Higher Risk of Future Diabetes Among Women Without Gestational Diabetes Mellitus Diabetes Care, May 1, 2008; 31(5): 1037 - 1039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.P. Dasanayake, N. Chhun, A.C.R. Tanner, R.G. Craig, M.J. Lee, A.F. Moore, and R.G. Norman Periodontal Pathogens and Gestational Diabetes Mellitus J. Dent. Res., April 1, 2008; 87(4): 328 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Rowan and on behalf of the MiG Investigators A Trial in Progress: Gestational Diabetes: Treatment with metformin compared with insulin (the Metformin in Gestational Diabetes [MiG] trial) Diabetes Care, July 1, 2007; 30(Supplement_2): S214 - S219. [Full Text] [PDF]
|
|
|
|
|
|
J. L. Kitzmiller, L. Dang-Kilduff, and M. M. Taslimi Gestational Diabetes After Delivery: Short-term management and long-term risks Diabetes Care, July 1, 2007; 30(Supplement_2): S225 - S235. [Full Text] [PDF]
|
|
|
|
 |
|
 H. E. Virtanen, A. E. Tapanainen, M. M. Kaleva, A.-M. Suomi, K. M. Main, N. E. Skakkebaek, and J. Toppari Mild Gestational Diabetes as a Risk Factor for Congenital Cryptorchidism J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 4862 - 4865. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Rosenberg, S. Garbers, H. Lipkind, and M. A. Chiasson Maternal Obesity and Diabetes as Risk Factors for Adverse Pregnancy Outcomes: Differences Among 4 Racial/Ethnic Groups Am J Public Health, September 1, 2005; 95(9): 1545 - 1551. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
