The Journal of Maternal-Fetal & Neonatal Medicine
ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20
Obstetrical outcomes in patients with early onset gestational diabetes Simi Gupta, Cara Dolin, Ashwin Jadhav, Judith Chervenak, Ilan Timor-Tritsch & Ana Monteagudo To cite this article: Simi Gupta, Cara Dolin, Ashwin Jadhav, Judith Chervenak, Ilan Timor-Tritsch & Ana Monteagudo (2014): Obstetrical outcomes in patients with early onset gestational diabetes, The Journal of Maternal-Fetal & Neonatal Medicine To link to this article: http://dx.doi.org/10.3109/14767058.2014.991711
Accepted author version posted online: 26 Nov 2014. Published online: 23 Dec 2014. Submit your article to this journal
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Date: 05 November 2015, At: 20:39
http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, Early Online: 1–5 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.991711
ORIGINAL ARTICLE
Obstetrical outcomes in patients with early onset gestational diabetes Simi Gupta1,2, Cara Dolin1, Ashwin Jadhav1,3, Judith Chervenak1, Ilan Timor-Tritsch1, and Ana Monteagudo1 1
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA, Maternal Fetal Medicine Associates, New York, NY, USA, and 3Division of Maternal-Fetal Medicine, UMDNJ-Robert Wood Johnson Medical School, New York, NY, USA
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Abstract
Keywords
Objective: The objective of this study was to characterize patients with early onset gestational diabetes and compare outcomes to patients diagnosed with standard gestational diabetes and pregestational diabetes. Methods: This is a retrospective cohort study of patients diagnosed with gestational or pregestational diabetes. All patients received a glucose challenge test at their first prenatal visit to diagnose early onset gestational diabetes and were recommended to have postpartum glucose tolerance tests to detect undiagnosed type 2 diabetes. Outcomes were compared between patients with early onset gestational diabetes and both standard gestational diabetes and pregestational diabetes with p50.05 was used for significance. Results: Four hundred and twenty-four patients met the inclusion criteria. Nine percent of the patients with early onset gestational diabetes were found to have undiagnosed type 2 diabetes based on postpartum testing and 91% to have resolution in the postpartum period. No patient with early onset gestational diabetes and resolution in the postpartum period had abnormal screening for renal or ophthalmologic disease, but 5% had abnormal fetal echocardiograms. These patients were more likely to require pharmacotherapy for glycemic control than patients with standard gestational diabetes and less likely than patients with pregestational diabetes (55% versus 39% versus 81%). Conclusion: Most patients diagnosed with early onset gestational diabetes do not have undiagnosed type 2 diabetes but do have unique characteristics and obstetrical outcomes.
Gestational diabetes, postpartum glucose tolerance test, pregestational diabetes
Introduction Screening for gestational diabetes mellitus (GDM) has undergone much scrutiny in recent years [1]. Traditionally, patients at high risk for developing GDM based on clinical risk factors, have undergone early screening for detecting GDM, while patients at low risk have undergone screening at 24–28 weeks gestation. The rationale for early screening based on these risk factors, including advanced maternal age, obesity, history of gestational diabetes, delivery of a previous large for gestational age infant, polycystic ovary syndrome, or family history of diabetes, has been to detect undiagnosed type 2 diabetes [2–4]. Certain adverse pregnancy outcomes are associated with both pregestational and gestational diabetes. These include macrosomia, pre-eclampsia, polyhydramnios, stillbirth and neonatal morbidity. Other complications, such as increased rates of congenital anomalies and progression of retinopathy,
Address for correspondence: Simi Gupta, Maternal Fetal Medicine Associates, PLLC, 70 East 90th Street, New York, NY 10128, USA. Tel: 713-548-6998. Fax: 212-722-7185. E-mail: [email protected]
History Received 25 August 2014 Revised 18 November 2014 Accepted 21 November 2014 Published online 23 December 2014
are unique to pregestational diabetes. This is mainly due to the poor glycemic environment during fetal organogenesis and to preexisting vascular disease in patients with pregestational diabetes. Patients with early onset gestational diabetes have been shown to have worse outcomes than patients diagnosed at the standard 24–28 weeks of gestation. One study showed that these patients had a higher rate of requiring pharmacologic therapy, macrosomia and large for gestational age infants, cesarean section, and 3rd and 4th degree perineal lacerations [5]. Another study showed a similar finding of a higher rate of requiring pharmacologic therapy, but also showed higher rates of pre-eclampsia, neonatal hypoglycemia and perinatal deaths [6]. Unfortunately, prior studies have not separated patients with early onset gestational diabetes and undiagnosed type 2 diabetes mellitus from those patients without undiagnosed type 2 diabetes mellitus. This has left a large gap in knowledge regarding management of these patients, and subsequently some have chosen to treat all the patients with early onset gestational diabetes as having type 2 diabetes mellitus. In this study, we aimed to characterize patients with early onset
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gestational diabetes, and to compare pregnancy outcomes to both patients with standard gestational diabetes diagnosed at 24–28 weeks gestation and patients with pregestational diabetes.
Downloaded by [University of Pennsylvania] at 20:39 05 November 2015
Methods We conducted a retrospective cohort study of all the patients who were diagnosed with gestational or pregestational diabetes and delivered at a single urban public hospital between 1 January 2007 and 31 December 2011. Because a high percentage of patients at this hospital carry one of more risk factors for gestational diabetes, all patients, unless they have pregestational diabetes, are screened for gestational diabetes at their first prenatal visit with a 50-g, one-hour, oral-glucosechallenge test. Abnormal results, defined as a plasma glucose level 140 mg/dL, were followed-up with a 100-g, three-hour, oral-glucose-tolerance test. Patients with two or more abnormal results, defined as a fasting plasma glucose 105 mg/dL, 1 h 190 mg/dL, 2 h 165 mg/dL, or 3 h 145 mg/dL, were diagnosed with gestational diabetes [7]. Because these patients were diagnosed early in pregnancy before 24 weeks gestation, we consider these patients to have early onset gestational diabetes. Patients with a normal early glucose challenge test or glucose tolerance test repeated screening at 24–28 weeks gestation. Patients with abnormal glucose tolerance tests at 24–28 weeks gestation are diagnosed with standard gestational diabetes. Patients were categorized as having pregestational diabetes if they reported a history of type 1 or type 2 diabetes. Institutional review board approval was obtained for the review of maternal and infant charts. Patients were identified based on International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code at the time of delivery. Inclusion criteria were accurate screening and diagnosis, presentation for prenatal care prior to 24 weeks gestation, and prenatal care at the primary clinic affiliated with the hospital. Patients with pregestational diabetes and early onset gestational diabetes were managed similarly with baseline hemoglobin A1c (Hb A1c) levels, 24-h urine protein collections, fetal echocardiograms, ophthalmologic evaluations, maternal electrocardiograms, fetal growth scans, fetal antenatal testing and glycemic control with diet, oral medication or insulin as necessary. Patients with standard gestational diabetes were managed with fetal growth scans, fetal antenatal testing and glycemic control. Target glucose ranges were 95 mg/dL fasting and 140 mg/dL 2 h postprandial. Patients with pregestational diabetes were continued on glyburide or metformin if they were being treated with one of those medications prior to pregnancy and had good glycemic control. The need to initiate pharmacotherapy for any patient with glyburide or insulin was determined by the attending physician reviewing the patient’s glucose logs. Patients with early onset gestational diabetes or standard gestational diabetes underwent a 75 g, two-hour, glucose-tolerance test 6–12 weeks postpartum. Patients with a fasting plasma glucose 126 mg/dL or a 2 h 200 mg/dL were diagnosed with type 2 diabetes and were considered to likely have had previously undiagnosed type 2 diabetes mellitus. Data on maternal demographics and characteristics, test results, and
J Matern Fetal Neonatal Med, Early Online: 1–5
obstetrical outcomes were collected. Maternal demographics and characteristics included age, parity, self-reported BMI and ethnicity. Test results included glucose challenge test and glucose tolerance test values, Hb A1c levels, 24-h urine protein values, fetal echocardiograms, ophthalmologic evaluations, fetal growth scans and fetal antenatal testing. Obstetrical outcomes included therapy for glycemic control, infant birth weight and infant APGARs. Data were compared between groups using Chi-square, Mann–Whitney, and t-test as appropriate. p50.05 was used for significance.
Results During the study period, 424 patients were included in the study. An additional 81 patients did not meet inclusion criteria: 2 were not diagnosed by glucose tolerance tests, 60 were late transfers of care after 24 weeks gestation, and 19 did not have prenatal care at the primary clinic. Two patients were excluded because they did not undergo early screening at their first prenatal visit. Figure 1 shows the distribution of the 424 patients included in the study. There were 140 patients who were diagnosed with early onset gestational diabetes, 221 patients with standard gestational diabetes and 63 patients with pregestational diabetes. The gestational age at the time of the early glucose challenge test ranged from 2 to 23 weeks gestation with a mean of 9.8 weeks (standard deviation ± 4.3). Of the 140 patients with early onset gestational diabetes, 66 underwent the 2-h postpartum glucose tolerance test (47%). Of these, 32 (45%) had an abnormal postpartum glucose tolerance test. Six (9%) met criteria for diabetes and could be labeled with likely undiagnosed type 2 diabetes mellitus. The remaining 26 patients (39%) had tests that met criteria for prediabetes in whom either the fasting plasma glucose is 100– 125 mg/dL or the 2 h is 140–199 mg/dL. Sixty patients (91%) were labeled as true early onset gestational diabetics, including the 34 patients with normal postpartum glucose tolerance tests and the 26 patients with postpartum glucose tolerance tests that met criteria for prediabetes (Figure 1). Of the 221 patients with standard gestational diabetes, 119 underwent the 2-h postpartum glucose tolerance test (54%). One patient (0.8%) had a glucose tolerance test suggestive of undiagnosed type 2 diabetes and 33 (30.0%) had a glucose tolerance test suggestive of prediabetes. There was no significant difference in the age, parity, ethnicity or timing of the diagnosis of gestational diabetes in the patients who underwent a postpartum glucose tolerance test and those who did not (data not shown). Table 1 shows the maternal characteristics and screening outcomes of all patients with pregestational diabetes, early onset gestational diabetes, and standard gestational diabetes. The percentage of patients of a high-risk ethnicity (Hispanic, African American or South Asian) increased from standard gestational diabetics to early onset gestational diabetics to pregestational diabetics (82.2% versus 89.1% versus 93.3%, p ¼ 0.043). As expected, the early glucose challenge test value was higher in patients with early onset gestational diabetes versus those with standard gestational diabetes (182.1 mg/dL versus 129.8 mg/dL, p50.001). Table 2 compares the maternal demographics and characteristics of the patients with early onset gestational diabetes
Early onset gestational diabetes
DOI: 10.3109/14767058.2014.991711
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424 Diabetes
140 Gestaonal diabetes diagnosed before 24 weeks (Early Onset Gestaonal Diabetes)
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66 had PPGTT
60 Normal PP GTT (Early onset gestaonal diabetes without undiagnosed Type 2 Diabetes)
63 Pregestaonal Diabetes
102 did not have PP GTT
119 had PP GTT
74 did not have PP GTT
6 Abnormal PP GTT (Early onset gestaonal diabetes with undiagnosed Type 2 Diabetes
221 Gestaonal diabetes diagnosed 24-28 weeks
1 Abnormal PP GTT
118 Normal PP GTT
Figure 1. Flow diagram of included patients. PP GTT: Postpartum glucose tolerance test.
Table 1. Maternal demographics and characteristics of all the patients. Early onset Pregestational gestational diabetesy Standard gestational (n ¼ 140) diabetes (n ¼ 221) p Value diabetes (n ¼ 63)
Characteristic Age (in years, ±SD) Multiparous (%) High risk ethnicity* (%) Glucose challenge test (in mg/dL, ±SD)
31.3 (±7.2) 66.7 93.3 NA
31.8 (±5.8) 66.4 89.1 182.1 (±31.1)
31.0 (±5.4) 63.8 82.2 129.8 (±25.3)
0.414 0.843 0.043 50.001
*Hispanic, African-American, South Asian. yAll patients who were diagnosed with gestational diabetes prior to 24 weeks gestation.
Table 2. Comparison of maternal characteristics and demographics of patients with early onset gestational diabetes between patients with undiagnosed type 2 diabetes and true early onset gestational diabetes.
Characteristic Age (in years, ±SD) Multiparous (%) High risk ethnicity* (%) Body mass index (in kg/m2, ±SD) Body mass index classificationy (%) Glucose challenge test 200 mg/dL (%) Baseline Hemoglobin A1c (in %, ±SD) Baseline Hemoglobin A1c 5.7(%)
Early onset gestational diabetes with undiagnosed type 2 diabetes (n ¼ 6)
Early onset gestational diabetes without undiagnosed type 2 diabetes (n ¼ 60)
35.0 (±3.6) 100 83.3 31.0 (±5.1) Normal weight: 0 Overweight: 50 Obese: 50 67 6.4 (±0.62) 100
31.0 (±5.7) 53 90 29.1 (±5.0) Normal weight: 26.7 Overweight: 35 Obese: 38.3 27 5.7 (±0.53) 41
p Value 0.101 0.027 0.625 0.375 0.345 0.046 0.006 0.013
Overweight ¼ BMI 25 to 29.9 kg/m2. Obese ¼ BMI 39 kg/m2. *Hispanic, African-American, South Asian. yBody mass index (BMI) classification. Normal weight ¼ BMI 18.5 to 24.9 kg/m2.
with undiagnosed type 2 diabetes to patients with true early onset gestational diabetes. There was no difference in the gestational age in weeks of the early GCT between the two groups (10 ± 6 versus 9.5 ± 3.9, p ¼ 0.762). Patients who ultimately were labeled with undiagnosed type 2 diabetes were more likely to be multiparous than patients with true
early onset gestational diabetes (100% versus 53%, p ¼ 0.027). Patient with undiagnosed type 2 diabetes were also more likely to have a glucose challenge test 200 mg/dL than patients with true early onset gestational diabetes (67% versus 27%, p ¼ 0.046) and a Hb A1C 5.7 (100% versus 41%, p ¼ 0.013). A Hb A1C 5.7 was used as a cut off as
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J Matern Fetal Neonatal Med, Early Online: 1–5
Table 3. Comparison of obstetrical outcomes between patients with standard gestational diabtes, true early onset gestational diabetes, and pregestational diabetes.
Outcome
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Required treatment with medication (%) Required treatment with oral medication (%) Required treatment with insulin (%) Last ultrasound for growth 497 (%) Abnormal antenatal testing (%) Mean birthweight, in grams (±SD) Birthweight 44500g (%) Median Neonatal APGAR at 5 min (range)
Standard gestational diabetes (n ¼ 221)
p Value comparing standard gestational diabetes to early onset gestational diabetes
Early onset gestational diabetes (n ¼ 60)
p Value comparing early onset gestational diabetes to pregestational diabetes
39 38 2 6 15 3352 (±517) 2 9 (3–10)
0.030 0.038 0.637 0.910 0.943 0.151 0.239 0.811
55 53 3 5 14 3243 (±553) 0 9 (6–9)
0.002 0.040 50.001 0.336 0.650 0.114 0.013 0.102
values above this represent an increased risk for diabetes by the American Diabetes Association. No patients with true early onset gestational diabetes had abnormal screening 24-h urine proteins defined as 300 mg of protein (n ¼ 35), anatomy ultrasounds (n ¼ 60), or ophthalmologic exams (n ¼ 7). Five percent of the patients had abnormal fetal echocardiograms (n ¼ 22). The obstetrical outcomes of patients with pregestational diabetes and those with true early onset gestational diabetes are compared in Table 3. Patients with pregestational diabetes were more likely to require pharmacotherapy for glycemic control than patients with true early onset gestational diabetes (81% versus 55%, p ¼ 0.002). They were also more likely to deliver an infant weighing 44500 g (10% versus 0%, p ¼ 0.013). Table 3 also compares the obstetrical outcomes of patients with true early onset gestational diabetes and standard gestational diabetes. Patients with standard gestational diabetes were less likely to require pharmacotherapy for glycemic control than patients with true early onset gestational diabetes (55% versus 39%, p ¼ 0.030).
Discussion This study shows that only 9% of patients diagnosed with gestational diabetes early in pregnancy likely have undiagnosed type 2 diabetes. The rest appear to represent a unique set of patients with true early onset gestational diabetes that resolves in the postpartum period. Looking specifically at the additional screening done for patients with pregestational diabetes, none of the patients with true early onset gestational diabetes had abnormal testing for the renal or ophthalmologic complications of diabetes, but a percentage of patients had abnormal fetal echocardiograms. Patients with true early onset gestational diabetes fell in an intermediate risks category for requiring pharmacotherapy for glycemic control between patients with pregestational diabetes and standard gestational diabetes. They also were less likely to deliver an infant weighing 44500 g than patients with pregestational diabetes. All other obstetrical outcomes that were compared were similar to pregestational and standard gestational diabetics. The results of this study characterizing patients with early onset gestational diabetes show that most of these patients do not have persistence into the postpartum period or have
Pregestational diabetes (n ¼ 63) 81 33 63 10 11 3429 (±727) 10 9 (8–9)
undiagnosed type 2 diabetes, yet they are more likely to require pharmacotherapy than patients with standard gestational diabetes. This information affects management of these patients with early onset gestational diabetes. Based on this study, treating all patients with early onset gestational diabetes as though they have pregestational diabetes may be unnecessary. The risk for long-term vascular complications of pregestational diabetes appears to be unlikely, but the number studied in this study is too low to draw any conclusions. On the other hand, these patients do need to still be screened for congenital anomalies that may be a result of the poor glycemic environment present during the period of organogenesis. This may be done through early anatomy scans and fetal echocardiograms. Parity (100% sensitivity, 47% specificity), glucose challenge tests 200 mg/dL (67% sensitivity, 73% specificity), and Hb A1C 5.7 (100% sensitivity, 69% specificity) can help differentiate patients with undiagnosed type 2 diabetes mellitus from those with true early onset gestational diabetes. While there was no difference in BMI between the two groups, this was a self-reported BMI and therefore may be unreliable. The results regarding obstetrical outcomes are similar to those reported in prior studies. Specifically, this study agrees with prior studies that show that patients with early onset gestational diabetes are more likely to require pharmacologic therapy for glycemic control than patients with standard gestational diabetes. However, while previous studies did not differentiate patients with early onset gestational diabetes with undiagnosed type 2 diabetes from those without undiagnosed type 2 diabetes, this study does and is still able to show a higher requirement for pharmacotherapy. This may suggest that earlier diagnosis of this high risk group may have benefits beyond detecting undiagnosed type 2 diabetes. The results also show that although patients with early onset gestational diabetes have a low risk of an abnormal postpartum glucose tolerance test diagnostic of type 2 diabetes (9%), they have a high risk of a test diagnostic of prediabetes (39%). This risk is similar to the risk of prediabetes in patients with standard gestational diabetes (30%). This supports the fact that all the patients with gestational diabetes are at increased risk of developing type 2 diabetes later in life and emphasizes the importance of interventions geared towards prevention.
Early onset gestational diabetes
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DOI: 10.3109/14767058.2014.991711
The primary strength of this study is that the vast majority of patients who presented for prenatal care in this study received an early glucose challenge test. This takes away any selection bias from screening patients with an early glucose challenge test based on risk factors. Additionally, the care for these patients was fairly standardized since they all received prenatal care at a single clinic. Finally, the results of this study may be generalizable to any patient population with a high percentage of patients with risk factors for diabetes. With the increase in obesity nationwide, this is likely to characterize more and more patient populations. The study, however, does have limitations. One limitation is that only maternal and obstetrical outcomes were reviewed. Infant data was not available for review. Therefore, the risk of congenital anomalies is based off of antenatal anatomy ultrasounds and fetal echocardiograms and therefore may overestimate or underestimate the true risk. An additional limitation is that while 140 patients were diagnosed with early onset gestational diabetes, only 66 presented for a postpartum glucose tolerance test due to non compliance. However, a study by Russell et al. [8] on postpartum glucose testing in women with gestational diabetes who received prenatal care in a maternal diabetes clinic found that marital status was the only demographic significantly different between patients who received postpartum testing and those that did not. Furthermore, they found that there was no difference in the risk of diabetes, as measured by the magnitude of the antenatal fasting glucose abnormality, between those who underwent postpartum testing and those who did not [8]. Similarly, in this study, there was no difference in maternal demographics in patients who underwent postpartum testing and those who did not. Therefore, if there was selection bias in our study, it was likely limited. Gestational diabetes affects 2–10% of the pregnancies and this number is likely to rise with the rise in patients with risk factors for diabetes such as obesity and high risk ethnicities [9]. It is extremely important to accurately diagnose patients’ risks for certain adverse pregnancy outcomes in order to properly utilize resources. This study shows that the majority of patients with early onset gestational diabetes do not have undiagnosed type 2 diabetes and therefore may forgo screening tests for some of the vascular complications of pregestational diabetes. It also shows that an early glucose challenge test 4200 mg/dL and/or a Hb A1C 5.7% may help differentiate patients with undiagnosed type 2 diabetes from
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those with true early onset gestational diabetes. Finally, it shows that patients with early onset gestational diabetes are still at a higher risk for fetal congenital anomalies that may be a result of the poor glycemic environment during organogenesis. Early anatomy scans and fetal echocardiograms in these patients may help ensure that infants with congenital anomalies are detected early and delivered at institutions with the appropriate resources. They are also at a higher risk for requiring pharmacotherapy, and therefore, there may be some benefit to early diagnosis beyond the detection of undiagnosed type 2 diabetes. While larger studies need to be conducted in order to confirm these findings, this study can help guide clinicians as to the appropriate management of these high-risk patients.
Declaration of interest The authors report no conflict of interest.
References 1. Metzger BE, Gabbe SG, Persson B, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. International Association of Diabetes and Pregnancy Study Groups Consensus Panel. Diabetes Care 2010;33:676–82. 2. Standards of medical care in diabetes–2011. American Diabetes Association. Diabetes Care 2011;34: S11–61. 3. Gestational diabetes mellitus. Practice Bulletin No. 137. American College of Obstetricians and Gynecologists. Obstet Gynecol 2013; 122:406–16. 4. Moore TR, Catalano P. Diabetes in pregnancy. In: Creasy RK, Resnik R, Iams JD, eds. Creasy and Resnik’s maternal-fetal medicine: principles and practice. 6th ed. Philadelphia (PA): Sauners Elsevier; 2009:953–93. 5. Most O, Kim JH, Arslan A, Klauser C. Maternal and neonatal outcomes in early glucose tolerance testing in an obstetric population in New York City. J Perinat Med 2009;37:114–17. 6. Bartha JL, Martinez-Del-Fresno P, Comino-Delgado R. Gestational diabetes mellitus diagnosed during early pregnancy. Am J Obstet Gynecol 2000;182:346–50. 7. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2000;23:S4–19. 8. Russell M, Phipps M, Olson C, et al. Rates of postpartum glucose testing after gestational diabetes mellitus. Obstet Gynecol 2006; 108:1456–62. 9. Centers for Disease Control and Prevention. 2011. 2011 National Diabetes Fact Sheet. Available from: http://www.cdc.gov/diabetes/ pubs/estimates11.htm#8 [last accessed 9 Dec 2013].
ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20
Obstetrical outcomes in patients with early onset gestational diabetes Simi Gupta, Cara Dolin, Ashwin Jadhav, Judith Chervenak, Ilan Timor-Tritsch & Ana Monteagudo To cite this article: Simi Gupta, Cara Dolin, Ashwin Jadhav, Judith Chervenak, Ilan Timor-Tritsch & Ana Monteagudo (2014): Obstetrical outcomes in patients with early onset gestational diabetes, The Journal of Maternal-Fetal & Neonatal Medicine To link to this article: http://dx.doi.org/10.3109/14767058.2014.991711
Accepted author version posted online: 26 Nov 2014. Published online: 23 Dec 2014. Submit your article to this journal
Article views: 51
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijmf20 Download by: [University of Pennsylvania]
Date: 05 November 2015, At: 20:39
http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, Early Online: 1–5 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.991711
ORIGINAL ARTICLE
Obstetrical outcomes in patients with early onset gestational diabetes Simi Gupta1,2, Cara Dolin1, Ashwin Jadhav1,3, Judith Chervenak1, Ilan Timor-Tritsch1, and Ana Monteagudo1 1
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA, Maternal Fetal Medicine Associates, New York, NY, USA, and 3Division of Maternal-Fetal Medicine, UMDNJ-Robert Wood Johnson Medical School, New York, NY, USA
Downloaded by [University of Pennsylvania] at 20:39 05 November 2015
2
Abstract
Keywords
Objective: The objective of this study was to characterize patients with early onset gestational diabetes and compare outcomes to patients diagnosed with standard gestational diabetes and pregestational diabetes. Methods: This is a retrospective cohort study of patients diagnosed with gestational or pregestational diabetes. All patients received a glucose challenge test at their first prenatal visit to diagnose early onset gestational diabetes and were recommended to have postpartum glucose tolerance tests to detect undiagnosed type 2 diabetes. Outcomes were compared between patients with early onset gestational diabetes and both standard gestational diabetes and pregestational diabetes with p50.05 was used for significance. Results: Four hundred and twenty-four patients met the inclusion criteria. Nine percent of the patients with early onset gestational diabetes were found to have undiagnosed type 2 diabetes based on postpartum testing and 91% to have resolution in the postpartum period. No patient with early onset gestational diabetes and resolution in the postpartum period had abnormal screening for renal or ophthalmologic disease, but 5% had abnormal fetal echocardiograms. These patients were more likely to require pharmacotherapy for glycemic control than patients with standard gestational diabetes and less likely than patients with pregestational diabetes (55% versus 39% versus 81%). Conclusion: Most patients diagnosed with early onset gestational diabetes do not have undiagnosed type 2 diabetes but do have unique characteristics and obstetrical outcomes.
Gestational diabetes, postpartum glucose tolerance test, pregestational diabetes
Introduction Screening for gestational diabetes mellitus (GDM) has undergone much scrutiny in recent years [1]. Traditionally, patients at high risk for developing GDM based on clinical risk factors, have undergone early screening for detecting GDM, while patients at low risk have undergone screening at 24–28 weeks gestation. The rationale for early screening based on these risk factors, including advanced maternal age, obesity, history of gestational diabetes, delivery of a previous large for gestational age infant, polycystic ovary syndrome, or family history of diabetes, has been to detect undiagnosed type 2 diabetes [2–4]. Certain adverse pregnancy outcomes are associated with both pregestational and gestational diabetes. These include macrosomia, pre-eclampsia, polyhydramnios, stillbirth and neonatal morbidity. Other complications, such as increased rates of congenital anomalies and progression of retinopathy,
Address for correspondence: Simi Gupta, Maternal Fetal Medicine Associates, PLLC, 70 East 90th Street, New York, NY 10128, USA. Tel: 713-548-6998. Fax: 212-722-7185. E-mail: [email protected]
History Received 25 August 2014 Revised 18 November 2014 Accepted 21 November 2014 Published online 23 December 2014
are unique to pregestational diabetes. This is mainly due to the poor glycemic environment during fetal organogenesis and to preexisting vascular disease in patients with pregestational diabetes. Patients with early onset gestational diabetes have been shown to have worse outcomes than patients diagnosed at the standard 24–28 weeks of gestation. One study showed that these patients had a higher rate of requiring pharmacologic therapy, macrosomia and large for gestational age infants, cesarean section, and 3rd and 4th degree perineal lacerations [5]. Another study showed a similar finding of a higher rate of requiring pharmacologic therapy, but also showed higher rates of pre-eclampsia, neonatal hypoglycemia and perinatal deaths [6]. Unfortunately, prior studies have not separated patients with early onset gestational diabetes and undiagnosed type 2 diabetes mellitus from those patients without undiagnosed type 2 diabetes mellitus. This has left a large gap in knowledge regarding management of these patients, and subsequently some have chosen to treat all the patients with early onset gestational diabetes as having type 2 diabetes mellitus. In this study, we aimed to characterize patients with early onset
2
S. Gupta et al.
gestational diabetes, and to compare pregnancy outcomes to both patients with standard gestational diabetes diagnosed at 24–28 weeks gestation and patients with pregestational diabetes.
Downloaded by [University of Pennsylvania] at 20:39 05 November 2015
Methods We conducted a retrospective cohort study of all the patients who were diagnosed with gestational or pregestational diabetes and delivered at a single urban public hospital between 1 January 2007 and 31 December 2011. Because a high percentage of patients at this hospital carry one of more risk factors for gestational diabetes, all patients, unless they have pregestational diabetes, are screened for gestational diabetes at their first prenatal visit with a 50-g, one-hour, oral-glucosechallenge test. Abnormal results, defined as a plasma glucose level 140 mg/dL, were followed-up with a 100-g, three-hour, oral-glucose-tolerance test. Patients with two or more abnormal results, defined as a fasting plasma glucose 105 mg/dL, 1 h 190 mg/dL, 2 h 165 mg/dL, or 3 h 145 mg/dL, were diagnosed with gestational diabetes [7]. Because these patients were diagnosed early in pregnancy before 24 weeks gestation, we consider these patients to have early onset gestational diabetes. Patients with a normal early glucose challenge test or glucose tolerance test repeated screening at 24–28 weeks gestation. Patients with abnormal glucose tolerance tests at 24–28 weeks gestation are diagnosed with standard gestational diabetes. Patients were categorized as having pregestational diabetes if they reported a history of type 1 or type 2 diabetes. Institutional review board approval was obtained for the review of maternal and infant charts. Patients were identified based on International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code at the time of delivery. Inclusion criteria were accurate screening and diagnosis, presentation for prenatal care prior to 24 weeks gestation, and prenatal care at the primary clinic affiliated with the hospital. Patients with pregestational diabetes and early onset gestational diabetes were managed similarly with baseline hemoglobin A1c (Hb A1c) levels, 24-h urine protein collections, fetal echocardiograms, ophthalmologic evaluations, maternal electrocardiograms, fetal growth scans, fetal antenatal testing and glycemic control with diet, oral medication or insulin as necessary. Patients with standard gestational diabetes were managed with fetal growth scans, fetal antenatal testing and glycemic control. Target glucose ranges were 95 mg/dL fasting and 140 mg/dL 2 h postprandial. Patients with pregestational diabetes were continued on glyburide or metformin if they were being treated with one of those medications prior to pregnancy and had good glycemic control. The need to initiate pharmacotherapy for any patient with glyburide or insulin was determined by the attending physician reviewing the patient’s glucose logs. Patients with early onset gestational diabetes or standard gestational diabetes underwent a 75 g, two-hour, glucose-tolerance test 6–12 weeks postpartum. Patients with a fasting plasma glucose 126 mg/dL or a 2 h 200 mg/dL were diagnosed with type 2 diabetes and were considered to likely have had previously undiagnosed type 2 diabetes mellitus. Data on maternal demographics and characteristics, test results, and
J Matern Fetal Neonatal Med, Early Online: 1–5
obstetrical outcomes were collected. Maternal demographics and characteristics included age, parity, self-reported BMI and ethnicity. Test results included glucose challenge test and glucose tolerance test values, Hb A1c levels, 24-h urine protein values, fetal echocardiograms, ophthalmologic evaluations, fetal growth scans and fetal antenatal testing. Obstetrical outcomes included therapy for glycemic control, infant birth weight and infant APGARs. Data were compared between groups using Chi-square, Mann–Whitney, and t-test as appropriate. p50.05 was used for significance.
Results During the study period, 424 patients were included in the study. An additional 81 patients did not meet inclusion criteria: 2 were not diagnosed by glucose tolerance tests, 60 were late transfers of care after 24 weeks gestation, and 19 did not have prenatal care at the primary clinic. Two patients were excluded because they did not undergo early screening at their first prenatal visit. Figure 1 shows the distribution of the 424 patients included in the study. There were 140 patients who were diagnosed with early onset gestational diabetes, 221 patients with standard gestational diabetes and 63 patients with pregestational diabetes. The gestational age at the time of the early glucose challenge test ranged from 2 to 23 weeks gestation with a mean of 9.8 weeks (standard deviation ± 4.3). Of the 140 patients with early onset gestational diabetes, 66 underwent the 2-h postpartum glucose tolerance test (47%). Of these, 32 (45%) had an abnormal postpartum glucose tolerance test. Six (9%) met criteria for diabetes and could be labeled with likely undiagnosed type 2 diabetes mellitus. The remaining 26 patients (39%) had tests that met criteria for prediabetes in whom either the fasting plasma glucose is 100– 125 mg/dL or the 2 h is 140–199 mg/dL. Sixty patients (91%) were labeled as true early onset gestational diabetics, including the 34 patients with normal postpartum glucose tolerance tests and the 26 patients with postpartum glucose tolerance tests that met criteria for prediabetes (Figure 1). Of the 221 patients with standard gestational diabetes, 119 underwent the 2-h postpartum glucose tolerance test (54%). One patient (0.8%) had a glucose tolerance test suggestive of undiagnosed type 2 diabetes and 33 (30.0%) had a glucose tolerance test suggestive of prediabetes. There was no significant difference in the age, parity, ethnicity or timing of the diagnosis of gestational diabetes in the patients who underwent a postpartum glucose tolerance test and those who did not (data not shown). Table 1 shows the maternal characteristics and screening outcomes of all patients with pregestational diabetes, early onset gestational diabetes, and standard gestational diabetes. The percentage of patients of a high-risk ethnicity (Hispanic, African American or South Asian) increased from standard gestational diabetics to early onset gestational diabetics to pregestational diabetics (82.2% versus 89.1% versus 93.3%, p ¼ 0.043). As expected, the early glucose challenge test value was higher in patients with early onset gestational diabetes versus those with standard gestational diabetes (182.1 mg/dL versus 129.8 mg/dL, p50.001). Table 2 compares the maternal demographics and characteristics of the patients with early onset gestational diabetes
Early onset gestational diabetes
DOI: 10.3109/14767058.2014.991711
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424 Diabetes
140 Gestaonal diabetes diagnosed before 24 weeks (Early Onset Gestaonal Diabetes)
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66 had PPGTT
60 Normal PP GTT (Early onset gestaonal diabetes without undiagnosed Type 2 Diabetes)
63 Pregestaonal Diabetes
102 did not have PP GTT
119 had PP GTT
74 did not have PP GTT
6 Abnormal PP GTT (Early onset gestaonal diabetes with undiagnosed Type 2 Diabetes
221 Gestaonal diabetes diagnosed 24-28 weeks
1 Abnormal PP GTT
118 Normal PP GTT
Figure 1. Flow diagram of included patients. PP GTT: Postpartum glucose tolerance test.
Table 1. Maternal demographics and characteristics of all the patients. Early onset Pregestational gestational diabetesy Standard gestational (n ¼ 140) diabetes (n ¼ 221) p Value diabetes (n ¼ 63)
Characteristic Age (in years, ±SD) Multiparous (%) High risk ethnicity* (%) Glucose challenge test (in mg/dL, ±SD)
31.3 (±7.2) 66.7 93.3 NA
31.8 (±5.8) 66.4 89.1 182.1 (±31.1)
31.0 (±5.4) 63.8 82.2 129.8 (±25.3)
0.414 0.843 0.043 50.001
*Hispanic, African-American, South Asian. yAll patients who were diagnosed with gestational diabetes prior to 24 weeks gestation.
Table 2. Comparison of maternal characteristics and demographics of patients with early onset gestational diabetes between patients with undiagnosed type 2 diabetes and true early onset gestational diabetes.
Characteristic Age (in years, ±SD) Multiparous (%) High risk ethnicity* (%) Body mass index (in kg/m2, ±SD) Body mass index classificationy (%) Glucose challenge test 200 mg/dL (%) Baseline Hemoglobin A1c (in %, ±SD) Baseline Hemoglobin A1c 5.7(%)
Early onset gestational diabetes with undiagnosed type 2 diabetes (n ¼ 6)
Early onset gestational diabetes without undiagnosed type 2 diabetes (n ¼ 60)
35.0 (±3.6) 100 83.3 31.0 (±5.1) Normal weight: 0 Overweight: 50 Obese: 50 67 6.4 (±0.62) 100
31.0 (±5.7) 53 90 29.1 (±5.0) Normal weight: 26.7 Overweight: 35 Obese: 38.3 27 5.7 (±0.53) 41
p Value 0.101 0.027 0.625 0.375 0.345 0.046 0.006 0.013
Overweight ¼ BMI 25 to 29.9 kg/m2. Obese ¼ BMI 39 kg/m2. *Hispanic, African-American, South Asian. yBody mass index (BMI) classification. Normal weight ¼ BMI 18.5 to 24.9 kg/m2.
with undiagnosed type 2 diabetes to patients with true early onset gestational diabetes. There was no difference in the gestational age in weeks of the early GCT between the two groups (10 ± 6 versus 9.5 ± 3.9, p ¼ 0.762). Patients who ultimately were labeled with undiagnosed type 2 diabetes were more likely to be multiparous than patients with true
early onset gestational diabetes (100% versus 53%, p ¼ 0.027). Patient with undiagnosed type 2 diabetes were also more likely to have a glucose challenge test 200 mg/dL than patients with true early onset gestational diabetes (67% versus 27%, p ¼ 0.046) and a Hb A1C 5.7 (100% versus 41%, p ¼ 0.013). A Hb A1C 5.7 was used as a cut off as
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S. Gupta et al.
J Matern Fetal Neonatal Med, Early Online: 1–5
Table 3. Comparison of obstetrical outcomes between patients with standard gestational diabtes, true early onset gestational diabetes, and pregestational diabetes.
Outcome
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Required treatment with medication (%) Required treatment with oral medication (%) Required treatment with insulin (%) Last ultrasound for growth 497 (%) Abnormal antenatal testing (%) Mean birthweight, in grams (±SD) Birthweight 44500g (%) Median Neonatal APGAR at 5 min (range)
Standard gestational diabetes (n ¼ 221)
p Value comparing standard gestational diabetes to early onset gestational diabetes
Early onset gestational diabetes (n ¼ 60)
p Value comparing early onset gestational diabetes to pregestational diabetes
39 38 2 6 15 3352 (±517) 2 9 (3–10)
0.030 0.038 0.637 0.910 0.943 0.151 0.239 0.811
55 53 3 5 14 3243 (±553) 0 9 (6–9)
0.002 0.040 50.001 0.336 0.650 0.114 0.013 0.102
values above this represent an increased risk for diabetes by the American Diabetes Association. No patients with true early onset gestational diabetes had abnormal screening 24-h urine proteins defined as 300 mg of protein (n ¼ 35), anatomy ultrasounds (n ¼ 60), or ophthalmologic exams (n ¼ 7). Five percent of the patients had abnormal fetal echocardiograms (n ¼ 22). The obstetrical outcomes of patients with pregestational diabetes and those with true early onset gestational diabetes are compared in Table 3. Patients with pregestational diabetes were more likely to require pharmacotherapy for glycemic control than patients with true early onset gestational diabetes (81% versus 55%, p ¼ 0.002). They were also more likely to deliver an infant weighing 44500 g (10% versus 0%, p ¼ 0.013). Table 3 also compares the obstetrical outcomes of patients with true early onset gestational diabetes and standard gestational diabetes. Patients with standard gestational diabetes were less likely to require pharmacotherapy for glycemic control than patients with true early onset gestational diabetes (55% versus 39%, p ¼ 0.030).
Discussion This study shows that only 9% of patients diagnosed with gestational diabetes early in pregnancy likely have undiagnosed type 2 diabetes. The rest appear to represent a unique set of patients with true early onset gestational diabetes that resolves in the postpartum period. Looking specifically at the additional screening done for patients with pregestational diabetes, none of the patients with true early onset gestational diabetes had abnormal testing for the renal or ophthalmologic complications of diabetes, but a percentage of patients had abnormal fetal echocardiograms. Patients with true early onset gestational diabetes fell in an intermediate risks category for requiring pharmacotherapy for glycemic control between patients with pregestational diabetes and standard gestational diabetes. They also were less likely to deliver an infant weighing 44500 g than patients with pregestational diabetes. All other obstetrical outcomes that were compared were similar to pregestational and standard gestational diabetics. The results of this study characterizing patients with early onset gestational diabetes show that most of these patients do not have persistence into the postpartum period or have
Pregestational diabetes (n ¼ 63) 81 33 63 10 11 3429 (±727) 10 9 (8–9)
undiagnosed type 2 diabetes, yet they are more likely to require pharmacotherapy than patients with standard gestational diabetes. This information affects management of these patients with early onset gestational diabetes. Based on this study, treating all patients with early onset gestational diabetes as though they have pregestational diabetes may be unnecessary. The risk for long-term vascular complications of pregestational diabetes appears to be unlikely, but the number studied in this study is too low to draw any conclusions. On the other hand, these patients do need to still be screened for congenital anomalies that may be a result of the poor glycemic environment present during the period of organogenesis. This may be done through early anatomy scans and fetal echocardiograms. Parity (100% sensitivity, 47% specificity), glucose challenge tests 200 mg/dL (67% sensitivity, 73% specificity), and Hb A1C 5.7 (100% sensitivity, 69% specificity) can help differentiate patients with undiagnosed type 2 diabetes mellitus from those with true early onset gestational diabetes. While there was no difference in BMI between the two groups, this was a self-reported BMI and therefore may be unreliable. The results regarding obstetrical outcomes are similar to those reported in prior studies. Specifically, this study agrees with prior studies that show that patients with early onset gestational diabetes are more likely to require pharmacologic therapy for glycemic control than patients with standard gestational diabetes. However, while previous studies did not differentiate patients with early onset gestational diabetes with undiagnosed type 2 diabetes from those without undiagnosed type 2 diabetes, this study does and is still able to show a higher requirement for pharmacotherapy. This may suggest that earlier diagnosis of this high risk group may have benefits beyond detecting undiagnosed type 2 diabetes. The results also show that although patients with early onset gestational diabetes have a low risk of an abnormal postpartum glucose tolerance test diagnostic of type 2 diabetes (9%), they have a high risk of a test diagnostic of prediabetes (39%). This risk is similar to the risk of prediabetes in patients with standard gestational diabetes (30%). This supports the fact that all the patients with gestational diabetes are at increased risk of developing type 2 diabetes later in life and emphasizes the importance of interventions geared towards prevention.
Early onset gestational diabetes
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DOI: 10.3109/14767058.2014.991711
The primary strength of this study is that the vast majority of patients who presented for prenatal care in this study received an early glucose challenge test. This takes away any selection bias from screening patients with an early glucose challenge test based on risk factors. Additionally, the care for these patients was fairly standardized since they all received prenatal care at a single clinic. Finally, the results of this study may be generalizable to any patient population with a high percentage of patients with risk factors for diabetes. With the increase in obesity nationwide, this is likely to characterize more and more patient populations. The study, however, does have limitations. One limitation is that only maternal and obstetrical outcomes were reviewed. Infant data was not available for review. Therefore, the risk of congenital anomalies is based off of antenatal anatomy ultrasounds and fetal echocardiograms and therefore may overestimate or underestimate the true risk. An additional limitation is that while 140 patients were diagnosed with early onset gestational diabetes, only 66 presented for a postpartum glucose tolerance test due to non compliance. However, a study by Russell et al. [8] on postpartum glucose testing in women with gestational diabetes who received prenatal care in a maternal diabetes clinic found that marital status was the only demographic significantly different between patients who received postpartum testing and those that did not. Furthermore, they found that there was no difference in the risk of diabetes, as measured by the magnitude of the antenatal fasting glucose abnormality, between those who underwent postpartum testing and those who did not [8]. Similarly, in this study, there was no difference in maternal demographics in patients who underwent postpartum testing and those who did not. Therefore, if there was selection bias in our study, it was likely limited. Gestational diabetes affects 2–10% of the pregnancies and this number is likely to rise with the rise in patients with risk factors for diabetes such as obesity and high risk ethnicities [9]. It is extremely important to accurately diagnose patients’ risks for certain adverse pregnancy outcomes in order to properly utilize resources. This study shows that the majority of patients with early onset gestational diabetes do not have undiagnosed type 2 diabetes and therefore may forgo screening tests for some of the vascular complications of pregestational diabetes. It also shows that an early glucose challenge test 4200 mg/dL and/or a Hb A1C 5.7% may help differentiate patients with undiagnosed type 2 diabetes from
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those with true early onset gestational diabetes. Finally, it shows that patients with early onset gestational diabetes are still at a higher risk for fetal congenital anomalies that may be a result of the poor glycemic environment during organogenesis. Early anatomy scans and fetal echocardiograms in these patients may help ensure that infants with congenital anomalies are detected early and delivered at institutions with the appropriate resources. They are also at a higher risk for requiring pharmacotherapy, and therefore, there may be some benefit to early diagnosis beyond the detection of undiagnosed type 2 diabetes. While larger studies need to be conducted in order to confirm these findings, this study can help guide clinicians as to the appropriate management of these high-risk patients.
Declaration of interest The authors report no conflict of interest.
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