Keywords gestational diabetes - screening - glucose tolerance test - large for gestational
age
Gestational diabetes mellitus (GDM), defined as carbohydrate intolerance during pregnancy,
affects up to 10% of all pregnancies in the United States.[1 ] GDM is associated with maternal and fetal complications such as hypertensive disorders,
cesarean section, large for gestational age, shoulder dystocia, neonatal hypoglycemia,
and neonatal intensive care unit (NICU admissions).[2 ]
[3 ]
[4 ]
[5 ]
[6 ] Moreover, pregnant people diagnosed with GDM are at up to 60% risk of developing
type 2 diabetes later in life.[7 ]
[8 ]
[9 ] Timely diagnosis and treatment of GDM improves short-term maternal and fetal outcomes.[2 ]
[3 ]
[10 ]
[11 ]
To diagnose GDM, American College of Obstetrics and Gynecologists (ACOG) recommends
the two-step method, which entails completion of the screening 1-hour glucose challenge
test (GCT); if elevated (≥135–140 mg/dL), the completion of the 3-hour glucose tolerance
test (GTT) is required for diagnosis.[12 ]
[13 ]
[14 ] Approximately, 90% of maternal–fetal medicine specialists recommend diagnosis with
the two-step method.[15 ] Unfortunately, the diagnostic 3-hour GTT requires a fasting state and a lengthy
clinic visit, which may lead to a delay in testing, diagnosis, and ultimately intervention
for GDM.[16 ]
There are no current guidelines on the optimal length of time to completion of the
two-step method for GDM screening. In addition, there is a lack of data in examining
the relationship between length of time to completion of the GDM, two-step screening
method, and adverse outcomes. The aim of our study was to determine if the length
of time to completion of the two-step method GDM screening was associated with adverse
neonatal and maternal outcomes.
Materials and Methods
This was a retrospective cohort study taken place at the UT Health (University of
Texas Health Science Center at Houston) McGovern Medical School, an academic, tertiary
care system in Houston, TX from May 2021 to May 2022. An electronic medical record
chart review was conducted to identify all singleton, nonanomalous pregnant people
who were screened for GDM at ≥24 weeks' gestation. Exclusion criteria included: people
with pregestational diabetes, normal 50-g 1-hour GCT (<135 mg/dL) or individuals that
did not complete 3-hour GTT. Pregnant people with 1-hour GCT ≥ 135 mg/dL were considered
positive screening based on an institutional threshold. After completion of the diagnostic
100-g 3-hour GTT, diagnosis of GDM was based on Carpenter–Coustan criteria of ≥ 2
abnormal values (fasting blood glucose >90 mg/dL, 1 hour > 180 mg/dL, 2 hour > 155 mg/dL,
3 hour > 140 mg/dL) [7 ]. We compared outcomes among those who completed the 3-hour GTT in ≤14 versus >14
days from the 1-hour GCT, irrespective of whether they had GDM.
The study was approved by the Institutional Review Board at UTHealth McGovern Medical
School (IRB no.: HSC-MS-22-0292). Data were collected from the clinic and hospital
medical record system. Maternal records were culled for prenatal visits, including
laboratory values, diagnosis of GDM, need for hypoglycemic agents, and ultrasounds.
Hospital records were abstracted for admissions during pregnancy, labor, delivery,
and postpartum events. Neonatal records were also accessed for birth weight, Apgar
scores, length of hospital stay, need for NICU admission, or any other neonatal complications
after delivery.
The explanatory variable in this study was time to completion of the 3-hour GTT from
the 1-hour GCT, categorized as ≤14 versus > 14 days. As there is no recommended time
to completion of two-step GDM screening, the authors arbitrarily designated 14 days
to completion as the cutoff between the two groups. The hypothesis was that 14 days
is a clinically practical amount of time to allow for completion of screening as well
as initiation of GDM care, if required, and greater than 14 days may impact perinatal
outcomes.
The primary outcome was a composite neonatal morbidity and mortality (CNM) consisting
of any of the following: large for gestational age (defined as birth weight > 90%
for gestational age per Duryea et al nomogram),[17 ] shoulder dystocia or birth injury, respiratory distress, neonatal hypoglycemia,
or fetal or neonatal death. Shoulder dystocia or birth injury was defined as additional
maneuvers other than gentle downward traction for delivery. Birth injury included
clavicular fracture or brachial plexus injury. Respiratory distress was defined as
the need for at least 4 hours of respiratory support with supplemental oxygen, continuous
positive airway pressure, or ventilation at the first 24 hours of life. Neonatal hypoglycemia
was defined as blood glucose < 40 mg/dL in the first 24 hours of life or <50 mg/dL
after or requiring medical therapy.
The secondary adverse neonatal outcomes included: rates of preterm delivery, Apgar
score <7 at 5 minutes, need for continuous positive airway pressure ventilation neonatal
jaundice requiring phototherapy, and length of hospital stay. Secondary adverse maternal
outcomes that were collected included: hypertensive disorders of pregnancy, chorioamnionitis,
cesarean delivery (CD), postpartum hemorrhage, endometritis, or postpartum readmission
≤6 weeks. Preterm birth was defined as delivery at <37 weeks' gestation. Hypertensive
disorder of pregnancy included gestational hypertension, preeclampsia, or superimposed
preeclampsia based on the current Task Force Criteria for Hypertension in pregnancy.[18 ] Gestational hypertension defined as new onset hypertension (systolic ≥ 140 mm Hg
or diastolic ≥ 90 mm Hg) without proteinuria (either ≥300 mg per 24 hours or protein/Cr
ratio ≥ 0.3) after 20 weeks of gestation. Preeclampsia defined as hypertension (systolic
≥ 140 mm Hg or diastolic ≥ 90 mm Hg) with proteinuria or serum laboratory abnormalities
(platelets ≤ 100,000, serum aspartate aminotransferase ≥ 80 IU/mL, creatinine ≥ 1.1 mg/dL).
Preeclampsia with severe features defined as systolic ≥ 160 mm Hg, diastolic ≥ 110 mm
Hg, persistent headache, pulmonary edema, or any serum laboratory abnormalities as
above.
Statistical Analysis
We examined the differences in baseline characteristics and outcomes between time
groups (completion of 3-hour GTT in ≤14 versus > 14 days from abnormal 1-hour GCT)
using the chi-square test or Fischer's exact test for categorical variables and Student's
t- tests for continuous variables. Multivariable Poisson regression models were used
to evaluate the association between time groups (≤ 14 days [reference] vs. >14 days)
and the primary outcome, while adjusting for maternal age (<20, 20–34, ≥35 years),
maternal race, and ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, non-Hispanic-Other,
unknown), private insurance (private, government-issued insurance or no insurance),
nulliparity, obesity (body mass index [BMI] ≥ 30 kg/m2 ), hypertensive disorder, thyroid disease and gestational age at time of 1-hour GCT.
The results were presented as adjusted relative risk (aRR) with 95% confidence interval
(CI). Using the same approach, we also performed subgroup analyses among those diagnosed
with GDM. Statistical significance was noted to be a p -value of < 0.05 or if the 95% CI did not include the integer 1. Statistical analysis
was completed using STATA software, version 17 (Stata-Corp., College Station, TX).
Results
Among the 401 pregnancies with 1-hour GCT ≥ 135 mg/dL during the study period, 342
(85.3%) pregnant people had 3-hour GTT ordered. A total of 59 individuals did not
have 3-hour GTT ordered due to the following reasons: GDM was diagnosed based on elevated
1-hour GCT (N = 25) and 3-hour GTT not ordered by primary obstetrician (N = 34). A total of 29 people did not complete the ordered 3-hour GTT.
The final study sample included 313 (78.1%) pregnant people who completed the 3-hour
GTT. Among our study population, 171 (54.6%) completed the two-step method in ≤ 14
days and 142 (45.4%) completed >14 days ([Fig. 1 ]).
Fig. 1 Flow chart of pregnant people: eligibility and sample size. GDM, gestational diabetes;
1hGCT, 1-hour glucose challenge test; 3hGCT, 3-hour glucose tolerance test.
Baseline characteristics for the two groups were similar except for insurance status
([Table 1 ]). Those who completed the 3-hour GTT >14 days were more likely to be insured with
Medicaid (≤14 days 45% vs. >14 days 74%, p = 0.004).
Table 1
Baseline characteristics
Characteristics
Two-step completed
p -Value
≤14 d
>14 d
n = 171 (%)
n = 142 (%)
Maternal age (y)
< 20
5 (2.9)
6 (4.2)
0.550
20–34
134 (78)
104 (73)
≥35
32 (18.7)
32 (22.5)
Race/ethnicity
Non-Hispanic White
47 (27)
28 (20)
0.100
Non-Hispanic Black
20 (12)
29 (20)
Hispanic
27 (16)
21 (15)
Other
69 (40)
52 (37)
Unknown
8 (4.7)
12 (8.5)
Insurance status
Private
94 (55.0)
62 (44)
0.004
Medicaid
77 (45.0)
74 (52.1)
Self-pay/no insurance
0 (0.0)
6 (4.2)
Nulliparous
27 (15.8)
27 (19.0)
0.452
Obese (BMI ≥ 30 kg/m2 )
85 (49.7)
67 (47.2)
0.656
Hypertension
13 (7.6)
12 (8.5)
0.783
Thyroid disease
12 (7.0)
8 (5.6)
0.618
Substance use (tobacco or illicit drug)
Yes
5 (2.9)
5 (3.5)
0.496
No
150 (87.7)
118 (83.1)
Unknown
16 (9.4)
19 (13.4)
GA at screening 1 h GCT
26.4 (2.0)
26.7 (2.1)
0.321
1 h GCT
157.0 (16.7)
155.4 (15.8)
0.395
1 abnormal value of 3 h GTT[a ]
73.0 (42.7)
50.0 (35.2)
0.177
Diagnosis of GDM
48.0 (28.1)
41.0 (28.9)
0.875
Diabetes educator visit
42.0 (24.6)
36.0 (25.4)
0.872
Need for hypoglycemic agent
23.0 (13.5)
11.0 (7.7)
0.106
Abbreviations: BMI, body mass index; CGM, continuous glucose monitoring; GA, gestational
age; GCT, glucose challenge test; GTT, glucose tolerance test.
Note: Data are presented as number (percentage) or mean (standard deviation).
a GTT defined as abnormal based on Carpenter–Coustan criteria of ≥ 2 abnormal values:
fasting blood glucose > 90, 1 hour > 180, 2 hours > 155, 3 hours > 140 mg/dL.
Overall, the rate of the primary outcome was 28.8%; 25.7% in the group of ≤14 days,
whereas 32.4% in the group of >14 days (p = 0.195). The most common component of the primary outcome was neonatal hypoglycemia
(15.7%; 14.0% in ≤14 days and 17.6% >14 days, p = 0.387). After multivariable adjustment, the risk of the primary outcome was similar
between people who completed the two-step method in ≤14 days versus >14 days (aRR = 1.11;
95% CI = 0.81–1.52,). There was no difference in any component of the primary outcome
between the two groups ([Table 2 ]).
Table 2
The primary outcome: composite neonatal adverse outcome
Two-step method
p -Value
Adjusted RR (95% CI)
Completed in ≤14 d
Completed in > 14 d
n = 171 (%)
n = 142 (%)
Composite neonatal outcome
44 (25.7)
46 (32.4)
0.20
1.21 (0.85–1.73)
Large for gestational age[a ]
14 (8.2)
14 (9.9)
0.61
Shoulder dystocia or birth injury[b ]
5 (2.9)
5 (3.5)
0.77
Respiratory distress[c ]
8 (4.7)
14 (9.9)
0.07
Hypoglycemia[d ]
24 (14.0)
25 (17.6)
0.39
Fetal or neonatal death
0 (0)
0 (0)
N/C
Abbreviations: CI, confidence interval; CPAP, continuous positive airway pressure;
N/C, not calculable; RR, relative risk.
Notes: Data are presented as number (percentage) or median (standard deviation). Adjusted
for insurance status.
a Birth weight above 90th percentile using the nomogram by Duryea et al.
b Need for any extra maneuvers for delivery, clavicular fracture, or brachial plexus
injury.
c Need of at least 4 hours of respiratory support with supplemental oxygen, continuous
positive airway pressure, or ventilation at the first 24 hours of life.
d Blood glucose <40 mg/dL in the first 24 hours of life or <50 mg/dL after or requiring
medical therapy.
[Table 3 ] presents the secondary adverse neonatal and maternal outcomes. The results showed
that there was no difference in all the secondary adverse outcomes between the time
groups. The most common maternal complication was CD (40.4% in ≤14 days and 43.7%
in >14 days, p = 0.554; [Table 3 ]).
Table 3
The secondary neonatal and maternal adverse outcome
Outcomes
Two-step method
p -Value
Completed in ≤14 d
Completed in > 14 d
n = 171 (%)
n = 142 (%)
Neonatal adverse outcomes
Preterm delivery (<37 wk)
23 (13.5)
26 (18.3)
0.239
Birth weight (g)
3,214.4 (± 467.0)
3,149.1 (±566.6)
0.265
Apgar score <7 at 5 min
1 (0.6)
0 (0.0)
1.000
CPAP
11 (6.4)
11 (7.7)
0.651
Neonatal jaundice requiring phototherapy
25 (14.6)
16 (11.3)
0.381
Length of hospital stay (d)
2.6 (± 2.8)
3.4 (± 6.2)
0.118
Maternal adverse outcomes
Hypertensive disorders of pregnancy[a ]
39 (24.9)
37 (28.2)
0.474
Preeclampsia with severe features
11 (6.9)
6 (4.6)
0.444
Chorioamnionitis
6 (3.5)
10 (7.0)
0.158
Cesarean delivery
69 (40.4)
62 (43.7)
0.554
Postpartum hemorrhage
9 (5.3)
7 (4.9)
0.894
Endometritis
2 (1.2)
1(0.7)
1.000
Postpartum readmission ≤6 wk
7 (4.3)
4 (2.9)
0.557
Abbreviation: CPAP, continuous positive airway pressure.
Note: Data are presented as number (percentage) or mean (standard deviation).
a Hypertensive disorder of pregnancy including gestational hypertension, preeclampsia,
or superimposed preeclampsia.
There were a total of 89 (28.4%) pregnant people that were diagnosed with GDM. Of
them, 48 (53.9%) people completed the two-step method in ≤14 days and 41 (46.1%) people
completed in >14 days. Subgroup analysis showed there was no significant difference
in any component of the CNM between the two groups, similar to the primary analysis
(aRR = 1.01; 95% CI = 0.59–1.78). The most common CNM in both groups was neonatal
hypoglycemia (29.2% in ≤14 days and 29.3% >14 days). In addition, we did not find
any differences in all secondary neonatal and maternal outcomes in those diagnosed
with GDM ([Table 4 ]).
Table 4
Subgroup analyses: the primary and secondary outcomes in those diagnosed with gestational
diabetes mellitus
Two-step method
p -Value
Adjusted RR (95% CI)
Completed in ≤14 d
Completed in >14 d
n = 48 (%)
n = 41 (%)
Composite neonatal outcome
18 (37.5)
17 (41.5)
0.703
1.01 (0.59–1.78)
Large for gestational age[a ]
4 (8.3)
4 (9.8)
1.000
Shoulder dystocia or birth injury[b ]
1 (2.1)
2 (4.9)
0.593
Respiratory distress[c ]
1 (2.1)
4 (9.8)
0.176
Hypoglycemia[d ]
14 (29.2)
12 (29.3)
0.992
Fetal or neonatal death
0 (0.0)
0 (0.0)
N/C
Secondary neonatal outcomes
5 (10.4)
10 (24.4)
0.17
Preterm delivery (<37 wk)
5 (10.4)
10 (24.4)
0.079
Birth weight (g)
3,221.7 (±452.3)
3,114.3 (± 612.7)
0.345
Apgar score <7 at 5 min
1 (2.1)
0 (0.0)
1.000
CPAP
3 (6.3)
4 (9.8)
0.699
Neonatal jaundice requiring phototherapy
2 (4.2)
5 (12.2)
0.241
Length of hospital stay (d)
2.3 (± 1.5)
3.9 (± 5.9)
0.079
Secondary maternal outcomes
Hypertensive disorders of pregnancy[e ]
7 (14.9)
12 (29.3)
0.102
Chorioamnionitis
1 (2.1)
5 (12.2)
0.091
Cesarean delivery
22 (45.8)
25 (61.0)
0.154
Postpartum hemorrhage
3 (6.3)
3 (7.3)
1.000
Endometritis
0 (0.0)
0 (0.0)
N/C
Postpartum readmission ≤ 6 wk
4 (8.7)
2 (5.3)
0.685
Abbreviations: CI, CPAP, continuous positive airway pressure; N/C, not calculable;
RR, relative risk.
Notes: Data are presented as number (percentage) or median (standard deviation). Adjusted
for insurance status.
a Birth weight above 90th percentile using the nomogram by Duryea et al.
b Need for any extra maneuvers for delivery, clavicular fracture or brachial plexus
injury.
c Need of at least 4 hours of respiratory support with supplemental oxygen, continuous
positive airway pressure, or ventilation at the first 24 hours of life.
d Blood glucose <40 mg/dL in the first 24 hours of life or <50 mg/dL after or requiring
medical therapy.
e Hypertensive disorder of pregnancy including gestational hypertension, preeclampsia,
or superimposed preeclampsia.
Discussion
In this retrospective cohort study of the length of time to completion of two-step
method for diagnosis of GDM, there was no association with worse adverse neonatal
or maternal outcomes in people with longer period of time to completion of testing.
In our study, we observed that approximately 50% of people that received care at our
institution completed the two tests within 14 days, while 67% of people completed
the two-step method in ≤21 days.
In addition, subgroup analyses of those that were diagnosed with GDM did not show
a significantly higher rate of adverse outcomes among those that took >14 days to
diagnosis. Majority of people were able to be diagnosed with GDM in less than a month's
time allowing for appropriate intervention.
There have been no prior studies examining length of time to completion of GDM screening
and neonatal and maternal morbidity. However, many studies have explored the barriers
to completion of the 1-hour GCT. Several social and institutional factors have been
identified: inability to tolerate test, compliance with multiple prenatal appointments,
younger maternal age, and mental/social stressors.[19 ]
[20 ] These prior reports are consistent with our findings of those who completed the
GDM screening in ≤14 days had a significantly higher rate of private insurance as
compared with >14 days to completion (p = 0.004). Although we did not find a significant difference in the primary outcome
based on the length of time to completion of the two-step method of GDM screening,
we detected a higher-than-average rate of neonatal hypoglycemia. Prior research reported
that up to 10% of low risk, term newborns experience hypoglycemia defined as <40 to
45 mg/dL.[21 ]
[22 ] In our study, however, the rate of the neonatal hypoglycemia was 15.7%. The increased
rate may be due to high-risk pregnancies (those with GDM diagnosis or 48.5% of patients
with BMI ≥30) being included in our study population. This also reflects that hyperglycemia,
below the threshold of diagnosis, is associated with worse perinatal outcomes consistent
with the Landon et al findings study.[2 ] Despite completing and passing the two-step screening method, poor neonatal outcomes
that are associated with GDM were observed. Future studies should focus on exploring
other risk factors for neonatal hypoglycemia and whether the current method for GDM
diagnosis in pregnancy is sufficient for diagnosis and treatment of people with elevated
blood sugars during pregnancy.
Limitations and Strengths
We acknowledge the limitations of this study. It was a single-center, retrospective
analyses and was specific to a university practice. Causes of delay might be due to
several and all factors of social determinants of health, reflecting both a clinic
system's issue as well as disparities in access to health care.[19 ]
[20 ] We performed a multivariable adjustment analysis on the primary outcome of the composite
neonatal adverse outcome. However, this analysis was not completed on the secondary
outcomes due to small case numbers, and the bivariate analyses showed that there were
no significant results in all the secondary outcomes. Another limitation was the risk
of Type 2 error given small cohort sample; a significant difference between the two
groups may have been observed with a larger sample size, given the high rate of neonatal
hypoglycemia.
Our study has several strengths. To the best of our knowledge, this is the first study
that has explored neonatal and maternal outcomes associated with length of time to
completion of GDM screening. Although the study population was from a single center,
our sample included people from a greater metropolitan area. In addition, our overall
rate of GDM detection was approximately 6%, consistent with the overall national average.[5 ]
[13 ]
[23 ]
[24 ]
[25 ]
Conclusion
In conclusion, we did not find a difference in adverse neonatal and maternal outcomes
associated with the length of time to completion of the two-step GDM diagnosing method.
This study provides a clinically applicable quantification of the delay that happens
almost 50% of the time in the journey to diagnosis of GDM. This highlights that completion
of the two-step method is fraught with challenges and a more practical form of GDM
screening is needed for the ease of pregnant people.