One-Step Compared With Two-Step Gestational Diabetes Screening and Pregnancy Outcomes

Systematic Review
One-Step Compared With Two-Step

Gestational Diabetes Screening and
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Pregnancy Outcomes
A Systematic Review and Meta-analysis
Matthew Brady, MD, Drew M. Hensel, MD, Rachel Paul, MPH, Michelle M. Doering, MLIS,
Jeannie C. Kelly, MD, MS, Antonina I. Frolova, MD, PhD, Anthony O. Odibo, MD, MSCE,
Valene Garr Barry, PhD, Camille E. Powe, MD, Nandini Raghuraman, MD, MSC,
Methodius G. Tuuli, MD, MPH, and Ebony B. Carter, MD, MPH
1vYJzg== on 03/21/2023
OBJECTIVE: To estimate short-term maternal and neo- paring one-step and two-step GDM testing strategies
natal outcomes with one-compared with two-step test- before September 2021 was conducted. We searched
ing for gestational diabetes mellitus (GDM). Ovid Medline (1946–), EMBASE (1947–), Scopus (1960–),
DATA SOURCES: A systematic review of randomized Cochrane Central, and ClinicalTrials.gov. The primary
controlled trials (RCTs) and observational studies com- outcome was rate of large-for-gestational age (LGA) neo-
nates. Secondary outcomes were clinically relevant out-
See related editorial on page 710. comes for GDM that were selected a priori.
METHODS OF STUDY SELECTION: Titles, abstracts, and
From the Division of Maternal Fetal Medicine and the Division of Clinical manuscripts were screened, selected, and reviewed by
Research, Department of Obstetrics and Gynecology, and the Bernard Becker the first two authors. Four RCTs (24,966 patients) and 13
Medical Library, Washington University School of Medicine in St. Louis, St. observational studies (710,677 patients) were analyzed.
Louis, Missouri; the Departments of Medicine and Obstetrics, Gynecology, and
Reproductive Biology, Diabetes Unit, Massachusetts General Hospital and
TABULATION, INTEGRATION, AND RESULTS: Pooled
Harvard Medical School, Boston, Massachusetts; and the Department of
Obstetrics and Gynecology, Warren Alpert Medical School at Brown University, relative risks (RRs) were calculated with 95% CIs using
Providence, Rhode Island. random-effects models and were plotted graphically
Dr. Carter is funded by the American Diabetes Association Pathway to Stop with forest plots. Study heterogeneity was evaluated
Diabetes Award (1-19-ACE-02), the Robert Wood Johnson Foundation Grant using Cochran Q and Higgins I2 tests. The quality of
#74250, NIH/NICHD K23 grant (HD095075-03), and the Diabetes Research studies that met the inclusion criteria was evaluated
Center at Washington University School of Medicine (NIH/NIDDK
P30DK020579). The contents of this publication are solely the responsibility with the Downs and Black checklist. Publication bias
of the authors and do not necessarily represent the official view of the American was assessed by using asymmetry of funnel plots and
Diabetes Association or the Robert Wood Johnson Foundation. Harbord’s test. There was no difference in the rate of
Dr. Carter, Associate Editor (Equity) of Obstetrics & Gynecology, was not LGA neonates (pooled RR 0.95; 95% CI 0.88–1.04) by
involved in the review or decision to publish this article. testing strategy among RCTs, but patients who under-
Each author has confirmed compliance with the journal’s requirements for authorship. went one-step testing were more likely to be diagnosed
Corresponding author: Matthew Brady, MD, Clinical Fellow, Division of with GDM (pooled RR 2.13; 95% CI 1.61–2.82) and trea-
Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Washington ted with diabetes medications (pooled RR 2.24; 95% CI
University School of Medicine, St. Louis, MO; email: brady.m@wustl.edu.
1.21–4.15). One-step testing was associated with higher
Financial Disclosure rates of neonatal intensive care unit (NICU) admission
Jeannie C. Kelly reports that money was paid to her institution from PEW, the
Barnes Jewish Foundation, and Doris Duke. Ebony Carter’s institution received (pooled RR 1.12; 95% CI 1.00–1.26) and neonatal hypo-
payment from the American Diabetes Association NIH/NIMH Robert Wood glycemia (pooled RR 1.23; 95% CI 1.13–1.34). In analysis
Johnson Foundation. She received payment as part of Carter Expert Strategic of high-quality RCTs and observational studies, one-
Consulting and from Affinia Healthcare (board advisor, Mother Goose). The
other authors did not report any potential conflicts of interest.
step testing was associated with a lower rate of LGA
neonates (pooled RR 0.97; 95% CI 0.95–0.98), but higher
© 2022 by the American College of Obstetricians and Gynecologists. Published
by Wolters Kluwer Health, Inc. All rights reserved.
rates of GDM diagnosis, treatment, NICU admission,
ISSN: 0029-7844/22 and neonatal hypoglycemia.
712 VOL. 140, NO. 5, NOVEMBER 2022 OBSTETRICS & GYNECOLOGY
© 2022 by the American College of Obstetricians

and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
CONCLUSION: Despite a significant increase in GDM domain, Institutional Review Board approval was not
diagnosis and treatment with one-step testing, there is necessary.
no difference in rate of LGA neonates compared with
two-step testing among RCTs.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO, STUDY SELECTION
CRD42021252703. Randomized controlled trials and observational stud-
ies published in English before September 2021 that
(Obstet Gynecol 2022;140:712–23)

DOI: 10.1097/AOG.0000000000004943 compared the IADPSG one-step and the Carpenter-
Coustan two-step methods of GDM screening and
S ignificant time, energy, and resources have been

invested in determining optimal diagnostic criteria
for gestational diabetes mellitus (GDM). Yet, we are
diagnosis were included. Both study types were
included to understand and balance the findings of
“gold standard” RCTs with real-world clinical appli-
no closer to resolving the one-step compared with two- cation and generalizability informed by observational
step testing dilemma in 2022 than we were in 2008, studies. The inclusion of observational studies pro-
when the Hyperglycemia and Pregnancy Outcomes vided greater statistical power to address the primary
study was published.1 A 2017 Cochrane review con- outcome at the population level, because a much
cluded there was insufficient evidence to recommend smaller subgroup of the sample (approximately 18%
one strategy over the other based on available data.2 of patients with one-step testing and approximately
1vYJzg== on 03/21/2023
Several studies, including two large randomized con- 6% of patients with two-step testing) would be diag-
trolled trials (RCTs), published in the interim, nosed with GDM and drive GDM-related clinical out-
advanced our understanding of one-step testing com- comes. All other study designs, including cost-
pared with two-step testing.3,4 The objective of this effectiveness analyses, systematic reviews, and meta-
systematic review and meta-analysis was to use the analyses, were excluded.
collective power of pooled data to assess the implica- The primary outcome was rate of large-for-
tions of GDM testing strategy on pregnancy out- gestational-age (LGA) neonates (birth weight 90th per-
comes. centile or higher). Secondary outcomes were selected
based on clinical relevance to GDM, a priori, and
SOURCES inclusion in at least two studies that met criteria so
This study followed the PRISMA (Preferred Report- that results could be pooled. Maternal secondary out-
ing Items for Systematic Reviews and Meta-Analyses) comes included the rate of GDM diagnosis by one-
and MOOSE (Meta-Analysis of Observational Stud- step testing with IADPSG or two-step testing with
ies) reporting guidelines.5,6 PROSPERO registration Carpenter-Coustan criteria,8 hypertensive disorders
was completed before initiating the review and data of pregnancy (gestational hypertension or preeclamp-
extraction. Using the PICOT method to define the sia),9 primary cesarean delivery, and GDM treatment
study question and eligibility criteria,7 studies of preg- with oral diabetes medications or insulin. Fetal and
nant patients, comparing International Association of neonatal secondary outcomes were macrosomia (birth
the Diabetes and Pregnancy Study Groups (IADPSG) weight 4,000 g or more, as defined by the two largest
one-step testing with Carpenter-Coustan two-step test- RCTs included), neonatal intensive care unit (NICU)
ing in the late mid-trimester (targeting 24–28 weeks of admission during the first 28 days of life, small for
gestation) with clinically relevant outcomes were gestational age (birth weight 10th percentile or less),
included. A medical librarian (M.M.D.) created a preterm birth (delivery before 37 weeks of gestation),
search strategy for the diagnosis of GDM using one- respiratory distress syndrome with progressive respi-
step or two-step testing with a combination of stan- ratory failure in conjunction with characteristic chest
dardized terms and keywords, including “gestational radiograph findings shortly after birth,10 hyperbiliru-
diabetes,” “GDM,” “pregnancy induced diabetes,” binemia (requiring phototherapy), neonatal hypoglyce-
“one-step,” “two-step,” “GDM diagnosis,” “GDM mia (defined as a blood glucose level of less than 40
screening,” and “oral glucose tolerance test.” The mg/dL in the first 24 hours of life), stillbirth (fetal
search was run on August 29, 2021, without any filters death after 20 weeks of gestation with verified nonlive
in the databases Ovid Medline (1946–), EMBASE birth), neonatal death (within first 28 days of life), and
(1947–), Scopus (1960–), Cochrane Central, and shoulder dystocia (delivery of the shoulder requiring
ClinicalTrials.gov. Full electronic search strategies maneuvers). Outcomes reported in each study are
are provided in the supplementary material. Because shown in Appendix 1, available online at http://
all data were deidentified and available in the public links.lww.com/AOG/C876.
VOL. 140, NO. 5, NOVEMBER 2022 Brady et al One-Step vs Two-Step GDM Testing 713

1vYJzg== on 03/21/2023
Fig. 1. Flowchart showing the meth-

odology of study selection. GDM,
gestational diabetes mellitus; CC,
Carpenter-Coustan; IADPSG, Interna-
tional Association of the Diabetes and
Pregnancy Study Groups.
Brady. One-Step vs Two-Step GDM Test-
ing. Obstet Gynecol 2022.
Titles and abstracts were screened by two authors quality. Two authors (M.B. and D.M.H.) indepen-
(M.B. and D.M.H). Full-text articles were retrieved dently completed the checklist. Discrepancies were
based on relevance of the study question and out- resolved by the senior author.
comes included. Each article was reviewed separately Study heterogeneity was evaluated using the
by two authors (M.B. and D.M.H.) against inclusion Cochran Q test and Higgins I2 test.12 Heterogeneity
and exclusion criteria. Bibliographies of studies that was considered significant if P,.1 or I2.30%. The
met the criteria were reviewed for additional poten- DerSimonian-Laird random-effects model was used
tially relevant studies. Two authors (M.B. and to pool data from individual studies, even if there
D.M.H.) independently abstracted data into standard was no evidence of statistical heterogeneity. This
extraction forms. Discrepancies were resolved by the approach resulted in more conservative estimates of
senior author (E.B.C). effect sizes. Pooled relative risks (RRs) were calculated
Study quality was assessed with the Downs and with a 95% CI and plotted graphically with forest
Black checklist,11 a validated tool that scores studies plots. We conducted three versions of meta-analyses
based on 27 items that evaluated reporting, external including: 1) all studies, 2) stratified by design (RCT
validity, bias, internal validity, confounding, and or observational), and 3) high-quality studies only. We
power. We made the a priori decision that studies with visually inspected funnel plots to assess publication
a score in the top quartile would be deemed high- bias for the primary outcome. We tested asymmetry
714 Brady et al One-Step vs Two-Step GDM Testing OBSTETRICS & GYNECOLOGY

Table 1. Characteristics of Studies Included in the Final Meta-Analysis
Study Year Study Years Country Setting Inclusion Criteria Exclusion Criteria
RCTs
Davis et al3 2021 2015–2019 United 10 clinics in Pregnant, no Miscarriage, multiple
States Pittsburgh, PA preexisting gestation, younger than
diabetes age 18 y, history of

bariatric surgery,
change in health
insurance
Hillier 2021 2014–2017 United Hospital system in Age 18–45 y, Preexisting type I or type II
et al4 States Portland, OR, 18 0/7–28 weeks diabetes, diabetes
and Hawaii 6/7 wk GA at diagnosed before 24 wk
enrollment GA, inability to
complete screening
before 30 wk GA,
multifetal gestation,
major congenital
anomaly, anticipated
preterm birth before 28
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weeks GA,
corticosteroids 30
d before enrollment,
hypertension requiring
medication, HIV
infection, liver disease,
history of gastric bypass,
blood sugar level higher
than 200 on
prerandomization 1-h
screening
Khalifeh 2020 2016 United Large academic 24–28 wk GA Pregestational diabetes,
et al14 States hospital in history of bariatric
Philadelphia, PA surgery
Scifres 2015 2012–2013 United Large academic Age 18–45 y, both Pregestational diabetes,
et al15 States hospital in laboratory visits positive 1st-trimester
Pittsburgh, PA between 24 and GDM screen, multiple
30 wk GA gestation,
corticosteroids 30
d before enrollment,
history of bariatric
surgery, use of fertility
treatment to conceive,
plan to deliver at
different hospital,
inability to complete
glucose testing before
30 wk GA, anticipated
preterm delivery for
maternal or fetal
indications, blood sugar
level higher than 200
Observational
Studies
Aubry 2021 Two-step: 2005–2010 Switzerland 100 Swiss obstetric 24–28 wk GA Pregestational diabetes
et al16 One-step: hospitals
2012-2017
(continued )

Table 1. Characteristics of Studies Included in the Final Meta-Analysis (continued )
Study Year Study Years Country Setting Inclusion Criteria Exclusion Criteria
Costa 2019 Two-step: 2009–2011 Belgium Large academic 24–28 wk GA Pregestational diabetes,
et al17 One-step: center in multiple gestation, no
2013–2014 Brussels, Belgium screening data
available, patient did
not tolerate screening

Duran 2014 Two-step: April Spain Large community 24–28 wk GA Pregestational diabetes,
et al18 2011–March 2012 hospital in diabetes diagnosed
One-step: April Madrid, Spain before 24 wk GA
2012–March 2013
Feldman 2016 Two-step: 2010–2011 United Large community Managed starting in Pregestational diabetes,
et al21 One-step: States hospital in 1st trimester multiple gestation
2011–2013 Montebello, CA
Fuller 2014 Two-step: 2010–2011 United Tertiary care 24–28 wk gestation Pregestational diabetes,
et al19 One-step: States hospital in younger than age 18 y,
2011–2012 Hartford, CT history of gastric bypass
Ghaffari 2020 Two-step: 2012–2015 United Academic hospital 24–28 wk GA Pregestational diabetes,
et al20 One-step: States in San Francisco, multiple gestation
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2016–2018 CA
Huhn 2017 Two-step: 2008–2010 Switzerland Academic hospital Delivered at more Pregestational diabetes,
et al22 One-step: in Basel, than 22 wk GA multiple gestation,
2010–2013 Switzerland screening after 28 wk
GA, delivery elsewhere
Hung 2015 Two-step: 2009–2010 Taiwan Large community 24–28 wk GA, Pregestational diabetes,
et al23 One-step: hospital in delivered after multiple gestation, fetal
2012–2013 Taoyuan City, 24 wk GA anomalies
Taiwan
Kong 2015 Two-step: 2009 Canada Database with all All patients Pregestational diabetes
et al24 One-step: 2011 births in British delivering from
Columbia, April–September
Canada 2009 (CC) and
April–September
2011 (IADPSG)
Lee et al25 2019 2011–2013* United Academic hospital 24–28 wk GA Pre-existing diabetes,
States in Kansas City, multiple gestation, overt
MO diabetes mellitus
(fasting glucose level
126 or greater, HbA1c
6.5% or greater, random
200 or greater),
underwent 1st-trimester
GDM screening,
congenital anomalies
Lucovnik 2020 Two-step: 2004–2010 Slovenia Academic hospital Delivered at more Pregestational diabetes
et al13 One-step: in Ljubljana, than 22 wk GA,
2011–2017 Slovenia birth weight
greater than
500 g
Palatnik 2017 One-step: 2010–2013 United Academic hospital Older than age 18 Pregestational diabetes,
et al27 Two-step: States in Chicago, IL y, delivered at 37 multiple gestation,
2013–2015 wk GA or later HbA1c 6.5% or greater
at 1st prenatal visit
Wu et al26 2016 Two-step: 2010 Taiwan Academic hospital All singleton None reported
One-step: 2011 in Taipei, Taiwan pregnancies
delivered in 2011
RCT, randomized controlled trial; GA, gestational age; HIV, human immunodeficiency virus; GDM, gestational diabetes mellitus; CC,
Carpenter-Coustan; IADPSG, International Association of the Diabetes and Pregnancy Study Groups.
* Allowed clinicians to self-select screening method.

with Harbord’s test for categorical variables. Statistical (n54), stringent exclusion criteria limiting generaliz-
analyses were performed using Stata 17 with METAN ability (body mass index exclusions, excluded single-
software. tons, preterm births before 32 weeks of gestation,
patients with abnormal fasting values at screening
RESULTS visit) (n55), used a screening strategy other than
The electronic literature search yielded 2,456 citations IADPSG or Carpenter-Coustan (n510), conference
with 979 duplicates that were identified and removed, abstract with duplicate article (n510), one-step cohort
resulting in 1,477 unique citations (Fig. 1). Each title had more stringent blood glucose targets for medica-
was reviewed for relevance, 414 abstracts were re- tion initiation than the two-step cohort (n51), and
viewed, and 89 abstracts or full-text manuscripts were inability to obtain data after multiple attempts to con-
screened against inclusion and exclusion criteria. A tact authors (n52). One study (Lucovnik et al13) was
review of bibliographies of selected articles against removed from the macrosomia analysis due to a high-
study criteria did not result in additional studies for er macrosomia cutoff (more than 4,500 g) than other
consideration. Studies were excluded for the following included studies. A sensitivity analysis with inclusion
reasons: trial design article (n53), did not include of this study did not change outcomes (data not
clinical outcomes of interest (n519), did not compare shown).
one-step with two-step testing (n57), included only Seventeen studies including 735,643 patients
patients with GDM diagnosis rather than were analyzed: four RCTs (24,966 patients).3,4,14,15
1vYJzg== on 03/21/2023
population-level screening (n510), included only and 13 observational studies (710,677 patients)13,16–
27 Study characteristics, inclusion, and exclusion cri-
patients who tested negative for GDM (n51), retro-
spectively reclassified patients originally diagnosed teria are shown in Table 1. Quality scores on the
with Carpenter-Coustan to IADPSG for analysis Downs and Black checklist11 ranged from 15 to 28
Table 2. Comparison of Maternal and Neonatal Outcomes in Patients Undergoing One-Step Compared
With Two-Step Testing Among Randomized Controlled Trials
One-Step Testing Two-Step Testing I2

Outcome [n512,520 (50.15)] [n512,446 (49.85)] RR (95% CI) (%) P
Primary outcome
LGA neonate (greater than the 1,015 (8.8) 1,058 (9.2) 0.95 (0.88–1.04) 0.0 .716
90th percentile)
Secondary outcomes
Maternal outcomes
GDM 1,910 (16.3) 970 (8.3) 2.13 (1.61–2.82) 26.6 .252
GDM treatment (insulin or 833 (7.1) 446 (3.8) 2.24 (1.21–4.15) 67.9 .044
oral medication)
HDP 1,548 (13.6) 1,536 (13.6) 1.00 (0.94–1.07) 0.0 .391
Primary cesarean delivery 2,826 (24.0) 2,887 (24.7) 0.98 (0.93–1.02) 0.0 —*
Fetal and neonatal outcomes
Macrosomia (greater than 1,217 (11.2) 1,225 (11.3) 0.99 (0.92–1.07) 0.0 .695
4,000 g)
SGA neonate (less than the 993 (8.6) 948 (8.3) 1.04 (0.95–1.13) 0.0 .815
10th percentile)
Shoulder dystocia 240 (2.1) 224 (2.0) 1.06 (0.89–1.28) 0.0 .655
NICU admission 588 (5.1) 520 (4.5) 1.12 (1.00–1.26) 0.0 .466
Preterm birth (before 37 wk 728 (6.4) 721 (6.4) 1.00 (0.91–1.11) 0.0 .619
GA)
RDS 225 (2.0) 227 (2.0) 0.99 (0.82–1.16) 0.0 —*
Neonatal hypoglycemia 1,098 (9.3) 889 (7.6) 1.23 (1.13–1.34) 0.0 .371
Hyperbilirubinemia 506 (4.3) 494 (4.2) 1.18 (0.75–1.85) 45.5 .160
Stillbirth 61 (0.5) 67 (0.6) 0.90 (0.64–1.28) 0.0 .664
Neonatal death 7 (0.1) 12 (0.1) 0.58 (0.23–1.47) 0.0 —*
RR, relative risk; LGA, large for gestational age; GDM, gestational diabetes mellitus; HDP, hypertensive disorders of pregnancy; SGA, small
for gestational age; NICU, neonatal intensive care unit; GA, gestational age; RDS, respiratory distress syndrome.
Data are n (%) unless otherwise specified.
Bold indicates statistical significance (P,.05).
* Only one study included.

Fig. 2. Forest plot comparing one-step and two-step testing on large-for-gestational-age diagnosis, randomized controlled
trails. Weights are from random-effects model. DL, DerSimonian-Laird.
Brady. One-Step vs Two-Step GDM Testing. Obstet Gynecol 2022.
(median 21, interquartile range 21–22). Three RCTs evidence of publication bias (Harbord’s test P5.084)
1vYJzg== on 03/21/2023
and four observational studies were deemed high- (Fig. 3). Patients undergoing one-step testing were sig-
quality based on a Downs and Black score in the nificantly more likely to be diagnosed with GDM
top quartile (Appendix 2, available online at http:// (four studies: pooled rates 16.3% one-step vs 8.3%
links.lww.com/AOG/C876). two-step, pooled RR 2.13; 95% CI 1.61–2.82, number
In analysis limited to the 24,966 patients enrolled needed to screen [NNS] 13 patients) (Appendix 3,
in RCTs, the rate of LGA neonates was similar available online at http://links.lww.com/AOG/
between one-step and two-step testing (four studies: C876) and receive diabetes medication management
pooled rates 8.8% one-step compared with 9.2% two- (three studies: pooled rates 7.1% one-step vs 3.8%
step, pooled RR 0.95; 95% CI 0.88–1.04) (Table 2 and two-step, pooled RR 2.24; 95% CI 1.21–4.15, NNS
Fig. 2). There was no evidence of significant study 31 patients) (Table 2 and Appendix 4 [Appendix 4
heterogeneity (I250.0, P5.716; Fig. 2), but there was is available online at http://links.lww.com/AOG/
C876]). Newborns of patients who underwent one-
step testing had higher rates of NICU admission
(three studies; pooled rates 5.1% one-step vs 4.5%
two-step, pooled RR 1.12; 95% CI 1.00–1.26, NNS
167 patients) (Table 2 and Appendix 5 [Appendix 5
is available online at http://links.lww.com/AOG/
C876]) and neonatal hypoglycemia (four studies; 9.
3% one-step vs 7.6% two-step, pooled RR 1.23; 95%
CI 1.13–1.34, NNS 59 patients) (Table 2 and Appen-
dix 6 [Appendix 6 is available online at http://links.
lww.com/AOG/C876]). There were no differences in
other maternal or neonatal secondary outcomes
among RCTs (Table 2).
When only high-quality RCTs and observa-
tional studies were considered (363,950 patients),
Fig. 3. Funnel plot comparing one-step and two-step test- one-step testing was associated with a lower rate of
ing on large-for gestational-age diagnosis, randomized LGA neonates (pooled RR 0.97; 95% CI 0.95–0.98;
controlled trials (RCT) and high-quality observational Fig. 4). There was no evidence of significant study
studies. Note that the Khalifeh et al14 RCT was not deemed heterogeneity (I250.0, P5.733; Fig. 4) or publica-
high-quality but was added to illustrate all RCTs included in tion bias (Harbord’s test P5.330; Fig. 3). Results
the primary analysis. *Only three out of four observational
studies deemed high-quality reported rates of large-for- were otherwise similar to the RCT analysis with
gestational-age neonates. Two of the included studies are higher rates of GDM diagnosis (pooled RR 2.13;
overlapping at the apex of the graph. 95% CI 1.32–3.42), treatment (pooled RR 1.87;
Brady. One-Step vs Two-Step GDM Testing. Obstet Gynecol 2022. 95% CI 1.40–2.50), NICU admission (pooled RR

Table 3. Summary of Maternal and Neonatal Outcomes in Patients Undergoing One-Step Compared With
Two-Step Testing by Study Type and High Quality
RCT Pooled RR (95% High-Quality Pooled RR Observational Only Pooled RR

Outcome CI) (n524,966) (95% CI) (n5363,950) (95% CI) (n5710,677)
Primary outcome
LGA neonate (greater than 0.95 (0.88–1.04) 0.97 (0.95–0.98) 0.93 (0.90–0.96)
the 90th percentile)
Secondary outcomes
Maternal outcomes
GDM diagnosis 2.13 (1.61–2.82) 2.13 (1.32–3.42) 2.54 (1.92–3.37)
GDM treatment (insulin 2.24 (1.21–4.15) 1.87 (1.40–2.50) 1.15 (0.70–1.88)
or oral medication)
HDP 1.00 (0.94–1.07) 0.92 (0.82–1.04) 0.89 (0.82–0.95)
Primary cesarean 0.98 (0.93–1.02) 1.13 (0.95–1.34) 1.13 (1.04–1.23)
delivery
Fetal and neonatal
outcomes
Macrosomia (greater 0.99 (0.92–1.07) 0.86 (0.73–1.03) 0.81 (0.75–0.88)
than 4,000g)
1vYJzg== on 03/21/2023
SGA neonate (less than 1.04 (0.95–1.13) 1.00 (0.97–1.02) 1.00 (0.99–1.02)
the 10th percentile)
Shoulder dystocia 1.06 (0.89–1.28) 0.96 (0.84–1.09) 1.04 (0.91–1.20)
NICU admission 1.12 (1.00–1.26) 1.13 (1.05–1.21) 1.06 (0.96–1.18)
Preterm birth (before 37 1.00 (0.91–1.11) 1.00 (0.95–1.05) 1.00 (0.93–1.08)
wk GA)
Neonatal RDS 0.99 (0.82–1.18) 0.99 (0.82–1.18) 1.13 (1.09–1.16)
Neonatal hypoglycemia 1.23 (1.13–1.34) 1.25 (1.19–1.31) 1.19 (1.02–1.39)
Hyperbilirubinemia 1.18 (0.75–1.85) 1.06 (0.96–1.16) 1.00 (0.78–1.26)
Stillbirth 0.90 (0.64–1.28) 1.02 (0.92–1.12) 1.02 (0.92–1.12)
Neonatal death 0.58 (0.23–1.47) 0.58 (0.23–1.47) 1.08 (0.42–2.79)
RCT, randomized controlled trial; RR, relative risk; LGA, large for gestational age; GDM, gestational diabetes mellitus; HDP, hypertensive
disorders of pregnancy; SGA, small for gestational age; NICU, neonatal intensive care unit; GA, gestational age; RDS, respiratory distress
syndrome.
Bold indicates statistical significance (P,.05).
1.13; 95% CI 1.05–1.21) and neonatal hypoglyce- step testing (Table 3). There were no differences in
mia (pooled RR 1.25; 95% CI 1.19–1.31) (Table 3). other maternal or neonatal outcomes.
Results stratified by high-quality and low-quality
studies are shown in Appendix 7, available online
at http://links.lww.com/AOG/C876. DISCUSSION
Among 710,677 patients who participated in This meta-analysis of GDM screening tests showed
observational studies, those with one-step testing were that there was no difference in the rate of LGA
less likely to deliver LGA neonates (pooled RR 0.93; newborns by one-step testing strategy compared with
95% CI 0.90–0.96) (Table 3, Fig. 5). A sensitivity anal- a two-step testing strategy in analysis limited to
ysis that compared pooled adjusted and unadjusted RCTs. However, patients who were undergoing
results from observational studies that assessed rates one-step testing were more than twice as likely to
of LGA showed similar results (data not shown). be diagnosed with and treated for GDM while
Patients who received one-step testing for GDM were experiencing higher rates of NICU admission and
significantly more likely to be diagnosed with GDM, neonatal hypoglycemia. Analysis limited to high-
but not treated for it (Table 3). With regard to second- quality RCTs, and observational studies showed
ary outcomes, one-step testing was associated with a similar results, though those undergoing one-step
higher risk of primary cesarean delivery, neonatal testing had a modest decrease in rate of LGA
respiratory distress syndrome, and neonatal hypogly- neonates. Study quality varied greatly among obser-
cemia, but was associated with a lower risk of hyper- vational studies, but pooled results showed a signif-
tensive disorders of pregnancy compared with two- icant decrease in rate of LGA neonates and

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Fig. 4. Forest plot comparing one-step and two-step testing on large-for-gestational-age diagnosis, high-quality studies.
Weights and between-subgroup heterogeneity test are from random-effects model. RCT, randomized controlled trial; DL,
DerSimonian-Laird.
hypertensive disorders of pregnancy with one-step maternal and neonatal outcomes.3,14,31 Second, pool-
testing. These findings were offset by a significant ing high-quality studies provided adequate power to
increase in primary cesarean delivery, neonatal respi- detect differences in diabetes-related pregnancy out-
ratory distress syndrome, and neonatal hypoglycemia. comes that are difficult to detect with a population-
Our findings add critical insight to the literature based screening strategy when only 6%–18% of the
because the two most recent meta-analyses on this population receives a GDM diagnosis. In a recent
topic, published in 2018 and 2019,28,29 were limited commentary, Coustan et al argue that the largest
by lack of high-quality RCTs. The 2017 Cochrane RCT published to date, with more than 20,000
review analyzed several aspects of GDM diagnosis, patients, was not adequately powered to detect dif-
including one-step screening compared with two- ferences in pregnancy outcomes for this reason.32
step screening,2 but only one included study assessed We included a secondary analysis of high-quality
results by screening strategy.30 A 2019 systematic RCTs and observational studies of GDM testing
review and meta-analysis28 included three random- strategy, pooling nearly 400,000 patients, to address
ized trials, one of which is included here (Scifres this issue of power and minimize the risk of a type 2
CM, Abebe K, Simhan H, Catalano P, Costacou T, error. Although there were many more differences in
Comer DM, et al. Randomized clinical trial of the maternal and neonatal outcomes among observa-
IADPSG vs. Carpenter Coustan criteria for diagnosis tional studies overall, these findings should be taken
of gestational diabetes mellitus [abstract]. Diabetes with caution in the context of significant study het-
2020;69:187-OR. Doi: 10.2337/db20-187-OR). The erogeneity and varying levels of quality among these
two trials that we excluded were a cost-analysis and studies. Our analysis of high-quality studies is well-
a study that did not include patients with GDM in powered to conclude that the most likely differences
their analysis of outcomes. in pregnancy outcomes by testing strategy are higher
This meta-analysis builds on prior work in two rates of NICU admission and neonatal hypoglycemia
ways. First, the addition of three well-executed trials, with one-step testing and, potentially, a modest
published in the interim, provide further insight to decrease in rate of LGA neonates that is largely
determine the effect of testing strategy on short-term driven by observational studies.

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Fig. 5. Forest plot comparing one-step and two-step testing on large-for-gestational-age diagnosis, observational studies.
Weights are from random-effects model. DL, DerSimonian-Laird.
Expert editorials on the recently published RCTs patients in RCTs. This approach also allowed us to
concede that both favor two-step testing in the leverage the strengths of each study design—the gold
absence of demonstrable neonatal or parental benefit standard RCT designs that may have limited general-
with significantly higher rates of diagnosis and treat- izability compared with more pragmatic observational
ment with one-step testing.32,33 Our large, pooled, studies that more closely resemble real-world settings.
internationally representative sample provides further The Downs and Black checklist assessed the quality of
credence to this argument. We hypothesize that both RCTs and observational studies based on our
adverse outcomes associated with one-step testing cor- predetermined high-quality threshold.
respond to relatively lower-risk patients being given a Despite its strengths, this study should be consid-
diagnosis of GDM, such that the “treatment” may no ered in the setting of the following limitations. We
longer justify the “cure.” A GDM diagnosis likely limited our two-step eligibility criteria to studies using
changes the way that health care professionals engage Carpenter-Coustan criteria, both because it is most
with birthing people and neonates through seemingly commonly used clinically and to limit heterogeneity
risk-reducing interventions that may paradoxically among studies. Although preterm birth rates before
worsen outcomes. For example, pediatricians only 37 weeks of gestation were similar between groups,
screen for neonatal hypoglycemia when GDM or pooled data were not available to compare rates of
other risk factors are present, leading to greater detec- early preterm (before 34 or before 28 weeks of
tion and treatment with one-step testing, as seen in all gestation) or early term (37–38 6/7 weeks of gestation)
our analyses. This may also explain the higher rates of birth, which could have helped contextualize differ-
NICU admission seen in RCTs and high-quality study ences in hypertensive disorders of pregnancy and
analyses. respiratory distress syndrome for observational stud-
There are many strengths to this study. The ies. There were significant differences between obser-
recent publication of two well-executed RCTs allowed vational studies and RCTs beyond their study design.
us to pool high-quality data to help obstetricians All four RCTs were conducted in the United States at
decide which universal screening method to use. large tertiary care centers with a high-risk population
The large pooled sample size provided greater power compared with the general population. In contrast,
to detect smaller differences than would have been more than half of the observational studies were con-
possible by limiting the sample to the nearly 25,000 ducted internationally at both academic and

community hospitals. Given the major differences in 5. Arya S, Kaji AH, Boermeester MA. PRISMA reporting guide-
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lence of some secondary outcomes was significantly
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different between observational studies and RCTs. guidelines for meta-analyses of observational studies. JA-
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Systematic Review

One-Step Compared With Two-Step

712 VOL. 140, NO. 5, NOVEMBER 2022 OBSTETRICS & GYNECOLOGY

© 2022 by the American College of Obstetricians

(Obstet Gynecol 2022;140:712–23)

Coustan two-step methods of GDM screening and

S ignificant time, energy, and resources have been

© 2022 by the American College of Obstetricians

Fig. 1. Flowchart showing the meth-

714 Brady et al One-Step vs Two-Step GDM Testing OBSTETRICS & GYNECOLOGY

© 2022 by the American College of Obstetricians

diabetes age 18 y, history of

© 2022 by the American College of Obstetricians

not tolerate screening

716 Brady et al One-Step vs Two-Step GDM Testing OBSTETRICS & GYNECOLOGY

© 2022 by the American College of Obstetricians

One-Step Testing Two-Step Testing I2

© 2022 by the American College of Obstetricians

718 Brady et al One-Step vs Two-Step GDM Testing OBSTETRICS & GYNECOLOGY

© 2022 by the American College of Obstetricians

RCT Pooled RR (95% High-Quality Pooled RR Observational Only Pooled RR

© 2022 by the American College of Obstetricians

720 Brady et al One-Step vs Two-Step GDM Testing OBSTETRICS & GYNECOLOGY

© 2022 by the American College of Obstetricians

© 2022 by the American College of Obstetricians

for clinicians. J Can Chiropractic Assoc 2012;56:167–71.

the assessment of the methodological quality both of random-

722 Brady et al One-Step vs Two-Step GDM Testing OBSTETRICS & GYNECOLOGY

© 2022 by the American College of Obstetricians

© 2022 by the American College of Obstetricians

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