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Accepted Article
Use of a clinical-laboratory score to guide treatment of gestational diabetes
* Correspondence
Juliana Barros do Valle, Rua Barão do Rio Branco, 207 sala 7, Jaraguá do Sul, SC,
Brazil.
Email: julianabvalle@gmail.com
Abstract
This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process, which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1002/ijgo.12326
This article is protected by copyright. All rights reserved.
Methods: A retrospective before-and-after implementation analysis was undertaken
Accepted Article using data and neonatal outcomes for pregnant women with gestational diabetes
treated before (January 2011–December 2012; control group) and after (January
evaluate the effects of score adoption, odds ratios with 95% confidence intervals
Results: The control group included a greater proportion of women treated with diet
alone (170/312 [54.5%]) than the study group did (122/391 [31.2%]; P<0.001). By
contrast, more women in the study group received metformin (172 [44.0%] vs 77
[24.7%]; P<0.001). The neonatal outcomes, including low Apgar scores at 1 minute
and at 5 minutes and neonatal intensive care unit admission, were similar in both
groups. Multivariate logistic regression analysis showed that the adoption of the
score did not significantly affect the choice of treatment or the birth weight rating.
making and had no negative effect on the treatment choice and perinatal outcomes.
1 INTRODUCTION
For 10% of women whose pregnancies are complicated by diabetes, the diagnosis
occurs before conception and as such they are deemed to have pregestational
metabolic disorder defined as any reduction in the degree of glucose tolerance that
[3–5]. Recommended total weight gain, based on pre-pregnancy body mass index
(BMI) has previously been reported in the literature; this varies from 7 kg to 11 kg
and from 5 kg to 9 kg for overweight and obese patients, respectively [6]. The
treatment of GDM initially consists of diet and exercise with the aim of reducing
pregnant women without diabetes differ throughout the day depending on whether or
not patients are obese [13]. Bertini et al. [7] reported that differences in the treatment
extreme obesity usually required a two-fold higher insulin dose to achieve the
glycemic goal. Both obesity and excessive weight gain can increase the risks of
having a large for gestational age (LGA) neonate and macrosomia [3,8]. Glycemic
The Brazilian Diabetes Society (SBD) and the Brazilian Federation of Gynecology
measurement, with the result considered excellent when the glucose value is 3.33–
5.83 mmol/L (60–105 mg/dL) before meals, at bedtime, and at dawn, and 5.55–
7.77 mmol/L (100–140 mg/dL) 1 hour after eating [8,9] .By comparison, the
Association recommend the following blood glucose levels: 5.27 mmol/L (95 mg/dL)
or less before eating, 7.77 mmol/L (140 mg/dL) or less 1 hour after eating, and
[11–13].
FAC can serve as an indicator of excessive fetal growth and an indirect marker of
fetal hyperinsulinism, primarily from 28 weeks of pregnancy [14]. Values between the
70th and 75th percentiles relative to normal pregnancies have been associated with
satisfactory maternal and fetal outcomes. Irrespective of blood glucose levels, the
FAC can be used to identify pregnancies at low risk for fetal macrosomia and can
As for BMI, both pre-pregnancy obesity (BMI ≥30, calculated as weight in kilograms
divided by the square of height in meters) and a substantial weight gain during the
prenatal period are associated with an increased risk of diabetes and a LGA neonate
[16]. Additionally, the average blood glucose value throughout the day appears to be
0.28–0.56 mmol/L (5–10 mg/dL) higher in obese women without diabetes than in
nonobese women[17].A two-fold higher insulin dose is typically required for pregnant
The pregnancy duration at the onset of treatment and glycemic control values can
Joinville, Brazil, were usually based on the clinical experience of the attending
that integrates the information from these variables (Table 1, Table 2). The aim of
the present study was to assess the outcomes of the implementation of this tool in
treatment data and perinatal outcomes for women attending a clinic for pregnant
the supervisors of medical students, and other staff members. Data were collected
for patients who were treated between January 1, 2011, and December 31, 2014,
and whose prenatal care and birth occurred at Darcy Vargas Maternity Hospital. The
The inclusion criteria were diagnosis of GDM according to WHO criteria (fasting
blood glucose value ≥6.11 mmol/L [≥110 mg/dL] or blood glucose value
≥7.77 mmol/L [≥140 mg/dL] 2 hours after an oral glucose tolerance test), age of at
least 18 years, singleton pregnancy, absence of other conditions that might interfere
with perinatal outcomes or therapy, and availability of complete patient data. There
were no deleted records. The study and introduction of the Score were approved by
the Univille Ethics Committee. Written informed consent was obtained from all
participants upon first visit to the Diabetes Clinic and included use of patient data
psychologist, and nurse evaluations upon referral to the Diabetes Clinic. Diet was
adapted on an individual basis, and the calorie intake was calculated as 25 kcal/kg
body weight for obese patients and 35 kcal/kg body weight for nonobese patients.
Glycemic control was considered satisfactory when the fasting blood glucose value
was 5.00 mmol/L (90 mg/dL) and the 1-hour postprandial value was 7.77 mmol/L
(140 mg/dL).
Obstetric evaluations occurred every 14–21 days at the hospital's Diabetes Clinic
after the initial consultation and diagnosis, and other professional evaluations
occurred on medical request. At the first obstetric visit after diagnosis, the glycemic
values were assessed during the day at the hospital (fasting blood glucose and
glucose levels 1 hour after breakfast, lunch, and afternoon coffee). At subsequent
If glycemic control had not been achieved by the subsequent visit, medication
treatment was initiated with oral metformin (Glifage, Merck, Rio de Janeiro, Brazil),
to prescribe insulin or metformin was made using score points (the score group) or
The dose of metformin was 500 mg at lunch and dinner; it was increased by 500–
was 0.7 UI/kg/day, administered before each meal (approximately one third before
breakfast, one quarter before lunch, one quarter before the evening meal, and one
sixth administered before going to sleep at night) according to glucose profile results
basis), with regular insulin being used preprandially and neutral protamine Hagedorn
insulin used at bedtime. The medications were provided by the public health system.
Delivery was recommended at 40 weeks for patients treated with diet only, and at
39 weeks for those treated with medications. If the fetal weight was greater than the
97th percentile for the gestational age, delivery was medically indicated at 37 weeks.
From January 1, 2013, the clinical-laboratory score was applied at every medical
appointment. The patient received a score for each measure included in the tool
For the present study, medical records were reviewed for maternal age, pre-
pregnancy BMI, parity, total weight gain during pregnancy, pregnancy duration on
arrival at the clinic, fasting and postprandial blood glucose levels, and treatment
applied (diet only, metformin, insulin, or both medications). Women with a BMI
between 26 and less than 30 were classified as overweight, and those with a BMI of
30 or more were classified as obese. Women with BMI below 18.5 were considered
age at birth, premature birth, route of delivery, birth weight, Apgar score, and
neonatal intensive care unit (NICU) admission. Newborns whose weight was below
the 10th percentile on growth curves were considered SGA; those with a weight
above the 10th percentile and below the 90th percentile were considered appropriate
for gestational age; and those with a weight above the 90th percentile were
The primary outcome measures were the choice of treatment (diet alone, metformin,
insulin, or both metformin and insulin combined), and the neonatal outcomes.
Data were tabulated using Excel 2010 (Microsoft, Redmond, WA, USA) and
analyzed using SPSS version 21 (IBM, Armonk, NY, USA). All variables were
parametric t test, and non-normally distributed data were analyzed using the
nonparametric Mann–Whitney U test. For nominal variables, the χ2 test was used;
the Fisher exact test was used when the number of datapoints was less than five.
Multivariate logistic regression analysis was performed to calculate odds ratios with
score on the treatment choice and neonatal outcomes. P<0.05 was considered
statistically significant.
3 RESULTS
Of 703 pregnant women with diabetes treated over the entire study period, 391
patients (55.6%) were in the score group and 312 (44.4%) in the control group. No
Both groups had similar characteristics regarding age and parity (Table 3). A pre-
pregnancy BMI classified as obese and weight gain below the recommendation were
more frequent in the score group than in the control group (both P<0.001) (Table 3).
Compared with the score group, the control group included a higher percentage of
recommended weight gain (all P<0.001) (Table 3). The total weight gain in the
control group was higher than that in the control group (P<0.001) (Table 3).
With respect to data related to diabetes during pregnancy, the score group had a
longer pregnancy duration at arrival at the clinic and included a higher percentage of
With regard to the characteristics of the newborns, the gestational age at delivery
and the Apgar scores at 1 minute and 5 minutes were higher in the control group
than in the score group (all P<0.01) (Table 5). There were more cesarean deliveries
The adoption of the score did not affect the type of treatment or the classification of
factors such as maternal age, pre-pregnancy BMI, weight gain, pregnancy duration
at admission, mean fasting glucose value, and mean postprandial glucose value
(Table 6).
4 DISCUSSION
guide treatment of gestational diabetes had no effect on treatment choice and did not
The clinical-laboratory score was constructed using six measures (Table 1) that
included fasting blood glucose, postprandrial blood glucose, FAC, BMI, and duration
perinatal complications that can include a birth weight above the 90th percentile,
Outcomes study [21] demonstrated that the risks of maternal, fetal, and neonatal
weeks of pregnancy, even if the actual values remain within the range considered
complications have been described in the literature but remain controversial [5].
glucose monitoring during pregnancy. It was also noted, in the current study, that the
treatment only, whereas the score group included a greater proportion of patients
characterization of the groups. Preterm birth, birth weight, and NICU admission are
association between an infant weight above the 90th percentile and increased
maternal blood glucose levels. However, pursuing strict control and narrow glycemic
evaluation increases the incidence of SGA newborns. Kjos et al. [15] noted a
reduced use of insulin and a lower incidence of SGA newborns if pregnant women
with diabetes were managed on the basis of fetal growth instead of strict glycemic
control. Also, ensuring appropriate weight gain during pregnancy could improve
perinatal outcomes. Gante et al. [22] observed a higher frequency of SGA newborns
cesarean delivery were higher among obese pregnant women with diabetes and
score was the FAC. Some studies have employed the FAC as a follow-up tool for
above the 75th percentile frequently reflects a state of fetal hyperinsulinemia and
The aim of the present study was not to compare one treatment to another, but
rather to use an appropriate score to guide the choice of treatment from among
that the score group included a greater proportion of women undergoing metformin
treatment, as opposed to treatments including diet and/or insulin, compared with the
control group. Perinatal studies [23, 24] have revealed similar results for metformin
and insulin in pregnant women with diabetes. Moreover, the high cost, complexity,
birth weight among pregnant women with diabetes who received metformin
compared with those receiving glyburide [12, 25] A meta-analysis [23] concluded that
metformin reduced the incidence of maternal and neonatal adverse effects, including
studies are required to evaluate the potential risks associated with metformin therapy
Although a dietary treatment approach would be always preferable, not all patients
benefit from a diet-only treatment. The score aims, in this respect, to guide decisions
regarding treatment choice. The odds ratios and confidence intervals produced
indicated that the score did not influence on the choice of treatment, with the
Similarly, the score had no effect on neonatal outcomes. Results including birth
rating, low apgar scores, and neonatal care unit admission were similar in both
groups.
The present study was limited by not taking the time between diagnosis, referral to
the ambulatory clinic, and patient arrival into account, although the protocol for
diabetes screening used by the primary care network followed the recommendations
source of bias. Another potential limitation was the difference in the number of
participants in the two groups. Because the availability of complete data was an
inclusion criterion, greater care was taken completing the records once the score
was implemented; hence, the score group included a larger number of patients.
weight gain, pregnancy duration at the beginning of treatment, type of treatment, and
route of delivery. The nature of the present study must be considered; the two
samples were studied at different times and there may have been seasonal
(maternal age, BMI, weight gain during pregnancy, pregnancy duration at the
To summarize, the present analysis revealed that the adoption of the clinical-
laboratory score had no negative effects on the choice of treatment and neonatal
outcomes. Thus, the score could serve as a complement to clinical experience in the
planning of treatment for GDM. This tool could be particularly useful for guiding
prenatal care professionals at academic centers that train doctors and medical
students. The adoption of measures and protocols that facilitate therapeutic decision
clinical training to current and future health professionals. Accordingly, the score was
not designed to be the sole determinant of the therapeutic choice, but to serve as a
tool that is used in combination with the attending physician’s clinical experience.
Author contributions
JBdV and JCS supervised the conduct of the study. JCS designed and planned the
study. DSO, LM, and AL collected the data. JBdV and WH analyzed the data and
wrote the manuscript. All authors edited, revised, and approved the manuscript.
Conflicts of interest
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Table 2 Recommendations for the treatment of diabetes during pregnancy based on the clinical-
laboratory score.
Total score a Suggested therapy
<0 New consultation with nutritionist
≥0 to <2 Maintenance of diet and physical activity
≥2 to ≤4 Oral hypoglycemic drug
>4 Insulin concomitant with diet and/or oral hypoglycemic drug
a
Sum of scores for each individual measure, as shown in Table 1.
Table 6 Effect of adoption of the clinical-laboratory score on the type of treatment used and the
newborn weight rating.
Variable Unadjusted OR (95% CI) Adjusted OR (95% CI) a
Type of treatment
Diet 0.437 (0.240–0.798) 0.521 (0.242–1.119)
Metformin 1.405 (0.760–2.595) 1.502 (0.732–3.083)
Insulin 0.922 (0.472–1.799) 1.238 (0.570–2.689)
Metformin + insulin 1.260 (0.716–2.218) 0.825 (0.422–1.610)
Newborn weight rating
Small for gestational age 1.307 (0.535–3.194) 2.343 (0.790–6.946)
Appropriate for gestational age 0.911 (0.628–1.323) 0.936 (0.589–1.487)
Large for gestational age 1.071 (0.722–1.591) 0.899 (0.540–1.498)
Macrosomia 0.870 (0.409–1.851) 0.747 (0.351–1.592)
Abbreviations: OR, odds ratio; CI, confidence interval.
a
Adjusted for maternal age, pre-pregnancy body mass index, weight gain during pregnancy,
pregnancy duration at the start of treatment, mean fasting glucose value, and mean postprandial
glucose value.