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Pornpimol Ruangvutilert, M.D., Ph.D., anapa Rekhawasin, M.D., Chayawat Phatihattakorn, M.D., Dittakarn

Boriboonhirunsarn, M.D., Ph.D.

Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ailand.

Accuracy of Third Trimester Ultrasound for

Predicting Large-for-Gestational Age Newborn in

Women with Gestational Diabetes Mellitus

ABSTRACT

Objective: To determine the accuracy of ultrasonography during 32-36 weeks of gestation for predicting a large-

for-gestational-age (LGA) newborn in women with gestational diabetes mellitus (GDM).

Materials and Methods: Women with singleton pregnancy, aged ≥ 18 years old and diagnosed with GDM were

recruited. ey underwent ultrasonography at 32-36 weeks’ gestation for fetal biometry, namely, biparietal diameter

(BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). Estimated fetal weight

(EFW) was derived from these 4 parameters by Hadlock formula. Delivery of an LGA newborn in women with the

ultrasound nding of LGA fetus was the primary outcome of interest along with determination of predicting factors.

Results: Of 345 studied women, 107 (31%) had an LGA newborn. EFW of ≥ 90

percentile at third trimester

ultrasonography was found in 13 women, all of whom had an LGA newborn. It had a positive predictive value

(PPV), specicity, sensitivity and negative predictive value (NPV) of 100%, 100%, 12.1% and 71.7% respectively to

predict LGA at birth. Considering each fetal parameter individually, AC ≥ 90

percentile and HC ≥ 90

percentile

had odds ratios (OR) with 95% condence intervals of the newborn being LGA of 6.5 (3.3-12.8) and 2.0 (1.0-4.0)

respectively while EFW ≥ 85

percentile had the highest OR of 9.3 (1.1-77.9). Lowering cuto values of EFW to

and 70

percentile increased the sensitivity and NPV for prediction of LGA at birth while reducing the PPV

and specicity slightly.

Conclusion: EFW derived from the third trimester ultrasonography in women with GDM had high PPV and

specicity with low to moderate sensitivity and NPV to predict an LGA newborn in women with GDM.

Keywords: Estimated fetal weight; third trimester ultrasound; large-for-gestational age newborn; gestational diabetes

mellitus (Siriraj Med J 2021; 73: 322-329)

Corresponding author: Chayawat Phatihattakorn

E-mail: naeobgyn@gmail.com

Received 19 January 2021 Revised 22 February 2021 Accepted 24 February 2021

ORCID ID: http://orcid.org/0000-0002-7433-5386

http://dx.doi.org/10.33192/Smj.2021.42

INTRODUCTION

Gestational diabetes mellitus (GDM) is a condition

diagnosed during pregnancy associated with a lack of

tolerance to increased blood glucose level.

Approximately

7% of all pregnancies are aected, with a worldwide

incidence of more than 200,000 pregnancies annually.

During the past decade, the incidence of GDM in Siriraj

Hospital, a ailand national tertiary center, has increased

from 2-3% to 10-15%.

GDM can cause adverse maternal and fetal/

neonatal outcomes such as the need for cesarean delivery,

cephalopelvic disproportion, postpartum hemorrhage,

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pregnancy-induced hypertension, large-for-gestational age

(LGA) fetus, shoulder dystocia, neonatal hypoglycemia,

and jaundice.

3,4

e incidence of LGA fetus in women

with GDM was reported in the range of 15-20%.

3,5,6

e

ability to diagnose LGA fetus in GDM women in advance

would improve the management and outcomes of both

women and their babies.

Ultrasonography in the third trimester was proven

to be useful for predicting the actual birth weight.

7,8

Ultrasonography has been reported to help guide

management and improve pregnancy outcomes in

women with GDM.

However, to our knowledge, no

study has addressed the accuracy of the third trimester

ultrasound at 32-36 weeks’ gestation, which is the period

just aer the maximal fetal growth rate, for predicting

an LGA newborn in these women.

e current study was performed to determine the

accuracy of ultrasound during 32-36 weeks’ gestation

for predicting LGA newborn in women with GDM.

MATERIALS AND METHODS

is prospective cohort study was performed at

Department of Obstetrics and Gynecology, Faculty of

Medicine Siriraj Hospital, Mahidol University, Bangkok,

ailand during January 2017 to January 2018. Women

aged ≥ 18 years with a singleton pregnancy at 32-36

weeks’ gestation, diagnosed with GDM, and without

known fetal anomalies were included. e study was

approved by the Siriraj Institutional Review Board (SIRB)

(Si 007/2017). Written informed consent was obtained

from all women.

Gestational age was based on either crown-rump

length in the rst trimester or last menstrual period

correlating with BPD in the second trimester. Screening

for GDM with 50-g glucose challenge test (50-g GCT) was

performed in pregnant women with any of the following

risk factors: age ≥ 30 years old, BMI >25 kg/m

, family

history of diabetes mellitus, history of GDM in previous

pregnancy, history of dead fetus in utero (DFIU), fetal

anomaly or a macrosomic baby in a previous pregnancy

Women with an abnormal 50-g GCT (≥ 140 mg/dl)

underwent a 100-g oral glucose tolerance test (OGTT).

According to Carpenter-Coustan criteria, GDM was

diagnosed when two or more values were abnormal.

e women underwent ultrasound scanning using

a machine with a 2-5 MHz curvilinear transabdominal

transducer (Voluson E8; GE Healthcare, Zipf, Austria).

Fetal biometry, namely, biparietal diameter (BPD), head

circumference (HC), abdominal circumference (AC),

and femur length (FL), were measured by an experienced

physician. With inappropriate fetal position or acoustic

shadows, remeasurement was performed aer a short

break until standard planes were achieved in all pregnant

women. ree measurements were obtained for each

parameter and the averages were used to calculate the

estimated fetal weight (EFW) by Hadlock formula.

EFW percentile was determined and was classied as

small-for-gestational age (SGA) if the EFW was ≤ 10

percentile, LGA if the EFW was ≥ 90

percentile, and

appropriate-for-gestational age (AGA) if the EFW was

in the range between these two limits. Birth weight

was classied as LGA (≥ 90

percentile) or SGA (≤ 10

percentile) status based on 2004-2008 WHO Global

Survey on Maternal and Perinatal Health (WHOGS)

data.

Macrosomia was dened when birth weight was

4,000 grams or more.

Body mass index (BMI) was categorized into four

groups according to the 2009 Institute of Medicine

(IOM)/National Research Council (NRC) guidelines

as follows: underweight (BMI < 18.5 kg/m

), normal

(BMI 18.5-24.9 kg/m

), overweight (BMI ≥ 25.0-29.9

kg/m

), and obese (BMI ≥ 30.0 kg/m

). Recommended

total weight gain in each group is 13-18 kg, 11-16 kg,

7-11 kg, and 5-9 kg, respectively.

Overweight and obese

groups were dened as high BMI.

GDM management started wth proper exercise

and diet adjustment. Insulin would be added in cases

uncontrollable by these two strategies. Glycemic follow-

up checks were performed using either fasting blood

sugar (FBS) (normal value: < 95 mg/dl) with two-hour

postprandial (2-h PP) blood sugar (normal value:

< 120 mg/dl) or 2-h PP alone. GDM diagnosed before 24

weeks of gestation was dened as early GDM, and GDM

diagnosed aer 24 weeks was dened as late GDM.

Maternal complications, including gestational

hypertension, preeclampsia, shoulder dystocia, 3

or 4

degree laceration of birth canal, postpartum hemorrhage,

and preterm delivery were recorded. Neonatal outcomes,

including birth weight, birth asphyxia, subgaleal hematoma,

hypoglycemia, polycythemia, jaundice, respiratory distress

syndrome, and NICU admission, were also studied.

Statistical analysis

SPSS Statistics version 21 (SPSS, Inc., Chicago, IL,

USA) was used for statistical analyses. Sample size was

calculated based on the study of Scifres et al.

, showing

that the accuracy of third trimester ultrasound was 22.6%

for predicting LGA newborn in women with GDM. With

the error of 30% and loss of data of 10%, the required

total sample size was 360.

Demographic data were summarized using descriptive

statistics. Data are presented as number and percentage

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324

for categorical variables, and mean ± standard deviation

for continuous variables. Student’s t-test or Chi-square

test was used to compare patient data between groups.

Results of multivariate analysis are shown as adjusted odds

ratio and 95% condence interval. Sensitivity, specicity,

positive predictive value (PPV), negative predictive value

(NPV), and cut-o value of third trimester ultrasound

for predicting LGA newborn in women with GDM

were also calculated. P-value of < 0.05 was considered

statistically signicant.

RESULTS

Of the 360 pregnant women initially recruited, 15

women were lost to follow-up and 345 women were

included in the nal analysis. e demographic and

clinical characteristics of the women are shown in Table 1.

Forty percent of the women had a high BMI. Almost

two-thirds of women were diagnosed with GDM before

24 weeks’ gestation. Approximately 90% of women did

not need insulin therapy. e three most common risk

factors for GDM were age ≥ 30 years old, BMI > 25 kg/

and family history of diabetes mellitus.

Fetal parameters at 32-36 weeks’ gestation are

shown in Table 2. BPD, HC and FL of ≥ 90

percentile

each accounted for 35.9-38.0% of women, and 20.3%

of women had AC of ≥ 90

percentile. EFW of ≥ 90

percentile (LGA) was present in 13 (3.8%) fetuses.

Maternal and neonatal outcomes are described in

Table 3. Forty-two percent of women were delivered

vaginally while primary cesarean section was performed

in 36.5%. irty-one percent of the neonates were LGA

babies. e percentage of macrosomic newborns was

2.9%.

TABLE 1. Baseline demographic and clinical characteristics of study women (N = 345)

Characteristics n (%)*

Age (years), mean ± SD 34.4 ± 10.7

BMI (kg/m

), mean ± SD 24.7 ± 5.0

BMI classication

Normal (18.5-24.9 kg/m

) 207 (60.0)

Overweight (≥ 25 kg/m

) 83 (24.1)

Obese (≥ 30 kg/m

) 55 (15.9)

Nulliparity 141 (40.9)

GA at GDM diagnosis (weeks), mean ± SD 17.9 ± 9.1

Early GDM diagnosis 218 (63.2)

Well-controlled GDM

Yes 290 (84.1)

No 55 (15.9)

GDM control

Diet 308 (89.3)

Diet with insulin 37 (10.7)

Risk factors for GDM

Age ≥ 30 years 286 (82.9)

BMI > 25 kg/m

138 (40.0)

Family history of diabetes mellitus 124 (35.9)

History of GDM in previous pregnancy 17 (4.9)

History of DFIU in previous pregnancy 6 (1.7)

History of fetal anomaly in previous pregnancy 9 (2.6)

History of giving birth to macrosomic newborn 7 (2.0)

*unless stated otherwise

Abbreviations: SD = standard deviation; BMI = body mass index; GA = gestational age; GDM = gestational diabetes mellitus; DFIU = dead

fetus in utero

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TABLE 2. Fetal parameters at 32-36 weeks’ gestation (N=345)

Parameters Mean ± SD

Percentile, n (%)

   ≤10

 >10

-50

 51

-<90

 ≥90

BPD (mm) 83.5 ± 4.2 26 (7.5 %) 74 (21.4 %) 119 (34.5 %) 126 (36.5 %)

HC (mm) 303.0 ± 15.1 34 (9.9 %) 74 (21.4 %) 106 (30.7 %) 131 (38.0 %)

AC (mm) 295.8 ± 20.1 23 (6.7 %) 103 (29.9 %) 149 (43.2 %) 70 (20.3 %)

FL (mm) 62.6 ± 3.5 17 (4.9 %) 61 (17.7 %) 143 (41.4 %) 124 (35.9 %)

EFW (g) 2179.6 ± 375.0 56 (16.2 %) 201 (58.3 %) 75 (21.7 %) 13 (3.8 %)

Abbreviations: BPD = biparietal diameter; HC = head circumference; AC = abdominal circumference; FL = femur length; EFW = estimated

fetal weight

TABLE 3. Maternal and neonatal outcomes (N = 345)

Outcomes n (%)*

GA at delivery (weeks), mean ± SD 38.0 ± 1.2

Birth weight (grams), mean ± SD 3,148 ± 466

Delivery route

Spontaneous vaginal delivery 139 (40.3)

Instrument-assisted delivery 6 (1.7)

Primary cesarean section 126 (36.5)

Repeat cesarean section 74 (21.4)

LGA newborn 107 (31.0)

Macrosomia 10 (2.9)

Birth asphyxia 10 (2.9)

NICU admission 4 (1.2)

*unless stated otherwise

Abbreviations: GA = gestational age; LGA = large-for-gestational age; NICU = neonatal intensive care unit

Univariate analysis for factors associated with LGA

newborn in GDM is shown in Table 4. Women with

high BMI and women with any fetal parameter of ≥ 90

percentile at 32-36 weeks’ gestation were signicantly

more likely to deliver an LGA baby. All the 13 fetuses

with EFW of ≥ 90

percentile at 32-36 weeks’ gestation

were LGA at birth, resulting in PPV and specicity of

100%. However, the NPV and sensitivity were 71.7%

and 12.2% respectively.

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326

TABLE 4. Univariate analysis for factors associated with LGA newborn in GDM

No LGA newborn LGA newborn

 Variables (N=238) (N=107) p-value*

n (%) n (%)

BMI 0.038

Normal (18.5-24.9 kg/m

) 150 (72.5) 57 (27.5)

Overweight (≥ 25 kg/m

) 58 (69.9) 25 (30.1)

Obese (≥ 30 kg/m

) 30 (54.5) 25 (45.5)

Gestational weight gain 0.345

Below recommended range 99 (69.7) 43 (30.3)

Within recommended range 78 (72.9) 29 (27.1)

Above recommended range 61 (63.5) 35 (36.5)

Nulliparity 98 (69.5) 43 (30.5) 0.863

Multiparity 140 (68.6) 64 (31.4)

Early GDM 154 (70.6) 64 (29.4) 0.383

Late GDM 84 (66.1) 43 (33.9)

GDM control 0.116

Well-controlled 33 (60.0) 22 (40.0)

Poorly-controlled 205 (70.7) 85 (29.3)

BPD ≥ 90

percentile 66 (52.4) 60 (47.6) <0.001

< 90

percentile 172 (78.5) 47 (21.5)

HC ≥ 90

percentile 69 (51.9) 64 (48.1) <0.001

< 90

percentile 169 (79.7) 43 (20.3)

AC ≥ 90

percentile 19 (26.0) 54 (74.0) <0.001

< 90

percentile 219 (80.5) 53 (19.5)

FL ≥ 90

percentile 72 (55.4) 58 (44.6) <0.001

< 90

percentile 166 (77.2) 49 (22.8)

EFW ≥ 90

percentile 0 (0.0) 13 (100) <0.001

< 90

percentile 238 (71.7) 94 (28.3)

*p-value < 0.05 indicates statistical signicance

Abbreviations: LGA = large-for-gestational age; GDM = gestational diabetes mellitus; BMI = body mass index; BPD = biparietal diameter;

HC = head circumference; AC = abdominal circumference; FL = femur length; EFW = estimated fetal weight

e comparison between groups was performed using Chi-square test.

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Multivariate analysis for factors independently

associated with LGA newborn in GDM is shown in

Table 5. AC and HC of ≥ 90

percentile were independent

predictors of LGA newborn with adjusted odds ratio (OR)

of 6.5 and 2.0 respecitvely. We determined the adjusted

OR of EFW of ≥ 85

percentile because EFW ≥ 90

percentile would produce a “zero” value in calculation

formula. EFW of ≥ 85

percentile was the strongest factor

of LGA newborn with the adjusted OR of 9.3.

EFW of ≥ 90

percentile resulted in 100% positive

predictive value and 100% specicity for identication

of fetuses at risk to be born LGA. However, as this cuto

accounted for 3.8% of the fetuses measured at the third

trimester, the benet was limited. In addition, a number of

the actual LGA neonates would be missed. erefore, we

tried lower cuto percentiles in an attempt to increase the

sensitivity of third trimester ultrasonography to predict

LGA babies. Table 6 shows performance using various

cutos. Using cuto levels at 80

and 70

percentile

could increase the sensitivity while slightly reducing the

PPV and specicity.

Regarding dierent timing of ultrasonography, no

dierence of performance in predicting an LGA baby

was observed between examination at 32-34 weeks’ and

34-36 weeks’ gestation.

Variables Adjusted OR (95% CI) p-value*

BMI

Normal (18.5-24.9 kg/m

) 1 0.253

Underweight (<18.5 kg/m

) 0.8 (0.4-1.6) 0.53

Overweight and obese (≥25 kg/m

) 1.6 (0.7-3.5) 0.20

BPD ≥ 90

percentile 1.3 (0.6-2.7) 0.406

HC ≥ 90

percentile 2.0 (1.0-4.0) 0.048

AC ≥ 90

percentile 6.5 (3.3-12.8) <0.001

FL ≥ 90

percentile 1.7 (0.9-3.0) 0.059

EFW ≥ 85

percentile 9.3 (1.1-77.9) 0.038

TABLE 5. Multivariate analysis for factors independently associated with LGA newborn in GDM

*p-value < 0.05 indicates statistical signicance

Abbreviations: BMI = body mass index; BPD = biparietal diameter; HC = head circumference; AC = abdominal circumference; FL = femur

length; EFW = estimated fetal weight

TABLE 6. Estimated fetal weight (EFW) cuto percentile for predicting LGA newborn in GDM

Abbreviations: LGA = large-for-gestational age; GDM = gestational diabetes mellitus; PPV = positive predictive value

Cutoffpercentile PPV(%) Specicity(%) Sensitivity(%) NPV(%)

EFW ≥ 90

percentile 100 100 12.1 71.7

EFW ≥ 80

percentile 90.3 98.7 26.2 74.8

EFW ≥ 70

percentile 88.0 97.5 41.1 78.6

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DISCUSSION

is prospective cohort study demonstrated that

EFW obtained by ultrasound in the third trimester is

useful for predicting LGA newborn in women with

GDM, especially when all parameters (BPD, HC, AC,

and FL) were measured to calculate EFW. Considereing

these parameters individually, HC ≥ 90

percentile and

AC ≥ 90

percentile were able to predict LGA newborn,

with AC being the stronger associating parameter.

e present study found that EFW of ≥ 90

percentile

at 32-36 weeks’ gestation yielded a PPV of 100%, a

specicity of 100%, a NPV of 71.7%, and a sensitivity

of 12.2% in prediction of LGA at birth. Previous studies

reported lower PPV and specicity with higher NPV

and sensitivity,

9,14

whereas the most recent study showed

high specicity and low sensitivity, which is similar to

our study.

e disparity in ndings may be due to

dierences in study population, risk factors, and GDM

screening method. Inclusion criteria and the reference

growth chart used in other studies were dierent from

ours. Specically, one study included only women with

early GDM and pregestational diabetes,

and another

used a United States National Reference for Fetal Growth

that was published in 1996.

e study period during

gestation also varied, with one study performing ultrasound

during a gestational age range from 28 to 32

6,7

weeks’

gestation.

In addition, the previously cited studies used

EFW percentile cutos of 70

, 75

, and 80

percentile,

whereas the 90

percentile was used in this study.

e birth weight percentile used in this study was

based on 2004-2008 WHO Global Survey on Maternal

and Perinatal Health (WHOGS) data,

which recruited

pregnant women across most countries worldwide,

including ai women. is study, in addition, could be

more applicable in clinical practice in comparison to the

previous study

as the ultrasound was performed during

32-36 weeks’ gestation, just aer maximal acceleration

of fetal growth.

Among various formulas, Hadlock I and III perform

best in estimating fetal weight, with Hadlock I having

a lower mean absolute percentage error (MAPE).

11,17

Accordingly, Hadlock I formula was used in this study.

e present study reveals EFW as the best predictor

of LGA newborn in women with GDM. Among all

parameters evaluated in this study for estimating fetal

weight, AC was found to be the strongest individual

predictor of LGA newborn. is nding was similar to

that from a previous study which found that AC was the

parameter with highest sensitivity. is may be explained

by fat accumulation and liver glycogen storage when

fetal weight increases in late pregnancy.

is study suggests that the third trimester ultrasound

for fetal biometry should be performed in all women with

GDM to identify fetus at risk to be LGA at birth. EFW

using all parameters (AC, HC, BPD, and FL) provided

high PPV and high specicity. However, measuring only

AC may be acceptable when measuring all parameters

is not feasible due to improper fetal position or dicult

maternal habitus.

Despite a high PPV and a high specicity, EFW ≥ 90

percentile had a low sensitivity and low NPV to predict

LGA at birth. Lowering to 80

and 70

percentile cuto

values improved the sensitivity and NPV with a slightly

reduced PPV and specicity. Concerning gestational

age at examination, performance of ultrasonography

to predict an LGA neonate was comparable between

performing at 32-24 and 34-36 weeks’ gestation.

e strengths of the study include its prospective

cohort design, and the fact that the reference of EFW was

derived from an international standard. A few limitations

were also appreciated. Women’s glycemic control was

only assessed from the values of FBS and 2-h PP blood

sugar at antenatal visits, so blood sugar level trends

and uctuations were not examined. Moreover, GDM

management during the remaining time before birth

could aect the fetal growth.

is study may guide physicians to give special

attention for fetuses diagnosed with LGA from ultrasound

at a hospital in rural areas for delivery or referral planning

in advance.

CONCLUSION

Estimated fetal weight derived from the fetal biometry

measured in the third trimester had a high PPV and

specicity with a low to moderate sensitivity in predicting

LGA at birth.

ACKNOWLEDGEMENTS

e authors are grateful to medical personnel of the

Maternal-Fetal Medicine Unit, Department of Obstetrics

and Gynecology, Faculty of Medicine Siriraj Hospital,

Mahidol University for assistance with study.

Conict of interest declaration

All authors declare no conicts of interest.

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