Evaluation of Fetal Liver Volume by Tridimensional Ultrasound in Women With Gestational Diabetes Mellitus

Evaluation of Fetal Liver Volume by Tridimensional Ultrasound in Women With Gestational Diabetes Mellitus

Obstetrics Evaluation of Fetal Liver Volume by Tridimensional Ultrasound in Women With Gestational Diabetes Mellitus Marie-Christine Dubé, PhD,1,2 Ma...

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Obstetrics

Evaluation of Fetal Liver Volume by Tridimensional Ultrasound in Women With Gestational Diabetes Mellitus Marie-Christine Dubé, PhD,1,2 Mario Girard, RT,3 Anne-Sophie Morisset, MSc,2 André Tchernof, PhD,2,4 S. John Weisnagel, MD,1,2,5 Emmanuel Bujold, MD, MSc3 1

Diabetes Research Unit, Université Laval Medical Center, Québec City, Québec

2

Molecular Endocrinology and Genomics, Université Laval Medical Center, Québec City, Québec

3

Department of Obstetrics and Gynecology, Faculty of Medicine, Université Laval, Québec City, Québec

4

Department of Nutrition, Université Laval, Québec City, Québec

5

Division of Kinesiology, Faculty of Medicine, Université Laval, Québec City, Québec

Abstract

Résumé

Objective: To evaluate the effect of gestational diabetes mellitus (GDM) on fetal liver growth during the third trimester.

Objectif : Évaluer l’effet du diabète sucré gestationnel (DSG) sur la croissance du foie fœtal au cours du troisième trimestre.

Methods: We performed a longitudinal study of pregnant women recruited at the time of GDM screening (24 to 28 weeks of gestation), with follow-up visits at 32 weeks, 36 weeks, and delivery. Women with GDM were followed with nutritional recommendations and insulin when necessary according to the Canadian Diabetes Association guidelines. Fetal liver volume was evaluated using 3-D ultrasound at each antenatal visit, and fetal liver growth was compared between women with and without GDM.

Méthodes : Nous avons mené une étude longitudinale auprès de femmes enceintes recrutées au moment du dépistage du DSG (entre 24 et 28 semaines de gestation), le tout s’accompagnant de consultations de suivi à 32 semaines, à 36 semaines et au moment de l’accouchement. Les femmes présentant un DSG ont fait l’objet d’un suivi au moyen de recommandations nutritionnelles et d’insuline, au besoin, conformément aux lignes directrices de l’Association canadienne du diabète. Le volume hépatique fœtal a été évalué par échographie 3-D à l’occasion de chacune des consultations prénatales; de plus, la croissance du foie fœtal chez les femmes présentant un DSG a été comparée à celle qui était constatée chez les femmes ne présentant pas ce diabète.

Results: Twenty-seven women were recruited, 10 with normal glucose tolerance (NGT) and 17 with confirmed GDM, five who required insulin and 12 who were treated by diet only. We found no difference in fetal liver volume between groups at any of the three visits, and median birth weight was also similar between groups. On the other hand, we found a strong correlation between fetal liver volume at 36 weeks’ gestation and birth weight (ρ = 0.61, P < 0.001). Conclusions: In our preliminary study, we found that fetal liver volume could be a strong predictor of infant birth weight independent of GDM status. This suggests that fetal liver volume of offspring of women with NGT is similar to that of offspring of women with GDM treated following recommended targets. Larger studies are required.

J Obstet Gynaecol Can 2011;33(11):1095–1098 Key Words: 3-D ultrasound, fetal liver, gestational diabetes Competing Interests: None declared. Received on December 10, 2010 Accepted on February 8, 2011

Résultats : Vingt-sept femmes ont été recrutées : 10 qui présentaient une tolérance normale au glucose (TNG) et 17 qui présentaient un DSG confirmé (cinq qui ont nécessité de l’insuline et 12 qui n’ont été traitées que par modification du régime alimentaire). Nous n’avons constaté aucune différence en matière de volume hépatique fœtal entre les groupes (dans le cadre de l’une ou l’autre des trois consultations) et le poids de naissance médian s’est également avéré similaire d’un groupe à l’autre. Par contre, nous avons constaté une forte corrélation entre le volume hépatique fœtal à 36 semaines de gestation et le poids de naissance (ρ = 0,61, P < 0,001). Conclusions : Dans le cadre de notre étude préliminaire, nous avons constaté que le volume hépatique fœtal pouvait constituer un facteur prédictif solide du poids de naissance, indépendamment du statut quant au DSG. Cela laisse entendre que le volume hépatique fœtal de la progéniture des femmes présentant une TNG est similaire à celui de la progéniture des femmes présentant un DSG qui sont traitées conformément aux cibles recommandées. La tenue d’études de plus grande envergure s’avère requise.

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INTRODUCTION

T

he incidence of gestational diabetes mellitus is constantly increasing, as women are increasingly older and heavier at the time of conception.1 Management of GDM by a multidisciplinary team with serial assessment of glucose levels and sonographic factors helps to prevent obstetrical and neonatal complications.2 Follow-up using growth velocity evaluated by abdominal perimeter and hepatic length has recently been proposed as a novel monitoring tool.3 Anderson et al. found that fetal hepatic length was a reproducible measurement that was not affected by maternal age or BMI and could contribute to effective management of GDM.3 Since 3-D ultrasound could provide a better appreciation of fetal liver volume than hepatic length, we aimed to evaluate the feasibility of such a technique and to investigate GDM-related differences in fetal liver growth in the third trimester of pregnancy. MATERIAL AND METHODS

This preliminary study included 27 pregnant women recruited from March 2008 to September 2009 at the Centre Mère-Enfant of the Centre Hopitalier Universitaire de Québec. Women were screened for GDM with a 75-g oral glucose tolerance test between 24 and 28 weeks of gestation. The analysis included 17 women with a diagnosis of GDM according to the Canadian Diabetes Association guidelines4 and a control group of 10 women with normal glucose tolerance. Women with GDM were followed with nutritional recommendations (n = 12) and insulin treatment (n = 5) when necessary according to the CDA guidelines. Pre-pregnancy BMI was calculated from self-reported pre-pregnancy weight and height. Women were invited to undergo an evaluation of fetal liver volume using 3-D ultrasound at GDM screening at 32 weeks and at 36 weeks of gestation. Three-dimensional ultrasound was carried out with a Voluson E8 Expert system (GE Healthcare Inc., Milwaukee WI). Three-dimensional sweeps of the entire fetal abdomen were performed and analyzed by virtual organ computer-aided analysis (VOCAL) software (GE Healthcare Inc., Milwaukee WI) using 12 sections at 15-degree rotations from each other. The ultrasonographer was blinded to the study group when performing the 3-D ultrasound. The same ultrasonographer, still blinded

ABBREVIATIONS CDA

Canadian Diabetes Association

GDM

gestational diabetes

NGT

normal glucose tolerance

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to all clinical data, measured all fetal hepatic volumes in the same week at the end of the study to ensure optimal reproducibility. Delivery data and newborn measurements (weight, length, and cranial and thoracic perimeters) were collected from hospital charts. Wilcoxon tests were used to test group differences for variables of interest (P < 0.05). The Spearman correlation coefficient was computed to test the correlation between birth weight and fetal liver volume. This study was approved by the Centre Hopitalier Universitaire de Québec Ethics Review Board, and all subjects provided written informed consent before inclusion in the study. RESULTS

Maternal measurements at diagnosis, 32 weeks, and 36 weeks of gestation are shown in Table 1. There were no significant differences in the means of maternal age, pre-pregnancy BMI (near-significant, however), or parity between women with and without GDM. Length of gestation was significantly shorter and the proportion of Caesarean sections was significantly higher in women with GDM. The groups were comparable in the incidence of adverse outcomes and mean birth weight. The group of women with GDM had normal obstetrical outcomes overall; only three participants had a macrosomic fetus, and none had shoulder dystocia or neonatal hypoglycemia. Fetal and neonatal measurements are shown in Table 2. There was no significant difference between groups in anthropometric measurements at any antenatal visit or at delivery (values adjusted for gestational age). Serial 3-D ultrasounds showed that liver volume increased similarly in women with GDM and with NGT. Moreover, differences in liver volume between each ultrasound (diagnosis vs. 32 vs. 36 weeks of pregnancy) were similar between groups. However, we found a non-significant association between fetal liver volume at diagnosis and birth weight (ρ = 0.35, P = 0.08), a significant association between fetal liver volume at 32 weeks of gestation and birth weight (ρ = 0.42, P = 0.03), and a stronger correlation between fetal liver volume at 36 weeks of gestation and birth weight (ρ = 0.61, P < 0.001) (Figure). DISCUSSION

Results from the current study show that fetal liver growth is similar in offspring of women with and without GDM when those with GDM are treated following current practice guidelines. This finding is consistent with the clinical context in that women with GDM had few adverse obstetrical outcomes, likely as a result of the appropriate interventions

Evaluation of Fetal Liver Volume by Tridimensional Ultrasound in Women With Gestational Diabetes Mellitus

Table 2. Fetal and infant birth characteristics

Table 1. Maternal characteristics Variables

NGT

Subject, n

GDM

P

10

17

64.8 ± 12.4

77.4 ± 22.2

NS

Pre-pregnancy BMI, kg/m2

23.8 ± 3.80

29.5 ± 8.30

0.05

Parity, n (%) 3 (30)

7 (41)

1

5 (50)

5 (29)

2

2 (20)

4 (24)

3

0 (0)0

1 (6)0

NGT

NS

Liver volume, mL Weight, g

052 ± 24

NS

1196 ± 529

NS

261 ± 11

249 ± 48

NS

Thoracic perimeter, mm

238 ± 19

233 ± 52

NS

53 ± 3

050 ± 11

NS

089 ± 17

090 ± 16

NS

Femur length, mm Liver volume, mL Weight, g

2043 ± 259

2072 ± 290

NS

Cranial perimeter, mm

297 ± 10

297 ± 11

NS

294 ± 18

296 ± 19

NS

62 ± 3

61 ± 4

NS NS

31.3 ± 3.40

32.4 ± 4.30

NS

Thoracic perimeter, mm

Weight, kg

74.7 ± 13.6

85.9 ± 22.8

NS

Femur length, mm

BMI, kg/m

27.4 ± 4.10

32.8 ± 8.40

0.07

36 weeks’ gestation Liver volume, mL

32 weeks’ gestation Weight, kg

77.8 ± 14.8

88.6 ± 24.6

NS

BMI, kg/m

28.6 ± 4.50

33.8 ± 9.30

NS

Vaginal/Caesarean section, n

7/3

9/8

NS

Pregnancy duration, weeks

40.0 ± 0.90

38.4 ± 1.80

0.01

1/9

14/3

< 0.01

Delivery

Male/female, n

054 ± 16 1197 ± 201

Cranial perimeter, mm

Age, yrs

2

P

32 weeks’ gestation

Diagnosis

2

GDM

Diagnosis

Pre-pregnancy weight, kg

0

Variables

NS: not significant. Values are mean ± SD. P < 0.05 is considered statistically significant.

128 ± 31

124 ± 23

2881 ± 287

2828 ± 330

NS

Cranial perimeter, mm

318 ± 80

322 ± 11

NS

Thoracic perimeter, mm

332 ± 17

329 ± 20

NS

68 ± 3

67 ± 3

NS

Weight, g

Femur length, mm Changes in hepatic volume, mL 32 to 28 weeks

035 ± 17

036 ± 26

NS

36 to 32 weeks

039 ± 25

029 ± 22

NS

36 to 28 weeks

075 ± 37

070 ± 35

NS

Weight, g

3645 ± 562

3276 ± 692

NS*

Length, cm

52.2 ± 2.8

50.6 ± 2.9

NS*

Cranial perimeter, cm

35.0 ± 1.2

33.9 ± 2.3

NS*

Thoracic perimeter, cm

34.8 ± 2.5

32.5 ± 3.2

NS*

Delivery

NS: not significant. Values are mean ± SD. P < 0.05 is considered statistically significant; no values reached statistical significance. *Adjusted for gestational age.

with diet and possibly insulin. On the other hand, our results suggest that third trimester evaluation of 3-D fetal liver volume could still be useful in the follow-up of women with GDM because its measurement at 36 weeks was strongly associated with infant birth weight and fetal macrosomia. Although the study sample was small, our results suggest that appropriate management of GDM could be associated with normal fetal liver and overall growth. Our results differ from those of Mirghani et al.,5 who suggested that fetal liver length was increased in the second trimester among women with GDM because the liver is more sensitive and responsive to maternal glucose levels, or because major increases in liver size occur early in pregnancy. This discrepancy may be explained by the different trimesters studied (second vs. third) and by the parameters measured (length vs. volume). Unlike Mirghani

et al.,5 we recorded pregnancy outcomes and correlated them with fetal liver volume. In 2003, Boito et al.6 suggested that fetal liver volume assessed by 3-D ultrasound was associated with maternal glycemic control and played a role in fetal growth acceleration in pregnancies of type 1 diabetic women. Liver volume was also significantly higher in the fetuses of these women compared with control subjects. Again, discrepancies between our findings and theirs may be related to the populations studied (women with GDM vs. type 1 diabetes) and metabolic control (often more difficult in type 1 diabetic pregnancies). This may also suggest that an intervention following CDA guidelines, beginning after the second trimester, could be effective in decreasing excess fetal growth and in reducing or stabilizing fetal hepatic volume. However, because of the limited number of subjects and the absence of a control NOVEMBER JOGC NOVEMBRE 2011 l 1097

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Correlation between birth weight and fetal liver volume at 36 weeks’ gestation in women with GDM (black squares) and NGT (empty circles) (NGT group ρ = 0.63, P = 0.07; GDM group ρ = 0.56, P < 0.05; both groups ρ = 0.61, P < 0.01).

explore the usefulness of measuring fetal liver volume in the estimation of fetal weight and the management of women with GDM. ACKNOWLEDGEMENTS

We would like to thank all the women who took part for their valuable contribution and the obstetrical diabetes clinic team at the Centre Mère-Enfant of Centre Hospitalier Universitaire de Québec for their support. This study was supported by the research funds of the late Dr André Nadeau and the Chaire de recherche en périnatalité Jeanne et Jean-Louis Lévesque. André Tchernof is the recipient of a Senior Scholarship from Fonds de la Recherche en Santé du Québec. Anne-Sophie Morisset is the recipient of a doctoral scholarship from the Canadian Institutes of Health Research. Dr Emmanuel Bujold is supported by a Clinician Scientist Award from the Canadian Institutes of Health Research and by the Jeanne and Jean-Louis Lévesque Perinatal Research Chair at Université Laval. diabetic group without intervention, further studies are warranted to confirm and better document the observation reported herein. We plan to undertake a larger replicating study with measures throughout pregnancy to better understand the relationship between metabolic control and fetal liver volume. CONCLUSIONS

Three-dimensional evaluation of fetal volume at the end of the third trimester correlates with birth weight, and thus could be useful in estimating birth weight prenatally. We did not find differences in liver volume or fetal weight between women with NGT and those with GDM treated following CDA guidelines, suggesting that the multidisciplinary approach to GDM treatment aiming at tight glycemic control may have contributed to normal fetal liver volume and birth weight. These findings, all from a preliminary study, support the undertaking of a larger study to further

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REFERENCES 1. Ferrara A. Increasing prevalence of gestational diabetes mellitus: a public health perspective. Diabetes Care 2007;30(Suppl 2):S141–S146. 2. Langer O. Ultrasound biometry evolves in the management of diabetes in pregnancy. Ultrasound Obstet Gynecol 2005;26:585–95. 3. Anderson NG, Notley E, Graham P, McEwing R. Reproducibility of sonographic assessment of fetal liver length in diabetic pregnancies. Ultrasound Obstet Gynecol 2008;31:529–34. 4. Canadian Diabetes Association. 2008 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2008;32(Suppl 1):S1–S201. Available at: http://www.diabetes.ca. Accessed September 9, 2011. 5. Mirghani H, Zayed R, Thomas L, Agarwal M. Gestational diabetes mellitus: fetal liver length measurements between 21and 24 weeks’ gestation. J Clin Ultrasound 2007;35:34–7. 6. Boito SM, Struijk PC, Ursem NT, Stijnen T, Wladimiroff, JW. Assessment of fetal liver volume and umbilical venous volume flow in pregnancies complicated by insulin-dependent diabetes mellitus. BJOG 2003;110:1007–13.