Mild Gestational Diabetes Mellitus and Long-Term Child Health

Mark B. Landon; Madeline Murguia Rice; Michael W. Varner; Brian M. Casey; Uma M. Reddy; Ronald J. Wapner; Dwight J. Rouse; Joseph R. Biggio; John M. Thorp; Edward K. Chien; George Saade; Alan M. Peaceman; Sean C. Blackwell; J. Peter VanDorsten

doi:10.2337/dc14-2159

Clinical Care/Education/Nutrition/Psychosocial Research

Mild Gestational Diabetes Mellitus and Long-Term Child Health

Mark B. Landon¹ ⇑,
Madeline Murguia Rice²,
Michael W. Varner³,
Brian M. Casey⁴,
Uma M. Reddy⁵,
Ronald J. Wapner⁶,
Dwight J. Rouse⁷,
Joseph R. Biggio Jr.⁸,
John M. Thorp⁹,
Edward K. Chien¹⁰,
George Saade¹¹,
Alan M. Peaceman¹²,
Sean C. Blackwell¹³ and
J. Peter VanDorsten¹⁴
for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network

¹Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, OH
²George Washington University Biostatistics Center, Washington, DC
³Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, UT
⁴Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX
⁵Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD
⁶Department of Obstetrics and Gynecology, Columbia University, New York, NY
⁷Department of Obstetrics and Gynecology, Brown University, Providence, RI
⁸Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL
⁹Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC
¹⁰Department of Obstetrics and Gynecology, Case Western Reserve University–MetroHealth Medical Center, Cleveland, OH
¹¹Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX
¹²Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL
¹³Department of Obstetrics and Gynecology, University of Texas Health Science Center at Houston–Children’s Memorial Hermann Hospital, Houston, TX
¹⁴Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC

Corresponding author: Mark B. Landon, mark.landon{at}osumc.edu.

Diabetes Care 2015 Mar; 38(3): 445-452. https://doi.org/10.2337/dc14-2159

Article Figures & Tables

Tables

Table 1

Maternal baseline characteristics by mild GDM treatment group

Characteristic	Treated (n = 264)	Untreated (n = 236)	P value^†
Age (years)	29.2 ± 5.2	28.7 ± 5.5	0.31
Glucose after 50-g glucose-loading test (mg/dL)	158.2 ± 15.3	158.4 ± 15.4	0.90
Glucose in 3-h OGTT (mg/dL)
Fasting glucose	86.9 ± 5.7	86.5 ± 5.6	0.30
1-h OGTT	191.0 ± 21.2	192.9 ± 19.1	0.13
2-h OGTT	172.5 ± 21.4	172.5 ± 18.5	0.79
3-h OGTT	138.2 ± 29.1	133.7 ± 31.6	0.15
BMI at entry (kg/m²)	30.2 ± 5.1	30.6 ± 5.4	0.44
Gestational age at entry (weeks)	28.8 ± 1.6	29.0 ± 1.4	0.34
Race/ethnicity			0.53
Non-Hispanic black	28 (10.6)	27 (11.4)
Non-Hispanic white	84 (31.8)	65 (27.5)
Hispanic	144 (54.6)	132 (55.9)
Other	8 (3.0)	12 (5.1)

Data are mean ± SD and n (%). OGTT, oral glucose tolerance test.
↵† Based on the χ² test for categorical variables and Wilcoxon rank sum test for continuous variables.

Table 2

Birth outcomes by mild GDM treatment group, overall and by sex

	Overall			Male			Female
Outcome	Treated (n = 264)	Untreated (n = 236)	P value^†	Treated (n = 140)	Untreated (n = 121)	P value^†	Treated (n = 124)	Untreated (n = 115)	P value^†
Gestational age at delivery (weeks)	38.9 ± 1.8	39.0 ± 1.7	0.30	38.8 ± 1.9	39.2 ± 1.7	0.02	39.1 ± 1.6	38.9 ± 1.7	0.33
Birth weight (g)	3,283.2 ± 491.4	3,468.3 ± 546.4	<0.001	3,285.5 ± 507.2	3,557.6 ± 532.5	<0.001	3,280.6 ± 475.0	3,375.0 ± 547.5	0.08
Macrosomia (>4,000 g)	12 (4.6)	32 (13.6)	<0.001	7 (5.0)	21 (17.5)	0.001	5 (4.0)	11 (9.6)	0.09
Fat mass (g)	421.3 ± 173.3	482.9 ± 210.2	<0.001	407.3 ± 152.7	502.0 ± 213.8	<0.001	437.1 ± 193.3	463.3 ± 205.6	0.16
Fat mass >90th percentile	9 (3.8)	36 (16.7)	<0.001	1 (0.8)	20 (18.4)	<0.001	8 (7.2)	16 (15.1)	0.06
Cord C-peptide (units)	1.2 ± 0.9	1.4 ± 1.5	0.06	1.1 ± 0.7	1.4 ± 1.8	0.06	1.3 ± 1.0	1.3 ± 1.0	0.48
Cord C-peptide >95th percentile	35 (14.8)	48 (22.4)	0.04	15 (12.0)	25 (22.3)	0.03	20 (17.9)	23 (22.6)	0.39
Size for gestational age			0.003			0.003			0.35
Small	16 (6.1)	9 (3.8)		10 (7.1)	4 (3.3)		6 (4.8)	5 (4.4)
Appropriate	231 (87.5)	189 (80.4)		123 (87.9)	95 (79.2)		108 (87.1)	94 (81.7)
Large	17 (6.4)	37 (15.7)		7 (5.0)	21 (17.5)		10 (8.1)	16 (13.9)

Data are mean ± SD and n (%).
↵† Based on the χ² or Fisher exact test for categorical variables and Wilcoxon rank sum test for continuous variables.

Table 3

Follow-up outcomes (binomial) by mild GDM treatment group, overall and by sex

Outcome	Overall			Male			Female
Outcome	Treated	Untreated	Adjusted RR (95% CI)^*	Treated	Untreated	Adjusted RR (95% CI)^*	Treated	Untreated	Adjusted RR (95% CI)^*
BMI ≥95th percentile for age and sex	55 (20.8)	54 (22.9)	0.94 (0.68–1.28)	35 (25.0)	30 (24.8)	1.04 (0.70–1.55)	20 (16.1)	24 (20.9)	0.79 (0.48–1.33)
BMI ≥85th percentile for age and sex	86 (32.6)	91 (38.6)	0.88 (0.71–1.10)	49 (35.0)	46 (38.0)	0.94 (0.70–1.27)	37 (29.8)	45 (39.1)	0.81 (0.59–1.13)
Waist circumference >90th percentile for age, sex, and race/ethnicity	31 (11.7)	27 (11.4)	1.05 (0.65–1.69)	18 (12.9)	15 (12.4)	1.06 (0.56–2.00)	13 (10.5)	12 (10.4)	1.02 (0.49–2.13)
Impaired fasting glucose ≥100 mg/dL^†	12 (5.7)	13 (7.2)	0.76 (0.36–1.62)	9 (8.4)	2 (2.2)	3.50 (0.78–15.7)	3 (2.9)	11 (12.1)	0.24 (0.07–0.82)^‡
Elevated triglycerides ≥100 mg/dL 4–9 years; ≥130 mg/dL 10 years	38 (18.2)	29 (16.0)	1.11 (0.71–1.72)	18 (16.8)	11 (12.2)	1.31 (0.66–2.62)	20 (19.6)	18 (19.8)	0.99 (0.56–1.75)
Low HDL cholesterol <40 mg/dL	27 (13.0)	22 (12.2)	1.03 (0.61–1.76)	13 (12.2)	8 (8.9)	1.31 (0.57–3.00)	14 (13.9)	14 (15.4)	0.88 (0.45–1.73)
Hypertension ≥95th percentile or age, sex, and height	30 (11.5)	23 (9.8)	1.23 (0.74–2.05)	20 (14.7)	13 (10.7)	1.41 (0.74–2.71)	10 (8.1)	10 (8.7)	0.97 (0.42–2.23)

Data are n (%) unless otherwise indicated. RR, relative risk.
↵* All models adjusted for race/ethnicity and log maternal baseline BMI, except waist circumference >90th percentile for age, sex, and race/ethnicity was adjusted only for log maternal baseline BMI. The data presented by child sex are based on multivariable adjusted models that included treatment group, sex, and a treatment group-by-sex interaction term.
↵† P = 0.007 for interaction between treatment group and sex.
↵‡ P = 0.02.

Table 4

Follow-up outcomes (continuous) by mild GDM treatment group, overall and by sex

	Adjusted mean (95% CI)
	Overall		Male		Female
Outcome	Treated	Untreated	Treated	Untreated	Treated	Untreated
BMI z score based on BMI percentile for age and sex	0.33 (0.15–0.51)	0.36 (0.17–0.55)	0.36 (0.12–0.60)	0.34 (0.09–0.60)	0.30 (0.05–0.56)	0.37 (0.10–0.64)
Waist circumference (cm)^*	57.28 (56.30–58.27)	57.56 (56.54–58.60)	57.69 (56.40–59.02)	58.02 (56.65–59.43)	56.87 (55.52–58.26)	57.10 (55.68–58.57)
Fasting glucose (mg/dL)^†	88.41 (87.33–89.50)	88.67 (87.56–89.78)	89.64 (88.25–91.04)	87.71 (86.25–89.18)	87.11 (85.65–88.57)	89.62 (88.12–91.12)^‡
HOMA-IR^*^§^\|\|	1.05 (0.94–1.17)	1.10 (0.99–1.24)	1.06 (0.92–1.22)	0.95 (0.81–1.10)	1.05 (0.90–1.22)	1.30 (1.11–1.52)^¶
Triglycerides (mg/dL)^*	58.91 (54.82–63.30)	57.38 (53.33–61.73)	57.99 (52.83–63.67)	54.85 (49.73–60.51)	60.15 (54.57–66.31)	60.20 (54.45–66.56)
HDL cholesterol (mg/dL)	54.35 (52.42–56.28)	55.10 (53.16–57.05)	55.06 (52.60–57.53)	56.65 (54.05–59.26)	53.42 (50.81–56.04)	53.43 (50.77–56.09)
Systolic BP (mmHg)	100 (98–101)	100 (98–101)	101 (99–103)	100 (98–102)	99 (97–101)	99 (97–101)
Diastolic BP (mmHg)	60 (59–61)	59 (58–60)	60 (59–62)	60 (59–62)	61 (59–62)	58 (57–60)^¶

All models adjusted for race/ethnicity and log maternal baseline BMI; log waist circumference also adjusted for child’s sex (overall model) and child’s age in months; log triglycerides also adjusted for child’s age in months; and systolic and diastolic BPs also adjusted for child’s sex (overall model), child’s age in months, and child’s height. The data presented by child sex are based on multivariable adjusted models that included treatment group, sex, and a treatment group-by-sex interaction term. BP, blood pressure.
↵*Back transformation of the log value.
↵†P = 0.002 for interaction between treatment group and sex.
↵‡P = 0.01.
↵§Calculated as (fasting glucose [mmol/L] × fasting insulin [μU/mL]) / 22.5 (20).
↵||P = 0.02 for interaction between treatment group and sex.
↵¶P = 0.04.