Hyperglycemia and adverse pregnancy outcomes.
BACKGROUND
It is controversial whether maternal hyperglycemia less severe than that in diabetes mellitus is associated with increased risks of adverse pregnancy outcomes.


METHODS
A total of 25,505 pregnant women at 15 centers in nine countries underwent 75-g oral glucose-tolerance testing at 24 to 32 weeks of gestation. Data remained blinded if the fasting plasma glucose level was 105 mg per deciliter (5.8 mmol per liter) or less and the 2-hour plasma glucose level was 200 mg per deciliter (11.1 mmol per liter) or less. Primary outcomes were birth weight above the 90th percentile for gestational age, primary cesarean delivery, clinically diagnosed neonatal hypoglycemia, and cord-blood serum C-peptide level above the 90th percentile. Secondary outcomes were delivery before 37 weeks of gestation, shoulder dystocia or birth injury, need for intensive neonatal care, hyperbilirubinemia, and preeclampsia.


RESULTS
For the 23,316 participants with blinded data, we calculated adjusted odds ratios for adverse pregnancy outcomes associated with an increase in the fasting plasma glucose level of 1 SD (6.9 mg per deciliter [0.4 mmol per liter]), an increase in the 1-hour plasma glucose level of 1 SD (30.9 mg per deciliter [1.7 mmol per liter]), and an increase in the 2-hour plasma glucose level of 1 SD (23.5 mg per deciliter [1.3 mmol per liter]). For birth weight above the 90th percentile, the odds ratios were 1.38 (95% confidence interval [CI], 1.32 to 1.44), 1.46 (1.39 to 1.53), and 1.38 (1.32 to 1.44), respectively; for cord-blood serum C-peptide level above the 90th percentile, 1.55 (95% CI, 1.47 to 1.64), 1.46 (1.38 to 1.54), and 1.37 (1.30 to 1.44); for primary cesarean delivery, 1.11 (95% CI, 1.06 to 1.15), 1.10 (1.06 to 1.15), and 1.08 (1.03 to 1.12); and for neonatal hypoglycemia, 1.08 (95% CI, 0.98 to 1.19), 1.13 (1.03 to 1.26), and 1.10 (1.00 to 1.12). There were no obvious thresholds at which risks increased. Significant associations were also observed for secondary outcomes, although these tended to be weaker.


CONCLUSIONS
Our results indicate strong, continuous associations of maternal glucose levels below those diagnostic of diabetes with increased birth weight and increased cord-blood serum C-peptide levels.
Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. bem@northwestern.edu
Metzger
Boyd E
BE
Lowe
Lynn P
LP
Dyer
Alan R
AR
Trimble
Elisabeth R
ER
Chaovarindr
Udom
U
Coustan
Donald R
DR
Hadden
David R
DR
McCance
David R
DR
Hod
Moshe
M
McIntyre
Harold David
HD
Oats
Jeremy J N
JJ
Persson
Bengt
B
Rogers
Michael S
MS
Sacks
David A
DA
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D002585:Cesarean Section / Q000706:statistics & numerical data; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005320:Fetal Macrosomia / Q000453:epidemiology; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000150:complications*; D007003:Hypoglycemia / Q000453:epidemiology / Q000209:etiology; D007231:Infant, Newborn; D016017:Odds Ratio; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood; D011256:Pregnancy Outcome
D001786:Blood Glucose; D002096:C-Peptide