Large Babies Despite Good Control in Type 1 Diabetes Pregnancies

Becky McCall

July 18, 2018

Despite good glycemic control with continuous glucose monitoring (CGM) and intensive insulin management throughout pregnancy, women with type 1 diabetes still had babies who were large for gestational age, shows a small retrospective study in US women.

"These data indicate that the prevalence of fetal overgrowth in type 1 diabetes remains alarmingly high, even with modern diabetes management," write Bethany Mulla, MD, from Beth Israel Deaconess Medical Center, Boston, Massachusetts, and coauthors in their article published in the June issue of Diabetes Technology and Therapeutics.

Moreover, the authors acknowledge that although hyperglycemia in pregnant mothers is likely central to fetal overgrowth, "factors other than glycemic control may contribute to large for gestational age [babies]."

These include "differences in placental function," which could contribute to macrosomia risk, or "the rising prevalence of obesity in the type 1 diabetes population."

Is Controlling Hyperglycemia Prior to Conception the Key?

The only association the authors saw related to gestational period was between higher first trimester mean glucose and higher estimated fetal weight percentile. "Our results suggest that fetal overgrowth may emerge earlier in pregnancy than previous reports," they observe.

Interestingly, these observational results suggesting that large for gestational age babies occur despite good glycemic control contrasts with results from the acclaimed CONCEPTT study, reported by Medscape Medical News last year.

CONCEPTT was an international randomized controlled trial of CGM in 325 participants (pregnant mothers or those planning pregnancies) with type 1 diabetes. It found that the superior glycemic control with CGM halved the risk of large for gestational age babies versus finger prick tests.

Zoe Stewart, MBBS, PhD, from the University of Cambridge, UK, and coauthor of the CONCEPTT study, gave her views on these new findings by Mulla and colleagues.

"We know that reducing hyperglycemia can improve outcomes from the CONCEPTT study and that certain patterns of glycemic control might be associated with a greater risk of macrosomia," she said.

"But these results confirm previous findings that abnormal fetal growth patterns start much earlier in pregnancy than initially thought, so close attention should be paid to optimizing conditions prior to pregnancy."

However, she also pointed out that the study is small and retrospective and its results should therefore be interpreted with caution.

"There is limited information on maternal glucose control in this study; it may be that their metric is too crude and does not adequately characterize maternal glucose control," she noted.

Also, "there was no association found between mean glucose and fetal growth in the other trimesters, which differs from what others have found."

Nevertheless, she acknowledged that — as suggested by Mulla and colleagues — it could be that "placental factors, weight gain, obesity, or other factors had a greater influence on fetal growth than glucose variability."

No Correlation Between Glycemic Variability and Fetal Weight  

Mulla and colleagues conducted the retrospective cohort study in 41 pregnant women with type 1 diabetes and used the CGM data to calculate glycemic variability over a median 7-day interval in each trimester.

Data from medical records were used for fetal biometry, birth weight, and perinatal complications. All the women received multispecialty care at the Beth Israel Deaconess Medical Center.

"To our knowledge, we are the first to examine detailed prenatal ultrasound data in pregnancies complicated by type 1 diabetes," they observe.

Participants used a range of different CGM devices, and as such, glycemic variability (measured by the coefficient of variation of glucose) was considered to be the most reliable measure to ensure consistency across different CGM systems. Other studies have used "time in [glucose] range", but this is not consistent across different CGM systems.

Results showed that mean HbA1c in the first, second, and third trimester was 6.5%, 6.1%, and 6.4%, respectively; 63% of infants were large for gestational age.

Estimated fetal weight and abdominal circumference from ultrasounds increased during pregnancy in a manner that was consistent with accelerated prenatal growth.

Average birth weight was 4 kg (8.8 Ibs) and mean birth weight percentile was 93rd. Overall,  37% of infants were admitted to the neonatal intensive care unit with hypoglycemia.

There were no significant correlations between trimester-specific glycemic variability and estimated fetal weight, abdominal circumference, and birth weight, adjusted for maternal age.

"Our analysis of the timing of accelerated growth across abdominal circumference percentile and estimated fetal weight percentile may help predict when fetal overgrowth starts to occur, which may identify important therapeutic windows for future intervention studies," say Mulla and coauthors.

Adverse Outcomes Common With Type 1 Diabetes in Pregnancy

Meanwhile, Peter Hammond, MD, Harrogate and District NHS Foundation Trust, UK, noted, "There is no comparator group of women not using CGM, so while the rate of large for gestational age babies is disappointingly high, this study does not address whether those using CGM have better outcomes than those not using it."

"These data show there is more to do in terms of reducing the incidence of large for gestational age babies and that glucose control alone may not be the answer."

He observed that, even with significant developments in diabetes technologies including use of CGM and insulin pumps, adverse outcomes for women with type 1 diabetes and their babies remain common.

"From the information we have available, the best we can do is try to assist women to achieve as close to normal glucose control as possible. Regular self-glucose testing, education, dietary advice, and close clinical contact are still the most important factors, with CGM, pumps, and other technologies being useful adjuncts for some women."

Mulla and Stewart have reported no relevant financial relationships. Hammond reports receiving honoraria for speaking and advisory board attendance from Medtronic, Roche, and Abbott.

Diabetes Technol Ther. 2018;20:413-419. Abstract

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