Elevated but ‘normal’ HbA1c increases odds for neonatal hypoglycemia
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An elevated HbA1c that is still in the prediabetes range was associated with increased risk for neonatal hypoglycemia, particularly among white infants born prematurely, data show.
“Maternal diabetes, including gestational diabetes, typically diagnosed by an oral glucose tolerance test in the second trimester, is a known risk factor for neonatal hypoglycemia and infants born large for gestational age,” Venkatesh Sampath, MD, MRCPCh, professor of pediatrics, neonatologist, medical director of the neonatal diseases research program at Children’s Mercy Kansas City, told Healio. “Clinicians have suspected that some infants born to mothers without overt diabetes or gestational diabetes may still have an increased risk for hypoglycemia and tend to be larger at birth. However, this has not been systematically evaluated during pregnancy, especially in the context of long-term glucose control in pregnant women. In this study, we wanted to evaluate if long-term maternal glucose homeostasis in the normal range can impact neonatal outcomes such as birth weight and early hypoglycemia. Furthermore, we wanted to investigate whether these relationships are race dependent.”
Glucose data for mothers, infants
In a retrospective chart review published in The Journal of Pediatrics, Sampath and colleagues analyzed data from 4,769 infants born at 34 weeks’ gestation or later at Hurley Medical Center from 2015 to April 2018, including 21,482 blood glucose measurements (mean gestational age at delivery, 37.3 weeks; 63% delivered vaginally; 54% white; 50% male). HbA1c values were available for 4,391 mothers with 6,312 measurements during pregnancy. Mothers and infants were stratified into four groups: mothers without documented pregnancy conditions; prenatal exposure to beta-blockers; prenatal exposure to diabetes; or prenatal exposure to beta-blockers and diabetes.
Within the cohort, 4.9% of infants were born large for gestational age.
Among infants born to mothers with no documented pregnancy conditions, researchers observed a relationship between pregnancy HbA1c level and birth weight for white infants (n = 1,756; P < .001) and black infants (n = 1,872; P = .002).
Researchers found that, overall, third trimester HbA1c was higher among mothers whose infants had hypoglycemia vs. mothers whose infants did not have hypoglycemia (mean, 5.3% vs. 5.1%; P < .001), with the trend manifesting at a lower HbA1c level for infants born to white mothers (mean HbA1c, 5.2%) vs. black mothers (mean HbA1c, 5.4%; P = .04)
In multiple logistic regression analyses adjusted for confounding variables, HbA1c, white race, premature birth and cesarean section delivery increased odds for neonatal hypoglycemia, whereas being born appropriate size for gestation age decreased odds for hypoglycemia.
Among infants born to white mothers, increases in HbA1c levels from 4.8% to 6% increased the risk for hypoglycemia from 25% to 48% in late preterm, and from 12% to 22% in term deliveries. Among infants born to black mothers, the same maternal HbA1c range increased hypoglycemia risk from 15% to 26% in late preterm and from 5% to 10% in deliveries.
Additionally, each 0.1% increase in HbA1c levels between 4.8% and 6% increased the odds of neonatal hypoglycemia by 6.4% among blank infants (P = .01) and by 12% among white infants (P < .001).
Compared with infants born to mothers with no documented conditions, odds for neonatal hypoglycemia were 1.7 for infants exposed to beta-blockers, 2.1 for infants exposed to diabetes, and 3.1 for infants exposed to beta-blockers and diabetes.
“We found that maternal HbA1c levels — even within the range often considered acceptable during pregnancy — influenced the incidence of neonatal hypoglycemia and increased birth weight, especially among infants born to white mothers,” Sampath said. “In late-preterm infants, we found that an HbA1c of at least 5.2% is a risk factor for neonatal hypoglycemia. This linear relationship and strength of the relationship was certainly surprising to our team.”
Closer monitoring needed
Sampath said the findings, if confirmed in other studies, could suggest tighter glucose regulation during pregnancy is needed.
“For clinicians, these findings, if confirmed in prospective study, can help identify at-risk infant populations who would need closer monitoring to prevent early neonatal hypoglycemia,” Sampath said. “Further, clinicians may consider routine screening of HbA1c of mothers and incorporate such testing into clinical practice. Such measure may decrease the incidence of hypoglycemia potentially, a common clinical problem in the neonate.
“That said, this study warrants further investigation of ‘optimal’ HbA1c levels during pregnancy to assess if our findings can be generalized to other populations, and to well babies without risk factors for glucose screening. A prospective study [that] evaluates HbA1c levels serially in the second and third trimester, with evaluation of neonatal insulin levels and blood glucose level, is needed.”
For more information:
Venkatesh Sampath, MD, MRCPCh, can be reached at the Division of Neonatology, Children’s Mercy Hospital, 2401 Gillham Road, Kansas City, MO 64108; email: vsampath@cmh.edu.
Perspective
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These results are not necessarily surprising; however, there were challenges with these data. First, we don’t know the exact timing of the HbA1c results — was testing done 3 months vs. 3 weeks before delivery? We do not know what maternal ambient glucose levels were at the time. Nor did I see a correlation between HbA1c and maternal blood glucose levels at the time of labor and delivery, because that can also impact fetal hypoglycemia. As an example, even a mother with a “perfect” HbA1c — say, 5.1% or 5.2% — if develops hyperglycemia during labor and delivery, that can lead to a neonate with hypoglycemia after delivery. We also don’t have information on red blood cell turnover or anemia status among the mothers; this can influence HbA1c readings and make them less accurate.
We are lacking some information here, but these findings raise some really intriguing questions. Ironically, the HbA1c measurement may not be the perfect tool to predict which infants will develop hypoglycemia; there may be a better mechanism to assess this risk. Finger sticks during labor and delivery, or even glucose sensors, would have been helpful to further assess the impact of the HbA1c. The HbA1c may be a helpful tool, but it does not tell the full story.
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