Transient neonatal hypoglycemia and later cognitive performance

Study Summary

Previous data on the effects of transient newborn hypoglycemia, although not generated from large studies or average-risk populations, suggested that transient hypoglycemia did not have adverse developmental consequences. This study reviewed outcomes among children cared for in the newborn nursery at one large pediatric academic medical center in 1998. Newborn blood glucose levels were matched with student achievement test scores from 2008, when the children were 10 years old. The hypothesis was that transient hypoglycemia in the newborn period would be associated with lower performance on these standardized examinations. The investigators sought to address limitations of previous studies by obtaining extensive socioeconomic and demographic information from the mothers and children to adequately control for environmental factors that might influence student achievement.

The children were born at 23-42 weeks' gestation at one academic medical center, and all had at least one recorded blood glucose measurement. Infants with prolonged hypoglycemia were excluded. The investigators matched university records with state birth certificates and Department of Education data to construct newborn information and educational achievement for each child. From maternal records, they obtained information on maternal education, prenatal care, maternal medical conditions, complications of pregnancy, route of delivery, as well as potential tobacco exposure or substance abuse.

The outcome of interest was performance on the mandated, standardized achievement test completed by children in grades 3 through 8 in that state. The focus was on whether the children achieved "proficiency" on the fourth grade literacy and mathematics components of the test.

More than 1900 children were eligible for the study, and the investigators were able to match newborn and achievement test records for 1395 (71.8%) of these children. This was a largely Medicaid population, with only 25.4% of the mothers having an educational level higher than high school. The analysis controlled for gestational age group, race, sex, multifetal gestation, insurance status, maternal educatio
nal level and socioeconomic status, and gravidity.

Infants born preterm, with smaller birthweights, or with multiple gestations were more likely to experience hypoglycemia. Three thresholds of hypoglycemia were considered—35 mg/dL, 40 mg/dL, and 45 mg/dL—in the analysis. The results, including the proportions of infants who experienced each degree of transient hypoglycemia and corresponding school test scores, are summarized in the Table.

Table. Summary of Results

Threshold of Hypoglycemia	Infants Affected	Odds of Achieving Proficiency
		Literacy	Mathematics
<35 mg/dL	6.4%	0.49	0.49
<40 mg/dL	10.3%	0.43	0.51
<45 mg/dL	19.3%	0.62	0.78

All three levels of hypoglycemia were associated with lower academic performance on fourth grade proficiency testing in the logistic regression model that accounted for newborn and maternal factors. Protective factors for achieving proficiency included female sex, singleton birth, full-term, private insurance, higher maternal educational levels, and primiparous pregnancy. The investigators concluded that transient hypoglycemia in the newborn may be associated with long-term cognitive outcomes. They are cautious in their conclusions and suggest that further cohort analyses be conducted.

Viewpoint

The big-picture question at hand is whether it might be beneficial to conduct universal screening for hypoglycemia in all newborns. This study has the potential to be of real landmark importance if additional observational cohorts suggest an untoward relationship between transient hypoglycemia and later cognitive performance. As the investigators commented, their findings go against conventional wisdom (that transient hypoglycemia in the newborn period has no detrimental effects), and so they are reluctant to make very strong recommendations for what providers should do on the basis of these data. They appropriately express the need to urgently obtain similar cohort data to address this question. Given that almost 20% of the children in their study experienced hypoglycemia below 45 mg/dL, the societal impact of transient hypoglycemia could very well be enormous and seems to be worthy of additional investigation.

http://www.medscape.com/viewarticle/854580?nlid=92083_491&src=wnl_edit_medp_wir&uac=60196BR&spon=17&impID=907177&faf=1

Kaiser JR, Bai S, Gibson N, Holland G, Lin TM, Swearingen CJ, Mehl JK,
ElHassan NO. Association Between Transient Newborn Hypoglycemia and Fourth-Grade
Achievement Test Proficiency: A Population-Based Study. JAMA Pediatr. 2015 Oct
1;169(10):913-21.

Abstract

IMPORTANCE:

Prolonged neonatal hypoglycemia is associated with poor long-term neurocognitive function. However, little is known about an association between early transient newborn hypoglycemia and academic achievement.

OBJECTIVE:

To determine if early (within the first 3 hours of life) transient hypoglycemia (a single initial low glucose concentration, followed by a second value above a cutoff) is associated with subsequent poor academic performance.

DESIGN, SETTING, AND PARTICIPANTS:

A retrospective population-based cohort study of all infants born between January 1, 1998, and December 31, 1998, at the University of Arkansas for Medical Sciences who had at least 1 recorded glucose concentration (a universal newborn glucose screening policy was in effect) was conducted. Medical record data from newborns with normoglycemia or transient hypoglycemia were matched with their student achievement test scores in 2008 from the Arkansas Department of Education and anonymized. Logistic regression models were developed to evaluate the association between transient hypoglycemia and school-age achievement test proficiency based on perinatal factors. Common hypoglycemia cutoffs of a glucose level less than 35 mg/dL (primary) and less than 40 and 45 mg/dL (secondary) were investigated. All 1943 normoglycemic and transiently hypoglycemic infants (23-42 weeks' gestation) were eligible for inclusion in the study. Infants with prolonged hypoglycemia, congenital anomalies, or chromosomal abnormalities were excluded from the study.

EXPOSURE:

Hypoglycemia as a newborn.

MAIN OUTCOMES AND MEASURES:

The primary outcome was proficiency on fourth-grade literacy and mathematics achievement tests at age 10 years. We hypothesized a priori that newborns with early transient hypoglycemia would be less proficient on fourth-grade achievement tests compared with normoglycemic newborns.

RESULTS:

Perinatal data were matched with fourth-grade achievement test scores in 1395 newborn-student pairs (71.8%). Transient hypoglycemia (glucose level <35, <40, and <45 mg/dL) was observed in 6.4% (89 of 1395), 10.3% (143 of 1395), and 19.3% (269 of 1395) of newborns, respectively. After controlling for gestational age group, race, sex, multifetal gestation, insurance status, maternal educational level and socioeconomic status, and gravidity, transient hypoglycemia was associated with decreased probability of proficiency on literacy and mathematics fourth-grade achievement tests. For the 3 hypoglycemia cutoffs, the adjusted odds ratios (95% CIs) for literacy were 0.49 (0.28-0.83), 0.43 (0.28-0.67), and 0.62 (0.45-0.85), respectively, and the adjusted odds ratios (95% CIs) for mathematics were 0.49 (0.29-0.82), 0.51 (0.34-0.78), and 0.78 (0.57-1.08), respectively.

CONCLUSIONS AND RELEVANCE:

Early transient newborn hypoglycemia was associated with lower achievement test scores at age 10 years. Given that our findings are serious and contrary to expert opinion, the results need to be validated in other populations before universal newborn glucose screening should be adopted.