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Costantine, Maged M.; Tita, Alan T. N.; Mele, Lisa; Casey, Brian M.; Peaceman, Alan M.; Varner, Michael W.; Reddy, Uma M.; Wapner, Ronald J.; Thorp, John M., Jr.; & Saade, George R., et al. (Online ahead of print). The Association between Infant Birth Weight, Head Circumference, and Neurodevelopmental Outcomes. American Journal of Perinatology. PMCID: PMC10425571


OBJECTIVE: The aim of this study was to evaluate whether being small for gestational age (SGA) or large for gestational age (LGA) or having a small or large head circumference (HC) at birth is associated with adverse neurodevelopmental outcomes.
STUDY DESIGN: This is a secondary analysis of a multicenter negative randomized trial of thyroxine therapy for subclinical hypothyroid disorders in pregnancy. The primary outcome was child intelligence quotient (IQ) at 5 years of age. Secondary outcomes included several neurodevelopmental measures. Associations between the outcomes in children with SGA (<10th percentile) or LGA (>90th percentile) birth weights, using ethnicity- and sex-specific population nomogram as well as nomograms from the National Fetal Growth (NFG) study, were compared with the referent of those with appropriate for gestational age (AGA) birth weight. Similar analyses were performed for HC.
RESULTS: Using the population nomogram, 90 (8.2%) were SGA and 112 (10.2%) were LGA. SGA neonates were more likely to be born preterm to mothers who were younger, smoked, and were less likely to have less than a high school education, whereas LGA neonates were more likely to be born to mothers who were older and have higher body mass index, compared with AGA neonates. SGA at birth was associated with a decrease in the child IQ at 5 years of age by 3.34 (95% confidence interval [CI], 0.54-6.14) points, and an increase in odds of child with an IQ < 85 (adjusted odds ratio [aOR], 1.9; 95% CI, 1.1-3.2). There was no association between SGA and other secondary outcomes, or between LGA and the primary or secondary outcomes. Using the NFG standards, SGA at birth remained associated with a decrease in the child IQ at 5 years of age by 3.14 (95% CI, 0.22-6.05) points and higher odds of an IQ < 85 (aOR, 2.3; 95% CI, 1.3-4.1), but none of the other secondary outcomes. HC was not associated with the primary outcome, and there were no consistent associations of these standards with the secondary outcomes.
CONCLUSION: In this cohort of pregnant individuals with hypothyroid disorders, SGA birth weight was associated with a decrease in child IQ and greater odds of child IQ < 85 at 5 years of age. Using a fetal growth standard did not appear to improve the detection of newborns at risk of adverse neurodevelopment.


Reference Type

Journal Article

Year Published

Online ahead of print

Journal Title

American Journal of Perinatology


Costantine, Maged M.
Tita, Alan T. N.
Mele, Lisa
Casey, Brian M.
Peaceman, Alan M.
Varner, Michael W.
Reddy, Uma M.
Wapner, Ronald J.
Thorp, John M., Jr.
Saade, George R.
Rouse, Dwight J.
Sibai, Baha M.
Mercer, Brian M.
Caritis, Steve N.

Article Type





Thorp - 0000-0002-9307-6690