Original Articles
Intrauterine growth restriction and postnatal steroid treatment effects on insulin sensitivity in preterm neonates,☆☆

https://doi.org/10.1067/mpd.2002.126725Get rights and content

Abstract

Objectives: To study whether intrauterine growth restriction (IUGR) is associated with decreased sensitivity to the main fetal growth factor, insulin, and the effect of glucocorticoid therapy on insulin sensitivity in preterm infants. Study design: Newborn infants with a birth weight (BW) of< 1500 g were classified as appropriate for gestational age ([AGA], BW within ± 1 SD, n = 10), or small for gestational age ([SGA], BW <–2 SD, n = 13); 5 AGA infants and 8 SGA infants received systemic steroids. An abbreviated modified minimal model test was performed, consisting of sequential blood samples for glucose and insulin assays, and intravenous infusions of 0.3 g/kg glucose and 0.02 U/kg regular human insulin. The insulin sensitivity index (SI) was calculated using a computer program. Results: The basal insulin/glucose ratio (I/G) and SI did not differ between the AGA and SGA groups. Steroids did not influence the I/G nor the SI of AGA infants (10.2 ± 6.7 vs 8.2 ± 2.3), but decreased the SI in the SGA group (12.2 ± 5.1 vs 5.3 ± 2.7, P <.05). Conclusions: Insulin sensitivity of neonates can be measured by the modified minimal model. IUGR is not associated with impaired fetal glucose tolerance. Early neonatal steroid treatment decreases insulin sensitivity in SGA infants, which may contribute to their risk of having hyperglycemia. (J Pediatr 2002;141:472-6)

Section snippets

Subjects

The study was performed in the Neonatal Intensive Care Unit of the Hospital for Children and Adolescents, University of Helsinki, between April 1998 and December 2000. Infants with a BW <1500 g and an indwelling arterial line were eligible if the BW was <–2 SD (small for gestational age [SGA]) or within ± 1 SD range (appropriate for gestational age [AGA]) (Table I).Gestational ages were determined by fetal ultrasonography. Mothers of all AGA and SGA infants received antenatal steroid (in one

Results

There were no significant differences in sex and gestational age between the 2 study groups (Table I), nor between the AGA and SGA infants not receiving postnatal steroid. The lowest and highest blood glucose concentrations during the MMM did not differ between the groups (Table II).

. Lowest and highest blood glucose (mmol/L) of the AGA and SGA infants during the study

Empty CellBefore insulin administrationAfter insulin administration
Empty CellAGASGAAGASGA
Lowest blood glucose6.3 ± 2.1 (3.7-9.6)7.4 ± 3.3 (3.7-14.4)

Discussion

Reduced glucose tolerance has been observed in 2 rat models of IUGR, after maternal semistarvation15, 16 and placental insufficiency caused by uterine artery ligation (the offspring studied at 3-4 months of age).17 In humans, clinically significant IUGR often results in an extremely preterm birth, but no data have been reported on the insulin sensitivity of newborn SGA infants. The glucose clamp technique has been applied to measure insulin sensitivity in AGA preterm infants.18, 19 The clamp

Acknowledgements

We thank Dr Richard N. Bergman for fruitful discussions.

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    Supported by the Finnish Pediatric Research Foundation and the Medical Society of Finland (Finska Läkarsällskapet).

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    Reprint requests: Jaana A. Leipälä, 4th Floor, Ruskin Wing, King's College Hospital, London SE5 9RS, United Kingdom.

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