Published online March 19, 2007
PEDIATRICS Vol. 119 No. 4 April 2007, pp. e983-e990 (doi:10.1542/peds.2006-2523)
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ARTICLE

A New Phenotypical Variant of Intrauterine Growth Restriction?

Claudio DeFelice, MDa, Rossana Tassi, MDb, Bruno De Capua, MDc, Francis Jaubert, MD, PhDd, Mattia Gentile, MDe, Lorenzo Quartulli, MDf, Gabriele Tonni, MD, PhDg, Daniele Costantinih, Mirella Strambi, MDi and Giuseppe Latini, MDf,j

a Neonatal Intensive Care Unit, Azienda Ospedaliera Universitaria Senese
b Laboratory of Ultrasonology, Department of Neurosciences
c Clinical Audiology Unit, Dipartimento Cefalico-scheletrico, Azienda Ospedaliera Universitaria Senese, AOUS Nose and Throat
i Department of Pediatrics, Obstetrics, and Reproductive Medicine, University of Siena, Siena, Italy
h Neonatal Audiologic Screening Service, USL7, Siena, Italy
f Division of Neonatology, Perrino Hospital, Brindisi, Italy
j Clinical Physiology Institute, National Research Council of Italy (IFC-CNR), Lecce Section, Italy
e Medical Genetics Unit, Ospedale Di Venere, Bari, Italy
g Division of Obstetrics and Gynecology, Guastalla Civil Hospital, AUSL Reggio Emilia, Guastalla, Italy
d Service d'Anatomie et de Cytologie Pathologiques, Hôpital Necker-Enfants-Malades, Paris, France

OBJECTIVES. A link between intrauterine growth restriction and major adult-onset diseases has been reported. In this study we observed a series of hitherto-unrecognized clinical features in a population of children with intrauterine growth restriction.

PATIENTS AND METHODS. A total of 77 Italian children (aged 9.45 ± 2.08 years) with antenatally diagnosed intrauterine growth restriction and small-for-gestational-age birth, along with their parents, were examined. The children with intrauterine growth restriction and were small for gestational age were subdivided into 2 groups ("variant" versus control subjects) according to evidence of auricle morphology deviation from normal. The following variables were determined: (1) external ear auricle geometry; (2) function of the posterior communicating arteries of the circle of Willis, as assessed by transcranial Doppler ultrasonography; (3) articular mobility, as assessed by Beighton's 9-point scale; (4) skin softness; and (5) distortion product–evoked otoacoustic emissions.

RESULTS. Intrauterine growth restriction–variant children (n = 27) showed a significant female predominance, a lower proportion of maternal pregnancy-induced hypertension/ preeclampsia, and a higher head circumference as compared with intrauterine growth restriction control subjects. Mothers of small-for-gestational-age–variant children showed significantly different auricular geometry parameters as compared with the intrauterine growth restriction controls mothers. An excess of bilaterally nonfunctioning posterior communicating arteries was observed both in the children with the intrauterine growth restriction–variant phenotype and their mothers as compared with the control groups. Significantly increased proportions of joint hypermobility and skin softness were observed in the intrauterine growth restriction–variant children as compared with controls subjects. Children with the intrauterine growth restriction–variant phenotype and their mothers showed bilateral distortion product–evoked otoacoustic emissions notches versus none in the control subjects, with an associated reduction of the area under the curve in both the intrauterine growth restriction–variant children and their mothers. No significant differences between the variant and control groups regarding the fathers were observed.

CONCLUSIONS. We propose that the observed phenotypical constellation may represent an unrecognized variant of intrauterine growth restriction.

Key Words: intrauterine growth restriction • circle of Willis • auricle • joint hypermobility • skin • marker

Abbreviations: IUGR—intrauterine growth restriction • SGA—small for gestational age • PCoA—posterior communicating artery • LA—longest axis of the auricle • SA—shortest axis of the auricle • SA-D—distance of SA from the lowest auricle point • CCA—common carotid artery • DPOAE—distortion product–evoked otoacoustic emission • AUC—area under the curve • SPL—sound pressure level • ECM—extracellular matrix

Accepted Oct 23, 2006.