Renal Developmental Arrest in Sudden Infant Death Syndrome

Abstract

Investigations linking sudden infant death syndrome (SIDS) and type II intrauterine growth retardation (IUGR) have thus far failed due in part to technical limitations. Recently developed stereological methods for the unbiased estimation of total nephron number in the human kidney are capable of detecting deviations from normal values of greater than 10%. We compared the total number of nephrons in the kidneys of 24 SIDS victims with those from 16 controls with the same age range. Mean nephron number was significantly (P < 0.001) reduced in ex-IUGR SIDS cases (birthweight under the 10th centile, n = 9, mean number 635,000, range 327,000-1,010,000) in comparison with controls (903,000, 740,000-1,060,000). A similarly significant (P < 0.01) reduction in the "normal birthweight" SIDS group (birthweight over 10th centile, n = 15, 690,000, 361,000-1,040,000) was found. This hitherto unreported renal developmental arrest may be only one manifestation of a general, somatic developmental defect, reflecting adverse intrauterine conditions; other organ systems, similarly critical to homeostasis may be comparably affected. The findings, although not proposed as direct cause of SIDS, may represent a potential explanation for the recognized association of IUGR and SIDS, and provide--we believe--the first quantitative evidence of intrauterine growth retardation in, at least a number of, children of average birthweight.

Renal Developmental Delay Expressed by Reduced Glomerular Number and Its Association with Growth Retardation in Victims of Sudden Infant Death Syndrome and in “Normal” Infants

“…Hinchliffe et al [2,3] showed that glomerular number was reduced in infants suffering from IUGR [2] and that the glomerular number was significantly reduced in SIDS infants of both NBW and LBW [3]. Our mean glomerular number for 13 non-SIDS NBW infants was 653,997, which is considerably less than Hinchliffe et al's [3] 903,000 and that found by Gilbert et al [6], who reported a mean number of 975,000 glomeruli.…”

“…We also excluded cases in which the individual had suffered a chronic illness at any time, as it is also not known how these illnesses may affect normal organogenesis. Therefore, the infants used in the control group of both this study and that by Hinchliffe et al [3] were very similar. Even so, statistical comparison of the present non-SIDS NBW data to the non-SIDS NBW data from Hinchliffe et al [3] shows that there is a statistically significant difference between the two groups ( p Ͻ 0.01).…”

“…Infants suffering from intrauterine growth retardation (IUGR) had significantly reduced numbers of glomeruli [2] and as glomerular number development was complete at 36 weeks, these infants would have been unable to form additional glomeruli after birth to compensate postnatally for intrauterine deficiencies in renal organogenesis. Later it was shown that glomerular number was significantly reduced in both normal birth weight (NBW) and low birth weight (LBW) sudden infant death syndrome (SIDS) victims [3]. The present study examined kidney development in a similar cohort of SIDS and control cases.…”

Microanatomical development of the equine kidney and defects associated with intra-uterine growth retardation

“…The IUGR animals were defined using parameters previously described in infants (Battaglia and Lubchenco, 1967). Using design-based, unbiased stereological techniques (Hinchliffe et al, 1993), whole kidney and cortex volume, total glomerular number and glomerular volume were determined. Functional tests, including amniotic and allantoic fluid analysis, inulin/paraaminohippuric acid and fractional excretion of electrolytes, have already been performed (Holdstock, 1995), and were correlated to the stereological findings of the kidneys.…”

“…In man, IUGR has been defined when an infant is born at a birth weight significantly below (10 th percentile) the mean for gestation, irrespective of any clinical features shown (Battaglia and Lubchenco, 1967). In spite of the absence of macroscopic organ defects, stereological techniques have revealed important micro-anatomical deficiencies and, in particular, glomerular number in the kidneys of infants suffering from IUGR and SIDS (Hinchliffe et al, 1992(Hinchliffe et al, , 1993. Little is known about normal renal organogensis in the horse and stereological techniques are novel in their application to equine tissue.…”