This study compares how effectively the ponderal index and the body mass index adjust birthweight for length at different gestations, and derives an improved index suitable for all gestations. The study was a cross-sectional survey, in a London teaching hospital, using a total of 999 neonates of 33 weeks gestation or later. Main outcome measures were the ponderal index (birthweight/length3), body mass index (birthweight/length2), and Benn index (birthweight/length(n)), where the length power n varies with gestation and is estimated by log-log regression. Results showed that up to 39 weeks gestation, the ponderal index is uncorrelated with length and so is a good index of birthweight for length. Past 39 weeks gestation, the ponderal index is negatively correlated with length, while the body mass index is uncorrelated, so that the body mass index is better. Neither index is optimal at all gestations. Deriving the Benn index (birthweight/length(n)) for each week of gestation, choosing n to make the index uncorrelated with length, shows that n falls steadily and very significantly (p < 0.0001) with increasing gestation. This in turn means that predicted birthweight for length depends on gestation: for a neonate 48 cm long, predicted birthweight varies from 2485 g at 34 weeks to 3030 g at 43 weeks, a 20% range. However, for a 54 cm long infant, predicted birthweight is the same at all gestations. A Benn index where the value of n changes linearly with gestation is described. We conclude that the ponderal index is not appropriate for measuring intra-uterine malnutrition, as it fails to adjust for length at all gestations. No other index of birthweight/length(n) with constant n is any better, as different gestations require different indices. Birthweight predicted from an infant's length depends on the infant's gestation. If, as Barker proposes, thinness at birth assessed by birthweight for length is used to predict later health status, more account needs to be taken of the complex relationship between birthweight, length and gestation.

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Head circumference/abdominal circumference (HC/AC) ratios of the fetus are accepted as a means of distinguishing different patterns of growth retardation with a high ratio implying malnutrition of the fetus. Ponderal index ( birthweight/length3) is used by paediatricians as a measure of neonatal wasting and would therefore be expected to correlate with HC/AC ratios at delivery. Anthropometric data on 999 newborn infants have been collected and analyzed by multiple regression. The results show a poor correlation between ponderal index and HC/AC ratio, worse than that between ponderal index and AC alone. The use of HC/AC ratios antenatally to identify subgroups of intrauterine malnutrition should be abandoned. The prediction of intrauterine malnutrition by weight/length ratios should be investigated further.The concept of intrauterine growth retardation (IUGR) as defined by low birthweight for gestational age is now outdated since a proportion of malnourished infants will in fact have a birthweight >loth centile (Altman & Hytten 1989).Birthweight is not a valid measure of fetal Royal Devon and Exeter Hospital (Heavitree), Gladstone Road, Exeter, EX1 2ED.