Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies

Background Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence. Methods and findings We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries. Conclusions This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.This collaborative project received funding from the European Union's Horizon 2020 research and innovation programme (Grant Agreement No. 733206 LifeCycle, Grand Recipient VWVJ; Grant Agreement No. 824989 EUCAN-Connect, Grand Recipient AMNA). Please, see S1 Appendix for list of cohort-specific funding/support. DAL is supported by the UK Medical Research Council (MC_UU_00011/6) and British Heart Foundation (CH/F/20/90003 and AA/18/7/34219). RCW is supported by UKRI Innovation Fellowship with Health Data Research UK [MR/S003959/1]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Three-Dimensional Structure of N-Terminal Domain of DnaB Helicase and Helicase-Primase Interactions in Helicobacter pylori

Replication initiation is a crucial step in genome duplication and homohexameric DnaB helicase plays a central role in the replication initiation process by unwinding the duplex DNA and interacting with several other proteins during the process of replication. N-terminal domain of DnaB is critical for helicase activity and for DnaG primase interactions. We present here the crystal structure of the N-terminal domain (NTD) of H. pylori DnaB (HpDnaB) helicase at 2.2 Å resolution and compare the structural differences among helicases and correlate with the functional differences. The structural details of NTD suggest that the linker region between NTD and C-terminal helicase domain plays a vital role in accurate assembly of NTD dimers. The sequence analysis of the linker regions from several helicases reveals that they should form four helix bundles. We also report the characterization of H. pylori DnaG primase and study the helicase-primase interactions, where HpDnaG primase stimulates DNA unwinding activity of HpDnaB suggesting presence of helicase-primase cohort at the replication fork. The protein-protein interaction study of C-terminal domain of primase and different deletion constructs of helicase suggests that linker is essential for proper conformation of NTD to interact strongly with HpDnaG. The surface charge distribution on the primase binding surface of NTDs of various helicases suggests that DnaB-DnaG interaction and stability of the complex is most probably charge dependent. Structure of the linker and helicase-primase interactions indicate that HpDnaB differs greatly from E.coli DnaB despite both belong to gram negative bacteria

Azimuthal anisotropy and correlations in the hard scattering regime at RHIC

Azimuthal anisotropy (v(2)) and two-particle angular correlations of high p(T) charged hadrons have been measured in Au+Au collisions at roots(NN) = 130 GeV for transverse momenta up to 6 GeV/c, where hard processes are expected to contribute significantly. The two-particle angular correlations exhibit elliptic flow and a structure suggestive of fragmentation of high p(T) partons. The monotonic rise of v(2)(p(T)) for p(T) 3 GeV/c, a saturation of v(2) is observed which persists up to p(T) = 6 GeV/c

Coherent rho(0) production in ultraperipheral heavy-ion collisions

The STAR Collaboration reports the first observation of exclusive rho(0) photoproduction, AuAu-->AuAurho(0), and rho(0) production accompanied by mutual nuclear Coulomb excitation, AuAu-->Au(star)Au(star)rho(0), in ultraperipheral heavy-ion collisions. The rho(0) have low transverse momenta, consistent with coherent coupling to both nuclei. The cross sections at s(NN)=130 GeV agree with theoretical predictions treating rho(0) production and Coulomb excitation as independent processes

d̅ and 3He̅ Production in √sNN = 130 GeV Au+Au Collisions

A report on the first measurements of light antinucleus production in Au + Au collisions at the Relativistic Heavy-Ion Collider (RHIC) was presented. The production rates for d̄ and He were observed to be much larger than in lower energy nucleus-nucleus collisions. A little or no increase in the antinucleon freeze-out volume compared to CERN Super Proton Synchrotron (SPS) energy was indicated by a coalescence model analysis. The He freeze-out volume was indicated to be smaller than the d̄ freeze-out volume

Pion interferometry of root s(NN)=130 GeV Au+Au collisions at RHIC

Two-pion correlation functions in An + Au collisions at roots(NN) = 130 GeV have been measured by the STAR (solenoidal tracker at RHIC) detector. The source size extracted by fitting the correlations grows with event multiplicity and decreases with transverse momentum. Anomalously large sizes or emission durations, which have been suggested as signals of quark-gluon plasma formation and rehadronization, are not observed. The Hanbury Brown-Twiss parameters display a weak energy dependence over a broad range in roots(NN)