Objective: To characterize the metabolic variation in neonatal hair samples associated with intrauterine growth discordance in dichorionic-diamniotic (DCDA) twins and to evaluate the effects of specific metabolic alterations on later neurobehavioural outcomes in infancy. Design: Cohort-based case-control study Setting: Peking University Third Hospital Population: DCDA twins with birth weight discordance(DCDA-D) and birthweight concordance (DCDA-C) within a twin cohort recruited between September 2017 and December 2018 in Beijing, China. Methods: A specific hair metabolic profile of 14 pairs of DCDA-D twins was revealed using gas chromatography-mass spectrometry by comparing that of 28 pairs of DCDA-C twins. Pearson’s correlation was used to assess the relationship between the neonatal hair metabolome and neurocognitive outcomes, assessed using the Ages and the Infant’s Stages Questionnaires, third edition (ASQ-3) at 2 or 3 years of age. Main outcome measure: neonatal hair metabolome and long-term neurodevelopment. Results: A total of seventeen hair metabolites were significantly different within DCDA-D twin pairs compared to DCDA-C twins. Particularly, reduced levels of cysteine, threonine, and leucine were identified in both the larger and smaller DCDA-D twins compared with DCDA-C twins. The deregulated metabolic pathways including cysteine, methionine, aminoacyl-tRNA, nicotinate, and nicotinamide metabolism biosynthesis pathways in DCDA-D groups were positively correlated with infant neurocognitive development at 2 or 3 years of age, especially in problem-solving domains. Conclusion: Neonatal hair metabolic variations in utero of growth discordance in DCDA twins may be associated with poor neurocognitive development. Metabolome profiles of hair may be novel predictors of infant neurodevelopment longitudinally.

Background Household studies are crucial for understanding the transmission of SARS-CoV-2 infection, which may be underestimated from PCR testing of respiratory samples alone. We aim to combine assessment of household mitigation measures; nasopharyngeal, saliva and stool PCR testing; along with mucosal and systemic SARS-CoV-2 specific antibodies, to comprehensively characterise SARS-CoV-2 infection and transmission in households. Methods Between March and September 2020, we obtained samples from 92 participants in 26 households in Melbourne, Australia, in a 4-week period following onset of infection with ancestral SARS-CoV-2 variants. Results The secondary attack rate was 36% (24/66) when using nasopharyngeal swab (NPS) PCR positivity alone. However, when respiratory and non-respiratory samples were combined with antibody responses in blood and saliva, the secondary attack rate was 76% (50/66). SARS-CoV-2 viral load of the index case and household isolation measures were key factors that determine secondary transmission. In 27% (7/26) of households, all family members tested positive by NPS for SARS-CoV-2 and were characterised by lower respiratory Ct-values than low transmission families (Median 22.62 vs 32.91; IQR 17.06 to 28.67 vs 30.37 to 34.24). High transmission families were associated with enhanced plasma antibody responses to multiple SARS-CoV-2 antigens and the presence of neutralising antibodies. Three distinguishing saliva SARS-CoV-2 antibody features were identified according to age (IgA1 to Spike 1, IgA1 to nucleocapsid protein (NP), suggesting that adults and children generate distinct mucosal antibody responses during the acute phase of infection. Conclusion Utilising respiratory and non-respiratory PCR testing, along with measurement of SARS-CoV-2 specific local and systemic antibodies, provides a more accurate assessment of infection within households and highlights some of the immunological differences in response between children and adults.

Abstract Objective: We aimed to preliminarily assess whether low-dose aspirin（LDA）is beneficial in preventing preeclampsia in twin pregnancies. Design: An observational cohort study. Setting: Two hospital centers in Chongqing, China. Population: 932 twin-pregnant women. Methods: Among 932 participants, 277 in the First Affiliated Hospital of Chongqing Medical University were routinely treated with aspirin (100mg daily) from 12-16 weeks to 35 weeks of gestational age, while 655 in Chongqing Health Center for Women and Children were not taking aspirin during the whole pregnancy. We followed each subject and the individual details were recorded. Main Outcome Measures: The main outcome was to compare the incidence of preeclampsia in women with or without aspirin intaking. Results: LDA significantly reduced the risk of PE (OR: 0.48, 95% CI: 0.24-0.95, p=0.048) and ＜34 weeks preterm birth (OR: 0.50, 95% CI: 0.29-0.86, p=0.013), but showed possible benefits to lower the rate of SGA babies (OR: 0.74, 95% CI: 0.55-1.00, p=0.063). Moreover, the risk of postpartum hemorrhage was not increased by LDA (OR: 0.89, 95% CI: 0.35-2.26, p=1.000). Conclusions: Treatment with low-dose aspirin in women pregnant with twins could offer some protection against adverse pregnancy outcomes in the absence of any significantly increased risk of postpartum hemorrhage. Funding: The National Key Research and Development Program of China (2018YFC1002900), and National Natural Science Foundation of China (81520108013, 81771613, 81671488, 81871189). Keywords: Twin pregnancy, low-dose aspirin, preeclampsia, preterm birth, small for gestational age