Objective We hypothesised that a multi-compartment magnetic resonance imaging (MRI) technique that is sensitive to fetal blood oxygenation would identify changes in placental blood volume and fetal blood oxygenation in pregnancies complicated by earlyonset fetal growth restriction (FGR). Design Case-control study. Setting London, UK. Population Women with uncomplicated pregnancies (estimated fetal weight [EFW] >10th centile for gestational age [GA] and normal maternal and fetal Doppler ultrasound, n = 12) or earlyonset FGR (EFW <3rd centile with or without abnormal Doppler ultrasound <32 weeks GA, n = 12) were studied. Methods All women underwent MRI examination. Using a multicompartment MRI technique, we quantified fetal and maternal blood volume and feto-placental blood oxygenation. Main outcome measures Disease severity was stratified according to Doppler pulsatility index and the relationship to the MRI parameters was investigated, including the influence of GA at scan. Results The FGR group (mean GA 27 +5 weeks, range 24 +2 to 33 +6 weeks) had a significantly lower EFW compared with the control group (mean GA 29 +1 weeks; −705 g, 95% CI −353 to −1057 g). MRI-derived feto-placental oxygen saturation was higher in controls compared with FGR (75 AE 9.6% versus 56 AE 16.2%, P = 0.02, 95% CI 7.8-30.3%). Feto-placental oxygen saturation estimation correlated strongly with GA at scan in controls (r = −0.83). Conclusion Using a novel multimodal MRI protocol we demonstrated reduced feto-placental blood oxygen saturation in pregnancies complicated by early-onset FGR. The degree of abnormality correlated with disease severity defined by ultrasound Doppler findings. Gestational age-dependent changes in oxygen saturation were also present in normal pregnancies.

Background Pregnant women have been identified as a potentially at‐risk group concerning COVID‐19 infection, but little is known regarding the susceptibility of the fetus to infection. Co‐expression of ACE2 and TMPRSS2 has been identified as a prerequisite for infection, and expression across different tissues is known to vary between children and adults. However, the expression of these proteins in the fetus is unknown. Methods We performed a retrospective analysis of a single cell data repository. The data were then validated at both gene and protein level by performing RT‐qPCR and two‐colour immunohistochemistry on a library of second‐trimester human fetal tissues. Findings TMPRSS2 is present at both gene and protein level in the predominantly epithelial fetal tissues analysed. ACE2 is present at significant levels only in the fetal intestine and kidney, and is not expressed in the fetal lung. The placenta also does not co‐express the two proteins across the second trimester or at term. Interpretation This dataset indicates that the lungs are unlikely to be a viable route of SARS‐CoV2 fetal infection. The fetal kidney, despite presenting both the proteins required for the infection, is anatomically protected from the exposure to the virus. However, the gastrointestinal tract is likely to be susceptible to infection due to its high co‐expression of both proteins, as well as its exposure to potentially infected amniotic fluid. Tweetable abstract This work provides detailed mechanistic insight into the relative protection & vulnerabilities of the fetus & placenta to SARS‐CoV‐2 infection by scRNAseq & protein expression analysis for ACE2 & TMPRSS2. The findings help to explain the low rate of vertical transmission.

Fetal growth restriction (FGR) is a complication of pregnancy that reduces birth weight, markedly increases infant mortality and morbidity and is associated with later-life cardiometabolic disease.  No specific treatment is available for FGR. Placentas of human FGR infants have low abundance of sodium-coupled neutral amino acid transporter 2 (Slc38a2/SNAT2), which supplies the fetus with amino acids required for growth. We determined the mechanistic role of placental Slc38a2/SNAT2 deficiency in the development of restricted fetal growth, hypothesizing that placenta-specific Slc38a2 knockdown causes fetal growth restriction in mice. Using lentiviral transduction of blastocysts with a small hairpin RNA, we achieved 59% knockdown of placental Slc38a2, without altering fetal Slc38a2 expression. Placenta-specific Slc38a2 knockdown reduced near-term fetal and placental weight, fetal viability, trophoblast plasma membrane SNAT2 protein abundance, and both absolute and weight-specific placental uptake of the amino acid transport System A tracer, 14C-methylaminoisobutyric acid. We also measured human placental SLC38A2 gene expression in a well-defined term clinical cohort and found that SLC38A2 expression was decreased in late-onset, but not early-onset FGR, compared to appropriate for gestational age control placentas. The results demonstrate that low placental Slc38a2/SNAT2 causes fetal growth restriction and could be a target for clinical therapies for late-onset FGR.