In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk of severe COVID-19 related complications, and maternal morbidity and mortality. To analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes, when Omicron was the variant of concern. INTERCOVID-2022 is a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes, as well as vaccine effectiveness (VE). Women diagnosed with laboratory-confirmed COVID-19 in pregnancy were compared with two 'non-diagnosed', unmatched women recruited concomitantly and consecutively in pregnancy or at delivery. Mother/newborn dyads were followed until hospital discharge. Primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index (SNMI), severe perinatal morbidity and mortality index (SPMMI), preterm birth, neonatal death, referral to neonatal intensive care unit (NICU), and diseases during the neonatal period. VE was estimated adjusted by maternal risk profile. We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) non-diagnosed mothers. Amongst diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (RR=0.46; 95%CI=0.23, 0.91) the risk of being diagnosed with COVID-19 compared to those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically-indicated preterm birth, respiratory distress syndrome and number of days in NICU. Newborns of unvaccinated mothers had double the risk of neonatal death (RR=2.06; 95% CI=1.06, 4.00) compared to those of non-diagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the significantly highest VE (64%; 95% CI=10-86%); VE was not as high for mRNA vaccines only. VE against moderate/severe neonatal outcomes was much lower: 13% in the booster-vaccinated group (all vaccines), and 25% and 28% in the completely and booster-vaccinated groups, respectively (mRNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women 100 days (14 weeks) or less before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks).. Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk of infecting newborns. When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk of neonatal death. Neonates of vaccinated mothers had a decreased risk of preterm birth and adverse neonatal outcomes. As the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19 mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

Based on epidemiological and experimental evidence, the origins of childhood obesity and early onset metabolic syndrome can be extended back to developmental processes during intrauterine life. It is necessary to actively investigate antecedent conditions that affect fetal growth by developing reliable measures to identify variations in fetal fat deposition and body composition. Recently, the resolution of ultrasonography has remarkably improved, which enables better tissue characterization and quantification of fetal fat accumulation. In addition, fetal fractional limb volume has been introduced as a novel measure to quantify fetal soft tissue volume, including fat mass and lean mass. Detecting extreme variations in fetal fat deposition may provide further insights into the origins of altered fetal body composition in pathophysiological conditions (i.e., fetal growth restriction or fetal macrosomia), which are predisposed to the metabolic syndrome in later life. Further studies are warranted to determine the maternal or placental factors that affect fetal fat deposition and body composition. Elucidating these factors may help develop clinical interventions for altered fetal growth and body composition, which could potentially lead to primary prevention of the future risk of metabolic dysfunction.

Introduction: The average birth weight in Japan has gradually decreased and the number of low birth weight infant has increased over the last 30 years. Japanese pregnant women are characterized with lower prevalence of obesity than those in other developed countries, and maternal underweight before pregnancy is independently associated with low birth weight. However, the association between maternal inadequate gestational weight gain (GWG) and the risk of small for gestational age (SGA) in Japanese uncomplicated pregnant women has not been fully understood. This study aimed to examine the effect of maternal inadequate GWG on the risk of SGA in Japanese uncomplicated pregnancies. Methods: We retrospectively analyzed uncomplicated Japanese singleton pregnancies that delivered at term gestation in our institution from 2006 to 2016. The association between GWG and birth weight was analyzed by multiple linear regression. Potential confounding factors included maternal age, parity, prepregnancy BMI, and neonatal sex. The association between inadequate GWG and SGA was also examined by logistic regression. Results: A total of 3837 mother–neonate dyads were analyzed. Maternal GWG was 10.1 ± 3.7 kg (mean ± SD), and 2529 (66%) had inadequate GWG. After adjusting for confounding factors, GWG significantly correlated with birth weight (standardized β = 0.199, p < .001). Inadequate GWG increased the risk of delivering SGA neonate (adjusted odds ratio (aOR) = 1.97 [1.45–2.68], p < .001). This association was particularly pronounced in underweight (aOR = 2.95 [1.38–6.29], p = .005) and normal weight mothers (aOR = 1.79 [1.27–2.52], p = .001), and not in overweight/obese mothers (p = .115). Conclusion: Maternal GWG is associated with birth weight in Japanese women with uncomplicated singleton pregnancies. Inadequate GWG is an important risk factor of SGA, particularly in non-obese women. The present finding would potentially provide further evidence that promoting adequate gestational weight gain in Japanese underweight and normal weight mothers would reduce SGA, as well as metabolic dysfunction in later life.