Nowadays, the vaccination with COVID-19 vaccines is being promoted worldwide, professionals and common people are very concerned about the efficacy and safety of COVID-19 vaccines. No published systematic review and meta-analysis has assessed the efficacy and safety of the COVID-19 vaccines based on data from phase III clinical trials. Therefore, this study has estimated the efficacy and safety of COVID-19 vaccines and the differences between vaccine types. PubMed, Embase, the Cochrane Library, CNKI, Wanfang, medRxiv databases and two websites were used to retrieve the studies. Random-effects models were used to estimate the pooled efficacy and safety with risk ratio (RR). A total of eight studies, seven COVID-19 vaccines and 158,204 subjects were included in the meta-analysis. All the vaccines had a good preventive effect on COVID-19 (RR = 0.17, 95% CI: 0.09–0.32), and the mRNA vaccine (RR = 0.05, 95% CI: 0.03–0.09) was the most effective against COVID-19, while the inactivated vaccine (RR = 0.32, 95% CI: 0.19–0.54) was the least. In terms of safety, the risk of overall adverse events showed an increase in the vaccine group after the first (RR = 1.46, 95% CI: 1.03–2.05) or second (RR = 1.52, 95% CI: 1.04–2.20) injection. However, compared with the first injection, the risk of local (RR = 2.64, 95% CI: 1.02–6.83 vs. RR = 2.25, 95% CI: 0.52–9.75) and systemic (RR = 1.33, 95% CI: 1.21–1.46 vs. RR = 1.59, 95% CI: 0.84–3.01) adverse events decreased after the second injection. As for the mRNA vaccine, the risk of overall adverse events increased significantly, compared with the placebo, no matter whether it was the first (RR = 1.83, 95% CI = 1.80–1.86) or the second (RR = 2.16, 95% CI = 2.11–2.20) injection. All the COVID-19 vaccines that have published the data of phase III clinical trials have excellent efficacy, and the risk of adverse events is acceptable. The mRNA vaccines were the most effective against COVID-19, meanwhile the risk and grade of adverse events was minimal, compared to that of severe symptoms induced by COVID-19.

A prime–boost strategy of COVID-19 vaccines brings hope to limit the spread of SARS-CoV-2, while the immunogenicity of the vaccines is waning over time. Whether a booster dose of vaccine is needed has become a widely controversial issue. However, no published meta-analysis has focused on the issue. Therefore, this study assessed the immunogenicity and safety of the different combinations of prime–boost vaccinations. Electronic databases including PubMed, the Cochrane Library, Embase, medRxiv, Wanfang and CNKI were used to retrieve the original studies. A total of 28 studies, 9 combinations of prime–boost vaccinations and 5870 subjects were included in the meta-analysis, and random effect models were used to estimate pooled immunogenicity and safety. The immunity against COVID-19 after the prime vaccination waned over time, especially in the populations primed with inactivated vaccines, in which the seropositive rate of antibodies was only 28% (95% CI: 17–40%). Booster vaccination could significantly increase the antibody responses, and heterologous immunization was more effective than homologous immunization (neutralization titers: 1.65 vs. 1.27; anti-RBD IgG: 1.85 vs. 1.15); in particular, the combination of inactivated–mRNA vaccines had the highest antibody responses (neutralization titers: MRAW = 3.64, 95% CI: 3.54–3.74; anti-RBD IgG: 3.73, 95% CI: 3.59–3.87). Moreover, compared with the initial two doses of vaccines, a booster dose did not induce additional or severe adverse events. The administration of the booster dose effectively recalled specific immune responses to SARS-CoV-2 and increased antibody levels, especially in heterologous immunization. Considering the long-term immunogenicity and vaccine equity, we suggest that now, only individuals primed with inactivated vaccines require a booster dose.

Objectives Along with the development of the times and progress of the society, the total fertility rate (TFR) markedly changed in each country. Therefore, it is critical to describe the trend of TFR and explore its influencing factors. However, previous studies did not consider the time lag and cumulative effect in the associations between the influencing factors and TFR. Thus, our study aimed to analyze the associations from a new dimension. Methods The study was employed using national-level data from the World Bank and United Nations Development Programme. Distributed lag non-linear models with 5-year lag were used to examine the independent associations between the relevant factors and TFR. Results The cumulative exposure-TFR curves were inverted U-shaped for log gross domestic product (GDP) per capita and life expectancy at birth, while the cumulative exposure-response curves were approximately linear for female expected years of schooling and human development index (HDI). However, it is worth noting that in the developed regions, TFR increased slightly with the high level of GDP per capita, female expected years of schooling and HDI. Conclusions Nowadays, with the growth of GDP per capita, life expectancy at birth, female expected years of schooling and HDI, TFR are on a drastic downward trend in most regions. Besides, with the development of society, when levels of the factors continued to increase, TFR also showed a slight rebound. Therefore, governments, especially those in developing countries, should take measures to stimulate fertility and deal with a series of problems caused by declining TFR.

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Objective: We aimed to explore the effect of single nucleotide polymorphism (SNP) in the genes of the vitamin D (VitD) metabolic pathway and its interaction with VitD level during pregnancy on the development of hypertensive disorders of pregnancy (HDP). Methods: The study was conducted in the Zhoushan Maternal and Child Health Care Hospital, China, from August 2011 to May 2018. The SNPs in VitD metabolic pathway-related genes were genotyped. Plasma 25-hydroxyvitamin vitamin D (25(OH)D) levels was measured at first (T1), second (T2), and third (T3) trimesters. The information of systolic blood pressure (SBP) and diastolic blood pressure (DBP), and the diagnosis of HDP were extracted from the electronic medical record system. Multivariable linear and logistic regression models and crossover analysis were applied. Results: The prospective cohort study included 3699 pregnant women, of which 105 (2.85%) were diagnosed with HDP. After adjusting for potential confounders, VitD deficiency at T2, as well as the change of 25(OH)D level between T1 and T2, were negatively associated with DBP at T2 and T3, but not HDP. Polymorphisms in CYP24A1, GC, and LRP2 genes were associated with blood pressure and HDP. In addition, VitD interacted with CYP24A1, GC, and VDR genes’ polymorphisms on blood pressure. Furthermore, participants with polymorphisms in CYP24A1-rs2248137, LRP2-rs2389557, and LRP2-rs4667591 and who had VitD deficiency at T2 showed an increased risk of HDP. Conclusions: The individual and interactive association between VitD deficiency during pregnancy and SNPs in the genes of the VitD metabolic pathway on blood pressure and HDP were identified.

Maternal hemoglobin (Hb) is related to nutritional status, which affects neonatal birth weight. However, it is very common for maternal Hb to fluctuate during pregnancy. To evaluate the associations of maternal Hb in different time points and its changes during pregnancy with neonatal birth weight, small for gestational age (SGA)/low birth weight (LBW) and large for gestational age (LGA)/macrosomia, we conducted this study by using data from the Electronic Medical Record System (EMRS) database of Zhoushan Maternal and Child Care Hospital in Zhejiang province, China. The pregnancy was divided into five periods: first, early-second, mediate-second, late-second, early-third and late-third trimesters; we further calculated the maternal Hb changes during pregnancy. Overall, the socio-demographic characteristics, health-related information and childbirth-related information of 24,183 mother–infant pairs were obtained. The average Hb concentration during the different periods were 123.95 ± 10.14, 117.95 ± 9.84, 114.31 ± 9.03, 113.26 ± 8.82, 113.29 ± 8.68 and 115.01 ± 8.85 g/L, respectively. Significant dose–response relationships between maternal Hb and birth weight were observed in the first, late-second and later trimesters (p non-linear < 0.05). Maternal Hb < 100 g/L was related to a high risk of LGA/macrosomia in the late-second (OR: 1.47, 95% CI: 1.18, 1.83) and later trimesters; additionally, high maternal Hb (>140 g/L) increased the risk of SGA/LBW in the first (OR: 1.26, 95% CI: 1.01, 1.57) and late-third trimesters (OR: 1.96, 95% CI: 1.20, 3.18). In addition, the increase in maternal Hb from the late-second to late-third trimesters had a positive correlation with SGA/LBW. In conclusion, maternal Hb markedly fluctuated during pregnancy; the negative dose–response association of maternal Hb in the late-second and third trimesters, and Hb change during pregnancy with neonatal birth weight outcomes were observed, respectively. Furthermore, the phenomenon of high Hb in the first trimester and after the late-second trimester and the increase of maternal Hb from the late-second to late-third trimesters more significantly increasing the risk of SGA/LBW should especially be given more attention. Its biological mechanism needs to be further explored.

A number of SARS-CoV-2 variants that have evolved to have significant immune escape have emerged worldwide since the COVID-19 outbreak. The efficacy of prime vaccination is waning with the evolution of SARS-CoV-2, and the necessity of booster doses is more and more prominent. Therefore, this study aimed to compare the neutralization activity against the wild type and variants (Beta, Delta, and Omicron) in different prime–boost vaccination regimens. Electronic databases including PubMed, the Cochrane Library, Embase, medRxiv, Wanfang and CNKI were used to retrieve original studies. A total of 16 studies, 9 prime–boost vaccination regimes, and 3134 subjects were included in the meta-analysis and random effect models were used to estimate pooled neutralization titers. The neutralization activity against SARS-CoV-2 showed a significant decline with the evolution of the virus, especially in the populations primed with inactivated vaccines. For homologous immunization, only the populations boosted with mRNA vaccines consistently had a significant rise in neutralization titers (Beta: MD = 0.97; Delta: MD = 1.33; Omicron: MD = 0.74). While the heterologous immunization was more effective, the increment of neutralization titers against wild type, Beta, Delta and Omicron was 1.65 (95% CI: 1.32–1.96), 1.03 (95% CI: 0.53–1.54), 1.46 (95% CI: 1.07–1.85) and 1.15 (95% CI: 0.68–1.61), respectively. With the evolution of SARS-CoV-2, the effectiveness of prime immunization is waning. Although the administration of the booster dose could ameliorate the neutralization titers, homologous immunization regimens were gradually losing their effectiveness. Therefore, a heterologous booster dose is required, especially in populations primed with inactivated vaccines.

The association between vitamin D and hemoglobin has been suggested. Vitamin D can affect erythropoiesis by the induction of erythroid progenitor cell proliferation and enhance iron absorption by regulating the iron-hepcidin-ferroportin axis in monocytes. However, this relationship in pregnant women is scarce. The purpose of this study was to investigate the association between plasma vitamin D levels with hemoglobin concentration in pregnant women considering each trimester and iron supplementation. The data were obtained from Zhoushan Pregnant Women Cohort, collected from 2011 to 2018. Plasma 25(OH)D was measured in each trimester using liquid chromatography–tandem mass spectrometry. Generalized estimating equations and multiple linear regressions were performed. Finally, 2962 pregnant women and 4419 observations in the first trimester were included in this study. Plasma 25(OH)D in first trimester (T1) (β = 0.06, p = 0.0177), second trimester (T2) (β = 0.15, p < 0.0001), and third trimester (T3) (β = 0.12, p = 0.0006) were positively associated with Hb. Association between plasma 25(OH)D levels in T1 and Hb concentration was positively associated with gestational age (β = 0.005, p = 0.0421). Pregnant women with VD deficiency in T1 (OR = 1.42, 95% CI: 1.07–1.88) or T2 (OR = 1.94, 95% CI: 1.30–2.89) presented an increased risk of anemia, compared with women without VD deficiency. Moreover, the significant relationship between VD and Hb was only observed among women with iron supplementation during pregnancy. Plasma 25(OH)D levels in each trimester were positively associated with Hb concentration. Iron supplementation might be an important factor affecting the relationship between VD and Hb.