Jiang-Nan Wu

Objective: The aim of this study was to investigate the relationship between human epididymis protein 4 (HE4) levels in seminal plasma and semen liquefaction in males. Methods: A total of 314 healthy men from the andrology department were included. The correlations between HE4 levels and prostate‐specific antigen (PSA) levels as well as conventional semen parameters (sperm density, the proportion of non‐progressively motile spermatozoa, seminal liquefaction time) were analyzed, and logistic regression was further employed to examine the association between HE4 levels and the risk of poor semen liquefaction. Results: The level of HE4 in seminal plasma was negatively correlated with semen liquefaction time (r = −0.207, p < 0.001) and positively correlated with seminal plasma PSA levels ( r = 0.280, p < 0.001), suggesting a potential link to the process of semen liquefaction. Continuous HE4 levels were standardized by dividing by 100, and participants were then categorized into quartiles (Q1–Q4) based on the standardized HE4 values. After adjusting for confounding factors, the risk of poor semen liquefaction in the Q3, Q2, and Q1 groups of the lower HE4 level was 4.024 times (95% CI: 1.908–8.485; p < 0.001), 6.320 times (95% CI: 2.818–14.175; p < 0.001), and 5.190 times (95% CI: 2.217–12.15; p < 0.001) higher, respectively, compared to the highest HE4 quartile (Q4). Conclusion: This suggests that a low level of HE4 in seminal plasma is an independent risk factor for poor semen liquefaction.

The effects of thyroid hormone replacement or suppression therapy in women with thyroid cancer on thyroid function during pregnancy and subsequent adverse fetal outcomes are still largely unknown. To compare thyroid function at 8 weeks of gestation and its changes during pregnancy between the survivors and controls, and to assess the association of these differences with adverse fetal outcomes. This was a retrospective cohort-based parallel control study. A total of 140 survivors and 280 controls delivery time-matched controls were extracted from 46,610 singleton pregnant women who received prenatal examinations in a second-level specialized hospital between January 2019 and March 2024. The primary outcomes were birth defects, small for gestational age (SGA, defined as birth weight < 10th percentile by gestational week), preterm birth (< 37 weeks), and neonatal asphyxia (defined as fetuses with a 1 min-Apgar score of < 7). Apgar scores at 1 and 5 min and umbilical arterial blood gas (ABG) indexes were surrogate indicators of neonatal asphyxia. Compared to the control group, FT3 was lower in the survivors, while FT4 was higher. Change of FT3 between 8 and 16 weeks of gestation in survivors was significantly smaller than that in the controls (-0.08 vs. -0.30, P < 0.005). The survivors had an insignificant association with SGA/preterm birth (adjusted OR 2.06, 0.68-6.23, P = 0.20), a slightly higher risk of fetal asphyxia (Peto OR, 6.49; 95% CI: 0.81-52.0; P = 0.078), and a lower 1 min Apgar score (β, -0.10; 95% CI: -0.16 to -0.03;P = 0.004). Change in FT3 between 8 and 16 weeks was associated with SGA/preterm birth (adjusted OR, 4.42, 95%CI: 1.32-14.84, P = 0.016). FT3 at 8 weeks of gestation and its changes between 16 and 32 weeks of gestation were negatively correlated with the umbilical ABG index, with both β of -0.02(p = 0.015 and 0.019, respectively). This study found differences in FT3 and FT4 levels and their changes during pregnancy between the survivors and controls. These differences, especially the changes in FT3 during pregnancy, might suggest a potential biological link, though further studies are needed to establish causality.

To assess the value of early gestational head circumference (HC) for predicting subsequent fetal death in women whose fetuses had increased nuchal translucency (NT). Gestational age-specific NT and HC Z scores were calculated. The threshold for NT was confirmed by comparing the difference in HC predictive value for fetal death (including early fetal death [12–19 weeks] and stillbirth [≥ 20 weeks]) between NT groups (normal or increased NT). Thresholds for HC prediction of fetal death in fetuses with increased NT were confirmed, with corresponding sensitivity and specificity. The performance and clinical value of the model were evaluated. Multiple imputation method was conducted to assess the robustness of the results. A total of 16,436 women and their fetuses were included in the analysis. Fetal HC was lower in fetal deaths than in live births (P < 0.005). The 80th percentile was a preferred threshold for increased NT. The difference in HC between live and dead fetuses persisted in fetuses with NT > 80th percentile (median of HC Z score: − 0.66 vs. 0.34, P < 0.001), but not in those with NT ≤ 80th percentile. The HC Z score was valuable for predicting fetal death in fetuses with increased NT, with a sensitivity of 74% and specificity of 76%. The prediction was useful for early fetal death, not stillbirth. Internal validation showed that the model has good predictive performance and clinical utility. Multiply imputation analysis shows that the association of low HC with fetal death and its predictive value were weakened. The early gestational age-specific HC Z score was associated with fetal death, particularly early fetal death, in fetuses with NT above the 80th percentile. Definitive validation through large-scale cohorts with protocol-based routine HC measurements is warranted before considering clinical application.

To clarify the uncertain association between maternal total triiodothyronine (TT3) levels and preeclampsia risk. In a hospital-based cohort of pregnant women with universal thyroid testing, we assessed the association between TT3 and preeclampsia using directed acyclic graphs (DAG) to control confounders. Maternal TT3 levels were associated with preeclampsia risk, with an adjusted odd ratio (OR) of 2.32 (95% confidence interval (CI) 2.02–2.68) in women with the highest TT3 quartile comparing to those in the lowest quartile. A J-shaped association was identified for early onset preeclampsia, with particularly strong association when thyroid-stimulating hormone exceeded 2.5 μIU/mL (OR, 17.22, 95% CI 4.52–65.60). Gestational age > 18 weeks at measurement significantly modified the effect of TT3 on preeclampsia risk, with an interaction OR of 3.22 (95% CI 1.56–6.62). Increased maternal TT3 levels were associated with preeclampsia. TT3 may contribute to preeclampsia pathogenesis and serve as a clinical biomarker, especially for early onset cases with thyroid dysfunction.

Background: Folic acid (FA) supplementation is associated with a lower risk of the neural tube and heart defects and is recommended for women of childbearing age. Although there are detailed recommendations, differences in the initiation time and duration of FA supplementation remain poorly studied. Methods: A multicentre prospective study of 17,713 women was conducted. The incidence of congenital malformations in women taking a recommended dosage (e.g. 0.4 or 0.8 mg/day) of FA was compared with that in women without supplementation. The predicted probability of malformations by the initiation time and duration of FA use was estimated to determine optimal options. Results: Periconceptional FA supplementation was associated with a lower and insignificant risk of congenital malformations (1.59% vs. 2.37%; odds ratio [OR] 0.69; 95% confidence interval [CI]: 0.44–1.08), heart defects (3.8 vs. 8.0 per 1000 infants; OR, 0.47; 0.21–1.02), and neural tube defects (7.0 vs. 11.5 per 10,000 infants; OR, 0.64; 0.08–5.15). FA use after pregnancy provided greater protection against total malformations. Statistically significant associations were found in women who initiated FA supplementation in the first month of gestation (OR, 0.55; 95% CI: 0.33–0.91) and in those who supplemented for 1 to 2 months (OR, 0.59; 95% CI: 0.36–0.98). Similar results were found for heart defects. The optimal initiation time was 1.5 (optimal range: 1.1 to 1.9) months before pregnancy and a duration of 4.0 (3.7 to 4.4) months was reasonable to achieve the lowest risk of congenital malformations. Heart defect prevention required an earlier initiation (2.2 vs. 1.1 months before pregnancy) and a longer duration (4.7 vs. 3.7 months) than the prevention of other malformations. Conclusions: The timely initiation of FA supplementation for gestation was associated with a decreased risk of congenital malformations, which was mainly attributed to its protection against heart defects. The initiation of FA supplementation 1.5 months before conception with a duration of 4 months is the preferred option for congenital malformation prevention. Trial registration: Chictr.org.cn identifier: ChiCTR-SOC-17010976.

Introduction: The potential teratogenic risk of traditional Chinese medicine (TCM) is of widespread concern; however, related evidence is largely absent in humans. This study aimed to compare the prevalence of congenital malformations between pregnant women with and without TCM exposure.Material and methods: This was a multicenter prospective cohort study of 17 713 women who participated in a survey on periconceptional TCM exposure. Primary outcome was congenital malformations diagnosed from a survey conducted on the day 42 after delivery.Results: A total of 16 751 pregnant women with 273 congenital malformations were included in the analysis. Fetuses exposed to TCM had an increased risk of congenital malformations compared to those without exposure (odds ratio [OR] 2.10; 95% confidence interval [CI] 1.09–4.02) after controlling for potential confounders. There were significant associations with congenital malformations in women with early pregnant exposure (OR 2.04, 95% CI 1.00–4.20) and for those who received ≥2 TCM formulas (OR 5.84, 95% CI 1.44–23.65). Pre‐pregnancy TCM exposure was significantly associated with an increased risk of congenital heart defects (OR 12.69; 95% CI 3.01–53.51).Conclusions: Periconceptional TCM exposure is associated with an increased risk of congenital malformation. This effect was cumulative and sensitive to periconceptional age. Therefore, TCM deserves more attention and should be used cautiously for pregnant women and those trying to become pregnant.

Background: Female offspring was associated with a high risk of postpartum depression (PPD) during the one-child policy period in China. However, little is known about the association between maternal expectations on fetal gender and the risk of PPD in the context of the new two children policy implemented in 2016. Methods: We conducted a hospital-based cohort study of women with singleton pregnancies between 2017 and 2018 (n = 991) to address this concern. Logistic regression was run to estimate the association between unexpected fetal gender and the risk of PPD. Results: A total of 127 women (12.8%) were diagnosed with PPD. Compared with women who achieved fetal gender expectations, the odds ratio (OR) for PPD among those who had an unexpected fetal gender was 2.44 (95% confidence interval (CI): 1.30–4.58) (in the backward method logistic regression model) and 2.25 (95% CI: 1.21–4.18) (in the forward method model), respectively. The disparity of the association was significant among primiparous and pluriparous women (OR, 2.52, 95% CI: 1.32–4.84, P = 0.005 vs. OR, 0.91, 95% CI: 0.09–8.75, P = 0.932). Fetal gender expectations accounted for about 15% of the risk of PPD in the structural equation models. Conclusions: These results indicated that unexpected fetal gender was associated with an increased risk of PPD among Chinese primiparous women.

The increased dose of hepatitis B vaccine has been adopted for newborns since 2013 in Fujian, China. However, little is known about the impact of this measure on hepatitis B virus (HBV) prevention. We used the seroepidemiological surveys conducted in 2014 and 2020 to address the concern. Compared with subjects who received a 5 μg hepatitis B vaccine, participants who took a 10 μg hepatitis B vaccine were associated with a lower risk of HBV infection (adjusted odds ratio [OR] 0.26, 95% confidence interval [CI]: 0.10–0.68) and a marginal reduction risk of anti-HBc positive (OR, 0.37; 95% CI: 0.13–1.08; P = .07), but not for HBsAg carrier risk. The relation between vaccine dose and risk of anti-HBc positive (OR, 0.20; 95% CI: 0.05–0.81) became slightly stronger and significant among children investigated in 2020 who probably received universal vaccination. No significant association was found for subjects whose mothers were positive for HBsAg. The current 10 μg hepatitis B vaccines for universal vaccination for newborns are reasonable and effective in HBV prevention. More measures should be taken to reduce the risk of HBsAg carriers for infants whose mothers are positive for HBsAg.

China has regulated its hepatitis B vaccination policy. However, data on the prevalence of hepatitis B virus (HBV) infection have not been updated since 2014. In addition, the impact of the policy on awareness of hepatitis B is limited, especially in Fujian Province where HBV infection is highly prevalent. We conducted a sero-epidemiological survey in five national monitoring counties to address these concerns. A total of 5,873 subjects were included and classified into four birth cohorts according to the policy time nodes (1981, 1992, and 2002). The HBsAg carrier rate for the general population was 8.6% (95% confidence interval [CI]: 7.9–9.3). Compared with those born before 1981, adjusted odds ratios (OR) for HBV infection were 0.51 (95% CI: 0.43–0.62), 0.10 (0.08–0.12), and 0.015 (0.01–0.023) among the 1981–1991, 1992–2001, and ≥2002 birth cohorts, respectively; while the OR was 1.26 (1.00–1.57), 0.39 (0.26–0.58), and 0.019 (0.006–0.06) for HBsAg carriage, respectively. Among the 4865 residents aged ≥15 years, hepatitis B awareness has been declining since the introduction of the hepatitis B vaccine into the immunization program (β = −0.25, SE = 0.08, P = .001, and β = −0.20, SE = 0.08, P = .017 for 1992–2001 and ≥2002 birth cohort, respectively). This decline was obvious for the initiation time of the first dose of the hepatitis B vaccine. Although the hepatitis B vaccination policies have helped reduce the infection, the awareness has declined. More measures on the target population are warranted to improve the public’s awareness of hepatitis B vaccination in the context of great achievements.