Risk-prediction nomogram for congenital heart disease in offspring of Chinese pregnant women.

BACKGROUND: The identification and assessment of environmental risks are crucial for the primary prevention of congenital heart disease (CHD). We were aimed to establish a nomogram model for CHD in the offspring of pregnant women and validate it using a large CHD database in Northwest China. METHODS: A survey was conducted among 29,204 women with infants born between 2010 and 2013 in Shaanxi province, Northwest China. Participants were randomly assigned to the training set and to the validation set at a ratio of 7:3. The importance of predictive variables was assessed using random forest. A multivariate logistic regression model was used to construct the nomogram for the prediction of CHD. RESULTS: Multivariate analyses revealed that the gravidity, preterm birth history, family history of birth defects, infection, taking medicine, tobacco exposure, pesticide exposure and singleton/twin pregnancy were significant predictive risk factors for CHD in the offspring of pregnant women. The area under the receiver operating characteristic curve for the prediction model was 0.716 (95% CI: 0.671, 0.760) in the training set and 0.714 (95% CI: 0.630, 0.798) in the validation set, indicating moderate discrimination. The prediction model exhibited good calibration (Hosmer-Lemeshow χ2 = 1.529, P = 0.910). CONCLUSIONS: We developed and validated a predictive nomogram for CHD in offspring of Chinese pregnant women, facilitating the early prenatal assessment of the risk of CHD and aiding in health education.

The Interactions between Maternal Iron Supplementation and Iron Metabolism-Related Genetic Polymorphisms on Birth Outcomes: A Prospective Study in Chinese.

BACKGROUND: The effect of iron supplementation during pregnancy on birth outcomes may vary with maternal genetic background and needs more investigation. OBJECTIVES: This prospective study aimed to evaluate the interactions between maternal iron supplementation and iron metabolism-related genetic polymorphisms on birth outcomes. METHODS: This was a substudy from a community-based randomized control trial conducted in Northwest China, which included 860 women from the 2 micronutrient supplementation groups (folic acid [FA] and FA + iron group). Maternal peripheral blood, sociodemographic and health-related information, and neonatal birth outcomes were collected. Six single nucleotide polymorphisms in iron metabolism-related genes were genotyped. The alleles associated with decreased iron/hemoglobin status were used as the effect alleles. The genetic risk score (GRS) that reflected the genetic risk of low iron/hemoglobin status was estimated using the unweighted and weighted methods. Generalized estimating equations with small-sample corrections were applied to evaluate the interactions between iron supplementation and SNPs/GRS on birth outcomes. RESULTS: There were significant interactions between maternal iron supplementation and rs7385804 (P = 0.009), rs149411 (P = 0.035), rs4820268 (P = 0.031), the unweighted GRS (P = 0.018), and the weighted GRS (P = 0.009) on birth weight. Compared with FA supplementation only, FA + iron supplementation significantly increased birth weight among women with more effect alleles in rs7385804 (ß: 88.8 g, 95% CI: 9.2, 168.3) and the GRSs (the highest unweighted GRS, ß: 135.5 g, 95% CI: 7.7, 263.4; the highest weighted GRS, ß: 145.9 g, 95% CI: 43.4, 248.5); it had a trend of decreasing birth weight and increasing low birth weight risk among women with fewer effect alleles. CONCLUSIONS: In our population, maternal genetic background related to iron metabolism plays a significant role in determining the efficacy of iron supplementation. Routine iron supplementation could be more beneficial to fetal weight growth among mothers with higher genetic risk for low iron/hemoglobin status.

Maternal Dietary Inflammatory Potential and Offspring Birth Outcomes in a Chinese Population.

BACKGROUND: Chronic inflammation perturbations during pregnancy may impact fetal growth; however, research on the association between dietary inflammation and birth outcomes is limited and inconsistent. OBJECTIVES: This study seeks to assess whether the dietary inflammatory potential is related to birth outcomes among pregnant women in China. METHODS: A total of 7194 mothers aged 17-46 y and their infants in China were included in this cross-sectional study. Dietary intake was assessed by a FFQ, which yielded scores on the energy-adjusted dietary inflammatory index (E-DII). Birth outcomes included birth weight, gestational age, birth weight z score, low birth weight (LBW), macrosomia, preterm birth, small-for-gestational-age (SGA), large-for-gestational-age (LGA), and birth defects. Generalized estimating equation and restricted cubic spline fit each outcome on continuous or quartiles of E-DII after adjusting for covariates. RESULTS: The maternal E-DII ranged from -5.35 to 6.77. Overall, birth weight and gestation age (mean ± SD) were 3267.9 ± 446.7 g and 39.6 ± 1.3 wk, respectively, and the birth weight z score was 0.02 ± 1.14. A total of 3.2% of infants were born with LBW, 6.1% with macrosomia, 3.0% were preterm birth, 10.7% were born SGA, 10.0% were born LGA, and 2.0% were born with birth defects. E-DII was associated with a 9.8 g decrease in birth weight (95% CI: -16.9, -2.6) and a 1.09-fold (95% CI: 1.01, 1.18), 1.11-fold (95% CI: 1.02, 1.21), and 1.12-fold (95% CI: 1.02, 1.24) greater risk of LBW, preterm birth, and birth defects, respectively. The maternal E-DII score was nonlinearly associated with gestational age (P for linearity = 0.009, P for curvature = 0.044). CONCLUSIONS: Among pregnant Chinese women, proinflammatory diets during pregnancy were related to reduced offspring birth weight and an increased risk of LBW, preterm birth, and birth defects. These findings might inform potential prevention strategies for pregnant women in China.

Maternal exposure to housing renovation during the periconceptional period and the risk of offspring with isolated congenital heart disease: a case-control study.

BACKGROUND: Congenital heart disease (CHD) is the most prevalent birth defect in recent decades. The aim of this research was to examine the association between maternal housing renovation exposure during the periconceptional period and isolated congenital heart disease (CHD) in their offspring. METHODS: A multi-hospitals case-control study was conducted from six tertiary A hospitals in Xi'an, Shaanxi, Northwest China based on questionnaires and interviews to address this question. The cases included fetuses or newborns diagnosed with CHD. Controls consisted of healthy newborns without birth defects. In total, 587 cases and 1180 controls were enrolled in this study. The association between maternal periconceptional housing renovation exposure and isolated CHD for offspring was assessed by estimating odds ratios (OR) with multivariate logistic regression models. RESULTS: After adjusting for potential confounding variables, it was found that maternal exposure to home improvement projects was associated with a higher probability of isolated CHD in offspring (adjusted OR: 1.77, 95% CI: 1.34, 2.33). Additionally, the risk of the ventricular septal defect (VSD) and patent ductus arteriosus (PDA) for CHD types was significantly associated with maternal exposure to housing renovations (VSD: adjusted OR = 1.56, 95% CI: 1.01, 2.41; PDA: adjusted OR = 2.50, 95% CI: 1.41, 4.45). CONCLUSIONS: Our study suggests that maternal exposure to housing renovation during the periconceptional period was associated with an increased risk of isolated CHD in offspring. Consequently, it would be beneficial to avoid living in a renovated home from 12 months before pregnancy through the first trimester to lower isolated CHD in infants.

Association of antenatal vitamin B complex supplementation with neonatal vitamin B12 status: evidence from a cluster randomized controlled trial.

PURPOSE: Evidence about the effect of maternal vitamin B12 supplementation on offspring's vitamin B12 status is limited. The present interventional study sought to evaluate the association of antenatal vitamin B complex supplementation with neonatal vitamin B12 status. METHODS: In an ongoing cluster randomized controlled trial conducted in three rural counties in northwest China, pregnant women < 20 weeks of gestation were randomized to three treatment groups: blank control, iron supplements, or vitamin B complex supplements. All women were administered folic acid supplements during the periconceptional period. In a sub-study, we collected cord blood samples of 331 participants from the control or vitamin B complex groups in the Xunyi county from January 2017 to December 2017. Plasma concentrations of folate, vitamin B12, and homocysteine were measured. Linear mixed models with a random intercept for cluster were used to compare biochemical indexes between groups after controlling for covariates. RESULTS: Compared with newborns whose mothers were in the control group, newborns of the vitamin B complex-supplemented women had significantly higher cord plasma vitamin B12 (P = 0.001) and lower homocysteine concentrations (P = 0.043). The association of antenatal vitamin B complex supplementation with cord blood vitamin B12 concentrations appeared to be more pronounced among newborns with high folate status than those with low folate status (Pinteraction = 0.060). CONCLUSIONS: Maternal vitamin B complex supplementation during pregnancy was associated with better neonatal vitamin B12 status in rural northwest China.

Maternal dietary patterns during pregnancy derived by reduced-rank regression and birth weight in the Chinese population.

Few studies have investigated the association between maternal dietary patterns (DP) during pregnancy, derived from reduced-rank regression (RRR), and fetal growth. This study aims to identify DP during pregnancy associated with macro- and micronutrient intakes, using the RRR method, and to examine their relationship with birth weight (BW). We used data of 7194 women from a large-scale cross-sectional survey in Northwest China. Dietary protein, carbohydrate, haem Fe density and the ratio of PUFA and MUFA:SFA were used as the intermediate variables in the RRR model to extract DP. Generalised estimating equation models were applied to evaluate the associations between DP and BW and related outcomes (including BW z-score, low birth weight (LBW) and small for gestational age (SGA)). Four DP during pregnancy were identified. Socio-demographically disadvantaged pregnant women were more likely to have lower BW and lower adherence to DP1 (high legumes, soyabean products, vegetables and animal-source foods, with relative low wheat and oils). Women with medium and high adherence to DP1 had significantly increased BW (medium 28·6 (95 % CI 7·1, 50·1); high 25·2 (95 % CI 2·7, 47·6)) and BW z-score and had significantly reduced risks of LBW and SGA. The associations were stronger among women with babies <3100 g. There is no association between other DP and outcomes. Higher adherence to the DP that was high in legumes, soyabean products, vegetables and animal-source foods was associated with improved BW in the Chinese pregnant women, particularly among those with disadvantageous socio-demographic conditions.

Lipid/Hyaluronic Acid-Coated Doxorubicin-Fe3O4 as a Dual-Targeting Nanoparticle for Enhanced Cancer Therapy.

Development of a delivery system to lower systemic toxicity and enhance doxorubicin (DOX) antitumor efficacy against multi-drug resistant (MDR) tumors is of great clinical significance. Here, lipid/hyaluronic acid (HA)-coated DOX-Fe3O4 was characterized to determine its optimal safety and efficacy on a tumor. DOX was first conjugated onto the Fe3O4 NPs surface, which was subsequently coated with phosphatidylcholine (PC) lipids, which consisted of a tumor cell-targeting HA ligand, to generate a dual-targeting nanoparticle (NP). DOX-Fe3O4 synthesis was validated by the Fourier-transform infrared (FT-IR) analysis results. Core-shell PC/HA@DOX-Fe3O4 formation, which had an average particle size of 48.2 nm, was observed based on the transmission electron microscopy (TEM) and dynamic laser light scattering (DLS) results. The saturation magnetization value of PC/HA@DOX-Fe3O4 was discovered to be 28 emu/g using vibrating-sample magnetometry. Furthermore, the designed PC/HA@DOX-Fe3O4 achieved greater MCF-7/ADR cellular uptake and cytotoxicity as compared with DOX. In addition, PC/HA@DOX-Fe3O4 exhibited significant DOX tumor-targeting capabilities and enhanced tumor growth inhibition activity in the xenograft MCF-7/ADR tumor-bearing nude mice following magnetic attraction and ligand-mediated targeting, with less cardiotoxicity. Therefore, PC/HA@DOX-Fe3O4 is a potential candidate for MDR tumor chemotherapy. Graphical abstract.

The association of maternal dietary folate intake and folic acid supplementation with small-for-gestational-age births: a cross-sectional study in Northwest China.

The effect of maternal folate intake on small-for-gestational-age (SGA) births remains inconclusive. The present study aimed to investigate the associations of maternal folate intake from diet and supplements with the risk of SGA births using data from a cross-sectional study in Shaanxi Province of Northwest China. A total of 7307 women who were within 12 months (median 3; 10th-90th percentile 0-7) after delivery were included. Two-level models were adopted to examine the associations of folate (dietary folate, supplemental folic acid and total folate) intake with the risk of SGA births and birth weight Z score, controlling for a minimum set of confounders that were identified in a directed acyclic graph. Results showed that a higher supplemental folic acid intake during the first trimester was negatively associated with the risk of SGA births (≤60 d v. non-use: OR 0·80; 95 % CI 0·66, 0·96; >60 d v. non-use: OR 0·78; 95 % CI 0·65, 0·94; Ptrend = 0·010; per 10-d increase: OR 0·97; 95 % CI 0·95, 0·99). A higher total folate intake during pregnancy was associated with a reduced risk of SGA births (highest tertile v. lowest tertile: OR 0·77; 95 % CI 0·64, 0·94; Ptrend = 0·010; per one-unit increase in the log-transformed value: OR 0·81; 95 % CI 0·69, 0·95). A similar pattern was observed for the birth weight Z score. Our study suggested that folic acid supplementation during the first trimester and a higher total folate intake during pregnancy were associated with a reduced risk of SGA births.

Socioeconomic disparity in the diet quality of pregnant women in Northwest China.

BACKGROUND AND OBJECTIVES: Few studies have described the socioeconomic disparity of dietary quality in Northwest China. The present study aimed to evaluate the diet quality of pregnant women in Shaanxi province of Northwest China by using the Diet Balance Index for Pregnancy (DBI-P) and explored the relationships with socioeconomic status (SES). METHODS AND STUDY DESIGN: A cross-sectional analysis of data from 7,630 women who were pregnant during 2012-2013 was performed. Dietary intake during the whole pregnancy was assessed by FFQ within 12 months (median, 3 months; 10th-90th percentile, 0-7 months) after delivery. Diet quality evaluated by the DBI-P was related to socioeconomic factors. RESULTS: Most women had insufficient consumption of vegetables (72.27%), dairy (89.58%), meat (82.07%), fish and shrimp (92.23%), eggs (62.54%), and dietary variety (97.92%). 67.76% of women had excessive intake of grains, and 87.77% and 69.79% of participants had surplus consumption of edible oil and salt respectively. Women with higher education, occupation and household wealth index (HWI) consumed more vegetables, fruit, dairy, soybean and nuts, meat, fish and shrimp, eggs, edible oil, alcohol and dietary variety but less grains and salt. After adjusting for confounders, education, occupation and HWI were negatively associated with the level of inadequate dietary intake. Conversely, individuals with medium HWI had higher level of excessive dietary intake compared to low HWI groups. CONCLUSIONS: The diet quality of pregnant women in Northwest China was associated with SES. Socioeconomic disparities in diet quality should be considered when planning nutrition interventions for pregnant women.

Glutathione depletion and dihydroorotate dehydrogenase inhibition actuated ferroptosis-augment to surmount triple-negative breast cancer.

Ferroptosis is a promising therapeutic approach for combating malignant cancers, but its effectiveness is limited in clinical due to the adaptability and self-repair abilities of cancer cells. Mitochondria, as the pivotal player in ferroptosis, exhibit tremendous therapeutic potential by targeting the intramitochondrial anti-ferroptotic pathway mediated by dihydroorotate dehydrogenase (DHODH). In this study, an albumin-based nanomedicine was developed to induce augmented ferroptosis in triple-negative breast cancer (TNBC) by depleting glutathione (GSH) and inhibiting DHODH activity. The nanomedicine (ATO/SRF@BSA) was developed by loading sorafenib (SRF) and atovaquone (ATO) into bovine serum albumin (BSA). SRF is an FDA-approved ferroptosis inducer and ATO is the only drug used in clinical that targets mitochondria. By combining the effects of SRF and ATO, ATO/SRF@BSA promoted the accumulation of lipid peroxides within mitochondria by inhibiting the glutathione peroxidase 4 (GPX4)-GSH pathway and downregulating the DHODH-coenzyme Q (CoQH2) defense mechanism, triggers a burst of lipid peroxides. Simultaneously, ATO/SRF@BSA suppressed cancer cell self-repair and enhanced cell death by inhibiting the synthesis of adenosine triphosphate (ATP) and pyrimidine nucleotides. Furthermore, the anti-cancer results showed that ATO/SRF@BSA exhibited tumor-specific killing efficacy, significantly improved the tumor hypoxic microenvironment, and lessened the toxic side effects of SRF. This work presents an efficient and easily achievable strategy for TNBC treatment, which may hold promise for clinical applications.