Background/objectives: Hypertensive disorders in pregnancy (HDP) are associated with an increased risk of neonatal complications; however, their effects on neonatal metabolism remain inadequately understood. The aim of this study was to assess the association between HDP and neonatal amino acid and acylcarnitine levels.Methods: In this retrospective case–control study, 1,228 singleton pregnant women diagnosed with HDP and 1,228 normal singleton pregnant women whose newborns underwent newborn screening for 11 amino acids and 31 acylcarnitines were recruited from January 2021 to December 2023.Results: After adjusting for potential confounding factors, including gestational age at delivery, birth weight and neonatal sex, nine amino acids exhibited significant differences between infants born to mothers in the HDP subgroups compared to those born to mothers with normal pregnancies. These amino acids were involved in arginine and proline metabolism and the urea cycle pathway. Amino acid levels also varied among the HDP subgroups. Additionally, the levels of short-, medium-, and long-chain acylcarnitines were significantly higher in newborns born to mothers in the HDP subgroups than in newborns born to mothers in the normal pregnancy group. However, no statistically significant differences were observed among the four HDP subgroups.Conclusion: Our findings revealed a significant link between HDP and neonatal amino acid and acylcarnitine levels, which were involved in arginine and proline metabolism, the urea cycle, and fatty acid oxidation. These results underscore the significance of identifying maternal conditions that affect newborn metabolites to ensure adequate nutrition and enhance neonatal health outcomes.

Introduction: Fetal macrosomia is related to adverse neonatal and maternal health outcomes. Therefore, we aimed to evaluate the risk factors for macrosomia and establish multivariable prediction models to enable early identification, prevention, and mitigation of its adverse outcomes.Methods: This retrospective case-control study included 800 singleton pregnant women who delivered in 2022 at Fujian Maternity and Child Health Hospital and Quanzhou Women and Children's Hospital. They were categorized into the macrosomia [birth weight (BW) ≥ 4,000 g, n = 400] and non-macrosomia (BW = 2,500–3,999 g, n = 400) groups according to the BW of the newborns. Prediction models in singleton fetuses during mid-to-late pregnancy and before delivery were constructed.Results: Maternal height ≥ 165 cm [odds ratio (OR) = 2.303, 95% confidence interval (CI): 1.232–4.305], pre-pregnancy overweight (OR = 2.166, 95% CI: 1.119–4.195), pre-pregnancy obesity (OR = 3.189, 95% CI: 1.020–9.968), excessive gestational weight gain in the second trimester (OR = 2.083, 95% CI: 1.250–3.470), and at least two abnormal blood glucose values in the oral glucose tolerance test (OR = 5.267, 95% CI: 1.814–15.29) were identified as risk factors for macrosomia. Additionally, maternal abdominal circumference (AC) plus fundal length ≥ 140 cm (OR = 6.283, 95% CI: 3.976–9.927), fetal biparietal diameter ≥ 10 cm (OR = 3.373, 95% CI: 1.103–10.31), fetal head circumference ≥ 35 cm (OR = 3.473, 95% CI: 1.334–9.041), and fetal AC ≥ 36 cm at pre-delivery (OR = 23.46, 95% CI: 14.81–37.16) were risk factors for macrosomia.Discussion: The construction of the macrosomia prediction model in singleton fetuses during mid-to-late pregnancy and before delivery showed a strong predictive value. This study identified key high-risk factors for macrosomia during the perinatal period. The macrosomia prediction model developed here is expected to enable early identification of macrosomia, allowing for timely interventions aimed at reducing the risk of adverse perinatal outcomes.

The estimated prevalence of tetrahydrobiopterin deficiency (BH4D) and the mutational spectrum of the causal 6-pyruvoyl-tetrahydropterin synthase (PTS) gene vary widely according to race and region. This study assessed the prevalence and genetic characteristics of BH4D in Fujian Province, southeastern China. A total of 3,204,067 newborns were screened between 2012 and 2022 based on the phenylalanine level and the phenylalanine/tyrosine ratio in dried blood spots. Differential diagnosis was determined by the urine purine spectrum, dihydropteridine reductase activity in red blood cells, and genetic testing. The PTS mutation spectrum and genotypes were determined by next-generation sequencing. A total of 189 newborns were diagnosed with hyperphenylalaninemia (HPA) over the study period, including 159 with phenylalanine hydroxylase deficiency and 30 with BH4D. Therefore, the prevalence of BH4D in Fujian was 9.36 per 1,000,000 live births (30/3,204,067) and the proportion of BH4D among patients with HPA was 15.87% (30/189). A total of 58 PTS alleles were identified in the 29 patients with PTS deficiency (PTPSD), and those alleles were composed of 10 different variants, including eight missense variants and two splice-site variants. The most prevalent variants were c.155A>G, p.Asn52Ser (44.83%); c.259C>T, p.Pro87Ser (39.66%); and c.84-291A>G, p.Tyr27Argfs*8 (3.45%). The predominant genotype was c [155A>G]; [259C>T] (11/29, 37.93%). The prevalence of BH4D and the spectrum of associated PTS mutations were successfully determined for the first time in Fujian Province, southeastern China. Since the mutation spectrum of PTS is region-specific, such data will facilitate molecular diagnosis and genetic counseling in PTPSD cases.

Excessive cobalt exposure adversely affects the nervous system, yet the underlying neurotoxic mechanisms remain largely elusive. In the present study, using human neuroblastoma H4 cells exposed to cobalt chloride (CoCl₂) as an in vitro model, we demonstrate for the first time that CoCl₂ induces widespread alterations in m7G modification in genes associated with neurodegenerative disease. MeRIP-sequencing (MeRIP-seq) analysis revealed significant remodeling of m7G modification features, including sequence motifs, genomic distribution, and peak densities following CoCl₂ exposure. Differentially methylated genes were enriched in pathways governing nervous system function, neurotransmitter transport, neuronal projection guidance, axonogenesis, and axonal guidance. Integration of MeRIP-seq and RNA-seq data further demonstrated that CoCl₂ concurrently induced differential m7G methylation and expression of genes implicated in central nervous system function and neurodegenerative disease pathways. Mechanistically, CoCl₂ suppressed m7G modification levels by downregulating the methyltransferase complex components methyltransferase-like 1 (METTL1) and WD repeat domain 4 (WDR4). More importantly, METTL1 overexpression attenuated CoCl₂-induced downregulation of neurodegenerative disease-associated genes runt-related transcription factor 2 (RUNX2), repulsive guidance molecule A (RGMA), and unc-5 netrin receptor C (UNC5C) by modulating mRNA decay. Moreover, MeRIP-qPCR further confirmed that cobalt exposure significantly reduced m7G modification on these transcripts, and this reduction was restored by METTL1 overexpression, thereby supporting a regulatory role of m7G modification in target mRNA expression. These findings establish a pivotal role for m7G modification in environmental neurotoxicant-induced neurodegeneration and reveal cobalt-related RNA regulatory paradigm that expands our understanding of heavy metal-driven epitranscriptomic dysregulation, and hence offering novel therapeutic targets.

Objective: This study investigated iron-deficiency anemia (IDA), third-trimester hepcidin and ferroportin levels, and perinatal outcomes in twin pregnancies. Study design: Pregnant women with twin gestations ( n = 195) were enrolled and classified into an IDA group ( n = 63; further subdivided into adverse and non-adverse perinatal-outcome subgroups) and a non–iron-deficiency anemia group ( n = 132). Serum hepcidin and ferroportin were measured at ≥28 weeks of gestation. Analyses included multivariate logistic regression and receiver operating characteristic curve assessments. Results: The prevalence of IDA was 32.3%. Hepcidin showed positive correlations with red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. Ferroportin showed negative correlations with these indices as well as with hepcidin. Adverse outcomes occurred in 84.1% of pregnancies complicated by iron-deficiency anemia. The combined decrease in hepcidin and hemoglobin levels, together with an increase in ferroportin concentrations, yielded an area under the curve of 0.940 for predicting adverse outcomes. Conclusion: IDA is common in twin pregnancies and is strongly associated with unfavorable maternal–fetal outcomes. The combined measurement of hepcidin, ferroportin, and hemoglobin has diagnostic and predictive value in assessing iron-deficiency anemia in twin pregnancies.

Background/objectives: Maternal hypothyroidism during pregnancy, including overt and subclinical hypothyroidism, is a common endocrine disorder complicating pregnancy and is associated with increased risks of adverse maternal and fetal outcomes. However, its effects on neonatal metabolism remain inadequately understood. This study aimed to assess the association between hypothyroidism in pregnancy and neonatal amino acid and acylcarnitine levels. Methods: This retrospective case–control study included 1,987 pregnant women with overt hypothyroidism in pregnancy, 2,023 with subclinical hypothyroidism in pregnancy, and 2,043 euthyroid pregnant women from Fujian Provincial Maternity and Children’s Hospital between 2016 and 2024. Their newborns all underwent newborn screening for 11 amino acids and 31 acylcarnitines using tandem mass spectrometry. Results: After adjusting for potential confounding factors including gestational age at delivery, birth weight, and neonatal sex, newborns born to mothers with hypothyroidism in pregnancy (overt and subclinical) showed significant differences in the levels of 9 amino acids compared with those born to mothers with normal thyroid function. These amino acids are involved in the arginine-proline metabolism, glycine metabolism, and the urea cycle pathway. Amino acid levels also differed between the two subtypes. In addition, the levels of short-chain, medium-chain, and long-chain acylcarnitines in newborns from the hypothyroidism groups were significantly higher than those in the control group, with several acylcarnitine indicators (C16, C16:1, C16OH, C18:1OH, and C6DC) exhibiting characteristic differences between the two subtypes. The levels of thyroid-stimulating hormone (TSH) in newborns from both hypothyroidism groups were significantly higher than those in the control group, whereas no statistically significant difference in TSH levels was observed between the overt and subclinical hypothyroidism groups. Conclusion: Our findings revealed a significant association between hypothyroidism in pregnancy (overt and subclinical) and neonatal amino acid and acylcarnitine levels, which were mainly involved in branched-chain amino acid, arginine, proline, and glycine metabolism, as well as the urea cycle and fatty acid oxidation pathways. These results underscore the importance of identifying maternal conditions that correlate with neonatal metabolites, providing a reference for exploring strategies to optimize neonatal nutrition and improving long-term health outcomes.