bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early-Pregnancy Intermediate Hyperglycemia and Adverse Pregnancy Outcomes Among Women Without Gestational Diabetes
Authors: Ye Yunzhen , Xiong Yu , Zhou Qiongjie , Xiao Xirong , Li Xiaotian 
Published: December 2021

Abstract

Context
Universal early-pregnancy screening for overt diabetes reveals intermediate hyperglycemia (fasting plasma glucose [FPG] [5.1-6.9 mM]).

Objective
We evaluated the association between early-pregnancy intermediate hyperglycemia and adverse pregnancy outcomes among women without gestational diabetes.

Methods
This retrospective cohort study was conducted at the Obstetrics and Gynecology Hospital, Shanghai, China, from 2013 to 2017. All singleton pregnancies with FPG less than or equal to 6.9 mM in early pregnancy and receiving a 75-g oral glucose tolerance test (OGTT) were included. Women with prepregnancy diabetes were excluded. Individuals with normal OGTT were analyzed. Pregnancy outcomes for FPG less than 5.1 mM and intermediate hyperglycemia were evaluated. The primary outcomes were large for gestational age (LGA) and primary cesarean delivery. Multivariate logistic regressions were conducted. Statistical significance was defined as P less than .05.

Results
In total, 24 479 deliveries were included, of which 23 450 (95.8%) had normal OGTTs later in pregnancy (NGT). There were 807 (3.4%) women who had an FPG of 5.1 to 6.9 mM in early pregnancy. Compared to the NGT group with an FPG of less than 5.1 mM in early pregnancy (N = 20692), the intermediate hyperglycemia NGT group (N = 693) had a higher age and body mass index (BMI), and significantly higher rates of LGA, primary cesarean delivery, preterm birth, preeclampsia, and neonatal distress. The rates of primary cesarean delivery (adjusted odds ratio [AOR] 1.24; 95% CI, 1.05-1.45), preterm birth (AOR 1.75; 95% CI, 1.29-2.36), and neonatal distress (AOR 3.29; 95% CI, 1.57-6.89) remained statistically significantly higher after adjustments for maternal age, BMI, and other potential confounding factors.

Conclusion
Women with intermediate hyperglycemia in early pregnancy are at an increased risk for adverse maternal-fetal outcomes, even with normal future OGTTs.
Maternal Polycystic Ovary Syndrome and Offspring Birth Weight: A Mendelian Randomization Study
Authors: Gan Yuexin , Lu Donghao , Yan Chonghuai , Zhang Jun , Zhao Jian 
Published: December 2021

Abstract

Context
Observational associations between maternal polycystic ovary syndrome (PCOS) and offspring birth weight (BW) have been inconsistent and the causal relationship is still uncertain.

Objective
We conducted a 2-sample Mendelian randomization (MR) study to estimate the causal effect of maternal PCOS on offspring BW.

Methods
We constructed genetic instruments for PCOS with 14 single nucleotide polymorphisms (SNPs) which were identified in a genome-wide association study (GWAS) meta-analysis including 10 074 PCOS cases and 103 164 controls of European ancestry from 7 cohorts. The genetic associations of these SNPs with the offspring BW were extracted from summary statistics estimated by the Early Growth Genetics consortium (n = 406 063 European ancestry individuals) using the weighted linear model, an approximation method of structural equation model, which separated maternal genetic effects from fetal genetic effects. We used a 2-sample MR design to examine the causal relationship between maternal PCOS and offspring BW. Sensitivity analyses were conducted to assess the robustness of the MR results.

Results
We found little evidence for a causal effect of maternal PCOS on offspring BW (–6.1 g, 95% CI –16.8 g, 4.6 g). Broadly consistent results were found in the sensitivity analyses.

Conclusion
Despite the large scale of this study, our results suggested little causal effect of maternal PCOS on offspring BW. MR studies with a larger sample size of women with PCOS or more genetic instruments that would increase the variation of PCOS explained are needed in the future.
Conventional and Bidirectional Genetic Evidence on Resting Heart Rate and Cardiometabolic Traits
Authors: Huang Tao , Wang Wenxiu , Wang Jingjia , Lv Jun , Yu Canqing , Guo Yu , Pei Pei , Huang Ninghao , Yang Ling , Millwood Iona Y , Walters Robin G , Chen Yiping , Du Huaidong , Su Jian , Chen Junshi , Chen Zhengming , Tang Yida , Li Liming 
Published: December 2021

Abstract

Context
Observational studies have suggested that higher resting heart rate (RHR) may be associated with increased cardiometabolic risk. However, causal associations are not fully understood.

Objective
We aimed to examine the direction, strength, and causality of the associations of RHR with cardiometabolic traits.

Methods
We assessed the strength of associations between measured RHR and cardiometabolic traits in 506 211 and 372 452 participants from China Kadoorie Biobank (CKB) and UK Biobank (UKB). Mendelian randomization (MR) analyses were used to make causal inferences in 99 228 and 371 508 participants from CKB and UKB, respectively.

Results
We identified significant directionally concordant observational associations between RHR and higher total cholesterol, triglycerides (TG), low-density lipoprotein, C-reactive protein (CRP), glucose, body mass index, waist-hip ratio (WHR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) after the Bonferroni correction. MR analyses showed that 10 beat/min higher genetically predicted RHR was trans-ethnically associated with a higher DBP (beta 2.059 [95% CI 1.544, 2.574] mmHg in CKB; 2.037 [1.845, 2.229] mmHg in UKB), higher CRP (0.180 [0.057, 0.303] log mg/L in CKB; 0.154 [0.134, 0.174] log mg/L in UKB), higher TG (0.052 [−0.009, 0.113] log mmol/L in CKB; 0.020 [0.010, 0.030] log mmol/L in UKB) and higher WHR (0.218 [−0.033, 0.469] % in CKB; 0.225 [0.111, 0.339] % in UKB). In the opposite direction, higher genetically predicted SBP, TG, glucose, and WHR, and lower high-density lipoprotein, were associated with elevated RHR.

Conclusion
Our large-scale analyses provide causal evidence for associations between RHR and cardiometabolic traits, highlighting the importance of monitoring heat rate as a means of alleviating the adverse effects of metabolic disorders.
Risk Factors for and Effects of Persistent and Severe Hypophosphatemia Following Ferric Carboxymaltose
Authors: Schaefer Benedikt , Zoller Heinz , Wolf Myles 
Published: December 2021

AbstractContextHypophosphatemia, osteomalacia, and fractures are complications of certain intravenous iron formulations.ObjectiveThis study investigated risk factors for incident, severe, and persistent hypophosphatemia, and associated alterations in bone and mineral biomarkers following intravenous iron treatment.MethodsWe analyzed data from the PHOSPHARE-IDA randomized clinical trials, comprising 245 patients aged 18 years or older with iron deficiency anemia at 30 outpatient clinics in the United States who received intravenous ferric carboxymaltose (FCM) or ferric derisomaltose (FDI). Outcome measures included serum phosphate, intact fibroblast growth factor-23 (iFGF23), 1,25-dihydroxyvitamin D (1,25(OH)2D), ionized calcium, parathyroid hormone (PTH), and alkaline phosphatase.ResultsFCM was the only consistent risk factor for incident hypophosphatemia (&lt; 2.0 mg/dL; odds ratio vs FDI: 38.37; 95% CI: 16.62, 88.56; P &lt; 0.001). Only FCM-treated patients developed severe hypophosphatemia (&lt; 1.0 mg/dL; 11.3%; 13/115) or persistent hypophosphatemia (&lt; 2.0 mg/dL at study end; 40.0%; 46/115). More severe hypophosphatemia associated with significantly greater increases in iFGF23, PTH, and alkaline phosphatase, and more severe decreases in 1,25(OH)2D and ionized calcium (all P &lt; 0.05). Patients with persistent vs resolved hypophosphatemia demonstrated significantly greater changes in iFGF23, PTH, 1,25(OH)2D, and N-terminal procollagen-1 peptide levels (all P &lt; 0.01), but alkaline phosphatase increased similarly in both groups.ConclusionTreatment with FCM was the only consistent risk factor for hypophosphatemia. Patients who developed severe or persistent hypophosphatemia after FCM treatment manifested more severe derangements in bone and mineral metabolism. Changes in bone biomarkers continued beyond resolution of hypophosphatemia, suggesting ongoing effects on bone that may help explain the association of FCM with osteomalacia and fractures.
Prevalence and Determinants of Transient Congenital Hypothyroidism in Children With Eutopic Gland in France: A Retrospective Cohort Study
Authors: Barry Yaya , Mandereau-Bruno Laurence , Bonaldi Christophe , Cheillan David , Coutant Régis , Léger Juliane , Regnault Nolwenn 
Published: December 2021

Abstract

Context
The increase in the incidence of congenital hypothyroidism (CH) reported worldwide may partly be explained by an increase in the transient form of CH.

Objective
We aimed to estimate the proportion of transient CH (TCH) in France, and to identify associated neonatal and young child characteristics.

Methods
We used probabilistic record linkage to link children with eutopic gland born between 2006 and 2012 recorded in the national French CH registry and the French national health data system (SNDS). Of the 703 children recorded, 484 (68.8%) were linked. We retrospectively examined reimbursement for oral levothyroxine (LT4) between January 1, 2006, and December 31, 2017. Children who had discontinued treatment for 6 months or more before December 31, 2017, were classified as having TCH. We used a Cox model to examine the factors associated with TCH.

Results
Among the main study sample (n = 471), 53.5% were female, 14.2% were preterm, and 13.8% had low birth weight. One-quarter (n = 111, 24.3%) had mild CH (thyroid-stimulating hormone [TSH] &lt; 50 mU/L, serum) at diagnosis and a median LT4 dose at treatment initiation of 30 μg/day. One-third (n = 155, 32.9%) had TCH. Premature birth (adjusted hazard ratio = 2.1 [1.0–4.2]), a TSH &lt; 50 mU/L at CH screening (7.4 [3.2–17.1]), LT4 dose received at 12 months of age (0.98 [0.97–0.99, P = 0.003]), congenital cardiac malformations (6.6 [1.5–29.0]), and year of birth (1.2 [1.1–1.4]) were all associated with TCH.

Conclusion
One-third of the children had TCH, and it was associated with several characteristics at birth and postpartum. These data are useful for CH medical management and epidemiological surveillance.
Blood Pressure Variability and the Risk of Fracture: A Nationwide Cohort Study
Authors: Yoo Jung Eun , Yoon Ji Won , Park Hyo Eun , Han Kyungdo , Shin Dong Wook 
Published: December 2021

Abstract

Context
Although blood pressure variability (BPV) is associated with various health outcomes, only 1 study suggested that BPV is correlated with hip fractures. As cardiovascular disease and fractures share similar pathophysiology, there might be a link between BPV and fractures.

Objective
To investigate the association between BPV and the incident fractures.

Design
Retrospective cohort study.

Setting
Population-based, using the Korean National Health Insurance System database.

Patients or Other Participants
A total of 3 256 070 participants aged ≥50 who participated in ≥3 health examinations within the previous 5 years, including the index year (2009-2010), were included. Outcome data were obtained through the end of 2016.

Exposure
BPV was calculated using variability independent of the mean. High variability was defined as the highest quartile of variability.

Main Outcome Measures
Newly diagnosed fractures.

Results
During the median follow-up of 7.0 years, there were 337 045 cases of any fracture (10.4%). After adjusting for age, sex, income, lifestyle factors, and comorbidities, a higher risk of fracture was observed with higher quartiles of BPV than the lowest quartile group: the adjusted hazard ratios (95% CIs) for incident any fracture were 1.07 (1.06-1.08) in the higher quartile of systolic BPV, 1.06 (1.05-1.07) in that of diastolic BPV, and 1.07 (1.06-1.08) in that of both systolic and diastolic BPV. Consistent results were noted for vertebral fractures and hip fractures, as well as in various subgroup analyses.

Conclusions
A positive association was noted between higher BPV and fracture incidence. BPV is an independent predictor for developing fracture.
Osteoglycin Across the Adult Lifespan
Authors: Woessner Mary N , Hiam Danielle , Smith Cassandra , Lin Xuzhu , Zarekookandeh Navabeh , Tacey Alexander , Parker Lewan , Landen Shanie , Jacques Macsue , Lewis Joshua R , Brennan-Speranza Tara , Voisin Sarah , Duque Gustavo , Eynon Nir , Levinger Itamar 
Published: December 2021

Abstract

Context
Osteoglycin (OGN) is a proteoglycan released from bone and muscle which has been associated with markers of metabolic health. However, it is not clear whether the levels of circulating OGN change throughout the adult lifespan or if they are associated with clinical metabolic markers or fitness.

Objective
We aimed to identify the levels of circulating OGN across the lifespan and to further explore the relationship between OGN and aerobic capacity as well as OGN’s association with glucose and HOMA-IR.

Methods
107 individuals (46 males and 61 females) aged 21-87 years were included in the study. Serum OGN levels, aerobic capacity (VO2peak), glucose, and homeostatic model assessment for insulin resistance (HOMA-IR) were assessed. T-tests were used to compare participant characteristics between sexes. Regression analyses were performed to assess the relationship between OGN and age, and OGN and fitness and metabolic markers.

Results
OGN displayed a nonlinear, weak “U-shaped” relationship with age across both sexes. Men had higher levels of OGN than women across the lifespan (β = 0.23, P = .03). Age and sex explained 16% of the variance in OGN (adjusted R2 = 0.16; P &lt; .001). Higher OGN was associated with higher VO2peak (β = 0.02, P = .001); however, those aged &lt;50 showed a stronger positive relationship than those aged &gt;50. A higher OGN level was associated with a higher circulating glucose level (β = 0.17, P &lt; .01). No association was observed between OGN and HOMA-IR.

Conclusion
OGN was characterized by a U-shaped curve across the lifespan which was similar between sexes. Those with a higher aerobic capacity or higher glucose concentration had higher OGN levels. Our data suggest an association between OGN and aerobic fitness and glucose regulation. Future studies should focus on exploring the potential of OGN as a biomarker for chronic disease.
Impact of Cortisol on Reduction in Muscle Strength and Mass: A Mendelian Randomization Study
Authors: Katsuhara Shunsuke , Yokomoto-Umakoshi Maki , Umakoshi Hironobu , Matsuda Yayoi , Iwahashi Norifusa , Kaneko Hiroki , Ogata Masatoshi , Fukumoto Tazuru , Terada Eriko , Sakamoto Ryuichi , Ogawa Yoshihiro 
Published: December 2021

Abstract

Context
Prolonged exposure to pathological cortisol, as in Cushing’s syndrome causes various age-related disorders, including sarcopenia. However, it is unclear whether mild cortisol excess, for example, accelerates sarcopenia due to aging or chronic stress.

Objective
We used Mendelian randomization (MR) analysis to assess whether cortisol was causally associated with muscle strength and mass.

Methods
Three single-nucleotide polymorphisms associated with plasma cortisol concentrations in the CORtisol NETwork consortium (n = 12 597) were used as instrumental variables. Summary statistics with traits of interest were obtained from relevant genome-wide association studies. For the primary analysis, we used the fixed-effects inverse-variance weighted analysis accounting for genetic correlations between variants.

Results
One SD increase in cortisol was associated with SD reduction in grip strength (estimate, −0.032; 95% CI −0.044 to −0.020; P = 3e-04), whole-body lean mass (estimate, −0.032; 95% CI, −0.046 to −0.017; P = 0.004), and appendicular lean mass (estimate, −0.031; 95% CI, −0.049 to −0.012; P = 0.001). The results were supported by the weighted-median analysis, with no evidence of pleiotropy in the MR-Egger analysis. The association of cortisol with grip strength and lean mass was observed in women but not in men. The association was attenuated after adjusting for fasting glucose in the multivariable MR analysis, which was the top mediator for the association in the MR Bayesian model averaging analysis.

Conclusion
This MR study provides evidence for the association of cortisol with reduced muscle strength and mass, suggesting the impact of cortisol on the development of sarcopenia.
Maternal and Neonatal 3-epi-25-hydroxyvitamin D Concentration and Factors Influencing Their Concentrations
Authors: Mao Di , Yuen Lai-Yuk , Ho Chung-Shun , Wang Chi-Chiu , Tam Claudia Ha-Ting , Chan Michael Ho-Ming , Lowe William L , Ma Ronald Ching-Wan , Tam Wing-Hung 
Published: December 2021

Abstract

Background
Little is known about the presence of 3-epi-25 hydroxyvitamin D in maternal and neonatal circulation, the extent of its contribution to total 25 hydroxyvitamin D, or factors influencing its levels.

Methods
A total of 1502 and 1321 archived maternal and umbilical cord serum samples from the Hyperglycemia and Adverse Pregnancy Outcome Study cohort from Hong Kong were assayed for 25(OH)D2, 25(OH)D3, and isomeric form of 25(OH)D3 (3-epi-25(OH)D3) by a liquid chromatography-tandem mass spectrometry method.

Results
Vitamin D deficiency (total serum 25(OH)D level &lt; 50 nmol/L) and severe vitamin D deficiency (total serum 25(OH)D level &lt; 25 nmol/L) occurred in 590 (39.3%) and 25 (1.7%) mothers, respectively. 3-epi-25(OH)D3 could be detected in 94.5% of maternal and 92.1% of neonatal umbilical sera, with the highest 3-epi-25(OH)D3 levels contributing to 19.9% and 15.3% of the maternal and umbilical cord sera 25(OH)D3 levels, respectively. Pregnancy with a male fetus, ambient solar radiation, and maternal glycemia and 25(OH)D3 levels were independent factors associated with maternal 3-epi-25(OH)D3 level. Advanced maternal age, multiparity, maternal gestational weight gain below the Institute of Medicine recommendation, maternal glycemic status, and earlier gestational age at delivery were significantly associated with higher umbilical cord serum 3-epi-25(OH)D3.

Conclusions
3-epi-25(OH)D3 accounted for a significant portion of total 25(OH)D in maternal and neonatal circulations. Further study is needed to determine the possible mechanism underlying this observation.
Racial Disparities in Acromegaly and Cushing’s Disease: A Referral Center Study in 241 Patients
Authors: Ioachimescu Adriana G , Goswami Neevedita , Handa Talin , Pappy Adlai , Veledar Emir , Oyesiku Nelson M 
Published: December 2021

Abstract

Context
Acromegaly (ACM) and Cushing’s disease (CD) are caused by functioning pituitary adenomas secreting growth hormone and ACTH respectively.

Objective
To determine the impact of race on presentation and postoperative outcomes in adults with ACM and CD, which has not yet been evaluated.

Methods
This is a retrospective study of consecutive patients operated at a large-volume pituitary center. We evaluated (1) racial distribution of patients residing in the metropolitan area (Metro, N = 124) vs 2010 US census data, and(2) presentation and postoperative outcomes in Black vs White for patients from the entire catchment area (N = 241).

Results
For Metro area (32.4% Black population), Black patients represented 16.75% ACM (P = .006) and 29.2% CD (P = .56). Among the total 112 patients with ACM, presentations with headaches or incidentaloma were more common in Black patients (76.9% vs 31% White, P = .01). Black patients had a higher prevalence of diabetes (54% vs 16% White, P = .005), significantly lower insulin-like growth factor (IGF)-1 deviation from normal (P = .03) and borderline lower median growth hormone levels (P = .09). Mean tumor diameter and proportion of tumors with cavernous sinus invasion were similar. Three-month biochemical remission (46% Black, 55% White, P = .76) and long-term IGF-1 control by multimodality therapy (92.3% Black, 80.5% White, P = .45) were similar. Among the total 129 patients with CD, Black patients had more hypopituitarism (69% vs 45% White, P = .04) and macroadenomas (33% vs 15% White, P = .05). At 3 months, remission rate was borderline higher in White (92% vs 78% Black, P = 0.08), which was attributed to macroadenomas by logistic regression.

Conclusion
We identified disparities regarding racial distribution, and clinical and biochemical characteristics in ACM, suggesting late or missed diagnosis in Black patients. Large nationwide studies are necessary to confirm our findings.
Delayed Follow-up Visits and Thyrotropin Among Patients With Levothyroxine During the COVID-19 Pandemic
Authors: Inoue Kosuke , Noh Jaeduk Yoshimura , Yoshihara Ai , Watanabe Natsuko , Matsumoto Masako , Fukushita Miho , Suzuki Nami , Hoshiyama Ayako , Mitsumatsu Takako , Suzuki Ai , Kinoshita Aya , Mikura Kentaro , Yoshimura Ran , Sugino Kiminori , Ito Koichi 
Published: December 2021

Abstract

Context
The indirect effects of the COVID-19 pandemic on clinical practice have received great attention, but evidence regarding thyroid disease management is lacking.

Objective
We aimed to investigate the association between delayed follow-up visits during the pandemic and their serum thyrotropin (TSH) levels among patients being treated with levothyroxine.

Methods
This study included 25 361 patients who made a follow-up visit as scheduled (n = 9063) or a delayed follow-up visit (&lt; 30 d, n = 10 909; ≥ 30 d, n = 5389) during the pandemic (after April 2020) in Japan. We employed modified Poisson models to estimate the adjusted risk ratio (aRR) of TSH greater than 4.5 mIU/L and greater than 10 mIU/L during the pandemic according to the 3 types of follow-up visit group (ie, as scheduled, delayed &lt; 30 d, and delayed ≥ 30 d). The models included age, sex, city of residence, TSH levels, underlying thyroid disease, dose of levothyroxine, and duration of levothyroxine prescriptions.

Results
The mean age was 52.8 years and women were 88%. Patients who were older and had a higher dose or longer duration of levothyroxine prescriptions were more likely to make a delayed follow-up visit during the pandemic. Changes in TSH were larger among the delayed-visit groups than the scheduled-visit group. We found increased risks of elevated TSH levels during the pandemic among the delayed visit groups, particularly those with delayed visit of 30 or more days (TSH &gt; 4.5 mIU/L, aRR [95% CI] = 1.72 [1.60-1.85]; and TSH &gt; 10 mIU/L, aRR [95% CI] = 2.38 [2.16-2.62]).

Conclusion
A delayed follow-up visit during the COVID-19 pandemic was associated with less well-controlled TSH among patients with levothyroxine.