Choline and betaine are important in the body, from cell membrane components to methyl donors. We aimed to investigate trends in dietary intake and food sources of total choline, individual choline forms and betaine in Chinese adults using data from the China Health and Nutrition Survey (CHNS) 1991–2011, a prospective cohort with a multistage, random cluster design. Dietary intake was estimated using three consecutive 24-h dietary recalls in combination with a household food inventory. Linear mixed-effect models were constructed using R software. A total of 11 188 men and 12 279 women aged 18 years or older were included. Between 1991 and 2011, total choline intake increased from 219·3 (95 % CI 215·1, 223·4) mg/d to 269·0 (95 % CI 265·6, 272·5) mg/d in men and from 195·6 (95 % CI 191·8, 199·4) mg/d to 240·4 (95 % CI 237·4, 243·5) mg/d in women (both P-trends < 0·001). Phosphatidylcholine was the major form of dietary choline, and its contribution to total choline increased from 46·9 % in 1991 to 58·8 % in 2011. Cereals were the primary food source of total choline before 2000, while eggs had ranked at the top since 2004. Dietary betaine intake was relatively steady over time with a range of 134·0–151·5 mg/d in men (P-trend < 0·001) and 111·7–125·3 mg/d in women (P-trend > 0·05). Chinese adults experienced a significant increase in dietary intake of choline, particularly phosphatidylcholine during 1991–2011 and animal-derived foods have replaced plant-based foods as the main food sources of choline. Betaine intake remained relatively stable over time. Future efforts should address the health effects of these changes.

Previous animal studies found beneficial effects of choline and betaine on maternal glucose metabolism during pregnancy, but few human studies explored the association between choline or betaine intake and incident gestational diabetes mellitus (GDM). We aimed to explore the correlation of dietary choline or betaine intake with GDM risk among Chinese pregnant women. A total of 168 pregnant women with GDM cases and 375 healthy controls were enrolled at the Seventh People’s Hospital in Shanghai during their GDM screening at 24–28 gestational weeks. A validated semi-quantitative FFQ was used to estimate choline and betaine consumption through face-to-face interviews. An unconditional logistic regression model was adopted to examine OR and 95 % CI. Compared with the controls, those women with GDM incidence were likely to have higher pre-pregnancy BMI, be older, have more parities and have higher plasma TAG and lower plasma HDL-cholesterol. No significant correlation was observed between the consumption of choline or betaine and incident GDM (adjusted OR (95 % CI), 0·77 (0·41, 1·43) for choline; 0·80 (0·42, 1·52) for betaine). However, there was a significant interaction between betaine intake and parity on the risk of GDM (Pfor interaction = 0·01). Among those women with no parity history, there was a significantly inverse correlation between betaine intake and GDM risk (adjusted OR (95 % CI), 0·25 (0·06, 0·81)). These findings indicated that higher dietary betaine intake during pregnancy might be considered a protective factor for GDM among Chinese women with no parity history.

This study aims to assess the correlation between NAA (N-acetyl-l-aspartate), CHO (choline), and CRE (creatine) levels in the hippocampus regions of individuals suffering from obsessive-compulsive disorder (OCD) and defensive styles of the ego.

The study group was composed of twenty patients with OCD and twenty healthy controls. NAA, CHO, and CRE values in the hippocampal region using proton magnetic resonance spectroscopy (1H-MRS) were measured. Participants’ defense styles were ascertained by administering the Defense Style Questionnaire-40.

The patient group’s NAA levels were considerably lower than the control group’s on both sides of the hippocampus. The levels of CHO and CRE did not significantly differ between the two groups. The following statistically significant correlations were discovered: in the comparison group, there were negative correlations between the scores of mature defense styles and the right and left CHO levels, as well as between the immature defense mechanism scores and the right NAA levels in both the patient and control groups. In the patient group, there were also negative correlations between the left NAA values and the scores of mature defense styles.

OCD patients have lower levels of NAA in the hippocampus. To validate and extend the current findings, more research involving a greater sample size is required.

It is inconclusive whether trimethylamine N-oxide (TMAO) and choline and related metabolites, namely trimethylamine (TMA), l-carnitine, betaine and dimethylglycine (DMG), are associated with non-alcoholic fatty liver disease (NAFLD). Our objective was to investigate these potential associations. Additionally, we sought to determine the mediating role of TMAO. In this 1:1 age- and sex-matched case–control study, a total of 150 pairs comprising NAFLD cases and healthy controls were identified. According to the fully adjusted model, after the highest tertile was compared with the lowest tertile, the plasma TMAO concentration (OR = 2·02 (95 % CI 1·04, 3·92); P trend = 0·003), l-carnitine concentration (OR = 1·79 (1·01, 3·17); P trend = 0·020) and DMG concentration (OR = 1·81 (1·00, 3·28); P trend = 0·014) were significantly positively associated with NAFLD incidence. However, a significantly negative association was found for plasma betaine (OR = 0. 50 (0·28, 0·88); P trend = 0·001). The restricted cubic splines model consistently indicated positive dose–response relationships between exposure to TMAO, l-carnitine, and DMG and NAFLD risk, with a negative association being observed for betaine. The corresponding AUC increased significantly from 0·685 (0·626, 0·745) in the traditional risk factor model to 0·769 (0·716, 0·822) when TMAO and its precursors were included (l-carnitine, betaine and choline) (P = 0·032). Mediation analyses revealed that 14·7 and 18·6 % of the excess NAFLD risk associated with l-carnitine and DMG, respectively, was mediated by TMAO (the P values for the mediating effects were 0·021 and 0·036, respectively). These results suggest that a higher concentration of TMAO is associated with increased NAFLD risk among Chinese adults and provide evidence of the possible mediating role of TMAO.

Methyl donor micronutrients might affect muscle strength via DNA methylation. We aimed to evaluate the combined relationship of dietary methyl donor micronutrients containing betaine, choline, methionine, vitamin B12, vitamin B6 and folate on muscle strength. This cross-sectional study was conducted on 267 subjects including 113 men and 154 women. Dietary intake of micronutrients was assessed utilising a validated 168-item semi-quantitative FFQ, and methyl donor micronutrient score (MDMS) was calculated. The muscle strength of the participants was measured using a digital handgrip dynamometer. The association was determined using linear regression analysis. The mean age of participants was 36·8 ± 13·2 years. After taking into account potential confounding variables, there was no significant association between dietary methyl donor micronutrient score (MDMS) and the mean left-hand muscle strength (β: 0·07, se: 0·05, P = 0·07); however, the changes were significant in the mean right-hand muscle strength (β: 0·09, se: 0·04, P = 0·03). There was also a significant positive relationship between mean muscle strength and methyl donors’ intake after fully adjusting for potential confounders (β: 0·08, se: 0·04, P = 0·04). In conclusion, our findings revealed that higher dietary methyl donor micronutrient consumption is associated with enhanced muscle strength. As a result, advice on a higher intake of methyl donor-rich foods including grains, nuts, dairy products and seafood might be recommended by dietitians as a general guideline to adhere to. Additional prospective studies are needed to confirm the findings.

Aflatoxins in contaminated corn do not degrade in corn fermentation solution (CFS) during biofuel production; rather, they are enriched in the co-product, dried distillers grain. Aflatoxin B1 (AfB1) is the most toxic form of all aflatoxins. Removing AfB1 from CFS is desirable to minimize its toxicity to animals. Smectites can adsorb AfB1 from aqueous solutions and, therefore, inactivate the toxin, but proteins in CFS inhibit the adsorption of AfB1 by smectites. The current study aimed to minimize the interference by CFS in adsorption of AfB1 on smectite by modifying a calcium-smectite (Ca-3MS) with a small nutritive organic compound, e.g. carnitine, choline, arginine, histidine, or tryptophan. The organo-smectites were characterized by X-ray diffraction (XRD) and Fourier-transform infrared (FTIR) spectroscopy, and adsorption of AfB1 in CFS by these composites was examined. Various degrees of intercalation of the organic nutrients into the smectites were observed with XRD and FTIR. After immersing the smectite and organo-smectites in the CFS, the d001 values of Ca-3MS expanded to ~1.82 nm due to protein interaction, but the organo-smectites were confined to ~1.39 nm, which indicated that the protein had limited access to the organo-smectite interlayers. The IR bands at ~1652, 1544, 1538, and 1454 cm–1 from the organo-smectites revealed, however, that complete protein inhibition was not achieved. The organo-smectites were capable of adsorbing AfB1 in simple aqueous solution with maximal adsorption capacity up to 0.55 mol kg–1. Significantly greater (p ≤ 0.05) AfB1 adsorption was achieved by choline- and carnitine-modified smectites compared with the original Ca-3MS in the presence of competing protein (pepsin) in simple aqueous solution. In real CFS, both AfB1 adsorption capacities (Qmax) and affinities (K) by all organo-smectites were greater (Qmax = up to 0.45 mol kg–1 and K = up to 0.165 μM–1) than those by Ca-3MS (Qmax = 0.22 mol kg–1 and K = 0.031 μM–1). The study suggested that using smectites modified with an organic nutritive compound could be an effective, economical, and safe strategy for removing mycotoxins, including aflatoxins, during biofuel production.

The objective of this study was to design new, functional, nanostructured materials from the abundant clay mineral kaolinite, in spite of development problems with the interlayer chemistry of kaolinite because of its non-swelling properties. A particular goal of this work was to graft, in a controlled way, alkylammonium groups onto the aluminol interlayer surfaces of kaolinite. This was successfully achieved by soft-chemical approaches, more specifically by the melting intercalation process of alkylammonium ionic liquids which were synthesized for this purpose. The resulting nanohybrid materials were characterized chemically and structurally by X-ray diffraction analysis, thermal analysis (TG/DTA), 13C cross polarization magic angle spinning nuclear magnetic resonance spectroscopy, and Fourier-transform infrared spectroscopy. The amount of grafted organic material was quantified from TGA results. Alkylammonium salts with a short alkyl chain were grafted directly using a melting reaction at 180°C under N2 involving the in situ displacement of dimethylsulfoxide (DMSO) from a DMSO-kaolinite pre-intercalate; for longer alkyl chains, the grafting was done in two steps. In the first step, the corresponding amino-alcohol was grafted into the kaolinite by displacement of DMSO from the interlayer space. The second step consisted of quaternarization of the grafted material by reaction with iodomethane or iodoethane.

Choline plays a crucial role in hepatic lipid homeostasis by acting as a major methyl-group donor. However, despite this well-accepted fact, no study has yet explored how choline’s methyl-donor function contributes to preventing hepatic lipid dysregulation. Moreover, the potential regulatory role of Ire-1α, an ER-transmembrane transducer for the unfolded protein response (UPRer), in choline-mediated hepatic lipid homeostasis remains unexplored. Thus, this study investigated the mechanism by which choline prevents hepatic lipid dysregulation, focusing on its role as a methyl-donor and the involvement of Ire-1α in this process. To this end, a model animal for lipid metabolism, yellow catfish (Pelteobagrus fulvidraco) were fed two different diets (adequate or deficient choline diets) in vivo for 10 weeks. The key findings of studies are as follows: 1. Dietary choline, upregulated selected lipolytic and fatty acid β-oxidation transcripts promoting hepatic lipid homeostasis. 2. Dietary choline ameliorated UPRer and prevented hepatic lipid dysregulation mainly through ire-1α signalling, not perk or atf-6α signalling. 3. Choline inhibited the transcriptional expression level of ire-1α by activating site-specific DNA methylations in the promoter of ire-1α. 4. Choline-mediated ire-1α methylations reduced Ire-1α/Fas interactions, thereby further inhibiting Fas activity and reducing lipid droplet deposition. These results offer a novel insight into the direct and indirect regulation of choline on lipid metabolism genes and suggests a potential crosstalk between ire-1α signalling and choline-deficiency-induced hepatic lipid dysregulation, highlighting the critical contribution of choline as a methyl-donor in maintaining hepatic lipid homeostasis.

Perkinsus olseni is an industrially significant protozoan parasite of Manila clam, Ruditapes philippinarum. So far, various media, based on Dulbecco's Modified Eagle Medium and Ham's F-12 nutrient mixture with supplementation of fetal bovine serum (FBS), have been developed to proliferate the parasitizing trophozoite stage of P. olseni. The present study showed that P. olseni did not proliferate in FBS-deficient Perkinsus broth medium (PBMΔF), but proliferated well in PBMΔF supplemented with tissue extract of host Manila clams, indicating that FBS and Manila clam tissue contained molecule(s) required for P. olseni proliferation. Preliminary characterization suggested that the host-derived molecule(s) was a heat-stable molecule(s) with a molecular weight of less than 3 kDa, and finally a single molecule required for the proliferation was purified by high-performance liquid chromatography processes. High-resolution electrospray ionization mass spectrometry and nuclear magnetic resonance analyses identified this molecule as glycine betaine (=trimethylglycine), and the requirement of this molecule for P. olsseni proliferation was confirmed by an assay using chemically synthesized, standard glycine betaine. Although glycine betaine was required for the proliferation of all examined Perkinsus species, supplementation of glycine betaine precursors, such as choline and betaine aldehyde, enhanced the proliferation of 4 Perkinsus species (P. marinus, P. chesapeaki, P. mediterraneus and P. honshuensis), but not of 2 others (P. olseni and P. beihaiensis). Thus, it was concluded that the ability to biosynthesise glycine betaine from its precursors varied among Perkinsus species, and that P. olseni and P. beihaiensis lack the ability required to biosynthesize glycine betaine for proliferation.

Folate and choline are methyl donor nutrients that may play a role in fetal brain development. Animal studies have reported that prenatal folate and choline supplementation are associated with better cognitive outcomes in offspring and that these nutrients may interact and affect brain development. Human studies that have investigated associations between maternal prenatal folate or choline levels and neurodevelopmental outcomes have reported contradictory findings and no human studies have examined the potential interactive effect of folate and choline on children’s neurodevelopment. During the second trimester of pregnancy, maternal red blood cell folate was measured from blood samples and choline intake was estimated using a 24-h dietary recall in 309 women in the APrON cohort. At 3–5 years of age, their children’s neurodevelopment was assessed using the Wechsler Preschool and Primary Scales of Intelligence – Fourth EditionCND, NEPSY-II language and memory subtests, four behavioral executive function tasks, and the Movement Assessment Battery for Children – Second Edition. Adjusted regressions revealed no associations between maternal folate and choline levels during pregnancy and most of the child outcomes. On the Dimensional Change Card Sort, an executive function task, there was an interaction effect; at high levels of choline intake (i.e., 1 SD above the mean; 223.03 mg/day), higher maternal folate status was associated with decreased odds of receiving a passing score (β = −0.44; 95%CI −0.81, −0.06). In conclusion, maternal folate status and choline intake during the second trimester of pregnancy were not associated with children’s intelligence, language, memory, or motor outcomes at 3–4 years of age; however, their interaction may have an influence children’s executive functions.

The transfer of one-carbon units between molecules in metabolic pathways is essential for maintaining cellular homeostasis, but little is known about whether the circulating concentrations of metabolites involved in the one-carbon metabolism are affected by the prandial status. Epidemiological studies do not always consistently use fasting or non-fasting blood samples or may lack information on the prandial status of the study participants. Therefore, the main aim of the present study was to investigate the effects of a light breakfast on serum concentrations of selected metabolites and B-vitamins related to the one-carbon metabolism; i.e. the methionine-homocysteine cycle, the folate cycle, the choline oxidation pathway and the transsulfuration pathway. Sixty-three healthy adults (thirty-six women) with BMI ≥ 27 kg/m2 were included in the study. Blood was collected in the fasting state and 60 and 120 min after intake of a standardised breakfast consisting of white bread, margarine, white cheese, strawberry jam and orange juice (2218 kJ). The meal contained low amounts of choline, betaine, serine and vitamins B2, B3, B6, B9 and B12. Serum concentrations of total homocysteine, total cysteine, flavin mononucleotide, nicotinamide and pyridoxal 5’-phosphate were significantly decreased, and concentrations of choline, betaine, dimethylglycine, sarcosine, cystathionine and folate were significantly increased following breakfast intake (P < 0·05). Our findings demonstrate that the intake of a light breakfast with low nutrient content affected serum concentrations of several metabolites and B-vitamins related to the one-carbon metabolism.

Blood pressure (BP) is a known cardiovascular risk factor that is hypothesised to be inversely related to choline intake. A previous study suggested that this association may be more apparent in older adults and may differ according to demographic and health characteristics. The primary study objectives are to investigate the cross-sectional associations of total choline intake with BP (n 843) and prevalent hypertension (n 2113) among USA adults aged ≥ 65 years using the sample from the 2011 to 2014 National Health and Nutrition Examination Survey. Logistic and multiple linear regression models for complex surveys were employed for hypertension status and BP, respectively. Effect modification by sex, race, BMI and comorbidity status were separately investigated using an interaction term. Choline intake interacted with BMI (P–interaction = 0·04) such that choline intake tended to be associated with lower odds of hypertension among people with BMI < 18·5 kg/m2 (OR (95 % CI): 0·64 (0·4, 1·00); P = 0·052). Choline intake was not associated with systolic BP (mean ± sem change per 100 mg of choline: −1·03 ± 0·74 mmHg; P = 0·16). In contrast, its relation to diastolic BP differed by cardiovascular comorbidity (P–interaction = 0·03) with a non-significant (P = 0·13) negative direction of association observed among those who were free of comorbidities and a non-significant (P = 0·26) positive direction observed among those with comorbidities. Collectively, these results suggested that the associations of choline intake with BP levels and hypertension risk among older adults are dependent on other risk factors.

Dietary choline, which is converted to phosphatidylcholine (PC) in intestinal enterocytes, may benefit inflammatory bowel disease patients who typically have reduced intestinal choline and PC. The present study investigated the effect of dietary choline supplementation on colitis severity and intestinal mucosal homoeostasis using a Citrobacter rodentium-induced colitis model. C57BL/6J mice were fed three isoenergetic diets differing in choline level: choline-deficient (CD), choline-sufficient (CS) and choline-excess (CE) for 3 weeks prior to infection with C. rodentium. The effect of dietary choline levels on the gut microbiota was also characterised in the absence of infection using 16S rRNA gene amplicon sequencing. At 7 d following infection, the levels of C. rodentium in CD mice were significantly greater than that in CS or CE groups (P < 0·05). CD mice exhibited greater damage to the surface epithelium and goblet cell loss than the CS or CE mice, which was consistent with elevated pro-inflammatory cytokine and chemokine levels in the colon. In addition, CD group exhibited decreased concentrations of PC in the colon after C. rodentium infection, although the decrease was not observed in the absence of challenge. Select genera, including Allobaculum and Turicibacter, were enriched in response to dietary choline deficiency; however, there was minimal impact on the total bacterial abundance or the overall structure of the gut microbiota. Our results suggest that insufficient dietary choline intake aggravates the severity of colitis and demonstrates an essential role of choline in maintaining intestinal homoeostasis.

We critically review potential involvement of trimethylamine N-oxide (TMAO) as a link between diet, the gut microbiota and CVD. Generated primarily from dietary choline and carnitine by gut bacteria and hepatic flavin-containing mono-oxygenase (FMO) activity, TMAO could promote cardiometabolic disease when chronically elevated. However, control of circulating TMAO is poorly understood, and diet, age, body mass, sex hormones, renal clearance, FMO3 expression and genetic background may explain as little as 25 % of TMAO variance. The basis of elevations with obesity, diabetes, atherosclerosis or CHD is similarly ill-defined, although gut microbiota profiles/remodelling appear critical. Elevated TMAO could promote CVD via inflammation, oxidative stress, scavenger receptor up-regulation, reverse cholesterol transport (RCT) inhibition, and cardiovascular dysfunction. However, concentrations influencing inflammation, scavenger receptors and RCT (≥100 µm) are only achieved in advanced heart failure or chronic kidney disease (CKD), and greatly exceed pathogenicity of <1–5 µm levels implied in some TMAO–CVD associations. There is also evidence that CVD risk is insensitive to TMAO variance beyond these levels in omnivores and vegetarians, and that major TMAO sources are cardioprotective. Assessing available evidence suggests that modest elevations in TMAO (≤10 µm) are a non-pathogenic consequence of diverse risk factors (ageing, obesity, dyslipidaemia, insulin resistance/diabetes, renal dysfunction), indirectly reflecting CVD risk without participating mechanistically. Nonetheless, TMAO may surpass a pathogenic threshold as a consequence of CVD/CKD, secondarily promoting disease progression. TMAO might thus reflect early CVD risk while providing a prognostic biomarker or secondary target in established disease, although mechanistic contributions to CVD await confirmation.

The present study aimed to investigate whether dietary choline can regulate lipid metabolism and suppress NFκB activation and, consequently, attenuate inflammation induced by a high-fat diet in black sea bream (Acanthopagrus schlegelii). An 8-week feeding trial was conducted on fish with an initial weight of 8·16 ± 0·01 g. Five diets were formulated: control, low-fat diet (11 %); HFD, high-fat diet (17 %); and HFD supplemented with graded levels of choline (3, 6 or 12 g/kg) termed HFD + C1, HFD + C2 and HFD + C3, respectively. Dietary choline decreased lipid content in whole body and tissues. Highest TAG and cholesterol concentrations in serum and liver were recorded in fish fed the HFD. Similarly, compared with fish fed the HFD, dietary choline reduced vacuolar fat drops and ameliorated HFD-induced pathological changes in liver. Expression of genes of lipolysis pathways were up-regulated, and genes of lipogenesis down-regulated, by dietary choline compared with fish fed the HFD. Expression of nfκb and pro-inflammatory cytokines in liver and intestine was suppressed by choline supplementation, whereas expression of anti-inflammatory cytokines was promoted in fish fed choline-supplemented diets. In fish that received lipopolysaccharide to stimulate inflammatory responses, the expression of nfκb and pro-inflammatory cytokines in liver, intestine and kidney were all down-regulated by dietary choline compared with the HFD. Overall, the present study indicated that dietary choline had a lipid-lowering effect, which could protect the liver by regulating intrahepatic lipid metabolism, reducing lipid droplet accumulation and suppressing NFκB activation, consequently attenuating HFD-induced inflammation in A. schlegelii.

Little is known about the association between dietary choline intake and mortality. We evaluated the link between choline consumption and overall as well as cause-specific mortality by using both individual data and pooling prospective studies by meta-analysis and systematic review. Furthermore, adjusted means of cardiometabolic risk factors across choline intake quartiles were calculated. Data from the National Health and Nutrition Examination Survey (1999–2010) were collected. Adjusted Cox regression was performed to determine the risk ratio (RR) and 95 % CI, as well as random-effects models and generic inverse variance methods to synthesise quantitative and pooling data, followed by a leave-one-out method for sensitivity analysis. After adjustments, we found that individuals consuming more choline had worse lipid profile and glucose homeostasis, but lower C-reactive protein levels (P < 0·001 for all comparisons) with no significant differences in anthropometric parameters and blood pressure. Multivariable Cox regression models revealed that individuals in the highest quartile (Q4) of choline consumption had a greater risk of total (23 %), CVD (33 %) and stroke (30 %) mortality compared with the first quartile (Q1) (P < 0·001 for all comparison). These results were confirmed in a meta-analysis, showing that choline intake was positively and significantly associated with overall (RR 1·12, 95 % CI 1·08, 1·17, I2 = 2·9) and CVD (RR 1·28, 95 % CI 1·17, 1·39, I2 = 9·6) mortality risk. In contrast, the positive association between choline consumption and stroke mortality became non-significant (RR 1·18, 95 % CI 0·97, 1·43, P = 0·092, I2 = 1·1). Our findings shed light on the potential adverse effects of choline intake on selected cardiometabolic risk factors and mortality risk.

Maternal one-carbon metabolism during pregnancy is crucial for fetal development and programming by DNA methylation. However, evidence on one-carbon biomarkers other than folate is lacking. We, therefore, investigated whether maternal plasma methyl donors, that is, choline, betaine and methionine, are associated with birth outcomes. Blood samples were obtained from 115 women during gestation (median 26·3 weeks, 90 % range 22·7–33·0 weeks). Plasma choline, betaine, methionine and dimethylglycine were measured using HPLC-tandem MS. Multivariate linear and logistic regression models were used to estimate the association between plasma biomarkers and birth weight, birth length, the risk of small-for-gestational-age and large-for-gestational-age (LGA). Higher level of maternal betaine was associated with lower birth weight (–130·3 (95 % CI –244·8, –15·9) per 1 sd increment for log-transformed betaine). Higher maternal methionine was associated with lower risk of LGA, and adjusted OR, with 95 % CI for 1 sd increase in methionine concentration was 0·44 (95 % CI 0·21, 0·89). Stratified analyses according to infant sex or maternal plasma homocysteine status showed that reduction in birth weight in relation to maternal betaine was only limited to male infants or to who had higher maternal homocysteine status (≥5·1 µmol/l). Higher maternal betaine status was associated with reduced birth weight. Maternal methionine was inversely associated with LGA risk. These findings are needed to be replicated in future larger studies.