Measurement of serum vitamin B12-related metabolites in newborns: implications for new cutoff values to detect B12 deficiency.

OBJECTIVE: Our aim was to determine the prevalence of maternal and neonatal vitamin B12 (vit-B12) and folate deficiencies, a new cutoff value of serum vit-B12 in newborns using vit-B12-related metabolites and also cutoff values of homocysteine (Hcy), propionyl (C3) carnitine, and methyl malonic acid (MMA) in newborns using a vit-B12 cutoff value of 200 pg/mL. METHODS: Healthy pregnant women (without iron deficiency) and 98 healthy, term, singleton babies were included. Blood samples were obtained from women 0-8 h before birth and from cord blood during birth for hemogram and to measure serum vit-B12, folate, and Hcy levels. Maternal and cord blood serum vit-B12 levels were classified as low < 200 pg/mL, marginal 200-300 pg/mL, and normal ≥ 300 pg/mL. Neonatal urine MMA levels were analyzed in mothers with a vit-B12 concentration < 300 pg/mL. C3 carnitine levels of newborns were acquired from extended newborn screening. Receiver operating characteristics curve (ROC) analysis was used for serum vit-B12, urine MMA, C3 carnitine, and Hcy. RESULTS: Of total, 98 pregnant women (28.6 ± 5.5-year-old) and 98 newborn were included. Vit-B12 level was lower than 300 pg/mL in 93% of the pregnant women and 61% of cord blood samples. Folate deficiency was not found in either group. There was statistically significant negative correlation between baby C3 carnitine, cord blood folate (r = -0.265, p = .008) and cord blood vit-B12 (r = -0.220, p = .029). In backward stepwise linear regression analysis, maternal vit-B12 level exerted the most marked effect on cord blood vit-B12 level (adjusted R2 = 0.457). In ROC analysis, the Hcy cutoff value was 4.77 µmol/L (68.4% sensitivity, 58.3% specificity, p = .012) for the detection of vit-B12 deficiency. CONCLUSION: Vit-B12 deficiency remains an important health issue for pregnant women and newborns. Our study revealed a cutoff value for Hcy for the detection of nutritional vit-B12 deficiency that could be used in practice for newborns.

Determination of insulin resistance and its relationship with hyperandrogenemia,anti-Müllerian hormone, inhibin A, inhibin B, and insulin-like peptide-3 levels in adolescent girls with polycystic ovary syndrome

Background/aim: This study aims to investigate the association between polycystic ovary syndrome (PCOS) and obesity and insulin resistance (IR) with respect to anti-Müllerian hormone (AMH), inhibin A (INH-A), inhibin B (INH-B), and insulin-like peptide 3 (INSL3) levels, all factors which may have an impact on IR. Materials and methods: In this cross sectional study, 52 adolescent girls diagnosed with PCOS[groups:nonobese (NO), n = 23; overweight/obese (OW/O), n = 29] were included. Blood samples were obtained to measure AMH, INH-B, INH-A, and INSL3 levels, together with hormonal and biochemical assessments. Oral glucose tolerance test (OGTT) was performed and the indexes of IR [homeostasis model assessment: insulin resistance (HOMA-IR) and Matsuda index] were calculated. Results: Insulin resistance was 56.5% with OGTT and 30.4% with HOMA-IR in nonobese-PCOS girls. There was a correlation between INH-A and HOMA-IR even when controlled for body mass index (BMI). INH-B and FAI also had correlations with HOMA-IR which disappeared when controlled for BMI. In regression analyses, AMH (odds ratio = [0.903, P = 0.015) and FAI (odds ratio = 1.353, P = 0.023) are found to be contributors to IR. Their effect was BMI-independent. In ROC analysis, the cutoff value for FAI was 5.93 (sensitivity 71%) to define IR in PCOS girls. Conclusion: AMH and FAI may contribute to IR (defined by OGTT) in PCOS. FAI might be used as a supporting IR marker (defined by OGTT) in adolescent girls with PCOS.

Anti-Müllerian Hormone and Inhibin-A, but not Inhibin-B or Insulin-Like Peptide-3, may be Used as Surrogates in the Diagnosis of Polycystic Ovary Syndrome in Adolescents: Preliminary Results.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common endocrine problem in adolescents with an increasing prevalence of 30%. Pursuing new biomarkers with high specificity and sensitivity in the diagnosis of PCOS in adolescents is currently an active area of research. We aimed to investigate the diagnostic value of anti-Müllerian hormone (AMH), insulin-like peptide-3 (INSL3), inhibin-A (INH-A), and inhibin-B (INH-B) in adolescents with PCOS and also to determine the association, if any, between these hormones and clinical/laboratory findings related with hyperandrogenism. METHODS: The study group comprised 53 adolescent girls aged between 14.5 and 20 years who were admitted to our outpatient clinic with symptoms of hirsutism and/or irregular menses and diagnosed as having PCOS in accordance with the Rotterdam criteria. Twenty-six healthy peers, eumenorrheic for at least two years and body mass index-matched, constituted the controls. Fasting blood samples for hormones [luteinizing hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone-sulfate (DHEAS), androstenedione (D4-A), total/free testosterone (T/fT), sex hormone binding globulin (SHBG), AMH, INSL3, INH-A, INH-B] were drawn after an overnight fast. RESULTS: In the PCOS group, 83% of the subjects were oligomenorrheic/amenorrheic and 87% had hirsutism. The LH, LH/FSH ratio, total T, fT, free androgen-index (FAI), DHEAS levels were significantly higher (p=0.005, p=0.042, p=0.047, p<0.001, p=0.007, p=0.014, respectively) and SHBG was significantly lower (p=0.004) in PCOS patients as compared to the controls. Although the INSL-3 and INH-B levels showed no difference between the groups (p>0.05), AMH and INH-A levels were found to be significantly higher in the PCOS group compared to the controls (p<0.001, p<0.001, respectively). In multiple linear regression analysis, WC SDS (p=0.028), logD4-A (p=0.033), logSHBG (p=0.031), and total ovarian volume (p=0.045) had significant effects on AMH levels, and LH (p=0.003) on INH-A levels. In receiver-operating characteristic analysis, the cut-off values for AMH and INH-A were 6.1 ng/mL (sensitivity 81.1%) and 12.8 pg/mL (sensitivity 86.8%), respectively, to diagnose PCOS. When AMH and INH-A were used in combination, the sensitivity (96.2%) increased. CONCLUSION: INSL3 and INH-B were not found to have diagnostic value in adolescents with PCOS. On the other hand, it was shown that INH-A could be used as a new diagnostic biomarker in addition to AMH.