Quantification of urinary gonadotropins by specific assays may improve the evaluation of sex-specific hormonal changes in early infancy.

OBJECTIVE: The aim of this study was to investigate the feasibility of different gonadotropin assays for determining total and intact luteinizing hormone (LH), and follicle-stimulating hormone (FSH) immunoreactivity in urine (U-LH-ir and U-FSH-ir, respectively) during early infancy. DESIGN, PATIENTS AND MEASUREMENTS: Morning urine samples were obtained from 31 infants, aged between 0 and 6 months, to study the age-related course of urinary gonadotropins. Additionally, we investigated bi-hourly urine samples of a 5-day-old male neonate for 24 h to observe the course of urinary gonadotropins during a daily cycle. We employed different immunofluorometric assays for measuring total and intact U-LH-ir, and U-FSH-ir. RESULTS: In neonates up to 21 days of age, the U-LH-ir levels measured by the regular LH assay (also detecting hCG) were significantly higher than those determined by the total (specific) LH assays (p = .004). U-FSH-ir was higher in girls than boys during both the first and the next 5 months (p = .02 and p < .001, respectively), whereas total U-LH-ir was higher in boys until 6 months of age (p < .001). Total U-LH-ir/U-FSH-ir ratio was significantly higher in boys than girls across the first half-year (p < .001). CONCLUSIONS: The assessment of total U-LH-ir and U-FSH-ir, and their respective ratio constitutes a noninvasive, practical and scalable tool to investigate sex-specific changes during early infancy, with the ratio being significantly higher in boys than girls. Only highly specific LH assays detecting beta-subunit and its core fragment in addition to intact LH should be used for determining U-LH-ir in the neonatal period to avoid potential cross-reactivity with hCG of placental origin.

Maternal caffeine intake during pregnancy and the risk of delivering a small for gestational age baby: Kuopio Birth Cohort.

PURPOSE: High caffeine intake during pregnancy is associated with restricted fetal growth. We aimed to evaluate the association between maternal caffeine intake during early and late pregnancy and the risk of delivering a small for gestational age (SGA) baby. METHODS: Kuopio Birth Cohort (KuBiCo) is a prospective cohort study including women whose pregnancies and deliveries were treated at the prenatal clinics in outpatient healthcare centers and in Kuopio University Hospital, Finland. Maternal diet and caffeine intake during the first (n = 2007) and third (n = 4362) trimester of pregnancy were assessed using a 160-item food frequency questionnaire (2013-2022). SGA was defined as birth weight corrected for gestational age below - 2 standard deviations from the mean, according to the sex-specific Finnish fetal growth curves. RESULTS: Altogether in 32 and 38% (1st and 3rd trimester) of all women and in 44 and 52% of coffee drinkers, caffeine intake exceeded the recommendation for caffeine intake ( ≤ 200 mg/day) during pregnancy. The women with moderate (51-200 mg/day) (aOR 1.87; 95% CI: 1.16-3.02) and high (> 200 mg/day) (aOR 1.51; 95% CI: 1.08-2.10) caffeine intake during the first trimester were in the highest risk of having an SGA newborn. Caffeine intake in the third trimester of pregnancy was not associated with SGA. CONCLUSIONS: Moderate and high caffeine intake during early pregnancy is associated with SGA. As the results suggest that even moderate caffeine intake during the first trimester may increase the risk of SGA, the intake within recommendation limits does not necessarily appear to be safe for pregnant women and their newborns.

Serum testosterone and oestradiol predict the growth response during puberty promoting treatment.

OBJECTIVE: The influence of androgens and oestrogens on growth is complex, and understanding their relative roles is important for optimising the treatment of children with various disorders of growth and puberty. DESIGN: We examined the proportional roles of androgens and oestrogens in the regulation of pubertal growth in boys with constitutional delay of growth and puberty (CDGP). The study compared 6-month low-dose intramuscular testosterone treatment (1 mg/kg/month; n = 14) with per oral letrozole treatment (2.5 mg/day; n = 14) which inhibits conversion of androgens to oestrogen. PATIENTS: Boys with CDGP were recruited to a randomized, controlled, open-label trial between 2013 and 2017 (NCT01797718). MEASUREMENTS: The patients were evaluated at 0-, 3- and 6-month visits, and morning blood samples were drawn. Linear regression models were used for data analyses. RESULTS: In the testosterone group (T-group), serum testosterone concentration correlated with serum oestradiol concentration at the beginning of the study and at 3 months, whereas in the letrozole group (Lz-group) these sex steroids correlated only at baseline. Association between serum testosterone level and growth velocity differed between the T and Lz groups, as each nmol/L increase in serum testosterone increased growth velocity 2.7 times more in the former group. Serum testosterone was the best predictor of growth velocity in both treatment groups. In the Lz-group, adding serum oestradiol to the model significantly improved the growth estimate. Only the boys with serum oestradiol above 10 pmol/L had a growth velocity above 8 cm/year. CONCLUSIONS: During puberty promoting treatment with testosterone or aromatase inhibitor letrozole, growth response is tightly correlated with serum testosterone level. A threshold level of oestrogen appears to be needed for an optimal growth rate that corresponds to normal male peak height velocity of puberty. Serum testosterone 1 week after the injection and serum testosterone and oestradiol 3 months after the onset of aromatase inhibitor treatment can be used as biomarkers for treatment response in terms of growth.

Bone structure assessed with pQCT in prepubertal males with delayed puberty or congenital hypogonadotropic hypogonadism.

OBJECTIVE: Congenital hypogonadotropic hypogonadism (CHH) is associated with impaired bone mineral density in adulthood, whereas the estimates on bone structure in adolescents with CHH has not been previously evaluated. This study describes bone structure in CHH patients and compares it to that in boys with constitutional delay of growth and puberty (CDGP). DESIGN: A cross-sectional study. METHODS: Peripheral quantitative computed tomography (pQCT) of non-dominant arm and left leg were performed. Volumetric bone mineral density (BMD), bone mineral content, and area in trabecular and cortical bone compartments were evaluated, and bone age-adjusted Z-scores for the bone parameters were determined. RESULTS: The participants with CHH had more advanced bone age and were older, taller and heavier than the CDGP boys, yet they had lower trabecular BMD in distal radius (147.7 mg/mm3 [95% CI, 128-168 mg/mm3 ] vs. 181.2 mg/mm3 [172-192 mg/mm3 ], p = .002) and distal tibia (167.6 mg/mm3 [145-190 mg/mm3 ] vs. 207.2 mg/mm3 [187-227 mg/mm3 ], p = .012), respectively. CHH males had lower cortical thickness at diaphyseal tibia than the participants with CDGP (p = .001). These between-group differences remained significant in corresponding Z-scores adjusted for bone age and height (p = .001). In CDGP group, serum testosterone correlated positively with trabecular BMD (r = 0.51, p = .013) at distal radius, and estradiol levels correlated positively with trabecular BMD at the distal site of tibia (r = 0.58, p = .004). CONCLUSIONS: Five treatment-naïve male patients with CHH exhibited poorer trabecular BMD than untreated males with CDGP. We speculate that timely low-dose sex steroid replacement in CHH males may benefit skeletal health in adulthood.

Caffeine content in newborn hair correlates with maternal dietary intake.

PURPOSE: High-maternal caffeine intake during pregnancy may be harmful for perinatal outcomes and future child health, but the level of fetal cumulative exposure has been difficult to measure thus far. Here, we present maternal dietary caffeine intake during the last trimester and its correlation to caffeine content in newborn hair after birth. METHODS: Maternal third trimester diets and dietary caffeine intake were prospectively collected in Kuopio Birth Cohort (KuBiCo) using a 160-item food frequency questionnaire (n = 2840). Newborn hair was collected within 48 h after birth and analyzed by high-resolution mass spectrometry (HRMS) for caffeine (n = 316). Correlation between dietary caffeine intake and neonatal hair caffeine content was evaluated from 203 mother-child pairs. RESULTS: Mean dietary caffeine intake was 167 mg/days (95% CI 162-172  mg/days), of which coffee comprised 81%. Caffeine in the maternal diet and caffeine content in newborn hair correlated significantly (r = 0.50; p < 0.001). Older, multiparous, overweight women, and smokers had the highest caffeine levels in the maternal diet, as well as in their newborn babies' hair. CONCLUSION: Caffeine exposure, estimated from newborn hair samples, reflects maternal third trimester dietary caffeine intake and introduces a new method to assess fetal cumulative caffeine exposure. Further studies to evaluate the effects of caffeine exposure on both perinatal and postnatal outcomes are warranted, since over 40% of pregnant women consume caffeine more than the current suggested recommendations (European Food Safety Association, EFSA recommendations).

The effect of maternal alcohol and drug abuse on first trimester screening analytes: a retrospective cohort study.

BACKGROUND: The purpose of this study was to determine whether first trimester trisomy screening (FTS) parameters are affected by alcohol and drug use. METHODS: A routine combined FTS including measurements of maternal serum levels of free ß-human chorionic gonadotropin subunit (free ß-hCG) and pregnancy-associated plasma protein A (PAPP-A) were measured at 9-11 weeks of gestation, and fetal nuchal translucency thickness (NTT) at 11-13 weeks of gestation. In total 544 women with singleton pregnancies [71 alcohol and drug abusers, 88 smokers, 168 non-smokers delivering a small for gestational age (SGA) child, and 217 unexposed control women] were assessed. RESULTS: Free ß-hCG levels were higher in alcohol and drug abusing than in unexposed pregnant women [mean 1.5 vs. 1.2 multiples of medians (MoM); P = 0.013]. However, stepwise multiple linear regression analyses suggested that smoking could explain increased free ß-hCG. Additionally, we observed lower PAPP-A levels in the smoking mothers (0.9 vs. 1.2 MoM; P = 0.045) and in those giving birth to an SGA child compared to the controls (1.1 vs.. 1.2 MoM; P < 0.001). Fetal NTT did not differ significantly between any of the groups. CONCLUSIONS: The present study shows increased free ß-hCG levels in alcohol and drug abusers, but maternal smoking may explain the result. Maternal serum PAPP-A levels were lower in smoking than non-smoking mothers, and in mothers delivering an SGA child. However, FTS parameters (PAPP-A, free ß-hCG and NTT) seem not to be applicable for the use as alcohol biomarkers because of their clear overlap between alcohol abusers and healthy controls.

Associations of lifestyle factors with serum dehydroepiandrosterone sulphate and insulin-like growth factor-1 concentration in prepubertal children.

OBJECTIVE: Little is known about the relationships of dietary factors, physical activity and sedentary behaviour to dehydroepiandrosterone sulphate (DHEAS) and insulin-like growth factor-1 (IGF-1) concentrations among prepubertal children. Therefore, we studied the associations of these lifestyle factors with serum DHEAS and IGF-1 in children. DESIGN AND SUBJECTS: Cross-sectional analysis of a population sample of 431 prepubertal children aged 6-9 years. MEASUREMENTS: Assessment of dietary factors by food records and physical activity and sedentary behaviour by a combined heart rate and movement monitor and a questionnaire. Measurement of serum DHEAS and IGF-1. RESULTS: Consumption of low-fibre grain products (standardized regression coefficient ß = .118, P = .017) and intake of vegetable protein (ß = .100, P = .045) was positively and consumption of sugar-sweetened beverages (ß = -.117, P = .018) was inversely associated with DHEAS after adjustment for sex, age and body fat percentage. Energy intake (ß = .160, P = .001) was positively associated with IGF-1 adjusting for sex, age and body fat percentage. Vigorous physical activity was inversely associated with DHEAS after adjustment for sex and age (ß = -.120, P = .027), and total (ß = -.137, P = .007), moderate (ß = -.130, P = .012), vigorous (ß = -.136, P = .011) and moderate to vigorous physical activity (ß = -.160, P = .003) were inversely and total sedentary behaviour (ß = .151, P = .003) was positively associated with IGF-1 adjusting for sex and age. None of physical activity measures was associated with DHEAS or IGF-1 after additional adjustment for body fat percentage. CONCLUSIONS: Lifestyle factors have weak and moderate associations with biochemical markers of adrenarche in prepubertal children. These associations indicate body fat independent and dependent influences of diet and physical activity, respectively.

Birth size, body composition, and adrenal androgens as determinants of bone mineral density in mid-childhood.

BackgroundBirth weight has an impact on adult bone mass. Higher birth weight is associated with greater bone mineral content (BMC) and children born small for gestational age (SGA) are at an increased risk for impaired accrual of bone mass. Our aim was to study whether the impact of birth size or early childhood growth on bone mass is visible already in mid-childhood.MethodsWe studied 49 children born large for gestational age (LGA), 56 children born appropriate for gestational age (AGA), and 23 children born SGA at 5.0-8.7 years of age. Body composition was assessed by whole-body dual-energy X-ray absorptiometry. Fasting blood samples and anthropometric data were collected.ResultsThe children born SGA had lower bone mineral density (BMD) Z-score (P<0.001) and age- and sex-adjusted BMD (P<0.005) than the LGA and AGA children. Adjusted BMC, muscle mass, and body fat percentage (%BF) did not differ between the study groups. Muscle mass, BMI SD score (SDS), %BF, and serum dehydroepiandrosterone sulfate (DHEAS) concentration were the strongest predictors of high BMD in mid-childhood.ConclusionSGA-born children had lower BMD in mid-childhood compared with AGA- and LGA-born ones. Muscle mass or BMI SDS, %BF, and DHEAS were significant predictors of childhood BMD.

Future risk of metabolic syndrome in women with a previous LGA delivery stratified by gestational glucose tolerance: a prospective cohort study.

BACKGROUND: Whether the delivery of a large-for-gestational-age (LGA) infant predicts future maternal metabolic syndrome (MetS) is not known. To this aim, we investigated the incidence of MetS and its components in women with or without a history of gestational diabetes mellitus (GDM) with a view to the birth weight of the offspring. METHODS: Eight hundred seventy six women treated for their pregnancies in Kuopio University Hospital in 1989-2009 underwent a follow-up study (mean follow-up time 7.3 (SD 5.1) years), of whom 489 women with GDM and 385 normoglycemic controls. The women were stratified into two groups according to the newborn's birth weight: 10-90th percentile (appropriate-for-gestational-age; AGA) (n = 662) and > 90th percentile (LGA) (n = 116). MetS and its components were evaluated in the follow-up study according to the International Diabetes Federation criteria. RESULTS: LGA vs. AGA delivery was associated with a higher incidence of MetS at follow-up in women with a background of GDM (54.4% vs. 43.6%), but not in women without GDM. CONCLUSION: An LGA delivery in women with GDM is associated with a higher risk of future MetS and this group is optimal to study preventive measures for MetS. In contrast, an LGA delivery after a normoglycemic pregnancy was not associated with an increased future maternal MetS risk.

Kuopio birth cohort - design of a Finnish joint research effort for identification of environmental and lifestyle risk factors for the wellbeing of the mother and the newborn child.

BACKGROUND: A Finnish joint research effort Kuopio Birth Cohort (KuBiCo) seeks to evaluate the effects of genetics, epigenetics and different risk factors (medication, nutrition, lifestyle factors and environmental aspects) during pregnancy on the somatic and psychological health status of the mother and the child. METHODS: KuBiCo will ultimately include information on 10,000 mother-child pairs who have given their informed consent to participate in this cohort. Identification of foetal health risk factors that can potentially later manifest as disease requires a repository of relevant biological samples and a flexible open up-to-date data handling system to register, store and analyse biological, clinical and questionnaire-based data. KuBiCo includes coded questionnaire-based maternal background data gathered before, during and after the pregnancy and bio-banking of maternal and foetal samples that will be stored in deep freezers. Data from the questionnaires and biological samples will be collected into one electronic database. KuBiCo consists of several work packages which are complementary to each other: Maternal, foetal and placental metabolism and omics; Paediatrics; Mental wellbeing; Prenatal period and delivery; Analgesics and anaesthetics during peripartum period; Environmental effects; Nutrition; and Research ethics. DISCUSSION: This report describes the set-up of the KuBiCo and descriptive analysis from 3532 parturients on response frequencies and feedback to KuBiCo questionnaires gathered from June 2012 to April 2016. Additionally, we describe basic demographic data of the participants (n = 1172). Based on the comparison of demographic data between official national statistics and our descriptive analysis, KuBiCo represents a cross-section of Finnish pregnant women.

Prepubertal children born large for gestational age have lower serum DHEAS concentrations than those with a lower birth weight.

BackgroundChildren born small for gestational age (SGA) have higher serum dehydroepiandrosterone sulfate (DHEAS) concentrations than children born appropriate for gestational age (AGA). The overall metabolic risk associated with birth weight is U-shaped, but it is not known whether children born large for gestational age (LGA) have elevated serum DHEAS levels.MethodsA cohort of 49 children born LGA, 56 children born AGA, and 23 children born SGA were studied at 5-8 years of age. Anthropometric data at birth, at the age of 2 years, and at examination were recorded. Fasting blood samples were collected for serum analyses of DHEAS, insulin-like growth factor 1 (IGF-1), and insulin concentrations.ResultsThe children born LGA had lower serum DHEAS levels adjusted for body mass index (BMI) standard deviation score (SDS) and age than the rest of the children. Lower birth weight SDS and higher weight gain during the first 2 years of life predicted higher serum DHEAS levels. Higher serum IGF-1 levels were also associated with higher prevalence of adrenarchal DHEAS levels.ConclusionBeing born LGA was associated with lower DHEAS levels, whereas small birth size and early catch-up growth predicted higher levels. This suggests that genetic or early epigenetic factors have an impact on adrenarche. IGF-1 may be a mediator in this process.

The risk of metabolic syndrome in women with previous GDM in a long-term follow-up.

The aim of this study was to evaluate the incidence of metabolic syndrome (MetS) during long-term follow-up of women with gestational diabetes (GDM). Furthermore, we evaluated the glycemic measures from an oral glucose tolerance test (OGTT) during pregnancy as predictors of incident MetS. Women diagnosed with GDM were divided into two groups according to the results of OGTT: one abnormal value = GDM1 (n = 338) and two abnormal values = GDM2 (n = 151), while women with normal glucose tolerance (n = 385) served as controls. MetS and its components were evaluated in a follow-up study (mean follow-up time 7.3 ± 5.1 years) according to the International Diabetes Federation (IDF) criteria. Fasting plasma glucose in OGTT was the best predictor of incident MetS in ROC (area under the curve) analysis. The incidence of MetS during a <5-year follow-up was 22.2% in controls, 39.3% in GDM1 and 60.4% in GDM2; and >10-year follow-up 24.2%, 46.2% and 62.5%, respectively. In controls and GDM2, the incidence of MetS remained nearly constant during the follow-up, whereas in GDM1 it increased. In conclusion, already mild gestational glucose intolerance may progress to MetS and therefore merits intervention measures to prevent future cardiovascular disease.

Maternal drug or alcohol abuse is associated with decreased head size from mid-pregnancy to childhood.

AIM: Maternal alcohol abuse is poorly recognised and causes developmental problems. This study explored the foetal central nervous systems (CNS), head circumference and psychomotor development of children exposed to drugs or alcohol during pregnancy up to 2.5 years of age. METHODS: We recruited 23 pregnant women referred to Kuopio University Hospital, Finland, by their family doctor because of drug or alcohol abuse, and 22 control mothers. Foetal CNS parameters were measured by three-dimensional ultrasonography at the mean gestational age of 20 weeks and the Griffiths Mental Developmental Scales (GMDS), and anthropometric measurements were carried out at the mean ages of one and 2.5 years. RESULTS: The exposed foetuses had decreased biparietal and occipito-frontal distances and head circumferences, but unchanged cerebellar volume at 20 weeks, and decreased head circumferences and length and height at birth, one and 2.5 years of age. They scored lower than the controls on the GMDS general quotient and the hearing, language and locomotor subscales at 2.5 years of age. CONCLUSION: Maternal alcohol or drug exposure was associated with decreased head size from mid-pregnancy to childhood and reduced development at 2.5 years. Foetal head circumference at mid-pregnancy was a useful indicator of substance abuse affecting the CNS.

Markers of Insulin Sensitivity in 12-Year-Old Children Born from Preeclamptic Pregnancies.

OBJECTIVE: To determine whether maternal preeclampsia influences insulin sensitivity (IS) or its biochemical markers in offspring. STUDY DESIGN: Sixty children born from a preeclamptic pregnancy (PRE) and 60 matched control subjects born from a normotensive pregnancy (non-PRE) were studied at age 12 years. IS was estimated using the Quantitative Insulin Sensitivity Check Index (QUICKI), and serum concentrations of adiponectin, leptin, insulin-like growth factor (IGF)-1, IGF-2, IGF-binding protein-1 (IGFBP-1), sex hormone-binding globulin, lipids, and casual blood pressure (BP) were measured. RESULTS: The mean values of QUICKI, serum adiponectin, leptin, IGF-1, IGF-2, IGFBP-1, and sex hormone-binding globulin did not differ between the PRE group and non-PRE group (P > .05 for all). The PRE subjects with the lowest IS (the lowest QUICKI tertile; n = 20) had significantly higher mean serum leptin (P = .007), triglyceride (P = .008), and IGF-1 (P = .005) levels and systolic BP (P = .019), and lower serum IGFBP-1 level (P = .007) compared with PRE subjects with higher QUICKI values (n = 40). Similarly, in logistic regression analysis, higher serum leptin (OR, 1.2; P = .009), triglyceride (OR, 1.2; P = .040), and IGF-1 (OR, 1.1; P = .031) levels and systolic BP (OR, 5.8; P = .024) were associated with low QUICKI in the PRE group. CONCLUSION: Maternal preeclampsia did not produce decreased IS in offspring by age of 12 years. However, the offspring with the lowest IS had higher mean serum triglyceride level and systolic BP, suggesting that components of the metabolic syndrome may cluster in this subgroup.

Post-challenge glycemia during pregnancy as a marker of future risk of type 2 diabetes: a prospective cohort study.

The aim of this study was to evaluate the glycemic measures from an oral glucose tolerance test (OGTT) during pregnancy as predictors of incident type 2 diabetes mellitus (T2DM). Patients diagnosed with gestational diabetes mellitus (GDM) were divided into two groups according to the results of OGTT: one abnormal value = GDM1 (n = 338) and two abnormal values = GDM2 (n = 151), while women with normal glucose tolerance served as controls (n = 385). Glucose tolerance was re-evaluated with an OGTT in a follow-up study (average follow-up time 7.3 ± 5.1 years). The incidence of T2DM after 10 years follow-up increased progressively by the degree of the glycemic abnormality during pregnancy: 0.8% in controls, 3.8% in GDM1 (adjusted HR 17.6, 95% CI 1.9-162.3) and 25.0% in GDM2 (adjusted HR 72.9, 95% CI 9.6-553.7), respectively (p = <0.0001). The risk of T2DM is significantly increased in women with two or more abnormal values in OGTT during pregnancy. Post-challenge glucose levels in OGTT were the best predictors of the incident T2DM in ROC analysis and they therefore identify the greatest risk group for targeted prevention of T2DM after GDM.

Serum androgen bioactivity is low in children with premature adrenarche.

BACKGROUND: Clinical findings in children with premature adrenarche (PA) correlate only partly with circulating levels of adrenal androgens. It is not known whether the prepubertal low circulating concentrations of testosterone (T) and dihydrotestosterone, together with those of adrenal androgens, are capable of activating the androgen receptor. METHODS: This cross-sectional study was performed at a university hospital. Circulating androgen bioactivity was measured in 67 prepubertal children with clinical signs of PA and 94 control children using a novel androgen bioassay. RESULTS: Circulating androgen bioactivity was low in the PA and control children. In the subgroup of children (n = 28) with serum T concentration over the assay sensitivity (0.35 nmol/l) and a signal in the androgen bioassay, we found a positive correlation between androgen bioactivity and serum T (r = 0.50; P < 0.01) and the free androgen index (r = 0.61; P < 0.01) and a negative correlation with serum sex hormone-binding globulin concentration (r = -0.41; P < 0.05). CONCLUSION: Peripheral metabolism of adrenal androgen precursors may be required for any androgenic effects in PA. However, the limitations in the sensitivity of the bioassay developed herein may hide some differences between the PA and control children.

Long-term changes in glucose metabolism after gestational diabetes: a double cohort study.

BACKGROUND: Gestational diabetes (GDM) has been associated with an elevated risk of type 2 diabetes in women after the pregnancy. Recognition of the factors differentiating the women at highest risk of progression to overt disease from those who remain normoglycemic after gestational diabetes is of key importance for targeted prevention programmes. To this aim, we investigated the incidence and risk factors of prediabetes and type 2 diabetes with a view to the underlying pathophysiological mechanisms in a long-term follow-up of women with a history of gestational diabetes. METHODS: 489 women with GDM and 385 normoglycemic controls attended a follow-up study after pregnancy (mean follow-up time 7.3, SD 5.1 years) in Kuopio, Finland. Glucose tolerance was evaluated with an oral glucose tolerance test, insulin sensitivity by Matsuda insulin sensitivity index (ISI), and insulin secretion by Disposition Index 30 (DI30). RESULTS: GDM increased risk of pre-diabetes and diabetes (HR 3.7, 95% C.I. 2.8-4.7 and HR 40.7, 95% C.I. 5.3-310.1, respectively, after adjustment for confounding factors) and was associated with both increased fasting (P < 0.001) and 2-hour plasma glucose (P < 0.001) during OGTT at the follow-up study. This effect was attenuated when adjusted for Matsuda ISI but abolished after adjustments with DI30 suggesting insulin secretion is the key defect leading to type 2 diabetes after GDM pregnancy. Increase in waist circumference and weight after pregnancy predicted the development of hyperglycemic conditions in women with a history of GDM (P < 0.001, and P = 0.002, respectively). CONCLUSIONS: Pre-diabetic stages after GDM pregnancy are frequent and reflect the progressive risk of type 2 diabetes in long-term follow-up. Hyperglycemia after GDM pregnancy results from beta cell failure and inability to compensate the increased insulin resistance by insulin secretion. Importantly, increase in waist circumference and as well as weight gain during the follow-up is associated with progression to prediabetes and type 2 diabetes in women with a history GDM.

Health-related quality of life of young adult women with a history of premature adrenarche.

INTRODUCTION: Children with premature adrenarche (PA) have increased adrenal androgen concentrations and earlier pubertal development than their peers. Early sexual maturation and exposure to androgens have both been associated with an increased risk for neuropsychological adversities in adulthood. Such adversities would presumably influence the experienced health-related quality of life (HRQoL) of those affected. METHODS: A longitudinal case-control cohort study, in which 30 PA girls and 40 age-matched controls were followed from childhood to young adult age. The main outcome measure was the total 15D HRQoL score. In addition, we assessed specific dimensions of the questionnaire, the subjects' relationship statuses and living arrangements. RESULTS: There were no differences between the groups in the overall 15D scores (PA, 0.956 (0.052); control, 0.947 (0.055); p 0.482), or on any dimension of this instrument. CONCLUSION: The study suggests that a history of PA does not lead to impaired HRQoL in adult age.

Accelerated Early Childhood Growth Is Associated With the Development of Earlier Adrenarche and Puberty.

Context: Small birth size and increased postnatal growth have been associated with earlier timing of adrenarche and puberty, but it is not well known whether these factors alone or together lead to earlier maturation. Objective: This work aimed to search for different growth trajectories using a clustering approach to analyze the effects of birth size and postnatal growth on adrenarchal and pubertal development. Methods: Altogether 351 children (48% girls) were examined prospectively at ages 6 to 9 and 9 to 11 years. Birth and early-growth data were collected retrospectively. Main outcome measures included clinical signs of adrenarche and puberty, and serum androgen concentrations (dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, testosterone). Results: We detected 4 clusters with different birth sizes and postnatal growth trajectories: 1) children with average birth size and increased postnatal growth (AI), 2) children with small birth size and increased postnatal growth (SI), 3) children with average birth size and postnatal growth (AA), and 4) children with small birth size and average postnatal growth (SA). Thelarche at age 9 to 11 was most common and serum androgens at ages 6 to 9 and 9 to 11 years were highest in girls belonging to the AI and SI groups. Similar patterns in the onset of puberty and in androgen levels were not seen in the SA group. Conclusion: Increased early growth and weight gain predict higher serum androgen concentrations and earlier onset of puberty in girls. Adrenarche and puberty do not appear to be shifted earlier in children with small birth size who do not have catch-up growth.

Maternal caffeine, coffee and cola drink intake and the risk of gestational diabetes - Kuopio Birth Cohort.

AIMS: Coffee intake is associated with a decreased risk of type 2 diabetes among non-pregnant people. We aimed to investigate the association between caffeine, coffee and cola drink intake in early pregnancy and the risk of gestational diabetes (GDM). METHODS: Kuopio Birth Cohort (KuBiCo) is a prospective cohort study including pregnant women who were followed at the prenatal clinics in outpatient healthcare centers and gave birth in Kuopio University Hospital, Finland (n=2214). Maternal diet during the first trimester of pregnancy was assessed using a 160-item food frequency questionnaire. GDM was diagnosed by oral glucose tolerance test according to the Finnish national guidelines mainly between 24 and 28 gestational weeks. RESULTS: Women with moderate coffee intake in the first trimester were less likely diagnosed with GDM than women without coffee intake in an age-adjusted model (OR 0.87; 95% CI 0.76-0.99; p = 0.03), but the association was attenuated in multi-adjusted models (p = 0.11). No association was found between caffeine intake and GDM. One third (32.4%) of pregnant women consumed caffeine over the recommendation (> 200 mg/d). Women who consumed cola drinks more than the median (33.3 mL/d) had an increased risk of GDM (OR 1.29; 95% CI 1.02-1.63, p = 0.037) in multi-adjusted model compared to those who consumed less. CONCLUSIONS: Caffeine intake during the first trimester of pregnancy was not associated with the risk of GDM but a minor non-significant decrease was seen with moderate coffee intake. Although the average consumption of cola drinks was low in the KuBiCo cohort, higher consumption was associated with an increased risk of GDM. Further studies are needed to evaluate the safe amount of coffee during pregnancy, since the recommended caffeine intake was exceeded in almost half of the coffee drinkers.