Biomedical subjects

Katharina M Main

Publications and source records attributed to Katharina M Main.

At least 19 recordsLinked to original sources

PubMed2007

From mother to child: investigation of prenatal and postnatal exposure to persistent bioaccumulating toxicants using breast milk and placenta biomonitoring.

The exposure levels of placenta and paired breast milk samples to selected organochlorine compounds and pesticides from Danish and Finnish samples have been investigated. p,p'-DDE is the dominant pollutant, beta-HCH, hexachlorobenzene, endosulfan-I, dieldrin, oxychlordane, cis-heptachlor epoxide and p,p'-DDT being the other major constituents. Their concentrations are linearly correlated between milk and placenta in similar patterns for Danish and Finnish samples. Milk samples have higher levels of these pollutants than placenta on lipid base. However, the apparently not correlated compounds, such as alpha-HCH, pentachlorobenzene, pentachloroanisole and methoxychlor, are generally accumulated more in placenta, which may suggest a tissue specific metabolic activity. Thus, depending on the compound of interest, biomonitoring may be done in placenta only or in both matrices.

Adult↗

PubMed2006

Mild gestational diabetes as a risk factor for congenital cryptorchidism.

CONTEXT: Cryptorchidism is the most common malformation in newborn boys. Maternal diabetes has previously been suggested to be a risk factor for this disorder in one epidemiological study. OBJECTIVE: Evaluation of the prevalence of maternal glucose metabolism disorders during pregnancy in newborn boys having normal testicular descent or congenital cryptorchidism. DESIGN: Postnatal analysis of maternal history concerning glucose metabolism abnormalities during pregnancy among cryptorchid and healthy Finnish boys. SETTING AND PARTICIPANTS: The material of this case-control study comprises 1163 boys with normal testicular descent at birth and 125 boys with congenital cryptorchidism. All these singleton Finnish boys were born in Turku University Central Hospital (1997-2001) and were examined at birth and/or at the expected date of delivery. MAIN OUTCOME MEASURES: Information about maternal diabetes diagnosis and abnormality of the result of a 2-h 75-g oral glucose tolerance test during pregnancy were obtained from the hospital records after delivery. RESULTS: After adjustment for possible confounding factors, i.e. maternal smoking during pregnancy, maternal age at delivery, and risk factors of cryptorchidism, e.g. prematurity and weight for gestational age, abnormal maternal glucose metabolism was significantly more common in the group of cryptorchid boys [diet-treated gestational diabetes, P = 0.0001; odds ratio, 3.98 (95% confidence interval, 1.97-8.05); diet-treated gestational diabetes or only an abnormal result in oral glucose tolerance test, P = 0.0016; odds ratio, 2.44 (95% confidence interval, 1.40-4.25)] when compared with boys with normal testicular descent. CONCLUSIONS: Mildly abnormal glucose metabolism during pregnancy was associated with an increased risk for congenital cryptorchidism. The mechanism remains to be elucidated.

Adult↗

PubMed2006

Serum insulin-like growth factor-I (IGF-I) and growth in children born after assisted reproduction.

CONTEXT: Concern has been raised about the safety of assisted reproduction techniques for the offspring. OBJECTIVES: The objective of the study was to investigate postnatal growth and growth factors in children born after intra-cytoplasmatic sperm injection (ICSI) and in vitro fertilization (IVF). DESIGN: The study had two cohorts: a population-based longitudinal infant cohort 0-36 months [236 ICSI, 173 IVF, 1530 naturally conceived (NC)], and a cross-sectional child cohort at 5 yr (68 ICSI, 67 IVF, 70 NC). INTERVENTION: Anthropometrical measurements were made at birth, 3, 18, 36 (infant cohort), and 60 months (child cohort), and blood samples were collected at 3 or 60 months. MAIN OUTCOME MEASURES: Serum IGF-I, IGFBP-3, height, weight, head and abdominal circumference, body mass index, and fat folds were the main outcome measures. RESULTS: Anthropometrical measurements showed no significant differences between ICSI and IVF children and controls in either cohort. However, singleton ICSI girls [3.4 (0.6) kg, P = 0.008] had a slightly lower birth weight than IVF [3.5 (0.5) kg] and NC girls [3.5 (0.5) kg]. Birth weights of singleton boys [3.6 (0.5) kg], twin boys [2.6 (0.6) kg], and twin girls [2.4 (0.5) kg] did not differ between types of conception. In the infant cohort in 3-month-old singletons, serum IGF-I was lower in ICSI [78 (26) ng/ml] than NC boys [94 (27) ng/ml, P < 0.001] and IVF [74 (34) ng/ml], compared with NC girls [93 (43) ng/ml, P = 0.011]. ICSI children were also smaller than their target height (sd score) at 3 yr of age [mean -0.91 (1.2)], compared with NC children [-0.61 (0.9), P = 0.033]. In the child cohort, target height attainment (sd score) and growth factors did not differ among the three groups. CONCLUSIONS: The overall growth pattern of ICSI and IVF children in both cohorts was normal. Our findings of subtle differences in target height attainment and serum IGF-I levels between infants born after assisted reproduction techniques and controls may not be clinically significant. However, these observations indicate that further systematic follow-up of growth and puberty in these children is needed.

Body Height↗

PubMed2006

Larger testes and higher inhibin B levels in Finnish than in Danish newborn boys.

CONTEXT: Recent studies showed that male reproductive health problems, such as cryptorchidism, hypospadias, testicular cancer, and low sperm quality, are more prevalent in Denmark than in Finland. OBJECTIVES: We hypothesized that, if fetal testicular dysgenesis contributed to these observations, differences in gonadal development and the hypothalamus-pituitary-testis axis would already be detectable perinatally. Thus, we investigated healthy newborn boys in both countries. DESIGN: This was a prospective, longitudinal population-based study. SETTING: Two primary obstetric centers were included at the University Hospitals of Copenhagen, Denmark, and Turku, Finland. PARTICIPANTS: The participants of the study included 633 Danish and 1044 Finnish boys, born at term with appropriate weight for gestational age. INTERVENTIONS: Ultrasound determination of testis size at 0, 3, and 18 months and blood sampling (n = 727) at 3 months were analyzed. MAIN OUTCOME MEASURES: Testicular volume and reproductive hormones were measured. RESULTS: Testis volume was significantly higher at all ages in Finnish than in Danish boys (medians, 98 vs. 95, 185 vs. 119, and 188 vs. 136 mm(3), respectively; P < 0.00001). Testis growth from birth to 3 months was larger in Finnish than in Danish boys (mean, 75 vs. 26 mm(3); P < 0.0001). Serum hormone levels were higher in Finnish than Danish boys for inhibin B (median, 456 vs. 385 pg/ml; P < 0.0001), FSH (1.33 vs. 1.21 IU/liter; P < 0.036), and SHBG (143 vs. 136 nmol/liter; P < 0.022). Inhibin B was significantly positively correlated to testicular volume (r = 0.25; P < 0.006). CONCLUSIONS: The larger testes and higher inhibin B levels most likely represent a bigger volume of seminiferous tubules in Finnish compared with Danish boys. Although this phenomenon may be attributable to a genetic difference between the two countries, it may also reflect environmental factors influencing testicular development.

Adult↗

PubMed2006

[Growth hormone treatment of short children born small for gestational age].

Short children born small for gestational age (SGA) are defined as having a birth weight below -2 SD for gestational age and a reduced height at four years of age (height < -2.5 SD). Growth hormone (GH) treatment significantly improves final height (mean height gain 12 centimetres) in such children. Consequently, GH therapy has been an approved indication in Europe since 2003 for SGA children who remain short at four years of age. The Danish consensus guidelines for diagnosis, treatment and control of short SGA children are described in this review.

Body Height↗

PubMed2006

Impaired cognitive function in women with congenital adrenal hyperplasia.

CONTEXT: Congenital adrenal hyperplasia (CAH) is a disorder with a wide spectrum of severity. OBJECTIVE: The objective of this study was to investigate cognitive function in CAH women. DESIGN: This was a case-control study. SETTING: This study was conducted at a tertiary center for pediatric endocrinology at the University Hospital of Copenhagen. PARTICIPANTS: Thirty-five Danish CAH women (age 17-51 yr) were included, and participation rate was 84%. Control women were recruited through the Danish Civil Registration System and matched on age and education. MAIN OUTCOME MEASURES: An abbreviated form of the Wechsler Adult Intelligence Scale was used, i.e. full-scale intelligence quotient (IQ; five of 11 subtests), which included three of six verbal IQ subtests and two of five performance IQ subtests. RESULTS: A significantly lower IQ was found in CAH patients compared with controls with respect to mean full-scale IQ (84.5 vs. 99.1; P < 0.001), mean verbal IQ (86.6 vs. 97.3; P < 0.001), and mean performance IQ (85.7 vs. 101.3; P < 0.001). The salt-wasting CAH group had lower IQ scores than the simple-virilizing CAH group, which reached significance for mean total IQ (81.2 vs. 92.8, P = 0.04) and mean verbal IQ (84.7 vs. 95.5, P = 0.05), and additionally, lower scores than the late-onset CAH group, which reached significance for performance IQ (mean 81.5 vs. 96.2, P = 0.02). CONCLUSIONS: Impaired cognitive function was observed in patients with CAH, especially in salt-wasting CAH. These intriguing findings may reflect adverse effects of hyponatremic episodes, suboptimal postnatal hormone replacement therapy or prenatal adrenal androgen excess, and the potential psychosocial consequences of the disorder.

Adrenal Cortex Hormones↗

PubMed2006

Hormonal changes in 3-month-old cryptorchid boys.

CONTEXT: Hormonal dysregulation has been suggested to be one of many etiological factors of cryptorchidism. OBJECTIVES: The objective of this study was to assess the hypothalamic-pituitary-testicular axis in cryptorchid boys during the postnatal hormonal surge. DESIGN: This was a prospective, longitudinal, population-based study. SETTING: The study was performed at two primary obstetric centers. PARTICIPANTS: Study participants included 388 Finnish and 433 Danish boys (88 and 34 with cryptorchidism, respectively). INTERVENTIONS: Clinical examinations were performed at 0 and 3 months. Blood samples were taken at 3 months. MAIN OUTCOME MEASURES: The main outcome measures were testis position and reproductive hormone levels. RESULTS: Finnish cryptorchid boys had significantly higher FSH [1.59 (0.50-3.53) vs. 1.30 (0.49-2.92) IU/liter; P < 0.0001] and lower inhibin B [426 (254-770) vs. 459 (266-742) pg/ml; P < 0.015] levels than Finnish control boys [median (2.5th-97.5th percentiles)]. Danish cryptorchid boys had higher FSH levels than controls [1.47 (0.54-3.89) vs. 1.18 (0.41-3.04) IU/liter; P = 0.018]. Inhibin B levels in healthy Danish boys were lower than those in Finnish boys [380 (233-637) pg/ml; P < 0.0001] and were not reduced in Danish crypt-orchid boys [392 (236-672) pg/ml; P = 0.851]. Changes in hormone levels were strongest in boys with severe, persistent cryptorchidism, but were also detectable in mild and transient cryptorchidism. Effects on Leydig cell function were subtle, with an increase in LH in Finnish (but not Danish) cryptorchid boys vs. controls [1.97 (0.77-5.91) vs. 1.75 (0.58-4.04) IU/liter; P < 0.021], but testosterone levels remained within the normal range. CONCLUSIONS: Our results support the hypothesis that cryptorchidism is associated with a primary testicular disorder, which could be a cause or a consequence of cryptorchidism. This malfunction is reflected by low inhibin B production in the Finnish cohort and high gonadotropin drive in both the Finnish and Danish cohorts.

Child↗

PubMed2006

Is human fecundity declining?

Summary The decreasing trends in fertility rates in many industrialized countries are now so dramatic that they deserve much more scientific attention. Although social and behavioural factors undoubtedly play a major role for these trends, it seems premature, and not based on solid information, to conclude that these trends can be ascribed to social and behavioural changes alone. There is evidence to suspect that changing lifestyle and increasing environmental exposures, e.g. to endocrine disrupters, are behind the trends in occurrence of male reproductive health problems, including testis cancer, undescended testis and poor semen quality. These biological factors may also contribute to the extremely low fertility rates. However, the necessary research is complex and requires non-traditional collaboration between demographers, epidemiologists, clinicians, biologists, wild life researchers, geneticists and molecular biologists. This research effort can hardly be carried out without major support from governments and granting agencies making it possible to fund collaborative projects within novel research networks of scientists.

Environmental Pollutants↗

PubMed2006

Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age.

UNLABELLED: Phthalates adversely affect the male reproductive system in animals. We investigated whether phthalate monoester contamination of human breast milk had any influence on the postnatal surge of reproductive hormones in newborn boys as a sign of testicular dysgenesis. DESIGN: We obtained biologic samples from a prospective Danish-Finnish cohort study on cryptorchidism from 1997 to 2001. We analyzed individual breast milk samples collected as additive aliquots 1-3 months postnatally (n = 130; 62 cryptorchid/68 healthy boys) for phthalate monoesters [mono-methyl phthalate (mMP), mono-ethyl phthalate (mEP), mono-n-butyl phthalate (mBP), mono-benzyl phthalate (mBzP), mono-2-ethylhexyl phthalate (mEHP), mono-isononyl phthalate (miNP)]. We analyzed serum samples (obtained in 74% of all boys) for gonadotropins, sex-hormone binding globulin (SHBG), testosterone, and inhibin B. RESULTS: All phthalate monoesters were found in breast milk with large variations [medians (minimum-maximum)]: mMP 0.10 (< 0.01-5.53 microg/L), mEP 0.95 (0.07-41.4 microg/L), mBP 9.6 (0.6-10,900 microg/L), mBzP 1.2 (0.2-26 microg/L), mEHP 11 (1.5-1,410 microg/L), miNP 95 (27-469 microg/L). Finnish breast milk had higher concentrations of mBP, mBzP, mEHP, and Danish breast milk had higher values for miNP (p = 0.0001-0.056). No association was found between phthalate monoester levels and cryptorchidism. However, mEP and mBP showed positive correlations with SHBG (r = 0.323, p = 0.002 and r = 0.272, p = 0.01, respectively); mMP, mEP, and mBP with LH:free testosterone ratio (r = 0.21-0.323, p = 0.002-0.044) and miNP with luteinizing hormone (r = 0.243, p = 0.019). mBP was negatively correlated with free testosterone (r = -0.22, p = 0.033). Other phthalate monoesters showed similar but nonsignificant tendencies. CONCLUSIONS: Our data on reproductive hormone profiles and phthalate exposures in newborn boys are in accordance with rodent data and suggest that human Leydig cell development and function may also be vulnerable to perinatal exposure to some phthalates. Our findings are also in line with other recent human data showing incomplete virilization in infant boys exposed to phthalates prenatally.

Adult↗

PubMed2006

Persistent pesticides in human breast milk and cryptorchidism.

INTRODUCTION: Prenatal exposure to some pesticides can adversely affect male reproductive health in animals. We investigated a possible human association between maternal exposure to 27 organochlorine compounds used as pesticides and cryptorchidism among male children. DESIGN: Within a prospective birth cohort, we performed a case-control study; 62 milk samples from mothers of cryptorchid boys and 68 from mothers of healthy boys were selected. Milk was collected as individual pools between 1 and 3 months postpartum and analyzed for 27 organochlorine pesticides. RESULTS: Eight organochlorine pesticides were measurable in all samples (medians; nanograms per gram lipid) for cases/controls: 1,1-dichloro-2,2-bis(4-chlorophenyl) ethylene (p,p -DDE) : 97.3/83.8; beta-hexachlorocyclohexane (beta-HCH) : 13.6/12.3; hexachlorobenzene (HCB) : 10.6/8.8; alpha-endosulfan: 7.0/6.7; oxychlordane: 4.5/4.1; 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (p,p -DDT) : 4.6/4.0; dieldrin: 4.1/3.1 ; cis-heptachloroepoxide (cis-HE) : 2.5/2.2. Five compounds [octachlorostyrene (OCS); pentachlorobenzene, 1,1-dichloro-2,2-bis(4-chlorophenyl) ethane(p,p -DDD) ; o,p -DDT ; mirex] were measurable in most samples (detection rates 90.8-99.2%) but in lower concentrations. For methoxychlor, cis-chlordane, pentachloroanisole (PCA), gamma-HCH, 1,1-dichloro-2-(2-chlorophenyl) -2,2(4-chlorophenyl) ethane, trans-chlordane, alpha-HCH, and o,p -DDE, both concentrations and detection rates were low (26.5-71.5%). Heptachlor, HCH (lc delta, epsilon), aldrin, beta-endosulfan and trans-heptachloroepoxide were detected at negligible concentrations and low detection rates and were not analyzed further. Seventeen of 21 organochlorine pesticides [p,p -DDT, p,p-DDE, p,p-DDD, o,p-DDT, HCH (alpha, beta, gamma), HCB, PCA, alpha-endosulfan, cis-HE, chlordane (cis-, trans-) oxychlordane, methoxychlor, OCS, and dieldrin] were measured in higher median concentrations in case milk than in control milk. Apart from trans-chlordane (p = 0.012), there were no significant differences between cryptorchid and healthy boys for individual chemicals. However, combined statistical analysis of the eight most abundant persistent pesticides showed that pesticide levels in breast milk were significantly higher in boys with cryptorchidism (p = 0.032). CONCLUSION: The association between congenital cryptorchidism and some persistent pesticides in breast milk as a proxy for maternal exposure suggests that testicular descent in the fetus may be adversely affected.

Adult↗

PubMed2006

Postnatal penile length and growth rate correlate to serum testosterone levels: a longitudinal study of 1962 normal boys.

OBJECTIVE: Infant boys show a brief activation of their hypothalamic-pituitary-gonadal axis shortly after birth, the physiological significance of which is poorly understood. The objective of the study was to investigate the correlation between endogenous testosterone levels and penile size and growth. DESIGN: Prospective, longitudinal population-based study taking place at two large primary obstetric centres at the University Hospitals of Copenhagen, Denmark, and Turku, Finland. METHODS: Infant boys, 728 Danish and 1234 Finnish, underwent clinical examinations at 0, 3, 18 and 36 months in Denmark and at 0, 3 and 18 months in Finland with blood samples taken at 3 months (n = 630). Penile length and growth were registered and reproductive hormones (testosterone, sex hormone binding globulin, oestradiol) were analysed. RESULTS: Penile length increased from birth (3.49+/-0.4 cm) to 3 years of age (4.53+/-0.51 cm) with the highest growth velocity from birth to 3 months (1.0 mm/month). Penile length and growth were significantly, positively correlated to serum testosterone (r = 0.31 and 0.076, P = 0.006 and 0.001 respectively) and to free testosterone index (r = 0.385 and 0.094, P = 0.0001 and 0.0001 respectively). CONCLUSIONS: We found that endogenous testosterone was significantly associated with penile size and growth rate in infant boys. Thus, the postnatal surge in reproductive hormones appears to be important for genital growth. Our data may serve as an updated reference for normal penile length in Caucasian boys up to 3 years of age.

Aging↗

PubMed2006

Environmental chemicals and thyroid function.

There is growing evidence that environmental chemicals can disrupt endocrine systems. Most evidence originates from studies on reproductive organs. However, there is also suspicion that thyroid homeostasis may be disrupted. Several groups of chemicals have potential for thyroid disruption. There is substantial evidence that polychlorinated biphenyls, dioxins and furans cause hypothyroidism in exposed animals and that environmentally occurring doses affect human thyroid homeostasis. Similarly, flame retardants reduce peripheral thyroid hormone (TH) levels in rodents, but human studies are scarce. Studies also indicate thyroid-disruptive properties of phthalates, but the effect of certain phthalates seems to be stimulative on TH production, contrary to most other groups of chemicals. Thyroid disruption may be caused by a variety of mechanisms, as different chemicals interfere with the hypothalamic-pituitary-thyroid axis at different levels. Mechanisms of action may involve the sodium-iodide symporter, thyroid peroxidase enzyme, receptors for THs or TSH, transport proteins or cellular uptake mechanisms. The peripheral metabolism of the THs can be affected through effects on iodothyronine deiodinases or hepatic enzymes. Even small changes in thyroid homeostasis may adversely affect human health, and especially fetal neurological development may be vulnerable. It is therefore urgent to clarify whether the animal data showing effects of chemicals on thyroid function can be extended to humans.

Animals↗

PubMed2006

Quality of life in 70 women with disorders of sex development.

OBJECTIVE: The aim of this study was to assess the quality of life and psychosocial well-being in women with disorders of sex development (DSD). DESIGN: An open case-control study. METHODS: Social and psychiatric information was collected via a structured interview from 70 Danish women diagnosed with DSD, 70 controls matched on sex, age, and school education, and six women with isolated genital malformations. Quality of life and mental distress were assessed by 'Quality of Life-Assessment of Growth Hormone Deficiency in Adults' (QoL-AGHDA) and three symptom scales from the 'Hopkins Symptom Checklist' (SCL-90-R; i.e. somatization, depression, and anxiety) respectively. For both measures, higher scores reflected poorer outcomes. RESULTS: Present relationships and having children were less frequent in patients than in controls (P = 0.02 and P < 0.001 respectively). Previous suicidal thoughts (P = 0.002) and a higher frequency of psychological/psychiatric counseling for severe problems (P = 0.06) were more frequently reported in patients than in controls. The mean QoL-AGHDA score was significantly higher in patients than in controls (5.5 vs 2.9; P = 0.002), especially for congenital adrenal hyperplasia (CAH) females (P = 0.01) and virilized 46,XX and 46,XY females (P = 0.04). The total SCL score was higher in patients than in controls (mean 23.2 vs 20.0), reaching significance for anxiety (mean 6.3 vs 4.3, P = 0.03) with highest score in CAH (P = 0.01). CONCLUSION: An impaired quality of life and more affective distress were observed especially in CAH patients and virilized 46,XX and 46,XY females. This may be caused by trauma from distressing diagnostic procedures, the chronic illnesses per se, and psychosocial consequences of the disorders.

Adrenal Hyperplasia, Congenital↗

PubMed2005

Pegvisomant treatment in a 4-year-old girl with neurofibromatosis type 1.

BACKGROUND/AIMS: Growth hormone (GH) excess in childhood is a rare disorder. Current treatment options such as somatostatin analogues, pituitary surgery or irradiation can have serious side effects. Recently, a GH receptor antagonist, pegvisomant, was introduced for the treatment of adults with acromegaly. We wanted to investigate whether pegvisomant was effective in a child with octreotide-resistant GH excess. CASE: A 4-year-old girl with neurofibromatosis type 1 and GH excess associated with optic glioma received pegvisomant injections (10 mg subcutaneously) with increasing intervals from daily to every 4th day. RESULTS: IGF-I and IGFBP-3 decreased from +6.9 and 4.6 standard deviation scores (SDS), respectively, to within normal range. Height velocity dropped from 12.4 SDS to mean -0.7 SDS (range: -5.0 to 5.0) and height SDS decreased from +1.3 to +0.6 (target height: +0.2). Random non-fasting serum GH values were mean 5.0 mlU/l (range: 1.6-9.5). There was no change in fasting blood glucose (4.6-4.7 mmol/l) or glycosylated haemoglobin (5.5%) and no subjective or biochemical side effects. Repeated tests of thyroid, adrenal and gonadal function showed no alterations during the treatment period. Intracranial tumours remained unchanged in size and visual impairment did not deteriorate. CONCLUSION: Pegvisomant normalized IGF-I and IGFBP-3 levels. Growth velocity was normalized after initial catch-down growth, and it remains to be seen whether this result can be maintained during long-term treatment.

Antineoplastic Agents↗

PubMed2005

Enantiomeric ratios as an indicator of exposure processes for persistent pollutants in human placentas.

The enantiomeric ratios (ER) of alpha-HCH and o,p'-DDT ((+)-isomer concentration/(-)-isomer concentration) and o,p'-DDD (first eluting enantiomer/second enantiomer) were investigated in 112 human placentas from Finnish boys collected 1997-2001. Both o,p'-DDD and alpha-HCH showed changes in their ER depending on the total concentration of the compound in the sample. Their ERs are approaching a value close to racemic mixture (ER=1) at high concentrations. At low concentrations they often differ from 1. The relationship between concentration and ER is clearly identified and it has been shown that it is not affected by analytical uncertainty. This relationship appears to be important for assessing tissue- and species-specific exposure and risk and it may indicate whether net uptake or metabolic activity is dominant in exposure for the resulting exposure of the enantiomers.

DDT↗

PubMed2005

Determination of phthalate monoesters in human milk, consumer milk, and infant formula by tandem mass spectrometry (LC-MS-MS).

Daily exposure of humans to phthalates may be a health risk because animal experiments have shown these compounds can affect the differentiation and function of the reproductive system. Because milk is the main source of nutrition for infants, knowledge of phthalate levels is important for exposure and risk assessment. Here we describe the development and validation of a quantitative analytical procedure for determination of phthalate metabolites in human milk. The phthalate monoesters investigated were: monomethyl phthalate (mMP), monoethyl phthalate (mEP), mono-n-butyl phthalate (mBP), monobenzyl phthalate (mBzP), mono-(2-ethylhexyl) phthalate (mEHP), and monoisononyl phthalate (mNP). The method is based on liquid extraction with a mixture of ethyl acetate and cyclohexane (95:5) followed by two-step solid-phase extraction (SPE). Detection and quantification of the phthalate monoesters were accomplished by high-pressure liquid chromatography using a Betasil phenyl column (100 mmx2.1 mmx3 microm) and triple tandem mass spectrometry (LC-MS-MS). Detection limits were in the range 0.01 to 0.5 microg L(-1) and method variation was from 5 to 15%. Analysis of 36 milk samples showed that all these phthalates were present, albeit at different concentrations. Median values (microg L(-1)) obtained were 0.11 (mMP), 0.95 (mEP), 3.5 (mBP), 0.8 (mBzP), 9.5 (mEHP), and 101 (mNP). We also analysed seven samples of consumer milk and ten samples of infant formula. Only mBP and mEHP were detected in these samples, in the ranges 0.6-3.9 microg L(-1) (mBP) and 5.6-9.9 microg L(-1) (mEHP).

Chromatography, Liquid↗

PubMed2005

Delayed diagnosis of congenital adrenal hyperplasia with salt wasting due to type II 3beta-hydroxysteroid dehydrogenase deficiency.

Classical 3beta-hydroxysteroid dehydrogenase (3beta-HSD) deficiency is a rare cause of congenital adrenal hyperplasia. We report two sisters presenting with delayed diagnoses of classical 3beta-HSD, despite salt wasting (SW) episodes in infancy. Sibling 1 was referred for premature pubarche, slight growth acceleration, and advanced bone age, whereas sibling 2 had no signs of virilization. At referral, increased 17alpha-hydroxyprogesterone associated with premature pubarche at first suggested a nonclassical 21-hydroxylase deficiency. Sequencing of the CYP21 gene showed both girls only heterozygotes (V281L mutation). This result, combined with SW in infancy, suggested a 3beta-HSD deficiency because of increased dehydroepiandrosterone sulfate levels. Further hormonal studies showed markedly elevated Delta5-steroids, in particular 17alpha-hydroxypregnenolone greater than 100 nmol/liter (the clue to the diagnosis) and elevated Delta5-/Delta4-steroid ratios. Sequencing of the type II 3beta-HSD gene documented that both girls were compound heterozygotes for T181I and 1105delA mutations. Retrospectively, elevated levels of 17alpha-hydroxyprogesterone were found on blood spots from Guthrie's test. There is no previous report of the combination of SW and premature pubarche due to mutations in the type II 3beta-HSD gene. Because neonatal diagnosis could have prevented life-threatening crises in these girls, this report further supports the benefits for neonatal screening for congenital adrenal hyperplasia whatever the etiology.

3-Hydroxysteroid Dehydrogenases↗

PubMed2005

Circannual rhythm in the incidence of cryptorchidism in Finland.

Conflicting data on circannual variation in birth rates of urogenital malformations have been reported previously. To assess risk factors of cryptorchidism we studied the seasonal variation of cryptorchidism in Finland. We performed a prospective cryptorchidism study in Turku, Finland, from 1997 to 2001 to evaluate the incidence of cryptorchidism. Clinical examinations were performed at birth and at 3 months. Of 9511 liveborn boys (1471 preterm boys) 216 (53 preterm boys) were cryptorchid at birth and 106 (19 preterm boys) at 3 months. The incidence of cryptorchidism was significantly higher in spring (February-April) (3.0%) than in summer (May-July) (1.7%) (OR 1.79; 95% CI: 1.23-2.63). This seasonal difference was observed both among preterm and term boys. We conclude that a circannual fluctuation in the incidence of cryptorchidism exists, which indicates an influence by environmental factors. The underlying reason for cyclicity affects similarly both preterm and term boys.

Circadian Rhythm↗