Maternal bereavement and cryptorchidism in offspring.

BACKGROUND: Cryptorchidism (undescended testis) is a common anomaly with largely unexplained etiology. Animal studies have suggested maternal emotional stress as a potential risk factor, but this has not been studied in humans. We aimed to investigate whether maternal bereavement due to the death of a close relative in the antenatal period increases the occurrence of cryptorchidism in the offspring. METHODS: In a population-based cohort, we studied death of a close relative as the exposure and cryptorchidism entries in nationwide medical registries as the outcome. Danish national registries included 898,961 (23,609 exposed) boys born from 1978 to 2008 with a maximum of 30 years of follow-up. RESULTS: A total of 20,947 boys had cryptorchidism, of whom 13,524 also underwent corrective surgery. We found no increased occurrence of cryptorchidism in the offspring (hazard ratio = 1.02 [95% confidence interval = 0.92-1.14]). Results were similar when the diagnosis was verified with surgery. We adjusted for maternal and paternal age, birth year, and family history of cryptorchidism. CONCLUSION: We observed no association between maternal bereavement before and during pregnancy and the occurrence of cryptorchidism in the offspring.

Amniotic fluid phthalate levels and male fetal gonad function.

BACKGROUND: Prenatal exposure to phthalates may pose a threat to human male reproduction. However, additional knowledge about the in vivo effect in humans is needed, and reported associations with genital abnormalities are inconclusive. We aimed to study prenatal di(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DiNP) exposure in relation to cryptorchidism, hypospadias, and human fetal Leydig cell function. METHODS: We studied 270 cryptorchidism cases, 75 hypospadias cases, and 300 controls. Second-trimester amniotic fluid samples were available from a Danish pregnancy-screening biobank (n = 25,105) covering 1980-1996. We assayed metabolites of DEHP and DiNP (n = 645) and steroid hormones (n = 545) by mass spectrometry. We assayed insulin-like factor 3 by immunoassay (n = 475) and analyzed data using linear or logistic regression. RESULTS: Mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP, DEHP metabolite) was not consistently associated with cryptorchidism or hypospadias. However, we observed an 18% higher (95% confidence interval [CI] = 5%-33%) testosterone level, and a 41% lower (-56% to -21%) insulin-like factor 3 level in the highest 5cx-MEPP tertile compared with the lowest. Mono(4-methyl-7-carboxyheptyl) phthalate (7cx-MMeHP, DiNP metabolite) showed elevated odds ratio point estimates for having cryptorchidism (odds ratio = 1.28 [95% CI = 0.80 to 2.01]) and hypospadias (1.69 [0.78 to 3.67]), but was not consistently associated with the steroid hormones or insulin-like factor 3. CONCLUSIONS: Data on the DEHP metabolite indicate possible interference with human male fetal gonadal function. Considering the DiNP metabolite, we cannot exclude (nor statistically confirm) an association with hypospadias and, less strongly, with cryptorchidism.

Exploring educational disparities in risk of preterm delivery: a comparative study of 12 European birth cohorts.

BACKGROUND: An association between education and preterm delivery has been observed in populations across Europe, but differences in methodology limit comparability. We performed a direct cross-cohort comparison of educational disparities in preterm delivery based on individual-level birth cohort data. METHODS: The study included data from 12 European cohorts from Denmark, England, France, Lithuania, the Netherlands, Norway, Italy, Portugal, and Spain. The cohorts included between 2434 and 99 655 pregnancies. The association between maternal education and preterm delivery (22-36 completed weeks of gestation) was reported as risk ratios, risk differences, and slope indexes of inequality with 95% confidence intervals (CIs). RESULTS: Singleton preterm live delivery proportion varied between 3.7% and 7.5%. There were large variations between the cohorts in the distribution of education and maternal characteristics. Nevertheless, there were similar educational differences in risk of preterm delivery in 8 of the 12 cohorts with slope index of inequality varying between 2.2 [95% CI 1.1, 3.3] and 4.0 [95% CI 1.4, 6.6] excess preterm deliveries per 100 singleton deliveries among the educationally most disadvantaged, and risk ratio between the lowest and highest education category varying from 1.4 [95% CI 1.1, 1.8] to 1.9 [95% CI 1.2, 3.1]. No associations were found in the last four cohorts. CONCLUSIONS: Educational disparities in preterm delivery were found all over Europe. Despite differences in the distributions of education and preterm delivery, the results were remarkably similar across the cohorts. For those few cohorts that did not follow the pattern, study and country characteristics did not explain the differences.

Sex bias in ultrasound measures of gestational age: assessment by sex ratio in post-term births.

BACKGROUND: Estimation of fetal age by ultrasound assumes identical biometries for both sexes at identical gestational ages. However, late in the first trimester male fetuses become larger overall than female fetuses, which may introduce a sex bias with clinical consequences. A recent study showed that using due-date estimates based on biparietal diameter from the second trimester increased the post-term male-to-female ratio and the risk of stillbirth among female fetuses born at 43 gestational weeks. We aimed to evaluate whether this increased male-to-female ratio was also present when the due date was based on crown-rump length from the first trimester. METHODS: The study population included 3987 women with a certain last menstrual period (LMP), as well as a crown-rump length measured in the first trimester and a biparietal diameter measured in the second trimester. We defined birth after 42 completed weeks estimated by LMP as post-term. Labor was not routinely induced until after 42 weeks. Male-to-female ratios were estimated using logistic regression. RESULTS: When gestational age was estimated by biparietal diameter, the sex ratio steadily increased from 0.98 (95% confidence interval = 0.87-1.11) in week 40 to 1.54 (1.09-2.17) in week 42. A similar increase did not occur when using certain LMP or crown-rump length. CONCLUSIONS: The use of crown-rump length for the estimation of gestational age is not associated with an increased post-term male-to-female ratio. It can therefore be used for the estimation of due date without risk of the sex bias that occurs when using biparietal diameter in second trimester of pregnancy.

Gestational age, small for gestational age, and infantile colic.

BACKGROUND: Preterm and growth restricted infants may have developmental delays and deviations from normal organ function related to the gastrointestinal tract and the central nervous system. Since both organ systems are hypothesised to be involved in the pathogenesis of infantile colic, a condition characterised by excessive crying during the first months of life, impaired fetal growth and preterm birth may be risk factors for infantile colic. METHODS: A total of 62,761 liveborn singletons from the Danish National Birth Cohort (1996 to 2002) were studied. Infantile colic was defined according to Wessel's modified criteria based on maternal interview conducted at 6 months post-partum. RESULTS: A total of 2605 (4.2%) infants were born preterm, 54,441 (86.7%) at term, and 5715 (9.1%) post-term. A total of 4964 (7.9%) infants fulfilled Wessel's modified criteria for infantile colic. The risk for infantile colic increased with decreasing gestational age after adjustment for covariates. The highest odds [odds ratio (95% confidence interval)] was observed for infants born before 32 completed gestational weeks (1.5 [95% CI 1.0, 2.2], reference: 40 gestational weeks). Small for gestational age infants (birthweight below 10th percentile) had an increased odds of infantile colic (1.2 [95% CI 1.1, 1.3]) in all gestational age groups. CONCLUSIONS: We observed an increased risk of infantile colic in preterm and small for gestational age infants in a large cohort. Our results suggest that the aetiology of infantile colic may be found in the prenatal, perinatal, and neonatal period.

Socio-occupational class, region of birth and maternal age: influence on time to detection of cryptorchidism (undescended testes): a Danish nationwide register study.

BACKGROUND: Cryptorchidism (undescended testes) is associated with poor male fertility, but can be alleviated and fertility preserved to some degree by early detection and treatment. Here we assess the influence of socio-occupational class, geographical region, maternal age and birth cohort on time to detection and correction of cryptorchidism. METHODS: All boys born in Denmark, 1981 to 1987 or 1988 to 1994, with a diagnosis of cryptorchidism were identified in nationwide registers. The boys were followed for a diagnosis until their 16th birthday. The age at first diagnosis was noted and used as proxy for time to detection of cryptorchidism. Parental employment in the calendar year preceding birth was grouped into one of five socio-occupational classes. Geographical region was defined by place of birth in one of 15 Danish counties. Detection rate ratios of cryptorchidism were analyzed as a function of parental socio-occupational group, county, maternal age and birth cohort by use of Poisson regression. RESULTS: Some 6,059 boys in the early and 5,947 boys in the late cohort received a diagnosis of cryptorchidism. Time to detection was independent of parental socio-occupational group and maternal age but differed slightly between geographical regions. A similar pattern was obtained for surgical correction after a diagnosis. Age at diagnosis decreased by 2.7 years from the early to the late cohort. CONCLUSIONS: These results indicate that childhood socio-occupational inequality in detection and correction of cryptorchidism would play a negligible role in male infertility in a life course perspective. Geographical region may have exerted some influence, especially for the oldest cohort.

Predictors for an unsuccessful INtubation-SURfactant-Extubation procedure: a cohort study.

BACKGROUND: The INtubation-SURfactant-Extubation (INSURE) is a procedure that is increasingly being used to treat the respiratory distress syndrome in preterm infants. The objective of this study was to identify predictors for an unsuccessful INSURE procedure. METHODS: The neonates included were less than 32 weeks' gestation, treated with surfactant in the neonatal intensive care unit, and born 1998-2010. INSURE was defined as surfactant administration during intubation for less than 2 hours without the need for mechanical ventilation. INSURE success was defined as no re-intubation within 72 hours after INSURE, and INSURE failure was defined as re-intubation within 72 hours after INSURE. An unsuccessful INSURE procedure was either INSURE failure or mechanical ventilation for more than 24 hours immediately after surfactant administration. All predictors were defined a priori and were present before surfactant administration. Multivariate logistic regression was performed. RESULTS: In total, 322 neonates were included: 31% (n = 100) had INSURE success, 10% (n = 33) had INSURE failure, 49% (n = 158) needed mechanical ventilation for more than 24 hours, and the remaining 10% (n = 31) needed mechanical ventilation for less than 24 hours. Predictors for INSURE failure were low gestational age and hemoglobin below 8.5 mmol/l. Predictors for mechanical ventilation for more than 24 hours were low gestational age, Apgar at 5 minutes below 7, oxygen need above 50%, CO2 pressure above 7 kPa (~53 mmHg), pH below 7.3, lactate above 2.5 mmol/l, need for inotropes, and surfactant administration shortly after birth, whereas preeclampsia reduced the risk. CONCLUSIONS: We identified specific predictors associated with an unsuccessful INSURE procedure. Keeping high-risk neonates with one or several predictors intubated and treated with mechanical ventilation after surfactant may prevent a re-intubation procedure.

Cryptorchidism and hypospadias in a cohort of 934,538 Danish boys: the role of birth weight, gestational age, body dimensions, and fetal growth.

Early delivery and low birth weight are strong predictors of the urogenital anomalies cryptorchidism (undescended testis) and hypospadias. Understanding these associations may lead to important etiologic clues. Therefore, the authors revisited the prevailing hypotheses regarding fetal growth restriction as a risk factor for urogenital anomalies. They studied a population of 934,538 Danish boys born alive between January 1, 1980, and December 31, 2008. Cryptorchidism and hypospadias were associated with low weight-for-gestational-age, an indicator of fetal growth restriction, and furthermore the authors observed strong interaction with early delivery. Low birth weight in a singleton compared with the mean birth weight of all singleton brothers in the family or in a twin compared with the male co-twin was associated with higher risk of urogenital anomalies, suggesting an effect of relative fetal growth restriction within families. Contrary to previous reports, newborns' body dimensions assessed independently of birth weight were not associated with urogenital anomalies. The hypothesis that shared factors cause both fetal growth restriction and urogenital anomalies was supported by comparison of urogenital anomaly risks in singletons and twins and by patterns of cryptorchidism and hypospadias co-occurrence in individuals. These novel insights might also extend to other male reproductive conditions with prenatal etiology.

Age at cryptorchidism diagnosis and orchiopexy in Denmark: a population based study of 508,964 boys born from 1995 to 2009.

PURPOSE: Early treatment for cryptorchidism may be necessary to preserve fertility. International guidelines now recommend that congenital cryptorchidism be treated with orchiopexy before age 1 year. Acquired cryptorchidism should be treated at presentation. To our knowledge the rate of adherence to these guidelines in recent years is unknown. Thus, we present data on age at cryptorchidism diagnosis and orchiopexy in recent Danish birth cohorts. MATERIALS AND METHODS: A population of 508,964 Danish boys born alive from January 1, 1995 to December 31, 2009 was identified using the Danish Civil Registration System. Five birth cohorts were defined, including 1995 to 1997, 1998 to 2000, 2001 to 2003, 2004 to 2006 and 2007 to 2009. The boys were followed in the Danish National Patient Registry for a diagnosis of cryptorchidism and for an orchiopexy procedure. Data were analyzed using the Kaplan-Meier estimator and Cox regression models. RESULTS: During followup 10,094 boys were diagnosed with cryptorchidism, of whom 5,473 underwent orchiopexy. Mean age at diagnosis in boys followed at least 6 years was 3.3 years (95% CI 3.3-3.4) in the 1995 to 1997 cohort, 3.1 (95% CI 3.1-3.2) in the 1998 to 2000 cohort and 2.9 (95% CI 2.8-2.9) in the 2001 to 2003 cohort while mean age at orchiopexy was 3.8 (3.7-3.9), 3.6 (3.5-3.7) and 3.3 years (3.2-3.4), respectively. CONCLUSIONS: In the more recent birth cohorts of 1995 to 2009 we observed a shift toward younger age at cryptorchidism diagnosis and orchiopexy.

The risk of cryptorchidism among sons of women working in horticulture in Denmark: a cohort study.

BACKGROUND: Androgens are crucial for normal testicular descent. Studies show that some pesticides have estrogenic or antiandrogenic effects, and that female workers exposed to pesticides have increased risk of having a boy with cryptorchidism. The main objective of the present study was to investigate whether pregnant women exposed to pesticides due to their work in horticulture experience excess risk of having sons with cryptorchidism. METHODS: We conducted a cohort study of pregnant women working in horticulture using four cohorts including one cohort established with data from the departments of occupational medicine in Jutland and Funen and three existing mother-child cohorts (n=1,468). A reference group was established from the entire Danish population of boys born in the period of 1986-2007 (n=783,817). Nationwide Danish health registers provided information on birth outcome, cryptorchidism diagnosis and orchiopexy. The level of occupational exposure to pesticides was assessed by expert judgment blinded towards outcome status. Risk of cryptorchidism among exposed horticulture workers compared to the background population and to unexposed horticulture workers was assessed by Cox regression models. RESULTS: Pesticide exposed women employed in horticulture had a hazard ratio (HR) of having cryptorchid sons of 1.39 (95% CI 0.84; 2.31) and a HR of orchiopexy of 1.34 (0.72; 2.49) compared to the background population. Analysis divided into separate cohorts revealed a significantly increased risk of cryptorchidism in cohort 2: HR 2.58 (1.07;6.20) and increased risk of orchiopexy in cohort 4: HR 2.76 (1.03;7.35), but no significant associations in the other cohorts. Compared to unexposed women working in horticulture, pesticide exposed women had a risk of having sons with cryptorchidism of 1.34 (0.30; 5.96) and of orchiopexy of 1.93 (0.24;15.4). CONCLUSIONS: The data are compatible with a slightly increased risk of cryptorchidism in sons of women exposed to pesticides by working in horticulture.

Maternal use of acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy and risk of cryptorchidism.

BACKGROUND: Cyclooxygenase (COX) inhibitors-acetaminophen, ibuprofen and acetylsalicylic acid-have endocrine-disruptive properties in the rainbow trout. In humans, aspirin blocks the androgen response to human chorionic gonadotropin (hCG), and, because hCG-stimulated androgen production in utero is crucial for normal testicular descent, exposure to COX inhibitors at vulnerable times during gestation may impair testicular descent. We examined whether prenatal exposure to acetaminophen, ibuprofen, and acetylsalicylic acid was associated with increased occurrence of cryptorchidism. METHODS: Our study used data on 47,400 live-born singleton sons of mothers enrolled in the Danish National Birth Cohort during 1996-2002. Cryptorchidism was identified in 980 boys during childhood, of whom 565 underwent orchiopexy. The use of acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy was assessed in 3 computer-assisted telephone interviews and 1 self-administered questionnaire. We estimated adjusted hazard ratios (HRs) of cryptorchidism by Cox regression analysis. RESULTS: Exposure to acetaminophen during both the first and second trimesters was associated with increased occurrence of cryptorchidism (HR = 1.33 [95% confidence interval = 1.00-1.77]). Exposure for more than 4 weeks within the postulated time-window of programming testicular descent (gestational weeks 8-14) was associated with a HR of 1.38 (1.05-1.83) for cryptorchidism. Exposure to ibuprofen and acetylsalicylic acid was not associated with cryptorchidism. CONCLUSION: Maternal intake of acetaminophen for more than 4 weeks during pregnancy, especially during the first and second trimesters, may moderately increase the occurrence of cryptorchidism.

Alcohol binge drinking during pregnancy and cryptorchidism.

BACKGROUND: Recent studies have suggested gestational weeks 8-14 as a time window of particular importance to the intrauterine development of the male genitalia, and prenatal exposure to alcohol is under suspicion as a risk factor for cryptorchidism. We examined if prenatal exposure to alcohol, and especially binge drinking, during the suggested programming window is associated with an increased risk of cryptorchidism. METHODS: The authors used data on 41 268 live born singleton boys of mothers who were enrolled into the Danish National Birth Cohort in 1996-2002. During early childhood, 1598 cases of cryptorchidism were identified and 398 of these were orchiopexy verified. Maternal alcohol consumption including number and timing of binge drinking episodes was assessed in two computer-assisted telephone interviews around gestational weeks 17 and 32. Adjusted hazard ratios (HRs) of cryptorchidism were estimated by Cox regression. RESULTS: Average weekly alcohol consumption as well as frequency of binge drinking at any time during pregnancy was not associated with risk of cryptorchidism. Binge drinking in gestational weeks 7-15 was associated with a slightly increased risk of cryptorchidism with adjusted HRs between 1.03 and 1.66. CONCLUSION: Prenatal exposure to alcohol-measured as average intake as well as frequency and timing of binge drinking-was not associated with cryptorchidism. Our findings, however, do not rule out that binge drinking during the suggested male programming window may increase the risk of cryptorchidism.

Risk of cryptorchidism among sons of horticultural workers and farmers in Denmark.

OBJECTIVES: Previous studies indicate an increased risk of cryptorchidism, incomplete testicular descent, among sons of women working with pesticides. This study assessed the risk of cryptorchidism among boys of parents employed as horticultural workers and farmers using nationwide registers on occupation and cryptorchidism. METHODS: The cohort consisted of >600 000 boys born in Denmark from 1980-2007 with a parent in employment during pregnancy. These boys were followed for cryptorchidism from 1980-2009 comparing risks among sons of horticultural workers and farmers with sons of parents in other occupations. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Cox regression adjusting for parental age, birth years, parity, and geographical region. RESULTS: Sons of maternal farmers were at increased risk of cryptorchidism (157 cases; HR 1.31, 95% CI 1.12-1.53) compared to boys of mothers in other occupations (15 511 cases). Paternal occupation as farmer was unrelated to the risk among sons. Maternal occupation as a horticultural worker was associated with a non-significantly increased risk (72 cases; HR 1.20, 95% CI 0.95-1.52). A similar association was found for paternal horticultural workers. Sons of maternal farmers or horticultural workers who likely worked in the first trimester were not at increased risk of cryptorchidism. CONCLUSIONS: This nationwide cohort study found a slightly increased risk of cryptorchidism in sons of maternal horticultural workers and farmers. However, subgroup analyses indicated similar findings for paternal horticultural workers, and no association for women likely working in the first trimester. The main findings should therefore be interpreted with caution.

Risk of cryptorchidism and hypospadias among boys of maternal hairdressers - a Danish population-based cohort study.

OBJECTIVES: Pregnant hairdressers may be exposed to a mixture of chemicals in their working environment. The possible relationship between these chemical agents and male reproductive tract malformations has raised concern that the working environment of hairdressers might have adverse effects on fetal development. This study assessed the risk of cryptorchidism and hypospadias among boys of maternal hairdressers. METHODS: National population-based registers were used to determine maternal occupation and identify cases of cryptorchidism and hypospadias. The cohort comprised all children born in Denmark from 1980-2007. Using Cox regression, we estimated hazard ratios (HR) with 95% confidence intervals (95% CI) for hospitalization for cryptorchidism and hypospadias from 1980-2009. RESULTS: Boys of hairdressers were not at increased risk of cryptorchidism (134 cases, HR 0.91; 95% CI 0.77-1.08) or hypospadias (33 cases, HR 1.27; 95% CI 0.90-1.79) compared to children of mothers in other occupations (14 988 and 2556 cases of cryptorchidism and hypospadias, respectively). Additional analyses using children of shop assistants and receptionists as controls and restricted to (i) firstborns, (ii) cryptorchidism cases with corrective surgery, (iii) specific birth years, and (iv) women without social benefit payments in gestational weeks 8-14 produced consistent results of no increased risk. CONCLUSION: Our nationwide cohort study shows that, despite exposure to a complex chemical milieu, hairdressers do not have an increased risk of having boys with cryptorchidism and hypospadias.

Nicotine replacement therapy during pregnancy and infantile colic in the offspring.

OBJECTIVE: To investigate the associations between use of nicotine replacement therapy (NRT) and smoking during pregnancy and infantile colic in the offspring. METHODS: We used data from maternal interviews (from pregnancy and at 6 months post partum) from the Danish National Birth Cohort (1996-2002). We included 63 128 live-born singletons with complete information on nicotine exposure during pregnancy and infantile colic symptoms as recorded at 6 months of age. RESULTS: A total of 46 660 infants (73.9%) were unexposed to nicotine during pregnancy; 207 (0.3%) were exposed to NRT, 15 016 (23.8%) were exposed to smoking, and 1245 (2.0%) to both. A total of 4974 (7.9%) infants fulfilled Wessel's modified criteria for infantile colic. Prenatal nicotine exposure was associated with elevated risk for infantile colic in the offspring. Compared with the unexposed, NRT users had an adjusted odds ratio (OR) (95% confidence interval) of 1.6 (1.0-2.5; P = .03), smokers had OR = 1.3 (1.2-1.4), and women who both smoked and used NRT had OR = 1.6 (1.3-1.9). Partners' smoking was not associated with infantile colic after adjustment for maternal smoking. CONCLUSIONS: We corroborated the association between smoking and infantile colic after adjustment for several possible confounders in a large cohort study. Moreover, we found that infants exposed to NRT prenatally had an increased risk for infantile colic of the same magnitude as those exposed to tobacco smoke. Thus, nicotine may play a role in the pathogenesis of infantile colic.

Phthalates and perfluorooctanesulfonic acid in human amniotic fluid: temporal trends and timing of amniocentesis in pregnancy.

BACKGROUND: Measures of prenatal environmental exposures are important, and amniotic fluid levels may directly reflect fetal exposures during hypothesized windows of vulnerability. OBJECTIVES: We aimed to detect various phthalate metabolites and perfluorooctanesulfonic acid (PFOS) in human amniotic fluid, to study temporal exposure trends, and to estimate potential associations with gestational week of amniocentesis and maternal age and parity at amniocentesis. METHODS: We studied 300 randomly selected second-trimester amniotic fluid samples from a Danish pregnancy-screening biobank covering 1980 through 1996. We used only samples from male offspring pregnancies. We assayed the environmental pollutants by liquid chromatography/triple quadrupole mass spectrometry and analyzed data using generalized linear regression models. RESULTS: We detected the di(2-ethylhexyl) phthalate (DEHP) metabolite mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP) at a median concentration of 0.27 ng/mL [interquartile range (IQR): 0.20-0.37 ng/mL], the diisononyl phthalate (DiNP) metabolite mono(4-methyl-7-carboxyheptyl) phthalate (7cx-MMeHP) at 0.07 ng/mL (IQR: 0.05-0.11 ng/mL), and PFOS at 1.1 ng/mL (IQR: 0.66-1.60 ng/mL). An increase of 1 calendar year was associated with 3.5% lower [95% confidence interval (CI): -4.8%, -2.1%] 5cx-MEPP levels and with 7.1% higher (95% CI: 5.3%, 9.0%) 7cx-MMeHP levels. For each later gestational week of amniocentesis, 5cx-MEPP was 9.9% higher (95% CI: 4.8%, 15.2%), 7cx-MMeHP was 8.6% higher (95: CI: 2.7%, 14.9%), and PFOS was 9.4% higher (95: CI: 3.3%, 15.9%). We observed no associations with maternal age or parity. CONCLUSIONS: Measured metabolite levels appeared to parallel decreasing DEHP exposure and increasing DiNP exposure during the study period. The environmental pollutant levels were positively associated with later gestational age at amniocentesis during pregnancy weeks 12-22.

Cryptorchidism concordance in monozygotic and dizygotic twin brothers, full brothers, and half-brothers.

OBJECTIVE: To study concordance rates of cryptorchidism (undescended testis) in pairs of boys with varying family structure, to evaluate the risk contribution from the intrauterine environment and genetic factors. DESIGN: Population based study of 1,024,500 Danish boys born from January 1, 1973 to December 31, 2004. Classic twin method and computerized square dance design. SETTING: Hospitals and outpatient clinics. PATIENT(S): Six groups of boy pairs: boys with no relation, paternal half-brothers, maternal half-brothers, full brothers, dizygotic twin brothers, and monozygotic twin brothers. INTERVENTION(S): Observational study. MAIN OUTCOME MEASURE(S): Status on each individual regarding cryptorchidism and orchiopexy from the Danish National Patient Register. RESULT(S): Concordance rates of cryptorchidism in the groups were as follows: boys with no relation 3.2% (95% confidence interval 2.7%-3.6%), paternal half-brothers 3.4% (2.3%-4.7%), maternal half-brothers 6.0% (4.5%-7.7%), full brothers 8.8% (8.3%-9.8%), dizygotic twin brothers 24.1% (16.0%-33.6%), and monozygotic twin brothers 27.3% (15.5%-41.2%). CONCLUSION(S): The concordance rate was higher in maternal than in paternal half-brothers, and much higher but of equal magnitude in both twin groups. The findings strongly support that the intrauterine environment and maternal inheritance are contributing to the occurrence of cryptorchidism.