***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Background Prenatal exposure to alcohol can adversely affect the fetus . We investigated the association between  maternal alcohol consumption during pregnancy and  cryptorchidism ( undescended testis ) among newborn boys . Methods We examined 2,496 boys in a prospect i ve Danish – Finnish birth cohort study for cryptorchidism at birth ( cryptorchid/healthy : 128/2,368 ) and at 3 months of age ( 33/2,215 ) . Quantitative information on  alcohol consumption ( average weekly consumption of wine , beer , and spirits  and number of binge episodes ) , smoking , and caffeine intake  was obtained by question naire and /or interview once during the third trimester of pregnancy , before the outcome of the pregnancy was known . For a subgroup ( n = 465 ) , information on alcohol consumption was obtained twice during pregnancy by interviews . Results We investigated maternal alcohol consumption both as a continuous variable and categorized . The odds for cryptorchidism increased with increasing weekly alcohol consumption . After adjustment for confounders ( country , smoking , caffeine intake , binge episodes , social class , maternal age , parity , maturity , and birth weight ) the odds remained significant for women with a weekly consumption of five or more alcoholic drinks ( odds ratio = 3.10 ; 95 % confidence interval , 1.05–9.10 ) . Conclusions Regular alcohol intake during pregnancy appears to increase the risk of congenital cryptorchidism in boys . The mechanisms for this association are unknown . Counseling of pregnant women with regard to alcohol consumption should also consider this new finding Background Risk factors for  congenital cryptorchidism  were investigated in a prospect i ve birth cohort study in Denmark and Finl and from 1997 to 2001 . Methodology and Principal Findings In total , 2,496 boys were examined for cryptorchidism at birth ( cryptorchid/healthy : 128/2,368 ) and three months old ( 33/2,215 ) . Information on risk factors was obtained antenatally ( question naire/interview ) or at birth from birth records . Use of nicotine substitutes during pregnancy ( n = 40 ) and infertility treatment by intrauterine insemination ( n = 49 ) were associated with an increased risk for cryptorchidism , adjusted odds ratio ( 95 % confidence interval ) ( OR ( 95%CI ) ) 3.04 ( 95%CI 1.00–9.27 ) and 3.01 ( 95%CI 1.27–7.15 ) , respectively . No association was seen for mothers ( n = 79 ) who had infertility treatment in form of intracytoplasmic sperm injection ( ICSI ) or in vitro fertilization ( IVF ) treatment ( OR 0.71 95%CI 0.21–2.38 ) . In total , 728 ( 29 % ) reported to have smoked during pregnancy , however , no increased risk among maternal smokers was found . Furthermore , we found statistically significant associations between cryptorchidism and low birth weight , prematurity , being small for gestational age , substantial vaginal bleeding , and breech presentation , which are in accordance with other studies . Conclusions and Significance Our study revealed two novel risk factors for cryptorchidism : intrauterine insemination and the use of nicotine substitutes in pregnancy . This suggests that cryptorchidism may not only be associated to genetic factors , but also to maternal lifestyle and exposure OBJECTIVES Studies in rodents suggest that metformin treatment during pregnancy may have harmful effects on testicular development in offspring . Our aim was to determine whether metformin treatment of gestational diabetes mellitus ( GDM ) affects testicular size in male offspring . METHODS We compared the testicular size in prepubertal boys born to mothers who participated in a r and omized controlled trial ( RCT ) comparing metformin with insulin in the treatment of GDM . Twenty-five ( 42.4 % of invited ) and 27 ( 52.9 % of invited ) boys whose mothers had been treated with metformin or insulin , respectively , participated in the study . Testicular size was measured by a ruler , an orchidometer , and by ultrasonography at the age of 33 to 85 months . RESULTS The mean age of the boys was 60 months at the time of examination , and did not differ between the metformin and insulin group ( p = 0.88 ) . There was no difference in testicular size between the boys in the two groups ( p always ≥ 0.40 ) , and there were no significant differences in height , weight , BMI , BMI z-score , or waist-to-hip ratio ( WHR ) between the boys in the groups . CONCLUSIONS Prepubertal testicular size did not differ between offspring born to metformin-treated mothers and those born to insulin-treated mothers BACKGROUND Recently , over-the-counter mild analgesic use during pregnancy has been suggested to influence the risk of reproductive disorders in the offspring . We examined the influence of maternal exposure to mild analgesics  during pregnancy on the occurrence of cryptorchidism and hypospadia in their offspring . METHODS Associations between maternal exposure to mild analgesics during pregnancy and cryptorchidism or hypospadia in the offspring were studied in 3184 women participating in a large population -based prospect i ve birth cohort study from early pregnancy onwards in the Netherl and s ( 2002 - 2006 ) , the Generation R Study . Cryptorchidism and hypospadia were identified during routine screening assessment s performed in child health care centres by trained physicians . The use of mild analgesics was assessed in three prenatal question naires in pregnancy , result ing in four periods of use , namely , periconception period , first 14 weeks of gestation , 14 - 22 weeks of gestation and 20 - 32 weeks of gestation . Logistic regression analyses were used to study the associations between maternal exposure to mild analgesics and cryptorchidism and hypospadia . RESULTS The cumulative prevalence over 30 months of follow up was 2.1 % for cryptorchidism and 0.7 % for hypospadia . Use of mild analgesics in the second period of pregnancy ( 14 - 22 weeks ) increased the risk of congenital cryptorchidism [ adjusted odds ratio ( OR ) 2.12 ; 95 % confidence interval ( CI ) 1.17 - 3.83 ] , primarily due to the use of acetaminophen ( paracetamol ) ( adjusted OR 1.89 ; 95 % CI 1.01 - 3.51 ) . Among mothers of cryptorchid sons , 33.8 % reported ( 23 of 68 ) the use of  mild analgesics  during pregnancy , compared with 31.8 % ( 7 of 22 ) of mothers with a boy with hypospadia and 29.9 % ( 926 of 3094 ) of mothers with healthy boys . CONCLUSIONS Our results suggest that intrauterine exposure to mild analgesics , primarily paracetamol , during the period in pregnancy when male sexual differentiation takes place , increases the risk of 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 prospect i ve birth cohort , we performed a case – control study ; 62 milk sample s 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 sample s ( medians ; nanograms per gram lipid ) for cases/controls : 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene ( p , p′-DDE ) : 97.3/83.8 ; β-hexachlorocyclohexane ( β-HCH ) : 13.6/12.3 ; hexachlorobenzene ( HCB ) : 10.6/8.8 ; α -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 sample s ( detection rates 90.8–99.2 % ) but in lower concentrations . For methoxychlor , cis-chlordane , pentachloroanisole ( PCA ) , γ -HCH , 1,1-dichloro-2-(2-chlorophenyl)-2,2(4-chlorophenyl)ethane , trans-chlordane , α -HCH , and o , p′-DDE , both concentrations and detection rates were low ( 26.5–71.5 % ) . Heptachlor , HCH ( δ , ɛ ) , aldrin , β-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 ( α , β , γ ) , HCB , PCA , α -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 STUDY QUESTION Is first trimester phthalate exposure associated with anogenital distance ( AGD ) , a biomarker of prenatal and rogen exposure , in newborns ? SUMMARY ANSWER Concentrations of diethylhexyl phthalate ( DEHP ) metabolites in first trimester maternal urine sample s are inversely associated with AGD in male , but not female , newborns . WHAT IS KNOWN ALREADY AGD is a sexually dimorphic measure reflecting prenatal and rogen exposure . Prenatal phthalate exposure has been associated with shorter male AGD in multiple animal studies . Prior human studies , which have been limited by small sample size and imprecise timing of exposure and /or outcome , have reported conflicting results . STUDY DESIGN , SIZE , DURATION The Infant Development and the Environment Study ( TIDES ) is a prospect i ve cohort study of pregnant women recruited in prenatal clinics in San Francisco , CA , Minneapolis , MN , Rochester , NY and Seattle , WA in 2010 - 2012 . Participants delivered 787 infants ; 753 with complete data are included in this analysis . PARTICIPANTS / MATERIAL S , SETTING , METHODS Any woman over 18 years old who was able to read and write English ( or Spanish in CA ) , who was < 13 weeks pregnant , whose pregnancy was not medically threatened and who planned to deliver in a study hospital was eligible to participate . Analyses include all infants whose mothers provided a first trimester urine sample and who were examined at or shortly after birth . Specific gravity ( SpG ) adjusted concentrations of phthalate metabolites in first trimester urine sample s were examined in relation to genital measurements . In boys ( N = 366 ) , we obtained two measures of anogenital distance ( AGD ) ( anoscrotal distance , or AGDAS and anopenile distance , AGDAP ) as well as penile width ( PW ) . In girls ( N = 373 ) , we measured  anofourchette distance ( AGDAF ) and anoclitoral distance ( AGDAC ) . We used multivariable regression models that adjusted for the infant 's age at exam , gestational age , weight-for-length Z-score , time of day of urine collection , maternal age and study center . MAIN RESULTS AND THE ROLE OF CHANCE Three metabolites of DEHP were significantly and inversely associated with both measures of boys ' AGD . Associations ( β , 95 % confidence interval ( CI ) ) between AGDAS and ( log10 ) SpG-adjusted phthalate concentrations were : -1.12 ( -2.16 , -0.07 ) for mono-2-ethylhexyl phthalate ( MEHP ) , -1.43 , ( -2.49 , -0.38 ) for mono-2-ethyl-5-oxohexyl phthalate 
    Output:
    
Consistent effects of analgesic and phthalate exposure on human fetal germ cell development are demonstrated in experimental models , correlating with evidence from epidemiological studies and animal models .
Furthermore , analgesic-induced reduction in fetal testosterone production , which predisposes to the development of male reproductive disorders , has been reported in studies involving human tissues , which also supports data from animal and epidemiological studies .