Prenatal iodine supplementation and early childhood neurodevelopment: the PoppiE trial - study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Observational studies suggest both low and high iodine intakes in pregnancy are associated with poorer neurodevelopmental outcomes in children. This raises concern that current universal iodine supplement recommendations for pregnant women in populations considered to be iodine sufficient may negatively impact child neurodevelopment. We aim to determine the effect of reducing iodine intake from supplements for women who have adequate iodine intake from food on the cognitive development of children at 24 months of age. METHODS AND ANALYSIS: A multicentre, randomised, controlled, clinician, researcher and participant blinded trial with two parallel groups. Using a hybrid decentralised clinical trial model, 754 women (377 per group) less than 13 weeks' gestation with an iodine intake of ≥165 µg/day from food will be randomised to receive either a low iodine (20 µg/day) multivitamin and mineral supplement or an identical supplement containing 200) µg/day (amount commonly used in prenatal supplements in Australia), from enrolment until delivery. The primary outcome is the developmental quotient of infants at 24 months of age assessed with the Cognitive Scale of the Bayley Scales of Infant Development, fourth edition. Secondary outcomes include infant language and motor development; behavioural and emotional development; maternal and infant clinical outcomes and health service utilisation of children. Cognitive scores will be compared between groups using linear regression, with adjustment for location of enrolment and the treatment effect described as a mean difference with 95% CI. ETHICS AND DISSEMINATION: Ethical approval has been granted from the Women's and Children's Health Network Research Ethics Committee (HREC/17/WCHN/187). The results of this trial will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04586348.

Trends and outcomes of open, laparoscopic, and robotic inguinal hernia repair in the veterans affairs system.

PURPOSE: Robotic inguinal hernia repair (RHR) is an evolving technique but is comparatively expensive and has yet to show superior outcomes versus open (OHR) or laparoscopic (LHR) approaches. The utilization and clinical outcomes of RHR have not been reported within the veterans affairs (VA) system. This study analyzes trends in utilization and 30-day post-operative outcomes between OHR, LHR, and RHR in veterans. METHODS: This is a retrospective review of patients that underwent inguinal herniorrhaphy using the Veterans Affairs Quality Improvement Program database. Multivariable analysis of outcomes was performed adjusting for pre-operative confounding covariates between OHR, LHR, and RHR. Trends in utilization, complication rates, and operative times were also reported. RESULTS: From 2008-2019, 124,978 cases of inguinal herniorrhaphy were identified: 100,880 (80.7%) OHR, 18,035 (14.4%) LHR, and 6063 (4.9%) RHR. Compared to LHR, RHR was associated with 4.94 times higher odds of complications, 100 min longer mean operative time, and 1.5 days longer median length of stay (LOS). Compared to OHR, RHR was associated with 5.92 times higher odds of complications, 57 min longer mean operative time, and 1.1 days longer median LOS. Utilization of RHR and LHR significantly increased over time. RHR complication rates decreased over time (2008: 20.8% to 2019: 3.2%) along with mean operative times (2008: 4.9 h to 2019: 2.8 h; p < 0.05). CONCLUSION: While this study demonstrated inferior outcomes after RHR, the temporal trends are encouraging. This may be due to increased surgeon experience with robotics. Further prospective data will elucidate the role of RHR as this technique increases.

Evaluating resident involvement and the 'July effect' in parotidectomy.

OBJECTIVE: This study aimed to evaluate the effect of resident involvement and the 'July effect' on peri-operative complications after parotidectomy. METHOD: The American College of Surgeons National Surgical Quality Improvement Program database was queried for parotidectomy procedures with resident involvement between 2005 and 2014. RESULTS: There were 11 733 cases were identified, of which 932 involved resident participation (7.9 per cent). Resident involvement resulted in a significantly lower reoperation rate (adjusted odds ratio, 0.18; 95 per cent confidence interval, 0.05-0.73; p = 0.02) and readmission rate (adjusted odds ratios 0.30; 95 per cent confidence interval, 0.11-0.80; p = 0.02). However, resident involvement was associated with a mean 24 minutes longer adjusted operative time and 23.5 per cent longer adjusted total hospital length of stay (respective p < 0.01). No significant difference in surgical or medical complication rates or mortality was found when comparing cases among academic quarters. CONCLUSION: Resident participation is associated with significantly decreased reoperation and readmission rates as well as longer mean operative times and total length of stay. Resident transitions during July are not associated with increased risk of adverse peri-operative outcomes after parotidectomy.

Embryo blastulation and quality between days 5 and 6 of extended embryo culture.

PURPOSE: This study aims to know what proportion of culture day 5 pre-blastocyst-stage embryos develop into blastocysts by culture day 6 and what patient and cycle characteristics are associated with delayed blastocyst formation. METHODS: A retrospective observational cohort analysis was performed including a total of 9886 embryos from 1008 IVF cycles in 835 patients, who underwent treatment between January 1, 2016, and December 31, 2018. Autologous fresh in vitro fertilization (IVF) cycles at a single academic center were included in the analysis. Embryos were group-cultured using single-step culture media. Blastulation was defined as the presence of a new blastocyst. Usable blastulation was defined as the presence of a new good or excellent quality, expanded, hatching, or hatched blastocysts. RESULTS: The mean blastulation rate between days 5 and 6 of extended embryo culture was 30.9%. The mean percentage of embryos developing into usable blastocyst-stage embryos was 19.8%. The factors associated with blastulation on day 6 included the total number of embryos and the number of pre-blastocysts on day 5, as well as the use of ICSI. Age, the number of total embryos, those remained in culture and pre-blastocysts, as well as the blastulation rate on day 5 were associated with usable blastulation. CONCLUSION: It is important to know the usable blastocyst development rate between culture days 5 and 6 in order to adequately counsel patients debating whether to proceed with fresh ET on day 5 or forego ET with the expectation that embryos will be biopsied for PGT and/or cryopreserved on culture day 6. Our findings provide evidence to help guide patients in this difficult decision.

Asymmetry of medullary veins on multiphase CT-angiography in patients with acute ischemic stroke.

BACKGROUND: It was previously demonstrated that decreased cortical venous drainage is a predictive factor of poor clinical outcome in patients with an acute ischemic stroke. The aim of this investigation is to test the hypothesis that the decline in blood flow in medullary veins (MV) on CT angiogram (CTA) of patients with acute ischemic stroke (AIS) can also be predictive of clinical outcome. METHODS: We retrospectively reviewed a database of patients with AIS who were evaluated by multiphase CTA and enrolled individuals with AIS and evidence of occlusion of the intracranial internal carotid artery, the M1 or M2 segment of the middle cerebral artery, or combination of two occlusions. To characterize asymmetry of MV we used similar principle that was previously established for MV on SWI MR-images; asymmetry was defined was presence of 5 or more contrast opacified MV in one hemisphere as compared to the contralateral side. Clinical outcomes were evaluated by mRS in 90 days. The Fisher Exact test was used to examine the significance of the MV asymmetry. Odds ratio and interrater variability were calculated. RESULTS: 66 patients with AIS were included. The presence of asymmetry in MV was associated with the higher frequency of poor clinical outcomes (84.6% vs 50.9%); the OR was 5.3. Interrater agreement in assessment on MV was moderate in our study (κ=0.55). CONCLUSION: This study shows that (a) medullary veins can be reliably assessed on multiphase CTA, (b) in patients with AIS, asymmetric appearance of MV is associated with poor clinical outcome.

Senescence in immunity against helminth parasites predicts adult mortality in a wild mammal.

Our understanding of the deterioration in immune function in old age-immunosenescence-derives principally from studies of modern human populations and laboratory animals. The generality and significance of this process for systems experiencing complex, natural infections and environmental challenges are unknown. Here, we show that late-life declines in an important immune marker of resistance to helminth parasites in wild Soay sheep predict overwinter mortality. We found senescence in circulating antibody levels against a highly prevalent nematode worm, which was associated with reduced adult survival probability, independent of changes in body weight. These findings establish a role for immunosenescence in the ecology and evolution of natural populations.

Standard terminology for reproductive tissue and cell products for use in ART.

Medical products of human origin (MPHO) distributed for use in assisted reproduction are currently labelled and identified using national or local systems. Products may be distributed internationally with potentially confusing identification labelling due to inconsistent terminology and definitions. In other fields of MPHO activity terminology has previously been standardized through professional collaboration as a precursor to adoption of a global standard for identification, coding and labelling. The International Council for Commonality in Blood Bank Automation (ICCBBA), an international nongovernmental organization in official relations with the World Health Organization, brought together representatives from professional societies to develop a terminology using a well-established methodology. The terminology was reviewed by professional associations and released for public comment. Further refinements were made following the comment period. Representatives of the American Society for Reproductive Medicine (ASRM), ESHRE, the Reproductive Tissue Council of the American Association of Tissue Banks (AATB) and ICCBBA met by international conference call and interacted by email. The terminology was developed using a standard model previously used across many areas of MPHO. A terminology comprising six classes, and six attribute groups has been developed. The terminology design is such that additional classes, attribute groups and attribute values can be added to meet the developing needs of the ART community. The level of detail incorporated into the terminology is based on the consensus view of the experts. The objective has been to provide sufficient detail to satisfy clinical need in product identification but there is the possibility that the level of detail may need to be adjusted in the future. The terminology is designed in a way that can readily accommodate such adjustments. Adoption of a standard terminology provides the basis for standardization of identification, coding and labelling and the use of internationally standardized barcoding to improve the accuracy and efficiency of information transfer and to reduce the risks of harm due to manual transcriptions errors.

Phthalate exposure and semen quality in fertile US men.

Several experimental and observational studies have demonstrated the antiandrogenicity of several phthalates. However, there is limited evidence of an association between phthalate exposure in adult life and semen quality. The aim of this study was to examine phthalate exposure during adulthood in relation to semen quality in fertile US men. This multi-center cross-sectional study included 420 partners of pregnant women who attended a prenatal clinic in one of five US cities during 1999-2001. Nine phthalate metabolites [mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP)], as well as mono-n-butyl phthalate (MBP) and mono-isobutyl phthalate (MiBP), mono (three carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP), and monoethyl phthalate (MEP)] were measured in urine collected at the same time as the semen sample. We regressed natural log-transformed (ln) sperm concentration, ln(total sperm count), ln(total motile sperm count), percent motile spermatozoa, and percent spermatozoa with normal morphology on each of the nine natural log-transformed metabolite concentrations and on the molar-weighted sum of DEHP metabolites in separate models. We fit unadjusted models and models that adjusted for confounders determined a priori. In unadjusted models, ln(MiBP) was significantly and positively associated with motility and ln(MBzP) significantly negatively associated with ln(total sperm count). In adjusted linear models, urinary metabolite concentrations of DEHP, DBP, DEP, and DOP were not associated with any semen parameter. We found an inverse association between ln(MBzP) concentrations and sperm motility (ß = -1.47, 95% CI: -2.61, -0.33), adjusted for ln(creatinine concentration), geographic location, age, race, smoking status, stress, recent fever, time from sample collection and time to complete analysis. Several sensitivity analyses confirmed the robustness of these associations. This study and the available literature suggest that impacts of adult exposure to phthalates at environmental levels on classical sperm parameters are likely to be small.

Host Preference of Megacopta cribraria (Hemiptera: Plataspidae) on Selected Edible Beans and Soybean.

Megacopta cribraria (F.) (Hemiptera: Plataspidae) is an Old World pest of legumes in Asia. Since its 2009 discovery in Georgia, it has become an economic pest of soybeans in the southeastern United States. The objective of this study was to determine the host preference of M. cribraria on edible legumes that might incur economic damage from injury of this pest. From 2012 to 2013 choice, no-choice, and field trials were conducted to evaluate the host suitability of several beans of commercial interest including pinto bean, lima bean, winter pea, and black-eyed pea. Choice and no-choice studies were conducted under greenhouse conditions. Plants in greenhouse trials were infested with adults and egg masses collected from kudzu and soybean and monitored for ∼2 wk. Field trials were allowed to be infested by naturally occurring M. cribraria populations. Sweep and whole plant counts of adults, egg masses, and nymphs were used to quantify field infestations. The legume crops found to be suitable developmental hosts are soybean, edamame, and pigeon pea. Low levels of development were seen on fava bean and none on the remaining entries.

Efficacy of Silk Channel Injections with Insecticides for Management of Lepidoptera Pests of Sweet Corn.

The primary Lepidoptera pests of sweet corn (Zea mays L. convar. saccharata) in Georgia are the corn earworm, Helicoverpa zea (Boddie), and the fall armyworm, Spodoptera frugiperda (J. E. Smith). Management of these pests typically requires multiple insecticide applications from first silking until harvest, with commercial growers frequently spraying daily. This level of insecticide use presents problems for small growers, particularly for "pick-your-own" operations. Injection of oil into the corn ear silk channel 5-8 days after silking initiation has been used to suppress damage by these insects. Initial work with this technique in Georgia provided poor results. Subsequently, a series of experiments was conducted to evaluate the efficacy of silk channel injections as an application methodology for insecticides. A single application of synthetic insecticide, at greatly reduced per acre rates compared with common foliar applications, provided excellent control of Lepidoptera insects attacking the ear tip and suppressed damage by sap beetles (Nitidulidae). While this methodology is labor-intensive, it requires a single application of insecticide at reduced rates applied ∼2 wk prior to harvest, compared with potential daily applications at full rates up to the day of harvest with foliar insecticide applications. This methodology is not likely to eliminate the need for foliar applications because of other insect pests which do not enter through the silk channel or are not affected by the specific selective insecticide used in the silk channel injection, but would greatly reduce the number of applications required. This methodology may prove particularly useful for small acreage growers.

Characterization of ascaris from ecuador and zanzibar.

To shed light on the epidemiology of ascariasis in Ecuador and Zanzibar, 177 adult worms retrieved by chemo-expulsion from either people or pigs were collected, measured and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the ribosomal internal transcribed spacer (ITS) region. Upon double digestion with RsaI and HaeIII, PCR-RFLP analysis revealed the presence of A. lumbricoides in people and A. suum in pigs in Ecuador. In contrast, while there are no pigs on Zanzibar, of the 56 worms obtained from people, one was genotyped as A. suum. No additional genetic variation was detected upon further PCR-RFLP analysis with several other restriction enzymes. Upon measurement, worm mass and length differed by location and by species, A. suum being lighter and longer. While there is no evidence to suggest zoonotic transmission in Ecuador, an enduring historical signature of previous zoonotic transmission remains on Zanzibar.

The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate.

Multi-state trials of Bt sweet corn varieties for control of the corn earworm (Lepidoptera: Noctuidae).

Field tests in 2010-2011 were performed in New York, Minnesota, Maryland, Ohio, and Georgia to compare Bt sweet corn lines expressing Cry1A.105 + Cry2Ab2 and Cry1Ab with their non-Bt isolines, with and without the use of foliar insecticides. The primary insect pest in all locations during the trial years was Heliocoverpa zea (Boddie), which is becoming the most serious insect pest of sweet corn in the United States. At harvest, the ears were measured for marketability according to fresh market and processing standards. For fresh market and processing, least squares regression showed significant effects of protein expression, state, and insecticide frequency. There was a significant effect of year for fresh market but not for processing. The model also showed significant effects of H. zea per ear by protein expression. Sweet corn containing two genes (Cry1A.105 + Cry2Ab2) and a single gene (Cry1Ab) provided high marketability, and both Bt varieties significantly outperformed the traditional non-Bt isolines in nearly all cases regardless of insecticide application frequency. For pest suppression of H. zea, plants expressing Bt proteins consistently performed better than non-Bt isoline plants, even those sprayed at conventional insecticide frequencies. Where comparisons in the same state were made between Cry1A.105 + Cry2Ab2 and Cry1Ab plants for fresh market, the product expressing Cry1A.105 + Cry2Ab2 provided better protection and resulted in less variability in control. Overall, these results indicate Cry1A.105 + Cry2Ab2 and Cry1Ab plants are suitable for fresh market and processing corn production across a diversity of growing regions and years. Our results demonstrate that Bt sweet corn has the potential to significantly reduce the use of conventional insecticides against lepidopteran pests and, in turn, reduce occupational and environmental risks that arise from intensive insecticide use.

Semen parameters in fertile US men: the Study for Future Families.

Establishing reference norms for semen parameters in fertile men is important for accurate assessment, counselling and treatment of men with male factor infertility. Identifying temporal or geographic variability in semen quality also requires accurate measurement of semen parameters in well-characterized, defined populations of men. The Study for Future Families (SFF) recruited men who were partners of pregnant women attending prenatal clinics in Los Angeles CA, Minneapolis MN, Columbia MO, New York City NY and Iowa City IA. Semen samples were collected on site from 763 men (73% White, 15% Hispanic/Latino, 7% Black and 5% Asian or other ethnic group) using strict quality control and well-defined protocols. Semen volume (by weight), sperm concentration (hemacytometer) and sperm motility were measured at each centre. Sperm morphology (both WHO, 1999 strict and WHO, 1987) was determined at a central laboratory. Mean abstinence was 3.2 days. Mean (median; 5th-95th percentile) values were: semen volume, 3.9 (3.7; 1.5-6.8) mL; sperm concentration, 60 (67; 12-192) × 10(6) /mL; total sperm count 209 (240; 32-763) × 10(6) ; % motile, 51 (52; 28-67) %; and total motile sperm count, 104 (128; 14-395) × 10(6) respectively. Values for sperm morphology were 11 (10; 3-20) % and 57 (59; 38-72) % normal forms for WHO (1999) (strict) and WHO (1987) criteria respectively. Black men had significantly lower semen volume, sperm concentration and total motile sperm counts than White and Hispanic/Latino men. Semen parameters were marginally higher in men who achieved pregnancy more quickly but differences were small and not statistically significant. The SFF provides robust estimates of semen parameters in fertile men living in five different geographic locations in the US. Fertile men display wide variation in all of the semen parameters traditionally used to assess fertility potential.

p53 is activated in response to disruption of the pre-mRNA splicing machinery.

In this study, we show that interfering with the splicing machinery results in activation of the tumour-suppressor p53. The spliceosome was targeted by small interfering RNA-mediated knockdown of proteins associated with different small nuclear ribonucleoprotein complexes and by using the small-molecule splicing modulator TG003. These interventions cause: the accumulation of p53, an increase in p53 transcriptional activity and can result in p53-dependent G(1) cell cycle arrest. Mdm2 and MdmX are two key repressors of p53. We show that a decrease in MdmX protein level contributes to p53 activation in response to targeting the spliceosome. Interfering with the spliceosome also causes an increase in the rate of degradation of Mdm2. Alterations in splicing are linked with tumour development. There are frequently global changes in splicing in cancer. Our study suggests that p53 activation could participate in protection against potential tumour-promoting defects in the spliceosome. A number of known p53-activating agents affect the splicing machinery and this could contribute to their ability to upregulate p53. Preclinical studies indicate that tumours can be more sensitive than normal cells to small-molecule spliceosome inhibitors. Activation of p53 could influence the selective anti-tumour activity of this therapeutic approach.

Lack of cortico-limbic coupling in bipolar disorder and schizophrenia during emotion regulation.

Bipolar disorder (BD) and schizophrenia (Sz) share dysfunction in prefrontal inhibitory brain systems, yet exhibit distinct forms of affective disturbance. We aimed to distinguish these disorders on the basis of differential activation in cortico-limbic pathways during voluntary emotion regulation. Patients with DSM-IV diagnosed Sz (12) or BD-I (13) and 15 healthy control (HC) participants performed a well-established emotion regulation task while undergoing functional magnetic resonance imaging. The task required participants to voluntarily upregulate or downregulate their subjective affect while viewing emotionally negative images or maintain their affective response as a comparison condition. In BD, abnormal overactivity (hyperactivation) occurred in the right ventrolateral prefrontal cortex (VLPFC) during up- and downregulation of negative affect, relative to HC. Among Sz, prefrontal hypoactivation of the right VLPFC occurred during downregulation (opposite to BD), whereas upregulation elicited hyperactivity in the right VLPFC similar to BD. Amygdala activity was significantly related to subjective negative affect in HC and BD, but not Sz. Furthermore, amygdala activity was inversely coupled with the activity in the left PFC during downregulation in HC (r=-0.76), while such coupling did not occur in BD or Sz. These preliminary results indicate that differential cortico-limbic activation can distinguish the clinical groups in line with affective disturbance: BD is characterized by ineffective cortical control over limbic regions during emotion regulation, while Sz is characterized by an apparent failure to engage cortical (hypofrontality) and limbic regions during downregulation.

Cognitive regulation of emotion in bipolar I disorder and unaffected biological relatives.

OBJECTIVE: We examined the use of particular cognitive strategies for regulating negative emotion in relation to mood and temperament in BD-I, unaffected relatives of bipolar patients (UR), and healthy controls (HC). METHOD: Participants were 105 patients with BD-I, 124 UR, and 63 HC; all participants completed the Cognitive Emotion Regulation Questionnaire (CERQ), the Depression Anxiety Stress Scales (DASS), and the Hypomanic Personality Scale (HPS). RESULTS: The BD-I group reported more frequent use of rumination, catastrophizing and self-blame, and less frequent use of putting into perspective, in response to negative life events, relative to the UR and HC groups. In BD-I, more frequent use of rumination was associated with increased DASS and HPS scores. By contrast, within the UR group, more frequent use of catastrophizing and self-blame were associated with increased DASS and HPS scores. In all participants, less frequent use of adaptive cognitive reframing strategies (e.g. putting into perspective) were associated with increased DASS scores. CONCLUSION: Both BD-I and UR groups reported more frequent use of maladaptive regulatory strategies previously associated with depression. Emotion regulation strategies of catastrophizing, self-blame, and cognitive reframing techniques may be associated with vulnerability for mood disorders, with the latter active within the general population regardless of biological vulnerability to disorder.

Associations between urinary metabolites of di(2-ethylhexyl) phthalate and reproductive hormones in fertile men.

Widely used man-made chemicals, including phthalates, can induce hormonal alterations through a variety of cellular and molecular mechanisms. A number of rodent and observational studies have consistently demonstrated the anti-androgenic effect of several phthalates. However, there are only limited data on the relationship between exposure to these chemicals and reproductive hormone levels in men. All men (n=425) were partners of pregnant women who participated in the Study for Future Families in five US cities and provided urine and serum samples on the same day. Eleven phthalate metabolites were measured in urine and serum samples were analysed for reproductive hormones, including follicle-stimulating hormone, luteinizing hormone, testosterone, inhibin B and oestradiol and sex hormone-binding globulin (SHBG). Pearson correlations and parametric tests were used for unadjusted analyses, and multiple linear regression analysis was performed controlling for appropriate covariates. We observed weak or no associations with urinary phthalates other than di(2-ethylhexyl) phthalate (DEHP). All measures of testosterone [total, calculated free testosterone and the free androgen index (FAI)] were inversely correlated with the urinary concentrations of four DEHP metabolites. After adjustment by appropriate covariates, there was no longer an association between urinary DEHP metabolite concentrations and total testosterone levels; however, FAI was significantly associated with the urinary concentrations of several DEHP metabolites. SHBG was positively related to the urinary concentrations of mono(2-ethylhexyl) phthalate, but not with other DEHP metabolites, an association that was attenuated after adjustment. Our results suggest that DEHP exposure of fertile men is associated with minor alterations of markers of free testosterone.

Achievement test performance in children conceived by IVF.

BACKGROUND: Long-term follow-up studies of children conceived by IVF are limited. We examine academic performance on standardized tests [Iowa Tests of Basic Skills/Educational Development (ITBS/ITED)] of children conceived by IVF. METHODS: Parents of children 8-17 years of age at the onset of the study (March 2008) who were conceived by IVF at the University of Iowa Hospitals and Clinics and living in the state of Iowa were contacted by mail. Parents completed questionnaires on their child's health and education and parental education. ITBS/ITED scores from school grades 3-12 were obtained on IVF children and a group of anonymous children matched by grade, year, gender and school district. Scores were analyzed using linear mixed models. RESULTS: Four hundred and ninety-seven couples were contacted. Two hundred and ninety-five couples (463 children) agreed to participate (59.4% of parents), with ITBS/ITED scores available on 423 children (91.4% of participants). IVF children scored higher than the national mean (P < 0.0001) across all grades and subtests and higher than their matched peers for grades 3-11. A trend toward lower test scores in multiple gestations was present (but not significant). Factors found to affect test scores included parental level of education, maternal age, divorce and child's BMI. Cryopreservation, length of embryo culture and method of insemination did not affect scores. CONCLUSIONS: IVF children scored higher on standardized tests than their matched peers, suggesting that IVF does not have a negative effect on cognitive development. However, long-term follow-up of IVF children is still limited. Further research should be performed on the effect of multiple gestation on academic performance.