The negative association between pre-eclampsia and breast cancer risk may depend on the offspring's gender

If the negative association between pre-eclampsia and subsequent breast cancer risk differs by gender, this would strengthen the hypothesis that factors intrinsic to the particular pregnancy may explain the association. The study included 701 006 parous Norwegian women with follow-up for breast cancer through the Cancer Registry of Norway. Breast cancer risk was lower in women with pre-eclampsia/hypertension in their first pregnancy, compared to other women (relative risk, 0.86, 95% CI, 0.78–0.94), after adjustment for age at first birth, maternal birth year, length of gestation, marital status, and parity. The risk reduction was slightly greater if the woman delivered a son as opposed to a daughter (relative risks of 0.79 vs 0.94, P-value for interaction, 0.06), and if pre-eclampsia/hypertension was combined with pre-term delivery, these differences were more pronounced (relative risks, 0.62 vs 1.07, P-value for interaction 0.03). A subanalysis among 176 036 primiparous women showed a substantial risk reduction if the mother delivered a son (relative risk, 0.62, 95% CI, 0.47–0.82), but essentially null if she delivered a daughter (relative risk, 0.92, 95% CI, 0.72–1.18; P-value for interaction, 0.05). These results suggest that the effect of pre-eclampsia/hypertension may be attributed to factors associated with the particular pregnancy rather than an underlying biological trait of the mother. The stronger risk reduction related to having a son suggests a role for sex-dependent hormones in pregnancy

Uteroplacental bleeding disorders during pregnancy: do missing paternal characteristics influence risk?

BACKGROUND: Several studies have assessed the risks of uteroplacental bleeding disorders in relation to maternal characteristics. The association between uteroplacental bleeding disorders and paternal characteristics, however, has received considerably less attention. Data on paternal demographics, notably race and age, from birth certificate data are becoming increasingly incomplete in recent years. This pattern of increasingly underreporting of paternal demographic data led us to speculate that pregnancies for which paternal characteristics are partially or completely missing may be associated with increased risk for uteroplacental bleeding disorders. The objective of this study is to examine the association between placenta previa and placental abruption and missing paternal age and race. METHODS: A retrospective cohort study using U.S. linked birth/infant death data from 1995 through 2001 (n = 26,336,549) was performed. Risks of placenta previa and placental abruption among: (i) pregnancies with complete paternal age and race data; (ii) paternal age only missing; (iii) paternal race only missing; and (iv) both paternal age and race missing, were evaluated. Relative risk (RR) with 95% confidence interval (CI) for placenta previa and placental abruption by missing paternal characteristics were derived after adjusting for confounders. RESULTS: Adjusted RR for placental abruption were 1.30 (95% CI 1.24, 1.37), 1.00 (95% CI 0.95, 1.05), and 1.08 (95% CI 1.06, 1.10) among pregnancies with "paternal age only", "paternal race only", and "both paternal age and race" missing, respectively. The increased risk of placental abruption among the "paternal age only missing" category is partly explained by increased risks among whites aged 20–29 years, and among blacks aged ≥30 years. However, no clear patterns in the associations between missing paternal characteristics and placenta previa were evident. CONCLUSION: Missing paternal characteristics are associated with increased risk of placental abruption, likely mediated through low socio-economic conditions

Risk estimates of recurrent congenital anomalies in the UK: a population-based register study

BACKGROUND: Recurrence risks for familial congenital anomalies in successive pregnancies are known, but this information for major structural anomalies is lacking. We estimated the absolute and relative risks of recurrent congenital anomaly in the second pregnancy for women with a history of a congenital anomaly in the first pregnancy; for all major anomaly groups and subtypes. METHODS: Population-based register data on 18,605 singleton pregnancies affected by major congenital anomaly occurring in 872,493 singleton stillbirths, live births and terminations of pregnancy for fetal anomaly were obtained from the Northern Congenital Abnormality Survey, North of England, UK, for 1985-2010. Absolute risks (ARs) and relative risks (RRs) for recurrent congenital anomaly (overall, from a similar group, from a dissimilar group) in the second pregnancy were estimated by history of congenital anomaly (overall, by group, by subtype) in the first pregnancy. RESULTS: The estimated prevalences of congenital anomaly in first and second pregnancies were 276 (95% CI 270-281) and 163 (95% CI 159-168) per 10,000 respectively. For women whose first pregnancy was affected by congenital anomaly, the AR of recurrent congenital anomaly in the second pregnancy was 408 (95% CI 365-456) per 10,000; 2.5 (95% CI 2.3-2.8, p<0.0001) times higher than for those with unaffected first pregnancies. For similar anomalies, the recurrence risk was considerably elevated (RR=23.8, 95% CI 19.6-27.9, P<0.0001) while for dissimilar anomalies the increase was more modest (RR=1.4, 95% CI 1.2-1.6, P=0.001), although the ARs for both were 2%. CONCLUSIONS: Absolute recurrence risks varied between 1 in 20 and 1 in 30 for most major anomaly groups. At pre-conception and antenatal counselling, women whose first pregnancy was affected by a congenital anomaly and who are planning a further pregnancy may find it reassuring that despite high relative risks, the absolute recurrence risk is relatively low

Alpha-foetoprotein in umbilical cord in relation to severe pre-eclampsia, birth weight and future breast cancer risk

Women born after pre-eclamptic pregnancies have been reported to be at reduced risk of breast cancer as adults, because of reduced intrauterine oestrogen influence on breast tissue; high levels of α-foetoprotein (a glycoprotein with anti-oestrogenic properties), however, could also be important. In severe pre-eclampsia, placental function and foetal growth are reduced, and umbilical cord plasma levels of α-foetoprotein could reflect the underlying processes. Umbilical cord blood was collected in 12 804 consecutive deliveries. Among 307 pregnancies with clinical pre-eclampsia, 66 singleton pregnancies were identified as clinically severe, and 610 singleton pregnancies were selected as controls. Oestradiol and α-foetoprotein were measured from umbilical plasma, and birth weight was standardized as the ratio between the observed and expected birth weight, adjusted for differences in gestation length and offspring sex. Cord plasma levels of α-foetoprotein were significantly higher in severe pre-eclampsia than controls (P<0.01) after adjustment for gestational age and birth weight. For oestradiol, there was no difference in cord plasma levels between the severe pre-eclampsia group and controls, after adjustment for length of gestation and birth weight. These results suggest that an anti-oestrogenic effect associated with pre-eclampsia may be mediated through high levels of α-foetoprotein rather than low levels of oestradiol

Risk Factors for Congenital Cryptorchidism in a Prospective Birth Cohort Study

Background: Risk factors for congenital cryptorchidism were investigated in a prospective birth cohort study in Denmark and Finland 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 (questionnaire/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 geneti

The role of sexually transmitted infections in male circumcision effectiveness against HIV – insights from clinical trial simulation

BACKGROUND: A landmark randomised trial of male circumcision (MC) in Orange Farm, South Africa recently showed a large and significant reduction in risk of HIV infection, reporting MC effectiveness of 61% (95% CI: 34%–77%). Additionally, two further randomised trials of MC in Kisumu, Kenya and Rakai, Uganda were recently stopped early to report 53% and 48% effectiveness, respectively. Since MC may protect against both HIV and certain sexually transmitted infections (STI), which are themselves cofactors of HIV infection, an important question is the extent to which this estimated effectiveness against HIV is mediated by the protective effect of circumcision against STI. The answer lies in the trial data if the appropriate statistical analyses can be identified to estimate the separate efficacies against HIV and STI, which combine to determine overall effectiveness. OBJECTIVES AND METHODS: Focusing on the MC trial in Kisumu, we used a stochastic prevention trial simulator (1) to determine whether statistical analyses can validly estimate efficacy, (2) to determine whether MC efficacy against STI alone can produce large effectiveness against HIV and (3) to estimate the fraction of all HIV infections prevented that are attributable to efficacy against STI when both efficacies combine. RESULTS: Valid estimation of separate efficacies against HIV and STI as well as MC effectiveness is feasible with available STI and HIV trial data, under Kisumu trial conditions. Under our parameter assumptions, high overall effectiveness of MC against HIV was observed only with a high MC efficacy against HIV and was not possible on the basis of MC efficacy against STI alone. The fraction of all HIV infections prevented which were attributable to MC efficacy against STI was small, except when efficacy of MC specifically against HIV was very low. In the three MC trials which reported between 48% and 61% effectiveness (combining STI and HIV efficacies), the fraction of HIV infections prevented in circumcised males which were attributable to STI was unlikely to be more than 10% to 20%. CONCLUSION: Estimation of efficacy, attributable fraction and effectiveness leads to improved understanding of trial results, gives trial results greater external validity and is essential to determine the broader public health impact of circumcision to men and women

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT