Abstract-Hypertension during preeclampsia is associated with an increase in plasma levels of tumor necrosis factor (TNF)-␣, a cytokine known to contribute to endothelial dysfunction. Recently, our laboratory reported that a 2-fold increase in plasma TNF-␣ produces hypertension in pregnant rats. Endothelin is also elevated in preeclampsia and endothelin synthesis is enhanced by TNF-␣. The purpose of this study was to determine the role of endothlelin in mediating TNF-␣-induced hypertension in pregnant rats. To achieve this goal, TNF-␣ (50 ng/d for 5 days) was infused into control pregnant rats and pregnant rats treated with an endothelin receptor A antagonist, ABT 627 (5 mg/kg per day for 5 days). At day 19 of gestation, arterial pressure was measured and aorta, kidneys, and placentas were harvested. Infusion of TNF-␣ into pregnant rats increased plasma concentration of TNF-␣ (13.5Ϯ0.8 to 28.0Ϯ3.7 pg/mL) and arterial pressure (101Ϯ2 to 122Ϯ1 mm Hg). The increase in arterial pressure was associated with an increase in preproendothelin mRNA expression in placenta, aorta, and kidneys measured by real-time polymerase chain reaction (PCR). Pretreatment with the endothelin receptor A antagonist completely abolished the blood pressure response to TNF-␣ in pregnant rats (105Ϯ1 versus 97Ϯ2 mm Hg). In sharp contrast, the ET A receptor antagonist had no effect on arterial pressure in normal pregnant rats (97Ϯ2 versus 101Ϯ2 mm Hg). Moreover, chronic infusion of TNF-␣ had no significant effect on arterial pressure or renal preproendothelin levels in virgin rats. These results suggest an important role for endothelin in mediating TNF-␣-induced hypertension in pregnant rats.

Abstract-The purpose of this study was to determine the role of interleukin (IL) 6 in mediating the increase in arterial pressure (AP) in response to chronic reductions in uterine perfusion pressure (RUPP) in pregnant rats. AP was higher in RUPP rats (138Ϯ1 mm Hg) than in normal pregnant (NP) rats (104Ϯ1 mm Hg). Serum IL-6 levels in the RUPP rats were 104.5Ϯ28.6 pg/mL as compared with 36.6Ϯ7.4 pg/mL in NP rats. To determine the long-term effects of a 2-to 3-fold elevation in plasma IL-6 on renal function and AP in pregnant rats, we infused IL-6 for 5 days (2.5 ng/day) in NP rats starting at day 14 of gestation. Five days later, serum IL-6 levels were 55.5Ϯ6.5 pg/mL in the control NP rats and 157.0Ϯ36.1 pg/mL in the IL-6 -treated NP rats. AP was higher in the IL-6 -treated NP rats (115Ϯ3 mm Hg) as compared with NP controls (101Ϯ1 mm Hg) at day 19 of gestation. Renal plasma flow and GFR were lower in the IL-6 -treated NP rats than in the NP group. IL-6 increased plasma renin activity but did not affect endothelin in IL-6 -treated NP rats. In contrast to the NP rats, IL-6 had no effect on AP or renal hemodynamics in virgin rats. In summary, these data indicate that plasma IL-6 is elevated in response to chronic reductions in uterine perfusion in pregnant rats and that a comparable elevation in plasma IL-6 increases AP and reduces renal function in pregnant rats.

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Objective: Design, setting and participants: A population‐based study of 789 240 term singleton births in public and private hospitals in 2001–2004, using data from the National Perinatal Data Collection. Main outcome measures: Third‐ and fourth‐degree perineal injury, requirement for high level of neonatal resuscitation, Apgar score < 7 at 5 minutes, admission to neonatal intensive care unit or special care nursery, and perinatal death. Results: 31.4% of the term singleton births occurred in private hospitals. After adjusting for maternal age, Indigenous status, parity, smoking status, diabetes, hypertension, remoteness of usual residence, and method of birth, the rates of all adverse outcomes studied were higher for public hospital births. For women, the adjusted odds ratio (AOR) for third‐ or fourth‐degree perineal injury was 2.28 (95% CI, 2.16–2.40). For babies, the odds of a high level of resuscitation (AOR, 2.37; 95% CI, 2.17–2.59), low Apgar score (AOR, 1.75; 95% CI, 1.65–1.84), intensive care requirement (AOR, 1.48; 95% CI, 1.45–1.51) and perinatal death (AOR, 2.02; 95% CI, 1.78–2.29) were all higher in public hospitals. Conclusion: For women delivering a single baby at term in Australia, the prevalence of adverse perinatal outcomes is higher in public hospitals than in private hospitals.

Objective: To present updated national birthweight percentiles for gestational age by sex for singletons born in Australia.Design and setting: Cross-sectional population-based study of 2.53 million singleton live births of infants born in Australia between 1998 and 2007.Main outcome measures: Birthweight percentiles by gestational age and sex.Results: Between 1998 and 2007 women in Australia gave birth to 2,539,237 live singleton births. Of these, 2,537,627 had gestational age between 20 and 44 weeks and non-missing sex and birthweight. Birthweight percentiles are presented by sex and gestational age for a total of 2,528,641 births after excluding 8,986 births for having outlying birthweight. Since the publication of the previous Australian birthweight percentiles in 1999, median birthweight for term babies has increased between 0 and 25g for boys and between 5 and 45g for girls.Conclusions: There has been only a small increase in birthweight percentiles for babies of both sexes and most gestational ages since 1991-1994. These national percentiles will provide a current Australian reference for clinicians and researchers assessing size at birth.3

Fertility preservation in the cancer setting, known as oncofertility, is a field that requires cross-disciplinary interaction between physicians, basic scientists, clinical researchers, ethicists, lawyers, educators, and religious leaders. Funded by the National Institutes of Health, the Oncofertility Consortium (OC) was formed to be a scientifically grounded, transparent, and altruistic resource, both intellectual and monetary, for building this new field of practice capable of addressing the unique needs of young patients with cancer. The OC has expanded its attention to include other nonmalignant conditions that can threaten fertility, and the work of the OC now extends around the globe, involving partners who together have created a community of shared effort, resources, and practices. The OC creates materials that are translated, disseminated, and amended by all participants in the field, and local programs of excellence have developed worldwide to accelerate the pace and improve the quality of oncofertility research and practice. Here we review the global oncofertility programs and the capacity building activities that strengthen these research and clinical programs, ultimately improving patient care.

Estimates of the lifetime risk of tuberculosis have varied widely and may not be applicable in all current settings. The aim of this study was to measure the incidence of reactivation of latent tuberculosis in a cohort of 15,489 predominantly Southeast Asian refugees aged 12 yr and over who arrived in Sydney, Australia during the period 1984 to 1994 and who had a clear chest X-ray on arrival. Tuberculin skin test (TST) reaction size and the presence of a BCG scar were recorded at entry. Incident cases of tuberculosis, occurring before June 1998, were identified by record linkage analysis with confirmatory review of case notes. There were 122 cases of tuberculosis over an average 10.3 yr of follow-up (crude annual incidence, 76.2/100,000). There was a linear increase in risk with increasing TST reaction size above 10 mm. The risk, and the relation of risk to TST reaction size, were unrelated to BCG scar status. Among those whose initial TST reaction was >/= 15 mm, the annual incidence rate in the first 3 yr was 213 (95% CI, 150 to 300) per 100,000 person-years and in the subsequent 10 yr the rate averaged 122 (95% CI, 90 to 165) per 100,000 person-years. The observed rates are similar to those estimated in the general population of the United States in the 1950s and 1960s. Further data on the prognosis of tuberculosis and the effects of isoniazid preventive therapy in Southeast Asian migrants to Western countries are required to inform policy and practice for the prevention of tuberculosis in this population.

Objective To describe the epidemiology of rheumatic heart disease (RHD) in pregnancy in Australia and New Zealand (A&NZ). Design Prospective population‐based study. Setting Hospital‐based maternity units throughout A&NZ. Population Pregnant women with RHD with a birth outcome of ≥20 weeks of gestation between January 2013 and December 2014. Methods We identified eligible women using the Australasian Maternity Outcomes Surveillance System (AMOSS). De‐identified antenatal, perinatal and postnatal data were collected and analysed. Main outcome measures Prevalence of RHD in pregnancy. Perinatal morbidity and mortality. Results There were 311 pregnancies associated with women with RHD (4.3/10 000 women giving birth, 95% CI 3.9–4.8). In Australia, 78% were Aboriginal or Torres Strait Islander (60.4/10 000, 95% CI 50.7–70.0), while in New Zealand 90% were Māori or Pasifika (27.2/10 000, 95% CI 22.0–32.3). One woman (0.3%) died and one in ten was admitted to coronary or intensive care units postpartum. There were 314 births with seven stillbirths (22.3/1000 births) and two neonatal deaths (6.5/1000 births). Sixty‐six (21%) live‐born babies were preterm and one in three was admitted to neonatal intensive care or special care units. Conclusion Rheumatic heart disease in pregnancy persists in disadvantaged First Nations populations in A&NZ. It is associated with significant cardiac and perinatal morbidity. Preconception planning and counselling and RHD screening in at‐risk pregnant women are essential for good maternal and baby outcomes. Tweetable abstract Rheumatic heart disease in pregnancy persists in First Nations people in Australia and New Zealand and is associated with major cardiac and perinatal morbidity.