A case of anterior fibroneural stalk, cervicothoracic junction anomaly, enteric duplication cyst, and diaphragmatic hernia: validation of a recently reported notochordal development disorder with pre- and postnatal multimodality imaging.

The syndrome of anterior fibroneural stalk, vertebral anomaly, enteric duplication cyst, and diaphragmatic hernia is a manifestation of abnormal notochordal development due to persistence of the neurenteric canal beyond early fetal gestational age. Our description of the third such published case to date supports this novel tetralogy and further illustrates the role of both pre- and postnatal imaging in achieving the diagnosis.

Routine transabdominal cervical length screening in mid-pregnancy for the prevention of preterm birth: Is it good enough to use as a screening test?

BACKGROUND: Preterm birth (PTB) is a major pregnancy complication. There is evidence that a short cervical length in mid-pregnancy may predict women at increased risk of PTB. AIMS: To evaluate the utility of population-based, transabdominal cervical length (TACL) measurement screening in mid-pregnancy for PTB prediction in women. MATERIALS AND METHODS: A transabdominal approach was initially performed, with a transvaginal (TVCL) approach offered when the TACL was <35 mm, could not be accurately measured, or the pregnancy had risk factors for PTB. TACL was compared to the directly related TVCL, when both were performed at the same assessment. Women with risk factors of PTB were included when they had both TACL and TVCL measurements performed at the same visit. RESULTS: Data were provided for 9355 singleton pregnancies from 13 participating imaging centres. A transabdominal approach was used in 9006 (96.3%), including 682 (7.3%) TVCL combined with TACL. There were 349 (3.7%) women who had TVCL only. The median TACL was longer (40 mm) than the TVCL (38 mm). In 682 paired TACL and TVCL measurements, TACL <35 mm correctly identified 96.2% of pregnancies with TVCL <25 mm, compared with 65.4% of cases when using a TACL <30 mm. A TVCL <25 mm occurred in 59 (0.6%) women. A TACL <35 mm was associated with birth <37 weeks of gestation in 12.1% of women and birth <32 weeks of gestation in 3.9%. CONCLUSIONS: Universal TACL is a feasible option for population screening of cervical length in a low-risk population, progressing to TVCL if the TACL is <35 mm or the cervix cannot be transabdominally accurately measured.

Willingness to pay for expanded non-invasive prenatal screening - An online discrete choice experiment from the perspective of women living in Western Australia.

INTRODUCTION: Ongoing advances in genetic technology may soon provide prenatal screening for multiple genetic conditions. AIMS: The aims were to investigate what prenatal screening test characteristics women prioritise and their willingness to pay for these tests. METHODS: We designed an online survey incorporating a series of discrete choice scenarios. Dimensions and levels were selected based on existing prenatal tests and a hypothetical prenatal test that could non-invasively detect multiple genetic disorders in pregnancy. Participants were recruited from social media platforms. Data were analysed using conditional logistic regression and latent class analysis (LCA). RESULTS: A total of 219 women completed the survey. Women with higher incomes and those with a tertiary education were willing to pay more than other groups. The maximum willingness to pay was AUD1870 (95% confidence interval: 1630, 2112) for a hypothetical non-invasive test to detect multiple genetic conditions in early pregnancy. An LCA demonstrated considerable heterogeneity in preferences, differing in both overall preference for testing and test characteristics considered most attractive. Among the participants, decision factors cited by 14.5% of participants were the risk of pregnancy loss, making them less likely to undergo testing; for 32.1% participants, accuracy was a major factor, and they were very likely to have testing; for 12.9%, test availability early in pregnancy was a decision factor. CONCLUSIONS: If a non-invasive test that could detect the greatest number of genetic disorders in pregnancy was available, the priorities were test accuracy, risk of pregnancy loss and a test available early in pregnancy.

Balloon catheters versus vaginal prostaglandins for labour induction (CPI Collaborative): an individual participant data meta-analysis of randomised controlled trials.

BACKGROUND: Induction of labour is one of the most common obstetric interventions globally. Balloon catheters and vaginal prostaglandins are widely used to ripen the cervix in labour induction. We aimed to compare the effectiveness and safety profiles of these two induction methods. METHODS: We did an individual participant data meta-analysis comparing balloon catheters and vaginal prostaglandins for cervical ripening before labour induction. We systematically identified published and unpublished randomised controlled trials that completed data collection between March 19, 2019, and May 1, 2021, by searching the Cochrane Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and PubMed. Further trials done before March 19, 2019, were identified through a recent Cochrane review. Data relating to the combined use of the two methods were not included, only data from women with a viable, singleton pregnancy were analysed, and no exclusion was made based on parity or membrane status. We contacted authors of individuals trials and participant-level data were harmonised and recoded according to predefined definitions of variables. Risk of bias was assessed with the ROB2 tool. The primary outcomes were caesarean delivery, indication for caesarean delivery, a composite adverse perinatal outcome, and a composite adverse maternal outcome. We followed the intention-to-treat principle for the main analysis. The primary meta-analysis used two-stage random-effects models and the sensitivity analysis used one-stage mixed models. All models were adjusted for maternal age and parity. This meta-analysis is registered with PROSPERO (CRD42020179924). FINDINGS: Individual participant data were available from 12 studies with a total of 5460 participants. Balloon catheters, compared with vaginal prostaglandins, did not lead to a significantly different rate of caesarean delivery (12 trials, 5414 women; crude incidence 27·0%; adjusted OR [aOR] 1·09, 95% CI 0·95-1·24; I2=0%), caesarean delivery for failure to progress (11 trials, 4601 women; aOR 1·20, 95% CI 0·91-1·58; I2=39%), or caesarean delivery for fetal distress (10 trials, 4441 women; aOR 0·86, 95% CI 0·71-1·04; I2=0%). The composite adverse perinatal outcome was lower in women who were allocated to balloon catheters than in those allocated to vaginal prostaglandins (ten trials, 4452 neonates, crude incidence 13·6%; aOR 0·80, 95% CI 0·70-0·92; I2=0%). There was no significant difference in the composite adverse maternal outcome (ten trials, 4326 women, crude incidence 22·7%; aOR 1·02, 95% CI 0·89-1·18; I2=0%). INTERPRETATION: In induction of labour, balloon catheters and vaginal prostaglandins have comparable caesarean delivery rates and maternal safety profiles, but balloon catheters lead to fewer adverse perinatal events. FUNDING: Australian National Health and Medical Research Council and Monash Health Emerging Researcher Fellowship.

Double-vs single-balloon catheter for induction of labor: Systematic review and individual participant data meta-analysis.

INTRODUCTION: Evidence comparing double-balloon vs single-balloon catheter for induction of labor is divided. We aim to compare the efficacy and safety of double-vs single-balloon catheters using individual participant data. MATERIAL AND METHODS: A search of Ovid MEDLINE, Embase, Ovid Emcare, CINAHL Plus, Scopus, and clinicaltrials.gov was conducted for randomized controlled trials published from March 2019 until April 13, 2021. Earlier trials were identified from the Cochrane Review on Mechanical Methods for Induction of Labour. Randomized controlled trials that compared double-balloon with single-balloon catheters for induction of labor in singleton gestations were eligible. Participant-level data were sought from trial investigators and an individual participant data meta-analysis was performed. The primary outcomes were rates of vaginal birth achieved, a composite measure of adverse maternal outcomes and a composite measure of adverse perinatal outcomes. We used a two-stage random-effects model. Data were analyzed from the intention-to-treat perspective. RESULTS: Of the eight eligible randomized controlled trials, three shared individual-level data with a total of 689 participants, 344 women in the double-balloon catheter group and 345 women in the single-balloon catheter group. The difference in the rate of vaginal birth between double-balloon catheter and single-balloon catheter was not statistically significant (relative risk [RR] 0.93, 95% confidence interval [CI] 0.86-1.00, p = 0.050; I2 0%; moderate-certainty evidence). Both perinatal outcomes (RR 0.81, 95% CI 0.54-1.21, p = 0.691; I2 0%; moderate-certainty evidence) and maternal composite outcomes (RR 0.65, 95% CI 0.15-2.87, p = 0.571; I2 55.46%; low-certainty evidence) were not significantly different between the two groups. CONCLUSIONS: Single-balloon catheter is at least comparable to double-balloon catheter in terms of vaginal birth rate and maternal and perinatal safety outcomes.

Western Australian women's expectations for expanded NIPT-An online survey regarding NIPT for single gene, recessive and chromosomal conditions.

Prenatal screening has evolved rapidly following the introduction of non-invasive prenatal testing (NIPT), with screening now available for an increasing number of conditions. We explored the attitudes and expectations of women within the context of using NIPT to detect multiple different single gene and chromosome conditions during pregnancy. An online survey was used to assess these issues with a sample of 219 women from Western Australia. In our study, the majority of women (96%) support of the concept of expanded NIPT for single gene and chromosome conditions provided the test involves no risk to the pregnancy and can provide the parents with relevant medical information about the fetus at any stage of pregnancy. 80% believed that expanded NIPT for single gene and chromosome conditions should be available at any stage during pregnancy and 68% of women indicated that test cost would be a factor in determining their participation in testing. Under half (43%) of the women favored an option to terminate a pregnancy at any stage if the fetus had a medical condition that would interfere with day to day functioning. The majority (78%) of women believed that testing for multiple genetic conditions would provide reassurance and lead to the delivery of a healthy child.

Mifepristone priming and subsequent misoprostol for second trimester medical abortion in women with previous caesarean delivery.

AIMS: To assess clinical outcomes and complications in women with ≥1 prior caesarean delivery (CS) during mid-pregnancy medical abortion with misoprostol following mifepristone priming. MATERIALS AND METHODS: Retrospective analysis of abortions at 13-28 weeks gestation using sequential mifepristone and misoprostol at a single centre from 1/2008-12/2018. Procedural outcomes were compared between cases with no prior CS, one prior and ≥2 prior CS. RESULTS: There were 1399 consecutive women who underwent a medical abortion, with 304 (21.7%) having ≥1 prior lower segment CS (241 one, 49 two, 12 three, one four) and one a prior classical CS. Median gestation was 19 weeks (interquartile range (IQR) 17-21) among nulliparas, multiparas with no prior CS and multiparas with prior CS, P = 0.505. Compared with nulliparas (median procedural duration 10.8 h, IQR 7.5-16.5; adjusted hazards ratio (aHR) = 1.20 95%CI 1.04-1.40, P = 0.015), multiparas with prior CS had a shorter procedural duration (9.5 h, IQR 6.5-13.5) while multiparas with no CS had the shortest duration (7.0 h, IQR 5.0-9.8; aHR = 2.28 95%CI 2.01-2.58, P < 0.001). Complications were more frequent with prior CS: estimated blood loss (medians: 100 cc no CS vs 150 cc ≥1 CS, P = 0.002), blood loss >1000 cc (3.6% no CS vs 7.2% ≥1 CS; odds ratio (OR) = 2.11 95%CI 1.23-3.62, P = 0.007) and placental retention (17.3% no CS vs 25.3% ≥1 CS; adjusted OR = 1.44 95%CI 1.05-1.99, P = 0.024). Uterine rupture occurred in 4/304 women with ≥1 prior CS (1.3%). CONCLUSIONS: Mifepristone-misoprostol abortion in women with prior CS is generally safe but associated with an increased risk of procedural complications. Lowering of the misoprostol dosage with prior CS may reduce uterine rupture, although this hypothesis requires ongoing research.

The Impact of Prenatal Diagnosis on Clinical Outcomes of Isolated Vascular Rings From a Statewide Paediatric Cardiology Tertiary Service.

BACKGROUND: Vascular rings, including right aortic arch with aberrant left subclavian artery (RAA-ALSCA), double aortic arch (DAA) and pulmonary artery sling (PAS), are congenital anomalies that may cause airway and oesophageal compression. As prenatal detection has improved, literature comparing clinical outcomes of antenatally versus postnatally diagnosed cases continues to emerge. The aim is to define a statewide tertiary paediatric institution's clinical profile and outcomes of prenatal versus postnatally diagnosed isolated vascular rings. METHOD: A retrospective single-centre review of isolated RAA-ALSCA, DAA and PAS between 1 January 1999 and 31 December 2020 was conducted. Clinical characteristics, surgical and follow-up information were collected. Antenatal and postnatally diagnosed groups were compared. RESULTS: Out of 123 cases diagnosed with isolated vascular rings, 98 (79.7%) cases had RAA-ALSCA, 21 (17.1%) with DAA, 4 (3.3%) with PAS. The antenatal detection rate was 73.6% in the past decade; 20.3% had a genetic disorder, of which 48% had 22q11.21 microdeletion. Of prenatally diagnosed cases, 31.3% developed symptoms, commonly stridor and dysphagia, at a median age of 2.0 months (IQR 0.0-3.0), compared to a median age of diagnosis for the postnatal cohort of 9 months (IQR 1.0-40.7). Postnatally diagnosed cases were more likely to present with symptoms, primarily respiratory distress, than prenatally diagnosed cases (p=0.006). Fifty-nine (59) cases (50% antenatally diagnosed) required vascular ring division; 6.8% had residual symptoms following surgery. DISCUSSION: Antenatal diagnosis has improved and leads to better parental awareness and more timely, appropriate intervention. Postnatally diagnosed patients were older, more likely to be symptomatic, underwent more investigations and were commenced on more medications for symptom management prior to diagnosis. One in five cases of isolated vascular ring anomalies carried a genetic diagnosis, which has important implications on prenatal counselling and genetic testing.

Perinatal outcomes of women with gestational breast cancer in Australia and New Zealand: A prospective population-based study.

OBJECTIVE: To determine the epidemiology, clinical management, and outcomes of women with gestational breast cancer (GBC). METHODS: A population-based prospective cohort study was conducted in Australia and New Zealand between 2013 and 2014 using the Australasian Maternity Outcomes Surveillance System (AMOSS). Women who gave birth with a primary diagnosis of breast cancer during pregnancy were included. Data were collected on demographic and pregnancy factors, GBC diagnosis, obstetric and cancer management, and perinatal outcomes. The main outcome measures were preterm birth, maternal complications, breastfeeding, and death. RESULTS: Forty women with GBC (incidence 7.5/100 000 women giving birth) gave birth to 40 live-born babies. Thirty-three (82.5%) women had breast symptoms at diagnosis. Of 27 women diagnosed before 30 weeks' gestation, 85% had breast surgery and 67% had systemic therapy during pregnancy. In contrast, all 13 women diagnosed from 30 weeks had their cancer management delayed until postdelivery. There were 17 preterm deliveries; 15 were planned. Postpartum complications included the following: hemorrhage (n = 4), laparotomy (n = 1), and thrombocytopenia (n = 1). There was one late maternal death. Eighteen (45.0%) women initiated breastfeeding, including 12 of 23 women who had antenatal breast surgery. There were no perinatal deaths or congenital malformations, but 42.5% of babies were preterm, and 32.5% were admitted for higher-level neonatal care. CONCLUSIONS: Gestational breast cancer diagnosed before 30 weeks' gestation was associated with surgical and systemic cancer care during pregnancy and planned preterm birth. In contrast, cancer treatment was deferred to postdelivery for women diagnosed from 30 weeks, reflecting the complexity of managing expectant mothers with GBC in multidisciplinary care settings.

Women's responses to prenatal genetic diagnosis and attitudes to termination of pregnancy after non-invasive prenatal testing: An online survey of Western Australian women.

BACKGROUND: Non-invasive prenatal testing (NIPT) using cell-free DNA (cfDNA) has expanded from detecting chromosome aneuploidy to testing for a variety of genetic conditions, including some select single gene disorders. As next generation sequencing/whole exome sequencing technology develops, it may be possible to expand NIPT of cfDNA to identify hundreds of single gene and chromosomal disorders in a fetus, thereby increasing the complexity of pretest counselling and parental decision-making. AIM: The aim of this study was to assess the views of women on the phenotypes of genetic conditions potentially detectable with expanded NIPT that they would consider severe enough to warrant pregnancy termination. MATERIALS AND METHODS: Using multiple clinical scenarios, we asked women via an online survey about the early detection of several well-described genetic phenotypes in pregnancy that in theory could be detected by expanded NIPT. RESULTS: Two hundred and nineteen women participated in this study. There was high support for early diagnosis and the option for termination of pregnancy in conditions perceived as severe (52-71%). Women expressed a preference for testing to be provided by general practitioners and assigned a high value to genetic counselling support (75-90%). In the case of a continuing pregnancy, women recognised the essential role of ongoing psychosocial counselling for family members and childhood early intervention programs. CONCLUSION: Women expressed clear preferences for termination of pregnancy for severe conditions and as early in gestation as feasible. Information and support from genetic counsellors are a highly valued resource in decision-making following a prenatal diagnosis of a fetal genetic abnormality.

The perceptions of obstetric care providers about cervical length screening for preterm birth prevention.

BACKGROUND: Routine cervical length (CL) measurement at the mid-pregnancy ultrasound is a central recommendation of the Western Australian Preterm Birth Prevention Initiative (Initiative). AIM: To evaluate the perceptions and changes in practice of Western Australian obstetric care providers regarding routine CL screening for preterm birth (PTB) prevention following the Initiative introduction. METHODS: Two self-administered questionnaires were completed by providers from a range of practices. The first was during site visits with the Initiative Outreach team in 2015-2016. The questionnaire was re-issued in 2021 via online dissemination. Participant demographic data and opinions on CL screening for PTB prevention were collected. RESULTS: Two hundred and fourteen providers participated in 2015-2016 and 109 in 2021. In both surveys, providers were more likely to discuss transvaginal CL screening with high-risk women (48.1%, 76.1%; P < 0.001) compared with low-risk (7.5%, 18.3%; P = 0.002) and the importance of CL screening (13.5%, 40.4%; P < 0.001), in 2015-2016 and 2021, respectively. Responses relating to CL screening, including what constitutes a short cervix on ultrasound were varied. A transabdominal CL <35 mm was classified as short by 46.2% and 37.6% and <25 mm on transvaginal ultrasound by 49.1% and 64.2%, in the respective surveys. Most providers ceased progesterone (68.6%, 75.2%) at >28 weeks gestation. CONCLUSIONS: Providers focused on women with overt PTB risk factors, rather than a universal CL screening approach. Although there was improvement between the surveys, the definition of what constitutes a short cervix on ultrasound and how to treat and monitor women with a short CL remained varied.

Severe congenital cutis laxa: Identification of novel homozygous LOX gene variants in two families.

We report three babies from two families with a severe lethal form of congenital cutis laxa. All three had redundant and doughy-textured skin and two siblings from one family had facial dysmorphism. Echocardiograms showed thickened and poorly contractile hearts, arterial dilatation and tortuosity. Post-mortem examination in two of the babies further revealed widespread ectasia and tortuosity of medium and large sized arteries, myocardial hypertrophy, rib and skull fractures. The presence of fractures initially suggested a diagnosis of osteogenesis imperfecta. Under light microscopy bony matrices were abnormal and arterial wall architecture was grossly abnormal showing fragmented elastic fibres. Molecular analysis of known cutis laxa genes did not yield any pathogenic defects. Whole exome sequencing of DNA following informed consent identified two separate homozygous variants in the LOX (Lysyl Oxidase) gene. LOX belongs to the 5-lysyl oxidase gene family involved in initiation of cross-linking of elastin and collagen. A mouse model of a different variant in this gene recapitulates the phenotype seen in the three babies. Our findings suggest that the LOX gene is a novel cause of severe congenital cutis laxa with arterial tortuosity, bone fragility and respiratory failure.

The perceptions of pregnant women about cervical length screening for preterm birth prevention.

BACKGROUND: The Western Australian Preterm Birth Prevention Initiative was officially launched in November 2014. It demonstrated an initial decrease in the preterm birth rate in Western Australia. One of the key points of this initiative is the routine ultrasound measurement of the cervical length in mid-pregnancy. AIM: The aim of this study was to evaluate the perceptions and attitudes of Western Australian women regarding transvaginal cervical length (TVCL) screening for preterm birth prevention. MATERIALS AND METHODS: Self-administered questionnaires were completed by pregnant women before and after their mid-trimester obstetric ultrasound. Maternal demographical and medical data were collected in addition to opinions of TVCL screening. RESULTS: A total of 598 women participated with the maternal age range representative of the Western Australian obstetric population. There was a high rate of acceptance of TVCL imaging, with 2% of the 149 women declining a transvaginal ultrasound (TVU) offered in this study, 1.5% refusing a TVU in the past and 5.7% reporting that they would have a concern in having a TVU in the future. Women stated that they either had declined TVCL in the past (11%) or would decline in the future (30.7%) as they wanted to discuss the procedure with their clinician first, had been advised not to have a TVU by their clinician (11% in the past and 47.7% in the future) or felt uncomfortable with the operator (22% at a previous TVU and 34.4% in the future). CONCLUSION: Pregnant women participating in this study had a high acceptance of TVCL screening for preterm birth prevention.

Rheumatic heart disease in pregnancy: Profile of women admitted to a Western Australian tertiary obstetric hospital.

This retrospective study assessed maternal and perinatal outcomes for women with rheumatic heart disease (RHD) admitted to the largest tertiary obstetric hospital in Western Australia from 2009 to 2016. Of 54 women identified, 75.9% were Indigenous, 59.3% lived in rural areas and 40.7% had severe RHD. Heart failure developed in 10% who gave birth. Indigenous women were younger, had higher gravidity (P = 0.0305), were more likely to receive secondary prophylaxis (P = 0.0041) and have sub-optimal antenatal clinic attendance (P = 0.0078). There were no maternal deaths and two perinatal deaths (4.0%), reflecting vigilance in the obstetric management of women with RHD in Western Australia.

In utero exposure to breast cancer treatment: a population-based perinatal outcome study.

Chemotherapy during a viable pregnancy may be associated with adverse perinatal outcomes. We conducted a prospective cohort study to examine the perinatal outcomes of babies born following in utero exposure to chemotherapy in Australia and New Zealand. Over 18 months we identified 24 births, of >400 g and/or >20-weeks' gestation, to women diagnosed with breast cancer in the first or second trimesters. Eighteen babies were exposed in utero to chemotherapy. Chemotherapy commenced at a median of 20 weeks gestation, for a mean duration of 10 weeks. Twelve exposed infants were born preterm with 11 by induced labour or pre-labour caesarean section. There were no perinatal deaths or congenital malformations. Our findings show that breast cancer diagnosed during mid-pregnancy is often treated with chemotherapy. Other than induced preterm births, there were no serious adverse perinatal outcomes.

A before and after study of the impact on obstetric and perinatal outcomes following the introduction of an educational package of fetal heart rate monitoring education coupled with umbilical artery lactate sampling in a low resource setting labor ward in South Africa.

INTRODUCTION: Rates of cesarean section (CS) are increasing and abnormal fetal heart rate tracing and concern about consequent acidosis remain one of the most common indications for primary CS. Umbilical artery (UA) lactate sampling provides clinicians with point of care feedback on CTG interpretation and intrapartum care and may result in altered future practice. MATERIALS AND METHODS: From 3rd March - 12th November 2014 we undertook a before and after study in Pretoria, South Africa, to determine the impact of introducing a clinical package of fetal heart rate monitoring education and prompt feedback with UA cord lactate sampling, using a hand-held meter, on maternal and perinatal outcomes. RESULTS: Nine hundred thirty-six consecutive samples were analyzed (pre n = 374 and post n = 562). There was no difference in mean lactate (4.6 mmol/L [95%CI 4.4-4.8] compared with 4.9 mmol/L [95%CI 4.7-5.1], p = 0.089). Suspected fetal compromise was reduced in the post-intervention period: 30·2% vs 22·1%, aOR 0·71, 95% CI 0·52-0·96, p = 0·027. Cesarean section rates were significantly reduced in the univariate analysis: pre- 40·3% vs post-intervention 31·6% (p = 0·007). This reduction remained significant when adjusted for previous cesarean section, primiparity, maternal HIV infection and preterm birth (aOR 0·72, 95%CI 0·54-0·98, p = 0·035). Neonatal outcomes did not differ between the two groups. CONCLUSION: The introduction of a clinical practice package of fetal heart rate monitoring education combined with routine UA cord lactate sampling has the potential to reduce the cesarean section rate without increasing adverse neonatal outcomes in a low-resource setting.

Differentiation of Islet Progenitors Regulated by Nicotinamide into Transcriptome-Verified ß Cells That Ameliorate Diabetes.

Developmental stage-specific differentiation of stem or progenitor cells into safe and functional cells is of fundamental importance in regenerative medicine, including ß-cell replacement. However, the differentiation of islet progenitor cells (IPCs) into insulin-secreting ß cells remains elusive. Here, we report that the multifunctional molecule nicotinamide (NIC) is a specific differentiation regulator of mouse IPCs. The differentiated cells regulated by NIC exhibited many characteristics of adult ß cells, including ameliorating preclinical diabetes and a highly comparable transcriptome profile. Gene set enrichment analysis showed that during differentiation, numerous IPC transcription factor genes, including Ngn3, Pax4, Fev, and Mycl1, were all down regulated. Pharmacological, biochemical, and gene knockdown analyses collectively demonstrated that NIC regulated the differentiation via inhibiting Sirt1 (silent information regulator transcript 1). Finally, NIC also regulates human IPC differentiation. Thus, our study advances islet developmental biology and impacts on translational research and regenerative therapies to diabetes and other diseases. Stem Cells 2017;35:1341-1354.

The impact of antenatal Bisphenol A exposure on male reproductive function at 20-22 years of age.

Bisphenol A (BPA) is a ubiquitous chemical suspected to possess oestrogenic hormonal activities. Male population studies suggest a negative impact on testicular function. As Sertoli cell proliferation occurs during fetal or early postnatal life, it is speculated that oestrogenic environmental exposures may influence mature testicular function. Among 705 Western Australian Pregnancy Cohort (Raine) Study men aged 20-22 years, 404 underwent testicular ultrasound examination (149 had maternal serum available), and/or 365 provided semen (136 had maternal serum) and/or 609 serum samples for sex steroids, gonadotrophins and inhibin B analysis (244 had maternal serum). Maternal serum collected at 18 and 34 weeks' gestation was pooled and assayed for concentrations of total BPA (free plus conjugated) as an estimate of antenatal exposure. Testicular volume was calculated by ultrasonography, and semen analysis performed. Serum LH, FSH and inhibin B were measured by immunoassay; testosterone, oestradiol, oestrone andBPA were measured by liquid chromatography-mass spectrometry. BPA levels were detectable in most (89%) maternal serum samples. After adjustment for maternal smoking, abstinence and varicocele, sperm concentration and motility were significantly correlated to maternal serum BPA (r = 0.18; P = 0.04 for both). No other associations of maternal serum BPA with testicular function were observed.

Congenital diaphragmatic hernia: Impact of contemporary management strategies on perinatal outcomes.

OBJECTIVE: This study aims to review temporal changes in perinatal management and 1-year survival outcomes of cases of congenital diaphragmatic hernia (CDH) from 1996 to 2015 in Western Australia (WA). METHOD: This research is a retrospective study of all cases of CDH in WA from 1996 to 2015 identified from five independent databases within the WA health network. Detailed information pertaining to pregnancy and survival outcomes were obtained from review of maternal and infant medical records. RESULTS: There were 215 cases of CDH with 164 diagnosed prenatally. Between 1996 and 2010, a decline in live birth rates for CDH-affected pregnancies was observed, reaching a nadir of 5.3 per 10 000 births before increasing to a peak of 9.73 per 10 000 births in 2011-2015. A corresponding decline was seen in the number of pregnancies terminated in the same period from 8.3 to 4.6 per 10 000 births (P = 0.14) and an increase in survival of live births from 38.9% to 81.3% (P = 0.01). CONCLUSION: The improved overall survival rate in infants with CDH over the last 20 years may have resulted in an increased tendency for women to continue their pregnancy with a concomitant decline in termination rates. Information from this study will help in the counselling of women following prenatal detection of CDH.