Performance of six birth-weight and estimated-fetal-weight standards for predicting adverse perinatal outcome: a 10-year nationwide population-based study.

OBJECTIVE: To evaluate three birth-weight (BW) standards (Australian population-based, Fenton and INTERGROWTH-21st ) and three estimated-fetal-weight (EFW) standards (Hadlock, INTERGROWTH-21st and WHO) for classifying small-for-gestational age (SGA) and large-for-gestational age (LGA) and predicting adverse perinatal outcomes in preterm and term babies. METHODS: This was a nationwide population-based study conducted on a total of 2.4 million singleton births that occurred from 24 + 0 to 40 + 6 weeks' gestation between 2004 and 2013 in Australia. The performance of the growth charts was evaluated according to SGA and LGA classification, and relative risk (RR) and diagnostic accuracy based on the areas under the receiver-operating-characteristics curves (AUCs) for stillbirth, neonatal death, perinatal death, composite morbidity and a composite of perinatal death and morbidity outcomes. The analysis was stratified according to gestational age at delivery (< 37 + 0 vs ≥ 37 + 0 weeks). RESULTS: Following exclusions, 2 392 782 singleton births were analyzed. There were significant differences in the SGA and LGA classification and risk of adverse outcomes between the six BW and EFW standards evaluated. For the term group, compared with the other standards, the INTERGROWTH-21st BW and EFW standards classified half the number of SGA (< 10th centile) babies (3-4% vs 7-11%) and twice the number of LGA (> 90th centile) babies (24-25% vs 8-15%), resulting in a smaller cohort of term SGA at higher risk of adverse outcome and a larger LGA cohort at lower risk of adverse outcome. For term SGA (< 3rd centile) babies, the RR of perinatal death using the two INTERGROWTH-21st standards was up to 1.5-fold higher than those of the other standards (including the WHO-EFW and Hadlock-EFW), while the INTERGROWTH-21st -EFW standard indicated a 12-26% reduced risk of perinatal death for LGA cases across centile thresholds. Conversely, for the preterm group, the WHO-EFW and Hadlock-EFW standards identified a higher SGA classification rate than did the other standards (18-19% vs 10-11%) and a 20-65% increased risk of perinatal death in term LGA babies. All BW and EFW charts had similarly poor performance in predicting adverse outcomes, including the composite outcome (AUC range, 0.49-0.62) for both preterm (AUC range, 0.58-0.62) and term (AUC range, 0.49-0.50) cases and across centiles. Furthermore, specific centile thresholds for identifying adverse outcomes varied markedly by chart between BW and EFW standards. CONCLUSIONS: This study addresses the recurrent problem of identifying fetuses at risk of morbidity and perinatal mortality associated with growth disorders and provides new insights into the applicability of international growth standards. Our findings of marked variation in classification and the similarly poor performance of prescriptive international standards and the other commonly used standards raise questions about whether the prescriptive international standards that were constructed for universal adoption are indeed applicable to a multiethnic population such as that of Australia. Thus, caution is needed when adopting universal standards for clinical and epidemiological use. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Parity: A key measure of confounding in data-linkage studies of outcomes after medically assisted reproduction.

Parity is a potential confounder of the association between medically assisted reproduction (MAR) and health outcomes. This concept paper describes a population-based record linkage study design for selecting MAR-unexposed women matched to the parity of MAR-exposed women, at the time of the first exposure to MAR. Women exposed to MAR were identified from claims for government subsidies for relevant procedures and prescription medicines, linked to perinatal records. Women unexposed to MAR were identified from linked perinatal and death records, matched to exposed women by age, rurality, age of first child (if any) and parity at the date of first MAR. The availability of a longitudinal, whole-of-population dataset ("population spine") based on enrolments in Australia's universal health insurance scheme was a critical design element. The example application examines cancer risk in women after exposure to MAR. Parity is a confounder in this setting because it is associated with MAR and hormone-sensitive cancers.

Are singleton pregnancies after assisted reproduction technology (ART) associated with a higher risk of placental anomalies compared with non-ART singleton pregnancies? A systematic review and meta-analysis.

BACKGROUND: Placental anomalies (placenta praevia, placental abruption, morbidly adherent placenta and cord insertion anomalies) are associated with maternal and fetal morbidity and mortality. It has been suggested these might be more prevalent in pregnancies after assisted reproduction technology (ART). OBJECTIVES: To determine whether ART singleton pregnancies are associated with an increased risk of placental anomalies compared with non-ART singleton pregnancies. SEARCH STRATEGY: MEDLINE, EMBASE, CENTRAL, Web of Science and Scopus (January 2018). SELECTION CRITERIA: Cohort studies reporting placental anomalies in ART and non-ART singleton pregnancies. DATA COLLECTION AND ANALYSIS: We report pooled odds ratios (OR) for the comparisons: (1) ART versus SC (spontaneously conceived), (2) ART versus non-ART (unspecified), (3) FET-ART (frozen-embryo transfer) versus SC, (4) ART versus non-ART (subfertile patients). Study quality was assessed using a modified Newcastle -Ottawa scale. MAIN RESULTS: 33 low/moderate quality studies evaluated 124 215 ART and 6 054 729 non-ART singleton pregnancies. Risk of placenta praevia, placental abruption and morbidly adherent placenta was higher in ART than SC pregnancies: odds ratio (OR) (OR 3.76, 95% CI 3.09-4.59); (OR 1.87, 95% CI 1.70-2.06) and (OR 2.27, 95% CI 1.79-2.87) respectively. Risk of placenta praevia and placental abruption was higher in ART than in non-ART (subfertile patients): (OR 2.51, 95% CI 2.12-2.98) and (OR 1.61, 95% CI 1.33-1.95) respectively. Results were similar when comparing ART with unspecified non-ART pregnancies. Risk of placenta praevia was higher, but not significantly so, in FET-ART than in SC pregnancies (OR 2.42, 95% CI 0.63-9.30). CONCLUSIONS: Singleton ART pregnancies are associated with an increased risk of placental anomalies compared with non-ART singleton pregnancies. TWEETABLE ABSTRACT: A review of over 6 million singleton pregnancies finds increased risk of placental anomalies after ART.

Social capital strategies to enhance hepatitis C treatment awareness and uptake among men in prison.

Prisoner populations are characterized by high rates of hepatitis C (HCV), up to thirty times that of the general population in Australia. Within Australian prisons, less than 1% of eligible inmates access treatment. Public health strategies informed by social capital could be important in addressing this inequality in access to HCV treatment. Twenty-eight male inmates participated in qualitative interviews across three correctional centres in New South Wales, Australia. All participants had recently tested as HCV RNA positive or were receiving HCV treatment. Analysis was conducted with participants including men with experiences of HCV treatment (n=10) (including those currently accessing treatment and those with a history of treatment) and those who were treatment naïve (n=18). Social capital was a resourceful commodity for inmates considering and undergoing treatment while in custody. Inmates were a valuable resource for information regarding HCV treatment, including personal accounts and reassurance (bonding social capital), while nurses a resource for the provision of information and care (linking social capital). Although linking social capital between inmates and nurses appeared influential in HCV treatment access, there remained opportunities for increasing linking social capital within the prison setting (such as nurse-led engagement within the prisons). Bonding and linking social capital can be valuable resources in promoting HCV treatment awareness, uptake and adherence. Peer-based programmes are likely to be influential in promoting HCV outcomes in the prison setting. Engagement in prisons, outside of the clinics, would enhance opportunities for linking social capital to influence HCV treatment outcomes.

International Committee for Monitoring Assisted Reproductive Technologies world report: Assisted Reproductive Technology 2008, 2009 and 2010.

STUDY QUESTION: What were utilization, outcomes and practices in assisted reproductive technology (ART) globally in 2008, 2009 and 2010? SUMMARY ANSWER: Global utilization and effectiveness remained relatively constant despite marked variations among countries, while the rate of single and frozen embryo transfers (FETs) increased with a concomitant slight reduction in multiple birth rates. WHAT IS KNOWN ALREADY: ART is widely practised in all regions of the world. Monitoring utilization, an approximation of availability and access, as well as effectiveness and safety is an important component of universal access to reproductive health. STUDY DESIGN, SIZE, DURATION: This is a retrospective, cross-sectional survey on utilization, effectiveness and safety of ART procedures performed globally from 2008 to 2010. PARTICIPANTS, SETTING, METHODS: Between 58 and 61 countries submitted data from a total of nearly 2500 ART clinics each year. Aggregate country data were processed and analyzed based on forms and methods developed by the International Committee for Monitoring Assisted Reproductive Technologies (ICMART). Results are presented at country, regional and global level. MAIN RESULTS AND THE ROLE OF CHANCE: For the years 2008, 2009 and 2010, >4 461 309 ART cycles were initiated, resulting in an estimated 1 144 858 babies born. The number of aspirations increased by 6.4% between 2008 and 2010, while FET cycles increased by 27.6%. Globally, ART utilization remained relatively constant at 436 cycles/million in 2008 and 474 cycles/million population in 2010, but with a wide country range of 8-4775 cycles/million population. ICSI remained constant at around 66% of non-donor aspiration cycles. The IVF/ICSI combined delivery rate (DR) per fresh aspiration was 19.8% in 2008; 19.7% in 2009 and 20.0% in 2010, with corresponding DRs for FET of 18.8, 19.7 and 20.7%. In fresh non-donor cycles, single embryo transfer increased from 25.7% in 2008 to 30.0% in 2010, while the average number of embryos transferred fell from 2.1 to 1.9, again with wide regional variation. The rates of twin deliveries following fresh non-donor transfers were, in 2008, 2009 and 2010, 21.8, 20.5 and 20.4%, respectively, with a corresponding triplet rate of 1.3, 1.0 and 1.1%. Fresh IVF and ICSI carried a perinatal mortality rate per 1000 births of 22.8 (2008), 19.2 (2009) and 21.0 (2010), compared with 15.1, 12.8 and 14.6/1000 births following FET in the same periods of observation. The proportion of women aged 40 years or older undergoing non-donor ART increased from 20.8 to 23.2% from 2008 to 2010. LIMITATIONS, REASON FOR CAUTION: The data presented are reliant on the quality and completeness of data submitted by individual countries. This report covers approximately two-thirds of the world ART activity. WIDER IMPLICATIONS OF FINDINGS: The ICMART World Reports provide the most comprehensive global statistical census and review of ART utilization, effectiveness, safety and quality. While ART treatment continues to increase globally, the wide disparities in access to treatment and embryo transfer practices warrant attention by clinicians and policy makers. STUDY FUNDING/COMPETING INTERESTS: The authors declare no conflict of interest and no specific support from any organizations in relation to this manuscript. ICMART acknowledges financial support from the following organizations: American Society for Reproductive Medicine; European Society for Human Reproduction and Embryology; Fertility Society of Australia; Japan Society for Reproductive Medicine; Japan Society of Fertilization and Implantation; Red Latinoamericana de Reproduccion Asistida; Society for Assisted Reproductive Technology; Government of Canada (Research grant), Ferring Pharmaceuticals (Grant unrelated to World Reports). TRIAL REGISTRATION: not applicable.

High burden of RSV hospitalization in very young children: a data linkage study.

Linked administrative population data were used to estimate the burden of childhood respiratory syncytial virus (RSV) hospitalization in an Australian cohort aged <5 years. RSV-coded hospitalizations data were extracted for all children aged <5 years born in New South Wales (NSW), Australia between 2001 and 2010. Incidence was calculated as the total number of new episodes of RSV hospitalization divided by the child-years at risk. Mean cost per episode of RSV hospitalization was estimated using public hospital cost weights. The cohort comprised of 870 314 children. The population-based incidence/1000 child-years of RSV hospitalization for children aged <5 years was 4·9 with a rate of 25·6 in children aged <3 months. The incidence of RSV hospitalization (per 1000 child-years) was 11·0 for Indigenous children, 81·5 for children with bronchopulmonary dysplasia (BPD), 10·2 for preterm children with gestational age (GA) 32-36 weeks, 27·0 for children with GA 28-31 weeks, 39·0 for children with GA <28 weeks and 6·7 for term children with low birthweight. RSV hospitalization was associated with an average annual cost of more than AUD 9 million in NSW. RSV was associated with a substantial burden of childhood hospitalization specifically in children aged <3 months and in Indigenous children and children born preterm or with BPD.

Hospital utilization, costs and mortality rates during the first 5 years of life: a population study of ART and non-ART singletons.

STUDY QUESTION: Do singletons conceived following assisted reproduction technologies (ARTs) have significantly different hospital utilization, and therefore costs, compared with non-ART children during the first 5 years of life? SUMMARY ANSWER: ART singletons have longer hospital birth-admissions and a small increased risk of re-admission during the first 5 years of life resulting in higher costs of hospital care. WHAT IS KNOWN ALREADY: ART singletons are at greater risk of adverse perinatal outcomes compared with non-ART singletons. Long-term physical and mental health outcomes of ART singletons are generally reassuring. There is a scarcity of information on health service utilization and the health economic impact of ART conceived children. STUDY DESIGN, SIZE, DURATION: A population cohort study using linked birth, hospital and death records. Perinatal outcomes, hospital utilization and costs, and mortality rates were compared for non-ART and ART singletons to 5 years. Adjustments were made for maternal age, parity, sex, birth year, socioeconomic status and funding source. Australian Diagnosis Related Groups cost-weights were used to derive costs. All costs are reported in 2009/2010 Australian dollars. PARTICIPANTS/MATERIALS, SETTING, METHODS: All babies born in Western Australia between 1994 and 2003 were included; 224 425 non-ART singletons and 2199 ART conceived singletons. Hospital admission and death records in Western Australia linked to 2008 were used. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, ART singletons had a significantly longer length of stay during the birth-admission (mean difference 1.8 days, P < 0.001) and a 20% increased risk of being admitted during the first 5 years of life. The average adjusted difference in hospital admission costs up to 5 years of age was $2490, with most of the additional cost occurring during the birth-admission ($1473). The independent residual cost associated with ART conception was $342 during the birth-admission and an additional $548 up to 5 years of age, indicating that being conceived as an ART child predicts not only higher birth-admission costs but excess costs to at least 5 years of age. LIMITATIONS, REASONS FOR CAUTION: This study could not investigate the impact of different ART practices and techniques on perinatal outcomes or hospital utilization, nor could it adjust for parental characteristics such as cause of infertility and treatment-seeking behaviour. This study related to ART treatment undertaken before 2003. WIDER IMPLICATIONS OF THE FINDINGS: Clinicians and patients should be aware of the risk of poorer perinatal outcomes and increased hospitalization of ART singletons compared with non-ART singletons. These differences are significant enough to affect health-care resource consumption, but are substantially and significantly less than those associated with ART multiple birth infants. Understanding the short- and long-term health services and economic impact of ART is important for setting the research agenda in ART, for informing economic evaluations of infertility and treatment strategies, and for providing an important input to clinical and administrative decision making. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was used to undertake this study and the authors report no conflicts of interest. A number of the authors receive Research Grants to their institutions from the Australian Government. G.M.C. receives grant support to her institution from the Australian Government, Australian Research Council (ARC) Linkage Grant No LP1002165; ARC Linkage Grant Partner Organisations are IVFAustralia, Melbourne IVF and Queensland Fertility Group. V.P.H. is employed as an Economics Research Associate on the same grant. TRIAL REGISTRATIONS NUMBER: NA.

Socioeconomic disparities in access to ART treatment and the differential impact of a policy that increased consumer costs.

STUDY QUESTION: What was the impact on access to assisted reproductive technology (ART) treatment by different socioeconomic status (SES) groups after the introduction of a policy that increased patient out-of-pocket costs? SUMMARY ANSWER: After the introduction of a policy that increased out-of-pocket costs in Australia, all SES groups experienced a similar percentage reduction in fresh ART cycles per 1000 women of reproductive age. Higher SES groups experienced a progressively greater reduction in absolute numbers of fresh ART cycles due to existing higher levels of utilization. WHAT IS KNOWN ALREADY: Australia has supportive public funding arrangements for ARTs. Policies that substantially increase out-of-pocket costs for ART treatment create financial barriers to access and an overall reduction in utilization. Data from the USA suggests that disparities exist in access to ART treatment based on ethnicity, education level and income. STUDY DESIGN, SIZE, DURATION: Time series analysis of utilization of ART, intrauterine insemination (IUI) and clomiphene citrate by women from varying SES groups before and after the introduction of a change in the level of public funding for ART. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women undertaking fertility treatment in Australia between 2007 and 2010. MAIN RESULTS AND THE ROLE OF CHANCE: Women from higher SES quintiles use more ART treatment than those in lower SES quintiles, which likely reflects a greater ability to pay for treatment and a greater need for ART treatment as indicated by the trend to later childbearing. In 2009, 10.13 and 5.17 fresh ART cycles per 1000 women of reproductive age were performed in women in the highest and lowest SES quintiles respectively. In the 12 months after the introduction of a policy that increased out-of-pocket costs from ∼$1500 Australian dollars (€1000) to ∼$2500 (€1670) for a fresh IVF cycle, there was a 21-25% reduction in fresh ART cycles across all SES quintiles. The absolute reduction in fresh ART cycles in the highest SES quintile was double that in the lowest SES quintile. LIMITATIONS, REASONS FOR CAUTION: In this study, SES was based on the average relative socioeconomic advantage and disadvantage of small geographic areas, and therefore may not reflect the SES of an individual. Additionally, the policy impact was limited to the 12 months following its introduction, and may not reflect longer term trends in ART treatment. WIDER IMPLICATIONS OF THE FINDINGS: While financial barriers are an important obstacle to equitable access to ARTs, socioeconomic differences in utilization are likely to persist in countries with supportive public funding, due in part to differences in childbearing patterns and treatment seeking behaviour. Policy makers should be informed of the impact that changes in the level of cost subsidization have on access to ART treatment by different socioeconomic groups. STUDY FUNDING/COMPETING INTEREST(S): G.M.C. receives grant support to her institution from the Australian Government, Australian Research Council (ARC) Linkage Grant No LP1002165; ARC Linkage Grant Partner Organisations are IVFAustralia, Melbourne IVF and Queensland Fertility Group. V.P.H. is employed as an Economics Research Associate on the same grant. P.J.I. is Medical Director of the IVF Clinic, IVFAustralia and has a financial interest in the parent group, Virtus. TRIAL REGISTRATION NUMBER: N/A.

Age of Anopheles gambiae Giles male mosquitoes at time of mating influences female oviposition.

Female Anopheles gambiae were more likely to oviposit when they mated with males that were two days old than when they mated with older males. The females' age at the time of mating and blood feeding did not influence ovipositional patterns. Females were no less likely to oviposit when they mated after blood feeding and maturing eggs. Sperm were present in the seminal vesicles of males 28 hours after eclosion, and their accessory glands were replete by 76-100 hours. The mean life span of sucrose-fed unmated females and males was 22 days.

Effect of body size on host seeking and blood meal utilization in Anopheles gambiae sensu stricto (Diptera: Culicidae): the disadvantage of being small.

The survival, metabolic reserves, and host-seeking response of unfed Anopheles gambiae Giles sensu stricto females of different size classes were investigated from 1 to 6 d after emergence. In addition, the effect of blood meal size and frequency of feeding on the accumulation of metabolic reserves and reproductive development were investigated during the 1st gonotrophic cycle. Large females survived longer and contained significantly more protein, glycogen, and lipid at emergence than did small females. Over 6 d, the host-seeking response of large mosquitoes was greater than that of small ones. There was no gonotrophic development in unfed small females after emergence, whereas < or = 52% of large females developed oocytes to Christophers stage II. One blood meal, given by enema, resulted in gonotrophic development to stage II in small females, whereas only large females matured oocytes to Christophers stage V. In both large and small females, egg development was related to the size of the blood meal, but large females were better able to utilize the meals. Two successive blood meals enhanced the ability of small females to develop eggs. The pregravid condition commonly observed in An. gambiae appears to be determined by insufficient metabolic reserves at emergence, and the probability for small individuals to be pregravid is greater than for large mosquitoes because of the need to build up sufficient energy reserves before gonotrophic development can occur. The consequence of this behavior in relation to malaria transmission is discussed.

Distention and sugar feeding induce autogenous egg development by the Asian tiger mosquito (Diptera:Culicidae).

Mechanisms initiating autogenous egg development were studied using a selected strain of Asian tiger mosquito, Aedes albopictus (Skuse), that required a sugar meal to develop eggs autogenously. Caloric intake and the abdominal distention produced by ingesting sucrose solutions were interrelated in their effects on autogeny. Distention of the abdomen with 2 microliters of saline, with no caloric intake, induced autogenous egg maturation in 66% of the females. Abdominal distention produced by 2 microliters of saline did not induce egg development if the ventral nerve cord was transected. However, eggs were produced when females ingested 200 micrograms of sucrose in 2 microliters of water following ventral nerve cord transection. A meal containing at least 100 micrograms of sucrose was required for egg development if abdominal distention was < 1 microliter. Mating influenced autogeny in only 10% of the population. Neither distention, caloric intake nor mating affected the number of eggs that matured.

Nutritional reserves of autogenous and anautogenous selected strains of Aedes albopictus (Diptera: Culicidae).

Autogeny in Aedes albopictus (Skuse) females was increased from 5% in wild-type parental stock to 84% by selection through 20 generations and was decreased to 0% by selection through nine generations. Concomitantly, the mean number of eggs per female that matured autogenously increased from 6.4 to 18.3 in sugar-fed mosquitoes that developed eggs. Although the duration of the larval period of the two strains was not different, autogenous females emerged with greater amounts of metabolizable protein and lipid and total available energy reserves than did anautogenous females, but with lesser amounts of glycogen. Dry weights did not differ significantly. The difference in the energy reserves between strains was slightly more than the total energy invested in 20 autogenous eggs. Autogenous females survived 1.3 d longer than did anautogenous females when starved from emergence.

Reproductive and metabolic differences between Aedes aegypti and Ae. albopictus (Diptera: Culicidae).

Aedes albopictus (Skuse) females were more likely to develop eggs after they ingested small blood meals than were Aedes aegypti (L.) when both species were maintained under the same suboptimal adult nutritional regimen. The longevity of adult female Ae. albopictus under conditions of starvation was also significantly greater than that of Ae. aegypti. Analyses of total body proteins, lipids, and glycogen indicated that the increased reproductive efficiency of Ae. albopictus may be a result of its greater reserves accumulated during a longer larval period.

Correlation of nutritional reserves with a critical weight for pupation in larval Aedes aegypti mosquitoes.

The relationships between the readiness of fourth instar Aedes aegypti to metamorphose and their weight, nutritional reserves and sex were examined. Both the critical larval weight required for metamorphosis and the potential weight were influenced by the temperature at which the larvae were reared, and were greater for females than for males. Caloric levels of soluble carbohydrates and soluble lipids correlated strongly with weight. The accumulations of both carbohydrates and lipids were sex-dependent and were increased in both sexes at the higher temperature, but caloric levels of glycogen at the critical weights were all similar. We suggest that weight per se is not a critical factor in determining readiness to pupate, and that carbohydrate levels may be one important causal variable.

Effects of larval nutrition on the host-seeking behavior of adult Aedes aegypti mosquitoes.

Adult female Aedes aegypti that were reared on a suboptimal diet as larvae were less likely to engage in host-seeking behavior than were adults derived from larvae reared on an optimal diet. A postemergence carbohydrate diet of either 1 or 10% sucrose solution did not affect this response. When the progeny of field-collected Aedes vexans were reared in the laboratory, the adults were significantly larger than their parents. This indicated that the larvae of the field population were not as adequately nourished as their laboratory-reared progeny.