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Background In vitro fertilisation (IVF) is a common mode of conception. Understanding the long-term implications for these children is important. The aim of this study was to determine the causal effect of IVF conception on primary school-age childhood developmental and educational outcomes, compared with outcomes following spontaneous conception. Methods and findings Causal inference methods were used to analyse observational data in a way that emulates a target randomised clinical trial. The study cohort comprised statewide linked maternal and childhood administrative data. Participants included singleton infants conceived spontaneously or via IVF, born in Victoria, Australia between 2005 and 2014 and who had school-age developmental and educational outcomes assessed. The exposure examined was conception via IVF, with spontaneous conception the control condition. Two outcome measures were assessed. The first, childhood developmental vulnerability at school entry (age 4 to 6), was assessed using the Australian Early Developmental Census (AEDC) (n = 173,200) and defined as scoring The study included 412,713 children across the 2 outcome cohorts. Linked records were available for 4,697 IVF-conceived cases and 168,503 controls for AEDC, and 8,976 cases and 333,335 controls for NAPLAN. There was no causal effect of IVF-conception on the risk of developmental vulnerability at school-entry compared with spontaneously conceived children (AEDC metrics), with an adjusted risk difference of -0.3% (95% CI -3.7% to 3.1%) and an adjusted risk ratio of 0.97 (95% CI 0.77 to 1.25). At age 7 to 9 years, there was no causal effect of IVF-conception on the NAPLAN overall z-score, with an adjusted mean difference of 0.030 (95% CI -0.018 to 0.077) between IVF- and spontaneously conceived children. The models were adjusted for sex at birth, age at assessment, language background other than English, socioeconomic status, maternal age, parity, and education. Study limitations included the use of observational data, the potential for unmeasured confounding, the presence of missing data, and the necessary restriction of the cohort to children attending school. Conclusions In this analysis, under the given causal assumptions, the school-age developmental and educational outcomes for children conceived by IVF are equivalent to those of spontaneously conceived children. These findings provide important reassurance for current and prospective parents and for clinicians., Author(s): Amber L. Kennedy 1,2, Beverley J. Vollenhoven 3,4,5, Richard J. Hiscock 1,2, Catharyn J. Stern 1,6,7, Susan P. Walker 1,2, Jeanie L. Y. Cheong 1,8,9, Jon L. Quach 1,8, [...]

Background Preterm infants are a group at high risk of having experienced placental insufficiency. It is unclear which growth charts perform best in identifying infants at increased risk of stillbirth and other adverse perinatal outcomes. We compared 2 birthweight charts (population centiles and INTERGROWTH-21st birthweight centiles) and 3 fetal growth charts (INTERGROWTH-21st fetal growth charts, World Health Organization fetal growth charts, and Gestation Related Optimal Weight [GROW] customised growth charts) to identify which chart performed best in identifying infants at increased risk of adverse perinatal outcome in a preterm population. Methods and findings We conducted a retrospective cohort study of all preterm infants born at 24.0 to 36.9 weeks gestation in Victoria, Australia, from 2005 to 2015 (28,968 records available for analysis). All above growth charts were applied to the population. Proportions classified as Conclusions In this study, fetal charts classified greater proportions of preterm and stillborn infants as SGA, which more accurately reflected true fetal growth restriction. Of the intrauterine charts, INTERGROWTH classified the smallest number of preterm infants as SGA, although it identified a particularly high-risk cohort, and GROW customised charts classified the greatest number at increased risk of perinatal mortality., Author(s): Natasha L. Pritchard 1,2, Richard J. Hiscock 1,2, Elizabeth Lockie 1, Michael Permezel 1,2, Monica F. G. McGauren 2, Amber L. Kennedy 1,2, Brittany Green 1, Susan P. Walker [...]

Objectives: Sex impacts birthweight, with male babies heavier on average. Birthweight charts are thus sex specific, but ultrasound fetal weights are often reported by sex neutral standards. We aimed to identify what proportion of infants would be re-classified as SGA if sex-specific charts were used, and if this had a measurable impact on perinatal outcomes. Methods: Retrospective cohort study including all infants born in Victoria, Australia, from 2005–2015 (529,261 cases). We applied GROW centiles, either adjusted or not adjusted for fetal sex. We compared overall SGA populations, and the populations of males considered small by sex-specific charts only (SGAsex-only), and females considered small by sex-neutral charts only (SGAunadjust-only). Results: Of those <10th centile by sex-neutral charts, 39.6% were male and 60.5% female, but using sex-specific charts, 50.3% were male and 49.7% female. 19.2% of SGA females were reclassified as average for gestational age (AGA) using sex-specific charts. These female newborns were not at increased risk of stillbirth, combined perinatal mortality, NICU admissions, low Apgars or emergency CS compared with an AGA infant, but were at greater risk of being iatrogenically delivered on suspicion of growth restriction. 25.0% male infants were reclassified as SGA by sex-specific charts. These male newborns, compared to the AGAall infant, were at greater risk of stillbirth (RR 1.94, 95%CI 1.30–2.90), combined perinatal mortality (RR 1.80, 95%CI 1.26–2.57), NICU admissions (RR 1.38, 95%CI 1.12–1.71), Apgars <7 at 5 minutes (RR 1.40, 95%CI 1.25–1.56) and emergency CS (RR 1.12, 95%CI 1.06–1.18). Conclusions: Use of growth centiles not adjusted for fetal sex disproportionately classifies female infants as SGA, increasing their risk of unnecessary intervention, and fails to identify a cohort of male infants at increased risk of adverse outcomes, including stillbirth. Sex-specific charts may help inform decisions and improve outcomes. [ABSTRACT FROM AUTHOR]

Objective: Many growth charts provide single centile cutoffs for each week of gestation, yet fetuses gain weight throughout the week. We aimed to assess whether using a single centile per week distorts the proportion of infants classified as small and their risk of stillbirth across the week. Design: Retrospective cohort study. Setting: Victoria, Australia. Population: Singleton, non-anomalous infants born from 2005–2015 (529,261). Methods: We applied growth charts to identify small-for-gestational-age (SGA) fetuses on week-based charts (single centile per gestational week) and day-based charts (centile per gestational day). Main outcome measures: Proportions <10th centile by each chart, and stillbirth risk amongst SGA infants. Results: Using week-based charts, 12.1% of infants born on the first day of a gestational week were SGA, but only 7.8% on the final day; ie. an infant born at the end of the week was 44% less likely to be classed as SGA (p<0.0001). The relative risk of stillbirth amongst SGA infants born on the final day of the week compared with the first was 1.47 (95%CI 1.09–2.00, p = 0.01). Using day charts, SGA proportions were similar and stillbirth risk equal between the beginning and end of the week (9.5% vs 9.9%). Conclusions: Growth standards using a single cutoff for a gestational week overestimate the proportion of infants that are small at the beginning of the week and underestimate the proportion at the end. This distorts the risk of stillbirth amongst SGA infants based on when in the week an infant is born. Day-based charts should be used. [ABSTRACT FROM AUTHOR]

Study Question: Does IVF using donor sperm increase the risk of hypertensive disorders of pregnancy and fetal growth restriction (FGR)?Summary Answer: IVF conceptions arising from sperm donation are not associated with an increased risk of hypertensive disorders of pregnancy or FGR.What Is Known Already: It has been hypothesized that the absence of prior exposure to factors within the paternal ejaculate increases the risk of preeclampsia and FGR among nulliparous women or women with a new partner-the concept of 'primipaternity'. It remains unclear which element of the ejaculate is responsible: the sperm cell or the constituents of seminal fluid. IVF pregnancies arising from donor sperm where the seminal fluid is absent provide a unique opportunity to test the theory of primipaternity and the relative contribution of the sperm cell. Pregnancies conceived via artificial reproductive technology are at increased risk of preeclampsia and FGR.Study Design, Size, Duration: Theories about the development of preeclampsia and the relative contribution of spermatic factors were explored by comparing the risk of hypertensive disorders of pregnancy and FGR among IVF pregnancies conceived with autologous gametes (own eggs and partner sperm) and those conceived with donor sperm, donor egg (and partner sperm) and donor embryo. To do this, we performed a retrospective cohort analysis of pregnancy outcomes among singleton pregnancies (n = 15 443) conceived through fertility clinics within Australia between 2009 and 2017.Participants/materials, Setting, Methods: All pregnancies resulting in a singleton pregnancy delivering after 20 weeks' gestation were included. The cohort was divided into donor sperm, donor egg and donor embryo (where both gametes came from a donor to create an embryo, or in a surrogate pregnancy) groups. We also compared the data with a control group, defined as IVF-conceived pregnancies from autologous cycles. A multivariable regression model was used to calculate an adjusted odds ratio (aOR).Main Results and the Role Of Chance: The final cohort contained 1435, 578 and 239 pregnancies conceived by donor sperm, donor egg and donor embryo, respectively, and 13 191 controls. There were a very small number of women lost to follow-up (31 women; 0.2% of total cohort). Compared to control pregnancies, there was no increase in the risk of hypertensive disorders among pregnancies conceived via donor sperm (aOR 0.94; 95% CI 0.73-1.21). Subgroup analysis was performed for a cohort where parity was known (n = 4551), and of these, 305 multigravida pregnancies were conceived via donor sperm. Among this cohort, no increased risk of preeclampsia or pregnancy-induced hypertension was found (aOR 1.18; 95% CI: 0.69-2.04) as a result of primipaternity (new sperm donor).A significantly increased risk for hypertensive disorders of pregnancy was associated with the use of donor eggs (but partner sperm; aOR 2.34; 95% CI 1.69-3.21). However, the association was no greater among pregnancies conceived with donor embryos (i.e. donated egg and sperm; aOR 2.0; 95% CI 1.25-3.17) than among the donor oocyte group. The overall incidence of FGR (defined as birthweight <10th centile) was 18%. There were no significant differences observed between donor sperm, or donor embryo pregnancies; however, egg donation was associated with a 1.5-fold increase in FGR.Limitations, Reasons For Caution: This study was limited by a lower than expected rate of hypertensive disorders of pregnancy (n = 862, 5.6%), which is contrary to the well-established increased risk among women using IVF. However, this is likely to be evenly distributed across the study groups and, therefore, unlikely to have introduced significant bias.Wider Implications Of the Findings: These findings suggest that exposure to new sperm may not be implicated in the pathogenesis of preeclampsia. The mechanism of increased risk seen in conceptions arising from egg or embryo donation remains unclear. Further investigation is required to elucidate these mechanisms and, ultimately, improve pregnancy outcomes following IVF.Study Funding/competing Interest(s): This study was supported by the Australian Commonwealth Government-Graduate Research Scheme (A.K.). Salary support was provided by the National Health and Medical Research Council of Australia (S.T.), Mercy Foundation (A.L.), and the Department of Obstetrics and Gynaecology at the University of Melbourne (R.H.). There are no competing interests. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this analysis was to quantify the risk factors associated with maternal morbidity among women in Victoria, Australia, focusing particularly on sociodemographic factors. Design: Case–control analysis. Participants: Data on all maternities in Victoria from 1 January 2006 to 31 December 2008. Methods: A case–control analysis was conducted using unconditional logistic regression to calculate adjusted ORs (aORs). Cases were defined as all women noted to have had a severe complication during the index pregnancy. Severe maternal morbidity was defined by the validated, composite Australian Maternal Morbidity Outcome Indicator. Socioeconomic position was defined by Socio-Economic Indices for Areas (SEIFA), specifically the Index of Relative Socioeconomic Disadvantage (IRSD), and other variables analysed were age, parity, Indigenous background, multiple pregnancy, country of birth, coexisting medical condition, previous caesarean section, spontaneous abortion or ectopic pregnancy. Results: The study population comprised 211 060 women, including 1119 cases of severe maternal morbidity (0.53%). Compared with the highest IRSD quintile, the aOR for the 2nd quintile was 1.23 (95% CI 1.03 to 1.49), 0.98 (95% CI 0.79 to 1.21) for the 3rd quintile, 1.55 (95% CI 1.28 to 1.87) for the 4th and 1.21 (95% CI 1.00 to 1.47) for the lowest (most deprived) quintile. Indigenous status was associated with twice (aOR 2.02; 95% CI 1.32 to 3.09) the odds of being a case. Other risk factors for severe maternal morbidity were age ≥35 years (aOR 1.22; 95% CI 1.04 to 1.44), coexisting medical condition (aOR 1.39; 95% CI 1.16 to 1.65), multiple pregnancy (aOR 2.30; 95% CI 1.71 to 3.10), primiparity (aOR 1.36; 95% CI 1.18 to 1.57), previous caesarean section (aOR 1.79; 95% CI 1.53 to 2.10) and previous spontaneous miscarriage (aOR 1.25; 95% CI 1.08 to 1.44). Conclusions: The findings from Victoria strongly suggest that social disadvantage needs to be acknowledged and further investigated as an independent risk factor for adverse maternal outcomes in Australia and incorporated into appropriate policy planning and healthcare programmes. [ABSTRACT FROM AUTHOR]