Obstetrics and Gynaecology - Research Publications
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ItemDefer or deliver? Two-year outcomes after late preterm pre-eclampsia(WILEY, 2022-09)Linked article: This is a mini commentary on Alice Beardmore‐Gray et al., pp. 1654–1663 in this issue. To view this article visit https://doi.org/10.1111/1471-0528.17167
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ItemRisk of obstetric anal sphincter injury among women who birth vaginally after a prior caesarean section: A state-wide cohort study(WILEY, 2022-07)OBJECTIVE: Vaginal birth after caesarean (VBAC) has been suggested to be associated with an increased risk of obstetric anal sphincter injury (compared with primiparous women who birth vaginally). However, prior studies have been small or have used outdated methodology. We set out to validate whether the risk of obstetric anal sphincter injury among women having their first VBAC is greater than that among primiparous women having a vaginal birth. DESIGN: State-wide retrospective cohort study. SETTING: Victoria, Australia. POPULATION: All births (455 000) between 2009 and 2014. METHODS: The risk of severe perineal injury between the first vaginal birth and the first VBAC was compared, after adjustment for potential confounding variables. Covariates were examined using logistic regression for categorical data and the Wilcoxon rank-sum test for continuous data. Missing data were handled using multiple imputation; the analysis was performed using regression adjustment and stata 16 multiple imputation and suite of effects commands. RESULTS: Women having a VBAC (n = 5429) were significantly more likely than primiparous women (n = 123 353) to sustain a third- or fourth-degree tear during vaginal birth (7.1 versus 5.7%, p < 0.001). After adjustment for mode of birth, body mass index, maternal age, infant birthweight, episiotomy and epidural, there was a 21% increased risk of severe perineal injury (RR 1.21, 95% CI 1.07-1.38). CONCLUSIONS: Women having their first VBAC have a significantly increased risk of sustaining a third- or fourth-degree tear, compared with primiparous women having a vaginal birth. Patient counselling and professional guidelines should reflect this increased risk.
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ItemAdjusting growth standards for fetal sex improves correlation of small babies with stillbirth and adverse perinatal outcomes: A state-wide population study(PUBLIC LIBRARY SCIENCE, 2022-10-10)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.
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ItemCognitive, psychosocial, and behaviour gains at age 31 years from the Jamaica early childhood stimulation trial(WILEY, 2022-06)BACKGROUND: There is little evidence on adult benefits from early childhood interventions in low and middle-income countries. We assessed adult cognition, psychosocial skills and behaviour from a stimulation trial conducted in Jamaica. METHODS: Children with stunted growth (height-for age <-2SD of references) aged 9-24 months were enrolled in a two-year randomised-controlled trial of nutritional supplementation and/or stimulation. At mean age 31.79 (SD 0.40) years, 95 of 127 participants (74.8%; 53.7% male) were assessed. Children without stunted growth were also followed as a comparison group (64 of 84 participants, 76.2%). Measurements included IQ, executive function, mental health, psychosocial skills, personality traits and risk behaviours. A block permutation test, valid for small sample sizes, was used. Analyses accounted for the randomisation protocol, multiple hypothesis testing and attrition. RESULTS: Treatment group participants (stimulation intervention with or without supplementation, n = 48) had significantly greater IQ (Hedges g effect size 0. 57; 95%CI 0.20, 0.95) and cognitive flexibility (0.61; 0.25, 0.98) compared with no-treatment (no-intervention and supplementation only, n = 47). They also had reduced depressive symptoms (0.61; 0.28, 1.00), increased grit (0.53; 0.16, 0.92) and conscientiousness (0.66; 0.31, 1.07), lower substance use (rank mean score, 0.45; 0.08, 0.81) and risk taking related to health and work (0.64; 0.27, 1.00). There were 18 significant outcomes of 33 assessed. Comparison participants had higher IQ than no-treatment (1.17; 0.81, 1.54) and treatment groups (0.62; 0.18, 1.07); and better executive function, lower social inhibition and risk taking than the no-treatment group. CONCLUSIONS: The wide-ranging benefits at 31 years from the stimulation intervention supports investment in larger scale programmes to promote early childhood development in disadvantaged children. The lower IQ in the treatment group compared with comparison participants, emphasises the need for continued efforts to prevent early childhood growth retardation.
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ItemMaternal sleep behaviours preceding fetal heart rate events on cardiotocography(WILEY, 2022-04)In Australia, a significant proportion of stillbirths remain unexplained. Recent research has highlighted nocturnal maternal behaviours as potentially modifiable contributors. This study determined whether sleep-related behaviours including sleep position and sleep-disordered breathing adversely affect fetuses overnight, in both uncomplicated pregnancies and those at increased risk due to hypertensive disorders or fetal growth restriction (FGR). All participants underwent polysomnography with time-synchronized fetal heart rate (FHR) monitoring (cardiotocography - CTG) in late pregnancy. CTGs were analysed for abnormal FHR events, including decelerations and reduced variability, by two blinded observers and exported into the sleep study to temporally align FHR events with sleep behaviours. For each FHR event, 10 control epochs with normal FHR were randomly selected for the same participant. Conditional logistic regression assessed the relationships between FHR events and sleep behaviours. From 116 participants, 52 had a total of 129 FHR events overnight; namely prolonged decelerations and prolonged periods of reduced variability. Significantly more FHR events were observed in women with FGR and/or a hypertensive disorder compared with uncomplicated pregnancies (P = 0.006). FHR events were twice as likely to be preceded by a change in body position within the previous 5 min, compared with control epochs (P = 0.007), particularly in hypertensive pregnancies both with and without FGR. Overall, FHR events were not temporally related to supine body position, respiratory events or snoring. Our results indicate that most fetuses tolerate sleep-related stressors, but further research is needed to identify the interplay of maternal and fetal conditions putting the fetus at risk overnight. KEY POINTS: Maternal sleep behaviours including supine position and sleep-disordered breathing are potential contributors to stillbirth but much of this work is based on self-reported data. Using time-synchronized polysomnography and cardiotocography, we found that nocturnal fetal heart rate decelerations were more likely to be preceded by a change in body position compared with epochs containing normal fetal heart rate, particularly in hypertensive pregnancies with or without fetal growth restriction. There was no temporal relationship between maternal sleeping position, snoring or apnoeic events and an abnormal fetal heart rate overnight. We conclude that most fetuses can tolerate sleep-related stressors with no evidence of fetal heart rate changes indicating compromised wellbeing. Further work needs to identify how sleep behaviours contribute to stillbirth risk and how these intersect with underlying maternal and fetal conditions.
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ItemFetal heart rate events during sleep, and the impact of sleep disordered breathing, in pregnancies complicated by preterm fetal growth restriction: An exploratory observational case-control study(WILEY, 2022-12)OBJECTIVES: To evaluate fetal heart rate (FHR) patterns during sleep in pregnancies complicated by preterm fetal growth restriction (FGR). To determine whether co-existing sleep-disordered breathing (SDB) impacts on acute FHR events or perinatal outcome. DESIGN: Observational case control study. SETTING AND POPULATION: Women with preterm FGR and gestation-matched well grown controls (estimated fetal weight above the 10th percentile with normal Doppler studies); tertiary maternity hospital, Australia. METHODS: A polysomnogram, a test used to measure sleep patterns and diagnose sleep disorders, and concurrent cardiotocography (CTG), were analysed for respiratory events and FHR changes. MAIN OUTCOME MEASURES: Frequency of FHR events overnight in FGR cases versus controls and in those with or without SDB. RESULTS: Twenty-nine patients with preterm FGR and 29 controls (median estimated fetal weight 1st versus 60th percentile, P < 0.001) underwent polysomnography with concurrent CTG at a mean gestation of 30.2 weeks. The median number of FHR events per night was higher among FGR cases than among controls (3.0 events, interquartile range [IQR] 1.0-4.0, versus 1.0 [IQR 0-1.0]; P < 0.001). Women with pregnancies complicated by preterm FGR were more likely than controls to be nulliparous, receive antihypertensive medications, be supine at sleep onset, and to sleep supine (32.9% of total sleep time versus 18.3%, P = 0.03). SDB was common in both FGR and control pregnancies (48% versus 38%, respectively, P = 0.55) but was generally mild and not associated with an increase in overnight FHR events or adverse perinatal outcome. CONCLUSIONS: Acute FHR events overnight are more common in pregnancies complicated by preterm FGR than in pregnancies with normal fetal growth. Mild SDB was common in late pregnancy and well tolerated, even by fetuses with preterm FGR. TWEETABLE ABSTRACT: Mild sleep-disordered breathing seems well tolerated even by highly vulnerable fetuses.
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ItemNo Preview AvailableEndothelial protein C receptor is increased in preterm preeclampsia and fetal growth restriction(WILEY, 2022-12)Placental dysfunction is the leading cause of both preeclampsia and fetal growth restriction. This study aimed to characterize endothelial protein C receptor (EPCR) in preterm preeclampsia, term preeclampsia, and fetal growth restriction (defined by delivery of a small for gestational age [SGA] infant [<10% birthweight centile]) and examine its regulation in primary syncytiotrophoblast. Placental EPCR mRNA and protein were significantly increased in patients with preterm preeclampsia (<34 weeks gestation) compared to gestation-matched controls (p < .0001). In the plasma, EPCR was also significantly elevated (p = .01) in established preterm preeclampsia while its substrate, protein C (PC) was significantly reduced (p = .0083). Placentas from preterm small for gestational age (SGA) cases, had elevated EPCR mRNA expression (p < .0001) relative to controls. At 36 weeks, no significant changes in plasma EPCR were detected in samples from patients destined to develop preeclampsia or deliver an SGA infant at term. In terms of syncytiotrophoblast, hypoxia significantly increased EPCR mRNA expression (p = .008), but Tumor Necrosis Factor Alpha (TNF-α) decreased EPCR mRNA. Interleukin-6 (IL-6) had no significant effect on EPCR mRNA expression. When isolated syncytiotrophoblast was treated with metformin under hypoxia (1% O2 ) or normoxia (8% O2 ), EPCR mRNA expression was significantly reduced (p = .008) relative to control. In conclusion, EPCR is markedly elevated in the placenta and the circulation of patients with established preterm preeclampsia and placental increases may be associated with hypoxia. Additionally, fetal growth-restricted pregnancies (as defined by the delivery of an SGA infant) also demonstrated elevated placental EPCR.
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ItemNo Preview AvailablePolysomnographic analysis of maternal sleep position and its relationship to pregnancy complications and sleep-disordered breathing(OXFORD UNIV PRESS INC, 2022-04-11)Links between supine "going to sleep" position and stillbirth risk have led to campaigns regarding safe maternal sleep position. This study profiles the distribution of sleep positions overnight and relationships to sleep onset position during pregnancy, and the relationships between supine sleep, sleep-disordered breathing (SDB), and pregnancy outcomes. Data from three prospective cohort studies evaluating SDB in healthy and complicated pregnancies were pooled. All participants underwent one night of polysomnography in late pregnancy and birth outcome data were collected. 187 women underwent polysomnography at a median gestation of 34 weeks'. The left lateral position was preferred for falling asleep (52%) compared to supine (14%), but sleep onset position was the dominant sleep position overnight in only half (54%) of women. The median percentage of sleep time in the supine position was 24.2%; women who fell asleep supine spent more time supine overnight compared to those who began non-supine (48.0% (30.0,65.9) vs. 22.6% (5.7,32.2), p < .001). Women with growth-restricted fetuses were more likely to fall asleep supine than those with well-grown fetuses (36.6% vs. 7.5%, p < .001). Positional SDB was observed in 46% of those with an RDI ≥ 5. Sleep onset position was the dominant position overnight for half of the sample, suggesting that sleep onset position is not always a reliable indicator of body position overnight. Supine sleep was related to fetal growth restriction and birthweight at delivery, though causality cannot be inferred. It is critical that we pursue research into verifying the important relationship between supine sleep and increased stillbirth risk, and the mechanisms behind it.
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ItemNo Preview AvailableEstimation of neonatal body fat percentage predicts neonatal hypothermia better than birthweight centile(TAYLOR & FRANCIS LTD, 2022)INTRODUCTION: PEA POD™ air displacement plethysmography quickly and noninvasively estimates neonatal body fat percentage (BF%). Low PEA POD™ BF% predicts morbidity better than classification as small-for-gestational-age (SGA; <10th centile), but PEA PODs are not widely available. We examined whether skinfold measurements could effectively identify neonates at risk; comparing skinfold BF%, PEA POD™ BF% and birthweight centiles' prediction of hypothermia - a marker of reduced in utero nutrition. METHODS: Neonates had customized birthweight centiles calculated, and BF% prospectively estimated by: (i) triceps and subscapular skinfolds using sex-specific equations; and (ii) PEA POD™. Medical record review identified hypothermic (<36.5 °C) episodes. RESULTS: 42/149 (28%) neonates had hypothermia. Skinfold BF%, with an area under the curve (AUC) of 0.66, predicted hypothermia as well as PEA POD™ BF% (AUC = 0.62) and birthweight centile (AUC = 0.61). Birthweight <10th centile demonstrated 11.9% sensitivity, 38.5% positive predictive value (PPV) and 92.5% specificity for hypothermia. At equal specificity, skinfold and PEA POD™ BF% more than doubled sensitivity (26.2%) and PPV increased to 57.9%. CONCLUSION: Neonatal BF% performs better to predict neonatal hypothermia than birthweight centile, and may be a better measure of true fetal growth restriction. Estimation of neonatal BF% by skinfold measurements is an inexpensive alternative to PEA POD™.
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ItemNo Preview AvailableExamining differences in placental efficiency following exposure to antidepressants and current depression: Findings from an Australian pregnancy cohort study(W B SAUNDERS CO LTD, 2022-03-04)INTRODUCTION: Placental dysfunction and inefficiency, is important in understanding fetal growth restriction and low birth weight. Two recent studies have examined the relationship between antidepressant use in pregnancy and placental weight ratios; one found lower placental weight ratio associated with antidepressant use and the other found a higher ratio. METHODS: This study examined 342 women recruited in early pregnancy, including 75 taking antidepressants, 29 with current depression and 238 controls. Antidepressant use was measured through self-report in early and late pregnancy, hospital records at delivery and drug concentrations in umbilical cord and maternal blood obtained at delivery. Maternal depression was measured using the Structured Clinical Interview for the DSM IV (SCID) at recruitment. Placentas were collected at delivery and weighed, and infant birth weight recorded. Placental efficiency was measured using standardised placental weight residuals and included as the outcome in general linear models (ANOVA/ANCOVA) to test hypotheses. RESULTS: While placental weight was higher for those on antidepressants compared to controls (z=.30 c.f. Z=-0.08, p=.012), there were no significant differences between the three groups after adjusting for maternal body mass index at recruitment. When comparing antidepressant groups separately there were small-to-moderate positive associations between (SSRI) concentrations and placental weight (rho's > 0.20, p's > 0.05), which did not reach significance. CONCLUSION: Antidepressant use in pregnancy was not associated with significant changes in placental efficiency after adjustment for confounding variables. Future research should expand on this to examine other aspects of placental function and include a wide range of potential confounding variables to draw clinically meaningful conclusions.