ORCID Profile
0000-0002-2225-0188
Current Organisation
University of Queensland
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Publisher: Informa UK Limited
Date: 15-02-2018
DOI: 10.1080/14767058.2017.1387889
Abstract: This paper investigated whether a cerebroplacental ratio (CPR) < 10th centile (measured between 23 + 0-36 + 0 weeks gestation) is predictive of any preterm birth, birth within 2 weeks of the ultrasound scan or spontaneous preterm birth. This was a retrospective cohort study of 8977 women during 2014 and 2015 at a major tertiary referral hospital. Selection criteria included women who had a nonanomalous, singleton fetus and underwent an ultrasound scan between 23 + 0-36 + 6 weeks gestation. A low CPR increased the risk of preterm birth or birth within 2 weeks of the scan with the highest odds of birth within 2 weeks seen at 28-week gestation (odds ratio (OR) 3.78, 95%CI 1.63-8.77) - the mode of delivery was most likely emergency caesarean section for nonreassuring fetal status (aOR 2.11, 95%CI 1.69-2.64, p < .001). Neonatal outcomes were worse in the low CPR cohort particularly with higher odds of death (aOR 2.30, 95%CI 1.46-3.63) and composite adverse outcome (aOR 1.46, 95%CI 1.24-1.73). The low CPR cohort had a significantly shorter interval to delivery (Cox Proportional Hazard - aHR 1.41, 95%CI 1.33-1.51, p < .001) and earlier gestation at birth. A low CPR is associated with an increased risk of preterm birth and birth within 2 weeks but not spontaneous preterm birth.
Publisher: Springer Science and Business Media LLC
Date: 04-2023
DOI: 10.1038/S41588-023-01343-9
Abstract: The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration ( n = 195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed seven associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles ( n = 136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal–fetal relationship between gestational duration and birth weight.
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.PLACENTA.2019.08.086
Abstract: Placental growth factor (PLGF) is a biomarker of placental function. The aim of this study was to define reference ranges for maternal PLGF levels in a normotensive cohort ≥36 + 0 weeks. Prospective observational data from Mater Mothers' Hospital, Brisbane. PLGF levels were measured in women at ≥36 + 0 weeks with singleton, non-anomalous pregnancies. Women with hypertension and fetal growth restriction were excluded. PLGF (pg/mL) was assayed using DELFIA® Xpress (PerkinElmer Inc). The Generalised Additive Model for Location, Shape and Scale (GAMLSS) method was used for the calculation of gestational age-adjusted centiles. Data analysis was performed with Stata 13 (StataCorp, LLC) and R software (R Foundation for Statistical Computing, Vienna, Austria). In all women, PLGF was measured within 2 weeks of delivery. The study cohort comprised of 845 women (36 weeks n = 73, 37 weeks n = 230, 38 weeks n = 214, 39 weeks n = 172, 40 weeks n = 115, 41weeks n = 41). PLGF levels were negatively correlated with gestational age (r = -0.20, p < 0.001). Median PLGF levels dropped significantly from 36 weeks to 41 weeks (169.0 pg/mL to 96.6 pg/mL, p < 0.001). Gestational age specific maternal PLGF centiles were reported using fractional polynomial additive term and Box-Cox t distribution. PLGF did not perform adequately as a predictive test for adverse perinatal outcomes (AUC <0.6). We have created gestational centile reference ranges for maternal PLGF from a normotensive cohort. These novel data suggest maternal PLGF levels decline ≥36 + 0 weeks. The utility of PLGF as a predictor of adverse perinatal outcomes at term, should be further investigated with clinical trials.
Publisher: Springer Science and Business Media LLC
Date: 05-10-2023
Publisher: Walter de Gruyter GmbH
Date: 19-12-2017
Abstract: Birth-weight is an important determinant of perinatal outcome with low birth-weight being a particular risk factor for adverse consequences. To investigate the impact of neonatal sex, mode of birth and gestational age at birth according to birth-weight centile on serious adverse neonatal outcomes in singleton term pregnancies. This was a retrospective cohort study of singleton term births at the Mater Mother’s Hospital, Brisbane, Australia. Serious adverse neonatal outcome was defined as a composite of severe acidosis at birth (pH ≤7.0 and/or lactate ≥6 mmol/L and/or base excess ≤−12 mmol/L), Apgar at 5 min, neonatal intensive-care unit admission and antepartum or neonatal death. The main exposure variable was birth-weight centile. Of the 69,210 babies in our study, the overall proportion of serious adverse neonatal outcomes was 9.1% (6327/69,210). Overall, neonates in the rd birth-weight centile category had the highest adjusted odds ratio (OR) for serious adverse neonatal outcomes [OR 3.53, 95% confidence interval (CI) 3.06–4.07], whilst those in the ≥97 th centile group also had elevated odds (OR 1.51, 95% CI 1.30–1.75). Regardless of birth modality, smaller babies in the rd centile group had the highest adjusted OR and predicted probability for serious adverse neonatal outcomes. When stratified by sex, male babies consistently demonstrated a higher predicted probability of serious adverse neonatal outcomes across all birth-weight centiles. The adjusted odds, when stratified by gestational age at birth, were the highest from 37+0 to 38+6 weeks in the rd centile group (OR 5.97, 95% CI 4.60–7.75). Low and high birth-weights are risk factors for serious adverse neonatal outcomes. The adjusted OR appears to be greatest for babies in the rd birth-weight centile group, although an elevated risk was also found in babies within the ≥97 th centile category.
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.EJOGRB.2017.02.001
Abstract: This study aimed to assess the relationship between the cerebro-placental ratio (CPR) and intrapartum and perinatal outcomes in pregnancies complicated by pre-existing insulin dependent diabetes (pT1DM) mellitus, pre-existing non-insulin dependent diabetes mellitus (pT2DM) and gestational diabetes mellitus (GDM). This was a retrospective cohort study of 1281 women with diabetes mellitus birthing at the Mater Mothers' Hospital in Brisbane between 2007 and 2015. The CPR in non-anomalous singleton fetuses was measured between 34+0 and 36+6 weeks gestation and compared between types of DM treatment groups and correlated with intrapartum and perinatal outcomes. Of the study cohort, 9.7% (124/1281) had pT1DM, 5.3% (68/1281) had pT2DM and 85.0% (1089/1281) had GDM. Of women with pT2DM and GDM, 61.8% (42/68) and 28.9% (315/1089) respectively, required insulin during pregnancy. Women with pT1DM had an increased odds of having a CPR <5th centile (OR 3.73, 95%CI: 1.90-6.96, p=0.0001) or a CPR <10th centile (OR 3.01, 95% CI: 1.80-4.91, p 90th centile (OR 2.69, 95% CI: 1.60-4.39, p=0.0001) was higher in the pT1DM cohort. There was however no significant difference in the mean MCA PI between the three groups. Stratification by CPR centiles (<10th centile vs. ≥10th centile) demonstrated a lower birth weight in the CPR <10th centile cohort for all DM categories. The proportion of neonates with birth weights <10th centile were higher in the CPR <10th centile cohort with the GDM cohort having an odds ratio of 8.28 (95% CI 4.22-16.13, p<0.0001) of this complication. The CPR <10th centile cohort also had a greater proportion of adverse composite neonatal outcome regardless of type of DM. Regardless of the type of DM, a low CPR was associated with poorer neonatal outcomes. Women with pT1DM also had the highest mean UA PI and lowest mean CPR despite no difference in the mean MCA PI between the three groups.
Publisher: Wiley
Date: 05-09-2017
DOI: 10.1002/UOG.17371
Abstract: To evaluate whether the magnitude of change in the cerebroplacental ratio (CPR) after 30 weeks' gestation is a better predictor of adverse pregnancy outcome compared with a single CPR measurement at 35-37 weeks. A secondary aim was to evaluate whether the utility of CPR at 35-37 weeks was enhanced after adjusting for change in gestational age. This was a retrospective cohort study of women who had at least two ultrasound scans between 30 and 37 weeks' gestation, with the final scan at 35-37 weeks. Exclusion criteria were major congenital abnormality, aneuploidy, multiple pregnancy and unknown middle cerebral artery pulsatility index or umbilical artery pulsatility index. A normal reference range for CPR was derived from a separate cohort of women with normal outcome and a Generalised Additive Model for Location, Scale and Shape was fitted to derive standardized centiles. These reference centiles were then used to calculate Z-scores for the study cohort. Logistic regression models and receiver-operating characteristics (ROC) curves were used to evaluate the predictive utility of CPR Z-score at last CPR measurement and the change in CPR on mode of delivery, neonatal outcome and composite neonatal outcome. The area under the ROC curve (AUC) for each model was compared before and after adjustment for parity, hypertension, diabetes, body mass index and smoking status. A total of 1860 women met the inclusion criteria. There was no association between the magnitude of change in CPR and composite adverse pregnancy outcome (P = 0.92). Of the outcomes that made up the composite, an increase in CPR Z-score over time was associated with a lower risk for emergency Cesarean delivery (P < 0.001) and emergency Cesarean delivery for non-reassuring fetal status (P = 0.02). It was also associated with a lower risk of birth weight < 10 Our results suggest that both the in idual CPR Z-score and the magnitude and direction of change in CPR Z-score can identify pregnancies at risk of various adverse perinatal outcomes. However, the CPR Z-score at 35-37 weeks' gestation appears to be a better predictor. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Publisher: Wiley
Date: 16-10-2020
DOI: 10.1002/IJGO.12979
Abstract: To develop a model for predicting emergency cesarean for fetal distress (ECFD) at term using a combination of maternal and late pregnancy ultrasound parameters measured at more than 36 gestational weeks. A study of prospectively collected data, including ultrasound scans at 36-38 weeks, for singleton non-anomalous deliveries at Mater Mother's Hospital, Brisbane, Australia, between January 2010 and April 2017. Univariable and multivariable mixed-effects generalized linear models were generated. The final model was validated by the K-fold cross validation technique. Overall, 5439 women met the inclusion criteria of these, 230 (4.2%) underwent ECFD. There were more nulliparous women and women with induction of labor (IOL) in the ECFD cohort (both P < 0.001). ECFD neonates had lower z-scores for estimated fetal weight (EFW), cerebroplacental ratio (CPR), and middle cerebral artery pulsatility index and higher scores for umbilical artery pulsatility index. Ethnicity, nulliparity, IOL, EFW z-score, and CPR z-score were included in the final prediction model, which showed high accuracy with an area under the receiver operator characteristic curve of 0.77. The study shows that a prediction model combining the continuous standardized measures of CPR and EFW and several maternal factors was able to identify ECFD with improved accuracy.
Publisher: Springer Science and Business Media LLC
Date: 02-2016
DOI: 10.1038/BJC.2015.471
Publisher: Oxford University Press (OUP)
Date: 17-05-2023
DOI: 10.1093/HMG/DDAD086
Abstract: Preterm birth is a major burden to neonatal health worldwide, determined in part by genetics. Recently, studies discovered several genes associated with this trait or its continuous equivalent—gestational duration. However, their effect timing, and thus clinical importance, is still unclear. Here, we use genotyping data of 31 000 births from the Norwegian Mother, Father and Child cohort (MoBa) to investigate different models of the genetic pregnancy ‘clock’. We conduct genome-wide association studies using gestational duration or preterm birth, replicating known maternal associations and finding one new fetal variant. We illustrate how the interpretation of these results is complicated by the loss of power when dichotomizing. Using flexible survival models, we resolve this complexity and find that many of the known loci have time-varying effects, often stronger early in pregnancy. The overall polygenic control of birth timing appears to be shared in the term and preterm, but not very preterm, periods and exploratory results suggest involvement of the major histocompatibility complex genes in the latter. These findings show that the known gestational duration loci are clinically relevant and should help design further experimental studies.
Publisher: Springer Science and Business Media LLC
Date: 21-01-2016
DOI: 10.1038/JP.2015.220
Abstract: To determine intrapartum and perinatal outcomes following successful external cephalic version for breech presentation at term. This was a retrospective cohort study of outcomes following successful external cephalic version in 411 women at an Australian tertiary maternity unit between November 2008 and March 2015. The study cohort was compared with a control group of 1236 women with cephalic presentation who underwent spontaneous labor. Intrapartum intervention rates and adverse neonatal outcomes were compared between both groups. The success rate of external cephalic version (ECV) was 66.4%. The spontaneous vaginal delivery rate in the study cohort was 59.4% (224/411) vs 72.8% (900/1236) in the control cohort (P<0.001). Intrapartum intervention rates (emergency cesarean section (CS) and instrumental delivery) were higher in the ECV group (38% vs 27.2%, P<0.001). Rates of emergency CS for non-reassuring fetal status (9.5%, 39/411 vs 4.4%, 54/1236, P⩽0.001) and failure to progress (13.4%, 55/411 vs 4.1%, 51/1236, P<0.001) were higher in the study cohort. Neonatal outcomes were worse in the study cohort-Apgar score <7 at 5 min (2.2%, 9/411 vs 0.6%, 8/1236, P<0.001) and abnormal cord gases (8.5%, 35/411 vs 0.2%, 3/1236, P<0.001). Rates for resuscitation at birth and admission to the neonatal intensive care unit were higher in the study cohort (6.1% vs 4.1% and 1.9% vs 1.1%, respectively) but these were not statistically significant. Labor following successful ECV is more likely to result in increased intrapartum intervention rates and poorer neonatal outcomes.
Publisher: Wiley
Date: 17-07-2018
DOI: 10.1111/AJO.12849
Abstract: Maternal smoking is associated with a number of adverse outcomes with a dose-dependent increase in risk. The aim of this study was to evaluate the obstetric and perinatal outcomes in women who smoked during pregnancy. This was a retrospective cohort study of women who smoked during pregnancy and birthed at a major perinatal centre in Australia between January 2000 and April 2017. The study cohort was compared to a cohort of women who did not smoke in pregnancy. Smoking status was ascertained on history and included all types of smoking. Demographic characteristics and obstetric, intrapartum and perinatal outcomes were compared between the two groups. The study cohort included 20 477 (14.6%) women who smoked during pregnancy and 119 396 controls. Women who smoked tended to be younger, of higher body mass index (BMI), Caucasian and Indigenous ethnicity. Smokers were less likely to be nulliparous, but more likely to be hypertensive and have a lower socioeconomic status compared to non-smokers. Women who smoked were more likely to have a caesarean section for non-reassuring fetal status (adjusted odds ratio (aOR) 1.16, 95%CI 1.07-1.26, P < 0.001). The infants of women who smoked were more likely to be born preterm, have a lower median birth weight and birth weights <10th (aOR 1.76, 95%CI 1.66-1.86, P < 0.001) and <5th centile (aOR 2.00, 95%CI 1.86-2.16, P < 0.001). Neonatal outcomes in the smoking cohort were worse with an increase in neonatal intensive care unit admission (aOR 1.34, 95%CI 1.27-1.43, P < 0.001), severe acidosis (aOR 1.41, 95%CI 1.27-1.43, P < 0.001) and a composite of severe neonatal outcomes (18.0% vs 12.0%, aOR 1.35, 95%CI 1.28-1.43, P < 0.001). Women who smoke in pregnancy have worse obstetric and perinatal outcomes compared to controls and should be managed as high risk.
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.EJOGRB.2019.06.026
Abstract: To investigate the association between decreased growth velocity at term, measured by estimated fetal weight z-score change, and adverse neonatal outcome and operative birth for intrapartum fetal compromise in a cohort of non-small for gestational age infants. A prospective observational study was conducted at Mater Mothers' Hospital, Brisbane, Australia. Serial ultrasound assessment was undertaken every two weeks from 36 weeks gestation until delivery to determine estimated fetal weight on 436 women with uncomplicated pregnancies. Intrapartum and neonatal outcomes were recorded. The outcome measures were adverse neonatal outcome [severe acidosis (cord pH 6 mmol/L), low Apgar score (<7 at 5 min) or neonatal intensive care unit admission] and operative delivery for intrapartum fetal compromise. Estimated fetal weight z-score change was compared between those with and without adverse neonatal outcome and operative delivery for intrapartum fetal compromise using Generalised Linear Mixed Models. The estimated fetal weight z-score per week declined for infants with the adverse neonatal outcome whilst those without demonstrated an increase [-0.04 (0.18) vs. 0.02 (0.21), p = 0.02]. There was no difference in estimated fetal weight z-score change per week in those with and without operative delivery for intrapartum fetal compromise. Reduced growth velocity in non-small for gestational age fetuses at term is associated with an increased risk of adverse neonatal outcomes.
Publisher: Informa UK Limited
Date: 05-05-2019
Publisher: Wiley
Date: 04-09-2019
DOI: 10.1111/AJO.13045
Abstract: Epidural analgesia increases length of labour and risk of operative delivery (caesarean or instrumental). This study aimed to assess the impact of epidural anaesthesia on maternal and neonatal adverse outcomes when the second stage of labour was prolonged. A retrospective cohort study of women delivering at term at the Mater Mother's Hospital, Brisbane between 2008 and 2017. Intrapartum, maternal and neonatal outcomes were assessed and dichotomised according to the presence of prolonged second stage of labour and further by epidural use. Prolonged second stage of labour was defined as: nulliparous women ≥3 h (with epidural) and ≥2 h (without) multiparous women ≥2 h (with epidural) and ≥1 h (without). There were 48 352 women who met the inclusion criteria - 43 676 without and 4676 with prolonged second stage of labour. The overall epidural rate was 35.9%. Women with epidural had significantly lower odds of achieving a spontaneous vaginal birth and higher odds of an operative birth regardless of length of second stage. While rates of several adverse maternal and neonatal outcomes were higher when the second stage was prolonged, after adjusting for clinically relevant confounders, epidural use was not associated with increased odds of the majority of these adverse outcomes. Indeed, epidural use was associated with a significant reduction in the odds of obstetric anal sphincter injuries and reduced odds of neonatal acidosis in women with prolonged second stage. While epidural increases the risk of operative birth, this is not associated with an increase in adverse maternal or neonatal outcomes.
Publisher: Springer Science and Business Media LLC
Date: 21-03-2022
DOI: 10.1038/S42255-022-00549-1
Abstract: Early childhood obesity is a growing global concern however, the role of common genetic variation on infant and child weight development is unclear. Here, we identify 46 loci associated with early childhood body mass index at specific ages, matching different child growth phases, and representing four major trajectory patterns. We perform genome-wide association studies across 12 time points from birth to 8 years in 28,681 children and their parents (27,088 mothers and 26,239 fathers) in the Norwegian Mother, Father and Child Cohort Study. Monogenic obesity genes are overrepresented near identified loci, and several complex association signals near LEPR, GLP1R, PCSK1 and KLF14 point towards a major influence for common variation affecting the leptin-melanocortin system in early life, providing a link to putative treatment strategies. We also demonstrate how different polygenic risk scores transition from birth to adult profiles through early child growth. In conclusion, our results offer a fine-grained characterization of a changing genetic landscape sustaining early childhood growth.
Publisher: Walter de Gruyter GmbH
Date: 28-08-2018
Abstract: This study aimed to determine maternal and obstetric factors associated with emergency caesarean section (CS) for non-reassuring foetal status (NRFS). This was a retrospective analysis of term singleton births between January 2007 and December 2015 at the Mater Mother’s Hospital in Brisbane. The study group comprised all cases of emergency CS for NRFS, and the control cohort comprised all other births meeting the inclusion criteria but excluding those in the study cohort. Over the study period, there were 74,177 births fulfilling the inclusion criteria. The overall rate of emergency CS for NRFS was 4.2% (3132/74,177). Multivariate analysis showed that being overweight and obese, Indian and “other” ethnicity, artificial reproductive techniques, smoking, induction of labour and gestation at 39–42 weeks were associated with an increased risk, whereas being underweight, female sex, hypertension and birth without labour conferred a lower risk. Many maternal and obstetric factors were associated with emergency CS for NRFS and influenced adverse perinatal outcomes. Recognition of these risk factors could help risk stratify women prior to labour.
Publisher: Wiley
Date: 08-2017
DOI: 10.1002/UOG.17242
Abstract: To assess the relationship between the cerebroplacental ratio (CPR) and intrapartum and perinatal outcomes in pregnancies complicated by gestational diabetes mellitus (GDM). This was a retrospective cohort study of women with a non-anomalous singleton pregnancy diagnosed with GDM who delivered at Mater Mothers' Hospital between 2007 and 2015. CPR was measured in 1089 cases between 34 + 0 and 36 + 6 weeks' gestation. CPR values were compared between groups categorized according to GDM treatment (by diet, oral hypoglycemic agent (OHA) or insulin). The association between CPR and intrapartum and perinatal outcomes was evaluated. No difference in CPR was observed between treatment groups. Fetuses with CPR < 10 Regardless of the type of treatment, a low CPR is associated with poorer neonatal outcome in women with GDM. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Publisher: Informa UK Limited
Date: 20-10-2016
DOI: 10.1080/14767058.2016.1240161
Abstract: The objective of this study is to evaluate the association between birth weight centiles and the risk of intrapartum compromise and adverse neonatal outcomes in term pregnancies. Retrospective study of 32 468 term singleton births at a major tertiary maternity hospital in Australia. Data comprised gestation, mode, and indication for delivery and adverse perinatal outcomes. Fetal sex and gestational age-specific birth weight centiles were the main exposure variable. Neonates <21st birth weight centile had an increased risk of intrapartum compromise, the highest risk was in babies <3rd centile (OR 4.04, 95% CI 3.34-4.89). The risk of adverse perinatal outcomes was increased in neonates 91st birth weight centiles. The highest risk was in those <3rd centile (OR 2.35, 95% CI 2.00-2.75). Fetal size measurements near term may be used as part of screening test for identifying fetuses at an increased risk of intrapartum compromise and adverse perinatal outcomes.
Publisher: Wiley
Date: 18-07-2021
DOI: 10.1111/AJO.13400
Abstract: Hypertensive disorder in pregnancy is common and the optimal ultrasound surveillance of the fetus in this setting is unclear. The aim of this study is to assess the relationship between the fetal cerebroplacental ratio (CPR) and perinatal outcomes in pregnancies complicated by maternal hypertension. A retrospective cohort study was performed over ten years at a single centre. All women who had an ultrasound scan between 34 and 37 weeks gestation with a non‐anomalous singleton pregnancy were included. The hypertensive cohorts were compared to a non‐hypertensive cohort. Each cohort was ided into low CPR for gestational age, or normal/high CPR and these were correlated with intrapartum and perinatal outcomes. A low CPR in a hypertensive pregnancy is associated with an increased risk of induction of labour, emergency caesarean section and poor perinatal outcome. This significance persists when adjusted for gestational age and birth weight. The diagnosis of pre‐ecl sia combined with a low CPR markedly increases the risk of poor perinatal outcome, with 52.6% ( P 0.001) of fetuses in this group having either neonatal intensive care unit admission, respiratory distress, low Apgar score, or acidosis. The odds ratio of a fetus with low CPR in a woman with pre‐ecl sia having a poor composite outcome is 4.09 (95% CI: 1.85−9.06). There is an association between low CPR and the perinatal outcomes of pregnancies complicated by a hypertensive disorder. This association appears to be stronger in pregnancies complicated by pre‐ecl sia than in other types of hypertensive disorders.
Publisher: Informa UK Limited
Date: 18-02-2018
DOI: 10.1080/14767058.2018.1438394
Abstract: In high-risk pregnancies combining the cerebro-placental ratio (CPR) with the estimated fetal weight (EFW) improves the identification of vulnerable fetuses. The purpose of this study was to assess the CPR and EFW's ability to predict adverse obstetric and perinatal outcomes in a low-risk pregnancy, when measured late in gestation. This was a retrospective study of women who birthed at Mater Mothers Hospitals, Brisbane, Australia between 2010 and 2015. We included all nonanomalous singleton pregnancies that had an ultrasound scan performed between 36 and 38 weeks gestation. Excluded was any major congenital abnormality, aneuploidy, multiple pregnancy, preterm birth, maternal hypertension, or diabetes. The primary outcome was a severe composite neonatal outcome (SCNO) defined as severe acidosis (umbilical cord artery pH <7.0, cord lactate ≥6 mmol/L, cord base excess ≤-12 mmol/L) Apgar score ≤3 at 5 minutes, admission to the neonatal intensive care unit (NICU), and death. A low CPR was defined as <10th centile for gestation and small for gestational age (SGA) was defined as an EFW <10th centile and appropriate for gestational age (AGA) was defined as EFW ≥10th centile. Of 2425 pregnancies, 13.2% (321/2425) had a fetus with a CPR <10th centile and 13.7% (332/2425) with an EFW <10th centile. Both a low CPR and SGA predicted the SCNO. In idually a low CPR and SGA had sensitivity for detection of SCNO of 23.3% and 24.7%, respectively which increased to 36.7% when combined. Both were associated with emergency caesarean for nonreassuring fetal status (NRFS), as well as early-term birth and admission to NICU. Stratifying the population into EFW <10th centile and EFW ≥10th centile, a low CPR maintained its association with the SCNO, early-term birth and emergency caesarean for NRFS in the cohort with an EFW 10th cohort. Stratifying the population into CPR 10th centile, a low EFW was associated with early-term birth, induction of labor, admission to NICU, and the SCNO. In a low-risk cohort both the CPR and EFW in idually and in combination predicts adverse obstetric and perinatal outcomes when measured late in pregnancy. However, the predictive value was enhanced when both were used in combination.
Publisher: Wiley
Date: 10-0004
DOI: 10.1111/AJO.12677
Publisher: Cold Spring Harbor Laboratory
Date: 27-11-2022
DOI: 10.1101/2022.11.25.22282723
Abstract: A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight after term delivery as a proxy for placental growth, we report genome-wide association analyses in the fetal ( n = 65,405), maternal ( n = 61,228), and paternal ( n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are confidently classified as fetal only, four maternal only, and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1 . Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but twelve loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with risk of preecl sia or shorter gestational duration. Moreover, these analyses support a role for insulin produced by the fetus in regulating the growth of the placenta, providing a key link between fetal and placental growth.
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.AMJCARD.2015.02.005
Abstract: Insulin resistance (IR) and inflammation are associated with an increased risk of cardiovascular disease and may contribute to obesity cardiomyopathy. The earliest sign of obesity cardiomyopathy is impaired left ventricular (LV) diastolic function, which may be evident in obese children and adolescents. However, the precise metabolic basis of the impaired LV diastolic function remains unknown. The aims of this study were to evaluate cardiac structure and LV diastolic function by tissue Doppler imaging in overweight and obese (OW) youth and to assess the relative in idual contributions of adiposity, IR, and inflammation to alterations in cardiac structure and function. We studied 35 OW (body mass index standard deviation score 2.0±0.8 non-IR n=19, IR n=16) and 34 non-OW youth (body mass index standard deviation score 0.1±0.7). LV diastolic function was reduced in OW youth compared with non-OW controls, as indicated by lower peak myocardial relaxation velocities (p<0.001) and greater filling pressures (p<0.001). OW youth also had greater LV mass index (p<0.001), left atrial volume index, and LV interventricular septal thickness (LV-IVS both p=0.02). IR-OW youth had the highest LV filling pressures, LV-IVS, and relative wall thickness (all p<0.05). Homeostasis model of assessment-insulin resistance and C-reactive protein were negative determinants of peak myocardial relaxation velocity and positive predictors of filling pressure. Adiponectin was a negative determinant of LV-IVS, independent of obesity. In conclusion, OW youth with IR and inflammation are more likely to have adverse changes to cardiovascular structure and function which may predispose to premature cardiovascular disease in adulthood.
Publisher: Public Library of Science (PLoS)
Date: 17-11-2017
Publisher: Springer Science and Business Media LLC
Date: 04-10-2023
Publisher: Wiley
Date: 14-09-2017
DOI: 10.1111/AJO.12718
Abstract: Shoulder dystocia is an uncommon and unpredictable obstetric emergency. It is associated with significant neonatal, maternal and medico-legal consequences. To ascertain the impact shoulder dystocia has on severe neonatal and maternal outcomes specific to the type of manoeuvre. This was a retrospective study of 48 021 term singleton vaginal deliveries the Mater Mothers' Hospital in Brisbane between 2007 and 2015. Maternal and neonatal outcomes were compared between deliveries complicated by shoulder dystocia and those uncomplicated. Deliveries complicated by shoulder dystocia are associated with low Apgar scores (≤3) at five minutes (odds ratio (OR) 5.25, 95% CI 3.23-8.56, P < 0.001), acidosis (OR 3.10, 95% CI 2.76-3.50, P < 0.001), postpartum haemorrhage (OR 2.28, 95% CI 1.90-2.75, P < 0.001) and perineal trauma (OR 1.92, 95% CI 1.54-2.39, P < 0.001). Compared to McRoberts' manoeuvre and suprapubic pressure alone, the odds of serious neonatal outcome are increased with internal rotational manoeuvres (OR 3.82, 95% CI 2.54-5.74, P < 0.001) and delivery of the posterior arm (OR 4.49, 95% CI 3.54-5.69, P < 0.001). The OR of maternal injury is 2.07 (95% CI 1.77-2.45, P < 0.001), 2.26 (95% CI 1.21-4.21, P < 0.001) and 2.29 (95% CI 1.58-3.32, P < 0.001) with McRoberts'/suprapubic pressure, internal rotation and posterior arm delivery, respectively. Brachial plexus injuries and fractures complicate 1.4 and 0.9% of deliveries, with the risk of injury increasing when greater than one manoeuvre is required. The risk of neonatal and maternal trauma is strongly associated with the number and types of manoeuvres. Given the associated implications, adequate antenatal counselling, simulation training and enhanced labour surveillance are essential.
Publisher: MDPI AG
Date: 29-06-2020
DOI: 10.3390/JCM9072035
Abstract: While there is clear evidence that severe maternal morbidity (SMM) contributes significantly to poor maternal health outcomes, limited data exist on its impact on perinatal outcomes. We undertook a systematic review and meta-analysis to ascertain the association between SMM and adverse perinatal outcomes in high-income countries (HICs). We searched for full-text publications in PubMed, Embase, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Scopus databases. Studies that reported data on the association of SMM and adverse perinatal outcomes, either as a composite or in idual outcome, were included. Two authors independently assessed study eligibility, extracted data, and performed quality assessment using the Newcastle–Ottawa Scale. We used random-effects modelling to calculate odds ratios (ORs) with 95% confidence intervals. We also assessed the risk of publication bias and statistical heterogeneity using funnel plots and Higgins I2, respectively. We defined sub-groups of SMM as hemorrhagic disorders, hypertensive disorders, cardiovascular disorders, hepatic disorders, renal disorders, and thromboembolic disorders. Adverse perinatal outcome was defined as preterm birth (before 37 weeks gestation), small for gestational age (SGA) (birth weight (BW) 10th centile for gestation), low birthweight (LBW) (BW 2.5 kg), Apgar score 7 at 5 min, neonatal intensive care unit (NICU) admission, stillbirth and perinatal death (stillbirth and neonatal deaths up to 28 days). A total of 35 studies consisting of 38,909,426 women were included in the final analysis. SMMs associated with obstetric hemorrhage (OR 3.42, 95% CI: 2.55–4.58), severe hypertensive disorders (OR 6.79, 95% CI: 6.06–7.60), hepatic (OR 3.19, 95% CI: 2.46–4.13) and thromboembolic disorders (OR 2.40, 95% CI: 1.67–3.46) were significantly associated with preterm birth. SMMs from hypertensive disorders (OR 2.86, 95% CI: 2.51–3.25) or thromboembolic disorders (OR 1.48, 95% CI: 1.09–1.99) were associated with greater odds of having SGA infant. Women with severe hemorrhage had increased odds of LBW infant (OR 2.31, 95% CI: 1.57–3.40). SMMs from obstetric hemorrhage (OR 4.16, 95% CI: 2.54–6.81) or hypertensive disorders (OR 4.61, 95% CI: 1.17–18.20) were associated with an increased odds of low 5-min Apgar score and NICU admission (Severe obstetric hemorrhage: OR 3.34, 95% CI: 2.26–4.94 and hypertensive disorders: OR 3.63, 95% CI: 2.63–5.02, respectively). Overall, women with SMM were 4 times more likely to experience stillbirth (OR 3.98, 95% CI: 3.12–7.60) compared to those without SMM with cardiovascular disease (OR 15.2, 95% CI: 1.29–180.60) and thromboembolic disorders (OR 9.43, 95% CI: 4.38–20.29) conferring greatest risk of this complication. The odds of neonatal death were significantly higher in women with SMM (OR 3.98, 95% CI: 2.44–6.47), with those experiencing hemorrhagic (OR 7.33, 95% CI: 3.06–17.53) and hypertensive complications (OR 3.0, 95% CI: 1.78–5.07) at highest risk. Overall, SMM was also associated with higher odds of perinatal death (OR 4.74, 95% CI: 2.47–9.12) mainly driven by the increased risk in women experiencing severe obstetric hemorrhage (OR 6.18, 95% CI: 2.55–14.96). Our results highlight the importance of mitigating the impact of SMM not only to improve maternal health but also to ameliorate its consequences on perinatal outcomes.
Publisher: MDPI AG
Date: 09-04-2021
DOI: 10.3390/NU13041239
Abstract: Properly working antioxidant defence systems are important for fetal development. One of the nutrients with antioxidant activity is selenium. Increased maternal selenium intake has been associated with reduced risk for being small for gestational age and preterm delivery. Based on the Norwegian Mother, Father, and Child Cohort Study and the Medical Birth Registry of Norway, we investigated the association of maternal selenium intake from food and dietary supplements during the first half of pregnancy (n = 71,728 women) and selenium status in mid-pregnancy (n = 2628 women) with neonatal health, measured as two composite variables (neonatal morbidity/mortality and neonatal intervention). Low maternal dietary selenium intake ( µg/day) was associated with increased risk for neonatal morbidity/mortality (adjusted odds ratio (adjOR) 1.36, 95% confidence interval (95% CI) 1.08–1.69) and neonatal intervention (adjOR 1.16, 95% CI 1.01–1.34). Using continuous variables, there were no associations between maternal selenium intake (from diet or supplements) or whole-blood selenium concentration and neonatal outcome in the adjusted models. Our findings suggest that sufficient maternal dietary selenium intake is associated with neonatal outcome. Adhering to the dietary recommendations may help ensure an adequate supply of selenium for a healthy pregnancy and optimal fetal development.
Publisher: Informa UK Limited
Date: 26-04-2017
DOI: 10.1080/14767058.2017.1315666
Abstract: To investigate the relationship between the five-minute Apgar score categories (low, intermediate, and normal), mode of birth and neonatal outcomes. This was a retrospective cross sectional study of term singleton deliveries at Mater Mothers' Hospital in Brisbane, Australia between January 2007 and December 2015. The five minute score was sub ided in to three categories - low (0-3), intermediate (4-6), and normal (≥7). These were correlated with adverse neonatal outcomes and mode of birth. The referent cohort was the normal Apgar group. The study cohort consisted of 39,258 births with a recorded five minute Apgar score. Of these, 38,705 (98.6%) neonates had a normal (≥7) Apgar score, 439 (1.1%) had an intermediate score (4-6) and 114 (0.3%) had a low (0-3) score. Neonatal complications including respiratory distress, feeding problems, hypothermia, and seizures were all significantly associated with both low and intermediate Apgar scores. Emergency operative birth (caesarean and instrumental) conveyed a higher risk of low and intermediate scores and poorer neonatal outcomes. Low and intermediate five minute Apgar scores were strongly associated with mode of birth and poorer neonatal outcomes.
Publisher: Informa UK Limited
Date: 29-10-0004
Publisher: Springer Science and Business Media LLC
Date: 18-02-2016
DOI: 10.1007/S00520-016-3125-2
Abstract: Anxiety is a major component of breathlessness and is often palliated with benzodiazepines. Midazolam is a short-acting water-soluble benzodiazepine with a rapid onset of action and short half-life. Intranasal midazolam had been shown to be of marked clinical benefit in an uncontrolled pilot study for the control of dyspnoea. A blinded randomised controlled study was therefore undertaken across four Australasian palliative care services. All participants received six numbered study nasal spray (SNS) bottles, three of which contained midazolam and three placebo. They were instructed to use one SNS bottle on each day they were breathless, for 6 days within 2 weeks. Dyspnoea scores were recorded before and at set time intervals following the first use of each SNS bottle. Across all SNS bottles, the maximum change of 2.1 on an 11-point numerical rating scale was seen at 60 min. There was no difference in dyspnoea score between the two arms. Approximately 50 % of participants in each arm had a positive response (i.e. ≥2 point change in dyspnoea score from baseline). Anxiety scores at baseline were low. The most common adverse event was local nasal reactions. Intranasal midazolam had no clinical benefit over intranasal placebo for the control of dyspnoea. The low level of anxiety at baseline and dose of active drug delivered may have been important factors. Many participants found the SNS bottles to be a challenging mode of drug delivery. This study confirms the importance of placebo-controlled trials for defining best clinical practise.
Publisher: Informa UK Limited
Date: 09-02-2017
DOI: 10.1080/14767058.2016.1202233
Abstract: To determine the association between maternal vitamin D levels and perinatal death. A retrospective cross-sectional study of all non-anomalous, singleton births (≥24 weeks) with perinatal death compared to a matched control group. Only pregnancies with a recorded vitamin D level at booking (8-19 weeks gestation) were included for analysis. Maternal vitamin D levels were categorized into normal, deficient and insufficient cohorts and variables compared between the three groups. There were 31 perinatal deaths which were compared to 111 controls. Median vitamin D levels were lower in the perinatal death cohort compared to the control group (55 nmol/L versus 64 nmol/L, p = 0.43). There was no significant increase in deaths between the normal and deficient (p = 0.33) or insufficient (p = 0.09) groups. Low maternal vitamin D levels at booking were not associated with an increased risk of perinatal demise.
Publisher: MDPI AG
Date: 23-03-2021
DOI: 10.3390/JCM10061319
Abstract: Although the risk of neonatal mortality is generally low for late preterm and early term infants, they are still significantly predisposed to severe neonatal morbidity (SNM) despite being born at relatively advanced gestations. In this study, we investigated maternal and intrapartum risk factors for early SNM in late preterm and early term infants. This was a retrospective cohort study of non-anomalous, singleton infants (34+0–38+6 gestational weeks) born at the Mater Mother’s Hospital in Brisbane, Australia from January 2015 to May 2020. Early SNM was defined as a composite of any of the following severe neonatal outcome indicators: admission to neonatal intensive care unit (NICU) in conjunction with an Apgar score at 5 min, severe respiratory distress, severe neonatal acidosis (cord pH 7.0 or base excess −12 mmol/L). Multivariable binomial logistic regression analyses using generalized estimating equations (GEE) were used to identify risk factors. Of the total infants born at 34+0–38+6 gestational weeks, 5.7% had at least one component of the composite outcome. For late preterm infants, pre-existing diabetes mellitus, instrumental birth and emergency caesarean birth for non-reassuring fetal status were associated with increased odds for early SNM, whilst for early term infants, pre-existing and gestational diabetes mellitus, antepartum hemorrhage, instrumental, emergency caesarean and elective caesarean birth were significant risk factors. In conclusion, we identified several risk factors contributing to early SNM in late preterm and early term cohort. Our results suggest that predicted probability of early SNM decreased as gestation increased.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.EJOGRB.2016.05.036
Abstract: The aim of this study was to investigate the relationship between the cerebro-umbilical ratio (CUR), measured at 30-34 weeks, and adverse intrapartum and perinatal outcomes. This was a retrospective cross-sectional cohort study of women delivering at the Mater Mothers' Hospital in Brisbane, Australia. Fetal Doppler indices for 1224 singleton pregnancies were correlated with maternal demographics and intrapartum and perinatal outcomes. Only women who attempted vaginal delivery were included in the study. Infants delivered by emergency cesarean section for fetal compromise had the lowest median CUR, 1.65 (IQR 1.17-2.12), compared to any other delivery group. The proportion of infants with a CUR ≤1 who required emergency cesarean section for fetal compromise was 33.3% compared to 9.3% of infants with a CUR >1 (adjusted OR 6.92 (95% CI 2.04-25.75), p<0.001). However, the detection rate of CUR ≤1 as a predictor for emergency cesarean delivery for fetal compromise was poor (18.9%). Detection rates increased in cohorts of infants born within two weeks of the scan or with birth weights <10th centile or <5th centile. Additionally, a CUR ≤1 was associated with lower median birth weight, higher rates of admission to the neonatal critical care unit and increased neonatal mortality. This study suggests that a CUR ≤1, measured at 30-34 weeks, is associated with a greater risk of emergency cesarean delivery for fetal compromise and a number of other adverse perinatal outcomes. The association was strongest in low birth weight babies.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.CLNU.2018.08.001
Abstract: Extremes of dysglycaemia as well as glycaemic variability are associated with excess mortality in critically ill patients. Glycaemic variability is an increasingly important measure of glucose control in the intensive care unit (ICU) due to this association however, there is limited data pertaining to the relationship between exogenous glucose from nutrition and glycaemic variability and clinical outcomes. The primary aim of this study was to determine if glycaemic variability is associated with an increase in mortality. Secondary objectives were to investigate any factors affecting glycaemic variability, and to characterise the role nutrition, particularly carbohydrate, plays as a contributing factor to glycaemic variability and other clinical outcomes (duration of ventilation and ICU length of stay). Data on patients in a combined medical/surgical tertiary Australian Intensive Care Unit (ICU), ventilated for >24 h and exclusively fed by artificial nutrition support was extracted from a clinical database of prospectively collected information over an 18 month period. Glycaemic variability was defined as the coefficient of variation (GV standard deviation/mean of blood glucose levels x 100). Statistical analysis was performed using logistic regression, zero-truncated negative binomial and linear regression as appropriate to the distribution of the outcome variable using R software. Data on up to 759 subjects was available. The average age of the study cohort was 56.9 years with a mean (standard deviation) APACHE III score of 72 (28). 66% of the study subjects were male. Glycaemic variability was associated with an increase in mortality (odds ratio 1.02 95% CI: 1.00-1.04, p = 0.03). Factors associated with glycaemic variability included Acute Physiology and Chronic Health Evaluation III score (0.09, 0.06-0.11, p < 0.001), being male (-1.67, -2.97 to -0.38), p = 0.01) and mean units of insulin per day (0.08, 0.06-0.09, p < 0.001). There was no effect of any nutritional factor on glycaemic variability. Further exploratory analyses though showed that for those patients who required insulin during ICU admission, increased insulin dose was associated with increasing carbohydrate (incidence rate ratio (IRR) 1.003, 1.001-1.005, p = 0.001). Mean daily carbohydrate provision (grams) was associated with an increase in ventilation hours (IRR, 95% CI: 1.009, 1.008-1.009, p < 0.001) and length of intensive care unit stay (IRR, 95% CI: 1.007, 1.006-1.008, p < 0.001). This study confirms that GV was associated with excess mortality. Furthermore, administration of increasing doses of insulin was associated with increased GV. Increased carbohydrate intake was associated with an increased insulin requirement, as well as increased duration of mechanical ventilation and ICU length of stay. These findings provide important context for further prospective trials investigating the effect of carbohydrate provision in mechanically ventilated critically ill patients requiring artificial nutritional support.
Publisher: BMJ
Date: 06-2019
DOI: 10.1136/BMJOPEN-2018-027100
Abstract: Severe maternal morbidity (SMM) includes conditions that are on a continuum of maternal morbidity to maternal death. Rates of SMM are increasing both in high-income countries (HICs) as well as in low/middle-income countries (LMICs). There is evidence that analysis of SMM trends and detailed investigation of factors implicated in these cases may reflect the standard of maternal healthcare both in HICs and LMICs. SMM is also associated with poorer perinatal outcomes. The aim of this protocol is to describe the proposed methodology for the synthesis and analyses of the data describing the relationship between SMM and adverse perinatal outcomes in a systematic review and meta-analysis. This systematic review and meta-analysis will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and will be registered with the International Prospective Register of Systematic Reviews (PROSPERO). Original peer-reviewed epidemiologic/clinical studies of observational (cross-sectional, cohort, case-control) and randomised controlled trial studies conducted in high-income countries will be included. An electronic search of PubMed, Embase, CINAHL and Scopus databases will be performed without restricting publication date/year. Two authors will independently screen the titles, review abstracts and perform data extraction. Where possible, meta-analyses will be done to calculate pooled estimates. As this is a protocol for systematic review and meta-analysis of published data, ethics review and approval are not required. The findings will be published in peer-reviewed journals and disseminated at scientific conferences. CRD42019130933.
Publisher: Wiley
Date: 03-04-2017
DOI: 10.1111/AJO.12620
Abstract: To characterise maternal demographics and ascertain whether clinically important differences exist in the intrapartum and neonatal outcomes associated with assisted reproductive technology (ART). A retrospective study was undertaken between January 2007 and December 2013 of all singleton pregnancies conceived via ART at a major tertiary unit in Brisbane, Australia. Intrapartum outcomes were mode of delivery and indication for emergency caesarean. Neonatal outcomes investigated were gestation at delivery, birth weight, Apgar scores, acidosis at birth, respiratory distress, need for resuscitation, admission to neonatal intensive care and stillbirth. There were 4733 (7.4%) ART and 59 277 (92.6%) spontaneous conception pregnancies. Women who conceived using ART were less likely to have a spontaneous vaginal delivery (odds ratio (OR) 0.60, 95% CI 0.57-0.64) and were more likely to require operative or assisted birth: elective caesarean (adjusted OR (aOR) 1.31, 95% CI 1.22-1.40), emergency caesarean (aOR 1.19, 95% CI 1.09-1.28), or instrumental delivery (aOR 1.45, 95% CI 1.32-1.58). Neonates who were conceived using ART were less likely to be born at term (aOR 0.64, 95% CI 0.58-0.71) and have lower birth weights. No differences were observed in rates of respiratory distress, admission to the neonatal intensive care unit, or stillbirth between the ART and spontaneous conception cohorts. The odds of neonatal acidosis (OR 0.71, 95% CI0.63-0.81) were lower in the ART cohort. Although higher rates of operative deliveries were seen for women who conceive using ART, neonatal outcomes were generally no different between the two cohorts.
Publisher: Wiley
Date: 29-05-2019
DOI: 10.1111/AJO.12983
Abstract: During pregnancy, the Epworth Sleepiness Scale can be used as a surrogate marker for maternal sleep-disordered breathing, a condition that is becoming increasingly prevalent in obstetric populations and is associated with a multitude of pregnancy complications. The aim of this observational study was to investigate the relationship between the Epworth Sleepiness Scale score and indication and mode of delivery during pregnancy. The Epworth Sleepiness Scale was completed by 178 women at Mater Mothers' Hospital, Brisbane, Australia. Women with a score ≥11 were less likely to achieve a spontaneous vaginal delivery (aOR 0.43, 95% CI 0.21-0.88, P = 0.02), and were more likely to have an instrumental (aOR 2.81, 95% CI 1.30-6.08, P = 0.01) or any operative birth (instrumental and caesarean section aOR 2.32, 95% CI 1.14-4.71, P = 0.02). These women were also more likely to have an operative birth for intrapartum fetal compromise (aOR 2.62, 95% CI 1.21-5.69, P = 0.015), as well as an infant with poor neonatal outcomes (aOR 2.77, 95% CI 1.09-7.03, P = 0.03). These results show that symptoms of sleep-disordered breathing are associated with emergency operative birth, particularly when the indication for operative birth was intrapartum fetal compromise.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.PLACENTA.2021.10.011
Abstract: The weight of the placenta can be indicative of efficacy in nutrient and oxygen supply. Furthermore, it has been suggested that a measure of the placenta's ability to adequately supply nutrients to the fetus can be found in the relationship between birth weight and placental weight expressed as a ratio. Our aim was to develop age adjusted placenta weight and birth weight to placenta weight ratio reference curves that are stratified by maternal parity and fetal sex. We included singleton, non-anomalous births with a gestational age inclusive of 28 + 0 weeks to 42 + 6 weeks. Excluded were pregnancies of multiplicity, fetuses with congenital abnormalities, stillbirths and pregnancies that had placental complications (ie placenta previa or abruption). Generalised additive model for location, shape and scale (GAMLSS) was used to fit reference curves. We stratified 97,882 pregnancies by maternal nulliparity status and fetal sex. Extensive assessment model goodness-of-fit showed appropriate modeling and accurate fit to the four parameters of distribution. Our results show accurate model fit of the reference curves to the data. We demonstrated that the influence that parity has on the placenta weight is far greater than that exerted by fetal sex, and that the difference is dependent on gestational age. This is the largest presentation of age and parity adjusted placenta weight and feto-placental weight ratio reference ranges to date. The difference observed between nulliparous and multiparous pregnancies could be explained by biological memory and the remnants of maternal endo-myometrial vascularity after the first pregnancy.
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.PLACENTA.2017.11.003
Abstract: Placental growth factor (PlGF) has important angiogenic function that is critical to placental development. Lower levels of PlGF are associated with fetal growth restriction, pre-ecl sia and intrapartum fetal compromise. The aim of this study was to investigate the effect of labour on maternal PlGF levels. This was a prospective observational cohort study. Normotensive women with a singleton, normally grown, non-anomalous, fetus between 37 + 0 and 42 + 0 weeks gestation were eligible for inclusion. PlGF was assayed at two time-points in labour. Women undergoing elective caesarean section served as controls. The primary outcome was the intrapartum change in maternal PlGF levels. Fifty-nine labouring and 43 non-labouring participants were included. Median PlGF decreased from 105.5 pg/mL to 80.9 pg/mL during labour (-23.9%, p < 0.001). PlGF levels were significantly lower in the second stage of labour irrespective of onset of labour, parity, mode of birth or gestation ≥40 weeks. Compared to multiparous women, nulliparous women had significantly lower PlGF levels at both time-points but had similar overall decline in PlGF. Women who required operative vaginal delivery or emergency caesarean section had lower median PlGF levels at both PlGF time-points and greater drop in PlGF during labour compared to spontaneous vaginal deliveries but these were not statistically significant. No correlation was observed between duration of labour and decline in PlGF levels. Overall, median PlGF levels fall by nearly one quarter during labour. This decline may reflect deteriorating placental function during labour.
Publisher: Cold Spring Harbor Laboratory
Date: 23-02-2023
DOI: 10.1101/2023.02.16.23286023
Abstract: Delivering preterm is the leading cause of death in neonates and children under five years of age. Both genetics and environmental factors play a role in timing of delivery, and these influences can be unique to a single pregnancy or shared across pregnancies of the same mother. The aim of this study was to understand how gestational duration is affected by parity and how parity modifies the association between history of preterm delivery and gestational duration. To investigate this, we analysed 1 118 318 spontaneous deliveries (1990 - 2012) from the Swedish Medical Birth Register, with access to pedigrees, using linear regressions and linear mixed models. We found that parity has a modest effect on the mean and a large effect on the variance of gestational duration. Interactions with a woman’s clinical and family history of preterm delivery revealed both pregnancy-specific and shared factors. For instance, the effect of a previous preterm delivery on gestational duration is present across pregnancies, but the magnitude of its effect is pregnancy specific. The access to pedigrees made it possible to apply linear mixed models, thus including all woman’s pregnancies in the model and accounting for unobserved mother-specific covariates. The linear mixed models highlighted a group effect bias when using linear regression to estimate the association between parity and gestational duration, likely caused by socioeconomic factors. Our study shed light on how parity affects gestational duration and modifies the effect of well-known risk factors of preterm delivery.
Publisher: Elsevier BV
Date: 04-1995
DOI: 10.1016/S0002-9149(99)80416-0
Abstract: Amyl nitrite may be used to provoke latent gradients in patients with hypertrophic cardiomyopathy (HC) without significant resting outflow tract gradients, but afterload reduction may not be comparable to a more physiologic stressor such as symptom-limited exercise testing. This study compared the ability of amyl nitrite and exercise testing to provoke outflow tract gradients in 57 patients (40 men and 17 women, mean age +/- SD 49 +/- 16 years) with HC (septal thickness 19 +/- 5 mm, average resting gradient 13 +/- 10 mm Hg) who underwent echocardiography at rest, after amyl nitrite inhalation, and after maximal exercise. No significant gradient (< 50 mm Hg) was induced after either provocation in 26 patients (46%) in 15 patients (26%), inducibility was achieved after both stressors, in 6 (11%) after exercise only, and in 10 (18%) after amyl only. Patients with amyl-induced gradients differed from those in whom gradients were noninducible on the basis of smaller outflow tract dimensions (p < 0.001), larger resting gradients (p < 0.001), and a greater prevalence of "septal bulge" morphology (p = 0.02). Those with exercise-induced gradients were able to attain a greater workload (p = 0.07), have larger resting gradients (p = 0.02), and also tended to have a septal bulge morphology (p < or = 0.01). Although outflow tract obstruction increased to similar levels after amyl nitrite (49 +/- 39 mm Hg) and symptom-limited exercise (47 +/- 39 mm Hg), gradients induced by exercise and amyl correlated poorly (r = 0.54).(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.EJOGRB.2018.09.010
Abstract: A low fetal cerebroplacental ratio (CPR) and nulliparity have independently been shown to be associated with adverse obstetric and perinatal outcomes. To assess the effect of parity on the CPR and investigate the utility of a CPR threshold of <10 This was a retrospective cohort study of low risk, singleton pregnancies delivering at term in Australia's largest maternity hospital. The primary outcome was emergency caesarean section for intrapartum fetal compromise (EmCS IFC). Data was dichotomised according to parity and further by CPR <10 4737 women were included for analysis, 2333 were nulliparous and 2404 were multiparous. Overall the z-score (mean [SD])(CPR standardised for gestation) was lower in nulliparous compared to multiparous women (-0.16 [-1.73 - 1.42] vs 0.04 [-1.63 - 1.69], p < 0.001). Multiparous women had a non-significantly lower mean z-score for those who delivered by EmCS IFC than nulliparous women (-0.52 [-2.23 - 2.02] vs -0.45 [-2.22 - 1.1]). Nulliparous women had greater odds of having a CPR <10 A CPR <10
Publisher: BMJ
Date: 03-2019
DOI: 10.1136/BMJPO-2018-000424
Abstract: The aim of this study was to develop a predictive model using maternal, intrapartum and ultrasound variables for a composite of severe adverse neonatal outcomes (SANO) in term infants. Prospectively collected observational study. Mixed effects generalised linear models were used for modelling. Internal validation was performed using the K-fold cross-validation technique. This was a study of women that birthed at the Mater Mother’s Hospital in Brisbane, Australia between January 2010 and April 2017. We included all term, non-anomalous singleton pregnancies that had an ultrasound performed between 36 and 38 weeks gestation and had recordings for the umbilical artery pulsatility index, middle cerebral artery pulsatility index and the estimated fetal weight (EFW). The components of the SANO were: severe acidosis arterial, admission to the neonatal intensive care unit, Apgar score of ≤3 at 5 min or perinatal death. There were 5439 women identified during the study period that met the inclusion criteria, with 11.7% of this cohort having SANO. The final generalised linear mixed model consisted of the following variables: maternal ethnicity, socioeconomic score, nulliparity, induction of labour, method of birth and z-scores for EFW and cerebroplacental ratio. The final model had an area under the receiver operating characteristic curve of 0.71. The results of this study demonstrate it is possible to predict infants that are at risk of SANO at term with moderate accuracy using a combination of maternal, intrapartum and ultrasound variables. Cross-validation analysis suggests a high calibration of the model.
Publisher: Cold Spring Harbor Laboratory
Date: 10-02-2023
DOI: 10.1101/2023.02.07.23285609
Abstract: Preterm birth is a major burden to neonatal health worldwide, determined in part by genetics. Recently, studies discovered several genes associated with this trait or its continuous equivalent – gestational duration. However, their effect timing, and thus clinical importance, is still unclear. Here, we use genotyping data of 31,000 births from the Norwegian Mother, Father and Child cohort (MoBa) to investigate different models of the genetic pregnancy “clock”. We conduct genome-wide association studies using gestational duration or preterm birth, replicating known maternal associations and finding one new foetal variant. We illustrate how the interpretation of these results is complicated by the loss of power when dichotomizing. Using flexible survival models, we resolve this complexity and find that many of the known loci have time-varying effects, often stronger early in pregnancy. The overall polygenic control of birth timing appears to be shared in the term and preterm, but not very preterm periods, and exploratory results suggest involvement of the major histocompatibility complex genes in the latter. These findings show that the known gestational duration loci are clinically relevant, and should help design further experimental studies.
Publisher: Informa UK Limited
Date: 17-09-2019
Publisher: Wiley
Date: 20-06-2017
DOI: 10.1111/AJO.12651
Abstract: Adolescent pregnancy is defined as pregnancy in girls aged 10-19 years and can be associated with increased risks. To investigate obstetric and perinatal outcomes in a cohort of adolescent girls from a major Australian tertiary centre. This was a nine-year retrospective cohort study of women who birthed at the Mater Mother's Hospital (MMH) in Brisbane, Australia between 1 January 2007 and 31 December 2015. The adolescent cohort was aged <19 years and the control group was aged 20-24 years. Over the study period the total study cohort comprised 8904 women. Of these, the adolescent cohort consisted of 1625 girls (18.2%) and the control group consisted of 7279 women (81.8%). Adolescents were more likely to be nulliparous, single, of Indigenous ethnicity or to have refugee status. They had higher rates of smoking, asthma, diabetes mellitus and thyroid disease. They were more likely to have an uncomplicated spontaneous vaginal delivery but were less likely to have an intact perineum and had higher rates of pre-term delivery and low birth weight babies. There were no differences in rates of postpartum haemorrhage. Teenage pregnancy results in poorer obstetric and perinatal outcomes. A focus on optimising maternal health care and providing culturally appropriate antenatal and intrapartum care is imperative to improving outcomes.
Publisher: Elsevier BV
Date: 05-2020
DOI: 10.1016/J.AJOG.2020.01.025
Abstract: Sildenafil citrate is a vasodilator used in erectile dysfunction and pulmonary hypertension. We tested whether it reduces emergency operative births for fetal compromise and improves fetal or uteroplacental perfusion in labor in a phase 2 double-blind randomized controlled trial. Women at term in early labor or undergoing scheduled induction of labor at Mater Mother's Hospital, Brisbane, Australia, were randomly allocated 50 mg of sildenafil citrate orally 8 hourly up to 150 mg or placebo. Intrapartum fetal monitoring followed Royal Australian and New Zealand College of Obstetricians and Gynaecologists guidelines. Primary outcomes were (1) emergency operative birth (by cesarean delivery or instrumental vaginal birth) for intrapartum fetal compromise and (2) mean indices of fetal and uteroplacental perfusion using Doppler ultrasound. Analysis was by intention-to-treat. ANZCTRN12615000319572 RESULTS: Between September 2015 and January 2019, 300 women were randomized equally to sildenafil citrate or placebo. Sildenafil citrate reduced the risk of emergency operative birth by 51% (18% vs 36.7% relative risk, 0.49, 95% confidence interval, 0.33-0.73, P=.0004, number needed to treat = 5 [3-11]). There was no difference in indices of fetal and uteroplacental perfusion, but these were ascertained in only 71 women. Sildenafil citrate reduced the risk of meconium-stained liquor or pathologic fetal heart rate patterns by 43% (25.3% vs 44.7% relative risk, 0.57, 95% confidence interval, 0.41-0.79, P=.0005), but its effects on fetal scalp s ling rates (2.0% vs 6.7% relative risk, 0.30, 95% confidence interval, 0.08-1.07, P=.06) and adverse neonatal outcome (20.7% vs 21.3% relative risk, 0.97, 95% confidence interval, 0.62-1.50, P=.89) were inconclusive. Only 3.6% of maternal levels of sildenafil citrate or its metabolite were detected in cord blood. No differences in maternal adverse events were seen. Sildenafil citrate reduced operative birth for intrapartum fetal compromise, but much larger phase 3 trials of its effects on mother and child are needed before it can be routinely recommended.
Publisher: Wiley
Date: 14-11-2020
DOI: 10.1002/JGH3.12278
Publisher: Wiley
Date: 02-2017
DOI: 10.1111/AJO.12576
Abstract: Induction of labor (IOL) is a common obstetric intervention, yet its impact on intervention rates and perinatal outcomes is conflicting. To evaluate the impact of IOL on intrapartum intervention rates and perinatal outcomes in women with singleton pregnancies at term. This was a retrospective, cross-sectional study of term singleton deliveries at the Mater Mother's Hospital in Brisbane, Australia in 2007-2013. The IOL cohort was compared to an expectantly managed group. Of the final cohort (44 698 women), 64.4% had expectant management and 35.6% had IOL. Multivariate analyses showed that IOL was associated with lower odds of spontaneous vaginal delivery from ≥37 weeks gestation. The risk of emergency caesarean for non-reassuring fetal status was also higher in the IOL cohort at 40 and 41 weeks gestation. For women who were managed expectantly, the highest rate of spontaneous vaginal delivery and the lowest rate of emergency caesareans occurred at 39 weeks gestation. For women who underwent IOL, the nadir emergency caesarean rate and the highest spontaneous vaginal delivery rate was also at 39 weeks. Rates of neonatal intensive car unit admission were higher in the IOL group at 37 weeks (adjusted odds ratio (aOR) 3.11, 95% CI: 2.62-3.68) and 38 weeks (aOR 1.78, 95% CI: 1.55-2.04) and lower at >42 weeks (OR 0.35, 95% CI: 0.14-0.81) respectively. IOL compared to expectant management is associated with lower spontaneous vaginal delivery rates and increased risk of emergency caesarean for intrapartum fetal compromise with broadly comparable perinatal outcomes.
Publisher: Public Library of Science (PLoS)
Date: 06-11-2020
DOI: 10.1371/JOURNAL.PONE.0241911
Abstract: Multiple factors contribute to gestational duration variability. Understanding the sources of variability allows to design better association studies and assess public health measures. Here, we aimed to assess geographical and temporal changes in the determination of gestational duration and its reporting in Sweden between 1973 and 2012. Singleton live births between 1973 and 2012 were retrieved from the Swedish Medical Birth Register. Gestational duration trends in percentiles and rates of pre- and post-term deliveries were analyzed by plotting the values over time. Temporal changes in gestational duration based on ultrasound and last menstrual period (LMP) estimation methods were compared. Intervals between LMP date and LMP-based due date were analyzed to assess changes in expected gestational duration. In total, 3 940 577 pregnancies were included. From 1973 until 1985, the median of gestational duration estimated based on LMP or ultrasound decreased from 283 to 278 days, and remained stable until 2012. The distribution was relatively stable when ultrasound-based estimates were used. Until the mid-1990s, there was a higher incidence than expected of births occurring on every seventh gestational day from day 157 onward. On an average, these gestational durations were reported 1.8 times more often than adjacent durations. Until 1989, the most common expected gestational duration was 280 days, and thereafter, it was 279 days. The expected gestational duration varied from 279 to 281 days across different Swedish counties. During leap years, the expected gestational duration was one day longer. Consequently, leap years were also associated with significantly higher preterm and lower post-term delivery rates than non-leap years. Changes in data handling and obstetrical practices over the years contribute to gestational duration variation. The resulting increase in variability might reduce precision in association studies and h er the assessment of public health measures aimed to improve pregnancy outcomes.
Publisher: Informa UK Limited
Date: 08-11-2018
Publisher: Informa UK Limited
Date: 10-09-2018
Publisher: Informa UK Limited
Date: 06-02-2018
DOI: 10.1080/14767058.2018.1432590
Abstract: The primary aim of this study was to create reference ranges for the fetal Middle Cerebral artery Pulsatility Index (MCA PI), Umbilical Artery Pulsatility Index (UA PI) and the Cerebro-Placental Ratio (CPR) in a clearly defined low-risk cohort using the Generalised Additive Model for Location, Shape and Scale (GAMLSS) method. Prospectively collected cross-sectional biometry and Doppler data from low-risk women attending the Mater Mother's Hospital, Maternal and Fetal Medicine Department in Brisbane, Australia between January 2010 and April 2017 were used to derive gestation specific centiles for the MCA PI, UA PI and CPR. All ultrasound scans were performed between 18 + 0 and 41 + 6 weeks gestation with recorded data for the MCA PI and/or UA PI. The GAMLSS method was used for the calculation of gestational age-adjusted centiles. Distributions and additive terms were assessed and the final model was chosen on the basis of the Global Deviance, Akaike information criterion (AIC) and Schwartz bayesian criterion (SBC), along with the results of the model and residual diagnostics as well as visual assessment of the centiles themselves. Over the study period 6013 women met the inclusion criteria. The MCA PI was recorded in 4473 fetuses, the UA PI in 6008 fetuses and the CPR was able to be calculated in 4464 cases. The centiles for the MCA PI used a fractional polynomial additive term and Box-Cox t (BCT) distribution. Centiles for the UA PI used a cubic spline additive term with BCT distribution and the CPR used a fractional polynomial additive term and a BCT distribution. We have created gestational centile reference ranges for the MCA PI, UA PI and CPR from a large low-risk cohort that supports their applicability and generalisability.
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.EJOGRB.2017.01.008
Abstract: To evaluate the specific maternal and perinatal variables associated with a low (≤3) or moderate (4-6) Apgar score, compared to a high (≥7) score. This was a retrospective, cohort study of 58429 term singleton babies born at the Mater Mother's Hospital in Brisbane, Australia in 2007-2013. Maternal demographics, socio-economic status using the Australian Socioeconomic Index for Areas (SEIFA) score, obstetric factors, and birth outcomes were compared for neonates grouped into three categories based on their five-minute Apgar: low (≤3), moderate (4-6) and high (≥7). The low- and moderate-score cohorts were in idually compared to the high-score cohort using both univariate and multivariate analysis. Logistic regression analysis confirmed that of the variables analysed, only maternal public insurance status (OR 2.1, 95% CI 1.5-3.1), breech presentation (OR 2.4, 95% CI 1.1-4.6), other non-cephalic presentation (OR 9.5, 95% CI 2.2-25.4), intramuscular narcotic use (OR 2.3, 95% CI 1.5-3.5), and presence of meconium (OR 3.7, 95% CI 2.5-5.4) were significantly associated with low Apgar scores. Variables significantly associated with a moderate score were: SEIFA ≤50th centile (OR 1.6, 95% CI 1.2-2.0) and 61st to 70th centile (OR 1.31, 95% CI 0.9-1.8) categories, maternal public insurance status (OR 2.7, 95% CI 2.2-3.3), nulliparity (OR 2.0, 95% CI 1.7-2.5), emergency caesarean birth (OR 2.6, 95% CI 2.1-3.2), instrumental birth (OR 2.3, 95% CI 1.9-2.9), and presence of meconium (OR 2.6, 95% CI 2.1-3.2). Factors associated with low and moderate Apgar scores vary in type and degree of influence. Distinctions in the perinatal background can help predict newborn compromise and accelerate delivery of care.
Publisher: Wiley
Date: 21-12-2018
DOI: 10.1111/AJO.12935
Abstract: Prolonged second stage of labour is known to be associated with higher caesarean section rates. However, the association between prolonged second stage of labour (PSSL) and adverse neonatal outcomes remains contradictory. The aim of this study was to assess the association between prolonged second stage of labour and obstetric and neonatal outcomes. This was a retrospective cohort study of women with term, singleton pregnancies at the Mater Mother's Hospital, Brisbane. Intrapartum, maternal and neonatal outcomes were assessed and stratified according to prolonged second stage of labour. Of 48 352 women, 9.7% had PSSL. Women with PSSL were more likely to be nulliparous and have received oxytocin for augmentation of their labour (P < 0.001), less likely to have an epidural or have undergone induction of labour (P < 0.001). Women with PSSL were less likely to achieve a spontaneous vaginal delivery (adjusted odds ratio (aOR) 0.13, 95%CI 0.12-0.14, P < 0.001), more likely to undergo an instrumental delivery (aOR 3.93, 95%CI 3.62-4.25, P < 0.001) or emergency caesarean section (aOR 9.08, 95%CI 8.00-10.29, P < 0.001). PSSL was associated with shoulder dystocia (aOR 1.61, 95%CI 1.42-1.81, P < 0.001), and postpartum haemorrhage (aOR 1.37, 95%CI 1.16-1.60, P < 0.001). Univariate analysis demonstrated prolonged second stage of labour was associated with low five-minute Apgar score, acidosis and neonatal intensive care admission. However, after adjusting for potential confounders only five-minute Apgar scores ≤3 remained significantly increased (aOR 2.36, 95% CI 1.36-4.09, P = 0.002). PSSL is associated with increased operative birth and maternal morbidity.
Publisher: Wiley
Date: 06-2023
DOI: 10.1002/CTM2.1291
Abstract: While polygenic risk scores hold significant promise in estimating an in idual's risk of developing a complex trait such as obesity, their application in the clinic has, to date, been limited by a lack of data from non‐European populations. As a collaboration model of the International Hundred K+ Cohorts Consortium (IHCC), we endeavored to develop a globally applicable trans‐ethnic PRS for body mass index (BMI) through this relatively new international effort. The polygenic risk score (PRS) model was developed, trained and tested at the Center for Applied Genomics (CAG) of The Children's Hospital of Philadelphia (CHOP) based on a BMI meta‐analysis from the GIANT consortium. The validated PRS models were subsequently disseminated to the participating sites. Scores were generated by each site locally on their cohorts and summary statistics returned to CAG for final analysis. We show that in the absence of a well powered trans‐ethnic GWAS from which to derive marker SNPs and effect estimates for PRS, trans‐ethnic scores can be generated from European ancestry GWAS using Bayesian approaches such as LDpred, by adjusting the summary statistics using trans‐ethnic linkage disequilibrium reference panels. The ported trans‐ethnic scores outperform population specific‐PRS across all non‐European ancestry populations investigated including East Asians and three‐way admixed Brazilian cohort. Here we show that for a truly polygenic trait such as BMI adjusting the summary statistics of a well powered European ancestry study using trans‐ethnic LD reference results in a score that is predictive across a range of ancestries including East Asians and three‐way admixed Brazilians.
Publisher: Informa UK Limited
Date: 03-04-2018
Publisher: Springer Science and Business Media LLC
Date: 24-12-2018
DOI: 10.1038/S41598-018-37364-2
Abstract: This was a nine-year retrospective cohort study to investigate obstetric and perinatal outcomes in a cohort of adolescent girls with twin pregnancies from a major Australian tertiary centre in Brisbane, Australia. The adolescent cohort was aged years and the control group was aged 20–24 years. The total study cohort comprised of 183 women. Of these, the adolescent cohort contained 29 girls (15.8%) and the control group comprised of 154 women (84.2%). Adolescent girls were less likely to delivery via an elective caesarean section compared to women in the control group (10.3% vs. 25.7%, p 0.001). There were no differences in duration of labour, post-partum haemorrhage or perineal trauma rates. After controlling for the confounding effects of parity, chronicity and birth weight, birth weeks remained significant (aOR 11.20, 95% CI 2.97–42.18, p 0.001) for the adolescent cohort. There was a higher proportion of adolescents whose babies had an adverse composite perinatal outcome (87.9% vs. 69.5%, OR 3.20 95% CI: 1.40–7.31, p = 0.01) however significance was lost after adjusting for parity, chorionicity, birthweight and gestation at birth (aOR 3.27 95% CI: 0.95–11.31, p = 0.06). Our results show that obstetric and perinatal outcomes for twin pregnancies in teenagers were broadly similar compared to controls although the risk of extreme preterm birth was increased after controlling for confounders.
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.AJOG.2018.02.008
Abstract: Small-for-gestational-age infants (birthweight <0th centile) are at increased risk of perinatal complications but are frequently not identified antenatally, particularly in low-risk women delivering at term (≥37 weeks gestation). This is compounded by the fact that late pregnancy ultrasound is not the norm in many jurisdictions for this cohort of women. We thus investigated the relationship between birthweight <10th centile and serious neonatal outcomes in low-risk women at term. We aimed to determine whether there is a difference of obstetric and perinatal outcomes for small-for-gestational-age infants, sub ided into fifth to 90th centile for gestational age) were excluded. Small-for-gestational-age infants were sub ided into 2 cohorts: infants with birthweights from the fifth to <10th centile and those less than the fifth centile. Serious composite neonatal morbidity was defined as any of the following: Apgar score ≤3 at 5 minutes, respiratory distress syndrome, acidosis, admission into the neonatal intensive care unit, stillbirth, or neonatal death. Univariate and multivariate analyses were performed using generalized estimating equations to compare obstetric and perinatal outcomes for small-for-gestational-age infants compared with appropriate-for-gestational age controls. The final study comprised 95,900 infants. Five percent were between the fifth and <10th centiles for birthweight and 4.3% were less than the fifth centile. The rate of serious composite neonatal morbidity was 11.1% in the control group, 13.7% in the fifth and <10th centile, and 22.6% in the less than the fifth centile cohorts, respectively. Even after controlling for confounders, both the fifth to <10th centiles and less than the fifth centile cohorts were at significantly increased risk of serious composite neonatal morbidity compared with controls (odds ratio, 1.25, 95% confidence interval, 1.15-1.37, and odds ratio, 2.20, 95% confidence interval, 2.03-2.39, respectively). Infants with birthweights <10th centile were more likely to have severe acidosis at birth, 5 minute Apgar score ≤3 and to be admitted to the neonatal intensive care unit. The serious composite neonatal morbidity was higher in infants less than the fifth centile compared with those in the fifth to <10th centile cohort (odds ratio, 1.71, 95% confidence interval, 1.52-1.92). The odds of perinatal death (stillbirth and neonatal death) were significantly higher in both small-for-gestational age groups than controls. After stratification for gestational age at birth, the composite outcome remained significantly higher in both small-for-gestational-age cohorts and was highest in the less than the fifth centile group at 37+0 to 38+6 weeks (odds ratio, 3.32, 95% confidence interval, 2.87-3.85). The risk of perinatal death was highest for infants less than the fifth centile at 37+0 to 38+6 weeks (odds ratio, 5.50, 95% confidence interval, 2.33-12.98). Small-for-gestational-age infants from term, low-risk pregnancies are at significantly increased risk of mortality and morbidity when compared with appropriate-for-gestational age infants. Although this risk is increased at all gestational ages in infants less than the fifth centile for birthweight, it is highest at early-term gestation. Our findings highlight that early-term birth does not necessarily improve outcomes and emphasize the importance of identifying this cohort of infants.
No related grants have been discovered for Christopher Flatley.