Obstetrics and Gynaecology - Research Publications
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ItemCustomised growth charts in large-for-gestational-age infants and the association with emergency caesarean section rate(WILEY, 2019-06)BACKGROUND AND AIM: Large-for-gestational-age (LGA) infants are at increased risk of intrapartum complications. However, some infants classified as LGA may be appropriate-for-gestational-age (AGA) if adjusted for maternal stature. We determined whether customisation of birthweight centiles by maternal height, or height and weight, improves the detection of LGA infants at risk of complications. METHODS: We conducted a retrospective analysis of 38 246 term, singleton nulliparous women. We compared population birthweight centiles to those customised by height, or height and weight for complications including intrapartum caesarean section, instrumental delivery, postpartum haemorrhage, anal sphincter injury and neonatal outcomes. RESULTS: Those considered LGA when customised for height but AGA by population centiles (LGA-ht-only) were at increased risk of intrapartum emergency caesarean section compared with infants AGA on all charts (AGA-all); odds ratio (OR) 4.64, 95% CI 3.22-6.76. In contrast, infants considered LGA on population charts, but AGA when customised by height (LGA-pop-only) were not at increased risk compared to the AGA-all group (OR 1.43, 95% CI 0.70-1.88). Infants classified as LGA-ht-only compared to LGA-pop-only remained at significantly higher risk after adjustment for potential confounders (aOR 3.27; 95% CI 2.02-5.31). No difference was seen for any other outcomes. No benefit was seen with customisation by both maternal height and weight. CONCLUSION: Women with an infant classified as AGA on population centiles but LGA when customised for height are at increased risk of intrapartum caesarean section. This is a population unrecognised in current practice. Fetal growth should be customised for maternal height when making assessments regarding the LGA infant.
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ItemIdentification of the optimal growth charts for use in a preterm population: An Australian state-wide retrospective cohort study(PUBLIC LIBRARY SCIENCE, 2019-10)BACKGROUND: Preterm infants are a group at high risk of having experienced placental insufficiency. It is unclear which growth charts perform best in identifying infants at increased risk of stillbirth and other adverse perinatal outcomes. We compared 2 birthweight charts (population centiles and INTERGROWTH-21st birthweight centiles) and 3 fetal growth charts (INTERGROWTH-21st fetal growth charts, World Health Organization fetal growth charts, and Gestation Related Optimal Weight [GROW] customised growth charts) to identify which chart performed best in identifying infants at increased risk of adverse perinatal outcome in a preterm population. METHODS AND FINDINGS: We conducted a retrospective cohort study of all preterm infants born at 24.0 to 36.9 weeks gestation in Victoria, Australia, from 2005 to 2015 (28,968 records available for analysis). All above growth charts were applied to the population. Proportions classified as <5th centile and <10th centile by each chart were compared, as were proportions of stillborn infants considered small for gestational age (SGA, <10th centile) by each chart. We then compared the relative performance of non-overlapping SGA cohorts by each chart to our low-risk reference population (infants born appropriate size for gestational age [>10th and <90th centile] by all intrauterine charts [AGAall]) for the following perinatal outcomes: stillbirth, perinatal mortality (stillbirth or neonatal death), Apgar <4 or <7 at 5 minutes, neonatal intensive care unit admissions, suspicion of poor fetal growth leading to expedited delivery, and cesarean section. All intrauterine charts classified a greater proportion of infants as <5th or <10th centile than birthweight charts. The magnitude of the difference between birthweight and fetal charts was greater at more preterm gestations. Of the fetal charts, GROW customised charts classified the greatest number of infants as SGA (22.3%) and the greatest number of stillborn infants as SGA (57%). INTERGROWTH classified almost no additional infants as SGA that were not already considered SGA on GROW or WHO charts; however, those infants classified as SGA by INTERGROWTH had the greatest risk of both stillbirth and total perinatal mortality. GROW customised charts classified a larger proportion of infants as SGA, and these infants were still at increased risk of mortality and adverse perinatal outcomes compared to the AGAall population. Consistent with similar studies in this field, our study was limited in comparing growth charts by the degree of overlap, with many infants classified as SGA by multiple charts. We attempted to overcome this by examining and comparing sub-populations classified as SGA by only 1 growth chart. CONCLUSIONS: In this study, fetal charts classified greater proportions of preterm and stillborn infants as SGA, which more accurately reflected true fetal growth restriction. Of the intrauterine charts, INTERGROWTH classified the smallest number of preterm infants as SGA, although it identified a particularly high-risk cohort, and GROW customised charts classified the greatest number at increased risk of perinatal mortality.
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ItemNo Preview AvailableDiagnostic Accuracy of Maternal Serum Macrophage Inhibitory Cytokine-1 and Pregnancy-Associated Plasma Protein-A at 6-10 Weeks of Gestation to Predict Miscarriage(LIPPINCOTT WILLIAMS & WILKINS, 2012-05)OBJECTIVE: To determine whether serum macrophage inhibitory cytokine-1, pregnancy-associated plasma protein-A (PAPP-A), anandamide, or β-human chorionic gonadotropin (hCG) measured in an asymptomatic population in the middle of the first trimester with a viable fetus predicts subsequent miscarriage. METHODS: We undertook a prospective cohort study at Mercy Hospital for Women between 2004 and 2008. Participants (N=782) were recruited from prenatal clinics, where samples were taken from asymptomatic women at 6 0/7 to 10 6/7 weeks of gestation. We collected samples from only those women for whom we were able to obtain ultrasound evidence of a singleton with fetal cardiac activity. Serum macrophage inhibitory cytokine-1, PAPP-A, anandamide, and β-hCG concentrations were assayed. RESULTS: Twenty-one (2.7%) miscarried and 761 did not. Among those who miscarried, macrophage inhibitory cytokine-1 and PAPP-A were significantly decreased at 63% (multiples of the median (MOM) 0.63, 25th-75th percentiles 0.33-0.88) and 23% (MOM 0.23, 25th-75th percentiles 0.12-0.48) of levels seen among those with ongoing pregnancies (P<.001 for both comparisons). In contrast, neither serum β-hCG (MOM 0.99, 25th-75th percentiles 0.46-1.86) nor anandamide (MOM 1.07, 25th-75th percentiles 0.87-1.19) was elevated or decreased among those who miscarried compared with those with ongoing pregnancies. At a fixed 10% false-positive rate (90% specificity), a test combining macrophage inhibitory cytokine-1 and PAPP-A yielded 63% sensitivity and a 6.6 positive likelihood ratio in predicting miscarriage. CONCLUSION: Low serum levels of macrophage inhibitory cytokine-1 and PAPP-A measured from asymptomatic women at 6-10 weeks of gestation with viable pregnancies can predict subsequent miscarriage. These analytes are likely to have an important biological role in early pregnancy and are likely to be useful clinical biomarkers for miscarriage and other early pregnancy complications. LEVEL OF EVIDENCE: II.
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ItemEffect of Supracervical Apposition and Spontaneous Labour on Apoptosis and Matrix Metalloproteinases in Human Fetal Membranes(HINDAWI LTD, 2013)BACKGROUND: Apoptosis and matrix metalloproteinase (MMP-9) are capable of hydrolysing components of the extracellular matrix and weakening the fetal membranes which leads to eventual rupture, a key process of human parturition. The aim of this study was to determine the effect of supracervical apposition and spontaneous labour on apoptosis and MMP-9 in human fetal membranes at term. METHODS: Fetal membranes were obtained from term non-labouring supracervical site (SCS) and compared to (i) a paired distal site (DS) or (ii) site of rupture (SOR) after spontaneous labour onset. RESULTS: The expression of the proapoptotic markers Bax, Smac, Fas, FasL, caspase-3, and PARP, was significantly higher in the non-labouring SCS chorion compared to paired DS. Bax, Smac, FasL, caspase-3, and PARP staining was higher in the non-labouring SCS fetal membranes than that in the post-labour SOR. MMP-9 expression and activity were higher in the post-labour SOR fetal membranes compared to non-labouring SCS fetal membranes. CONCLUSION: Components of the apoptotic signalling pathways and MMP-9 may play a role in rupture and labour. Non-labouring SCS fetal membranes display altered morphology and altered apoptotic biochemical characteristics in preparation for labour, while the laboured SOR displays unique MMP characteristics.