Objwtive: To study the population pharmacokinetics of caEeine after intravenous administration to... more Objwtive: To study the population pharmacokinetics of caEeine after intravenous administration to premature infants with apnea.
The population pharmacokinetics of amoxicillin were determined in 40 very premature infants (≤32 ... more The population pharmacokinetics of amoxicillin were determined in 40 very premature infants (≤32 week gestational age, <1500 g birth weight) who were receiving intravenous amoxicillin (50 mg/kg, every 12 h) during the first days after birth. Serum amoxicillin concentrations were measured by HPLC. Clearance (CL) and volume of distribution (Vd) were modeled alone and under the influence of demographic and clinical covariates with a 1-compartment model with first-order elimination. The final population models with influential covariates were: CL (L/h) = 0.0000610 · body weight (g) and CL (L/h) = 0.0000805 · body weight (g), for infants also receiving gentamicin and not receiving gentamicin, respectively; Vd (L) = 0.678. The interpatient standard deviation (SD) for CL was 0.0351 L/h, and for Vd was 0.365 L. The intrapatient variability (SD) among observed and model-predicted serum concentrations was 13.7 mg/L. Evaluation of the predictive performance of this model in another group of infants (n = 16) indicated statistically insignificant bias (p > 0.05) of 3 mg/L among pairs of observed and Bayesian-predicted amoxicillin concentrations. The average population CL was smaller, but the average Vd and terminal half-life (t1/2) were larger than previously reported for healthy adults.
The objective of this study was to develop a population model of the pharmacokinetics (PK) of caf... more The objective of this study was to develop a population model of the pharmacokinetics (PK) of caffeine after orogastric or intravenous administration to extremely premature neonates with apnea of prematurity who were to undergo extubation from ventilation. Infants of gestational age &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;30 weeks were randomly allocated to receive maintenance caffeine citrate dosing of either 5 or 20 mg/kg/d. Four blood samples were drawn at prerandomized times from each infant during caffeine treatment. Serum caffeine was assayed by enzyme-multiplied immunoassay technique. Concentration data (431 samples, median: 4 per subject) were obtained from 110 (52 male) infants of mean birth weight of 1009 g, current mean weight (WT) of 992 g, mean gestational age of 27.6 weeks, and mean postnatal age (PNA) of 12 days. Of 1022 doses given, 145 were orogastric, permitting estimation of absolute bioavailability. A 1-compartment model with first-order absorption was fitted to the data in NONMEM. Patient characteristics were screened (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) in nested models for pharmacokinetic influence. Model stability was assessed by nonparametric bootstrapping. Clearance (CL) increased nonlinearly with increasing PNA, whereas volume of distribution (Vd) increased linearly with WT, according to the following allometric models: CL (L/h) = 0.167 (WT/70) (PNA/12); Vd (L) = 58.7 (WT/70). The mean elimination half-life was 101. Interindividual variability (IIV) of CL and Vd was 18.8 % and 22.3 %, respectively. Interoccasion variability (IOV) of CL and Vd was 35.1% and 11.1%, respectively. This study established that the elimination of caffeine was severely depressed in extremely premature infants but increased nonlinearly after birth up to age 6 weeks. Caffeine was completely absorbed, which has favorable implications for switching between intravenous and orogastric routes. The interoccasion variability about CL was twice the interindividual variability, which, among other factors, indicates that routine serum concentration monitoring of caffeine in these patients is not warranted.
Background: Midazolam is used widely as a sedative to facilitate mechanical ventilation. This pro... more Background: Midazolam is used widely as a sedative to facilitate mechanical ventilation. This prospective study investigated the population pharmacokinetics of midazolam in very premature infants.
Aim: To compare post-neonatal mortality among urban and rural Indigenous babies in Queensland.Me... more Aim: To compare post-neonatal mortality among urban and rural Indigenous babies in Queensland.Methods: Registrations of deaths at ages 28 days to 12 months were linked to routine data from the Queensland Perinatal Data Collection.Results: Indigenous babies were 2.52 times more likely to die during the post-neonatal period than non-Indigenous babies (95% confidence interval: 1.99, 3.20). The differential remained when urban and rural areas were examined separately: the differential was 2.53 (1.81, 3.54) in urban areas and 2.26 (1.58, 3.23) in rural areas.Conclusion: The key demographic variable that determines post-neonatal mortality in Queensland is Indigenous status, not rurality. This has important policy implications because it means that interventions to reduce the disparity in mortality between Indigenous and non-Indigenous babies should be delivered in urban as well as rural areas. Better routine data are needed and in particular clinical classification of deaths, so that interventions can be monitored and avoidable factors identified.
Classifications of perinatal deaths have been undertaken for surveillance of causes of death, but... more Classifications of perinatal deaths have been undertaken for surveillance of causes of death, but also for auditing individual deaths to identify suboptimal care at any level, so that preventive strategies may be implemented. This paper describes the history and development of the paired obstetric and neonatal Perinatal Society of Australia and New Zealand (PSANZ) classifications in the context of other classifications. The PSANZ Perinatal Death Classification is based on obstetric antecedent factors that initiated the sequence of events leading to the death, and was developed largely from the Aberdeen and Whitfield classifications. The PSANZ Neonatal Death Classification is based on fetal and neonatal factors associated with the death. The classifications, accessible on the PSANZ website (http://www.psanz.org), have definitions and guidelines for use, a high level of agreement between classifiers, and are now being used in nearly all Australian states and New Zealand.
Bjog-an International Journal of Obstetrics and Gynaecology, 2005
A 23 year old woman of African origin was referred from a peripheral unit at 26 weeks and five da... more A 23 year old woman of African origin was referred from a peripheral unit at 26 weeks and five days of gestation in her second pregnancy because of preterm labour. She had previously had an uncomplicated pregnancy. On admission, we continued the tocolytic therapy with atosiban and the administration of steroids to mature the fetal lungs, which had already been started in the referring hospital. The uterine contractions continued and indomethacin was combined with atosiban for 24 hours. Finally, the contractions ceased. Ultrasound investigation showed one fetus with no obvious abnormalities. The estimated fetal weight was 800 g (10th-25th centile). The membranes were intact and there were no signs of infection: no fever and the urine sample and vaginal swab showed no abnormalities. On admission, her blood pressure was 115/75 mmHg and remained stable.
ISA was pleased to contribute to the activities of the 69 authors, from more than 50 institutions... more ISA was pleased to contribute to the activities of the 69 authors, from more than 50 institutions across 18 countries, to produce this series through a grant from the Gates Foundation. ISA was founded on the dream of three mothers of stillborn babies who shared a vision to make a ...
Background: Audit and classification of stillbirths is an essential part of clinical practice and... more Background: Audit and classification of stillbirths is an essential part of clinical practice and a crucial step towards stillbirth prevention. Due to the limitations of the ICD system and lack of an international approach to an acceptable solution, numerous disparate classification systems have emerged. We assessed the performance of six contemporary systems to inform the development of an internationally accepted approach.
Acta Obstetricia Et Gynecologica Scandinavica, 2005
Aim. The aim of this study is to assess the role of progesterone in preterm birth prevention.Met... more Aim. The aim of this study is to assess the role of progesterone in preterm birth prevention.Methods. A MEDLINE search (from 1966 to the present; date of last search January 2005) was performed – using the key words progesterone, pregnancy, preterm birth, preterm labor, and randomized, controlled trial – in order to identify randomized, controlled trials in which progesterone (either intramuscular or vaginal administration) was compared with placebo or no treatment. Data were extracted and a meta-analysis was performed.Results. Seven randomized, controlled trials were identified. Women who received progesterone were statistically significantly less likely to give birth before 37 weeks (seven studies, 1020 women, RR = 0.58, 95% CI = 0.48–0.70), to have an infant with birth weight of ≤2.5 kg (six studies, 872 infants, RR = 0.62, 95% CI = 0.49–0.78), or to have an infant diagnosed with intraventricular hemorrhage (one study, 458 infants, RR = 0.25, 95% CI = 0.08–0.82).Conclusions. For progesterone supplementation to be advocated for women at the risk of preterm birth, the prolongation of gestation demonstrated in this meta-analysis must translate into improved infant outcomes, including a reduction in mortality. There is currently insufficient information to allow recommendations regarding the optimal dose, route, and timing of administration of progesterone supplementation.
Australian & New Zealand Journal of Obstetrics & Gynaecology, 2009
Background: Decreased fetal movement (DFM) is associated with increased risk of adverse pregnanc... more Background: Decreased fetal movement (DFM) is associated with increased risk of adverse pregnancy outcome. However, there is limited research to inform practice in the detection and management of DFM.Aims: To identify current practices and views of obstetricians in Australia and New Zealand regarding DFM.Methods: A postal survey of Fellows and Members, and obstetric trainees of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists.Results: Of the 1700 surveys distributed, 1066 (63%) were returned, of these, 805 (76% of responders) were currently practising and included in the analysis. The majority considered that asking women about fetal movement should be a part of routine care. Sixty per cent reported maternal perception of DFM for 12 h was sufficient evidence of DFM and 77% DFM for 24 h. KICK charts were used routinely by 39%, increasing to 66% following an episode of DFM. Alarm limits varied, the most commonly reported was < 10 movements in 12 h (74%). Only 6% agreed with the internationally recommended definition of < 10 movements in two hours. Interventions for DFM varied, while 81% would routinely undertake a cardiotocograph, 20% would routinely perform ultrasound and 20% more frequent antenatal visits.Conclusions: While monitoring fetal movement is an important part of antenatal care in Australia and New Zealand, variation in obstetric practice for DFM is evident. Large-scale randomised controlled trials are required to identify optimal screening and management options. In the interim, high quality clinical practice guidelines using the best available advice are needed to enhance consistency in practice including advice provided to women.
We have performed a full cross-validation of this clinical Femina data collection against the rou... more We have performed a full cross-validation of this clinical Femina data collection against the routinely collected data of the Medical Birth Registry of Norway to validate the estimates of reduced mortality in the total population. The original estimate of fewer deaths during the intervention with OR 0.7 remains virtually unchanged for the original data collection.
Background: Delayed maternal reporting of decreased fetal movement (DFM) is associated with adver... more Background: Delayed maternal reporting of decreased fetal movement (DFM) is associated with adverse pregnancy outcomes. Inconsistent information on fetal activity to women during the antenatal period may result in delayed reporting of DFM. We aimed to evaluate an intervention of implementation of uniform information on fetal activity to women during the antenatal period. Methods: In a prospective before-and-after study, singleton women presenting DFM in the third trimester across 14 hospitals in Norway were registered. Outcome measures were maternal behavior regarding reporting of DFM, concerns and stillbirth. In addition, cross-sectional studies of all women giving birth were undertaken to assess maternal concerns about fetal activity, and population-based data were obtained from the Medical Birth Registry Norway. Results: Pre-and post-intervention cohorts included 19 407 and 46 143 births with 1 215 and 3 038 women with DFM respectively. Among primiparous women with DFM, a reduction in delayed reporting of DFM (≥48 hrs) OR 0.61 (95% CI 0.47-0.81) and stillbirths OR 0.36 (95% CI 0.19-0.69) was shown in the post-intervention period. No difference was shown in rates of consultations for DFM or maternal concerns. Stillbirth rates and maternal behavior among women who were of non-Western origin, smokers, overweight or >34 years old were unchanged. Conclusions: Uniform information on fetal activity provided to pregnant women was associated with a reduction in the number of primiparous women who delayed reporting of DFM and a reduction of the stillbirth rates for primiparous women reporting DFM. The information did not appear to increase maternal concerns or rate of consultation. Due to different imperfections in different clinical settings, further studies in other populations replicating these findings are required.
Stillbirth is a common adverse pregnancy outcome, with nearly 3 million third-trimester stillbirt... more Stillbirth is a common adverse pregnancy outcome, with nearly 3 million third-trimester stillbirths occurring worldwide each year. 98% occur in low-income and middle-income countries, and more than 1 million stillbirths occur in the intrapartum period, despite many being preventable. Nevertheless, stillbirth is practically unrecognised as a public health issue and few data are reported. In this fi nal paper in the Stillbirths Series, we call for inclusion of stillbirth as a recognised outcome in all relevant international health reports and initiatives. We ask every country to develop and implement a plan to improve maternal and neonatal health that includes a reduction in stillbirths, and to count stillbirths in their vital statistics and other health outcome surveillance systems. We also ask for increased investment in stillbirth-related research, and especially research aimed at identifying and addressing barriers to the aversion of stillbirths within the maternal and neonatal health systems of low-income and middle-income countries. Finally, we ask all those interested in reducing stillbirths to join with advocates for the improvement of other pregnancy-related outcomes, for mothers and their off spring, so that a united front for improved pregnancy and neonatal care for all will become a reality.
Background: Stillbirths need to count. They constitute the majority of the world's perinatal deat... more Background: Stillbirths need to count. They constitute the majority of the world's perinatal deaths and yet, they are largely invisible. Simply counting stillbirths is only the first step in analysis and prevention. From a public health perspective, there is a need for information on timing and circumstances of death, associated conditions and underlying causes, and availability and quality of care. This information will guide efforts to prevent stillbirths and improve quality of care.
Background Stillbirth rates in high-income countries have shown little or no improvement over the... more Background Stillbirth rates in high-income countries have shown little or no improvement over the past two decades. Prevention strategies that target risk factors could be important in rate reduction. This systematic review and metaanalysis was done to identify priority areas for stillbirth prevention relevant to those countries.
Acta Obstetricia Et Gynecologica Scandinavica, 2008
Maternal perception of decreased fetal movements (DFM) affects 5-15% of pregnancies. DFM is assoc... more Maternal perception of decreased fetal movements (DFM) affects 5-15% of pregnancies. DFM is associated with intra-uterine fetal death (IUFD) and intra-uterine growth restriction (IUGR). It has been proposed that maternal perception of DFM may be used as a screening tool for IUFD or IUGR. However, this proposal is complicated by variations in definitions and management of DFM. We hypothesised that uncertainties in the definition and management of women presenting with DFM leads to variation in clinical practice. A postal questionnaire was sent to midwives and consultant obstetricians in the UK. The majority of respondents enquired about the presence of fetal movements after 28 weeks gestation. There was little agreement on a definition of DFM, with a maternal perception of decreased movements for 24 h gaining the greatest acceptance. Few practitioners used formal fetal movement counting, with the majority of respondents stating they were ineffective in the prevention of IUGR or IUFD and led to increased intervention. There was large variation in the knowledge of associations with DFM and management of women presenting with DFM. There were wide variations in the practice of obstetricians and midwives with regard to women presenting with DFM; many aspects of practice were not based on the available evidence. The variation in practice may result from a lack of robust evidence on which to base the provision of care. Further research is needed to provide and disseminate evidence to direct the management of women presenting with DFM.
Objwtive: To study the population pharmacokinetics of caEeine after intravenous administration to... more Objwtive: To study the population pharmacokinetics of caEeine after intravenous administration to premature infants with apnea.
The population pharmacokinetics of amoxicillin were determined in 40 very premature infants (≤32 ... more The population pharmacokinetics of amoxicillin were determined in 40 very premature infants (≤32 week gestational age, <1500 g birth weight) who were receiving intravenous amoxicillin (50 mg/kg, every 12 h) during the first days after birth. Serum amoxicillin concentrations were measured by HPLC. Clearance (CL) and volume of distribution (Vd) were modeled alone and under the influence of demographic and clinical covariates with a 1-compartment model with first-order elimination. The final population models with influential covariates were: CL (L/h) = 0.0000610 · body weight (g) and CL (L/h) = 0.0000805 · body weight (g), for infants also receiving gentamicin and not receiving gentamicin, respectively; Vd (L) = 0.678. The interpatient standard deviation (SD) for CL was 0.0351 L/h, and for Vd was 0.365 L. The intrapatient variability (SD) among observed and model-predicted serum concentrations was 13.7 mg/L. Evaluation of the predictive performance of this model in another group of infants (n = 16) indicated statistically insignificant bias (p > 0.05) of 3 mg/L among pairs of observed and Bayesian-predicted amoxicillin concentrations. The average population CL was smaller, but the average Vd and terminal half-life (t1/2) were larger than previously reported for healthy adults.
The objective of this study was to develop a population model of the pharmacokinetics (PK) of caf... more The objective of this study was to develop a population model of the pharmacokinetics (PK) of caffeine after orogastric or intravenous administration to extremely premature neonates with apnea of prematurity who were to undergo extubation from ventilation. Infants of gestational age &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;30 weeks were randomly allocated to receive maintenance caffeine citrate dosing of either 5 or 20 mg/kg/d. Four blood samples were drawn at prerandomized times from each infant during caffeine treatment. Serum caffeine was assayed by enzyme-multiplied immunoassay technique. Concentration data (431 samples, median: 4 per subject) were obtained from 110 (52 male) infants of mean birth weight of 1009 g, current mean weight (WT) of 992 g, mean gestational age of 27.6 weeks, and mean postnatal age (PNA) of 12 days. Of 1022 doses given, 145 were orogastric, permitting estimation of absolute bioavailability. A 1-compartment model with first-order absorption was fitted to the data in NONMEM. Patient characteristics were screened (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) in nested models for pharmacokinetic influence. Model stability was assessed by nonparametric bootstrapping. Clearance (CL) increased nonlinearly with increasing PNA, whereas volume of distribution (Vd) increased linearly with WT, according to the following allometric models: CL (L/h) = 0.167 (WT/70) (PNA/12); Vd (L) = 58.7 (WT/70). The mean elimination half-life was 101. Interindividual variability (IIV) of CL and Vd was 18.8 % and 22.3 %, respectively. Interoccasion variability (IOV) of CL and Vd was 35.1% and 11.1%, respectively. This study established that the elimination of caffeine was severely depressed in extremely premature infants but increased nonlinearly after birth up to age 6 weeks. Caffeine was completely absorbed, which has favorable implications for switching between intravenous and orogastric routes. The interoccasion variability about CL was twice the interindividual variability, which, among other factors, indicates that routine serum concentration monitoring of caffeine in these patients is not warranted.
Background: Midazolam is used widely as a sedative to facilitate mechanical ventilation. This pro... more Background: Midazolam is used widely as a sedative to facilitate mechanical ventilation. This prospective study investigated the population pharmacokinetics of midazolam in very premature infants.
Aim: To compare post-neonatal mortality among urban and rural Indigenous babies in Queensland.Me... more Aim: To compare post-neonatal mortality among urban and rural Indigenous babies in Queensland.Methods: Registrations of deaths at ages 28 days to 12 months were linked to routine data from the Queensland Perinatal Data Collection.Results: Indigenous babies were 2.52 times more likely to die during the post-neonatal period than non-Indigenous babies (95% confidence interval: 1.99, 3.20). The differential remained when urban and rural areas were examined separately: the differential was 2.53 (1.81, 3.54) in urban areas and 2.26 (1.58, 3.23) in rural areas.Conclusion: The key demographic variable that determines post-neonatal mortality in Queensland is Indigenous status, not rurality. This has important policy implications because it means that interventions to reduce the disparity in mortality between Indigenous and non-Indigenous babies should be delivered in urban as well as rural areas. Better routine data are needed and in particular clinical classification of deaths, so that interventions can be monitored and avoidable factors identified.
Classifications of perinatal deaths have been undertaken for surveillance of causes of death, but... more Classifications of perinatal deaths have been undertaken for surveillance of causes of death, but also for auditing individual deaths to identify suboptimal care at any level, so that preventive strategies may be implemented. This paper describes the history and development of the paired obstetric and neonatal Perinatal Society of Australia and New Zealand (PSANZ) classifications in the context of other classifications. The PSANZ Perinatal Death Classification is based on obstetric antecedent factors that initiated the sequence of events leading to the death, and was developed largely from the Aberdeen and Whitfield classifications. The PSANZ Neonatal Death Classification is based on fetal and neonatal factors associated with the death. The classifications, accessible on the PSANZ website (http://www.psanz.org), have definitions and guidelines for use, a high level of agreement between classifiers, and are now being used in nearly all Australian states and New Zealand.
Bjog-an International Journal of Obstetrics and Gynaecology, 2005
A 23 year old woman of African origin was referred from a peripheral unit at 26 weeks and five da... more A 23 year old woman of African origin was referred from a peripheral unit at 26 weeks and five days of gestation in her second pregnancy because of preterm labour. She had previously had an uncomplicated pregnancy. On admission, we continued the tocolytic therapy with atosiban and the administration of steroids to mature the fetal lungs, which had already been started in the referring hospital. The uterine contractions continued and indomethacin was combined with atosiban for 24 hours. Finally, the contractions ceased. Ultrasound investigation showed one fetus with no obvious abnormalities. The estimated fetal weight was 800 g (10th-25th centile). The membranes were intact and there were no signs of infection: no fever and the urine sample and vaginal swab showed no abnormalities. On admission, her blood pressure was 115/75 mmHg and remained stable.
ISA was pleased to contribute to the activities of the 69 authors, from more than 50 institutions... more ISA was pleased to contribute to the activities of the 69 authors, from more than 50 institutions across 18 countries, to produce this series through a grant from the Gates Foundation. ISA was founded on the dream of three mothers of stillborn babies who shared a vision to make a ...
Background: Audit and classification of stillbirths is an essential part of clinical practice and... more Background: Audit and classification of stillbirths is an essential part of clinical practice and a crucial step towards stillbirth prevention. Due to the limitations of the ICD system and lack of an international approach to an acceptable solution, numerous disparate classification systems have emerged. We assessed the performance of six contemporary systems to inform the development of an internationally accepted approach.
Acta Obstetricia Et Gynecologica Scandinavica, 2005
Aim. The aim of this study is to assess the role of progesterone in preterm birth prevention.Met... more Aim. The aim of this study is to assess the role of progesterone in preterm birth prevention.Methods. A MEDLINE search (from 1966 to the present; date of last search January 2005) was performed – using the key words progesterone, pregnancy, preterm birth, preterm labor, and randomized, controlled trial – in order to identify randomized, controlled trials in which progesterone (either intramuscular or vaginal administration) was compared with placebo or no treatment. Data were extracted and a meta-analysis was performed.Results. Seven randomized, controlled trials were identified. Women who received progesterone were statistically significantly less likely to give birth before 37 weeks (seven studies, 1020 women, RR = 0.58, 95% CI = 0.48–0.70), to have an infant with birth weight of ≤2.5 kg (six studies, 872 infants, RR = 0.62, 95% CI = 0.49–0.78), or to have an infant diagnosed with intraventricular hemorrhage (one study, 458 infants, RR = 0.25, 95% CI = 0.08–0.82).Conclusions. For progesterone supplementation to be advocated for women at the risk of preterm birth, the prolongation of gestation demonstrated in this meta-analysis must translate into improved infant outcomes, including a reduction in mortality. There is currently insufficient information to allow recommendations regarding the optimal dose, route, and timing of administration of progesterone supplementation.
Australian & New Zealand Journal of Obstetrics & Gynaecology, 2009
Background: Decreased fetal movement (DFM) is associated with increased risk of adverse pregnanc... more Background: Decreased fetal movement (DFM) is associated with increased risk of adverse pregnancy outcome. However, there is limited research to inform practice in the detection and management of DFM.Aims: To identify current practices and views of obstetricians in Australia and New Zealand regarding DFM.Methods: A postal survey of Fellows and Members, and obstetric trainees of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists.Results: Of the 1700 surveys distributed, 1066 (63%) were returned, of these, 805 (76% of responders) were currently practising and included in the analysis. The majority considered that asking women about fetal movement should be a part of routine care. Sixty per cent reported maternal perception of DFM for 12 h was sufficient evidence of DFM and 77% DFM for 24 h. KICK charts were used routinely by 39%, increasing to 66% following an episode of DFM. Alarm limits varied, the most commonly reported was < 10 movements in 12 h (74%). Only 6% agreed with the internationally recommended definition of < 10 movements in two hours. Interventions for DFM varied, while 81% would routinely undertake a cardiotocograph, 20% would routinely perform ultrasound and 20% more frequent antenatal visits.Conclusions: While monitoring fetal movement is an important part of antenatal care in Australia and New Zealand, variation in obstetric practice for DFM is evident. Large-scale randomised controlled trials are required to identify optimal screening and management options. In the interim, high quality clinical practice guidelines using the best available advice are needed to enhance consistency in practice including advice provided to women.
We have performed a full cross-validation of this clinical Femina data collection against the rou... more We have performed a full cross-validation of this clinical Femina data collection against the routinely collected data of the Medical Birth Registry of Norway to validate the estimates of reduced mortality in the total population. The original estimate of fewer deaths during the intervention with OR 0.7 remains virtually unchanged for the original data collection.
Background: Delayed maternal reporting of decreased fetal movement (DFM) is associated with adver... more Background: Delayed maternal reporting of decreased fetal movement (DFM) is associated with adverse pregnancy outcomes. Inconsistent information on fetal activity to women during the antenatal period may result in delayed reporting of DFM. We aimed to evaluate an intervention of implementation of uniform information on fetal activity to women during the antenatal period. Methods: In a prospective before-and-after study, singleton women presenting DFM in the third trimester across 14 hospitals in Norway were registered. Outcome measures were maternal behavior regarding reporting of DFM, concerns and stillbirth. In addition, cross-sectional studies of all women giving birth were undertaken to assess maternal concerns about fetal activity, and population-based data were obtained from the Medical Birth Registry Norway. Results: Pre-and post-intervention cohorts included 19 407 and 46 143 births with 1 215 and 3 038 women with DFM respectively. Among primiparous women with DFM, a reduction in delayed reporting of DFM (≥48 hrs) OR 0.61 (95% CI 0.47-0.81) and stillbirths OR 0.36 (95% CI 0.19-0.69) was shown in the post-intervention period. No difference was shown in rates of consultations for DFM or maternal concerns. Stillbirth rates and maternal behavior among women who were of non-Western origin, smokers, overweight or >34 years old were unchanged. Conclusions: Uniform information on fetal activity provided to pregnant women was associated with a reduction in the number of primiparous women who delayed reporting of DFM and a reduction of the stillbirth rates for primiparous women reporting DFM. The information did not appear to increase maternal concerns or rate of consultation. Due to different imperfections in different clinical settings, further studies in other populations replicating these findings are required.
Stillbirth is a common adverse pregnancy outcome, with nearly 3 million third-trimester stillbirt... more Stillbirth is a common adverse pregnancy outcome, with nearly 3 million third-trimester stillbirths occurring worldwide each year. 98% occur in low-income and middle-income countries, and more than 1 million stillbirths occur in the intrapartum period, despite many being preventable. Nevertheless, stillbirth is practically unrecognised as a public health issue and few data are reported. In this fi nal paper in the Stillbirths Series, we call for inclusion of stillbirth as a recognised outcome in all relevant international health reports and initiatives. We ask every country to develop and implement a plan to improve maternal and neonatal health that includes a reduction in stillbirths, and to count stillbirths in their vital statistics and other health outcome surveillance systems. We also ask for increased investment in stillbirth-related research, and especially research aimed at identifying and addressing barriers to the aversion of stillbirths within the maternal and neonatal health systems of low-income and middle-income countries. Finally, we ask all those interested in reducing stillbirths to join with advocates for the improvement of other pregnancy-related outcomes, for mothers and their off spring, so that a united front for improved pregnancy and neonatal care for all will become a reality.
Background: Stillbirths need to count. They constitute the majority of the world's perinatal deat... more Background: Stillbirths need to count. They constitute the majority of the world's perinatal deaths and yet, they are largely invisible. Simply counting stillbirths is only the first step in analysis and prevention. From a public health perspective, there is a need for information on timing and circumstances of death, associated conditions and underlying causes, and availability and quality of care. This information will guide efforts to prevent stillbirths and improve quality of care.
Background Stillbirth rates in high-income countries have shown little or no improvement over the... more Background Stillbirth rates in high-income countries have shown little or no improvement over the past two decades. Prevention strategies that target risk factors could be important in rate reduction. This systematic review and metaanalysis was done to identify priority areas for stillbirth prevention relevant to those countries.
Acta Obstetricia Et Gynecologica Scandinavica, 2008
Maternal perception of decreased fetal movements (DFM) affects 5-15% of pregnancies. DFM is assoc... more Maternal perception of decreased fetal movements (DFM) affects 5-15% of pregnancies. DFM is associated with intra-uterine fetal death (IUFD) and intra-uterine growth restriction (IUGR). It has been proposed that maternal perception of DFM may be used as a screening tool for IUFD or IUGR. However, this proposal is complicated by variations in definitions and management of DFM. We hypothesised that uncertainties in the definition and management of women presenting with DFM leads to variation in clinical practice. A postal questionnaire was sent to midwives and consultant obstetricians in the UK. The majority of respondents enquired about the presence of fetal movements after 28 weeks gestation. There was little agreement on a definition of DFM, with a maternal perception of decreased movements for 24 h gaining the greatest acceptance. Few practitioners used formal fetal movement counting, with the majority of respondents stating they were ineffective in the prevention of IUGR or IUFD and led to increased intervention. There was large variation in the knowledge of associations with DFM and management of women presenting with DFM. There were wide variations in the practice of obstetricians and midwives with regard to women presenting with DFM; many aspects of practice were not based on the available evidence. The variation in practice may result from a lack of robust evidence on which to base the provision of care. Further research is needed to provide and disseminate evidence to direct the management of women presenting with DFM.
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Papers by Vicki Flenady