Preterm Infant Outcomes after Randomization to Initial Resuscitation with FiO2 0.21 or 1.0.

OBJECTIVE: To determine rates of death or neurodevelopmental impairment (NDI) at 2 years corrected age (primary outcome) in children <32 weeks' gestation randomized to initial resuscitation with a fraction of inspired oxygen (FiO2) value of 0.21 or 1.0. STUDY DESIGN: Blinded assessments were conducted at 2-3 years corrected age with the Bayley Scales of Infant and Toddler Development, Third Edition or the Ages and Stages Questionnaire by intention to treat. RESULTS: Of the 290 children enrolled, 40 could not be contacted and 10 failed to attend appointments. Among the 240 children for whom outcomes at age 2 years were available, 1 child had a lethal congenital anomaly, 1 child had consent for follow-up withdrawn, and 23 children died. The primary outcome, which was available in 238 (82%) of those randomized, occurred in 47 of the 117 (40%) children assigned to initial FiO2 0.21 and in 38 of the 121 (31%) assigned to initial FiO2 1.0 (OR, 1.47; 95% CI, 0.86-2.5; P = .16). No difference in NDI was found in 215 survivors randomized to FiO2 0.21 vs 1.0 (OR, 1.26; 95% CI, 0.70-2.28; P = .11). In post hoc exploratory analyses in the whole cohort, children with a 5-minute blood oxygen saturation (SpO2) <80% were more likely to die or to have NDI (OR, 1.85; 95% CI, 1.07-3.2; P = .03). CONCLUSIONS: Initial resuscitation of infants <32 weeks' gestation with initial FiO2 0.21 had no significant effect on death or NDI compared with initial FiO2 1.0. Further evaluation of optimum initial FiO2, including SpO2 targeting, in a large randomized controlled trial is needed. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Network Registry ACTRN 12610001059055 and the National Malaysian Research Registry NMRR-07-685-957.

Prediction of outcomes of extremely low gestational age newborns in Australia and New Zealand.

OBJECTIVE: To determine the accuracy of the National Institute of Child Health and Human Development (NICHD) calculator in predicting death and neurodevelopmental impairment in Australian and New Zealand infants. DESIGN: Population-based cohort study. SETTING: Australia and New Zealand. PATIENTS: Preterm infants 22-25 completed weeks gestation. INTERVENTIONS: Comparison of NICHD calculator predicted rates of death and death or neurodevelopmental impairment, with actual rates recorded in the Australian and New Zealand Neonatal Network cohort. MAIN OUTCOME MEASURES: Infant death and death or neurodevelopmental impairment rates. RESULTS: A total of 714 infants were included in the study. Of these infants, 100 (14.0%) were <24 weeks, 389 (54.5%) male, 529 (74.1%) were singletons, 42 (5.9%) had intrauterine growth restriction, 563 (78.9%) received antenatal steroids and 625 (87.5 %) were born in a tertiary hospital. There were 288 deaths (40.3%), 75 infants (10.5%) with neurodevelopment impairment and 363 (50.8%) with death or neurodevelopmental impairment. The area under the curve (AUC) for prediction of death and the composite death or neurodevelopmental impairment by the NICHD calculator in our population was 0.65(95% CI 0.61 to 0.69) and 0.65 (95% CI 0.61 to 0.69), respectively. When stratified and compared with gestational age outcomes, the AUC did not change substantially for the outcomes investigated. The calculator was less accurate with outcome predictions at the extreme categories of predicted outcomes-underestimation of outcomes for those predicted to have the lowest risk (<20%) and overestimation for those in the highest risk category (>80%). CONCLUSION: In our recent cohort of extremely preterm infants, the NICHD model does not accurately predict outcomes and is marginally better than gestational age based outcomes.

Targeted Oxygen in the Resuscitation of Preterm Infants, a Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Lower concentrations of oxygen (O2) (≤30%) are recommended for preterm resuscitation to avoid oxidative injury and cerebral ischemia. Effects on long-term outcomes are uncertain. We aimed to determine the effects of using room air (RA) or 100% O2 on the combined risk of death and disability at 2 years in infants <32 weeks' gestation. METHODS: A randomized, unmasked study designed to determine major disability and death at 2 years in infants <32 weeks' gestation after delivery room resuscitation was initiated with either RA or 100% O2 and which were adjusted to target pulse oximetry of 65% to 95% at 5 minutes and 85% to 95% until NICU admission. RESULTS: Of 6291 eligible patients, 292 were recruited and 287 (mean gestation: 28.9 weeks) were included in the analysis (RA: n = 144; 100% O2: n = 143). Recruitment ceased in June 2014, per the recommendations of the Data and Safety Monitoring Committee owing to loss of equipoise for the use of 100% O2. In non-prespecified analyses, infants <28 weeks who received RA resuscitation had higher hospital mortality (RA: 10 of 46 [22%]; than those given 100% O2: 3 of 54 [6%]; risk ratio: 3.9 [95% confidence interval: 1.1-13.4]; P = .01). Respiratory failure was the most common cause of death (n = 13). CONCLUSIONS: Using RA to initiate resuscitation was associated with an increased risk of death in infants <28 weeks' gestation. This study was not a prespecified analysis, and it was underpowered to address this post hoc hypothesis reliably. Additional data are needed.

Trends in Morbidity and Mortality of Extremely Preterm Multiple Gestation Newborns.

OBJECTIVES: To examine the risk of mortality and major morbidities in extremely preterm multiple gestation infants compared with singletons over time. METHODS: This is a retrospective study of 15,402 infants born ≤27 weeks' gestation, admitted to NICUs in the Australian and New Zealand Neonatal Network from 1995 to 2009. Mortality and major morbidities were compared between singletons and multiples across three 5-year epochs. RESULTS: Extreme preterm multiples were more likely to have lower birth weight; higher maternal age; and higher rates of assisted conception, antenatal steroid use, and cesarean delivery compared with singletons. The mortality rate was significantly higher in multiples compared with singletons even as there was a trend of decreasing gestational-age stratified mortality in multiples over the time period investigated. The rates of major morbidities or composite adverse outcomes were not different between multiples and singletons across all epochs. The adjusted odds ratio (AOR) for mortality in multiples was significantly higher in multiples compared with singletons (AOR 1.20, 95% confidence interval [CI] 1.08-1.34). There were no differences in the adjusted odds for poor outcomes in multiples compared with singletons in the most recent epoch: mortality (AOR 1.00, 95% CI 0.84-1.19), major morbidity (0.95, 95% CI 0.81-1.10), and composite adverse outcome (0.96, 95% CI 0.83-1.11). CONCLUSIONS: Over the 15-year period, the odds for mortality in extremely preterm NICU infants of multiple gestation was significantly higher compared with singletons. The adjusted odds of poor outcomes in multiples were not significantly different from that of singletons in the most recent epoch.

Hepatitis B virus surface antigen (HBsAg)-positive and HBsAg-negative hepatitis B virus infection among mother-teenager pairs 13 years after neonatal hepatitis B virus vaccination.

It is unclear whether a mother who is negative for hepatitis B virus surface antigen (HBsAg) but positive for hepatitis B virus (HBV) is at potential risk for mother-to-child transmission of HBV. This study, using a paired mother-teenager population, aimed to assess whether maternal HBsAg-negative HBV infection ((hn)HBI) is a significant source of child HBV infection (HBI). A follow-up study with blood collection has been conducted on the 93 mother-teenager pairs from the initial 135 pregnant woman-newborn pairs 13 years after neonatal HBV vaccination. Serological and viral markers of HBV have been tested, and phylogenetic analysis of HBV isolates has been done. The HBI prevalence was 1.9% (1 (hn)HBI/53) for teenage children of non-HBI mothers, compared with 16.7% (1 (hn)HBI/6) for those of (hn)HBI mothers and 2.9% (1 HBsAg-positive HBV infection [(hp)HBI]/34) for those of (hp)HBI mothers. Similar viral sequences have been found in one pair of whom both the mother and teenager have had (hn)HBI. In comparison with the (hp)HBI cases, those with (hn)HBI had a lower level of HBV load and a higher proportion of genotype-C strains, which were accompanied by differentiated mutations (Q129R, K141E, and Y161N) of the "a" determinant of the HBV surface gene. Our findings suggest that mother-to-teenager transmission of (hn)HBI can occur among those in the neonatal HBV vaccination program.

Donor age is a major determinant of success of oocyte donation/recipient programme.

BACKGROUND: In recent years, particularly in developed countries, women have tended to delay childbirth until over 40 years of age. Our study aims to identify whether the donor's age or recipient's age influences the pregnancy and live birth rate following oocyte recipient cycles. METHODS: A population study included 3889 fresh oocyte recipient cycles. Pregnancy and live delivery rates were compared in recipient age groups (<35, 35-39, 40-44 and ≥45 years) and donor age groups (<30, 30-34, 35-39 and ≥40 years). RESULTS: The highest live birth rate was of cycles in donors aged 30-34 years (25.0%), it decreased (P< 0.05) to 24.1% in donors aged <30 years, 20.7% in donors aged 35-39 years and 11.5% in donors aged ≥40 years. The multivariate analysis showed no significant differences in the success by recipient's age. Compared with cycles in donors aged 30-34 years, cycles in donors aged 35-39 years had 14 and 18% less chance to achieve a pregnancy [adjusted rate ratio (ARR) 0.86, 95% confidence interval (CI) 0.75-0.98] and a live delivery (ARR 0.82, 95% CI 0.71-0.96), while cycles in donors aged 40 years or older had 42 and 54% less chance to achieve a pregnancy (ARR 0.58, 95% CI 0.41-0.84) and a live delivery (ARR 0.46, 95% CI 0.29-0.73). CONCLUSIONS: Older recipients with younger donors did not have a poorer pregnancy outcome compared with younger recipients with younger donors. Choosing a donor aged <35 years would increase the chance of pregnancy and live delivery for older recipients.

Transfers of fresh blastocysts and blastocysts cultured from thawed cleavage embryos are associated with fewer miscarriages.

The literature shows an inconsistent relationship between miscarriage and assisted reproduction treatment factors. This study assessed the association between miscarriage and transfer of fresh or thawed embryos at cleavage/blastocyst stages. A population study included 52,874 pregnancies following autologous cycles. The miscarriage rate was compared by groups of transferred embryos (fresh cleavage embryo, fresh blastocyst, thawed cleavage embryo, blastocyst from thawed cleavage embryo, thawed blastocyst), IVF/intracytoplasmic sperm injection procedures, number of embryos transferred and woman's demographics. The overall miscarriage rate was 18.7%. Women aged 35-39 years and ≥40 years had a 51% and 177% increased hazard of miscarriage, respectively, compared with women <35 years. Women with history of miscarriage had 1.22 times hazard of miscarriage compared with those without previous miscarriage. Singleton pregnancies following fresh double-embryo transfer had 1.43 times higher rate of miscarriage than fresh single-embryo transfer. Fresh blastocyst transfer was associated with 8% less hazard of miscarriage than fresh cleavage-embryo transfer. Compared with pregnancies following thawed cleavage-embryo transfers, thawed blastocyst transfers were at 14% higher hazard of miscarriage. This study suggests that a practice model that includes transferring blastocysts and freezing cleavage embryos in fresh cycles would result in better outcomes.

Transfer of a selected single blastocyst optimizes the chance of a healthy term baby: a retrospective population based study in Australia 2004-2007.

BACKGROUND: The practice of single embryo transfer (SET) is highly accepted by clinicians in Australia. This study investigates whether the SET of blastocysts results in optimal perinatal outcomes. METHODS: This retrospective population-based study included 34 035 single or double embryo transfer cycles in women who had their first fresh autologous treatment in Australia during 2004-2007. Pregnancy, live delivery and 'healthy baby' (live born term singleton of > or = 2500 g birthweight and survived for at least 28 days without a notified/reported congenital anomaly) rates per transfer cycle were compared in four groups: selective single embryo transfer (SSET), unselective single embryo transfer (USSET), selective double embryo transfer (SDET) and unselective double embryo transfer (USDET). Live delivery and 'healthy baby' rates per transfer following SSET were further compared by number of embryos available. The analysis was stratified by woman's age and stage of embryo development. RESULTS: The highest rates of live delivery and 'healthy baby' per transfer cycle (46.2 and 38.0%) were achieved with transfer of a single blastocyst in women aged younger than 35 years. In women aged younger than 40 years, SSET had a significantly higher rate of 'healthy baby' per transfer cycle than did SDET regardless of stage of embryo development. In woman aged younger than 35 years who had SSET, there was no significant difference in live delivery and 'healthy baby' rates per transfer cycle whether two, three, four or five embryos were available. For all of these women, SSET of a cleavage embryo had significantly lower rates of live delivery and 'healthy baby' per transfer cycle compared with SSET of a blastocyst where only two blastocysts were available. CONCLUSIONS: Consultation with the patient with respect to the advantage of extended culture and selective single blastocyst transfer will result in better success rates following assisted reproductive technology treatment in Australia.

Better perinatal outcomes following transfer of fresh blastocysts and blastocysts cultured from thawed cleavage embryos: a population-based study.

BACKGROUND: Fresh embryo transfer results in higher live birth rates, while thawed embryo transfer appears to result in healthier babies. This study aims to investigate the association between the transfer of fresh or thawed embryos at the cleavage or blastocyst stage and the perinatal outcomes. METHODS: This analysis is a retrospective population-based study of 150 376 autologous embryo transfer cycles in Australia during 2002-2006. The rates of pregnancy, live delivery and 'healthy baby' delivery (a single baby born live at term, weighing >or=2500 g, surviving for at least 28 days post birth and not having congenital anomalies) were compared after transfer of fresh cleavage embryos, fresh blastocysts, thawed cleavage embryos, blastocysts from thawed cleavage embryos and thawed blastocysts. RESULTS: The live delivery rate was significantly higher for transfer of fresh blastocysts (27.9%) than for blastocysts cultured from thawed cleavage embryos (22.0%), fresh cleavage embryos (21.7%), thawed blastocysts (16.3%) and thawed cleavage embryos (15.2%). Compared with the transfer of fresh blastocysts, the likelihood of a 'healthy baby' was significantly lower for blastocysts from thawed cleavage embryos [adjusted odds ratios (AOR) 0.73, 95% confidence intervals (CI) 0.65-0.82], fresh cleavage embryos (AOR 0.67, 95% CI 0.64-0.69), thawed blastocysts (AOR 0.57, 95% CI 0.53-0.62) and thawed cleavage embryos (AOR 0.53, 95% CI 0.51-0.56). Of thaw cycles, transfers of thawed blastocysts (AOR 0.79, 95% CI 0.70-0.89) and thawed cleavage embryos (AOR 0.71, 95% CI 0.63-0.79) had significantly lower odds of 'healthy baby' than transfer of blastocysts from thawed cleavage embryos. CONCLUSIONS: These data suggest that an optimum practice model to maximize the outcomes of the birth of a 'healthy baby' is the transfer of blastocysts and the freezing of cleavage embryos in fresh cycles and subsequent transfer of blastocysts cultured from these thawed cleavage embryos.

Birth centers in Australia: a national population-based study of perinatal mortality associated with giving birth in a birth center.

BACKGROUND: Perinatal mortality is a rare outcome among babies born at term in developed countries after normal uncomplicated pregnancies; consequently, the numbers involved in large databases of routinely collected statistics provide a meaningful evaluation of these uncommon events. The National Perinatal Data Collection records the place of birth and information on the outcomes of pregnancy and childbirth for all women who give birth each year in Australia. Our objective was to describe the perinatal mortality associated with giving birth in "alongside hospital" birth centers in Australia during 1999 to 2002 using nationally collected data. METHODS: This population-based study included all 1,001,249 women who gave birth in Australia during 1999 to 2002. Of these women, 21,800 (2.18%) gave birth in a birth center. Selected perinatal outcomes (including stillbirths and neonatal deaths) were described for the 4-year study period separately for first-time mothers and for women having a second or subsequent birth. A further comparison was made between deaths of low-risk term babies born in hospitals compared with deaths of term babies born in birth centers. RESULTS: The total perinatal death rate attributed to birth centers was significantly lower than that attributed to hospitals (1.51/1,000 vs 10.03/1,000). The perinatal mortality rate among term births to primiparas in birth centers compared with term births among low-risk primiparas in hospitals was 1.4 versus 1.9 per 1,000; the perinatal mortality rate among term births to multiparas in birth centers compared with term births among low-risk multiparas in hospitals was 0.6 versus 1.6 per 1,000. CONCLUSIONS: This study using Australian national data showed that the overall rate of perinatal mortality was lower in alongside hospital birth centers than in hospitals irrespective of the mother's parity.

The urban-remote divide for Indigenous perinatal outcomes.

OBJECTIVE: To determine whether remoteness category of residence of Indigenous women affects the perinatal outcomes of their newborn infants. DESIGN AND PARTICIPANTS: A population-based study of 35 240 mothers identified as Indigenous and their 35 658 babies included in the National Perinatal Data Collection in 2001-2004. MAIN OUTCOME MEASURES: Australian Standard Geographical Classification remoteness category, birthweight, Apgar score at 5 minutes, stillbirth, gestational age and a constructed measure of perinatal outcomes of babies called "healthy baby" (live birth, singleton, 37-41 completed weeks' gestation, 2500-4499 g birthweight, and an Apgar score at 5 minutes >or= 7). RESULTS: The proportion of healthy babies in remote, regional and city areas was 74.9%, 77.7% and 77.6%, respectively. After adjusting for age, parity, smoking and diabetes or hypertension, babies born to mothers in remote areas were less likely to satisfy the study criteria of being a healthy baby (adjusted odds ratio [AOR], 0.87; 95% CI, 0.81-0.93) compared with those born in cities. Babies born to mothers living in remote areas had higher odds of being of low birthweight (AOR, 1.09; 95% CI, 1.01-1.19) and being born with an Apgar score < 7 at 5 minutes (AOR, 1.63; 95% CI, 1.39-1.92). CONCLUSIONS: Only three in four babies born to Indigenous mothers fell into the "healthy baby" category, and those born in more remote areas were particularly disadvantaged. These findings demonstrate the continuing need for urgent and concerted action to address the persistent perinatal inequity in the Indigenous population.

Birth outcomes associated with interventions in labour amongst low risk women: a population-based study.

INTRODUCTION: Despite concern over high rates of operative birth in many countries, particularly amongst low risk healthy women, the obstetric antecedents of operative birth are poorly described. We aimed to determine the association between interventions introduced during labour with interventions in the birth process amongst women of low medical risk. METHODS: We undertook a population-based descriptive study of all low risk women amongst the 753,895 women who gave birth in Australia during 2000-2002. Adjusted odds ratios (AOR) were calculated using multinomial logistic regression to describe the association between mode of birth and each of four labour intervention subgroups separately for primiparous and multiparous women. RESULTS: We observed increased rates of operative birth in association with each of the interventions offered during the labour process. For first time mothers the association was particularly strong. CONCLUSIONS: This study underlines the need for better clinical evidence of the effects of epidurals and pharmacological agents introduced in labour. At a population level it demonstrates the magnitude of the fall in rates of unassisted vaginal birth in association with a cascade of interventions in labour and interventions at birth particularly amongst women with no identified risk markers and having their first baby. This information may be useful for women wanting to explore other methods of influencing the course of labour and the management of pain in labour, especially in their endeavour to achieve a normal vaginal birth.

Does size matter? A population-based study of birth in lower volume maternity hospitals for low risk women.

OBJECTIVE: To study the association between volume of hospital births per annum and birth outcome for low risk women. DESIGN: Population-based study using the National Perinatal Data Collection (NPDC). SETTING: Australia. PARTICIPANTS: Of 750,491 women who gave birth during 1999-2001, there were 331,147 (47.14%) medically 'low risk' including 132,696 (40.07%) primiparae and 198,451 (59.93%) multiparae. METHODS: The frequency of each birth and infant outcome was described according to the size of the hospital where birth took place. We investigated whether unit size (defined by volume) was an independent risk factor for each outcome factor using public hospitals with greater than 2000 births per annum as a reference point. MAIN OUTCOME MEASURES: Rates of intervention at birth and neonatal mortality for low risk women in relation to hospitals with <100, 100-500, 501-1000, 1001-2000 and >2001 births per annum. RESULTS: Neonatal death was less likely in hospitals with less than 2000 births per annum regardless of parity. For multiparous low risk women in hospitals of 100 and 500 births per annum compared with hospitals of >2000 births per annum the adjusted odds of neonatal mortality [adjusted odds ratio (AOR) 0.36; 99% confidence interval (CI) 0.14-0.93]. For low risk primiparous women in hospitals with less than 100 births per annum, there were lower rates of induction of labour (AOR 0.62; 99% CI 0.54-0.73); intrathecal analgesia/anaesthesia (AOR 0.34; 99% CI 0.28-0.42); instrumental birth (AOR 0.80; 99% CI 0.69-0.93); caesarean section after labour (AOR 0.59; 99% CI 0.49-0.72) and admission to a neonatal unit (AOR 0.15; 99% CI 0.10-0.22) and for low risk multiparous women in hospitals with less than 100 births per annum: induction (AOR 0.69; 99% CI 0.62-0.76); intrathecal analgesia/anaesthesia (AOR 0.32; 99% CI 0.29-0.36); instrumental birth (AOR 0.52; 99% CI 0.41-0.67); caesarean section after labour (AOR 0.41; 99% CI 0.33-0.52); and admission to a neonatal unit (AOR 0.09; 99% CI 0.07-0.12). CONCLUSIONS: In Australia, lower hospital volume is not associated with adverse outcomes for low risk women.

Preterm birth and low birth weight after assisted reproductive technology-related pregnancy in Australia between 1996 and 2000.

OBJECTIVE: To describe patterns of preterm birth and low birth weight (LBW) for infants born after assisted reproductive technology (ART) and determine whether these were associated with maternal or treatment characteristics. DESIGN: Retrospective cohort study of national population data of infants conceived through ART. SETTING: Australian birth records from 1996 to 2000. PATIENT(S): Eighteen thousand, four hundred twenty-nine liveborn and stillborn infants conceived through ART. INTERVENTION(S): In vitro fertilization, intracytoplasmic sperm injection, and gamete intrafallopian transfer. MAIN OUTCOME MEASURE(S): Preterm birth and LBW. RESULT(S): Preterm birth and LBW were more common among singletons and twins conceived with IVF and born to nulliparous mothers. Preterm birth and LBW were, respectively, 1.3 times and 1.5 times more likely to occur among singletons conceived by transfer of fresh embryos, compared with transfer of frozen embryos. Preterm birth and LBW was more common among couples who had female-factor infertility compared with male-factor infertility. CONCLUSION(S): The transfer of fresh embryos and female-factor infertility were independently associated with preterm birth and LBW for both singletons and twins after ART.

Primary postpartum haemorrhage in an Australian tertiary hospital: a case-control study.

The present study aimed to determine the incidence of primary postpartum haemorrhage (PPH) after vaginal birth at an Australian tertiary hospital, and to investigate risk factors for primary PPH at this hospital. A case-control study of women delivering vaginally at a tertiary hospital from February to June 2003 was performed. Demographic, antenatal, intrapartum, treatment and outcome data were abstracted from patient records. The study population comprised 125 cases and 125 controls, with a primary PPH rate of 12.1 per 100 vaginal births. Risk factors on multivariate analysis were past history of PPH, second stage labour > 60 min, forceps delivery, and incomplete placenta/ragged membranes.