Safety and Immunogenicity of an Investigational Respiratory Syncytial Virus Vaccine (RSVPreF3) in Mothers and Their Infants: A Phase 2 Randomized Trial.

BACKGROUND: In a phase 1/2 study, a maternal respiratory syncytial virus vaccine candidate (RSVPreF3) demonstrated an acceptable safety profile and efficiently increased RSV-specific humoral immune responses in non-pregnant women. METHODS: In this phase 2 observer-blind, placebo-controlled, randomized clinical trial (NCT04126213), the safety of RSVPreF3 (60 or 120 µg), administered during late second or third trimester, was evaluated in 213 18- to 40-year-old healthy pregnant women through 6 months postdelivery and their offspring through infancy; immunogenicity was evaluated through day 43 postdelivery and day 181 postbirth, respectively. RESULTS: RSVPreF3 was well tolerated. No pregnancy-related or neonatal adverse events of special interest were considered vaccine/placebo related. In the 60 and 120 µg RSVPreF3 groups: (1) neutralizing antibody (nAb) titers in mothers increased 12.7- and 14.9-fold against RSV-A and 10.6- and 13.2-fold against RSV-B, respectively, 1 month postvaccination and remained 8.9-10.0-fold over prevaccination at day 43 postdelivery; (2) nAb titers were consistently higher compared to placebo recipients; (3) placental transfer ratios for anti-RSVPreF3 antibodies at birth were 1.62 and 1.90, respectively, and (4) nAb levels in infants were highest at birth and declined through day 181 postbirth. CONCLUSIONS: RSVPreF3 maternal vaccination had an acceptable safety risk profile and induced robust RSV-specific immune responses with successful antibody transfer to their newborns. CLINICAL TRIALS REGISTRATION: NCT04126213.

WHAT IS THE CONTEXT?: Infants, especially those less than 6 months of age, are at increased risk of lung infection caused by respiratory syncytial virus (RSV). However, this risk could be reduced with maternal vaccination against RSV during pregnancy. A previous clinical trial found that a vaccine candidate (named RSVPreF3) was well tolerated when given to non-pregnant women. WHAT IS NEW?: In pregnant women, RSVPreF3 was also well tolerated. Occurrence of unsolicited adverse events was similar between vaccine and placebo recipients. None of the serious adverse events or events of interest for pregnant women or newborns were considered related to the study intervention. One month after vaccination, mothers who received RSVPreF3 had 11­15 times higher levels of antibodies against RSV than before vaccination. These antibody levels remained similar until 43 days after delivery. In the infants born to mothers vaccinated during pregnancy with RSVPreF3, antibody levels were highest at birth, when levels were higher than in their mothers, and declined through day 181 postbirth. WHAT IS THE IMPACT?: RSVPreF3 had an acceptable safety risk profile in pregnant women and their babies. This vaccine induced potent immune responses against RSV, with maternal antibodies transferred to infants of the vaccinated mothers.

The randomized Tracheal Occlusion To Accelerate Lung growth (TOTAL)-trials on fetal surgery for congenital diaphragmatic hernia: reanalysis using pooled data.

BACKGROUND: Two randomized controlled trials compared the neonatal and infant outcomes after fetoscopic endoluminal tracheal occlusion with expectant prenatal management in fetuses with severe and moderate isolated congenital diaphragmatic hernia, respectively. Fetoscopic endoluminal tracheal occlusion was carried out at 27+0 to 29+6 weeks' gestation (referred to as "early") for severe and at 30+0 to 31+6 weeks ("late") for moderate hypoplasia. The reported absolute increase in the survival to discharge was 13% (95% confidence interval, -1 to 28; P=.059) and 25% (95% confidence interval, 6-46; P=.0091) for moderate and severe hypoplasia. OBJECTIVE: Data from the 2 trials were pooled to study the heterogeneity of the treatment effect by observed over expected lung-to-head ratio and explore the effect of gestational age at balloon insertion. STUDY DESIGN: Individual participant data from the 2 trials were reanalyzed. Women were assessed between 2008 and 2020 at 14 experienced fetoscopic endoluminal tracheal occlusion centers and were randomized in a 1:1 ratio to either expectant management or fetoscopic endoluminal tracheal occlusion. All received standardized postnatal management. The combined data involved 287 patients (196 with moderate hypoplasia and 91 with severe hypoplasia). The primary endpoint was survival to discharge from the neonatal intensive care unit. The secondary endpoints were survival to 6 months of age, survival to 6 months without oxygen supplementation, and gestational age at live birth. Penalized regression was used with the following covariates: intervention (fetoscopic endoluminal tracheal occlusion vs expectant), early balloon insertion (yes vs no), observed over expected lung-to-head ratio, liver herniation (yes vs no), and trial (severe vs moderate). The interaction between intervention and the observed over expected lung-to-head ratio was evaluated to study treatment effect heterogeneity. RESULTS: For survival to discharge, the adjusted odds ratio of fetoscopic endoluminal tracheal occlusion was 1.78 (95% confidence interval, 1.05-3.01; P=.031). The additional effect of early balloon insertion was highly uncertain (adjusted odds ratio, 1.53; 95% confidence interval, 0.60-3.91; P=.370). When combining these 2 effects, the adjusted odds ratio of fetoscopic endoluminal tracheal occlusion with early balloon insertion was 2.73 (95% confidence interval, 1.15-6.49). The results for survival to 6 months and survival to 6 months without oxygen dependence were comparable. The gestational age at delivery was on average 1.7 weeks earlier (95% confidence interval, 1.1-2.3) following fetoscopic endoluminal tracheal occlusion with late insertion and 3.2 weeks earlier (95% confidence interval, 2.3-4.1) following fetoscopic endoluminal tracheal occlusion with early insertion compared with expectant management. There was no evidence that the effect of fetoscopic endoluminal tracheal occlusion depended on the observed over expected lung-to-head ratio for any of the endpoints. CONCLUSION: This analysis suggests that fetoscopic endoluminal tracheal occlusion increases survival for both moderate and severe lung hypoplasia. The difference between the results for the Tracheal Occlusion To Accelerate Lung growth trials, when considered apart, may be because of the difference in the time point of balloon insertion. However, the effect of the time point of balloon insertion could not be robustly assessed because of a small sample size and the confounding effect of disease severity. Fetoscopic endoluminal tracheal occlusion with early balloon insertion in particular strongly increases the risk for preterm delivery.

Randomized Trial of Fetal Surgery for Moderate Left Diaphragmatic Hernia.

BACKGROUND: Fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased postnatal survival among infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia on the left side, but data are lacking to inform its effects in infants with moderate disease. METHODS: In this open-label trial conducted at many centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with a moderate isolated congenital diaphragmatic hernia on the left side to FETO at 30 to 32 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcomes were infant survival to discharge from a neonatal intensive care unit (NICU) and survival without oxygen supplementation at 6 months of age. RESULTS: In an intention-to-treat analysis involving 196 women, 62 of 98 infants in the FETO group (63%) and 49 of 98 infants in the expectant care group (50%) survived to discharge (relative risk , 1.27; 95% confidence interval [CI], 0.99 to 1.63; two-sided P = 0.06). At 6 months of age, 53 of 98 infants (54%) in the FETO group and 43 of 98 infants (44%) in the expectant care group were alive without oxygen supplementation (relative risk, 1.23; 95% CI, 0.93 to 1.65). The incidence of preterm, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (44% vs. 12%; relative risk, 3.79; 95% CI, 2.13 to 6.91), as was the incidence of preterm birth (64% vs. 22%, respectively; relative risk, 2.86; 95% CI, 1.94 to 4.34), but FETO was not associated with any other serious maternal complications. There were two spontaneous fetal deaths (one in each group) without obvious cause and one neonatal death that was associated with balloon removal. CONCLUSIONS: This trial involving fetuses with moderate congenital diaphragmatic hernia on the left side did not show a significant benefit of FETO performed at 30 to 32 weeks of gestation over expectant care with respect to survival to discharge or the need for oxygen supplementation at 6 months. FETO increased the risks of preterm, prelabor rupture of membranes and preterm birth. (Funded by the European Commission and others; TOTAL ClinicalTrials.gov number, NCT00763737.).

Spontaneous twin anemia polycythemia sequence: diagnosis, management, and outcome in an international cohort of 249 cases.

BACKGROUND: Twin anemia polycythemia sequence is a chronic form of unbalanced fetofetal transfusion through minuscule placental anastomoses in monochorionic twins, leading to anemia in the donor and polycythemia in the recipient. Owing to the low incidence of twin anemia polycythemia sequence, data on diagnosis, management, and outcome are limited. OBJECTIVE: This study aimed to investigate the diagnosis, management, and outcome in a large international cohort of spontaneous twin anemia polycythemia sequence. STUDY DESIGN: Data from the international twin anemia polycythemia sequence registry, retrospectively collected between 2014 and 2019, were used for this study. A total of 17 fetal therapy centers contributed to the data collection. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. RESULTS: A total of 249 cases of spontaneous twin anemia polycythemia sequence were included in this study, 219 (88%) of which were diagnosed antenatally and 30 (12%) postnatally. Twin anemia polycythemia sequence was diagnosed antenatally at a median gestational age of 23.7 weeks (interquartile range, 9.7-28.8; range, 15.1-35.3). Antenatal management included laser surgery in 39% (86 of 219), expectant management in 23% (51 of 219), delivery in 16% (34 of 219), intrauterine transfusion (with partial exchange transfusion) in 12% (26 of 219), selective feticide in 8% (18 of 219), and termination of pregnancy in 1% (3 of 219) of cases. Perinatal mortality rate was 15% (72 of 493) for the total group, 22% (54 of 243) for donors, and 7% (18 of 242) for recipients (P<.001). Severe neonatal morbidity occurred in 33% (141 of 432) of twins with twin anemia polycythemia sequence and was similar for donors (32%; 63 of 196) and recipients (33%; 75 of 228) (P=.628). Independent risk factors for spontaneous perinatal mortality were donor status (odds ratio, 3.8; 95% confidence interval, 1.9-7.5; P<.001), antenatal twin anemia polycythemia sequence stage (odds ratio, 6.3; 95% confidence interval, 1.4-27.8; P=.016 [stage 2]; odds ratio, 9.6; 95% confidence interval, 2.1-45.5; P=.005 [stage 3]; odds ratio, 20.9; 95% confidence interval, 3.0-146.4; P=.002 [stage 4]), and gestational age at birth (odds ratio, 0.8; 95% confidence interval, 0.7-0.9; P=.001). Independent risk factors for severe neonatal morbidity were antenatal twin anemia polycythemia sequence stage 4 (odds ratio, 7.9; 95% confidence interval, 1.4-43.3; P=.018) and gestational age at birth (odds ratio, 1.7; 95% confidence interval, 1.5-2.1, P<.001). CONCLUSION: Spontaneous twin anemia polycythemia sequence can develop at any time in pregnancy from the beginning of the second trimester to the end of the third trimester. Management for twin anemia polycythemia sequence varies considerably, with laser surgery being the most frequent intervention. Perinatal mortality and severe neonatal morbidity were high, the former especially so in the donor twins.

Post-Laser Twin Anemia Polycythemia Sequence: Diagnosis, Management, and Outcome in an International Cohort of 164 Cases.

The aim of this study was to investigate the management and outcome in the post-laser twin anemia polycythemia sequence (TAPS). Data of the international TAPS Registry, collected between 2014 and 2019, were used for this study. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. A total of 164 post-laser TAPS pregnancies were included, of which 92% (151/164) were diagnosed antenatally and 8% (13/164) postnatally. The median number of days between laser for TTTS and detection of TAPS was 14 (IQR: 7-28, range: 1-119). Antenatal management included expectant management in 43% (62/151), intrauterine transfusion with or without partial exchange transfusion in 29% (44/151), repeated laser surgery in 15% (24/151), selective feticide in 7% (11/151), delivery in 6% (9/151), and termination of pregnancy in 1% (1/151). The median gestational age (GA) at birth was 31.7 weeks (IQR: 28.6-33.7; range: 19.0-41.3). The perinatal mortality rate was 25% (83/327) for the total group, 37% (61/164) for donors, and 14% (22/163) for recipients (p < 0.001). Severe neonatal morbidity was detected in 40% (105/263) of the cohort and was similar for donors (43%; 51/118) and recipients (37%; 54/145), p = 0.568. Independent risk factors for spontaneous perinatal mortality were antenatal TAPS Stage 4 (OR = 3.4, 95%CI 1.4-26.0, p = 0.015), TAPS donor status (OR = 4.2, 95%CI 2.1-8.3, p < 0.001), and GA at birth (OR = 0.8, 95%CI 0.7-0.9, p = 0.001). Severe neonatal morbidity was significantly associated with GA at birth (OR = 1.5, 95%CI 1.3-1.7, p < 0.001). In conclusion, post-laser TAPS most often occurs within one month after laser for TTTS, but may develop up to 17 weeks after initial surgery. Management is mostly expectant, but varies greatly, highlighting the lack of consensus on the optimal treatment and heterogeneity of the condition. Perinatal outcome is poor, particularly due to the high rate of perinatal mortality in donor twins.

Fetoscopic endoluminal tracheal occlusion and reestablishment of fetal airways for congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a congenital anomaly with high mortality and morbidity mainly due to pulmonary hypoplasia and hypertension. Temporary fetal tracheal occlusion to promote prenatal lung growth may improve survival. Entrapment of lung fluid stretches the airways, leading to lung growth. METHODS: Fetal endoluminal tracheal occlusion (FETO) is performed by percutaneous sono-endoscopic insertion of a balloon developed for interventional radiology. Reversal of the occlusion to induce lung maturation can be performed by fetoscopy, transabdominal puncture, tracheoscopy, or by postnatal removal if all else fails. RESULTS: FETO and balloon removal have been shown safe in experienced hands. This paper deals with the technical aspects of balloon insertion and removal. While FETO is invasive, it has minimal maternal risks yet can cause preterm birth potentially offsetting its beneficial effects. CONCLUSION: For left-sided severe and moderate CDH, the procedure is considered investigational and is currently being evaluated in a global randomized clinical trial (https://www.totaltrial.eu/). The procedure can be clinically offered to fetuses with severe right-sided CDH.

The Impact of Entry Technique and Access Diameter on Prelabour Rupture of Membranes Following Primary Fetoscopic Laser Treatment for Twin-Twin Transfusion Syndrome.

OBJECTIVE: To evaluate the impact of entry method and access diameter at fetoscopic surgery for twin-twin transfusion syndrome in twin pregnancies with at least one survivor. The outcomes evaluated were prelabour rupture of membranes (PROM) and birth <4 weeks, preterm birth (PTB) <28 weeks, and latency to birth. METHODS: A retrospective analysis of prospectively collected data of consecutive laser procedures from 6 centers was performed. Three entry methods (sheath + trocar; cannula + trocar; cannula + Seldinger) and 6 access diameters (2.3, 3.0, 3.3, 3.5, 3.8, 4.0 mm) were used. Exclusion criteria were subsequent invasive interventions, termination of pregnancy or double fetal death after laser. Multivariate analysis was performed to determine risk factors for the study outcomes. RESULTS: Six hundred seventy three fetoscopic laser cases were analyzed. The use of different entry methods and access diameters did not affect PROM or birth <4 weeks, or latency from laser to birth. Access diameter was associated with PTB <28 weeks. Cervical length was associated with PROM and birth <4 weeks, and latency from laser to birth. CONCLUSION: Instrument choice at fetoscopic laser procedures did not affect outcomes <4 weeks. Access diameter may affect the likelihood for PTB <28 weeks. Cervical length is critically associated with obstetrical outcomes following laser surgery.

Tracheal Atresia with Segmental Esophageal Duplication: An Unusual Anatomic Arrangement.

An unusual anatomic configuration of segmental tracheal agenesis/atresia with esophageal duplication on autopsy in a fetus that demised in utero at 29 weeks is reported. The mother was scanned initially for a cardiac anomaly at 20 weeks and on follow-up scan at 27 weeks had polyhydramnios and underwent amnioreduction. The final autopsy diagnosis was vertebral, ano-rectal, cardiac, tracheoesophageal, renal, and limb malformations (VACTERL). We discuss the autopsy findings along with the embryological mechanisms and compare the configuration with Floyd's classification for tracheal agenesis. The difficulties in prenatal diagnosis are discussed.

Surgical management of abnormally invasive placenta: a retrospective cohort study demonstrating the benefits of a standardized operative approach.

INTRODUCTION: Abnormally invasive placenta is a major cause of maternal morbidity and mortality. The aim of this study was to assess the effectiveness of a standardized operative approach performed by gynecological oncologists in the surgical management of abnormally invasive placenta. MATERIALS AND METHODS: We performed a retrospective analysis of all cases of morbid placental adherence managed at the Mater Mothers' Hospitals, Brisbane, Australia between January 2000 and June 2013. A standard operative approach involving extensive retro-peritoneal and bladder dissection before delivery of the fetus, was undertaken when a gynecological oncologist was present at the start of the procedure. Main outcome measures were estimated blood loss, transfusion requirements, and maternal and neonatal morbidity. RESULTS: The study includes 98 cases of histologically confirmed abnormally invasive placenta. Median estimated blood loss for the entire cohort was 2150 mL (range 300-11 500 mL). Women were divided into three groups, (1) those who had a gynecological oncologist present at the start of the procedure (group 1; n = 43), (2) those who had a gynecological oncologist called in during the procedure (group 2; n = 23), and (3) those who had no gynecological oncologist involved (group 3; n = 32). Group 2 had a significantly higher blood loss than the other groups (p = 0.001) (median 4400 mL). Transfusion requirements were higher in groups 2 and 3 compared with group 1 (p = 0.004). Other maternal and neonatal morbidity was similar across all three groups. CONCLUSION: This study supports the early presence of a gynecological oncologist at delivery when abnormally invasive placenta is suspected and demonstrates that a "call if needed" approach is not acceptable for these complex cases.

Prenatal management of the fetus with isolated congenital diaphragmatic hernia in the era of the TOTAL trial.

Congenital diaphragmatic hernia (CDH) may be isolated or associated with other structural anomalies, the latter with poor prognosis. The defect allows viscera to herniate through the defect into the chest, competing for space with the developing lungs. At birth, pulmonary hypoplasia leads to respiratory insufficiency and persistent pulmonary hypertension that is lethal in up to 30% of patients. When isolated, survival chances can be predicted by antenatal measurement of lung size and liver herniation. Chromosomal microarrays and exome sequencing contribute to understanding genetic factors underlying isolated CDH. Prenatal intervention aims at stimulating lung development, clinically achieved by percutaneous fetal endoscopic tracheal occlusion (FETO) under local anesthesia. The Tracheal Occlusion To Accelerate Lung growth trial (www.totaltrial.eu) is an international randomized trial investigating the role of fetal therapy for severe and moderate pulmonary hypoplasia. Despite an apparent increase in survival following FETO, the search for lesser invasive and more potent prenatal interventions must continue.

Fetoscopic endoluminal tracheal occlusion (FETO) for congenital diaphragmatic hernia in Australia and New Zealand: are we willing, able, both or neither?

AIM: An estimated 140 pregnancies are diagnosed with congenital diaphragmatic hernia (CDH) in Australia and New Zealand each year, with these fetuses having a less than even chance of 1-year survival. Fetoscopic endoluminal tracheal occlusion (FETO) is a relatively new technique that offers a prenatal interventional strategy for selective cases of CDH. This is not routinely offered in Australia or New Zealand. The aim of this systematic review is to critically appraise controlled clinical trials investigating the role of FETO in moderate and severe isolated CDH and explore whether this treatment is justified within our region. METHODS: A systematic literature search of multiple electronic databases was undertaken, with restrictions to human subjects and controlled clinical trials. RESULTS: Nine relevant studies were identified. No current evidence was found in favour of FETO for moderate severity CDH. For severe CDH, the most recent evidence demonstrates significantly improved survival following FETO performed using contemporary percutaneous minimally invasive techniques. Optimum timing for balloon insertion, removal and occlusion duration remains conjectural. Substantial variation in survival rates observed among control groups highlights the impact of post-natal care in prenatally diagnosed CDH. CONCLUSION: Until recently, evidence to support a role for FETO in prenatal CDH management was weak. Recently reported and ongoing controlled trials give cause for optimism, with improved FETO safety and increased survival reported for severe CDH cases. Should Australasia embrace FETO for selected CDH cases, a co-ordinated, evidence-informed service should be established under the guidance of experienced international partnerships.

The outcome of isolated primary fetal hydrothorax: a 10-year review from a tertiary center.

INTRODUCTION: The management of primary fetal pleural effusion remains a challenge for clinicians given the paucity of clinical information to guide practice. MATERIALS AND METHODS: A retrospective descriptive study of cases referred for management to our fetal therapy center over a 10-year period. Survival to hospital discharge was evaluated against case characteristics and prenatal intervention. For this study, we categorized the severity of the pleural effusion at diagnosis as mild, moderate or severe, and the clinical course as regression, stable or progression. RESULTS: Forty-five of the 103 pregnancies complicated by fetal pleural effusions during the study period were managed for primary effusions. Termination of pregnancy was requested in 6 cases. Thirty-nine pregnancies continued management, with 14 undergoing prenatal intervention. The overall survival rate to hospital discharge was 51%, including 7 survivors after prenatal intervention. The rate of survival was low if the effusion was categorized as severe at diagnosis or if there was progression of the clinical course. CONCLUSIONS: Case characteristics at the time of diagnosis and clinical course can be used to guide patient counseling and decision-making regarding fetal therapy. Prenatal intervention may improve the chance of survival in cases with characteristics associated with a poor prognosis.

Customised birthweight models: do they increase identification of at-risk infants?

AIM: The study aims to describe the cohort of women and babies who are classified as small-for-gestational age (SGA) at term by both an Australian customised birthweight model (CBM) and a commonly used population-based standard, and to investigate and compare the utility of these models in identifying babies at risk of experiencing adverse outcomes METHODS: Routinely collected data on 54 890 singleton-term births at the Mater Mothers' Hospitals, Brisbane, with birthweight less than 4000 g between January 1997 and December 2008, was extracted. Each birth was classified as SGA (<10th centile) or not SGA by either and/or both methods: population-based standards (SGApop ) and CBM (SGAcust ). Babies classified as SGApop , SGAcust or SGAboth were compared with those not classified as SGA by both methods using relative risk and 95% confidence interval, and those only classified as SGAcust were compared with those only classified as SGApop . Maternal demographics, maternal risk factors for fetal growth restriction, pregnancy and labour complications and adverse neonatal outcomes are reported. RESULTS: A total of 4768 (8.7%) births were classified as SGApop , while 6479 (11.8%) were SGAcust of whom 4138 (63.9%) were also classified as SGApop . Maternal risk factors such as smoking and hypertension were statistically higher for the SGAcust group when compared with SGApop . For the majority of adverse neonatal outcomes, a trend was noted to increased identification using the CBM. CONCLUSION: The CBM provides a modest improvement when compared to a population-based standard to identity term infants at birth who are at risk of adverse neonatal outcomes.

Hospital versus outpatient care for preterm pre-labour rupture of membranes.

BACKGROUND: To report the outcomes of women admitted following preterm pre-labour rupture of membranes (pPROM) and to determine whether the location of care (hospital vs outpatient) influences maternal and perinatal outcomes. METHODS: A retrospective cohort study was performed using routinely collected de-identified data of 144 women (between June 2007 and June 2011) who presented to the Mater Mother's Hospital, Brisbane, Australia, with pPROM (prior to 34 weeks 0 days gestation) and who remained undelivered after 72 h from the time of ruptured membranes. Outcomes were compared for women who were subsequently managed as an outpatient (n = 53) versus those who were managed in hospital (n = 91). The two primary outcome measures were composite outcomes of (i) maternal morbidity and (ii) perinatal morbidity/mortality. The composite outcome of maternal morbidity comprised one or more of antepartum haemorrhage, clinical chorioamnionitis and/or endometritis, cord prolapse, blood transfusion, wound infection/haematoma/dehiscence/seroma. The composite outcome of perinatal morbidity/mortality comprised one or more of stillbirth, neonatal death, respiratory distress syndrome, neonatal infection, chronic neonatal lung disease, intraventricular haemorrhage, periventricular leukomalacia and necrotising enterocolitis. RESULTS: When adjusted for confounders, there was no difference between hospital care and outpatient care in the composite outcome measure of perinatal morbidity/mortality (aOR 1.37; 95%CI 0.55-3.47) or the composite outcome measure of maternal morbidity (aOR 1.62; 95%CI 0.67-3.89). CONCLUSIONS: Women with pPROM who remain undelivered after 72 h and are managed out of hospital do not appear to have significant differences in major adverse maternal or perinatal outcomes compared with those managed as inpatients.

A survey of policies for the monitoring of fetal growth in Australian and New Zealand hospitals.

BACKGROUND: Fetal growth restriction is associated with increased perinatal mortality and morbidity and adverse developmental outcome. However, evidence is lacking on optimal approaches to antenatal screening of fetal size and growth. AIMS: To determine the current policies and practices for assessment of fetal size and monitoring fetal growth with a view to informing future research in this area. METHODS: Web-based survey of Directors of Obstetrics and Gynaecology in maternity hospitals with over 1000 births per annum in Australia and New Zealand (ANZ). The survey focussed on the existence and details of guidelines for the clinical assessment of fetal size and growth in low- and high-risk pregnancies, techniques utilised for clinical assessment of fetal size and growth and the use of birthweight charts. RESULTS: Completed surveys were received from 49 (66%) of the 74 hospitals surveyed. Forty-four percent of hospitals have a fetal growth screening guideline, with abdominal palpation and symphysis fundal height (SFH) measurement the most common screening tools. Seventy-nine percent indicated that obstetric or birthweight charts were in use; 39% were unsure which chart/s were in use, and use differed by region. There was reasonable agreement regarding decision to take action following discrepancies between gestational age and SFH. Sixty-five percent of participants are interested in participating in a randomised controlled trial in this area. CONCLUSIONS: The survey revealed that while there is some agreement with respect to methods used in the clinical assessment of fetal size and growth, there is interest in ANZ hospitals to pursue this area of research further.

Neurodevelopmental outcome and risk factors for disability for twin-twin transfusion syndrome treated with laser surgery.

OBJECTIVE: This study was performed to report the neurodevelopmental outcome of survivors of twin-twin transfusion syndrome (TTTS) treated with laser surgery and to determine the risk factors for neurodevelopmental disability. STUDY DESIGN: A prospective study of TTTS cases treated with laser was performed. Survivors were assessed at 2 years corrected for prematurity. Neurodevelopmental disability was defined as the presence of cerebral palsy, deafness, blindness, or cognitive impairment with a developmental score >2 SDs below the mean. RESULTS: A total of 75 TTTS pregnancies were treated with a perinatal survival rate of 79.3%. A total of 113 survivors were assessed. The rate of cerebral palsy was 4.4% and cognitive impairment was 8%, with a neurodevelopmental disability rate of 12.4%. Quintero stage was the only independent risk factor for neurodevelopmental disability. CONCLUSION: The incidence of neurodevelopmental disability in TTTS survivors treated with laser is considerable, with Quintero stage being an independent risk factor.

Validation and refinement of an Australian customised birthweight model using routinely collected data.

BACKGROUND: Published customised birthweight models designed to account for individual constitutional variation have not been validated in an independent population to verify the results. AIMS: To validate our previously reported customised birthweight model with additional data from the same hospital and to revise this model using a larger, more refined dataset. METHODS: With the accumulation of further data, a set of coefficients was derived based on the 12-year dataset. Using shrinkage statistics, records between July 2005 and December 2008 were used to validate the model. Stepwise multiple regression using a more refined dataset of births between January 1997 and December 2008 was used to derive updated coefficients. Performance of the model was assessed using individualised birthweight ratios and the absolute difference between customised and actual birthweight. RESULTS: Previous coefficients were validated, with shrinkage of less than 1%, indicating that the model is stable over time. An updated set of coefficients based on a dataset of 61,630 births, including refined ethnicity categories and the addition of a smoking term, is presented, which resulted in improved model statistics (primarily an improved multiple correlation coefficient of 0.51). CONCLUSION: The customised birthweight model appears to be stable over time in the same hospital. Initial comparisons to literature indicate that models from different geographic locations may lead to similar coefficients; but, there remains a need to formally assess this aspect of birthweight models. The updated coefficients differ slightly from those previously published and are considered superior because of refinement in the dataset.

Selective fetoscopic laser ablation in 100 consecutive pregnancies with severe twin-twin transfusion syndrome.

AIMS: To report the perinatal outcomes of a large series of twin pregnancies with severe twin-twin transfusion syndrome (TTTS) managed with laser ablation surgery in an Australian tertiary perinatal centre and to compare the outcome with other large cohorts. METHODS: The outcomes of 100 consecutive pregnancies with severe TTTS managed with selective fetoscopic laser ablation from March 2002 to June 2007 were examined. Survival and neonatal morbidity were analysed. Comparisons were made with the results from other studies of laser surgery with at least 100 pregnancies. RESULTS: There were 100 women with TTTS treated with laser ablation; 34 stage II, 44 stage III and 22 at stage IV. Median gestation at time of laser was 21 weeks (range 18-28) and median gestation at delivery was 31 weeks (range 20-39). Overall perinatal survival rate was 151 of 200 (75.5%). Eighty five per cent had one or more surviving twins. The survival rate for stage IV TTTS was 88.6%, significantly better than for stage II (69.1%) and stage III (73.9%) pregnancies. The perinatal mortality rate for donors (30%) was not significantly different from recipients (19%), but the fetal death rate for donors was significantly greater than that for recipients (P = 0.03). Severe cerebral abnormalities were present in only 2.8% of newborns. The overall survival rate was comparable to other large series. CONCLUSIONS: These results for the management of severe TTTS are comparable to the best reported international series. Long-term follow-up is required and more research needs to be undertaken to further improve these results.

Prenatal and postnatal presentation of severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) due to the FGFR3 Lys650Met mutation.

We present prenatal and postnatal features of a patient with severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN). Mutation analysis confirmed the clinical diagnosis by detecting the FGFR3 Lys650Met mutation. This case, one of only six with molecular analysis reported in the literature, confirms the severe morbidity and adds to the reports with early mortality associated with SADDAN. Clinical-radiological characteristics of all reported cases of SADDAN are reviewed and discussed.