Patient blood management and the importance of the Transfusion Practitioner role to embed this into practice.

Patient blood management (PBM) is a widely established international initiative, with a multidisciplinary approach to reduce transfusion. The Transfusion Practitioner1 (TP) role is well embedded in the United Kingdom (UK) and Australia. The value of the TP in changing both culture and practice to implement an all-inclusive PBM approach to care will be discussed. The TP role was born from both a safety and haemovigilance culture, where the greatest identified risk to the patient undergoing a transfusion was human error. From this initial trigger for improved safety, the TP role has evolved to a multifaceted, highly specialised role, involved in both PBM and transfusion processes. As the transfusion paradigm shifted from product to patient, the TP role evolved to include PBM, with an emphasis on the patients and the impact transfusion has on them. A multidisciplinary team is required to drive both PBM and transfusion; the TP is recognised as a critical link in the multidisciplinary team. They are seen as a driving force for change, bridging the gap between the laboratory and clinical arenas. The TP plays a vital role in helping establish and embed PBM that improves patient and safety outcomes.

Neonatal mouse-derived engineered cardiac tissue: a novel model system for studying genetic heart disease.

RATIONALE: Cardiomyocytes cultured in a mechanically active 3-dimensional configuration can be used for studies that correlate contractile performance to cellular physiology. Current engineered cardiac tissue (ECT) models use cells derived from either rat or chick hearts. Development of a murine ECT would provide access to many existing models of cardiac disease and open the possibility of performing targeted genetic manipulation with the ability to directly assess contractile and molecular variables. OBJECTIVE: To generate, characterize, and validate mouse ECT with a physiologically relevant model of hypertrophic cardiomyopathy. METHODS AND RESULTS: We generated mechanically integrated ECT using isolated neonatal mouse cardiac cells derived from both wild-type and myosin-binding protein C (cMyBP-C)-null mouse hearts. The murine ECTs produced consistent contractile forces that followed the Frank-Starling law and accepted physiological pacing. cMyBP-C-null ECTs showed characteristic acceleration of contraction kinetics. Adenovirus-mediated expression of human cMyBP-C in murine cMyBP-C-null ECT restored contractile properties to levels indistinguishable from those of wild-type ECT. Importantly, the cardiomyocytes used to construct the cMyBP-C(-/-) ECT had yet to undergo the significant hypertrophic remodeling that occurs in vivo. Thus, this murine ECT model reveals a contractile phenotype that is specific to the genetic mutation rather than to secondary remodeling events. CONCLUSIONS: Data presented here show mouse ECT to be an efficient and cost-effective platform to study the primary effects of genetic manipulation on cardiac contractile function. This model provides a previously unavailable tool to study specific sarcomeric protein mutations in an intact mammalian muscle system.

Risk factors for necrotizing enterocolitis totalis: a case-control study.

OBJECTIVE: The objective of this study was to compare demographic and clinical events in three groups of preterm neonates: those with necrotizing enterocolitis totalis (NEC-T), those with NEC non-totalis (NEC non-T) and in preterm patients without NEC. STUDY DESIGN: This retrospective case-control study was conducted at Yale New Haven Children's Hospital using patient data from January 1991 to December 2007. Study patients were less than 36 weeks of gestational age (GA) at birth, without gastrointestinal (GI) malformations. Cases (NEC-T) were diagnosed at operation or at autopsy with observation of >80% necrosis of the GI tract. Two control groups were assigned: Group 1 or NEC non-T and Group II or Non-NEC. Two to four controls per case were matched to cases by GA at birth±2 weeks. Demographic and clinical data for the day of diagnosis and retrospectively up to 7 days preceding diagnosis were recorded for those with NEC-T and NEC. Group II controls were matched for date of birth and day of life, in addition to GA at birth. RESULT: A total of 14 075 patients were admitted to the Newborn Special Care Unit during the study interval. Overall 328 patients (2.3%) developed NEC≥Bell's Stage II; 39 patients met inclusion criteria for NEC-T case status; 148 NEC non-T and 110 non-NEC controls were assigned. In the comparison of NEC T and NEC non-T neonates, use of breast milk was associated with decreased risk of NEC-T, adjusted odds ratio (OR)=0.26, 95% confidence interval (CI) of OR=0.08-0.085, P=0.03. When NEC T and non-NEC patients were compared, having reached full-enteral feeds before the date of diagnosis of the matched case (adjusted OR=28.5, 95% CI of OR=2.7-299, P=0.005) and use of breast milk (adjusted OR=0.09, 95% CI of OR=0.02-0.56, P=0.01) were significantly different between the two groups. CONCLUSION: Breast milk usage was significantly associated with decreased occurrence of NEC-T in our comparison of NEC-T, NEC non-T and non-NEC patients. Although there were some differences, the majority of demographic and clinical variables assessed were not shown to be significantly different between cases and controls. This highlights the need for more biological data in assessing risk of developing NEC-T.

Toward prompt gamma spectrometry for monitoring boron distributions during extra corporal treatment of liver metastases by boron neutron capture therapy: a Monte Carlo simulation study.

A Monte Carlo calculation was carried out for boron neutron capture therapy (BNCT) of extra corporal liver phantom. The present paper describes the basis for a subsequent clinical application of the prompt gamma spectroscopy set-up aimed at in vivo monitoring of boron distribution. MCNP code was used first to validate the homogeneity in thermal neutron field in the liver phantom and simulate the gamma ray detection system (collimator and detector) in the treatment room. The gamma ray of 478 keV emitted by boron in small specific region can be detected and a mathematical formalism was used for the tomography image reconstruction.

Clinical parameters do not adequately predict outcome in necrotizing enterocolitis: a multi-institutional study.

OBJECTIVE: Necrotizing enterocolitis (NEC) remains a major cause of neonatal morbidity and mortality. Some infants recover uneventfully with medical therapy whereas others develop severe disease (that is, NEC requiring surgery or resulting in death). Repeated attempts to identify clinical parameters that would reliably identify infants with NEC most likely to progress to severe disease have been unsuccessful. We hypothesized that comprehensive prospective data collection at multiple centers would allow us to develop a model which would identify those babies at risk for progressive NEC. STUDY DESIGN: This prospective, observational study was conducted at six university children's hospitals. Study subjects were neonates with suspected or confirmed NEC. Comprehensive maternal and newborn histories were collected at the time of enrollment, and newborn clinical data were collected prospectively, thereafter. Multivariate logistic regression analysis was used to develop a predictive model of risk factors for progression. RESULT: Of 455 neonates analyzed, 192 (42%) progressed to severe disease, and 263 (58%) advanced to full feedings without operation. The vast majority of the variables studied proved not to be associated with progression to severe disease. A total of 12 independent predictors for progression were identified, including only 3 not previously described: having a teenaged mother (odds ratio, OR, 3.14; 95% confidence interval, CI, 1.45 to 6.96), receiving cardiac compressions and/or resuscitative drugs at birth (OR, 2.51; 95% CI, 1.17 to 5.48), and having never received enteral feeding before diagnosis (OR, 2.41; 95% CI, 1.08 to 5.52). CONCLUSION: Our hypothesis proved false. Rigorous prospective data collection of a sufficient number of patients did not allow us to create a model sufficiently predictive of progressive NEC to be clinically useful. It appears increasingly likely that further analysis of clinical parameters alone will not lead to a significant improvement in our understanding of NEC. We believe that future studies must focus on advanced biologic parameters in conjunction with clinical findings.

Validating a MCNPX model of Mg(Ar) and TE(TE) ionisation chambers exposed to 60CO gamma rays.

For an accurate determination of the absorbed doses in complex radiation fields (e.g. mixed neutron-gamma fields), a better interpretation of the response of ionisation chambers is required. This study investigates a model of the ionisation chambers using a different approach, analysing the collected charge per minute as a response of the detector instead of the dose. The MCNPX Monte Carlo code is used. In this paper, the model is validated using a well-known irradiation field only: a (60)Co source. The detailed MCNPX models of a Mg(Ar) and TE(TE) ionisation chamber is investigated comparing the measured charge per minute obtained free-in-air and in a water phantom with the simulated results. The difference between the calculations and the measurements for the TE(TE) chamber is within +/-2% whereas for the Mg(Ar) chamber is around +7%. The systematic discrepancy in the case of Mg(Ar) chamber is expected to be caused by an overestimation of the sensitive volume.

An international dosimetry exchange for BNCT part II: computational dosimetry normalizations.

The meaningful sharing and combining of clinical results from different centers in the world performing boron neutron capture therapy (BNCT) requires improved precision in dose specification between programs. To this end absorbed dose normalizations were performed for the European clinical centers at the Joint Research Centre of the European Commission, Petten (The Netherlands), Nuclear Research Institute, Rez (Czech Republic), VTT, Espoo (Finland), and Studsvik, Nyköping (Sweden). Each European group prepared a treatment plan calculation that was bench-marked against Massachusetts Institute of Technology (MIT) dosimetry performed in a large, water-filled phantom to uniformly evaluate dose specifications with an estimated precision of +/-2%-3%. These normalizations were compared with those derived from an earlier exchange between Brookhaven National Laboratory (BNL) and MIT in the USA. Neglecting the uncertainties related to biological weighting factors, large variations between calculated and measured dose are apparent that depend upon the 10B uptake in tissue. Assuming a boron concentration of 15 microg g(-1) in normal tissue, differences in the evaluated maximum dose to brain for the same nominal specification of 10 Gy(w) at the different facilities range between 7.6 and 13.2 Gy(w) in the trials using boronophenylalanine (BPA) as the boron delivery compound and between 8.9 and 11.1 Gy(w) in the two boron sulfhydryl (BSH) studies. Most notably, the value for the same specified dose of 10 Gy(w) determined at the different participating centers using BPA is significantly higher than at BNL by 32% (MIT), 43% (VTT), 49% (JRC), and 74% (Studsvik). Conversion of dose specification is now possible between all active participants and should be incorporated into future multi-center patient analyses.

Gel dosimetry in the BNCT facility for extra-corporeal treatment of liver cancer at the HFR Petten.

A thorough evaluation of the dose inside a specially designed and built facility for extra-corporeal treatment of liver cancer by boron neutron capture therapy (BNCT) at the High Flux Reactor (HFR) Petten (The Netherlands) is the necessary step before animal studies can start. The absorbed doses are measured by means of gel dosemeters, which help to validate the Monte Carlo simulations of the spheroidal liver holder that will contain the human liver for irradiation with an epithermal neutron beam. These dosemeters allow imaging of the dose due to gammas and to the charged particles produced by the (10)B reaction. The thermal neutron flux is extrapolated from the boron dose images and compared to that obtained by the calculations. As an additional reference, Au, Cu and Mn foil measurements are performed. All results appear consistent with the calculations and confirm that the BNCT liver facility is able to provide an almost homogeneous thermal neutron distribution in the liver, which is a requirement for a successful treatment of liver metastases.

Application of adjoint Monte Carlo to accelerate simulations of mono-directional beams in treatment planning for boron neutron capture therapy.

This paper deals with the application of the adjoint transport theory in order to optimize Monte Carlo based radiotherapy treatment planning. The technique is applied to Boron Neutron Capture Therapy where most often mixed beams of neutrons and gammas are involved. In normal forward Monte Carlo simulations the particles start at a source and lose energy as they travel towards the region of interest, i.e., the designated point of detection. Conversely, with adjoint Monte Carlo simulations, the so-called adjoint particles start at the region of interest and gain energy as they travel towards the source where they are detected. In this respect, the particles travel backwards and the real source and real detector become the adjoint detector and adjoint source, respectively. At the adjoint detector, an adjoint function is obtained with which numerically the same result, e.g., dose or flux in the tumor, can be derived as with forward Monte Carlo. In many cases, the adjoint method is more efficient and by that is much quicker when, for example, the response in the tumor or organ at risk for many locations and orientations of the treatment beam around the patient is required. However, a problem occurs when the treatment beam is mono-directional as the probability of detecting adjoint Monte Carlo particles traversing the beam exit (detector plane in adjoint mode) in the negative direction of the incident beam is zero. This problem is addressed here and solved first with the use of next event estimators and second with the application of a Legendre expansion technique of the angular adjoint function. In the first approach, adjoint particles are tracked deterministically through a tube to a (adjoint) point detector far away from the geometric model. The adjoint particles will traverse the disk shaped entrance of this tube (the beam exit in the actual geometry) perpendicularly. This method is slow whenever many events are involved that are not contributing to the point detector, e.g., neutrons in a scattering medium. In the second approach, adjoint particles that traverse an adjoint shaped detector plane are used to estimate the Legendre coefficients for expansion of the angular adjoint function. This provides an estimate of the adjoint function for the direction normal to the detector plane. In a realistic head model, as described in this paper, which is surrounded by 1020 mono-directional neutron/gamma beams and from which the best ones are to be selected, the example calculates the neutron and gamma fluxes in ten tumors and ten organs at risk. For small diameter beams (5 cm), and with comparable relative errors, forward Monte Carlo is seen to be 1.5 times faster than the adjoint Monte Carlo techniques. For larger diameter neutron beams (10 and 15 cm), the Legendre technique is found to be 6 and 20 times faster, respectively. In the case of gammas alone, for the 10 and 15 cm diam beams, both adjoint Monte Carlo Legendre and point detector techniques are respectively 2 and 3 times faster than forward Monte Carlo.

In vivo left ventricular functional capacity is compromised in cMyBP-C null mice.

Cardiac myosin binding protein-C (cMyBP-C) is a thick filament-associated protein that binds tightly to myosin and has a potential role for modulating myocardial contraction. We tested the hypothesis that cMyBP-C 1) contributes to the enhanced in vivo contractile state following beta-adrenergic stimulation and 2) is necessary for myocardial adaptation to chronic increases in afterload. In vivo pressure-volume relations demonstrated that left ventricular (LV) systolic and diastolic function were compromised under basal conditions in cMyBP-C(-/-) compared with WT mice. Moreover, whereas beta-adrenergic treatment significantly improved ejection fraction, peak elastance, and the time to peak elastance in WT mice, these functional indexes remained unchanged in cMyBP-C(-/-) mice. Morphological and functional changes were measured through echocardiography in anesthetized mice following 5 wk of aortic banding. Adaptation to pressure overload was diminished in cMyBP-C(-/-) mice as characterized by a lack of an increase in posterior wall thickness, increased LV diameter, deterioration of fractional shortening, and prolonged isovolumic relaxation time. These results suggest that the absence of cMyBP-C significantly diminishes in vivo LV function and markedly attenuates the increase in LV contractility following beta-adrenergic stimulation or adaptation to pressure overload.

Design of a rotating facility for extracorporal treatment of an explanted liver with disseminated metastases by boron neutron capture therapy with an epithermal neutron beam.

In 2001, at the TRIGA reactor of the University of Pavia (Italy), a patient suffering from diffuse liver metastases from an adenocarcinoma of the sigmoid was successfully treated by boron neutron capture therapy (BNCT). The procedure involved boron infusion prior to hepatectomy, irradiation of the explanted liver at the thermal column of the reactor, and subsequent reimplantation. A complete response was observed. This encouraging outcome stimulated the Essen/Petten BNCT group to investigate whether such an extracorporal irradiation could be performed at the BNCT irradiation facility at the HFR Petten (The Netherlands), which has very different irradiation characteristics than the Pavia facility. A computational study has been carried out. A rotating PMMA container with a liver, surrounded by PMMA and graphite, is simulated using the Monte Carlo code MCNP. Due to the rotation and neutron moderation of the PMMA container, the initial epithermal neutron beam provides a nearly homogeneous thermal neutron field in the liver. The main conditions for treatment as reported from the Pavia experiment, i.e. a thermal neutron fluence of 4 x 10(12) +/- 20% cm(-2), can be closely met at the HFR in an acceptable time, which, depending on the defined conditions, is between 140 and 180 min.

A parameter study to determine the optimal source neutron energy in boron neutron capture therapy of brain tumours.

The values of the parameters used in boron neutron capture therapy (BNCT) to calculate a given dose to human tissue vary with patients due to different physical, biological and/or medical circumstances. Parameters include the tissue dimensions, the 10B concentration and the relative biological effectiveness (RBE) factors for the different dose components associated with BNCT. Because there is still no worldwide agreement on RBE values, more often than not, average values for these parameters are used. It turns out that the RBE-problem can be circumvented by taking into account all imaginable parameter values. Approaching this quest from another angle: the outcome will also provide the parameters (and values) which influence the optimal source neutron energy. For brain tumours it turns out that the 10B concentration, the RBE factors for 10B as well as fast neutrons, together with the dose limit set for healthy tissue, affect the optimal BNCT source neutron energy. By using source neutrons of a few keV together with neutrons of a few eV, it ensures that, under all imaginable circumstances, a maximum of alpha (and lithium) particles can be delivered in the tumour.

Experimental and computational validation of BDTPS using a heterogeneous boron phantom.

The idea to couple the treatment planning system (TPS) to the information on the real boron distribution in the patient acquired by positron emission tomography (PET) is the main added value of the new methodology set-up at DIMNP (Dipartimento di Ingegneria Meccanica, Nucleare e della Produzione) of University of Pisa, in collaboration with the JRC (Joint Research Centre) at Petten (NL). This methodology has been implemented in a new TPS, called Boron Distribution Treatment Planning System (BDTPS), which takes into account the actual boron distribution in the patient's organ, as opposed to other TPSs used in BNCT that assume an ideal uniform boron distribution. BDTPS is based on the Monte Carlo technique and has been experimentally validated comparing the computed main parameters (thermal neutron flux, boron dose, etc.) to those measured during the irradiation of an ad hoc designed phantom (HEterogeneous BOron phantoM, HEBOM). The results are also in good agreement with those obtained by the standard TPS SERA and by reference calculations carried out using an analytical model with the MCNP code. In this paper, the methodology followed for both the experimental and the computational validation of BDTPS is described.

Primary reversed gastric tube reconstruction in long gap esophageal atresia.

BACKGROUND/PURPOSE: Esophageal reconstruction in long-gap esophageal atresia (EA) poses a technical challenge with several surgical options. The purpose of this study was to review the authors' experience with the reversed gastric tube (RGT) in esophageal reconstruction. METHODS: This series describes 7 babies with pure EA treated at 2 centers between 1989 and 2001. Data, gathered by retrospective chart review, included clinical details of the esophageal and associated malformations, technique and timing of repair, early and late complications, and long-term follow-up. Institutional review board (IRB) approval of this study has been obtained. RESULTS: Seven babies were included. Associated malformations were present in 4: trisomy 21 in 2 and imperforate anus in 2. After gastrostomy tube placement, patients were treated with gastrostomy tube feedings and continuous upper pouch suction. Median gap length was 5.5 vertebral segments (range, 3 to 9). RGT with a posterior mediastinal esophagogastric anastomosis was performed at median age of 62 days (range, 38 to 131). There were no anastomotic leaks. Three patients had strictures, one required resection. Exclusive oral nourishment was achieved in 5 patients by 6 months of age. At last follow-up (mean, 4.5 years), 6 patients were receiving oral nutrition exclusively, and all were maintaining growth curves. CONCLUSIONS: In long gap EA, early esophageal reconstruction using an RGT can be performed with minimal morbidity and promising short-term results.

The role of prospective randomized clinical trials in pediatric surgery: state of the art?

PURPOSE: This study sought to determine the role of randomized controlled trials (RCT) in the evolution of pediatric surgical practice. METHODS: The authors used a computer-assisted literature search to identify all clinical trials related to pediatric surgery published in the English-language literature from 1966 through 1999. Each article was reviewed in detail for purpose, content, conduct, and quality of the trial. The authors assessed quality with a previously validated instrument (Chalmers Qualitative Assessment). RESULTS: The authors identified 134 RCTs related to pediatric surgery over the past 33 years. This accounts for 0.17% of 80,377 articles published in the field. The areas of surgery studied were analgesia 65 (49%), antibiotics 17 (13%), extracorporeal membrane oxygenation (ECMO) 9 (7%), gastrointestinal, burns, oncology, minimally invasive surgery, vascular access, congenital anomalies, and trauma (each <5%). Only 16 (12%) trials compared 2 surgical therapies, 9 (7%) compared a medical versus a surgical therapy, and 109 (81%) compared 2 medical therapies in surgical patients. Fourteen (10%) RCTs were funded by peer-reviewed agencies. Only 17 (13%) RCTs included a biostatistician as an author or a consultant. Trial design included calculation of sample size and statistical power in 21 (16%) RCTs. Method of randomization was reported in only 51 (38%). The test statistic and observed probability value was reported in 15 (11%). CONCLUSIONS: Clinical trials are used infrequently to answer questions related to pediatric surgery. When RCTs are utilized, they often suffer from poor trial design, inadequate statistical analysis, and incomplete reporting. Pediatric surgery could benefit from increased expertise, funding, and participation in clinical trials.

Venoarterial versus venovenous extracorporeal membrane oxygenation in congenital diaphragmatic hernia: the Extracorporeal Life Support Organization Registry, 1990-1999.

BACKGROUND/PURPOSE: Venoarterial (VA) extracorporeal membrane oxygenation (ECMO) traditionally has been the mode of support used in congenital diaphragmatic hernia (CDH). A few studies report success using venovenous (VV) ECMO. The purpose of this study is to compare outcomes in CDH patients treated with VA and VV. METHODS: The authors queried the Extracorporeal Life Support Organization Registry for newborns with CDH treated with ECMO from January 1, 1990 through December 31, 1999. They analyzed the pre-ECMO data, ECMO course, and complications. RESULTS: VA was utilized in 2,257 (86%) and VV in 371 (14%) patients. The pre-ECMO status was similar, with greater use of nitric oxide, surfactant, and pressors in VV. Survival rate was similar (58.4% for VV and 52.2% for VA, P =.057). VA was associated with more seizures (12.3% v 6.7%, P =.0024) and cerebral infarction (10.5% v 6.7%, P =.03). Sixty-four treatments were converted from VV to VA (VV-->VA). Survival rate in VV-->VA was not significantly different than VA (43.8% v 52.2%, respectively; P =.23). VV-->VA and VA patients had similar neurologic complications. CONCLUSIONS: CDH patients treated with VV and VA have similar survival rates. VA had more neurologic complications. The authors identified no disadvantage to the use of VV as an initial mode of ECMO for CDH, although some infants may need conversion to VA.

A meta-analysis of peritoneal drainage versus laparotomy for perforated necrotizing enterocolitis.

BACKGROUND/PURPOSE: Both primary peritoneal drainage (PPD) and laparotomy (LAP) are used widely for treatment of perforated necrotizing enterocolitis (NEC). Published reports include only anecdotes and small series. The authors used techniques of meta-analysis to determine which treatment is most effective. METHODS: The authors identified published studies reporting surgical treatment of NEC from January 1, 1978 to December 31, 1999; there were 10 studies (n = 475). The authors were contacted and all available raw patient data for use in meta-analysis (n = 190) were obtained. The authors used logistic regression to determine the relative survival rate after PPD and LAP, controlling for the effect of gestational age and institution. RESULTS: The combined probability of survival in the 10 published studies did not show an advantage for PPD (55%) or LAP (67%; P =.27). When the authors corrected for the effect of birth weight on survival rate, they still did not observe a difference (P =.67). A marked bias in treatment assignment was found with smaller babies undergoing PPD than LAP (931 g versus 1,615 g, respectively; P =.0004). Analysis of raw data showed an even greater bias in treatment assignment. The authors found increased survival rate for LAP versus PPD (62.3% v 35.6%; P =.0009). However, a logistic regression model could not overcome the bias in assignment of patients with a much higher expected mortality rate to PPD. CONCLUSIONS: Using currently available data, it is not possible to determine whether PPD or LAP is superior. Bias in treatment assignment precludes conclusions regarding comparative survival. Only a randomized trial will determine which operation is best for the treatment of perforated NEC.

Fetal therapy with rhIGF-1 in a rabbit model of intrauterine growth retardation.

BACKGROUND: Intrauterine growth retardation (IUGR) may, in part, be due to a deficiency of insulin-like growth factor-1 (IGF-1). The objectives of this study were to determine the relationship between fetal serum IGF-1 levels and fetal and placental size in a rabbit model of IUGR and to compare two techniques of selective, exogenous IGF-1 administration (transamniotic and branch uterine arterial catheter infusion) to growth-retarded fetuses in utero. MATERIALS AND METHODS: Pregnant rabbits (n = 6) had their fetuses harvested near term (31 days) for fetal and placental weighing and serum collection. Growth-retarded fetuses were selectively infused for 7 days with recombinant human IGF-1 (rhIGF-1; 1,440 ng/day) either through a transamniotic catheter (n = 8) or via an adjacent uterine arterial branch catheter (n = 6). Opposite horn runts were sham catheterized, but not infused. At term, the fetal runt pairs and their placentas were harvested and weighed, and their serum was collected. The correlation between fetal and placental weight and endogenous serum IGF-1 was calculated (Pearson coefficient, r), while paired t-tests were used to compare the means between the IGF-1-infused and control groups. RESULTS: There was a significant correlation between fetal (r = 0.4230; P = 0.022) and placental weight (r = 0.4166; P = 0.025) and endogenous serum levels of IGF-1. Transamniotic infusion of rhIGF-1 was associated with an increase in serum IGF-1 level (254 +/- 79 vs 351 +/- 101 ng/ml, P = 0.04) and placental weight (5.4 +/- 2.3 vs 7.1 +/- 3.2 g, P = 0.005), and with a trend toward increased fetal weight between matched fetal runt pairs. Fetal mortality in the uterine arterial catheterized group was 76%, and there was no significant difference in fetal or placental weight or IGF-1 levels between infused and noninfused survivors. CONCLUSIONS: Endogenous fetal serum levels correlate with fetal and placental size in the rabbit IUGR model. Transamniotic administration of rhIGF-1 significantly increases serum IGF-1 levels and placental weight of fetal runts, while uterine vessel catheterization results in prohibitive fetal mortality and does not increase fetal or placental growth or IGF-1 levels.