Immune cell profiling in the joint following human and murine articular fracture.

OBJECTIVE: Human and in vivo animal research implicates inflammation following articular fracture as contributing to post-traumatic arthritis. However, relevant immune cell subsets present following injury are currently undefined. Immunophenotyping human and murine synovial fluid may help to identify immune cell populations that play key roles in the response to articular fracture. METHODS: Immunophenotyping by polychromatic flow cytometry was performed on human and mouse synovial fluid following articular fracture. Specimens were collected in patients with closed ankle fracture at the time of surgical fixation and from C57BL/6 mice with closed articular knee fracture. Immune cells were collected from injured and uninjured joints in mice via a novel cell isolation method. Whole blood samples were also collected. Immunohistochemistry (IHC) was performed on mouse synovial tissue to assess for macrophages and T cells. RESULTS: Following intra-articular fracture, the prominent human synovial fluid immune cell subset was CD3+ T cells, containing both CD4+ and CD8+ T cells. In mice, infiltration of CD45+ immune cells in synovial fluid of the fractured limb was dominated by CD19+ B cells and CD3+ T cells at 7 days after intra-articular fracture. We also detected adaptive immune cells, including macrophages, NK cells, dendritic cells and monocytes. Macrophage and T cell findings were supported by IHC of murine synovial tissue. CONCLUSIONS: Determining specific cell populations that mediate the immune response is essential to elucidating the chain of events initiated after injury and may be an important step in identifying potential immune signatures predictive of PTA susceptibility or potential therapeutic targets.

Intra-articular depletion of macrophages increases acute synovitis and alters macrophage polarity in the injured mouse knee.

OBJECTIVE: Acute synovial inflammation following joint trauma is associated with posttraumatic arthritis. Synovial macrophages have been implicated in degenerative changes. In this study, we sought to elucidate the role of intra-articular macrophages in the acute inflammatory response to fracture in the mouse knee. METHOD: A closed articular fracture was induced in two models of synovial macrophage depletion: genetically-modified MaFIA mice administered AP20187 to induce programmed macrophage apoptosis, and wild-type C57BL/6 mice administered clodronate liposomes, both via intra-articular injection. Synovial inflammation, bone morphology, and levels of F4/80+ macrophages, NOS2+ M1 macrophages, and CD206+ M2 macrophages were quantified 7 days after fracture using histology and micro-computed tomography. RESULTS: Intra-articular macrophage depletion with joint injury did not reduce acute synovitis or the number of synovial macrophages 7 days after fracture in either macrophage-depleted MaFIA mice or in clodronate-treated C57BL/6 mice. In macrophage-depleted MaFIA mice, macrophage polarity shifted to a dominance of M1 macrophages and a reduction of M2 macrophages in the synovial stroma, indicating a shift in M1/M2 macrophage ratio in the joint following injury. Interestingly, MaFIA mice depleted 2 days prior to fracture demonstrated increased synovitis (P = 0.003), reduced bone mineral density (P = 0.0004), higher levels of M1 macrophages (P = 0.013), and lower levels of M2 macrophages (not statistically significant, P=0.084) compared to control-treated MaFIA mice. CONCLUSION: Our findings indicate that macrophages play a critical immunomodulatory role in the acute inflammatory response surrounding joint injury and suggest that inhibition of macrophage function can have prominent effects on joint inflammation and bone homeostasis after joint trauma.

Schwartz's Reagent-Mediated Regiospecific Synthesis of 2,3-Disubstituted Indoles from Isatins.

An expeditious, functional group-tolerant synthesis of indoles from isatins is described. Isatins are treated with Grignard reagents to yield oxindoles. These, in turn, are reduced with Schwartz's reagent and subjected to nucleophile addition and dehydration to yield 2,3-disubstituted indoles regiospecifically. This represents a divergent approach to the synthesis of these medicinally and synthetically important compounds.

Sustained intra-articular delivery of IL-1RA from a thermally-responsive elastin-like polypeptide as a therapy for post-traumatic arthritis.

Post-traumatic arthritis (PTA) is a rapidly progressive form of arthritis that develops due to joint injury, including articular fracture. Current treatments are limited to surgical restoration and stabilization of the joint; however, evidence suggests that PTA progression is mediated by the upregulation of pro-inflammatory cytokines, such as interleukin-1 (IL-1) or tumor necrosis factor-α (TNF-α). Although these cytokines provide potential therapeutic targets for PTA, intra-articular injections of anti-cytokine therapies have proven difficult due to rapid clearance from the joint space. In this study, we examined the ability of a cross-linked elastin-like polypeptide (xELP) drug depot to provide sustained intra-articular delivery of IL-1 and TNF-α inhibitors as a beneficial therapy. Mice sustained a closed intra-articular tibial plateau fracture; treatment groups received a single intra-articular injection of drug encapsulated in xELP. Arthritic changes were assessed 4 and 8 weeks after fracture. Inhibition of IL-1 significantly reduced the severity of cartilage degeneration and synovitis. Inhibition of TNF-α alone or with IL-1 led to deleterious effects in bone morphology, articular cartilage degeneration, and synovitis. These findings suggest that IL-1 plays a critical role in the pathogenesis of PTA following articular fracture, and sustained intra-articular cytokine inhibition may provide a therapeutic approach for reducing or preventing joint degeneration following trauma.

Acute joint pathology and synovial inflammation is associated with increased intra-articular fracture severity in the mouse knee.

OBJECTIVE: Post-traumatic arthritis is a frequent cause of disability and occurs most commonly and predictably after articular fracture. The objective of this investigation was to examine the effect of fracture severity on acute joint pathology in a novel murine model of intra-articular fracture. DESIGN: Low and high energy articular fractures (n=25 per group) of the tibial plateau were created in adult male C57BL/6 mice. The acute effect of articular fracture severity on synovial inflammation, bone morphology, liberated fracture area, cartilage pathology, chondrocyte viability, and systemic cytokines and biomarkers levels was assessed at 0, 1, 3, 5, and 7 days post-fracture. RESULTS: Increasing intra-articular fracture severity was associated with greater acute pathology in the synovium and bone compared to control limbs, including increased global synovitis and reduced periarticular bone density and thickness. Applied fracture energy was significantly correlated with degree of liberated cortical bone surface area, indicating greater comminution. Serum concentrations of hyaluronic acid (HA) were significantly increased 1 day post-fracture. While articular fracture significantly reduced chondrocyte viability, there was no relationship between fracture severity and chondrocyte viability, cartilage degeneration, or systemic levels of cytokines and biomarkers. CONCLUSIONS: This study demonstrates that articular fracture is associated with a loss of chondrocyte viability and increased levels of systemic biomarkers, and that increased intra-articular fracture severity is associated with increased acute joint pathology in a variety of joint tissues, including synovial inflammation, cortical comminution, and bone morphology. Further characterization of the early events following articular fracture could aid in the treatment of post-traumatic arthritis.

Efficacy of commercial mosquito traps in capturing phlebotomine sand flies (Diptera: Psychodidae) in Egypt.

Four types of commercial mosquito control traps, the Mosquito Magnet Pro (MMP), the Sentinel 360 (S360), the BG-Sentinel (BGS), and the Mega-Catch Ultra (MCU), were compared with a standard Centers for Disease Control and Prevention (CDC) light trap for efficacy in collecting phlebotomine sand flies (Diptera: Psychodidae) in a small farming village in the Nile River Valley 10 km north of Aswan, Egypt. Each trap was baited with either carbon dioxide (CO2) from combustion of butane gas (MMP), dry ice (CDC and BGS traps), light (MCU and S360), or dry ice and light (CDC). Traps were rotated through five sites in a5 x 5 Latin square design, repeated four times during the height of the sand fly season (June, August, and September 2007) at a site where 94% of sand flies in past collections were Phlebotomus papatasi (Scopoli). A total of 6,440 sand flies was collected, of which 6,037 (93.7%) were P. papatasi. Of the CO2-baited traps, the BGS trap collected twice as many P. papatasi as the MMP and CDC light traps, and at least three times more P. papatasi than the light-only MCU and S360 traps (P < 0.05). Mean numbers (+/- SE) of P. papatasi captured per trap night were as follows: BGS 142.1 (+/- 45.8) > MMP 56.8 (+/- 9.0) > CDC 52.3 (+/- 6.1) > MCU 38.2 (+/- 6.4) > S360 12.6 (+/- 1.8). Results indicate that several types of commercial traps are suitable substitutes for the CDC light trap in sand fly surveillance programs.

The role of the PDE4D cAMP phosphodiesterase in the regulation of glucagon-like peptide-1 release.

BACKGROUND AND PURPOSE: Increases in intracellular cyclic AMP (cAMP) augment the release/secretion of glucagon-like peptide-1 (GLP-1). As cAMP is hydrolysed by cAMP phosphodiesterases (PDEs), we determined the role of PDEs and particularly PDE4 in regulating GLP-1 release. EXPERIMENTAL APPROACH: GLP-1 release, PDE expression and activity were investigated using rats and GLUTag cells, a GLP-1-releasing cell line. The effects of rolipram, a selective PDE4 inhibitor both in vivo and in vitro and stably overexpressed catalytically inactive PDE4D5 (D556A-PDE4D5) mutant in vitro on GLP-1 release were investigated. KEY RESULTS: Rolipram (1.5 mg x kg(-1) i.v.) increased plasma GLP-1 concentrations approximately twofold above controls in anaesthetized rats and enhanced glucose-induced GLP-1 release in GLUTag cells (EC(50) approximately 1.2 nmol x L(-1)). PDE4D mRNA transcript and protein were detected in GLUTag cells using RT-PCR with gene-specific primers and Western blotting with a specific PDE4D antibody respectively. Moreover, significant PDE activity was inhibited by rolipram in GLUTag cells. A GLUTag cell clone (C1) stably overexpressing the D556A-PDE4D5 mutant, exhibited elevated intracellular cAMP levels and increased basal and glucose-induced GLP-1 release compared with vector-transfected control cells. A role for intracellular cAMP/PKA in enhancing GLP-1 release in response to overexpression of D556A-PDE4D5 mutant was demonstrated by the finding that the PKA inhibitor H89 reduced both basal and glucose-induced GLP-1 release by 37% and 39%, respectively, from C1 GLUTag cells. CONCLUSIONS AND IMPLICATIONS: PDE4D may play an important role in regulating intracellular cAMP linked to the regulation of GLP-1 release.

Novel synovial fluid recovery method allows for quantification of a marker of arthritis in mice.

OBJECTIVE: We evaluated three methodologies--a calcium sodium alginate compound (CSAC), polyacrylate beads (PABs), and Whatman paper recovery (WPR)--for the ability to recover synovial fluid (SF) from mouse knees in a manner that facilitated biochemical marker analysis. METHODS: Pilot testing of each of these recovery vehicles was conducted using small volumes of waste human SF. CSAC emerged as the method of choice, and was used to recover and quantify SF from the knees of C57BL/6 mice (n=12), six of which were given left knee articular fractures. SF concentrations of cartilage oligomeric matrix protein (COMP) were measured by enzyme-linked immunosorbent assay. RESULTS: The mean concentration ratio [(COMP(left knee))/(COMP(right knee))] was higher in the mice subjected to articular fracture when compared to the non-fracture mice (P=0.026). The mean total COMP ratio (taking into account the quantitative recovery of SF) best discriminated between fracture and non-fracture knees (P=0.004). CONCLUSIONS: Our results provide the first direct evidence of accelerated joint tissue turnover in a mouse model responding to acute joint injury. These data strongly suggest that mouse SF recovery is feasible and that biomarker analysis of collected SF samples can augment traditional histological analyses in mouse models of arthritis.

Mechanisms underlying the metabolic actions of galegine that contribute to weight loss in mice.

BACKGROUND AND PURPOSE: Galegine and guanidine, originally isolated from Galega officinalis, led to the development of the biguanides. The weight-reducing effects of galegine have not previously been studied and the present investigation was undertaken to determine its mechanism(s) of action. EXPERIMENTAL APPROACH: Body weight and food intake were examined in mice. Glucose uptake and acetyl-CoA carboxylase activity were studied in 3T3-L1 adipocytes and L6 myotubes and AMP activated protein kinase (AMPK) activity was examined in cell lines. The gene expression of some enzymes involved in fat metabolism was examined in 3T3-L1 adipocytes. KEY RESULTS: Galegine administered in the diet reduced body weight in mice. Pair-feeding indicated that at least part of this effect was independent of reduced food intake. In 3T3-L1 adipocytes and L6 myotubes, galegine (50 microM-3 mM) stimulated glucose uptake. Galegine (1-300 microM) also reduced isoprenaline-mediated lipolysis in 3T3-L1 adipocytes and inhibited acetyl-CoA carboxylase activity in 3T3-L1 adipocytes and L6 myotubes. Galegine (500 microM) down-regulated genes concerned with fatty acid synthesis, including fatty acid synthase and its upstream regulator SREBP. Galegine (10 microM and above) produced a concentration-dependent activation of AMP activated protein kinase (AMPK) in H4IIE rat hepatoma, HEK293 human kidney cells, 3T3-L1 adipocytes and L6 myotubes. CONCLUSIONS AND IMPLICATIONS: Activation of AMPK can explain many of the effects of galegine, including enhanced glucose uptake and inhibition of acetyl-CoA carboxylase. Inhibition of acetyl-CoA carboxylase both inhibits fatty acid synthesis and stimulates fatty acid oxidation, and this may to contribute to the in vivo effect of galegine on body weight.

Viability and apoptosis of human chondrocytes in osteochondral fragments following joint trauma.

Post-traumatic arthritis is a frequent consequence of articular fracture. The mechanisms leading to its development after such injuries have not been clearly delineated. A potential contributing factor is decreased viability of the articular chondrocytes. The object of this study was to characterise the regional variation in the viability of chondrocytes following joint trauma. A total of 29 osteochondral fragments from traumatic injuries to joints that could not be used in articular reconstruction were analysed for cell viability using the fluorescence live/dead assay and for apoptosis employing the TUNEL assay, and compared with cadaver control fragments. Chondrocyte death and apoptosis were significantly greater along the edge of the fracture and in the superficial zone of the osteochondral fragments. The middle and deep zones demonstrated significantly higher viability of the chondrocytes. These findings indicate the presence of both necrotic and apoptotic chondrocytes after joint injury and may provide further insight into the role of chondrocyte death in post-traumatic arthritis.

Alcohol sclerotherapy for successful treatment of focal adenomyosis: a case report.

Adenomyosis is characterized by the presence of ectopic endometrial tissue within the myometrium. Treatment options range from use of non-steroidal anti-inflammatory drugs and hormonal suppression for symptomatic relief, to endometrial ablation or even hysterectomy. We report a case of successful ultrasound-guided aspiration of focal adenomyosis with intracavitary alcohol instillation in a patient with a recurrent intramural uterine lesion. This is the first report of the treatment of sclerotherapy by alcohol instillation, which may be considered as a reasonable alternative modality in treating rare cases of symptomatic adenomyosis. Published by John Wiley & Sons, Ltd.

Improving fracture toughness of dental nanocomposites by interface engineering and micromechanics.

The fracture toughness of dental nanocomposites fabricated by various methods of mixing, silanization, and loadings of nanoparticles had been characterized using fatigue-precracked compact-tension specimens. The fracture mechanisms near the crack tip were characterized using atomic force microscopy (AFM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The near-tip fracture processes in the nanocomposties were identified to involve several sequences of fracture events, including: (1) particle bridging, (2) debonding at the poles of particle/matrix interface, and (3) crack deflection around the particles. Analytical and finite-element methods were utilized to model the observed sequences of fracture events to identify the source of fracture toughness in the dental nanocomposites. Theoretical results indicated that silanization and nanoparticle loadings improved the fracture toughness of dental nanocomposites by a factor of 2 to 3 through a combination of enhanced interface toughness by silanization, crack deflection, as well as crack bridging. A further increase in the fracture toughness of the nanocomposites can be achieved by increasing the fracture toughness of the matrix, nano-filled particles, or the interface.

The effect of NCX4016 [2-acetoxy-benzoate 2-(2-nitroxymethyl)-phenyl ester] on the consequences of ischemia and reperfusion in the streptozotocin diabetic rat.

The aim of this study was to assess the effect of chronic administration of NCX4016 [2 acetoxy-benzoate 2-(2-nitroxymethyl)-phenyl ester], a nitric oxide-releasing aspirin derivative on the consequences of coronary artery occlusion in streptozotocin-diabetic rats. Rats were made diabetic by injection of streptozotocin (60 mg kg(-1)) and received insulin (2.5 U kg(-1) s.c.) daily for 4 weeks. Animals received vehicle (1 ml kg(-1) polyethylene glycol), aspirin (65.2 mg kg(-1)), NCX4016 (60 mg kg(-1)), or (iv) NCX4016 (120 mg kg(-1)) orally, once daily for the last 5 days before coronary artery occlusion (CAO). One hour after the last dose, pentobarbital-anesthetized rats were subjected to CAO for 30 min followed by 120-min reperfusion. Neither drug significantly modified initial hemodynamics or plasma glucose levels compared with vehicle treatment in either nondiabetic or diabetic rats. Neither drug modified the total ventricular premature beat (VPB) count in normal animals, although NCX4016, but not aspirin, reduced the total VPB count and the incidence of ventricular tachycardia in diabetic rats. In nondiabetic animals, both aspirin and NCX4016 reduced infarct size. However, in diabetic rats, infarct size was reduced only by the larger dose of NCX4016 (120 mg kg(-1)) but not by aspirin or the lower dose of NCX4016. These results demonstrate that the cardioprotective effects of NCX4016 are reduced in the presence of diabetes compared with the effects seen in nondiabetic animals. In summary, the present study confirms the protective effect of NCX4016 against ischemia-reperfusion injury in the normal rat heart and demonstrates for the first time its protective effect in the heart of streptozotocin-diabetic rats.

Fetal bradycardia and disseminated coagulopathy: atypical presentation of amniotic fluid emboli.

We present a parturient who developed an atypical case of amniotic fluid emboli presented by sudden fetal bradycardia, followed by maternal disseminated coagulopathy. The typical feature of cardiopulmonary collapse was absent in this patient implying that in some cases of amniotic fluid emboli (AFE), fetal hypoxia or acidemia is unrelated to maternal cardiopulmonary status.

Cyclic nucleotide phosphodiesterases in pancreatic islets.

Cyclic nucleotide phosphodiesterases (PDEs) comprise a family of enzymes (PDE1-PDE11) which hydrolyse cyclic AMP and cyclic GMP to their biologically inactive 5' derivatives. Cyclic AMP is an important physiological amplifier of glucose-induced insulin secretion. As PDEs are the only known mechanism for inactivating cyclic nucleotides, it is important to characterise the PDEs present in the pancreatic islet beta cells. Several studies have shown pancreatic islets or beta cells to contain PDE1C, PDE3B and PDE4, with some evidence for PDE10A. Most evidence suggests that PDE3B is the most important in relation to the regulation of insulin release, although PDE1C could have a role. PDE3-selective inhibitors augment glucose-induced insulin secretion. In contrast, activation of beta-cell PDE3B could mediate the inhibitory effect of IGF-1 and leptin on insulin secretion. In vivo, although PDE3 inhibitors augment glucose-induced insulin secretion, concomitant inhibition of PDE3B in liver and adipose tissue induce insulin resistance and PDE3 inhibitors do not induce hypoglycaemia. The development of PDE3 inhibitors as anti-diabetic agents would require differentiation between PDE3B in the beta cell and that in hepatocytes and adipocytes. Through their effects in regulating beta-cell cyclic nucleotide concentrations, PDEs could modulate beta-cell growth, differentiation and survival; some work has shown that selective inhibition of PDE4 prevents diabetes in NOD mice and that selective PDE3 inhibition blocks cytokine-induced nitric oxide production in islet cells. Further work is required to understand the mechanism of regulation and role of the various PDEs in islet-cell function and to validate them as targets for drugs to treat and prevent diabetes.

Assessment of backside wear from the analysis of 55 retrieved tibial inserts.

Fifty-five retrieved tibial inserts with four different locking mechanisms were evaluated for evidence for polyethylene wear between the inferior surface of the tibial insert and metal tray. This type of wear will be referred to as backside wear. Backside wear was assessed by evaluating manufacturer's stamped markings on the inferior polyethylene surface. Because these markings are embossed into the polyethylene surface, they were used as indicators of backside wear. Decreases in the depths of markings indicated that backside wear was clearly evident, regardless of design, in 24 (44%) of the inserts. In eight of these 24 inserts, the manufacturer's stamped markings were removed completely. The amount of polyethylene wear was as a high as 591 mg from the inferior surface. This corresponds to a polyethylene wear rate from the backside of the tibial insert of greater than 100 mg per year, which is two to four times higher than wear rates associated with total hip replacements. The current work provides direct evidence of backside wear in all four tibial insert designs. Backside wear of tibial inserts can be a significant contributor to polyethylene wear in total knee arthroplasty. Close attention should be given to the fixation of tibial inserts to metal trays by manufacturers and surgeons.

Twelve cases of placental chorioangioma. Pregnancy outcome and clinical significance.

INTRODUCTION: To determine perinatal complications and pregnancy outcome in 12 women with chorioangioma of placenta. STUDY DESIGN: During the period between January 1986 and December 1997, 12 women with histologic diagnosis of chorioangioma of placenta who delivered in our institution were studied. Case-control study was designed. Sixty women with histologic examination of the placenta without chorioangioma were randomly identified as control group matched for maternal age and parity. Statistical analyses included t-test, Chi-square test and Fisher's exact test when appropriate. RESULTS: Nine cases (75%) were diagnosed postnatal. The mean gestational age was significantly lower and preterm delivery rate was significantly higher among the chorioangioma group (34 vs. 38.8 weeks P<0.0001; 66% vs. 10%; P<0.001 respectively). CONCLUSIONS: Chorioangioma of the placenta, in a high risk population, although small, is associated with significantly higher risk for preterm delivery. This emphasizes the need for pathologic examination of all placentas of patients with preterm delivery

Uterine artery Doppler velocimetry in patients with idiopathic hydramnios.

OBJECTIVE: To evaluate the role of overdistended uterus on the uterine artery (UA) blood flow velocimetry by comparing UA Doppler in patients with idiopathic hydramnios to patients with normal amniotic fluid (AF) volume. METHODS: Pulsatility index (PI) of both UAs was determined prospectively between 26 and 41 weeks of gestation in 72 consecutive pregnant women with singleton pregnancies and idiopathic hydramnios and in 72 pregnant women with normal AF volume. Hydramnios was defined as an AF index (AFI) above 24 cm. A normal amount of AF was defined as an AFI of 6-24 cm. Patients with known fetal structural or chromosomal anomalies and those with diabetes mellitus were excluded. RESULTS: No significant differences were observed between the groups with regard to maternal age, gravidity, and gestational age at examination. Gestational age at delivery and accordingly birth weight were significantly lower in patients with hydramnios compared to those with a normal AFI (34.9 +/- 2.1 vs. 39.1 +/- 1.2, p < 0.001; 2,508 +/- 399 vs. 2,995 +/- 420, p < 0.001, respectively). No significant differences were noted between right UA PI (0.73 +/- 0.3 in the hydramnios group vs. 0.71 +/- 0.2 in the control group; p = 0.091) and left UA PI (0.91 +/- 0.3 in the hydramnios group vs. 0.84 +/- 0.3 in the control group; p = 0.131) of both groups. CONCLUSION: UA velocimetry in patients with idiopathic hydramnios was not significantly different from those with a normal AF volume.

Fetal serum levels of insulin, growth hormone and insulin-like growth factor-I in concordant and discordant twin gestations.

OBJECTIVE: To examine the role of insulin, growth hormone and insulin-like growth factor (IGF)-I in concordant and discordant twin pairs. METHODS: Umbilical cord serum samples were obtained from 20 twin pairs with weight discordancy (intertwin birth weight difference > 20%) and from 20 concordant twins (intertwin birth weight difference < 20%), both groups of similar gestational age, gravidity, and parity. The serum samples were analyzed for the levels of IGF-I, growth hormone and insulin in both maternal and fetal compartments. RESULTS: Among the group of discordant twins, the normally grown twin, in all cases, had significantly higher cord serum IGF-I levels than their growth-restricted co-twin (108 +/- 73 ng/ml vs. 39 +/- 24 ng/ml; p < 0.01). There were no significant intertwin differences in the cord blood IGF-I levels in the concordant twin pairs (87 +/- 44 vs. 88 +/- 48 ng/ml; p = 0.986). Insulin and growth hormone levels did not correlate with intertwin birth weight differences. CONCLUSION: These data demonstrate that IGF-I is important in the regulation of both normal and restricted fetal growth in utero, and its action appears to be, at least in part, through an endocrine action. The precise role of growth hormone and insulin in fetal growth restriction remains uncertain.

Comparison study between induced and spontaneous term and preterm births of small-for-gestational-age neonates.

OBJECTIVE: To compare perinatal and maternal outcome between induced and spontaneous small-for-gestational-age (SGA) neonates at term and preterm deliveries. STUDY DESIGN: A cross-sectional study was designed and two groups were identified at each gestational age: study group - SGA neonates born after induction of labor, comparison group - SGA neonates born after spontaneous onset of labor. SGA was decoded as birth weight below 10th percentile. The population consisted of 367 consecutive SGA singleton preterm neonates (24-36 weeks' gestation) and 3921 term SGA neonates (37-42 weeks' gestation) delivered between 1990 and 1997. Patients with antepartum death and congenital anomalies were excluded from this study. RESULTS: The prevalence of SGA neonates among preterm deliveries was significantly higher than among term deliveries (9.3 versus 6.1%, P<0.001). The rate of induction of labor among preterm SGA deliveries was significantly higher than term SGA deliveries (17.7 versus 13.4%, P=0.002). The rates hypertensive disorders, suspected IUGR, placental abruption, cesarean section, chorioamnionitis and endometritis were significantly higher among preterm SGA than in term SGA. A multiple logistic regression analysis demonstrated that suspected IUGR, severe PIH (but not mild PIH), chronic hypertension and placental abruption were independent risk factors for induction of labor among preterm SGA neonates. In addition to these factors, oligohydramnios was considered to be an independent risk factor only among term SGA. No significant differences were found in the mean birthweight and post-partum death rates between the induced and spontaneous preterm and term SGA. The incidence of Apgar score < 7 at 5 min was significantly lower only among induced term SGA. CONCLUSIONS: Induction of labor in preterm SGA neonates is performed mainly due to maternal severe hypertension disorders. The indications for induction of labor among term SGA include maternal hypertensive disorders (mild or severe) as well as neonatal status, represented mainly by oligohydramnios. In addition, induction of labor in preterm or term SGA neonates does not change neonatal outcome. Moreover, since no evidence of improved neonatal outcome was demonstrated in either indicated group, preterm or term, the question of timing and indications for induction of labor should be discussed.