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Many cases of intrauterine growth retardation (IUGR) result from placental insufficiency, but the molecular signals accompanying this event are unknown. Insulin-like growth factor 1 (IGF-1) is a potent mitogen for fetal tissues and is lowered in the serum of human infants with IUGR. The rabbit provides an optimal model for the study of IUGR based on fetal position. To determine if IGF-1 expression is altered in the growth-retarded fetus, this naturally occurring rabbit model of IUGR was used. Four fetal rabbit pairs were harvested on Days 21, 23, 25, 27, 29, and 31 of their normal 31-day gestation; they were identified based on uterine position as normal or growth retarded. Fetal weight was recorded and the serum, amniotic fluid, liver, kidney, and small intestine (SI) were collected. The SI was divided into three equal segments: proximal, middle, and distal. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure IGF-1/β-actin mRNA densitometric band ratios in all tissues. Radioimmunoassay (RIA) was used to measure IGF-1 protein levels in the serum and amniotic fluid. Statistical analysis was performed using ANOVA and the paired Student's t test. Weights were decreased in fetuses with IUGR at all time points (P < 0.05), further validating this rabbit model in the study of IUGR. Liver, proximal, and distal SI IGF-1 mRNA decreased during late gestation (P < 0.01). Kidney IGF-1 mRNA increased throughout late gestation (P < 0.01). Compared with their normal counterparts, fetuses with IUGR had a trend toward decreased IGF-1 mRNA in the kidney, liver, and SI at all time points, reaching significance in the liver on Day 27 (P = 0.002). Serum IGF-1 decreased throughout gestation in all fetuses (P < 0.05). Compared with normal fetuses, fetuses with IUGR had lower serum IGF-1 at all time points, reaching significance at Day 27 (P = 0.02). Amniotic fluid IGF-1 was lower in fetuses with IUGR than in normal fetuses, though not quite reaching significance. Compared with normal fetuses, growth-retarded fetal rabbits trend toward depressed liver, kidney, and intestinal expression of IGF-1 mRNA and lower serum and amniotic fluid IGF-1 protein. Serum IGF-1 levels correlate with fetal weight change. Further studies and potential manipulation of fetal IGF-1 are warranted to investigate potential prenatal intervention in the treatment of IUGR.

Purpose: After reconstruction of jejunal atresias at the ligament of Treitz, many patients do not respond to simple tapering and anastomosis requiring repetitive operations because of dysfunction of dilated proximal bowel. A new operative approach using lateral duodenectomy and duodenojejunostomy (LDAD) is reported. Methods: Three infants with atresias within 10 cm of the ligament of Treitz were treated with LDAD, and their records are reviewed retrospectively. The entire duodenum is visualized after creating a malrotation; this is followed by opening the dilated duodenum and resecting dilated proximal jejunum. The resection is extended proximally, incorporating the lateral duodenal incision, excising the lateral duodenal wall, and preserving the ampulla. The residual duodenum is fashioned into a tube and anastomosed to the spatulated distal jejunum. Results: Three infants underwent this procedure over a 4-year period. Two had undergone tapering enteroplasties previously but were unable to tolerate oral feedings; 1 infant had LDAD primarily. All were ultimately successfully managed by LDAD and were feeding within 14 days. Follow-up is from 14 to 49 months. Conclusion: Although experience is limited to 3 patients, the prompt return of intestinal function with LDAD may justify primary use of this more radical procedure in difficult-to-treat proximal atresias. J Pediatr Surg 35:353-356. Copyright © 2000 by W.B. Saunders Company.

Background/purpose Congenital diaphragmatic hernia (CDH) remains a significant cause of neonatal death. A wide spectrum of disease severity and treatment strategies makes comparisons challenging. The objective of this study was to create a standardized reporting system for CDH. Methods Data were prospectively collected on all live born infants with CDH from 51 centers in 9 countries. Patients who underwent surgical correction had the diaphragmatic defect size graded (A–D) using a standardized system. Other data known to affect outcome were combined to create a usable staging system. The primary outcome was death or hospital discharge. Results A total of 1,975 infants were evaluated. A total of 326 infants were not repaired, and all died. Of the remaining 1,649, the defect was scored in 1,638 patients. A small defect (A) had a high survival, while a large defect was much worse. Cardiac defects significantly worsened outcome. We grouped patients into 6 categories based on defect size with an isolated A defect as stage I. A major cardiac anomaly (+) placed the patient in the next higher stage. Applying this, patient survival is 99% for stage I, 96% stage II, 78% stage III, 58% stage IV, 39% stage V, and 0% for non-repair. Conclusions The size of the diaphragmatic defect and a severe cardiac anomaly are strongly associated with outcome. Standardizing reporting is imperative in determining optimal outcomes and effective therapies for CDH and could serve as a benchmark for prospective trials.

Enteric duplication cysts (EDC) are typically solitary lesions that occur throughout the alimentary tract. Postnatal diagnosis is often prompted when complications occur from bleeding, obstruction, or infection. We present a case of multiple EDC diagnosed prenatally, managed with prenatal and neonatal follow-up and resection in infancy. Prenatal detection allowed for optimal management prior to the development of symptoms or complications.

Congenital diaphragmatic hernia (CDH) and esophageal atresia (EA) are fairly common congenital anomalies, but the occurrence of both is exceedingly rare, with only anecdotal cases reported in the English literature. The primary objective of the current study is to assess the incidence and outcomes of CDH/EA using the Congenital Diaphragmatic Hernia Study Group registry.The Congenital Diaphragmatic Hernia Study Group registry was queried from January 2000 through August 2011. Patients with CDH/EA were identified. The primary end point was survival and the secondary end point was seeking to identify variables that might explain variances in outcomes.During the study period, 4,888 patients were reported to the Congenital Diaphragmatic Hernia Study Group registry. Twenty-three (0.5%) had an associated EA, with an overall survival significantly lower than the registry mean (26.1% vs 70.3%; p0.001). These patients had significantly lower birth weights (1.8 vs 2.94 kg), more cardiac abnormalities, and more chromosomal abnormalities (p0.001). Only 6 of the 23 CDH/EA patients had a CDH repair. In addition, the cohort had significantly fewer primary CDH repairs (4.3% vs 39.3%; p0.001). Logistic regression analysis identified birth weight, cardiac abnormalities, repair, and surfactant administration to be significantly associated with adverse outcomes. Esophageal atresia was the only variable not independently associated with survival.In patients with both CDH and EA, survival is significantly lower than other patients with CDH, but not uniformly lethal, therefore, intent to treat is a viable approach. Although the association of CDH with EA has a substantial impact on survival, it is the presence of low birth weight, cardiac and chromosomal abnormalities, surfactant use, and larger defects--and not the mere presence of EA--that influences the outcomes of this unique cohort.

Background Congenital pulmonary airway malformation (CPAM) is a rare congenital anomaly that occurs sporadically throughout fetal development. CPAM is usually a lobar process, but involvement of an entire lung is exceedingly rare. We present a small series of patients with multilobar CPAM who, to the best of our knowledge, are the first reported cases of giant CPAMs treated with pneumonectomy at birth. Methods After institutional review board approval, 93 medical records were reviewed for infants 0 to 12 months with congenital cystic adenomatoid malformation (CCAM) from 1990 to 2011. Three patients with entire lung involvement were included. Results Two patients were identified prenatally by ultrasonography and 1 was diagnosed at birth. Prenatally, the 2 patients exhibited mediastinal shift and steroids were administered. A pericardial effusion and decreased movement developed in 1 patient, requiring an emergent cesarean section at 31 weeks' gestation. All 3 patients underwent immediate newborn resection. One infant went into cardiac arrest on delivery and was resuscitated and taken for emergent resection. The 2 patients delivered vaginally at term tolerated spontaneous ventilation without positive pressure. All 3 patients underwent an emergent pneumonectomy on the first day of life. The premature infant died intraoperatively after CPAM removal from severe pulmonary hypertension (HTN) and contralateral lung hypoplasia. The hospital course for these patients was characterized by prolonged stays in the intensive care unit (ICU), pneumonia, ventilator dependence, and pulmonary HTN. Bronchoscopy revealed tracheomalacia in 1 patient that was relieved by aortopexy; the other patient had bronchomalacia requiring tracheotomy. Conclusions Emergent total pneumonectomy can be lifesaving, although significant pulmonary HTN can be expected. Management options may include fetal surgical intervention, ex utero intrapartum treatment (EXIT), and expectant management. Extracorporeal membrane oxygenation (ECMO), a prolonged ICU course, and symptomatic tracheomalacia/bronchomalacia may be anticipated. Families can be counseled that survival is achievable with adequate contralateral lung development.

As fetal swallowing is documented in utero, supplementation of the ingested amniotic fluid with nutrients or hormones has been postulated as a potential prenatal treatment for intrauterine growth retardation (IUGR). To study the effect of epidermal growth factor (EGF) on the developing fetal small intestine, 12 pregnant rabbits underwent operation on day 24 of a normal 31-day gestation. Bilateral ovarian end fetuses underwent catheterization of their respective amniotic cavities with attachment to a miniosmotic pump. Study fetuses received recombinant human EGF at approximately 300 micrograms/kg/d for 1 week; controls received carrier solution only at an equivalent rate. On gestational day 31, fetuses were delivered by cesarean section and somatic measurements were recorded. The small intestine was harvested and proximal, middle, and distal regions were analyzed for lactase and maltase enzyme activity. Additionally, the uptake of radiolabeled glucose and proline was measured by a standard everted mucosal sleeve technique for each segment. Results were analyzed by Student's paired t test and reported as mean +/- SEM. Nine fetal pairs survived (75%). Small intestinal (SI) length was increased in EGF fetuses (54.8 +/- 1.9 cm) versus control (50.4 +/- 2.7 cm) (P = .02). Lactase activity, reported as UE/g protein, was significantly increased in the proximal segments in the EGF-infused fetuses; maltase was significantly increased in both the proximal and middle segments (P.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Postoperative infectious complications in children following perforated appendicitis present in diverse ways. We present two unusual complications of appendectomy for perforated appendicitis: an acute scrotum after open and laparoscopic appendectomy. A retrospective review of two cases of scrotal abscess following appendectomy at our hospital as well as a MEDLINE search was performed to review the clinical presentation, etiology, type of treatment, and outcome of these patients. Although scrotal inflammation occurring postoperatively in a patient with perforated appendicitis may be due to an incarcerated hernia, it is much more likely to be due to a scrotal abscess. Patients without a patent processus vaginalis or inguinal hernia at initial presentation of peritonitis must be carefully followed in the postoperative period and explored early if testicular or scrotal pain becomes manifest.

Background and aims The transcription factor GATA4 is expressed throughout most of the small intestine except distal ileum, and restricts expression of the apical sodium-dependent bile acid transporter (ASBT), the rate-limiting intestinal bile acid transporter, to distal ileum. The hypothesis was tested that reduction of GATA4 activity in mouse small intestine results in an induction of bile acid transport in proximal small intestine sufficient to restore bile acid absorption and homeostasis after ileocaecal resection (ICR). Methods Bile acid homeostasis was characterised in non-surgical, sham or ICR mice using two recombinant Gata4 models in which Asbt expression is induced to different levels. Results Reduction of intestinal GATA4 activity resulted in an induction of ASBT expression, bile acid absorption and expression of bile acid-responsive genes in proximal small intestine, and a reduction of luminal bile acids in distal small intestine. While faecal bile acid excretion and bile acid pool size remained unchanged, the bile acid pool became more hydrophilic due to a relative increase in tauro-β-muricholate absorption. Furthermore, proximal induction of Asbt in both Gata4 mutant models corrected ICR-associated bile acid malabsorption, reversing the decrease in bile acid pool size and increase in faecal bile acid excretion and hepatic cholesterol 7α-hydroxylase expression. Conclusions Reduction of intestinal GATA4 activity induces bile acid absorption in proximal small intestine without inducing major changes in bile acid homeostasis. This induction is sufficient to correct bile acid malabsorption caused by ICR in mice.

Iatrogenic bronchial perforation is an uncommon complication in intubated premature infants. The authors present 2 cases of bronchial perforation caused by closed-tube endotracheal suction catheters. These presented in the first 3 days of life with pneumothorax requiring chest tube placement. Medical management was unsuccessful because of the high-volume air leak present and surgical intervention was required. A bronchial perforation of the right lower bronchus was identified in both cases and was repaired in the second case. This represents the first report in the literature of iatrogenic bronchial perforation in premature infants by closed-tube endotracheal suctioning catheters. Bronchial perforation requires early recognition and prompt repair if successful outcome is to be obtained.

Background/purpose. Graduates of a university surgical residency program were surveyed to identify the timing of specialty selection and the impact that studying in a research laboratory had on subsequent acceptance into a fellowship program. Methods. Between 1975 and 1990, 86 residents completed general surgery training at UCLA Medical Center. A survey was sent to all graduates to determine the focus of their previous laboratory research and when they selected their eventual surgical specialty. Responses were received from 67 of the 86 graduates (78%). Results. Forty-eight of the sixty-seven respondents (72%) took one or more years of surgical research during residency. Postresidency fellowship training was selected by 55 of 67 (82%); 50 applied to fewer than five programs; 49 of 55 (89%) received one of their top three choices. Twenty-seven of the sixty-seven residents pursued an academic career (40%). Residents who performed at least 2 years of research were more likely to become academicians (53%) than residents who did 1 year or less of research (22%). Only 39 of 67 residents (58%) had selected a specialty after 2 years of clinical training; 28 more made the selection after the third clinical year. All residents interested in cardiac surgery (n = 18) or plastic surgery (n = 4) prior to research were accepted into fellowships in those specialities, whereas only 37% of those who had an interest in other fields pursued the same specialty (P < 0.0001). Residents performing research in general surgery (n = 9), surgical oncology (n = 18), cardiac surgery (n = 14), and plastic surgery (n = 3) were more likely to practice in that specialty than those doing research in other specialty laboratories. Conclusions. General surgery residents performing research in a specialty laboratory are likely to pursue fellowship training relating to that field. Those who select a career in cardiac or plastic surgery prior to research are most likely to enter into these fields as their eventual specialty. Residents who perform 2 or more years of laboratory research publish more papers and often pursue an academic career.

Background/Purpose The diagnostic evaluation, patient stratification, and prenatal counseling for congenital obstructive uropathy remain sub-optimal. Matrix metalloproteinase (MMP) expression profiles are emerging as a valuable diagnostic tool in assorted disease processes. We sought to determine whether congenital obstructive uropathy impacts MMP expression in fetal urine. Methods Fetal lambs (n = 25) were divided in two groups: group I (n = 12) underwent a sham operation and group II (n = 13) underwent creation of a complete urinary tract obstruction. Gelatin zymography panels for 4 MMP species were performed on fetal urine in both groups at comparable times post-operatively. Statistical analysis was by the Fisher's exact test ( P Results Overall fetal survival was 80% (20/25). A variety of significant differences in MMP expression between the two groups were identified. The following profiles were present only in obstructed animals: any MMP other than MMP-2 ( P = .029), including any MMP other than 63 kDa and 65 kDa ( P = .009); 2 or more MMPs excluding MMP-2s (0.029); and 3 or more MMPs ( P = .029). Conclusions Limited matrix metalloproteinase expression is present in the urine of normal ovine fetuses. Fetal obstructive uropathy impacts urinary MMP expression in various distinguishable patterns. Prenatal urinary MMP profiling may become a practical and valuable diagnostic tool in the evaluation of congenital obstructive uropathy.

We present an unusual case of a congenital left subcostal hernia in a female born at 39 weeks by caesarean delivery to a 39 year-old gravida(2)para(1-2)abortus(0) mother. The pregnancy was complicated by gestational diabetes, although she had normal prenatal imaging. After an uneventful caesarean delivery, the patient's initial physical examination was normal although subsequently was found to have a left subcostal hernia. During surgical evaluation, a reducible hernia was found along with left renal agenesis and no underlying masses. At 4 weeks of age, the patient's hernia was successfully repaired with no sequela. We present the first reported case of a congenital subcostal hernia, evaluation, and treatment.

A 6-year-old boy with massive gastrointestinal bleeding was found to have a large patent ductus venosus (PDV). Systemic symptoms of PDV (eg, hypergalactosemia and hepatic, pulmonary, and cardiac dysfunction) are frequent. However, gastrointestinal bleeding with the presence of a large portosystemic shunt is not a known complication of this anomaly. The shunt was successfully treated with embolization by using the Amplatzer vascular plug, with immediate cessation of bleeding. The authors propose that relative ischemia of the bowel, rather than portal hypertension, was the cause of the gastrointestinal bleeding in this child.

The purpose of this study was to determine whether ex utero intrapartum treatment with extracorporeal membrane oxygenation (EXIT to ECMO) is a reasonable approach for managing patients antenatally diagnosed with severe congenital diaphragmatic hernia (CDH).A 6-year retrospective review was performed on fetuses with severe CDH (liver herniation and a lung/head ratio1.4, percentage of predicted lung volume15, and/or congenital heart disease). Fourteen of the patients underwent EXIT with a trial of ventilation. Fetuses with poor preductal oxygen saturations despite mechanical ventilation received ECMO before their delivery. Maternal-fetal outcomes were analyzed.There were no maternal-reported complications. Three babies passed the ventilation trial and survived, but 2 of them required ECMO within 48 hours. The remaining 11 fetuses received ECMO before their delivery. Overall survival after EXIT-to-ECMO was 64%. At 1-year follow-up, all survivors had weaned off supplemental oxygen, but 57% required diuretics and/or bronchodilators.This is the largest reported experience using EXIT to ECMO in the management of severe CDH. The EXIT-to-ECMO procedure is associated with favorable survival rates and acceptable pulmonary morbidity in fetuses expected to have a poor prognosis under conventional management.

Introduction Intrauterine growth–retarded (IUGR) infants have impaired gastrointestinal function with feeding difficulties and predisposition to necrotizing enterocolitis. The rabbit provides a model of IUGR based on uterine position. Sodium/glucose cotransporter–1 (SGLT-1) is a membrane protein responsible for carbohydrate transport across the intestinal brush border membrane. Previous studies demonstrate increases in small intestinal (SI) nutrient uptake in response to amniotic fluid supplementation with epidermal growth factor (EGF). To determine whether SGLT-1 expression plays a role in the intestinal response to EGF supplementation, this IUGR rabbit model was evaluated. Methods Eight pregnant rabbits underwent placement of intraamniotic catheters into 2 normal (Nl) and 2 IUGR fetuses per mother on gestational day 24. Mini-osmotic pumps infused either EGF (300 μ g/kg per day) or control solution forming 4 study groups (EGF-Nl vs Cont-Nl; EGF-IUGR vs Cont-IUGR). On gestational day 31, the fetal SI was harvested. Sodium/glucose cotransporter–1/glyceraldehyde-3-phosphate dehydrogenase messenger RNA (mRNA) densitometric band ratios were measured by reverse transcriptase polymerase chain reaction. Immunohistochemistry SGLT-1 staining was performed on middle SI. Statistical analysis was performed using the analysis of variance. Results Sodium/glucose cotransporter–1 was expressed in the gastrointestinal tract throughout the last one third of gestation. There were no native differences in SGLT-1 mRNA expression between Nl and IUGR fetuses at term. Epidermal growth factor infusion did not significantly affect SI SGLT-1 mRNA expression in either Nl or IUGR fetuses vs controls (EGF-Nl = 1.94 vs Cont-Nl = 1.94, P = .98; EGF-IUGR = 1.77 vs Cont-IUGR = 1.85, P = .74). Immunohistochemistry revealed increased SGLT-1 SI protein expression in infused IUGR fetuses. Conclusions Increases in previously documented up-regulation in SI nutrient transport after EGF infusion are independent of SGLT-1 mRNA expression. Further studies are warranted investigating SGLT-1 protein expression, localization, and functional kinetics in response to amniotic fluid supplementation with EGF.

Infants with gastroschisis (GS) commonly require total parenteral nutrition and prolonged hospitalization because of intestinal dysfunction resulting from dysmotility and/or malabsorption. To investigate prepartum small intestinal (SI) nutrient absorption in GS, a fetal rabbit model was surgically created on gestational day 24 (term, 31 to 33 days) in 11 time-mated New Zealand White does in each left ovarian-end fetus. Each right ovarian-end fetus served as a control (C) and was manipulated only. All does, 10 of 11 GS fetuses (91%), and 8 of 11 C fetuses (73%) survived to gestational day 30. GS fetuses had significantly reduced total body weights, SI weights, and SI lengths compared with C fetuses. Using the everted mucosal sleeve technique, the uptakes of an amino acid (proline) and a sugar (glucose) were determined. The uptakes of proline per milligram SI, proline per centimeter SI, and glucose per milligram SI were significantly impaired in GS fetuses compared with C fetuses (P.04 by Student's paired t test). The uptake of glucose per centimeter SI was also reduced in GS fetuses, but not significantly. Uptake capacities (a measure of the entire SI's ability to absorb a given nutrient) were significantly reduced in GS fetuses compared with C fetuses (proline, 2,670 +/- 612 nmol/min/entire SI v 6,842 +/- 399 nmol/min/entire SI, P.008 by Student's paired t test; glucose, 402 +/- 69 nmol/min/entire SI v 950 +/- 103, P.008 by Student's paired t test).

Coccidioidomycosis is a fungal infection endemic to the desert regions of the southwestern United States. Pulmonary symptoms predominate and are usually mild and self-limited. Dissemination is rare in the immunocompetent host. We present a case of disseminated, peritoneal coccidioidomycosis diagnosed during routine inguinal herniorrhaphy in an adult male. The current literature is summarized, and management recommendations are suggested.

Background. The gastrointestinal (GI) tract performs the digestion, propulsion, and absorption of nutrients both pre- and postnatally, although little is known about the development of fetal motility. We evaluated the development of GI motility using a novel fetal rabbit model. Methods. Nine pregnant rabbits were obtained and three litters were studied at day 24 (n = 24), 27 (n = 29), and 30 (n = 24) of their 31-day gestation. Under ultrasound guidance fetal position was identified, a spinal needle was percutaneously inserted into each fetal stomach, and fluorescein, labeled with color-coded microspheres, was injected. Two hours later, fetuses were delivered and weighed, and the small intestine was harvested. The absolute length of fluorescein traveled was measured by ultraviolet light optical density and the percentage motility was calculated by dividing the absolute length of fluorescein traveled by the total small intestinal length. Results. All injected fetuses survived. The length of fluorescein traveled significantly increased from day 24 (8.1 ± 2.1 cm) to day 27 (18.8 ± 4.6 cm) and 30 (22.6 ± 5.2 cm). The length of fluorescein traveled significantly correlated with body weight on day 27 and 30. Calculated percentage motility significantly increased from day 24 to 30. However, percentage motility showed no correlation with fetal weight. Conclusions. This study describes a novel rabbit model for the assessment of in vivo fetal GI motility. Motility matured during the last third of gestation when assessed by the absolute length of fluorescein travel and the percentage motility. These results confirm that late-gestation fetuses have developed sufficient motility to propel potential nutrients, drugs, or gene therapy vectors to the small intestinal absorptive surface area.

A patient was treated for lobar pneumonia due to coccidioidomycosis. When the pneumonia recurred, the patient was found to have an arteriovenous malformation, which had become infected. Complete resolution was achieved with resection and postoperative amphoterecin B therapy.

We sought to characterize practices and attitudes of maternal-fetal medicine (MFM) and fetal care pediatric (FCP) specialists regarding fetal abnormalities.This was a self-administered survey of 434 MFMs and FCPs (response rate: MFM 60.9%; FCP 54.2%).For Down syndrome (DS), congenital diaphragmatic hernia (CDH), spina bifida: MFMs were more likely than FCPs to support termination (DS 52% vs 35%, P.001; CDH 49% vs 36%, P.001; spina bifida 54% vs 35%, P.001), and consider offering termination options as highly important (DS 90% vs 70%, P.001; CDH 88% vs 69%, P.001; spina bifida 88% vs 70%, P.001). For DS only, MFMs were less likely than FCPs to think that pediatric specialist consultation should be offered prior to a decision regarding termination (54% vs 75%, P.001). MFMs reported report higher termination rates among patients only for DS (DS 51% vs 21%, P.001).MFM and FCP specialists' counseling attitudes differ for fetal abnormalities.

To examine the effect of prenatal steroids on fetal intestinal maturation, eight pregnant rabbits received either dexamethasone (Dex) or saline (Cont) on Days 25-27 of a 31-day gestation. As the rabbit provides a model of growth retardation based on uterine position, fetuses were identified as favored (Fav) or runt(Runt), generating four study groups: ContFav, ContRunt, DexFav, and DexRunt. On Day 31 the small intestinal uptake of glucose and proline was measured by an everted sleeve technique. Additionally, lactase and maltase activity was determined. Small intestinal length and nutrient uptake was significantly increased in the Dex fetuses. Control runts had a trend to decreased levels of nutrient uptake when compared to their favored counterparts. This trend reversed in the Dex fetuses with runt nutrient uptake surpassing that of the favored fetus. A trend to increased enzyme activity of both lactase and maltase was demonstrated. This report provides the first description of maternal steroid administration causing a marked increase in fetal small intestinal length and glucose and praline absorption in an in vivo model of intrauterine growth retardation.

Introduction: Uninterrupted passage of amniotic fluid (AF) through the GI tract appears necessary for normal fetal growth. Previous work suggests that this is related to defective nutrient transport when AF passage is eliminated by EL in normal weight animals. The rabbit provides a naturally occurring model of IUGR based on fetal position within the bicornuate uterus. The effect of in-utero EL on SI development in normal and IUGR fetuses was evaluated. Methods: Thirteen pregnant rabbits underwent operation on day 24 of their 31-day gestation. Ipsilateral normal and IUGR fetuses underwent EL; contralateral fetuses underwent cervical exploration only, forming 4 study groups (Cont-Nl, Cont-IUGR; EL-Nl, EL-IUGR). Fetuses were sacrificed on day 31. The SI was analyzed for: villus height, epithelial cell proliferation by PCNA staining, sodium-glucose cotransporter-1 (SGLT-1) expression by PCR against internal controls and SGLT-1 localization by immunohistochemistry. Statistical analysis was performed using the paired Student’s t-test. Results: Fetal survival was 92%. IUGR fetuses had decreased weight vs. normal (p < 0.0004) which was further decreased by EL. Villus height and SI epithelial proliferation were significantly decreased in IUGR fetuses in both groups yet not affected by EL. IUGR increased SGLT-1 mRNA production (Cont-IUGR = 1.3 vs. Cont-Nl = 1.2; p = 0.03). EL virtually eliminated villus enterocyte SGLT-1 protein expression in both groups. Conclusions: AF exclusion by in-utero EL decreased fetal weight and SGLT-1 protein expression. SI villus height and enterocyte proliferation is depressed in IUGR fetuses, but remains independent of AF passage. Exposure of the fetal GI tract to AF appears necessary for proper expression of nutrient transporter proteins.

To investigate the effect of normal fetal swallowing and amniotic fluid ingestion on small intestinal disaccharidase development, 13 pregnant New Zealand White rabbits underwent operation on day 24 of a normal 31-day gestation. The right ovarian fetus in the bicornuate uterus underwent esophageal ligation (EL), while the contralateral left fetus underwent cervical exploration only, and served as the control (C). Rabbits were sacrificed on gestational day 31, fetal somatic measurements obtained, and the midjejunum removed for determination of disaccharidase activity and protein content. There was one maternal death, and 9 of 12 fetal pairs survived the entire study period (75%). Results are reported as mean +/- SEM, analyzed by two-tailed Student's t testing with P < .05 being considered significant. Fetal weight was decreased in EL (48.6 +/- 2.7 g) versus C (51.4 +/- 3.2 g) (P = .06). Small intestinal length decreased in EL (49.2 +/- 2.0 cm) versus C (54.9 +/- 1.1 cm) (P = .01). Midjejunal protein content (mg/mL homogenate) was also significantly decreased in EL (38.4 +/- 3.4) versus C (46.2 +/- 3.7) (P = .05). Sucrase activity was not detectable in either group. Lactase activity in jejunal mucosa was not effected when expressed as units of enzyme per milliliter of homogenate (EL = 0.357 +/- 0.03 v C = 0.373 +/- 0.04; P = .70) and units enzyme per gram of protein (EL = 38.8 +/- 4.2 v C = 34.2 +/- 4.6; P = .44). We have confirmed previous studies demonstrating decreases in somatic growth, small intestinal length, and mucosal nutrient transport in rabbit fetuses following esophageal ligation.(ABSTRACT TRUNCATED AT 250 WORDS)