Outcomes of congenital diaphragmatic hernia: a 12-year experience.

OBJECTIVE: To determine outcomes for babies with congenital diaphragmatic hernia (CDH) diagnosed prenatally and postnatally presenting to a tertiary unit. METHOD: Fetal medicine database and neonatal surgical unit admission books were reviewed to identify cases of CDH over a 12-year period (Jan 1998- Dec 2009). RESULTS: A total of 132 cases of CDH were diagnosed prenatally and 39 cases diagnosed postnatally. Mean gestation at diagnosis was 22 weeks (range 13-37 weeks). Karyotyping was abnormal in 15.9%; abnormal karyotype in 3.6% of fetuses without other structural anomalies compared with 38.9% when other anomalies were identified. In 45 cases (34.1%) pregnancy was terminated. Two stillbirths occurred (2.3% of ongoing pregnancies). One hundred twenty-four babies were live born, of whom 98 babies underwent surgery. Survival to discharge of all live born babies was 72.6%; survival following surgery was 91.8%. Birthweight had a significant effect on survival (odds ratio 0.22, 95% confidence intervals 0.08-0.66). Survival for live born babies prenatally diagnosed was significantly lower (65.9%) than those diagnosed postnatally (92.3%). CONCLUSION: Abnormal karyotype was more common when CDH was associated with other anomalies. In multivariate analysis, lower birthweight and prenatal diagnosis had a significant impact on survival. Only prenatally diagnosed CDH survival figures should be utilised in prenatal counselling.

Gastroschisis and the risk of short bowel syndrome: outcomes and counselling.

BACKGROUND: Gastroschisis can be associated with short bowel syndrome (SBS). We present 4 cases with significant bowel shortening with very different ante- and postnatal presentations. CASES: Three of the cases demonstrated 'vanishing' gastroschisis with progressively worsening antenatal intra-abdominal bowel dilatation with no defect present at birth. The fourth case followed an uneventful course antenatally but developed SBS considered secondary to gastroschisis-related atresia and necrosis. All 4 cases were classified as having SBS and were enrolled within the paediatric Intestinal Rehabilitation Programme. This involves autologous gastrointestinal reconstruction following a period of bowel expansion with concomitant parenteral and enteral nutrition. DISCUSSION: These cases demonstrate that the serious complication of significant bowel loss cannot always be anticipated. Early multidisciplinary discussion with the parents enables a shared understanding of potential outcomes. It can aid the recognition of 'vanishing' gastroschisis enabling expedient investigations and early intervention, minimising morbidity and maximising bowel length.

Phosphodiesterase inhibitor effect on small artery function in preeclampsia.

OBJECTIVE: To determine if the phosphodiesterase type 5 inhibitor, sildenafil citrate improves endothelial-dependent relaxation of small arteries from women with preeclampsia. METHODS: Myometrial and omental biopsies were taken from women participating in a randomized placebo-controlled trial using sildenafil citrate in women with preeclampsia. Vasoconstriction and endothelial-dependent relaxation of small arteries was measured utilizing wire myography. RESULTS: Vasoconstriction and endothelial-dependent relaxation of myometrial and omental arteries were not altered in women taking sildenafil. CONCLUSION: Acute effects may have been lost as sildenafil administration occurred many hours prior to myography. Plasma sildenafil levels may have been lower than required for vascular response.

A randomised, double-blinded, placebo-controlled study of the phosphodiesterase type 5 inhibitor sildenafil for the treatment of preeclampsia.

OBJECTIVE: To determine if the phosphodiesterase type 5 inhibitor sildenafil prolongs pregnancy in women with preeclampsia. METHODS: Women with preeclampsia at gestational ages 24-34 weeks were recruited from nine hospitals in the UK, and randomly assigned to sildenafil citrate or placebo. Medication was increased every 3 days from 20 mg three times daily (tid), to 40 mg, and 80 mg tid. The primary endpoint was prolongation of pregnancy from randomisation to delivery (days). Secondary endpoints were markers of maternal disease and cord pH at delivery and infant weight. Details of all adverse events were also collected. Plasma samples were taken to establish pharmacokinetic information. Data analysed on a modified intention to treat analysis. The study had a power of >95% to detect a difference of 5 days. RESULTS: Of 35 women, 17 were allocated to sildenafil and 18 to placebo. There was no difference in time from randomisation to delivery in the two treatment groups, with a median time of 4 days (range 1-15) in the sildenafil group and 4.5 days (range 1-30) in the placebo group. Sildenafil achieved maximum drug concentrations of 48 ng/ml, 88 ng/ml, and 271 ng/ml after 3 days of 20 mg, 40 mg and 80 mg tid, respectively. CONCLUSION: We have safely conducted a clinical trial of a drug not routinely used during pregnancy. Sildenafil in the escalating dose regimen 20-80 mg tid was well tolerated, with no increase in maternal or fetal morbidity or mortality but did not prolong pregnancy duration in women with preeclampsia. (ClinicalTrials.gov number, NCT 00141310).