Joanna Gillham

An overview of endothelium-derived hyperpolarising factor (EDHF) in normal and compromised pregnancies

Normal pregnancy is associated with decreased peripheral vascular resistance, although the mechanisms are poorly understood. Pre-eclampsia is characterised by increased vessel resistance and a decreased relaxant capacity, contributing to the associated hypertension, multi-organ damage and intra-uterine growth restriction. An endothelium-derived vasoactive substance-endothelium-derived hyperpolarising factor may be responsible for the physiological changes in the maternal vasculature. This is a review of the current understanding of the complexities of vessel behaviour. Evidence is reviewed to support the possible contribution of endothelium-derived hyperpolarising factor to the compromised vascular state in pre-eclampsia. This is an important area of research which may help to understand further the pathogenesis of this specific pregnancy related disease, that contributes greatly to maternal and fetal morbidity and mortality.

Regulation of Endothelial-Dependent Relaxation in Human Systemic Arteries by SKCa and IKCa Channels:

Blockade of small-conductance Ca 2 + -activated K + channels (SK Ca ) and intermediate conductance Ca 2 + -activated K + channels (IK Ca ) can cause inhibition of endothelium-dependent hyperpolarizing factor (EDHF) in many vascular beds from animals, but there is a relative paucity of data in human vessels. Systemic arteries, isolated from women with healthy pregnancies, relax to the endothelial-dependent agonist bradykinin via a nonprostacyclin and non–nitric oxide pathway attributable to EDHF. Therefore, in this study, the authors investigated the effect of pharmacological blockade of SK Ca and IK Ca on EDHF-mediated relaxation of human omental and myometrial arteries preconstricted with either arginine vasopressin or U46619. Human arteries were isolated from omental and myometrial biopsies taken from healthy women undergoing planned cesarean section at term. Endothelial function was assessed using wire myography. In all vessels examined, nonspecific blockade of IK Ca with charybdotoxin attenuated EDHF-attributed relaxation. However, when Tram 34 was used to block IK Ca , the attenuation of relaxation was evident only with U46619 preconstriction. In arteries from both vascular beds, and with either preconstrictor, a combination of either apamin and charybdotoxin or apamin plus Tram 34 almost ablated EDHF-attributable relaxation. These data support the notion that in human systemic arteries, activation of, primarily, SK Ca and IK Ca K + channel subtypes underlies EDHF-mediated relaxation. These results have important implications for future studies ascertaining the molecular mechanisms of hypertensive disorders (eg, preeclampsia, in which EDHF is thought to be aberrant).

Antenatal diagnosis of bowel dilatation in gastroschisis is predictive of poor postnatal outcome

PURPOSE Although gastroschisis infants usually have a good outcome, there remains a cohort of babies who fare poorly. We inquired whether the presence of bowel dilatation in utero is predictive of postnatal course in infants with gastroschisis. METHODS We compared the clinical course of infants who had bowel dilatation with those who did not. Bowel dilatation was defined as more than 20 mm in cross-sectional diameter on ultrasound at any gestational age. Outcome measures used were length of time of parenteral nutrition, death, and surgery for intestinal failure. RESULTS A review of 170 infants with gastroschisis identified 74 who had dilatation of more than 20 mm (43.5%). There was no significant difference in the incidence of intestinal atresia in those with bowel dilatation and those without (P = .07). Those with bowel dilatation spent a longer period on parenteral nutrition. There were significantly more deaths in the group with bowel dilatation (P = .01). There was no significant difference in the number of infants requiring surgery for intestinal failure between the 2 groups (P = .47). CONCLUSIONS We found that sonographically detected bowel dilatation more than 20 mm in utero in fetuses with gastroschisis may have value in predicting clinically significant adverse postnatal outcomes.

A randomised controlled trial comparing standard or intensive management of reduced fetal movements after 36 weeks gestation-a feasibility study

BackgroundWomen presenting with reduced fetal movements (RFM) in the third trimester are at increased risk of stillbirth or fetal growth restriction. These outcomes after RFM are related to smaller fetal size on ultrasound scan, oligohydramnios and lower human placental lactogen (hPL) in maternal serum. We performed this study to address whether a randomised controlled trial (RCT) of the management of RFM was feasible with regard to: i) maternal recruitment and retention ii) patient acceptability, iii) adherence to protocol. Additionally, we aimed to confirm the prevalence of poor perinatal outcomes defined as: stillbirth, birthweight <10th centile, umbilical arterial pH <7.1 or unexpected admission to the neonatal intensive care unit.MethodsWomen with RFM ≥36 weeks gestation were invited to participate in a RCT comparing standard management (ultrasound scan if indicated, induction of labour (IOL) based on consultant decision) with intensive management (ultrasound scan, maternal serum hPL, IOL if either result was abnormal). Anxiety was assessed by state-trait anxiety index (STAI) before and after investigations for RFM. Rates of protocol compliance and IOL for RFM were calculated. Participant views were assessed by questionnaires.Results137 women were approached, 120 (88%) participated, 60 in each group, 2 women in the standard group did not complete the study. 20% of participants had a poor perinatal outcome. All women in the intensive group had ultrasound assessment of fetal size and liquor volume vs. 97% in the standard group. 50% of the intensive group had IOL for abnormal scan or low hPL after RFM vs. 26% of controls (p < 0.01). STAI reduced for all women after investigations, but this reduction was greater in the standard group (p = 0.02). Participants had positive views about their involvement in the study.ConclusionAn RCT of management of RFM is feasible with a low rate of attrition. Investigations decrease maternal anxiety. Participants in the intensive group were more likely to have IOL for RFM. Further work is required to determine the likely level of intervention in the standard care arm in multiple centres, to develop additional placental biomarkers and to confirm that the composite outcome is valid.Trial registrationISRCTN07944306

Outcomes of congenital diaphragmatic hernia: a 12-year experience

To determine outcomes for babies with congenital diaphragmatic hernia (CDH) diagnosed prenatally and postnatally presenting to a tertiary unit.

TNF-α Alters Nitric Oxide- and Endothelium-Derived Hyperpolarizing Factor-Mediated Vasodilatation in Human Omental Arteries

Objective: To investigate the effect of TNF-α on the endothelial function of human systemic arteries. Methods: Omental arteries were obtained from healthy pregnant women undergoing Cesarean section and examined using isometric wire myography. Results: Incubation with TNF-α (1nM) alone did not alter bradykinin-mediated endothelium-dependent relaxation of arteries. However, TNF-α did attenuate nitric oxide- (NO) and prostacyclin-independent endothelial-mediated relaxation. Similarly, in vessels constricted with a high potassium solution (60 mM), which inhibits vasodilatation via endothelial-derived hyperpolarising factor (EDHF), TNF-α incubation also attenuated bradykinin-induced vasodilatation. Conclusions: The vasorelaxant capacity of human systemic arteries is compromised by TNF-α incubation in the presence of NO/prostacyclin or EDHF-blockade.

Urinary protein selectivity in nephrotic syndrome and pregnancy: resurrection of a biomarker when renal biopsy is contraindicated

Significant proteinuria in pregnancy can indicate the presence of serious conditions requiring investigation and treatment. The nephrotic syndrome in pregnancy presents a multitude of difficulties and is a relative contraindication of renal biopsy, particularly in the third trimester. We present a case of nephrotic syndrome of unknown cause presenting at 33 weeks of pregnancy. With renal biopsy contraindicated, we used the urine protein selectivity test, a largely discarded test predicting steroid-responsive nephrotic syndrome, to help inform the decision to give steroids. This led to a successful clinical outcome including the avoidance of neonatal ICU care for baby.

Altered endothelial function in isolated human myometrial vessels induced by plasma from women with pre-eclampsia is not reproducible in isolated mouse vessels.

In order to facilitate characterization of the circulating factor(s) in pre-eclampsia, the present study aimed to determine whether plasma from women with pre-eclampsia, which induces attenuated endothelial-dependent relaxation in human myometrial arteries, is also capable of inducing altered endothelial function in mouse vessels. Human vessels were isolated from myometrial biopsies taken from women with uncomplicated pregnancies (n = 6). Mesenteric and uterine arteries were isolated from male, female, non-pregnant and pregnant C57B mice (n = 24). Vessels were studied using a wire myograph and incubated with plasma (2%) from women with pre-eclampsia (n = 12) or controls (n = 12). Incubation of myometrial vessels from normal pregnant women with plasma from women with pre-eclampsia reduced endothelial-dependent relaxation. This effect was not reproduced in male or female mouse mesenteric or uterine vessels incubated with plasma from women with pre-eclampsia. In conclusion, there are species-specific differences in the actions of the circulating factor(s) on endothelial-dependent relaxation of human and mouse small arteries.

A maternity priority algorithm for emergency obstetric admissions

Introduction Obstetric triage departments have been developed for pregnant women presenting to obstetric services with problems ranging from the trivial to potentially life threatening. There is a need to develop systems to prioritise these women appropriately. Methods A maternity priority algorithm was devised based on well established A&E systems. The algorithm divides women into Red, Amber, Yellow or Green categories, and stipulates time guidelines for midwifery or medical review. A pilot survey of the algorithm was conducted over 1 month to determine; proportions in each category; appropriateness of each categorisation; ease of application. Results There were 571 admissions. Nine (1.6%) cases were Red, 15 (2.6%) were Amber, 67 (11.4%) were Yellow and 472 (82.7%) were Green. Eight cases were not classified. 23 (4%) women were assigned to a higher category than appropriate; 23 (4%) women were under classified who all presented with reduced fetal movements. Allocated Red cases were seen immediately, as stipulated, in 78% of cases with remaining cases seen within 60 min. 60% of allocated Amber cases were seen within the recommended 15 min, with remaining cases seen within 1 h 46 min. 80.6% of allocated Yellow cases were seen within the recommended 45 min, with remaining cases seen within 1 h 40 min. Conclusions While the majority of obstetric admissions are in the lowest priority category, the algorithm has proved relatively straightforward to apply and has good specificity. Further training about utilising the maternity priority algorithm and emphasis about timings is required.

Breast milk: friend or foe?

Anaphylaxis can occur secondary to breastfeeding. The authors present a case of a 30-year-old woman who complained of chest tightness, shortness of breath and a rash on the third day postpartum. She was treated for anaphylaxis and her symptoms resolved. Because she had taken tramadol prior to this event, a drug reaction was initially suspected. However, she experienced further episodes related to breastfeeding, despite stopping tramadol. Effective control of her symptoms was achieved with regular antihistamines, enabling her to continue breastfeeding. Antihistamines were interrupted after 8 weeks at which point lactation (in hospital) was once again associated with anaphylaxis. The diagnosis of breastfeeding induced anaphylaxis was made. There are six previously reported cases of breastfeeding induced anaphylaxis. The authors describe the second case of breastfeeding anaphylaxis extending beyond the neonatal period, controlled with antihistamines.