SUMMARY CD41 CD25 1 T regulatory cells (T Reg ), suppress antigen-specific immune responses and are important for allograft tolerance. During pregnancy the mother tolerates an allograft expressing paternal antigens (the fetus) requiring substantial changes in immune regulation over a programmed period of time. We analysed whether immune-suppressive T Reg cells were altered during pregnancy and therefore might play a part in this tolerant state. The presence of T Reg cells was assessed in the blood of 25 non-pregnant, 63 pregnant and seven postnatal healthy women by flow cytometry. We observed an increase in circulating T Reg cells during early pregnancy, peaking during the second trimester and then a decline postpartum. Isolated CD25 1 CD4 1 cells expressed FoxP3 messenger RNA, a marker of T Reg cells, and suppressed proliferative responses of autologous CD4 1 CD25 -T cells to allogeneic dendritic cells. These data support the concept that normal pregnancy is associated with an elevation in the number of T Reg cells which may be important in maintaining materno-fetal tolerance.

The type 2 isoform of 11beta-hydroxysteroid dehydrogenase (11beta-HSD2), which inactivates cortisol (F) to cortisone (E), has been suggested to play a role in the ontogeny of the fetal pituitary-adrenal axis and also protect the developing fetus from the deleterious effects of circulating maternal glucocorticoids. The abundance of 11beta-HSD2 in the placenta and other fetal tissues was inferred from the F/E ratio in 17 term deliveries in both umbilical arterial (1.73 +/- 0.24, mean +/- SE) and umbilical venous blood (1.16 +/- 0.14) compared with adult peripheral venous blood (7.76 +/- 0.57, n = 70). Using sensitive assays for 11beta-HSD2 and an in-house human 11beta-HSD2 antibody, the expression and activity of this enzyme in fresh frozen human placenta increased progressively from first (8-12 weeks, n = 16) and second (13-20 weeks, n = 9) to third trimester (term) pregnancies (39-40 weeks, n = 50). Placental 11beta-HSD2 activity was significantly reduced in deliveries complicated by intrauterine growth restriction (IUGR) [25-36 weeks, n = 12, activity 380 pmol/mg/h median (225-671; 95% confidence interval)], compared with the term deliveries [888 (725-1362)] and with appropriately grown pre-term deliveries [27-36 weeks, n = 14, activity 810 (585-1269)], P < 0.05. In human pregnancy placental 11beta-HSD2 activity increases markedly in the third trimester of pregnancy at a time when maternal circulating levels of glucocorticoid are rising. The finding of attenuated placental 11beta-HSD2 activity in IUGR suggests that glucocorticoids may, in part, contribute to impaired fetal growth and that this is closely controlled in normal gestation through placental 11beta-HSD2 expression.

Congenital malformations of the diaphragm remain associated with considerable infant mortality. Most cases are now diagnosed before birth and the prognosis is adversely affected by the presence of other structural or chromosomal anomalies. This presents significant challenges for those involved in counselling the parents of affected fetuses.

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This descriptive case study documents the treatment of a cohort of 6 women with pregnancies complicated by red cell alloimmunization who in previous pregnancies had objective evidence of severe fetal anemia prior to 20 weeks of gestation, with accompanying high perinatal loss (66% mortality). In the pregnancies described, 5 singletons and 1 dichorionic, diamniotic twin pregnancy underwent alternate week, serial intraperitoneal transfusions between 16 and 21 weeks, until a gestation when classical fetal intravascular transfusions could be commenced. In addition, 4 women consented to have additional, adjuvant maternal intravenous gammaglobulin (IVIG) therapy (0.8 g/kg per week). At the first fetal blood sampling at a median gestational age of 22 weeks (95% CI 21.2–23.4 weeks) the median hemoglobin concentration was 10.1 g% (95% CI 7.4–13.4 g%). In only 2 cases were the fetal hemoglobin levels at fetal blood sampling between –2 SD and –5 SD for gestational age; in 1 case this was associated with fetal mortality. This cohort indicates that such treatment may prevent severe fetal anemia from developing prior to 20 weeks and, in this cohort, indicated an improved survival of pregnancies (86% survival (6/7)), as compared to the previous history. The only perinatal mortality occurred in a growth-restricted fetus whose mother had a chronic opiate addiction. The fetus died prior to 20 weeks. Of the pregnancies that progressed beyond 20 weeks and commenced classical fetal intravascular transfusions, the survival was 100%.

Recombinant activated factor VII (rFVIIa) is emerging as a novel therapy for the treatment of life or fertilitythreatening post-partum haemorrhage (PPH) unresponsive to standard therapy that in some cases may prevent the need for peripartum hysterectomy. The level of evidence to date for use of rFVIIa in PPH is limited to case reports and case series with one nonrandomised study. No high-quality randomised controlled trials have been published at this stage, precluding a quality systematic review. Guidelines have been published for the use of rFVIIa in non-obstetric haemorrhage, though to date none are available for PPH. A multidisciplinary group of Australian and New Zealand clinicians from the fields of obstetrics, anaesthesia and haematology, who have both clinical experience in and/or knowledge of rFVIIa was convened by the manufacturer. This group produced an opinion and guideline based on their experience and the published international literature on the use of rFVIIa. This is intended to be used as a guideline and algorithm for the use of rFVIIa, though any use should be tailored to local practice and resources.

Introduction: Maternal red cell alloimmunization is a potential cause of perinatal morbidity and mortality. The outcome of severe disease has been transformed by the use of in-utero and particularly, fetal intravascular transfusion. In the majority of instances this is performed by cordocentesis. However, this cohort study represents the experience in a large tertiary referral centre in performing fetal intravascular transfusions via the intrahepatic vein (IHV). Methods: Over an 8-year period, 1997–2004, 221 in-utero transfusions (IUT) were performed for rhesus disease in 66 pregnancies. 86% had severe fetal anaemia caused by anti-D, 10.6% by anti-Kell and 3.4% by anti-c. The median maternal age of the cohort was 31 years (range 19–43). The median gestation at initial IUT was 25 weeks (interquartile range (IQR) 23–29 weeks). Results: A median number of three IUT were performed in each fetus (IQR 2–5) with a median haemoglobin at first fetal blood sampling of 7.3 g% (IQR 4.6–8.8 g%) (73% ≤5 SD and 27% ≤2 SD). Of the total intravascular transfusions, 170 were performed via the IHV (71.7%), 33 via cordocentesis (13.9%) and 1 by intracardiac puncture (0.5%). There were ‘transient’ bradycardias complicating 4.1% of all transfusions and amniorrhexis following 1.4%. 92% of babies were live born at a median gestation of 34 weeks (range 21–38) with a birth weight centile of 50 (range 3–90). There was no significant difference in intravascular transfusion complication rate when the procedure was performed via the IHV (7.6%) as compared to cord root puncture (3.0%) (Fisher’s exact test, p < 0.47). Conclusion: IUT performed by fetal IHV puncture is safe and carries no excess morbidity when performed for severe rhesus disease.

Blood was obtained by cordocentesis from a fetus with non-immune hydrops demonstrated by ultrasound scanning at 27 weeks' gestation. Abnormalities of serum transferrin isoelectric focussing (IEF) were identified, characteristic of a congenital disorder of glycosylation type I (CDG-Ia). A diagnosis of CDG-Ia was confirmed by enzyme analysis of cultured amniocytes. This is the first report of CDG-Ia diagnosed by serum analysis in a fetus. Previous reports have warned that diagnostic abnormalities do not appear in serum until several weeks after birth. The sensitivity of cordocentesis transferrin IEF is unknown but is less than 100% effective because cases have been diagnosed postnatally after normal prenatal or neonatal studies. Enzyme analysis or mutation analysis is required for diagnosis of congenital disorder of glycosylation (CDGs) regardless of whether a diagnostic transferrin pattern is identified prenatally. The analysis of a small sample of serum, from cordocentesis, performed to check for fetal anemia, simplified the investigation, diagnosis, and genetic counselling of a case of non-immune hydrops detected at 27 weeks' gestation. This might be a useful test for other cases in these circumstances, as fetal blood is usually collected to check for anemia.