Human hypoblast formation is not dependent on FGF signalling.

Mouse embryos segregate three different lineages during preimplantation development: trophoblast, epiblast and hypoblast. These differentiation processes are associated with restricted expression of key transcription factors (Cdx2, Oct4, Nanog and Gata6). The mechanisms of segregation have been extensively studied in the mouse, but are not as well characterised in other species. In the human embryo, hypoblast differentiation has not previously been characterised. Here we demonstrate co-exclusive immunolocalisation of Nanog and Gata4 in human blastocysts, implying segregation of epiblast and hypoblast, as in rodent embryos. However, the formation of hypoblast in the human is apparently not dependent upon FGF signalling, in contrast to rodent embryos. Nonetheless, the persistence of Nanog-positive cells in embryos following treatment with FGF inhibitors is suggestive of a transient naïve pluripotent population in the human blastocyst, which may be similar to rodent epiblast and ES cells but is not sustained during conventional human ES cell derivation protocols.

Postnatal vaginal bleeding problems and General Practice.

OBJECTIVES: to investigate women's experiences of problems with vaginal loss from 28 days to three months postnatally and to describe the treatment and referral patterns for women who consult their GP about such problems during the first three months postnatally. DESIGN: a longitudinal questionnaire study of consecutively delivered postnatal women and a report-card survey of GP consultations by women with problems with postnatal vaginal loss. SETTING: two health districts in the south of England. PARTICIPANTS: women delivering in the two health districts during specified recruitment periods in 1995 and 1996. For the GP study, with her consent, the GP returned an anonymous registration card for each woman presenting. FINDINGS: in the survey of women, 20% (64/325) reported problems with postnatal loss occurring between 28 days and three months after the birth. Around a half of these consulted a GP. The GP study was disappointing in that only 26% (30/115) of practices agreed to take part and 16% (18/115) returned notification cards. Forty-eight women were included from 18 practices. The most common presenting symptoms were excessive bleeding (29/48; 60%) and prolonged bleeding (26/48; 54%). The commonest form of treatment was antibiotics alone (15/48; 31%) but 12 women (25%) were neither treated nor referred. Referral (n=19) was for hospital admission, out-patient appointment or direct referral for an ultrasound scan. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: morbidity related to abnormalities of postnatal vaginal fluid loss (lochia) has been shown to be significant, yet nothing was known about the outcome of related GP consultations during the first three months postnatally. A variety of treatment and referral patterns were revealed, highlighting the need for a systematic review of the literature on the management of secondary postpartum haemorrhage. Health care workers need to be aware of the significant morbidity experienced by postnatal women in relation to their lochial loss.

Risk factors for hospital admission related to excessive and/or prolonged postpartum vaginal blood loss after the first 24 h following childbirth.

A population case-control study was used to determine risk factors for excessive and/or prolonged vaginal bleeding (described collectively as vaginal loss problems) and uterine infection from 24 h to 3 months postpartum. Data were obtained from women whose maternity care took place in one of two health districts in the south of England. The cases were women remaining in or admitted to hospital with excessive or prolonged vaginal blood loss from 24 h to 3 months postpartum. Two controls for each case were identified; these were women whose delivery was the nearest in time and in the same location as the case delivery. Medical and midwifery records were searched retrospectively to cover hospital admissions for vaginal blood loss problems or uterine infection in postpartum women from 1 January 1994 to 31 December 1995. Data were analysed for 243 cases and 486 controls. Univariable analysis identified 28 variables associated with being a case. Using multivariable analysis, nine factors remained in the final model, with a history of secondary postpartum haemorrhage (PPH) being the most strongly predictive (OR [95% confidence interval] 6.0 [2.1, 16.8]). Vaginal bleeding prior to 24 weeks' gestation (OR 3.0 [1.6, 5.9]), third trimester hospital admission (OR 2.0 [1.4, 2.8]), maternal smoking (OR 2.7 [1.8, 3.9]), a prolonged (OR 3.1 [1.2, 7.5]) or incomplete third stage (OR 2.1 [1.0, 4.4]), and primary PPH (OR 4.7 [1.9, 11.6]) for blood loss >500 mL, were predictive of becoming a case. No significant association was identified for parity (OR 1.1 [0.8, 1.5]) or method of delivery, spontaneous (OR 1.0 [0.7, 1.3]), instrumental (OR 1.4 [0.9, 2.2]) or operative (OR 1.2 [0.8, 1.9]). This is a neglected area of women's health after childbirth, and the value of this study is in the identification of potential risk factors for postpartum morbidity related to vaginal blood loss. Where morbidity occurs, early diagnosis, management and treatment are likely to reduce its extent or duration. It is considered that raising awareness about these factors, both among healthcare professionals and women themselves, may play an important part in the recognition and treatment of postpartum morbidity.