The reported incidence of AFE ranged from 1.9 cases per 100 000 maternities (UK) to 6.1 per 100 000 maternities (Australia) (Table ). There was a clear distinction between rates estimated using different methodologies. The lowest estimated incidence rates were obtained through validated prospective case identification (range 1.9-2.5 cases per 100 000 maternities); rates obtained from retrospective analysis of population discharge databases were significantly higher (range 5.5-6.1 per 100 000 admissions with delivery diagnosis), with an intermediate estimated incidence obtained from analysis of a regional discharge database in which additional required criteria (at least one of the cardinal symptoms with no other potential explanation) were used to exclude false positive cases (3.3 cases per 100 000 maternities). When the latter database was used without the additional selection criteria, the estimated incidence was 6.3/100,000.
Mortality and case fatality
Mortality ratios ranged from 0.4 per 100 000 live births in the Netherlands from 1993-2005 to 1.3 per 100 000 live births in the United States in 1997-2001 and 1.1 in Australia excluding Victoria in 1994-2005. Case-fatality rates ranged from 11 to 43%. There were no clear differences in estimates of maternal mortality due to AFE or case fatality rates due to AFE using any different methodology, noting the limited power to detect differences due to small numbers of fatal cases (Tables and ). The studies with the highest case fatality rates (NSW and Victoria) were conducted using case validation. Note, however, the wide confidence intervals surrounding all case fatality estimates due to the rarity of the condition and the small numbers involved.
The only factors consistently associated with AFE across all five countries were induction of labour and maternal age; although with both of these factors, in one country the association was not statistically significant. The association with age was not statistically significant in the Dutch data, this could be due to limited study power since all cases occurred in women who were aged 29 years or greater (Table ). The methods of induction investigated varied. UK and Dutch data show a significant association between AFE and induction of labour (all methods); in the Canadian population, an association was observed with medical induction of labour, whereas in New South Wales there was only a statistically significant association with medical induction using vaginal prostaglandin. In the US study, induction of labour (all methods) was associated with raised odds (aOR 1.5), but this was not statistically significant. Where data were available, there were increased odds of AFE associated with placenta praevia and placental abruption. For all of the other factors examined (Tables , , , ), the associations varied in the direction of effect and statistical significance, which may reflect small numbers and consequent lack of study power.
Maternal factors associated with amniotic fluid embolism
Pregnancy factors associated with amniotic fluid embolism
Associations between induction of labour and amniotic fluid embolism
Delivery factors associated with amniotic fluid embolism
Other associations were noted with mode of delivery: forceps/vacuum and caesarean section, although these are challenging to interpret since information on the timing of delivery in relation to the AFE was not available for all of the data sources. In the UK data, where timing of the event and delivery was available, there was a statistically significant association noted with caesarean section delivery when the AFE occurred after delivery. There was no association with forceps or vacuum delivery, although the small number of women with AFE who had operative vaginal deliveries means there is limited statistical power to examine this association. Of note, eclampsia, a condition which may form one of the differential diagnoses for AFE, was strongly associated with AFE in the Canadian and US studies which did not use additional criteria to exclude false positive cases.
Very limited data were available on factors associated with fatality (Table ); there were no factors consistently associated with fatality across all of the countries.
Factors associated with fatality amongst AFE cases (risk ratio (RR) unless indicated)
For the majority of sources used, there was very limited information on maternal outcomes other than death. Cerebral injury was noted in 6% of women with AFE in the UK, and cerebral infarction occurred in 20% of women with AFE in New South Wales. Data were similarly limited on fetal and infant outcomes. Eight of 21 infants (38%) born to mothers with AFE in the Netherlands were stillborn or died in the neonatal period; the figure was 5 of 75 infants (7%) in the UK and 6 of 19 (32%) in NSW.