How great is the risk of H1N1 to pregnant women?

Pregnant women are more vulnerable to infections of all sorts, because their immune systems are suppressed. That means that the H1N1 flu epidemic could strike disproportionately hard at women who are pregnant, and that every effort should be made to monitor cases carefully.

So far two women in the UK have died in H1N1-infected maternities – out of a total of 29 H1N1 deaths since the epidemic began. The issue is to what extent this represents a higher level of mortality for pregnant women than for the rest of the female population.
Limitations of the available data make it difficult to assess their increased risk. We do not even know how many of the 29 H1N1 deaths occurred in women of an age to have become pregnant, because this information has not been published.
However, it is possible to make some estimates, based on population statistics, demography, and what we do know about the cases of H1N1 so far recorded. What follows is the best appraisal that I can presently make, together with suggestions on the data needed to improve it.
In particular, let’s try to establish: first, the UK’s number of past H1N1-affected maternities; second, the number of suspected H1N1-infected maternities in the next three weeks; third, how many maternities per 10,000 in the week beginning 18 August 2009 are actually swab-positive for H1N1; fourth, count H1N1deaths internationally in males versus females aged 16-44 years, and count how many maternities are among the female H1N1 deaths aged 16-44 years..
Female population: UK’s 2007 mid-year population of 61.0 millions (55.8m excluding Scotland) included 31.1 million females (28.4m excluding Scotland), of whom 10.1 million (34%; or 9.3m excluding Scotland) were aged 15-39 years and 12.2 millions aged 16-44 years (39%; or 11.2m excluding Scotland).
Virologically confirmed H1N1 cases in adult females by 16 June 2009: In England, Wales and Northern Ireland, there had been 320 non-imported H1N1 cases in known-age females, 113 or 91 (35% or 28%) of them in females aged 15-39 years if we make the assumption respectively that 50% or 30% of female H1N1 cases in the 10-19 year age-group were actually 15-19 years of age. Allowing for incompleteness of data on age or sex, we may assume 10 non-imported confirmed H1N1 cases per 1 million females aged 15-39 years by 16 June 2009.
Uncertainty about H1N1 infections in adult females by 21 July 2009: Assuming a doubling time one week, and no further drift in age-distribution, by 21 July 2009 we should have had at least 32 clinical H1N1 cases per 1 million females aged 15-39 years. Pre-H1N1, received wisdom was one sub-clinical infection for each person affected by influenza. The ratio may be higher for H1N1 so that by 21 July 2009 the cumulative H1N1 infection-rate in females aged 15-39 years could have reached 100 per 1 million, or 1 in 10,000.
Alternatively, if a sixth (to 20%) of last week’s estimated 30,000 to 85,000 H1N1 infections in the UK were women aged 15-39 years, then their past-week suspected infection rate could be between 5 (6) and 14 (17) per 10,000; and possibly 8(10) to 25 (30) per 10,000 cumulatively. We already have a 25-fold (30-fold) range of uncertainty on how many women aged 15-39 years have been H1N1-infected – even before we take into account that pregnant women’s lower immunity may mean that their H1N1-susceptibility, S, is higher so that 1S to 25S (30S) per 10,000 of them could have been infected.
Maternities, and maternal deaths in UK pre-H1N1: Maternities are defined as live-births together with still-births who have reach at least 24 weeks of gestation. There are 700,000 maternities a year in the UK, and the maternal death rate was 14 per 100,000 maternities in 2003-05, or 98 per annum.
Assuming that there have been some 175,000 maternities since swine flu reached UK, ordinarily we might expect around 25 maternal deaths, with the actual number ranging from 15 to 35.
H1N1-related maternal deaths: UK has reported two maternal deaths in H1n1-infected maternities.
If indeed under 20 maternities in the past three months had been infected by H1N1 (low cumulative H1N1 rate of 1 in 10,000), then two H1N1-related maternal deaths – albeit with pre-existing complications – are rightly of great concern because the associated case fatality rate in H1N1 maternities would then appear very high.
However, the number of H1N1 infected maternities in the past three months could have ranged above 400S, where S is greater than 1 (high-end cumulative H1N1 rate of 25 in 10,000). At S = 1.5, the observed case fatality rate in H1N1-maternities would be 2/600, around the upper bound for all H1N1 cases proposed by the Chief Medical Officer.
The UK’s two observed H1N1 maternal deaths are, of course, consistent with Poisson expectation ranging from 0.24 to 7.22, which adds further uncertainty.
UK’s H1N1-related deaths in adult females: How many of UK’s 29 H1N1-related deaths have been in adult females of an age to have become pregnant? There are no official  figures, but an unofficial website and press coverage fill in some of the gaps. Two were H1N1 maternal deaths.
These sources leave 8 out of the other 27 deaths unaccounted for. Of the other 19 who are known about,two are females in their fifties, including the US tourist who died in Inverness, and there is an adult of unknown sex. We may therefore guesstimate that {2.5/19 * 8} = 1 of the 8 H1N1 cases whose demography is unknown is an adult female. Thus, among guesstimated four women of an age to have become pregnant who are H1N1-related deaths in UK, two were maternities.
By contrast, in the three months since H1N1 reached UK, maternities accounted for around 175,000 (1.4%) of the 12.2 million women aged 16-44 years.
None of this gives any real clarity to pregnant women: Expectant mothers and their families will want to know what proportion of those 175,000 maternities were H1N1-infected (clinically or sub-clinically) when their infant was delivered.
Missing data that could help: There are around 13,500 maternities per week, mostly in hospital.
For any delivery in which the mother is suspected of being H1N1-infected, virological confirmation of H1N1 infection should be a priority; and delivery may be in isolation. There should be urgent central reporting of such maternities over the next three weeks. Also, retrospective reporting back to mid April should be feasible as these maternities are likely to have been memorable.
It is likely that the vast majority of women who are hospitalized for their maternity would be willing to give a nasal swab to be tested for H1N1 (and perhaps even a blood sample to test for H1N1 antibodies as a mark of past exposure). Over 10,000 swabs could be obtained in a week, such as in the week beginning 18 August, by which time the incident positive rate might be 8S to 400S per 10,000. Testing could be done anonymously, with swabs identified only by age last birthday, region, and hospital code.
Empirical data – on past H1N1-affected maternities, on suspected H1N1-infected maternities in the next three weeks, and on how many maternities per 10,000 in the week beginning 18 August 2009 are actually swab-positive for H1N1 - are urgently needed to narrow the range of uncertainty for expectant mothers.