ashley moffett: new approaches to maternal mortality in africa

How does the mother’s immune system affect the outcome of

pregnancy?

Ashley Moffett

The Norwegian Mother-Baby study

A cohort consisting of ~800 000 pregnancies

The Norwegian MoBa study

A cohort consisting of ~800 000 pregnancies

The Norwegian MoBa study

A cohort consisting of ~800 000 pregnancies

Pre-eclampsiaStillbirthPrematurity

The Norwegian MoBa study

A cohort consisting of ~800 000 pregnancies

ObstructedlabourHaemorrhageSepsis

Obstructedlabour

William Smellie‘s Sett of Anatomical Tables, 1752

“Perhaps the most clear-cut example of a human character subject to stabilizing (balancing)

selection is birth weight”from Cavalli-Sforza, L.L. &Bodmer, W.F. In The genetics of human populations (Freeman Press, San Francisco, 1971).

(n=13,730)

Birth weight and neonatal mortality rate

The maternal-fetal interface

NK cells and the success of human pregnancy

Failure of invasion of extravillous trophoblast cells in pre-eclampsia

Moffett

The immune system has evolved to discriminate between

self & non-self

Recipient immune cell

Transplantation

self

self label

non-self

non-self labelreceptor

Maternal immune cellPaternalnon-selflabel

Maternalselflabel

Pregnancy

self & non-self labels = HLA

Failure of invasion of extravillous trophoblast cells in pre-eclampsia

Moffett

Uterine NK cells Placenta

Maternal population

NK cells

Paternalnon-selflabels onplacenta

Placenta

NK cells

Placenta

NK cells

Placenta

Risk

NK cells

HLA-C2

HLA-C*07:02 = C1 group

9.0

0.0

58.7

18.0

30.0

(%)

Distribution of Neanderthal HLA-C*0702 allele (group C1) in modern populations

Abi-Rached et alScience 2011

Inverse correlation in human populations between C2 epitope and KIR A haplotype.

Parham 2012. Extending Hiby et al 2004, JEM.

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0.4

0.45

0 1000 2000 3000 4000 5000 6000 7000 8000

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0.4

0.45

0 1000 2000 3000 4000 5000 6000 7000 8000

Birth weight (grams)

Birth weight frequency

Neonate transfer frequency

The distributions of birth weight and transfer to neonatal special care units.1999-2009 Norway (MoBa)

% f

req

uen

cy