Objective: To investigate the association between spontaneous preterm
birth and placental histology at high and low altitude. Design: Crosss
ectional randomized prospective study. Setting: Mohayel (500 meters ab
ove sea level) and Abha (3,100 meters above sea level), cities in sout
hern Saudi Arabia. Subjects: Pregnant Saudi women living permanently a
t the areas of study and placentae from spontaneous preterm birth with
out an obvious cause, Methods: Paraffin sections of the placenta were
stained by Periodic Acid Schiff, Hematoxyllin and Eosin for identifica
tion of cytotrophoblastic cells and syncytial knots respectively by th
e light microscopy. The volume fraction of the fetal capillary lumina
and stromal tissue of the terminal villi was performed by the image an
alyser. Results: The total percentage of preterm birth was 1.93% at lo
w altitude compared to 4.41% at high altitude (p<0.01). The percentage
of preterm births without an apparent cause was 1.3% at low altitude
compared to 3.3% at high altitude (p<0.01). The histology of the termi
nal villi of placentae, comparing high with low altitude, showed, resp
ectively, syncytial knots in 45.4% and 13.1% (p<0,001) and cytotrophob
lastic cells in 52.7% and 28.6% (p<0.001) of the villi. In addition, c
omparing high to low altitude, there was a significant fail in the fra
ctional volume of their stromal tissue (p<0.001) and an equivalent ris
e in the fractional volume of their foetal capillary lumina ((p<0.005)
. Conclusion: It is concluded that stimulation of syncytial knots form
ation, persistence of villous cytotrophoblastic cells and hypercapilla
risation are features of placental hypoxia. Since, it is known that pl
acental hypoxia is associated with increased incidence of spontaneous
preterm birth, it is suggested that high altitude may be involved in t
he aetiology of spontaneous preterm birth.