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Cantabrian Crawford, who has made the long-distance event her own, will not compete because she is expecting her first child in July.
Crawford said she was upset about being unable to compete in one of her favourite events and hoped to be back competing in Wanaka by 2012.
Her disappointment at being unable to add a fourth straight title was tempered by the excitement of having a baby.
"My husband and I are overjoyed to be expecting a new addition to our family and I am greatly looking forward to this next chapter of my life," she said.
Top Australian contenders Rebekah Keat and Jodie Scott have also withdrawn.
Keat, a former World No 2 in the sport who came second in the Challenge Wanaka last year, has cited burn-out as a reason for not travelling to contest this year's event, while Scott is out injured.
Challenge Wanaka event director Victoria Murray-Orr said the three withdrawals were frustrating, but, as with any sporting code, "injuries and pregnancy are outside your control".
The withdrawals mean the elite female field will feature a sole professional triathlete, Joanna Carrit, of the United Kingdom, who will be guaranteed a winner's cheque by completing the event.
Crawford's withdrawal deprives Challenge Wanaka of its most-recognised individual triathlete and leaves Hamilton competitor Keegan Williams as the top Kiwi contender.
2010 men's champion Richard Ussher will not defend his title, having opted instead to compete in the teams event, alongside swimmer Aaron Barclay, of Gore - the world junior Olympic triathlon gold medallist - and Dunedin runner and New Zealand woman's marathon champion Shireen Crumpton.
Williams, who has finished second and third in the event during the past two years, will carry local hopes in the 226km race.
He will be joined by fellow Kiwi triathletes Jamie Whyte and Bevan McKinnon, both of Auckland.
The elite male field of the Challenge Wanaka is the largest in the event's five-year history and includes 14 professional triathletes, Ms Murray-Orr said.