U.S. stock index futures fell on Wednesday as investors assessed the implications of the federal government shutdown, which threatens to disrupt the release of key economic data and complicate the Federal Reserve's policy path.

The shutdown, which independent analysts warn could last longer than the budget-related closures of the past, comes at a time when markets are leaning heavily on hopes of a dovish Fed policy, and after equities posted the second straight quarter of gains.

While shutdowns have not derailed markets historically, the current episode coincides with a critical period when stock valuations are elevated and sentiment fragile.

The S&P 500 rose during each of the last six government shutdowns, according to a note from Deutsche Bank.

However, a longer shutdown could be a cause for concern.

In the seven instances where they lasted 10 days or more, the index fell four times and rose three times, according to data from Vanguard.

"While a government shutdown is disruptive in its own ways, now isn't exactly the time that investors, or the Fed, want to lose access to key economic data points," said Bret Kenwell, U.S. investment analyst at eToro.

At 04:21 a.m. ET, Dow e-minis YMcv1 were down 310 points, or 0.66%, U.S. S&P 500 E-minis EScv1 were down 52.5 points, or 0.78%, and Nasdaq 100 E-minis NQcv1 were down 234.5 points, or 0.94%.

With uncertainty around when the next nonfarm payrolls report will be released, upcoming data such as the ADP National Employment Report and the Institute for Supply Management's manufacturing PMI for September, due on Wednesday, will likely be scrutinised more closely for clues on the labour market and inflation.

Investors will also parse commentary from Federal Reserve Bank of Richmond President Thomas Barkin for any shift in tone as policymakers navigate a murkier data landscape.

Among the early movers was Nike, which rose 3% in premarket trading a day after reporting surprise revenue growth in the first quarter.

NYSE-listed shares of Lithium Americas surged 39% after it said the U.S. Department of Energy had taken a 5% stake in the company.

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