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Heart period data were recorded before, during, and after a heel lanced or wrist venipunctured blood draw for routine clinical evaluation. Pain response to the blood draw procedure and age\u2010related changes of HRV in low\u2010frequency and high\u2010frequency bands were modeled with linear mixed\u2010effects models. HRV in both bands decreased during pain, followed by a recovery to near\u2010baseline levels. Venipuncture and mechanical ventilation were factors that attenuated the HRV response to pain. HRV at the baseline increased with post\u2010menstrual age but the growth rate of high\u2010frequency power was reduced in mechanically ventilated infants. There was some evidence that low\u2010frequency HRV response to pain improved with advancing PMA. \u00a9 2009 Wiley Periodicals, Inc. 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