Patterns of heart rate variability responses to acute skin-breaking procedures in neonates: a systematic review and meta-analysis.

The current systematic review and meta-analysis aimed to uncover normative patterns of heart rate variability (HRV) responses following acute skin-breaking painful procedures in hospitalized preterm and full-term newborns within the first month of life. The review was preregistered with INPLASY (registration no. INPLASY202480007). Six databases (Medline, Embase, CINAHL, PsycINFO, Scopus, and Web of Science) were systematically searched most recently on December 4, 2025, leading to 2741 unique abstracts being identified and screened. Of these, 32 eligible studies reported on newborns' HRV patterns of pain-related stress reactivity or regulation to acute skin-breaking procedures within the first month of life and were thus included in the review. Risk of bias was assessed using an adapted tool developed for this review and informed by several published guidelines. Of the 32 included studies, 27 were meta-analyzed while 5 were described qualitatively. Results were synthesized by type of HRV measure, combination of gestational and postnatal ages, and, finally, by acute pain response phase. Four main themes emerged: (1) the effects of gestational and postnatal age on patterns of acute pain-related stress reactivity indexed by HRV; (2) variability in acute pain-related stress reactivity across distinct HRV measures; (3) normative patterns of pain-related stress regulation indexed by HRV; and (4) heterogeneity across HRV outcomes, particularly as newborns react to an acute skin-breaking procedure. Substantial heterogeneity and risk of bias across studies were significant limitations in the current review. Methodological considerations for future research and clinical considerations are discussed.