<p>Newborn bloodspot screening identifies babies with serious health conditions in a 2-stage process. Positive screening identifies those who need diagnostic tests. Although screening can improve physical health outcomes, research suggests that this initial screen positive stage has a profound psychological impact on families. This review systematically identifies, appraises, and synthesises the qualitative research on the impact of initial “positive screen” results on intrafamilial support systems. Studies fulfilled the inclusion criteria if they were research papers conducted with parents receiving an initial positive screen result and mentioned the impact on intrafamilial support systems. MEDLINE (Ovid), PsycINFO (Ovid) and CINAHL (EBSCO) databases were searched for qualitative research using search terms mapped onto the SPIDER framework. Title and abstracts were screened, and full texts independently reviewed by two researchers. A narrative synthesis of 25 papers was conducted and quality was appraised. All positive screen results, irrespective of diagnostic outcome, have consequences for intrafamilial support systems. Negative consequences included parents becoming the medical expert for other family members, family members becoming more distant through reducing communication, and parents questioning whether they want future children. Others experience reinforcement of strong intrafamilial support systems when family members displayed proactivity, offered reassurance, and provided adequate support in a timely manner. The synthesis findings imply screen positive results have a profound impact across family networks beyond the parent/couple dynamic, and whether this is positive or negative is complex. Further research is warranted to investigate how impact could be better addressed.</p>