<b><i>Background:</i></b> Perinatal clinical research to improve the quality of care and outcomes for newborn infants relies on transparency, trust, and respect for the autonomy and well-being of study participants and their families. <b><i>Methods:</i></b> Here we consider the underpinning principles of ethical research with a focus on perinatal clinical research in the acute care or emergency setting where particular challenges to parental engagement and informed consent exist. <b><i>Results:</i></b> Several approaches to improving the validity of the consent process for perinatal research have been proposed and evaluated. These include consent waiver, antenatal consent, deferred consent preceded by verbal assent, and continuous consent. These have strengths and weaknesses and uncertainty remains about their validity and acceptability in certain research contexts. Prior exploration with parents and parent-advocacy groups of approaches to engagement and consent, and independent evaluation and ongoing monitoring of research studies, can enhance adherence to the ethical principles of justice and autonomy, and ensure that benefits to participants and their families exceed harm. <b><i>Conclusions:</i></b> High-quality research and ethics are interdependent. Only research that meets ethical standards can be regarded as valid and applicable, and only research designs that are methodologically rigorous and appropriate can be regarded as ethical.