116 SIDS P. M. A. Siren & M. J. Siren Research has identiﬁed over 40 potential SIDS risk factors (5), making the investigation of the syndrome extremely complicated. However, the salient and uncontentious characteristics of SIDS are well known; it affects fewer than 1 in 1000 live births in the developed world and is associated with sleep, a bell-shaped mortality incidence rate (peak age 2–4 months), premature and low-birth-weight infants, male gender (60% of cases), episodes of non-lethal infections, and the prone sleeping position (6–8). So far, no convincing genetic or congenital mechanism for SIDS has been identiﬁed. SIDS is by deﬁnition a diagnosis of exclusion that has no identiﬁable cause of death. However, it is generally accepted that sudden death that is not caused by trauma must be due to either respiratory or circulatory failure (9). Clinical observations, heart- rate, and respiratory recording of infants who subse- quently succumb to SIDS and animal models strongly suggest a respiratory pathway for the syndrome (2). The absence of any obvious defects or abnormalities in the lungs or inspiratory muscles has led to the conclusion that respiratory failure in SIDS must be caused either by a dysfunctional control system (2,10) or upper airway obstruction (11). However, the dys- functional respiratory control system hypothesis fails to explain many of the salient features of SIDS (6), and studies have found no signiﬁcant respiratory abnormalities in infants who subsequently die of SIDS (12,13). Furthermore, both human and animal studies (14–17) suggest that upper airway occlusion is not a precipitating factor in SIDS, and obstructive apnea as the cause of SIDS is arguably doubtful. The respiratory failure hypothesis is still favored by many SIDS researchers (11), but so far no convincing mechanism has been identiﬁed. Surprisingly, the possible role of the diaphragm in the etiology of SIDS has been largely ignored. In October 2010, there were only 41 PubMed hits with the search words ‘SIDS and diaphragm’ from a total of over 9,500 SIDS articles (18). Yet, the diaphragm is the main respiratory muscle, and as Muller and Bryan observe ‘respiratory failure is frequently respiratory muscle failure’ (19). Diaphragm and survival Two muscles are essential for human survival, and while the vital role of the heart is obvious, the dia- phragm is often overlooked. The diaphragm is a thin muscle that is shaped like a parachute and that sepa- rates the thoracic from the abdominal cavity. It is the main engine of the vital respiratory pump (20), and its contraction is critical for intrathoracic pressure generation (21). Anraku and Shargall note that ‘in adults, the diaphragm represents less than 0.5% of body-weight, but it is the most important muscle in the human body after the heart’. The incapacitation of supportive respiratory muscles, such as the intercos- tals, is not lethal, but bilateral diaphragm paralysis usually results in respiratory failure (22). The adult diaphragm can generate indeﬁnitely approximately 40% of its maximum transdiaphragmatic pressure (Pdimax) (23), but it is susceptible to critical fatigue in certain conditions. Macklem succinctly observes that ‘the inspiratory muscles form a pump just as vital as the heart, and this pump can and does fail in much the same manner as the heart fails’ (20). In adults, respiratory muscle weakness is one of the most com- mon causes of ventilatory failure (24). We argue that the diaphragm is the locus minoris resistentiae in SIDS. The young infant has undevel- oped secondary respiratory muscles, and the dia- phragm is responsible for the majority of respiratory work (25). Assuming the same relative organ propor- tions as in the adult, a normal neonate weighing 3000 g would have a diaphragm that weighs approx- imately 12 g and is approximately 2 mm thick (26). Indeed, roughly similar dimensions are observed in preterm infants weighing between 1260 g and 2100 g who have diaphragms that are between 1.09 (±0.08) and 1.74 (±0.04) mm thick (27). An increase in diaphragm size correlates directly with inspiratory force (28), and full-term infants reach adult levels of Pdimax at approximately 6 months of age (25). The diaphragm in young infants is also structurally imma- ture and signiﬁcantly more susceptible to fatigue than a fully developed muscle. A premature infant’s dia- phragm consists of only 10%fatigue-resistant type I ﬁbers. The diaphragm of a full-term infant has 25% type I ﬁbers, increasing to 40% at 3 months and to 50%–55% (adult share) (22) by the age of 7–8 months (19).The younger the infant, the smaller the oxidative capacity of the respiratory muscles and the higher the risk for ventilatory muscle fatigue (19). We suggest this may be a reason why low-birth-weight or prema- ture infants have up to four times the risk of SIDS compared to full-term neonates (8). Overall, the respiratory muscles of the young infant appear to be poorly equipped to sustain increased work-loads. Muller and colleagues argue that ‘the normal preterm and term infant is very close to the threshold of diaphragmatic fatigue’ (29). Indeed, fatigue patterns can readily be observed if the work of breathing is increased in young infants (30). Still, some authors have suggested that the infant diaphragm is not at increased risk of fatigue and that it may be even more fatigue-resistant than the adult inspiratory muscle