120 P. M. A. Siren & M. J. Siren This increased respiratory work-load may contribute to diaphragm fatigue. The studies discussed above suggest that REM sleep is associated with increased diaphragmatic work-load and respiratory muscle fatigue in normal infants. Importantly, a fatigued diaphragm can be relieved only by decreasing the respiratory work- load or by activating the intercostals. If the critically fatigued muscle is not supported by the secondary respiratory muscles, ventilatory efﬁciency and muscle oxygenation will progressively decline and the risk of respiratory failure increases. The bell-shaped mortality rate in SIDS One of the more puzzling aspects of SIDS is the bell-shaped mortality incidence rate. SIDS seems closely related to the developmental status of the infant, because 95% of the cases occur before the age of 6 months, and SIDS is rare in infants 1 year and older. Paradoxically, SIDS is also rare in infants younger than 1 month (5). SIDS clearly has a differ- ent type of mortality incidence rate compared to the monotonic distribution in congenital anomalies (6). Others have argued that bacterial toxins cause SIDS and that maternal antibodies can protect the infant during the ﬁrst months of life (95). We suggest that the bell-shaped mortality distribution of SIDS is due to the passive immune protection maternal antibodies provide during the ﬁrst month of life when the respi- ratory muscles are most vulnerable. The age proﬁle of SIDS deaths is reciprocal to infants’ serum concentrations of immunoglobulin (96), and maternal antibodies can increase the immune resistance of neonates during the ﬁrst months of life (97,98). Infants have varying levels of passive immune protection because the maternal antibody concentration determines the neonatal titer at birth (99). Full-term infants seem to have higher antibody titers than premature ones (100). However, the passive immune protection wanes relatively rap- idly in all neonates. A study with 213 mother–infant pairs showed that the mean time to immunity loss for rubella and varicella was 2.1 months and 2.4 months, respectively (101). For measles the maternal antibo- dies endured for a median of 2.6 months (99). Mater- nal antibodies to the Varicellazoster virus (VZV) had a median half-life of 25.5 days in neonates (range 14.6–76.0 days) (102). Another study showed that 26% of infants had potentially protective antibody levels against pertussis (whooping cough) at delivery, but by week 6 nearly 90% had lost most of the original maternal antibodies (103). These and other studies (104,105) suggest that neonates can beneﬁt from passive maternal immune factors for 1–2 months post partum but that the temporary immune protection wanes relatively quickly. Concluding remarks We propose that the cause of death in SIDS is respiratory failure caused by CDF. It is well known that young infants have potentially vulnerable dia- phragms and that infections can produce severe respi- ratory muscle dysfunction. We argue that ‘non-lethal’ infections are the main cause of CDF in SIDS. As such, there is no speciﬁc underlying genetic or con- genital vulnerability in SIDS infants, and completely normal infants can die of SIDS. However, infants with weak or underdeveloped respiratory muscles who spend a large portion of the day in REM sleep and are exposed to infections are at increased risk. Dys- functional melatonin metabolism may also be a con- tributing factor in SIDS. By deﬁnition, the infections associated with SIDS are not considered to be lethal, but they can cause a signiﬁcant and acute loss of diaphragm strength. Additional stressors such as the prone sleeping position and REM sleep can move the infant closer to CDF and precipitate respi- ratory failure. Diagnosing CDF-precipitated respira- tory failure is challenging because it usually does not affect muscle mass or histology. An obvious question that the SIDS–CDF hypoth- esis might raise is that if young infants have vulnerable respiratory muscles and even minor infections can cause signiﬁcant loss of diaphragm strength, why is SIDS not more common? Diaphragm fatigue is not the same as diaphragm failure, and while young infants are susceptible to CDF, they also have effec- tive defense mechanisms that help preserve respira- tory function. First, the immune system actively attenuates the negative effects of infectious assaults. Second, the activation of the intercostal muscles can decrease the respiratory burden and support a fatigued diaphragm. Third, the diaphragm develops rapidly, and by age 6 months has the same distribu- tion of fatigue-resistant ﬁbers and pressure-generating capacity as the adult muscle. Thus, moving from diaphragm fatigue to CDF usually requires a relatively rare combination of events that include an infectious episode, insufﬁcient immune response, undeveloped respiratory muscles, continuous REM sleep, and often a prone resting position. Even if all these factors are present, the fatigued diaphragm may be rescued by altering the sleep state and activating the secondary respiratory muscles. The clinical impact of an infection is dependent on its intensity as well as the immune and developmental status of the host. A potent infection can alone be lethal to a young infant, but a less severe infection will