Appendix A

Appendix A presents a compilation of abstracts of studies that address relationships of the mode of infant feeding with the infant's subsequent survival. Abstracts are presented in either tabular or narrative form and are arranged chronologically by type of study (mortality rates, relative risk, or both; case fatality; and miscellaneous). Table A-1 presents a chronological listing of the data and indicates the location of each abstract.



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Nutrition During Lactation Appendix A Appendix A presents a compilation of abstracts of studies that address relationships of the mode of infant feeding with the infant's subsequent survival. Abstracts are presented in either tabular or narrative form and are arranged chronologically by type of study (mortality rates, relative risk, or both; case fatality; and miscellaneous). Table A-1 presents a chronological listing of the data and indicates the location of each abstract.

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Nutrition During Lactation TABLE A-1 Chronological Listing of Estimated Relative Risk (RR) of Mortality in Industrialized Countries Among Children Fed Formula Only or Formula Plus Human Milk Compared with Breastfed Infants and Childrena   RRb Type of Study and Abstract Providing Detailed Description   Period and Site of Study Bottle Mixed Reference 1869–1910, Three German states NAc NA Correlation, A-21 Knodel and van de Walle, 1967 1885–1886 Berlin, Germany 4.0– 10.8d NA Mortality rates, A-1 Thiemich and Bessau, 1930; reviewed in Mannheimer, 1955 1895–1896 Berlin, Germany 4.1– 14.2d NA Mortality rates, A-1 Thiemich and Bessau, 1930; reviewed in Mannheimer, 1955 1900–1903, Derby, England 2.83 1.41 Mortality rates, A-2 Howarth, 1905 1900–1904,  Kingdom of Bavaria, Germany NA NA Correlation, A-22 Greenwood and Brown, 1912 1901–1905, Finsbury, London 27.5 9.8 Case-control, A-3 Newman, 1906 NRe Liverpool, England 2.71f, 2.49g 1.59f, 0.92g Mortality rates, A-4 Armstrong, 1904 1903–1905, Brighton, England 35.1 3.1 Case-control, A-5 Newsholme, 1906, reviewed in Newman, 1906 1906, Berlin, Germany 2.6– 10.9d NA Mortality rates, A-1 Thiemich and Bessau, 1930; reviewed in Mannheimer, 1955 1910, Boston, Mass. 6.06 NA Mortality rates, A-6 Davis, 1913 1924–1929, Chicago, Ill. 5.6 4.6 Mortality rates, A-7 Grulee et al., 1934, 1935 NR, Birmingham, England 4.59 1.55 Case-fatality, A-17 Smellie, 1939 NR, Toronto, Canada 0.89 0.65 Case-fatality, A-18 Ebbs and Mulligan, 1942 1936–1942, Liverpool, England 5.62 2.52 Mortality rates, A-8 Robinson, 1951 1941–1942, Belfast, Ireland 5.15– 13.72d NA Mortality rates, A-9 Deeny and Murdock, 1944 1943–1947, Stockholm, Sweden 1.34– 1.75f 0.63– 0.66f Mortality rates, A-10 Mannheimer, 1955 1942 and 1943, Isleworth, England 1.96 NA Case-fatality, A-19 Gaidner, 1945

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Nutrition During Lactation 1943–1946, Louisville, Ky. NA NA Case-fatality, A-20 Prince and Bruce, 1948 1946, Great Britain 1.7h NA Mortality rates, A-11 Douglas, 1950 1956–1971, Copenhagen, Denmark NA NA Case-control, A-12 Biering-Sorensen et al., 1978 1959–1966, United States NA NA Mortality rates, A-13 Naeye et al., 1976 1962, Canada 2.03 NA Mortality rates, A-14 Department of National Health and Welfare, Canada, 1963, as quoted in Gerard and Tan (1978) 1973–1979, Sheffield, England NA NA Postnatal intervention, A-15 Carpenter et al., 1983 NR, United States NA NA Case-control, A-16 Arnon et al., 1982 a The bases for the estimates of relative risk are shown in Abstracts A-1 through A-19. Relative risks computed for these studies represent somewhat different comparisons. For example, mortality might be compared for infants at different ages or for infants hospitalized with diarrhea. b Relative risk for breastfed infants = 1.0. c NA = Data not available for estimating relative risk. d Range covers values from 1 to 12 months of age. e NR = Period not reported. f To age 1 year. g To age 2 weeks. h To age 2 years, comparison of infants breastfed for 8 weeks or longer with those breastfed for less than 8 weeks.

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Nutrition During Lactation MORTALITY RATES AND RELATIVE RISK OF MORTALITY ABSTRACT A-1 Infant Deaths/1,000 Births and Relative Risk (RR) of Death, by Feeding Method and Month of Age, Berlin, Germany, Between 1885 and 1906a,b     Number of Infant Deaths/1,000 Births by Feeding Method Years Age of Mortality, mo Breast Bottle RRc 1885–1886 1 22.4 142.0 6.3   2 9.0 82.7 9.2   3 6.8 72.2 10.6   4 6.4 61.8 9.7   5 5.3 57.1 10.8   6 4.9 50.7 10.3   7 4.7 46.5 9.9   8 4.5 40.8 9.1   9 5.3 33.3 6.3   10 5.4 29.5 5.5   11 6.3 24.9 4.0   12 NAd NA NA 1895–1896 1 19.6 111.9 5.7   2 7.3 58.7 8.0   3 4.3 49.7 11.6   4 3.6 46.6 12.9   5 2.6 37.0 14.2   6 2.5 31.0 12.4   7 2.5 27.7 11.1   8 2.3 24.1 10.5   9 2.0 21.3 10.7   10 3.8 19.1 5.0   11 3.1 16.7 5.4   12 3.6 14.6 4.1 1906 1 22.4 59.1 2.6   2 7.9 31.3 4.0   3 4.3 27.3 6.3   4 2.4 22.1 9.2   5 1.7 18.5 10.9   6 2.2 16.1 7.3   7 1.4 14.1 10.1   8 1.8 12.2 6.8   9 2.1 10.2 4.9   10 1.5 9.2 6.1   11 1.3 8.0 6.2   12 1.5 8.0 5.3 a From Thiemich and Bessau (1930), as quoted in Mannheimer (1955). b Data on feeding practices were collected for all deaths and during census for survivors. c Relative risk for breastfed infants = 1.0. d NA = Not available.

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Nutrition During Lactation ABSTRACT A-2 Infant Deaths/1,000 Births and Relative Risk (RR) of Mortality by Feeding Method, Derby, England, 1900 to 1903a   Number of Infant Deaths/1,000 Births (RR) by Feeding Method Specific Causes of Mortality Breast Bottle Mixed All causes 69.8 197.5 (2.83)b 98.7 (1.41) Respiratory diseases 14.1 26.5 (1.84) 12.6 (0.88) Gastrointestinal diseases 9.9 57.8 (5.84) 25.0 (2.53) Marasmus 12.5 39.4 (3.15) 18.8 (1.50) Tuberculosis 3.4 13.5 (3.97) 5.6 (1.65) Convulsions 15.0 25.9 (1.73) 20.9 (1.39) a From Howarth (1905). b Relative risk for breastfed infants = 1. COMMENTS: Feeding history was obtained during infant's life; of the 8,343 infants studied, 63.3% were breastfed, 27.3% were mixed fed, and 19.5% were formula fed. ABSTRACT A-3 Feeding Practices and Relative Risk (RR) of Death from Diarrhea in a Case-Control Study of Infants Aged 0 to 3 Months, Finsbury, London, England, 1901 to 1905a   Infants Fed by Each Method, % Feeding Method Infants Who Died (N = 118) Surviving Infants (N = 1,822) RR Breast 22.0 80.8 1.0 Bottle 52.5 7.0 27.5 Mixed 25.4 9.5 9.8 a From Newman (1906). COMMENTS: Fascinating review of evidence to 1906, including lowered infant mortality during closing of Lancashire mills secondary to cutoff of cotton during American Civil War. ABSTRACT A-4 Infant Deaths/1,000 Births and Relative Risk (RR) of Mortality by Feeding Method, Liverpool, Englanda,b   Number of Infant Deaths/1,000 Births (RR), by Feeding Method Specific Ages of Mortality Breast Bottle Mixed Up to age 1 yr 84 228 (2.71)b 134 (1.59) Age 1–2 yr 40 99 (2.49) 36 (0.92) a From Armstrong (1904). Period of study not reported. b Relative risk for breastfed infants = 1. COMMENTS: Data from 1,000 children of 224 mothers attending the Infirmary for Children; 68.9% were breastfed, 18.4% were bottle fed, and 12.7% were mixed fed to age 6 months.

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Nutrition During Lactation ABSTRACT A-5 Feeding Practices and Relative Risk (RR) of Epidemic Diarrhea Infant Death in a Case-Control Study in Brighton, England, 1903 to 1905a   Infants Fed by Each Method, % Feeding Method Infants Who Died (N = 121) Surviving Infants (N = 1,259) RR Breast 6.5 62.3 1.0 Bottle 80.3 21.9 35.1 Mixed 5.0 15.3 3.1 Unknown 8.2 0.5 NAb a From Newsholme (1906), as reviewed in Newman (1906). b NA = Not applicable. ABSTRACT A-6 Deaths/1,000 Births and Relative Risk (RR) of Mortality for Infants Aged 2 Weeks to 1 Year, by Feeding Method, Boston, 1910 a   Number of Infant Deaths/ 1,000 Births, by Feeding Method Cause of Mortality Breast Bottle RRb All causes 36 218 6.06 Diarrhea 9 98 12.25 a From Davis (1913). A case-control study of 1,600 deaths, plus mail questionnaires from mothers of 736 controls. It was unclear how mixed feeding was classified. b Relative risk for breastfed infants = 1. ABSTRACT A-7 Death Rates/1,000 Births and Relative Risk (RR) of Death for 20,061 Infants up to 1 Year of Age Served by Welfare Clinics in Chicago, 1924 to 1929a Feeding Method Death Rate/ 1,000 Births RR Breast 1.5 1.0 Bottle 8.4 5.6 Mixed 6.9 6.9 a From Grulee et al. (1934, 1935).

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Nutrition During Lactation ABSTRACT A-8 Death Rates/1,000 Births and Relative Risk (RR) of Death for 3,266 Infants Aged 7 Months or Less, Liverpool, England, 1936 to 1942a Feeding Method Mortality/1,000 to Age 7 Months RR Breast 10.2 1.0 Bottle 57.3 5.62 Mixed 25.7 2.52 a From Robinson (1951). COMMENTS: Excludes infants with birth weights of <2 kg (4.4 lb) who were ''weakly" or whose clinic visits were discontinued before age 7 months. Mortality was attributed almost entirely to infections. ABSTRACT A-9 Infant Deaths/1,000 Births and Relative Risk (RR) of Death, by Feeding Method and Age, Belfast, Ireland, June 1941 to June 1942a   Number of Infant Deaths/1,000 Births by Feeding Method Age of Mortality, mo Breast Bottle RRb <1 7.5 103.0 13.72 1–2 5.0 38.0 7.68 2–3 3.4 43.5 12.76 3–6 5.7 43.4 7.57 6–12 7.1 36.8 5.15 a From Deeny and Murdock (1944). Results were estimated from authors' data. Based on 554 infant deaths plus 477 survivors (every fifth child during first 6 months of age). b Relative risk for breastfed infants = 1.0.

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Nutrition During Lactation ABSTRACT A-10 Deaths/1,000 Births and Relative Risk (RR) of Death for 67, 738 Infants Who Survived the First Month, by Feeding Method, Age, and Cause of Death, 1943 to 1947, Stockholm, Swedena   Death Rate/1,000 Births (RR) by Feeding Method Age or Cause of Mortality Breastb Bottle Mixed Age 2–12 mo 4.63 8.12 (1.75) 3.08 (0.66) Age 3–12 mo 3.19 6.48 (2.03) 2.90 (0.91) Congenital disease NRc NR (1.73) NR Infections NR NR (1.28) NR Respiratory disease NR NR (2.55) NR Intestinal disease NR NR (6.79) NR Other causes NR NR (4.79)   a From Mannheimer (1955). b Relative risk for breastfed infants = 1.0. c NR = Not reported. COMMENTS: RRs were 3.66 and 4.32 for infants fed cow's milk exclusively from age 2 months. The apparent advantage of mixed feeding lasted less than 4 months. The apparent disadvantage of bottle feeding decreased after 6 months and was gone after 9 months. Compared with breastfed infants, a smaller proportion of bottle-fed infants received care at child welfare centers (64 and 48%, respectively). Rates were lower for mixed-fed than for breastfed infants in all categories except intestinal disease, for which they were equal. Excess deaths in the bottle-fed group were observed only among infants weighing >2,500 g at birth. Feeding method was unrelated to income. ABSTRACT A-11 Death Rates/1,000 Births for 4,669 Infants Aged 8 Weeks to 2 Years and Relative Risk (RR) of Death by Duration of Breastfeeding, Great Britain, March 1946a Duration of Breastfeeding, wk Death Rate/1,000 RR <8 18.5 1.7 ≥8 10.9 1.0 a From Douglas (1950). Excludes infants from the upper classes. COMMENTS: Among the upper classes, mortality was only slightly increased among those breastfed <8 weeks.

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Nutrition During Lactation ABSTRACT A-12 Case-Control Study of Feeding Methods of Infants Developing Sudden Infant Death Syndrome (SIDS) and Control Infants, Copenhagen, 1956 to 1971a   Feeding Method,b % (no.) of Infants Study Group Breast Bottle Mixed Cases 60.2 (74) 20.3 (25) 19.5 (24) Controls 79.2c (412) 7.7 (40) 13.1 (68) a From Biering-Sørensen et al. (1978). b Feeding histories were derived from the notes of health visitors for both the sudden infant deaths and a selection of infants used as controls. c p < .0005. COMMENTS: Odds ratio for bottle feeding versus any breastfeeding at 2 weeks of age = 3.06. Authors review past work on SIDS and breastfeeding. Given that breastfeeding rates declined from 1956 to 1971, but SIDS incidence did not, authors conclude relationship is not causal. ABSTRACT A-13 Naeye and colleagues (1976) investigated feeding methods in a study of 125 infants with sudden infant death syndrome (SIDS) and 375 controls, using data from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, 1959 to 1966. The odds ratio for bottle feeding compared with breastfeeding was 1.30. Infants with SIDS had frequent neonatal problems, including abnormal suck, need for gavage feeding, and late initiation of bottle feeding, suggesting that the choice of feeding method may have been secondary to neonatal problems. ABSTRACT A-14 Deaths/1,000 Births and Relative Risk (RR) of Death for 3,684 Infants Aged 1 to 12 Months, by Feeding Method, American Indians in Canada, 1962a   Deaths/1,000 Births, by Feeding Method Cause of Death Breast Bottle RRb All causes 26.6 53.8 2.03 Gastrointestinal or respiratory disease 3.9 32.7 8.29 a From Department of National Health and Welfare Canada (1963), as quoted in Gerard and Tan (1978). b Relative risk for breastfed infants = 1.0.

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Nutrition During Lactation ABSTRACT A-15 Carpenter and colleagues (1983) used a complex analytic method in their investigation of infant death rates between 1973 and 1979 in Sheffield, England. During that time there was a program of postnatal intervention by health visitors for high-risk infants in Sheffield. Postneonatal mortality (deaths to infants 28 days to 1 year of age) fell far more steeply in the study group than it did in all of England and Wales. Among "preventable" deaths, rates fell from 5.2 to 1.9 per 1,000 births. (Among the study group, intention to breastfeed rose from 40 to 70%.) The authors attributed 24% of the fall in the death rate, or 0.8 deaths/1,000 births, to increased rates of breastfeeding. ABSTRACT A-16 Feeding Methods of Infants Hospitalized with Infant Botulism, Infants with Sudden Infant Death Syndrome (SIDS), and Control Infants in California (1976 to 1979) and Elsewhere in the United States Through 1978a     Feeding Methods in Study Population, % Condition Subject Breast Formula Mixed Infant Cases (N = 50) 66.0b 24.0c 10.0d botulism Controls (N = 125) 43.2b 33.6c 23.2d SIDS Cases (N = 10) 0 80.0 20.0   Controls (N = 20) 30.0 35.0 35.0 a From Arnon et al. (1982). b Current breastfeeding. c Never breastfed. d Past breastfeeding. Case Fatality Studies ABSTRACT A-17 Case Fatality and Relative Risk (RR) of Death by Method of Infant Feeding Among Infants Hospitalized with Diarrhea, Birmingham, Englanda Feeding Method Number of Infants Hospitalized Number of Infant Deaths/1,000 Cases RR Breast 12 167 1.0 Bottle 209 766 4.59 Mixed 154 259 1.55 a From Smellie (1939). Of the 500 hospitalized infants, 375 were younger than 9 months of age.

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Nutrition During Lactation ABSTRACT A-18 Case Fatality and Relative Risk (RR) of Death Among 1,500 Infants Hospitalized with Infections, by Method of Infant Feeding, Toronto, Canadaa Feeding Method Number of Infants Hospitalized Infant Deaths/ 1,000 Cases RR Breast 227 185 1.0 Bottleb 836 164 0.89 Mixed 437 121 0.65 a From Ebbs and Mulligan (1942). b Never breastfed. COMMENTS: This study is exceptional, given that higher case-fatality rates were observed among breastfed infants. The reported results may imply lower case fatalities in bottle- and mixed-fed infants but could have arisen in other ways. For example, severity of infection was lower among breastfed infants: only the most severe cases might have been hospitalized. Furthermore, the results do not imply that death rates were higher among breastfed infants: if the incidence among them was lower, the opposite could have been true. Finally, the attending clinician may have been loathe to hospitalize breastfed infants, and this also would have possibly selected for higher severity among the breastfed infants. ABSTRACT A-19 Case Fatality and Relative Risk (RR) of Death of 216 Infants Hospitalized with Diarrhea, by Duration of Breastfeeding, Isleworth, England, 1942 and 1943a Duration of Breastfeeding, mo No. of Infant Deaths/1,000 Cases RR >1 300 1.00 <1 550 1.86 a From Gairdner (1945). ABSTRACT A-20 Prince and Bruce (1948) investigated case fatalities among 570 infants hospitalized with diarrhea in Louisville, Ky., from 1943 to 1946. Although the overall case fatality was 11%, there were no deaths among infants still breastfed at the time of admission.

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Nutrition During Lactation MISCELLANEOUS STUDIES ABSTRACT A-21 Indices of Breastfeeding Correlated with Infant Mortality in Three German States, by Location, 1869 to 1910a       Correlation Coefficients Between Infant Mortality and the Breastfeeding Index (number of cases) Breastfeeding Index Period of Breastfeeding Index Period of Infant Mortality State Rural Urban Total Proportion ever breastfed 1904–1906 1869–1878 Bavaria -.80 (88) -.87 (15) -.81   1901–1905 Bavaria -.76 (91) -.7 (17) -.76   1878–1882 Baden -.54 (47) NRb -.54 (52) Proportion  breastfed ≥6 mo 1911 1873–1875 Hessen -.59 (19) NR -.55 (24)   1906–1910 Hessen -.62 (19) NR -.61 (24) Duration of breastfeeding 1904–1906 1869–1878 Bavaria -.83 (76) -.92 (14) -.83; -.70   1901–1905 Bavaria -.71 (79) -.68 (16)   a From Knodel and van de Walle (1967). b NR = Not reported. ABSTRACT A-22 In a reanalysis of data of Groth and Hahn (1910), Greenwood and Brown (1912) reported a correlation of .76 ± 0.03 between the bottle-feeding rates and infant death rates from 92 districts of the Kingdom of Bavaria, Germany, between 1900 and 1904.

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Nutrition During Lactation REFERENCES Armstrong, H. 1904. A note on the comparative mortality of breastfed and hand-reared infants. Br. J. Child. Dis. 1:115-116. Arnon, S.S., K. Damus, B. Thompson, T.F. Midura, and J. Chin. 1982. Protective role of human milk against sudden death from infant botulism. J. Pediatr. 100:568-573. Biering-Sørensen, F., T. Jørgensen, and J. Hilden. 1978. Sudden infant death in Copenhagen 1956-1971. I. Infant feeding. Acta Paediatr. Scand. 67:129-137. Carpenter, R.G., A. Gardner, M. Jepson, E.M. Taylor, A. Salvin, R. Sunderland, J.L. Emery, E. Pursall, and J. Roe. 1983. Prevention of unexpected infant death: evaluation of the first seven years of the Sheffield Intervention Programme. Lancet 1:723-727. Davis, W.H. 1913. Statistical comparison of the mortality of breastfed and bottle-fed infants. Am. J. Dis. Child. 5:234-247. Deeny, J., and E.T. Murdock. 1944. Infant feeding in relation to mortality in the city of Belfast. Br. Med. J. 1:146-148. Department of National Health and Welfare, Canada. 1963. Survey of Maternal and Child Health of Canadian Registered Indians 1962. Cited in Gerard, J.W., and K.K.T. Tan. 1978. Hazards of formula feeding. Keeping Abreast, Journal of Human Nurturing. 3:20-25. Douglas, J.W.B. 1950. The extent of breastfeeding in Great Britain in 1946, with special reference to the health and survival of children. J. Obstet. Gynecol. Br. Emp. 57:335-361. Ebbs, J.H., and F. Mulligan. 1942. The incidence and mortality of breast- and artificially-fed infants admitted to hospital with infections. Arch. Dis. Child. 17:217-219. Gairdner, P. 1945. Infantile diarrhoea: an analysis of 216 cases with special reference to institutional outbreaks. Arch. Dis. Child. 20:22-27. Gerard, J.W., and K.K.T. Tan. 1978. Hazards of formula feeding. Keeping Abreast, Journal of Human Nurturing. 3:20-25. Greenwood, M., Jr., and J.W. Brown. 1912. An examination of some factors influencing the rate of infant mortality. J. Hyg. 12:5-45. Groth and Hahn. 1910. Die Säuglingsverhältnisse in Bayern. München (Lindauer) (Sonderabdr. a.d. Zeitschr. d. K. Bayer. Stat. Landesamts. Jahrg). Cited in Greenwood, M., Jr., and J.W. Brown. 1912. An examination of some factors influencing the rate of infant mortality. J. Hyg. 12:5-45. Grulee, C.G., H.N. Sanford, and P.H. Herron. 1934. Breast and artificial feeding: influences on morbidity and mortality of twenty thousand infants . J. Am. Med. Assoc. 103:735-739. Grulee, C.G., H.N. Sanford, and H. Schwartz. 1935. Breast and artificially fed infants: a study of the age incidence in the morbidity and mortality in twenty thousand cases. J. Am. Med. Assoc. 104:1986-1988. Howarth, W.J. 1905. The influence of feeding on the mortality of infants. Lancet 2:210-213. Knodel, J., and E. van de Walle. 1967. Breastfeeding, fertility and infant mortality: an analysis of some early German data. Popul. Stud. 21:109-131. Mannheimer, E. 1955. Mortality of breastfed and bottle fed infants: a comparative study. Acta Genet. Stat. Med. 5:134-163. Naeye, R.L., B. Ladis, and J.S. Drage. 1976. Sudden infant death syndrome: a prospective study. Am. J. Dis. Child. 130:1207-1210.

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Nutrition During Lactation Newman, G. 1906. Infant Mortality: A Social Problem. Methuen & Co, London. 356 pp. Newsholme, A. 1906. Domestic infection in relation to epidemic diarrhoea. J. Hyg. 6:139-148. Prince, G.E., and J.W. Bruce. 1948. Mortality of acute infantile diarrhea at the Louisville General Hospital from 1943 to 1947. J. Pediatr. 33:342-345. Robinson, M. 1951. Infant morbidity and mortality: a study of 3266 infants. Lancet 1:788-794. Smellie, J.M. 1939. Infantile diarrhoea. Lancet 236:969-973. Thiemich, M., and G. Bessau. 1930. Allgemeiner Teil. Pp. 1-100 in E. Feer, ed. Lehrbuch der Kinderheilkunde, 10th ed. Fischer, Jena, Germany.