by Julius H. Hess, M.D.
The term sepsis may be defined as an invasion of the system by pyogenic cocci or other equivalent organisms. These bacteria may attain entrance for through various atria and may spread by means of the blood stream or may remain at the point of invasion and from there discharge the products of their activity into the blood of the infant.
Bacteriology. -- The bacteria occupying the first place among those causing sepsis are the pyogenic cocci, the streptococcus and staphylococcus, both albus and aureus. With them may be included the pneumococcus and colon bacillus. The colon group includes the paracolon and paratyphoid varieties. Of other bacteria there are found more rarely the Bacillus pyocyaneus, Bacterium lactis aërogenes, Bacillus enteritidis (Gartner), proteus bacillus, the gonococcus, the influenza bacillus and the meningococcus. Infection with Treponema pallidum is treated as a specific disease.
Blood examination during life and immediately after death in cases of sepsis in the premature gave the following results :
Blood culture positive
Blood culture negative
75.3 per cent
Colon bacillus and influenza bacillus
Ylppö , in a small series of prematures, found:
Bacteria in Blood of Prematures
No. of cases
0 to 1
2 to 3
4 to 15
In 70 per cent of the infants perishing between the fourth and fifteenth day of life, Ylppö was able to demonstrate bacteria in the blood. In 12 cases the following organisms were noted:
The frequency of Bacillus coli, he believes, speaks for an internal basis for the infection.
The Time of Infection. -- This may be either intra-uterine, intra-partum or postpartum (extra-uterine). Intra-uterine infection may occur either through the placenta, or by way of the liquor amnii. Should the mother be suffering from a septic infection, the causative organisms may pass through the injured placental wall, which ordinarily is sufficient to exclude bacteria from the fetus.
Infection of the liquor amnii may occur before or after the rupture of the membranes. Before rupture the infection may occur by contiguity of tissue, the organisms coming from the peritoneal cavity, rectum or bladder. Infection through the vaginal canal with unruptured membranes probably does not occur, the cervical opening being obstructed by what Delestre  calls the "gelatinous stopper of pregnancy." Vaginal infection, therefore, usually stops below the internal os. But once the membranes rupture, infection can occur by the ascension of bacteria from the vagina. This, however, is uncommon.
Our knowledge of infection through the liquor amnii is more definite. Lehmann  states that bacteria can pass through uninjured membrane and reports cases in support of this statement.
Intrapartum infections occur during the passage of the infant through the maternal birth canal. Local infection occurs first and this may be followed by general sepsis. The atrium of infection may be the mouth, the digestive tract, the lungs after aspiration of infected vaginal mucus or amniotic fluid,or wounds of the skin. The eyes especially are subject to infection at the time of birth, but fortunately infection there remains local.
Post partum, the most important sources of entrance of infection are the umbilicus, the skin, the gastro-intestinal tract, and the respiratory apparatus. As compared with intra-uterine and intra-partum infections those of extra-uterine origin are much the most important.
Umbilical infections through the physiological wound made at the time the cord is severed are the most frequent of all infections after birth and this forms the most common portal of entry for sepsis. At birth the most important structures found in the umbilical cord are the two umbilical arteries which conduct the blood from the fetus to the placenta, and which arise from the common iliac arteries, and the umbilical vein which carries blood from the placenta to the inferior vena cava via the left branch of the portal vein and the ductus venosus arantii. Immediately after birth the cord is ligated and cut, there remaining a stump a few centimeters in length which undergoes dessication during the first few days of life and which separates on the fourth to the ninth day with a slight inflammatory reaction. In the premature and debilitated the falling off of the cord and subsequent cicatrization of the base often occurs later. Ordinarily the base is covered by epithelium by the end of the third week or a little before, but infection of the umbilical wound may occur at any time up to the moment of healing, and is especially common in prematures.
Of second importance as a gateway for the entrance of pathogenic bacteria is the skin. The frequent abrasions which occur during birth, erosions from too severe efforts at mechanical cleansing, the pemphigus lesions and the intertrigo so common in neglected weaklings, all form portals of entry for bacteria. In the premature especially the skin is delicate, lacking the horny layer which in the better developed tends to prevent the occurrence of abrasions. Furunculosis and abscess formation are often the precursors of a general infection.
The respiratory tract is a frequent means of entry through the occurrence of a simple or suppurative rhinitis, otitis media, bronchial infection with epithelial necrosis or bronchopneumonic inflammation. It must be remembered that pulmonary inflammations are prone to develop secondarily in sepsis and unless evidence of pulmonary affection can be shown early in the course of sepsis, it may be difficult to say whether it was primary or secondary.
Of nearly equal importance is the gastro-intestinal tract as an atrium of infection. The buccal mucosa may be the seat of mucous patches, of Bednar's aphthae on the palate, of thrush, of stomatitis, or gingivitis, of ulcerations from too vigorous cleansing, or of abrasions due to the passage of the tracheal catheter. The intestinal wall of the premature and even the full-term newly born weaklings may be permeable to bacteria which cannot pass through the intestinal wall of better developed infants.
We believe that though the gastro-intestinal tract is frequently the seat of ulceration in the stage of atrophy in infants, a condition more rapidly developing in the prematures than in full-term infants, and therefore offering numerous portals of entry for systemic infection, every attempt should be made to exclude all other atria before accepting the gastro-intestinal tract as the source of infection.
Genito-urinary infections are of importance as the source of sepsis in the premature newborn.
Susceptibility. -- The premature is especially receptive to infection with the organisms of sepsis, seemingly possessing an extremely low resistance. The organs in which the leucocytes are formed are but imperfectly developed and the leucocytes themselves are deficient in phagocytic power; other organs are incomplete, the individual cells are immature and the lymph glands are of little importance in these infants, and fail to enlarge in the presence of infection.
The frequent subnormal temperature of these weaklings encourages this ease of infection, experimental evidence showing that to lower the temperature of an organ is to lower its resistance and diminish phagocytic activity and the bactericidal energy of the blood. Without doubt there is also a deficient formation of antibodies in these premature infants (Pfaundler ).
Artificially-fed prematures possess a relatively greater susceptibility to septic infection than do breast-fed infants, a fact which may in part be explained by the fact that human milk is rich in protective substances in contradistinction to cow's milk.
In sepsis the difference between the infants born of healthy parents and those of diseased parents is marked. The healthy premature is formed of young cells, full of vitality and only requiring growth to perfect themselves, and capable to some degree of resisting the organisms of infection with which they are continually surrounded. The others are already affected by the toxemia of the parental disease, or are themselves directly involved, and thus their cells have their vitality reduced and so offer a medium already prepared for infection.
The frequency of sepsis among the new born is today very much less than it was in preaseptic days. Proper care of the hands and the conduct of labor, sterilization of instruments and dressings, has greatly reduced the incidence of this condition. The fact that infants tend more often to become septic in a hospital or asylum than in the home is to be accounted for by the greater frequency of infecting organisms in the former, where may sick are congregated, and by the fact that one attendant often cares for several infants in the same hospital or ward (Meyer ).
General Manifestations. -- The onset of sepsis may occur at any time during the first days of life or the infant may be born with an infection present. The course varies, some almost without any symptoms which can be interpreted as involving any one set of organs, death occurring suddenly after collapse.
Local symptoms, if present, are dependent upon the situation of the primary infection or of secondary metastatic foci, while the general symptoms are those of a septicemia.
The septic fever found in the premature infant does not possess those characteristics found in older children. The center for heat regulation lacks stability and the reaction to toxic influences is slight. The more robust infants may show a rise of temperature which may reach 105° F. or even higher, and which may run a more or less regular course. In those born considerably before term, and in the weaklings there may be little or no temperature reaction, in fact in these latter a subnormal temperature is the rule. Chills do not occur in these weaklings.
Loss of weight is likely to be rapid and great, depending upon the ability to take food and the degree of intestinal involvement, being due to disintegration of tissue, to loss of water, and to inability to take food and fluids. The pulse-rate is rapid and the quality is usually poor. Respirations are often irregular. Cerebral symptoms are common during the final stages, the infant has a prostrated appearance and is apathetic. The cry becomes more feeble and the movements less frequent than usual. The skin loses its turgor; anemia becomes evident and the skin color becomes grayish or, if icterus exists, yellowish. Occasionally there is a cyanotic tinge to the entire body surface. Hemorrhages are very common during the course of sepsis, occurring from the mouth, bowel, navel, or into the skin.
Skin. -- Icterus is a very frequent finding in the first few days or weeks of life and is especially frequent in premature infants and in the victims of sepsis. Particularly with umbilical infections is the icterus of marked degree. Edema of the feet and legs occasionally occurs and especially premature infants scleredema, or even sclerema, may occur toward the end of the disease. Hemorrhages into the skin are common in sepsis, being seen over the trunk and extremities, usually as petechiae. In some instances they may be purpuric, or effusive in character. Pemphigus-like blebs with bloody contents are a frequent complication.
Inflammation of the umbilical vessels is a frequent primary process in a general sepsis. Most often the umbilical arteries are involved, and less frequently the vein. The amount of involvement varies, occasionally extending just a short distance within the abdominal wall, sometimes the entire length of the vessel, in which latter instance the thickened vessel cannot infrequently be palpated through the abdominal wall. Septic thrombi or pus may be present in the umbilical vessels, and pus can often be squeezed out from the stump of the cord. Inflammation of the umbilicus or of the abdominal wall in its immediate neighborhood may be present.
Omphalitis alone is sometimes seen. The usual termination of this infection is in abscess formation, but occasionally an inflammation of an erysipelatous character spreads to the abdominal wall (Holt ).
Nervous symptoms are many. They may depend solely upon the toxemia, or be due to an intercurrent meningitis, encephalitis, or edema of the meninges. Most often the infant lies quietly in a stuporous condition, at other times there are restlessness, tremors, spasms, jactitation, dilated pupils, bulging fontanel, spasticity of the muscles with rigidity of the neck, and in cases of meningitis and encephalitis, paralyses.
Gastro-intestinal manifestations are practically always present. In the mouth are seen ulcers, fissures, stomatitis and purulent inflammations of the salivary glands. Not infrequently sepsis will run its course with clinical pictures of dyspepsia with secondary anhydremic intoxication, with vomiting and diarrhea as marked symptoms. The vomiting and diarrhea are manifestations of the toxemia, emesis being frequently cerebral in origin. The mesenteric glands are infiltrated and the gastric and intestinal mucosa are the seat of hemorrhages and frequently show evidence of inflammation.
Peritonitis is a rather frequent complication, either general or local. Oftentimes it is accompanied by an umbilical inflammation. Many cases are purulent, fluid being present. Adhesions of intestinal coils to each other or to the abdominal wall occur. The symptoms of this condition are abdominal distension and rigidity with tenderness, vomiting, umbilical protrusion, thoracic respiration and flexion of the thighs. Diagnosis of the condition is not at all easy as the presence of fluid is difficult to demonstrate. Probably the finding of greatest value in these infants is abdominal tenderness.
The spleen is usually enlarged. The liver shows evidence of an acute hepatitis, and not infrequently there are multiple foci of suppuration.
Involvement of the circulatory apparatus in sepsis does occur but is not very frequent. Pericarditis is commoner than endocarditis. The former usually arises by extension from the pleura.
The myocardium is frequently the seat of parenchymatous degeneration and hemorrhage.
The respiratory organs are involved very frequently in the picture of sepsis. Pneumonia is the most frequent lesion met with, and as usual in the weakling or premature, is difficult of diagnosis, especially when the process in the lung is not extensive, with lesions small and multiple. The lungs show areas of bronchopneumonia, areas of atelectasis, alveolar fatty degeneration, hemorrhages into the alveolar walls of multiple abscesses. Effusion into the pleura is uncommon.
Rapid respiration and cyanosis are about the only symptoms which are seen in these cases of pneumonia. Occasionally the rapidity of breathing may occasion the belief that the lungs are the seat of a pneumonic process, when its presence is only the result of severe intoxication.
The kidneys usually show parenchymatous degeneration and hemorrhagic nephritis, with occasional necrosis of the epithelium and pyelitis. The albumin which is found in the urine is either the result of the action of the absorbed toxins on the kidneys or is the expression of the nephritis or pyelitis. In nephritis there will be found hyalin, epithelial or granular casts, and in pyelitis, pus cells and epithelium.
Bones and Joint Inflammations. -- Rarely the bones are involved in an osteomyelitis and the joints are sometimes the seat of acute suppuration, usually several being involved at the same time. Immobility and swelling over the involved joints are the common symptoms seen. Pain is present and crepitus can be elicited when epiphysial separation has occurred.
Unfortunately the blood is of little value in completing the diagnosis, because of the usual absence of leucocytosis. A positive diagnosis is possible by finding the causative organism in the blood. The difficulties to be met in making blood cultures in premature infants must be remembered. The longitudinal sinus is the best source for obtaining blood.
Course. -- In the premature the course is usually acute. Often the first symptom is loss of appetite; the child refuses to take the breast, or if artificially fed, it vomits. Convulsions may usher in the condition, followed by icterus which increases in intensity and soon is accompanied by diarrhea. Cyanosis may next make its appearance, the accompanying dyspnea being hard to detect because of the slight amplitude of the respiratory movements. It is sometimes revealed by movements of the alae nasi or by an increased frequency of respiration, or by change in the respiratory rhythm, consisting of short inspirations followed by relatively long expirations. Occasionally the respiration is slow, feeble and superficial, because of the impermeability of the lungs involved by atelectasis.
Some cases of sepsis prove fatal in a few hours; the younger the infant and the weaker the condition at birth, the shorter the course as a rule. Symptomless sepsis is frequent in the premature.
Prognosis. -- Septic infection in the very young is a fatal disease and the more immature the infant, the worse the outlook. In the lesser degrees it offers a grave prognosis and in the severer forms it is practically always fatal. Involvement of a large number of organs makes the lethal outcome almost certain.
Prophylaxis. -- Since the treatment of sepsis in the premature new born offers so little, it becomes of prime importance to prevent the development of the disease, and sepsis may be considered as preventable. The vulnerability of the new born and particularly of the premature new born, who is deficient in vital functions, to the invading organisms of disease is notable, and the fact that sepsis occurs particularly in institutions makes the care of these infants of great importance.
Infection which reaches the child before birth is beyond our control, but subsequent to that time very much may be done to prevent the disease. The care of the umbilical wound is of great importance; instruments used in dividing the cord, the cord tape and dressings must all be aseptic. In hospitals the infant should be kept in a separate room from the mother, and the same attendant should not look after both mother and infant. The hands of the attendant and of the mother when she handles the child must be cleansed thoroughly before the child is touched. The nurse should wash her hands after the care of an infant before passing to another in the nursery. All articles which come into contact with the infant's mouth -- nipples, feeders, spoons, gavage tubes, etc., must be sterilized before use. All utensils should, so far as possible, be individual. The mouth of the infant must not be traumatized and all rough handling or other body trauma must be avoided. The breasts of the nursing mother must be washed thoroughly before each nursing and protected between the nursing periods by covering them with thin, clean gauze.
Strict asepsis during delivery will do a great deal toward reducing birth infection to the smallest amount, while care in internal examinations before delivery will do much toward lessening the infections of the amniotic fluid. Lochial secretions can become the source of infections and their care is important. They should be disposed of at once.
In private families where there is not sufficient help and one person must attend to mother and child, the infant must be taken care of first, and the mother later.
To facilitate cleanliness the new-born infant should be given a daily warm sponge, unless very weak, and the diaper should be changed frequently to prevent the development of intertrigo. The use of a dusting powder in the skin folds often acts as an irritant.
The room in which the infant spends its time should be kept at a temperature warm enough to meet the needs of its individual development if it is hypothermic. The air of its room should always be kept pure and fresh and light freely admitted. The clothing of the infant should be warm enough, but not too heavy, being suited to the surrounding temperature and to the individual needs of the child. It should not fit so tightly as to prevent movement of the arms and legs.
Only the greatest cleanliness of the skin and umbilicus will prevent infection. The falling-off of the cord and the subsequent cicatrization is, as a rule, delayed in prematures, and infection is favored. Wet compresses not infrequently macerate the delicate skin and so dry or alcoholic dressings are advised, best without dusting powder which is likely to cake and prevent absorption of the exudate.
The existence of an angina, rhinitis, bronchitis, or any other form of infection, in the mother or nurse, make the separation of the infant or a change of nurses imperative. Masks must be worn by all affected individuals coming in contact with the infant.
Active Treatment. -- This promises very little, as we possess no specific and our efforts must be directed chiefly toward the treatment of individual symptoms, as they arise. If abscesses occur they must be opened and drained. The strength must be supported by judicious breast-milk feeding if this be possible, and by the use of stimulants in 1 to 5-drop doses of brandy or whisky every two hours. In collapse stimulation must be resorted to, the most useful being camphor-in-oil, 1 to 3 minims hypodermically. Spiritus ammoniae aromaticus, 1 to 3 minims by mouth, well diluted, every three or four hours is often of benefit. Infusion of digitalis or digalen in minimum doses may be used to support a failing heart.
Fluids should be pushed by mouth in the endeavor to dilute the circulating poison. Gavage feeding should be instituted without too prolonged delay. The use of saline transfusion has found great favor in recent years. Seven-tenths of 1 per cent sodium chloride may be injected subcutaneously beneath the breasts or into the loose areolar tissue of the interscapular region in quantities of 1/2 to 2 ounces (15 to 60 cc) and repeated if indicated. The danger of infection must be remembered. Great elevations of temperature, if present, are to be controlled by tepid baths but care must be taken to avoid collapse. Often, these premature infants do not react to infection with temperature, and in such cases warm baths are indicated. Mustard baths or mustard compresses are of value in collapse.
 Delestre: Infections chez le prémature, Paris, 1901.
 Pathologisch-anatomische Studien bei Frühgeburten, Ztschr. f. Kinderh., 1919, 20, 371-372.
 Thèse, A Study of the Infections of the New Born, Paris, 1901.
 Thèse,, De l'infection amniotique et de ses consequences pour 18 enfants, Paris, 1899.
 Die Antikörperübertragung von Mutter auf Kind, Arch. f. Kinderh., 1908, 47, 260; 1908, 48, 245.
 Hospitalismus, Berlin, 1913; Ges. f. Gynäk., 1911.
 Diseases of Infancy and Childhood, D. Appleton and Company, New York, 1913.