Indian J Pediatr 1988; 55 : 955-960

Strategies which reduced sepsis-related neonatal mortality

Meharban Singh, V.K. Paul, Ashok K. Deorari, D. Ray, M.V. Murali and K.IL Sundaram*

The Neonatal Division, Depamnents of Pediatrics and *Biostatistics All India Institute of Medical Sciences, New Delhi

The neonatal mortality rate (per 1000 live births) dropped from 36.6 in 1985 to 23.9 in 1986. Neonatal sepsis ranked as number 2 as a cause of neonatal mortality in 1985, while it dropped to rank 4 (even lower than major malforma- tions) in 1986. The decline in the sepsis-related neonatal mortality was due to reduced incidence of sepsis (38.2 and 18.8per 1000 live births dwing 1985 and 1986 respectively) and improved survival (case fatality rmes of 24.6% vs 1Z 7% in 1985 and 1986 respectively). The strategies which reduced the incidence of nosocomial infections included decongestion of use of the nursery, discontinu- ation of use of heparinised saline for flushing intravenous lines and routine use of intravenous cannulas instead of metallic scalp vein needles.

Key words : Neonatal mortality;, Sepsis-related neonatal mortality;, Prevention of neonatal sepsis

While recent reports ~'6 from the devel- oped countries document neonatal mortal- ity rate (per 1000 live births) of less than 8.5, data from the tertiary care hospitals from India continues to project rates which are over 3 to 10 times this value. TM A major cause of neonatal mortality in India is bac- terial sepsis. It is responsible for one- fourth to nearly a half of the neonatal deaths. 7An Even with the most intensive management, sepsis in the newborn is fatal in a large proportion of cases. However, it

Reprint requests : Dr. Meharban Singh, Professor and Head, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110 029.

is possible to prevent neonatal infections to a si~ificant extent.

We report here a dramatic reduction in the neonatal mortality during the year 1986, largely attributable to the decline in the incidence of infections as a result of modification of a few of the routine prac- tices in our Intensive Care Nursery.

Material and Methods

Over 80% of pregnant women attending the antenatal clinics of AIIMS have one or more perinatal high risk factors. The usual problems include previous fetal/neonatal loss, conception after infertility, multiple fetuses, toxemia of pregnancy, hyperten-

955

956 THE INDIAN JOURNAL OF PEDIATRICS Vol. 55, No. 6

sion, systemic endocrinal disorders. All de- liveries are conducted by obstetricians and each neonate is managed at birth by one or more residents of the neonatology unit. The Neonatal Intensive Care Unit (NICU) at AIIMS looks after intramural births only. The facilities are adequate for provid- ing level I and level II care efficiently but infra-structure for level III care is incom- plete. For 8 beds in the NICU, 2 to 3 nurses provide a round-the-clock coverage.

Data on every neonate is recorded on a specially designed case sheet. Antenatal factors, information on labor and birth, an- thropometry, physical findings, neonatal problems, investigations and therapeutic modalities are recorded in detail. Cause of neonatal death is classified according to the criteria of Wigglesworth. 12 An admission- discharge register giving salient features is regularly maintained. A monthly report of the census and morbidity-mortality data is recorded on a special proforma and dis- cussed in a joint meeting of the staff of the obstetrics and neonatology services.

The ensuing information is based on these monthly reports.

Results

Table I shows the data on the live births in 1985 and 1986 and their distribution ac- cording to birth weight. The total number of live births in the two years were nearly the same. There was no significant differ- ence in the neonatal population in different birth weight groups.

In contrast to 66 neonatal deaths in 1985 only 43 neonates died in 1986 (Table II). This significant decline in ~ e neonatal mortality was attributable to reduction in the late neonatal deaths. The neonatal

Table I. Number of live births and distribution of neonatal populat ion according to birth weight characteristics

Live births and 1985 1986 their distribution

< 1000 g 14 11 1001-1500 g 59 45 1501-2000 g 102 93 2001-2500 g 319 297

> 2500 g 1309 1350

Total 1803 1796

The distribution of neonates according to various birth weight groups was similar during two years (x ~ = 4.06, N.S.)

Table II. Neonatal deaths in 1985 and 1986 (figures in parentheses denote neonatal mortality rate per 1000 live births)

Parameter 1985 1986

1. Live births 1803 1796

2. Neonatal death (overall)

Total (0-28 days)* 66 (36.6) 43 (23.9) Early (0-6 days) 46 (25.5) 39 (21.7) Late (7-28 days)* 20 (11.1) 4 (2.2)

*(P < 0.o5)

mortality rate (per 1000 live births) dropped by one third, from 36.6 in 1985 to 23.9 in 1986.

Neonatal mortality in different birth weight groups is depicted in Table HI. There is a decline in the neonatal mortality rate in birth weight groups from 1001-25~ g. The reduction in deaths in the birth weight group of 1001-1500 g was most pro- notmced. Neonatal mortality rate (per 1000

SINGH ET AL : DECLINE IN SEPSIS-RELATED NEONATAL MORTALITY 957

live births) dropped from 525.4 in 1985 to 377.7 in 1986 in this group. The overall neonatal mortality rate in babies weighing 2500 g or less declined by nearly a third, from 12.3 (61/494) to 8.5 percent (38/446). Because of smaller numbers, however, a statistically si~ificant difference in neona- tal deaths during the two years in the vari- ons birth weight groups was not noted.

The break up of neonatal deaths accord- ing to major causes is given in Table IV. The difference in the proportion of total neonatal deaths due to various causes in 1985 and 1986 is significant. On further scrutiny of the data, it was observed that the difference in the proportion of deaths in relation to individual causes was signifi- cant only in the case of sepsis.

The decline in the sepsis-related neona- tal mortality was a consequence of two fac- tors. Firstly, the incidence of neonatal sep- sis declined by nearly fifty per cent from 38.2 per 1000 live births to 18.8 per 1000 live births (69 cases in 1985 and 34 cases in 1986; P <0.001). Secondly a definite, though less pronounced improvement oc- curred in the case fatality rate (24.6 percent vs 17.7 percent in 1985 and 1986, respec- tively). Table IV gives details of early and late neonatal deaths within different groups according to the major causes of deaths. It is apparent that the significant decline in late neonatal deaths is largely at- tributed to the reduction in the sepsis-re- lated late neonatal deaths (16 vs 3). Sepsis ranked as number 2 as a cause of neonatal mortality in 1985 while it ranked as number 4 (even lower than major malformations) in 1986.

Discussion

Neonatal mortality rate (NNMR) of 23.9 per 1000 live births is the lowest in our

NICU since its inception in the late Sixties. Even more remarkable is the dramatic fall in the NNMR of around 30 percent in a single year. The foregoing data establishes that this decline is the consequence of re- duction in the sepsis-related late neonatal deaths. This in turn was related largely to the decline in the incidence of neonatal sepsis. A careful analysis of the various possible factors responsible for improve- ment in asepsis and reduction in bacterial infections was clone retrospectively. We be- lieve that the institution of the following practices in the day-to-day routines of the Neonatal Intensive Care Unit has led to this improved situation. These practices were implemented during the beginning of the year 1986. 1. In the past it. has been our practice to admit for observation all neonates born by cesarean section for a period of 12 to 48 hours. With increasing intake of high-risk pregnancies at AIIMS, the cesarean section rate rose to a level of 30 percent of all de- liveries in 1986. Consequently at any given time, 50 to 60 percent of neonates in the NICU used to be those babies born by ce- sarean section who otherwise did not qual- ify for nursery care. This obviously re~ulted in overcrowding of the limited space avail- able in the nursery. During the be~nning of 1986 this practice was discontinued and only those cesarean born babies were ad- mitted to NICU who had additional indica- tions for specialized nur-sery care. All other infants delivered by cesarean section were managed in the lying-in-ward. This practice has led to considerable deconges- tion of the nursery. In contrast to 765 ba- bies in 1985, 608 were admitted to the NICU in 1986. The care of the genuine high risk neonates has improved because the nurses and doctors have more time to

958 THE INDIAN JOURNAL OF PEDIATRICS Vol. 55, No. 6

Table HI. Details on neonatal mortality in different birth weight groups (figures in parentheses denote neonatal morality rate per 1000 live births in respective birth weight group)

Birth weight 1985 1986 groups Live Neonatal Live Neonatal

births deaths births deaths

< 1000 g 14 11 11 9

(785.7) (818.2)

1001-1500 g 59 31 45 17

(525.4) (377.7)

1501-2000 g 102 8 93 5

(78.4) (53 3)

2001 7..500 g 319 11 297 7

(34.5) (23.5) > 2500 g 1309 5 1350 5

(3.8) (3.7)

Table IV. Distribution of neonatal deaths due to diffvrent causes into early (0-6 days) and late (7-28 days) groups

Cause 1985 1986 Early Late Total Early Late Total

Immaturity* 22 2 24 20 0 20

Hypoxia 7 1 8 9 0 9

Sepsis 6 16 22* 1 3 4**

Malformations 5 1 6 6 1 7

Others 6 0 6 3 0 3

All causes 46 20 66 39 4 43

*Includes deaths due to gross immaturity (birth weight less than 750 g, hyaline membrane disease and intraventricular hemorrhage; **(P < 0.05).

SINGH ET AL : DECLINE IN SEPSIS-RELATED NEONATAL MORTALITY 959

devote to fewer neonates. The nursery per- sonnel including nurses and doctors adhere to the hand-washing and aseptic routines more willingly and with ease. The care of the cesarean born babies in the lying-in ward has not created any problems. 2. During the late 1985, a minor outbreak of pseudomonas septicemia in the NICU was traced to a stock solution of heparin from which small aliquots were being with- drawn every day for establishing and flush- ing the intravenous lines. Repeated needle insertions apparently led to contamination with Pseudomonas aerugenosa. Subsequent to this realisation, the practice of keeping a stock solution of heparinised saline has been abandoned and intravenous lines are flushed with a fresh stock of normal saline. 3. The insertion of an intravenous needle and infusion of intravenous fluids is associ- ated with an obvious risk of introduction of the pathogenic organisms. The metallic scalp vein needles are traumatic and liable to slip out of the vessels easily. Since the beginning of the year 1986, we have com- pletely discontinued the use of metallic scalp vein needles and introduced routine use of intravenous cannulas (Neoflon, Vent'lon). They are relatively atraumatic to insert and stay in the vessel for over 48 hours. A special effort has also been inade to reinforce the practice of sterilizing the local site thoroughly with betadine and spirit, and of frequent observation of the site for identifying extravasation. Nurses and doctors carry out periodic observation of the IV site as an integral part of the clinical monitoring of neonates. There has been significant reduction in the incidence of inflammatory nodules or microabscesses at IV puncture sites.

It is our strong belief that the reduction

in the incidence of nosocomial infectious in our NICU is related to the above modified rituals and routines. There were no other sigmificant changes in the working of the NICU. Indeed the trend of fewer neonatal infections and deaths is continuing well into the second half of 1987 at the time of writing this paper.

The reduction in the sepsis-related mor- tality was also, to some extent, due to re- duction in the case fatality rate from 23.2 percent (1985) to 17.7 percent (1986). These values are remarkably lower than that of 57.6 percent and 57.1 percent re- ported recently from other centres in In- dia. g~3 This improved outcome is attribut- able to the early diagnosis of neonatal sep- sis with the aid of screening tests and easy availability of amikacin and cefotaxime. The newer antibiotics were employed in some critically sick patients with good re- suits. It may be mentioned here that these drugs form the second line of therapy and are not given to all cases of suspected sep- sis.

The neonatal bacterial infectious which prove fatal after the first week of age, are by and large, horizontally transmitted and nosocomial in origin. This is in contrast to the vertically-transmitted infectious which cause most of the sepsis-related early neo- natal deaths. The vertically tran.~rnitted in- fections originate in the maternal genitou- rinary tract and are acquired either in- utero or during parturition.

The sources of nosocomial infectious are related to the immediate environment of the newborn infant. Evidently the preven- tion of the two types of bacterial infectious would necessitate different strategies. We have met with some success in the control of nosocomial infections. The lessons

960 THE INDIAN JOURNAL OF PEDIATRICS VoL 55, No. 6

learnt do have wider applicability and can be adopted with advantage in other neona- tal nurseries in the country.

References

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2. Thompson MH, Khot AS. Impact of neona- tal intensive care. Arch Dis Child 1985; 60: 213-214

3. Mutch LMM. Epidemiology, perinatal mor- tality and morbidity. In : Textbook. ofneona- tology. Ed: NC Roberton. Churchill Living- stone, Edinburgh 1986; 3-19

4. Vidyasagar D. Personal communication 5. Swyer PR. The organization of perinatal

care with particular reference to the new- born. In : Neonatology : pathophysiology and manage-ment of the newborn, ed Avery GB : JB Lip-pincott Company,

Philadelphia 1986:13-44 6. Anonymous. Birth weight-specific neonatal

mortality rates-Kentucky (USA). MMWR 1985; 34:487-488

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8. Bhakoo ON. Personal communication 9. Aggarwal K, Gupta SC, Roy Chowdhary S

et al. Some observations on perinatal mor- tality. Indian Pediatr 1982; 19:233-238

10. Santhanakrishnan BR, Gopal S, Jayam S. Perinatal mortality in a referral teaching hospital in Madras city. Indian J Pediatr 1986; 53: 359-363.

11. Bhatia BD, Mathur NB, Chaturvedi P, Dubey AP. Neonatal mortality pattern in a rural-based medical college hospital. In- dian J Pediatr 1984: 51:309-312

12. Wigglesworth JS. In : Pennatal pathology. Volume 15 Major problems in pathology. Benington JL, consulting ed. Philadelphia: WB Saunders Co. 1984; 19-26

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PROGNOSTIC FACTORS IN MENINGOCOCCAL SEPSIS

Gram-negative septicemia with purpura fulminans has a high mortality rate despite ag- gressive antibiotic treatment and progress in supportive care. This syndrome is more fre- quently due to Neisseria meningitidis.

In gram-negative septicemia, the lethal effect of endotoxin (lipopolysachharide) is me- diated by host cells. Macrophages react to lipopolysaccharide by secreting a large variety of cytokines responsible for inflammatory changes. One of these eytoldnes, tumor necrosis factor alpha, has been found to reproduce in vivo many of the biological effect of lipopoly- saccharide, such as hypotension, metabolic acidosis, and the formation of renal and p,lmo- nary lesions. Thus, tumor necrosis factor alpha may be an essential mediator in the patho- genesis of endotoxic shock. We studied cytokine, as well as others that may be involved in maerophage activation (such as gamma interferon) or are known to be released by acti- vated macrophages (such as interleukin-1 beta and alpha interferon), in order to obtain a more global view of the cellular events occuring during severe infections purpura.

Serum levels of tumor necrosis factor alpha, interleukin-1, and gamma interferon corre- la~ with the severity of meningoccoccemia in children.

Abstracted from : Giraden E et al. New Engl1Med 1988; 397-400